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Sample records for high-risk hematologic cancer

  1. DCB - Cancer Immunology, Hematology, and Etiology Research

    Science.gov (United States)

    Part of NCI’s Division of Cancer Biology’s research portfolio, studies supported include the characterization of basic mechanisms relevant to anti-tumor immune responses and hematologic malignancies.

  2. Adherence to, and outcomes of, a galactomannan screening protocol in high-risk hematology patients.

    Science.gov (United States)

    Harricharan, S; Biederman, K; Bombassaro, A M; Lazo-Langner, A; Elsayed, S; Fulford, A; Delport, J A; Xenocostas, A

    2018-04-01

    A twice-weekly galactomannan (gm) screening protocol was implemented in high-risk hematology inpatients. Study objectives were to determine adherence to the protocol, use of selected resources, and patient outcomes. This retrospective cohort study compared outcomes of interest before and after implementation of gm screening. Adults undergoing matched related allogeneic hematopoietic stem-cell transplantation or induction chemotherapy for acute leukemia were eligible. Patients could be enrolled more than once and were evaluated as episodes. Adherence to the gm protocol was assessed in post-implementation episodes. Use of broad-spectrum antifungals (bsafs), consultations (infectious diseases, respirology), and diagnostic procedures (computed tomography imaging, bronchoalveolar lavage) were compared between phases, as were the patient outcomes of all-cause mortality and clinical success (alive and not taking a bsaf). Of 182 episodes consecutively screened, 70 per phase were enrolled. Clinical characteristics and duration of assessment were similar for the phases. Full or partial adherence to the protocol was observed in 61 post-implementation episodes (87%), with full adherence in 40 episodes (57%). More episodes in the pre-implementation phase than in the post-implementation phase involved receipt of bsafs, consultations, and diagnostics (27% vs. 7%, p = 0.02; 46% vs. 26%, p = 0.014; and 46% vs. 31%, p = 0.083 respectively). Although mortality was similar in the two phases, clinical success at the final assessment was observed in fewer pre-implementation than post-implementation episodes (79% vs. 98%, p < 0.001). Implementation of a gm screening protocol was feasible and associated with significantly fewer episodes involving receipt of bsafs and consultations, and with significantly more episodes showing clinical success.

  3. Radical prostatectomy for high-risk prostate cancer.

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    Yossepowitch, Ofer; Eastham, James A

    2008-06-01

    Consensus recommendations for the identification and treatment of men whose apparent organ confined prostate cancer has high risk features are lacking. Despite ongoing refinements in surgical technique and improvements in morbidity and functional outcomes, the tradition of steering high-risk patients away from radical prostatectomy (RP) remains steadfast. We performed a medical literature search in English using MEDLINE/PubMed that addressed high risk prostate cancer. We analyzed the literature with respect to the historical evolution of this concept, current risk stratification schemes and treatment guidelines and related short and long term outcomes following RP. Contemporary evidence suggest that patients classified with high-risk prostate cancer by commonly used definitions do not have a uniformly poor prognosis after RP. Many cancers categorized clinically as high risk are actually pathologically confined to the prostate, and most men with such cancers who undergo RP are alive and free of additional therapy long after surgery. RP in the high-risk setting appears to be associated with a similar morbidity as in lower-risk patients. Men with clinically localized high-risk prostate cancer should not be categorically disqualified from local definitive therapy with RP. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.

  4. Optimizing the Management of High-Risk, Localized Prostate Cancer

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    Sundi, Debasish; Jeong, Byong Chang; Lee, Seung Bae; Han, Misop

    2012-01-01

    Prostate cancer has a high prevalence and a rising incidence in many parts of the world. Although many screen-detected prostate cancers may be indolent, prostate cancer remains a major contributor to mortality in men. Therefore, the appropriate diagnosis and treatment of localized prostate cancer with lethal potential are of great importance. High-risk, localized prostate cancer has multiple definitions. Treatment options that should be individualized to each patient include observation, radi...

  5. Screening for breast cancer in a high-risk series

    International Nuclear Information System (INIS)

    Woodard, E.D.; Hempelmann, L.H.; Janus, J.; Logan, W.; Dean, P.

    1982-01-01

    A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammograpy was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, use of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening

  6. The Very High Risk Prostate Cancer – a Contemporary Update

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    Mano, Roy; Eastham, James; Yossepowitch, Ofer

    2017-01-01

    Background Treatment of high-risk prostate cancer has evolved considerably over the past two decades, yet patients with very high-risk features may still experience poor outcome despite aggressive therapy. We review the contemporary literature focusing on current definitions, role of modern imaging and treatment alternatives in very high-risk prostate cancer. Methods We searched the MEDLINE database for all clinical trials or practice guidelines published in English between 2000 – 2016 with the following search terms: ‘prostatic neoplasms’ (MeSH Terms) AND (‘high risk’ (keyword) OR ‘locally advanced’ (keyword) OR ‘node positive’ (keyword)). Abstracts pertaining to very high-risk prostate cancer were evaluated and 40 pertinent studies served as the basis for this review. Results The term ‘very’ high-risk prostate cancer remains ill defined. The EAU and NCCN guidelines provide the only available definitions, categorizing those with clinical stage T3-4 or minimal nodal involvement as very-high risk irrespective of PSA level or biopsy Gleason score. Modern imaging with mpMRI and PET-PSMA scans plays a role in pretreatment assessment. Local definitive therapy by external beam radiation combined with androgen deprivation is supported by several randomized clinical trials whereas the role of surgery in the very high-risk setting combined with adjuvant radiation/ androgen deprivation therapy is emerging. Growing evidence suggest neoadjuvant taxane based chemotherapy in the context of a multimodal approach may be beneficial. Conclusions Men with very high-risk tumors may benefit from local definitive treatment in the setting of a multimodal regimen, offering local control and possibly cure in well selected patients. Further studies are necessary to better characterize the ‘very’ high-risk category and determine the optimal therapy for the individual patient. PMID:27618950

  7. Diagnosis and Management of High Risk Group for Gastric Cancer

    Science.gov (United States)

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

  8. The PIM kinases in hematological cancers.

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    Alvarado, Yesid; Giles, Francis J; Swords, Ronan T

    2012-02-01

    The PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance. PIM kinases are overexpressed in several hematopoietic tumors and support in vitro and in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. PIM kinases do not have an identified regulatory domain, which means that these proteins are constitutively active once transcribed. They appear to be critical downstream effectors of important oncoproteins and, when overexpressed, can mediate drug resistance to available agents, such as rapamycin. Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Preclinical studies in models of various hematologic cancers indicate that these novel agents show promising activity and some of them are currently being evaluated in a clinical setting. In this review, we profile the PIM kinases as targets for therapeutics in hematologic malignancies.

  9. Results of high-risk neutropenia therapy of hematology-oncology patients in a university hospital in Uruguay

    Directory of Open Access Journals (Sweden)

    Matilde Boada Burutaran

    2015-02-01

    Full Text Available Background: Febrile neutropenia is an important cause of mortality and morbidity in hematology-oncology patients undergoing chemotherapy. The management of febrile neutropenia is typically algorithm-driven. The aim of this study was to assess the results of a standardized protocol for the treatment of febrile neutropenia. Methods: A retrospective cohort study (2011-2012 was conducted of patients with high-risk neutropenia in a hematology-oncology service. Results: Forty-four episodes of 17 patients with a median age of 48 years (range: 18-78 years were included. The incidence of febrile neutropenia was 61.4%. The presence of febrile neutropenia was associated with both the duration and severity of neutropenia. Microbiological agents were isolated from different sources in 59.3% of the episodes with bacteremia iso- lated from blood being the most prevalent (81.3%. Multiple drug-resistant gram-negative bacilli were isolated in 62.5% of all microbiologically documented infections. Treatment of 63% of the episodes in which the initial treatment was piperacillin/tazobactam needed to be escalated to meropenem. The mortality rate due to febrile neutropenia episodes was 18.5%. Conclusion: The high rate of gram-negative bacilli resistant to piperacillin/tazobactam (frontline antibiotics in our protocol and the early need to escalate to carbapenems raises the question as to whether it is necessary to change the current protocol.

  10. Management of Skin Cancer in the High-Risk Patient.

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    Behan, James W; Sutton, Adam; Wysong, Ashley

    2016-12-01

    Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumor with aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, a high-risk patient with the ongoing development of multiple skin cancers, and a high-risk patient based on immunosuppression. We have recently proposed classifying NMSC as a chronic disease in a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1 year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

  11. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Vinayak Muralidhar

    2016-02-01

    Full Text Available Purpose : Recent retrospective data suggest that brachytherapy (BT boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA 20 ng/ml. Material and methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results : EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258, and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270. Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022. Conclusions : Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease.

  12. Tamoxifen for women at high risk of breast cancer

    OpenAIRE

    Nazarali, Safia A; Narod, Steven A

    2014-01-01

    Safia A Nazarali, Steven A Narod Women's College Research Institute, Women's College Hospital, and The University of Toronto, Toronto, Ontario, Canada Abstract: Tamoxifen has been used as a treatment for women who have been diagnosed with breast cancer for roughly four decades and has been approved as chemoprevention for over ten years. Although tamoxifen has been proven to be beneficial in preventing breast cancer in high-risk women, its use has not been widely embraced. To ...

  13. Predicting reattendance at a high-risk breast cancer clinic.

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    Ormseth, Sarah R; Wellisch, David K; Aréchiga, Adam E; Draper, Taylor L

    2015-10-01

    The research about follow-up patterns of women attending high-risk breast-cancer clinics is sparse. This study sought to profile daughters of breast-cancer patients who are likely to return versus those unlikely to return for follow-up care in a high-risk clinic. Our investigation included 131 patients attending the UCLA Revlon Breast Center High Risk Clinic. Predictor variables included age, computed breast-cancer risk, participants' perceived personal risk, clinically significant depressive symptomatology (CES-D score ≥ 16), current level of anxiety (State-Trait Anxiety Inventory), and survival status of participants' mothers (survived or passed away from breast cancer). A greater likelihood of reattendance was associated with older age (adjusted odds ratio [AOR] = 1.07, p = 0.004), computed breast-cancer risk (AOR = 1.10, p = 0.017), absence of depressive symptomatology (AOR = 0.25, p = 0.009), past psychiatric diagnosis (AOR = 3.14, p = 0.029), and maternal loss to breast cancer (AOR = 2.59, p = 0.034). Also, an interaction was found between mother's survival and perceived risk (p = 0.019), such that reattendance was associated with higher perceived risk among participants whose mothers survived (AOR = 1.04, p = 0.002), but not those whose mothers died (AOR = 0.99, p = 0.685). Furthermore, a nonlinear inverted "U" relationship was observed between state anxiety and reattendance (p = 0.037); participants with moderate anxiety were more likely to reattend than those with low or high anxiety levels. Demographic, medical, and psychosocial factors were found to be independently associated with reattendance to a high-risk breast-cancer clinic. Explication of the profiles of women who may or may not reattend may serve to inform the development and implementation of interventions to increase the likelihood of follow-up care.

  14. Postmastectomy irradiation in high-risk breast cancer patients

    International Nuclear Information System (INIS)

    Overgaard, M.; Juul Christensen, J.; Johansen, H.; Nybo-Rasmussen, A.; Brincker, H.; Kooy, P. van der; Frederiksen, P.L.; Laursen, F.; Panduro, J.; Soerensen, N.E.; Gadeberg, C.C.; Hjelm-Hansen, M.; Overgaard, J.; West Andersen, K.; Zedeler, K.

    1988-01-01

    All pre- and postmenopausal high-risk breast cancer patients in the protocols DBCG 77 of the Danish Breast Cancer Cooperative Group received postmastectomy irradiation before randomization to either adjuvant systemic therapy or no such treatment. The actuarial loco-regional recurrence rate at 9 years was 6-17%, with the lowest rate in patients who also received additional adjuvant chemotherapy or tamoxifen. In a subsequent study (DBCG 82) the role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients. Pre- and menopausal patients were randomized to postmastectomy irradiation+CMF (cyclophosphamide, methotrexate, 5-fluorouracil), CMF alone or CMF+TAM (tamoxifen). Postmenopausal patients were randomized to postmastectomy irradiation+TAM, TAM or CMF+TAM. At 4 years the loco-regional recurrence rate was significantly lower in the irradiated patients (5-7% vs. 23-33%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment. At present, there are no significant differences between survival in the treatment groups. Thus, adjuvant systemic treatment alone (chemotherapy and/or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumour control in high-risk breast cancer patients with respect to survival. (orig.)

  15. Radical prostatectomy in clinically localized high-risk prostate cancer

    DEFF Research Database (Denmark)

    Røder, Martin Andreas; Berg, Kasper Drimer; Christensen, Ib Jarle

    2013-01-01

    ) is regarded as primary therapy by others. This study examined the outcome for high-risk localized PCa patients treated with RP. Material and methods. Of 1300 patients who underwent RP, 231 were identified as high-risk. Patients were followed for biochemical recurrence (BCR) (defined as prostate-specific......Abstract Objective. The optimal therapeutic strategy for high-risk localized prostate cancer (PCa) is controversial. Supported by randomized trials, the combination of external beam radiation therapy (EBRT) and endocrine therapy (ET) is advocated by many, while radical prostatectomy (RP...... antigen ≥ 0.2 ng/ml), metastatic disease and survival. Excluding node-positive patients, none of the patients received adjuvant therapy before BCR was confirmed. Univariate and multivariate analysis was performed with Kaplan-Meier and Cox proportional hazard models. Results. Median follow-up was 4.4 years...

  16. Postoperative chemoradiotherapy in high risk locally advanced gastric cancer

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    Song, Sang Hyuk; Chie, Eui Kyu; Kim, Kyu Bo; Lee, Hyuk Joon; Yang, Han Kwang; Han, Sae Won; Oh, Do Youn; Im, Seok Ah; Bang, Yung Jue; Ha, Sung W. [Seoul National University College of Medicine, Seoul(Korea, Republic of)

    2012-12-15

    To evaluate treatment outcome of patients with high risk locally advanced gastric cancer after postoperative chemoradiotherapy. Between May 2003 and May 2012, thirteen patients who underwent postoperative chemoradiotherapy for gastric cancer with resection margin involvement or adjacent structure invasion were retrospectively analyzed. Concurrent chemotherapy was administered in 10 patients. Median dose of radiation was 50.4 Gy (range, 45 to 55.8 Gy). The median follow-up duration for surviving patients was 48 months (range, 5 to 108 months). The 5-year overall survival rate was 42% and the 5-year disease-free survival rate was 28%. Major pattern of failure was peritoneal seeding with 46%. Loco-regional recurrence was reported in only one patient. Grade 2 or higher gastrointestinal toxicity occurred in 54% of the patients. However, there was only one patient with higher than grade 3 toxicity. Despite reported suggested role of adjuvant radiotherapy with combination chemotherapy in gastric cancer, only very small portion of the patients underwent the treatment. Results from this study show that postoperative chemoradiotherapy provided excellent locoregional control with acceptable and manageable treatment related toxicity in patients with high risk locally advanced gastric cancer. Thus, postoperative chemoradiotherapy may improve treatment result in terms of locoregional control in these high risk patients. However, as these findings are based on small series, validation with larger cohort is suggested.

  17. Hematology

    International Nuclear Information System (INIS)

    Konrad, H.

    1976-01-01

    The latest state of nuclear medical functional diagnostics in hematology is reviewed. In addition to methods for determining the blood volume, iron kinetics, the survival time of erythrocytes as well as resorption and serum levels of vitamin B 12 kinetic investigations of thrombocytes, granulocytes, lymphocytes, and the spleen with the aid of radioisotopes are described in detail. Also included are tables with data about radiation doses to patients due to medical application of radioisotopes as well as a compilation of physical properties of radioisotopes which are used in hematological diagnosis such as 59 Fe, 51 Cr, 131 I, 125 I, 58 Co, 57 Co, 32 P, 3 H, sup(99m)Tc, 113 In. Finally, radiopharmaceuticals for hematological diagnostics are listed, which are commercially available in the German Democratic Republic. The booklet is intended for physicians working in outpatient departments and hospitals

  18. High risk bladder cancer: current management and survival

    Directory of Open Access Journals (Sweden)

    Anna M. Leliveld

    2011-04-01

    Full Text Available PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC in the Comprehensive Cancer Center North-Netherlands (CCCN and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18% patients with high risk NMIBC underwent a transurethral resection (TUR as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8 % in non-teaching hospitals (p 80 years OR 0.1 p = 0.001 and treatment in non-teaching hospitals (OR 0.25; p < 0.001 were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49% and progression in 84 /392 (21.4% patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8. CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.

  19. Hematology

    International Nuclear Information System (INIS)

    Price, D.C.; Ries, C.

    1975-01-01

    This paper reviews the wide variety of radioisotopic techniques available to pediatricians in hematologic evaluation of their patients, with comments on the tracer techniques, and an indication of some new territory in splenic evaluation and nonradioactive tracers which may prove to be of considerable interest in the future. The only differences in applying these techniques to the pediatric population, compared with the adult population, lie in the different spectrum of hematologic diseases under consideration in this age group and the greater sensitivity to problems of radiation exposure which the pediatrician and the nuclear medicine physician must have in administering the isotopes in vivo. With these considerations in mind, the usefulness of such radioisotopic techniques in the evaluation of pediatric hematologic disease remains unquestionable. Radiopharmaceuticals and the radiation doses associated with the various procedures are listed. It is hoped in the future that fluorescent excitation techniques will replace at least s []me of the radioisotope techniques, obviating all considerations of patient irradiation in such instances. (auth)

  20. Leveraging cancer genome information in hematologic malignancies.

    Science.gov (United States)

    Rampal, Raajit; Levine, Ross L

    2013-05-20

    The use of candidate gene and genome-wide discovery studies in the last several years has led to an expansion of our knowledge of the spectrum of recurrent, somatic disease alleles, which contribute to the pathogenesis of hematologic malignancies. Notably, these studies have also begun to fundamentally change our ability to develop informative prognostic schema that inform outcome and therapeutic response, yielding substantive insights into mechanisms of hematopoietic transformation in different tissue compartments. Although these studies have already had important biologic and translational impact, significant challenges remain in systematically applying these findings to clinical decision making and in implementing new technologies for genetic analysis into clinical practice to inform real-time decision making. Here, we review recent major genetic advances in myeloid and lymphoid malignancies, the impact of these findings on prognostic models, our understanding of disease initiation and evolution, and the implication of genomic discoveries on clinical decision making. Finally, we discuss general concepts in genetic modeling and the current state-of-the-art technology used in genetic investigation.

  1. Postoperative Chemotherapy Followed by Conformal Concomitant Chemoradiotherapy in High-Risk Gastric Cancer

    International Nuclear Information System (INIS)

    Quero, Laurent; Bouchbika, Zineb; Kouto, Honorine; Baruch-Hennequin, Valerie; Gornet, Jean-Marc; Munoz, Nicolas; Cojean-Zelek, Isabelle; Houdart, Remi; Panis, Yves; Valleur, Patrice; Aparicio, Thomas; Maylin, Claude; Hennequin, Christophe

    2012-01-01

    Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36–75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400–3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.

  2. High-risk bladder cancer: improving outcomes with perioperative chemotherapy

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

  3. Epigenetics in Cancer: A Hematological Perspective.

    Directory of Open Access Journals (Sweden)

    Maximilian Stahl

    2016-10-01

    Full Text Available For several decades, we have known that epigenetic regulation is disrupted in cancer. Recently, an increasing body of data suggests epigenetics might be an intersection of current cancer research trends: next generation sequencing, immunology, metabolomics, and cell aging. The new emphasis on epigenetics is also related to the increasing production of drugs capable of interfering with epigenetic mechanisms and able to trigger clinical responses in even advanced phase patients. In this review, we will use myeloid malignancies as proof of concept examples of how epigenetic mechanisms can trigger or promote oncogenesis. We will also show how epigenetic mechanisms are related to genetic aberrations, and how they affect other systems, like immune response. Finally, we will show how we can try to influence the fate of cancer cells with epigenetic therapy.

  4. Results of brachytherapy boost in high risk breast cancer patients

    International Nuclear Information System (INIS)

    Battermann, J.J.

    1996-01-01

    Introduction: in breast conserving therapy the role of brachytherapy as a boost after whole breast irradiation is not clear. The series from the Netherlands Cancer Institute show a very high local control rate, but the question could be raised whether all these patients need a brachy boost. Therefore, it was decided at our institute, to deliver a brachy boost only to high risk patients, viz. patients with incomplete resection margins and/or extensive in situ cancer (ECI). Materials and methods: in the period 1988 through 1993 a total of 148 patients with 151 breast tumours received a boost on the tumour bed using brachytherapy. Age varied from 25 till 74 years, with a mean age of 52.3 years. Incomplete resection margins were found in 60 patients, ECI in 31 and both in 49 patients. In the majority of patients, the ECI component was not completely removed. T-stage was unknown in 9 patients. T1 in 83, T2 in 49 and T3 in 10. Nodal status was N0 in 119 and N1 in 33 patients. Infiltrating duct carcinoma was the most common histology. No infiltrating growth was found in 6 patients, but one patient presented a positive node. The interval period between day of operation and day of brachytherapy implantation was between 3 and 4 months in 62%. The mean interval between completion of beam irradiation and day of implantation was 18 days, while 12 patients received their brachytherapy previous to the beam irradiation. External irradiation was with two tangential fields and a total dose of 50 Gy in 25 fractions over 6 weeks (9 fractions in two weeks). The number of needles in two planes. Most patients were implanted under local anaesthesia. Dose rate in 97 patients was 51 - 60 cGy/h. Results: follow-up for patients alive varied from 2 years till 7 years with a mean follow-up period of 4 years. One hundred and twenty five patients are alive, including 6 patients with manifest metastases. Local recurrence was encountered in 8 patients (interval 14 - 60 months, mean 30 months), with

  5. Managing work and cancer treatment: Experiences among survivors of hematological cancer.

    Science.gov (United States)

    Thomson, Maria D; Siminoff, Laura A

    2018-04-16

    The current study was performed to characterize the employment status of survivors of hematological cancer who have an informal caregiver from the time of diagnosis through the first 6 months of treatment. Using a mixed methods approach, semistructured interviews with survivors of hematological cancer were conducted within 6 months of the initiation of cancer treatment. Interviews assessed cancer treatment status, barriers and facilitators to employment, financial and insurance status, and relationship with the primary caregiver. These results are part of a longitudinal study of cancer survivors and informal caregivers. A total of 171 patients were enrolled. Within 6 months of beginning cancer treatments, approximately 35% were no longer employed. Reasons to remain employed included financial need, employee benefits, and a sense of purpose and normalcy. Employer accommodations and supportive colleagues facilitated continued employment. Logistic regression analysis demonstrated that having a higher household income, a desire to work, nonphysical job tasks, and congruent survivor-caregiver communication were associated with greater odds of remaining employed. Within 6 months of initiating cancer treatment, the majority of survivors of hematological cancer had maintained employment. Because of the limitations imposed by the physical stress of cancer treatments, as well as the need to maintain employment to continue receiving employee benefits to cover such treatments, survivors of hematological cancer likely would benefit from employment accommodations that are sensitive to their unique needs. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  6. Breast cancer in high-risk Afrikaner families: Is BRCAfounder ...

    African Journals Online (AJOL)

    Breast cancer is the most common form of cancer in women worldwide. Altogether 6 224 cases were reported in South Africa (SA) in 2009.[1] Up to 10% of breast cancer cases are attributable to germline mutations in cancer susceptibility genes, leading to hereditary syndromes.[2] The most well described of these cancer.

  7. Conditioning with Treosulfan and Fludarabine Followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

    Science.gov (United States)

    Nemecek, Eneida R.; Guthrie, Katherine A.; Sorror, Mohamed L.; Wood, Brent L.; Doney, Kristine C.; Hilger, Ralf A.; Scott, Bart L.; Kovacsovics, Tibor J.; Maziarz, Richard T.; Woolfrey, Ann E.; Bedalov, Antonio; Sanders, Jean E.; Pagel, John M.; Sickle, Eileen J.; Witherspoon, Robert; Flowers, Mary E.; Appelbaum, Frederick R.; Deeg, H. Joachim

    2010-01-01

    In this prospective study 60 patients of median age 46 (range 5–60) years, with acute myeloid leukemia (AML; n=44), acute lymphoblastic leukemia (ALL; n=3), or myelodysplastic syndrome (MDS; n=13) were conditioned for allogeneic hematopoietic cell transplantation with a treosulfan/fludarabine combination. Most patients were considered at high risk for relapse or non-relapse mortality (NRM). Patients received intravenous treosulfan, 12 g/m2/day (n=5) or 14 g/m2/day (n=55) on days -6 to -4, and fludarabine (30 mg/m2/day) on days -6 to -2, followed by infusion of marrow (n=7) or peripheral blood stem cells (n=53) from HLA-identical siblings (n=30) or unrelated donors (n=30). All patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median follow-up of 22 months, the 2-year relapse-free survival for all patients was 58% and 88% for patients without high risk cytogenetics. The 2-year cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML in first remission, 50% for AML or ALL beyond first remission and 63% for AML in refractory relapse). Thus, a treosulfan/fludarabine regimen was well tolerated and yielded encouraging survival and disease control with minimal NRM. Further trials are warranted to compare treosulfan/fludarabine to other widely used regimens, and to study the impact of using this regimen in more narrowly defined groups of patients. PMID:20685259

  8. Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0109 TITLE: Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Elizabeth A. Mittendorf, MD, PhD CONTRACTING ORGANIZATION: University of Texas MD Anderson Cancer Center Houston, TX 77030 REPORT DATE: October...CONTRACT NUMBER Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0109 5c. PROGRAM

  9. Adjuvant radiochemotherapy in patients with locally advanced high-risk cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Heinzelmann, F.; Henke, G.; Grafenstein, M. von; Weidner, N.; Paulsen, F.; Bamberg, M.; Weinmann, M. [Tuebingen Univ. (Germany). Dept. of Radiation Oncology; Staebler, A. [Tuebingen Univ. (Germany). Div. of Gynecologic Pathology; Brucker, S. [Tuebingen Univ. (Germany). Dept. of Gynecology

    2012-07-15

    Background and purpose: The aim of this retrospective study was to analyze the outcome of patients with locally advanced cervical carcinoma treated by adjuvant radiochemotherapy and to determine risk factors for local and distant relapse. Furthermore, acute and late effects of treatment were recorded. Patients and methods: A total of 72 patients with FIGO stages I-III cervical carcinoma were treated by radical hysterectomy, pelvic lymphadenectomy, and postoperative radiochemotherapy. Only patients with positive pelvic lymph nodes, parametrial involvement, positive margins, or tumor bulk were eligible. Patients were irradiated with a standard pelvic field (50.4 Gy in 28 fractions). The majority of patients received platinum-based chemotherapy. Results: After a median follow-up of 37 months, estimated 1-, 2-, and 4-year disease-free survival (DFS) and overall survival (OS) rates were 89%, 80%, 68% and 95%, 88%, 76%, respectively. Nine of the 72 patients had pelvic recurrences including only 1 isolated local failure; 23 of the 72 patients presented with distant relapse. The majority of relapses occurred within the first 3 years after adjuvant treatment. The number of positive pelvic lymph nodes (> 1) was the strongest prognostic factor for DFS. Treatment was well tolerated with transient acute hematologic ({proportional_to}30%) and gastrointestinal ({proportional_to}30%) grade 3 toxicity. Small bowel obstruction ({proportional_to}6%) was the only important late sequelae. Conclusion: Adjuvant radiochemotherapy in patients with advanced cervical cancer and several risk factors is highly effective to prevent local relapse. Future efforts to improve outcome should be placed on improvement of systemic control especially in subgroups with high-risk features for distant relapse. Combined treatment was well tolerated with moderate acute and late toxicity. (orig.)

  10. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

    Directory of Open Access Journals (Sweden)

    Monica Fung

    Full Text Available Invasive fungal disease (IFD causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN. These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients.We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates.Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85 and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87 or overall mortality (RR 0.95, 95% CI 0.46-1.99. The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing.Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality

  11. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

    Science.gov (United States)

    Fung, Monica; Kim, Jane; Marty, Francisco M; Schwarzinger, Michaël; Koo, Sophia

    2015-01-01

    Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We

  12. Relationship between Background Parenchymal Enhancement on High-risk Screening MRI and Future Breast Cancer Risk.

    Science.gov (United States)

    Grimm, Lars J; Saha, Ashirbani; Ghate, Sujata V; Kim, Connie; Soo, Mary Scott; Yoon, Sora C; Mazurowski, Maciej A

    2018-03-27

    To determine if background parenchymal enhancement (BPE) on screening breast magnetic resonance imaging (MRI) in high-risk women correlates with future cancer. All screening breast MRIs (n = 1039) in high-risk women at our institution from August 1, 2004, to July 30, 2013, were identified. Sixty-one patients who subsequently developed breast cancer were matched 1:2 by age and high-risk indication with patients who did not develop breast cancer (n = 122). Five fellowship-trained breast radiologists independently recorded the BPE. The median reader BPE for each case was calculated and compared between the cancer and control cohorts. Cancer cohort patients were high-risk because of a history of radiation therapy (10%, 6 of 61), high-risk lesion (18%, 11 of 61), or breast cancer (30%, 18 of 61); BRCA mutation (18%, 11 of 61); or family history (25%, 15 of 61). Subsequent malignancies were invasive ductal carcinoma (64%, 39 of 61), ductal carcinoma in situ (30%, 18 of 61) and invasive lobular carcinoma (7%, 4of 61). BPE was significantly higher in the cancer cohort than in the control cohort (P = 0.01). Women with mild, moderate, or marked BPE were 2.5 times more likely to develop breast cancer than women with minimal BPE (odds ratio = 2.5, 95% confidence interval: 1.3-4.8, P = .005). There was fair interreader agreement (κ = 0.39). High-risk women with greater than minimal BPE at screening MRI have increased risk of future breast cancer. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  13. Thyroid hormones and carcinoembryonic antigen in persons with a high risk of lung cancer

    International Nuclear Information System (INIS)

    Svetukhina, E.S.; Bukhteeva, N.F.; Sapozhkova, L.P.; Maripova, Eh.M.

    1984-01-01

    An attempt was made to study CEA and thyroid hormones in high risk groups as there is evidence of their change in lung cancer patients. A questionnaire to distinguish between 4 types of the probability of lung cancer development and a method of radioimmunoassay to study the concentration of CEA and thyroid hormones in the blood serum were used. A high risk group included 320 practically healthy persons, a control group 108 patients with verified lung cancer. The results of the study have shown that the concentration of CEA and thyroid hormones increases more often in persons of the high risk group with noncancerous diseases than in persons without pathological pulmonary changes. With an increase in the degree of probability the frequency of a high concentration of CEA and thyroid hormones grows. The older the persons with a high risk of lung cancer, the higher the frequency of concentration of the thyroid hormones. Studies of CEA and thyroid hormones can be used for dynamic observation of persons with a high risk of lung cancer

  14. Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

    Science.gov (United States)

    Molenaar, Remco J; Sidana, Surbhi; Radivoyevitch, Tomas; Advani, Anjali S; Gerds, Aaron T; Carraway, Hetty E; Angelini, Dana; Kalaycio, Matt; Nazha, Aziz; Adelstein, David J; Nasr, Christian; Maciejewski, Jaroslaw P; Majhail, Navneet S; Sekeres, Mikkael A; Mukherjee, Sudipto

    2017-12-18

    Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

  15. The role of cytokines in development of hematological and immune disorders at radiation therapy for uterine body cancer

    International Nuclear Information System (INIS)

    Sorochan, P.P.; Prokhach, N.E.; Gromakova, Yi.A.; Krugova, Yi.M.; Sukhyin, V.S.

    2013-01-01

    The changes in hematological and immune parameters in patients with uterine body cancer were analyzed by the stages of the combined treatment. The rol of cytokines in the development of hematologic and immune disorders was assessed

  16. DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer.

    Science.gov (United States)

    Di Cello, Annalisa; Di Sanzo, Maddalena; Perrone, Francesca Marta; Santamaria, Gianluca; Rania, Erika; Angotti, Elvira; Venturella, Roberta; Mancuso, Serafina; Zullo, Fulvio; Cuda, Giovanni; Costanzo, Francesco

    2017-06-01

    New reliable approaches to stratify patients with endometrial cancer into risk categories are highly needed. We have recently demonstrated that DJ-1 is overexpressed in endometrial cancer, showing significantly higher levels both in serum and tissue of patients with high-risk endometrial cancer compared with low-risk endometrial cancer. In this experimental study, we further extended our observation, evaluating the role of DJ-1 as an accurate serum biomarker for high-risk endometrial cancer. A total of 101 endometrial cancer patients and 44 healthy subjects were prospectively recruited. DJ-1 serum levels were evaluated comparing cases and controls and, among endometrial cancer patients, between high- and low-risk patients. The results demonstrate that DJ-1 levels are significantly higher in cases versus controls and in high- versus low-risk patients. The receiver operating characteristic curve analysis shows that DJ-1 has a very good diagnostic accuracy in discriminating endometrial cancer patients versus controls and an excellent accuracy in distinguishing, among endometrial cancer patients, low- from high-risk cases. DJ-1 sensitivity and specificity are the highest when high- and low-risk patients are compared, reaching the value of 95% and 99%, respectively. Moreover, DJ-1 serum levels seem to be correlated with worsening of the endometrial cancer grade and histotype, making it a reliable tool in the preoperative decision-making process.

  17. Complications of radiofrequency ablation for liver cancer in high-risk locations and their prevention

    Directory of Open Access Journals (Sweden)

    ZHANG Junchao

    2017-05-01

    Full Text Available Radiofrequency ablation (RFA is one of the most important methods for the treatment of liver cancer and has the advantages of small trauma, simple operation, and repeatability. However, for tumors in high-risk locations within 5 mm of the first and second branches of the hepatic portal vein, near the hepatic vein, the inferior vena cava, or the gallbladder, within 5 mm of the intestinal tract, under the Glisson’s capsule, and in the diaphragm, RFA has the issues of a low complete ablation rate, a high local recurrence rate, and serious complications. This article introduces the complications of RFA for liver cancer in high-risk locations and their prevention and points out that with the promotion of individualized and standardized RFA, liver cancer in these high-risk locations is no longer a contradiction for RFA.

  18. What is the optimal management of high risk, clinically localized prostate cancer?

    Science.gov (United States)

    Eastham, James A; Evans, Christopher P; Zietman, Anthony

    2010-01-01

    To summarize the presentations and debate regarding the optimal treatment of localized high-risk prostate cancer as presented at the 2009 Spring Meeting of the Society of Urologic Oncology. The debate was centered on presentations arguing for radical prostatectomy (RP) or radiotherapy as the optimal treatment for this condition. The meeting presentations are summarized by their respective presenters herein. Dr. James Eastham presents the varied definitions for "high-risk" prostate cancer as strongly influencing which patients end up in this cohort. Based upon this, between 3% and 38% of patients with high-risk features could be defined as "high-risk". Despite that, these men do not have a uniformly poor prognosis after RP, and attention to surgical principles as outlined improve outcomes. Disease-specific survival at 12 years is excellent and up to one-half of these men may not need adjuvant or salvage therapies, depending on their specific disease characteristics. Adjuvant or salvage radiotherapies improve outcomes and are part of a sequential approach to treating these patients. Dr. Anthony Zietman presented radiotherapy as the gold-standard based upon large, randomized clinical trials of intermediate- and high-risk prostate cancer patients. Compared with androgen deprivation alone, the addition of radiotherapy provided a 12% cancer-specific survival advantage and 10% overall survival advantage. Dose escalation seems to confer further improvements in cancer control without significant escalation of toxicities, with more data forthcoming. There are no randomized trials comparing RP to radiotherapy for any risk category. In high-risk prostate cancer patients, both approaches have potential benefits and cumulative toxicities that must be matched to disease characteristics and patient expectations in selecting a treatment course. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  19. Unification of favourable intermediate-, unfavourable intermediate-, and very high-risk stratification criteria for prostate cancer.

    Science.gov (United States)

    Zumsteg, Zachary S; Zelefsky, Michael J; Woo, Kaitlin M; Spratt, Daniel E; Kollmeier, Marisa A; McBride, Sean; Pei, Xin; Sandler, Howard M; Zhang, Zhigang

    2017-11-01

    To improve on the existing risk-stratification systems for prostate cancer. This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P prostate cancer-specific mortality (PCSM, P prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR with SHR patients, results in modestly improved prediction of outcomes, potentially allowing better personalisation of therapeutic recommendations. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  20. Establishing a Program for Individuals at High Risk for Breast Cancer

    Science.gov (United States)

    Cadiz, Fernando; Kuerer, Henry M.; Puga, Julio; Camacho, Jamile; Cunill, Eduardo; Arun, Banu

    2013-01-01

    Our need to create a program for individuals at high risk for breast cancer development led us to research the available data on such programs. In this paper, we summarize our findings and our thinking process as we developed our own program. Breast cancer incidence is increasing worldwide. Even though there are known risk factors for breast cancer development, approximately 60% of patients with breast cancer have no known risk factor, although this situation will probably change with further research, especially in genetics. For patients with risk factors based on personal or family history, different models are available for assessing and quantifying risk. Assignment of risk levels permits tailored screening and risk reduction strategies. Potential benefits of specialized programs for women with high breast cancer risk include more cost -effective interventions as a result of patient stratification on the basis of risk; generation of valuable data to advance science; and differentiation of breast programs from other breast cancer units, which can result in increased revenue that can be directed to further improvements in patient care. Guidelines for care of patients at high risk for breast cancer are available from various groups. However, running a high-risk breast program involves much more than applying a guideline. Each high-risk program needs to be designed by its institution with consideration of local resources and country legislation, especially related to genetic issues. Development of a successful high-risk program includes identifying strengths, weaknesses, opportunities, and threats; developing a promotion plan; choosing a risk assessment tool; defining “high risk”; and planning screening and risk reduction strategies for the specific population served by the program. The information in this article may be useful for other institutions considering creation of programs for patients with high breast cancer risk. PMID:23833688

  1. A novel method for monitoring high-risk breast cancer with tumor markers

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1993-01-01

    cancer. METHODS: Ninety females with high-risk breast cancer were included in the study. Response evaluation was based upon clinical examination, x-rays or histology and elaborated marker criteria. RESULTS: During the marker monitoring period, metastases in four patients were confined to skin or lymph......BACKGROUND: An early and reliable diagnosis of metastatic spread has increased interest in serum tumor markers. This study investigated the ability of CA 15.3, CEA, and TPA to identify, predict, and exclude metastases in bone/viscera during adjuvant treatment and follow-up of high-risk breast...

  2. Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

    International Nuclear Information System (INIS)

    Narang, Amol K.; Gergis, Carol; Robertson, Scott P.; He, Pei; Ram, Ashwin N.; McNutt, Todd R.; Griffith, Emily; DeWeese, Theodore A.; Honig, Stephanie; Singh, Harleen; Song, Danny Y.; Tran, Phuoc T.; DeWeese, Theodore L.

    2016-01-01

    Purpose: Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients. Methods and Materials: All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer–specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men. Results: Men with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05). Conclusions: NCCN high-risk prostate cancer patients who meet VHR

  3. Androgenic alopecia is not useful as an indicator of men at high risk of prostate cancer.

    NARCIS (Netherlands)

    Cremers, R.G.H.M.; Aben, K.K.H.; Vermeulen, S.; Heijer, M. den; Oort, I.M. van; Kiemeney, L.A.L.M.

    2010-01-01

    BACKGROUND: Androgens are assumed to play a central role in the pathophysiology of both prostate cancer (PC) and androgenic alopecia (AA). A correlation between the two phenotypes may be relevant for identification of men at high risk of PC. We evaluated the association between AA at different ages

  4. Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

    NARCIS (Netherlands)

    Oort, van I.M.; Witjes, J.A.; Kok, D.E.G.; Kiemeney, L.A.; Hulsbergen-van de Kaa, C.A.

    2008-01-01

    Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate

  5. Repeated participation in pancreatic cancer surveillance by high-risk individuals imposes low psychological burden

    NARCIS (Netherlands)

    Konings, Ingrid C. A. W.; Sidharta, Grace N.; Harinck, Femme; Aalfs, Cora M.; Poley, Jan-Werner; Kieffer, Jacobien M.; Kuenen, Marianne A.; Smets, Ellen M. A.; Wagner, Anja; van Hooft, Jeanin E.; van Rens, Anja; Fockens, Paul; Bruno, Marco J.; Bleiker, Eveline M. A.

    2016-01-01

    When assessing the feasibility of surveillance for pancreatic cancer (PC), it is important to address its psychological burden. The aim of this ongoing study is to evaluate the psychological burden of annual pancreatic surveillance for individuals at high risk to develop PC. This is a multicenter

  6. High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population

    DEFF Research Database (Denmark)

    Ingerslev, Kasper Hjorth; Hogdall, Estrid; Skovrider-Ruminski, Wojciech

    2016-01-01

    BACKGROUND: High-risk human papillomavirus (HPV) has been suspected to play a role in the carcinogenesis of epithelial ovarian cancer (EOC). However, results from previous studies are conflicting. In most of these studies, the number of tissue samples was small. The current study was therefore...... undertaken to examine the prevalence of high-risk HPV DNA in EOC in a large series of patients. METHOD: Formalin-fixed, paraffin-imbedded tumor tissue samples from 198 cases consecutively included in the Danish Pelvic Mass Study were analyzed. The material included 163 serous adenocarcinomas, 15 endometrioid...

  7. High-Risk Palliative Care Patients' Knowledge and Attitudes about Hereditary Cancer Testing and DNA Banking.

    Science.gov (United States)

    Quillin, John M; Emidio, Oluwabunmi; Ma, Brittany; Bailey, Lauryn; Smith, Thomas J; Kang, In Guk; Yu, Brandon J; Owodunni, Oluwafemi Patrick; Abusamaan, Mohammed; Razzak, Rab; Bodurtha, Joann N

    2017-12-04

    Even at the end of life, testing cancer patients for inherited susceptibility may provide life-saving information to their relatives. Prior research suggests palliative care inpatients have suboptimal understanding of genetic importance, and testing may be underutilized in this clinical setting. These conclusions are based on limited research. This study aimed to estimate genetic testing prevalence among high-risk palliative care patients in a National Cancer Institute-designated comprehensive cancer center. We also aimed to understand these patients' understanding of, and attitudes toward, hereditary cancer testing and DNA banking. Palliative care in-patients with cancer completed structured interviews, and their medical records were reviewed. Among patients at high risk for hereditary cancer, we assessed history of genetic testing/DNA banking; and related knowledge and attitudes. Among 24 high-risk patients, 14 (58.3%) said they/their relatives had genetic testing or they had been referred for a genetics consultation. Of the remaining 10 patients, seven (70%) said they would "probably" or "definitely" get tested. Patients who had not had testing were least concerned about the impact of future testing on their family relationships; two (20%) said they were "extremely concerned" about privacy related to genetic testing. Of patients without prior testing, five (50%) said they had heard or read "a fair amount" about genetic testing. No high-risk patients had banked DNA. Overall, 23 (95.8%) said they had heard or read "almost nothing" or "relatively little" about DNA banking. Written materials and clinician discussion were most preferred ways to learn about genetic testing and DNA banking. Overall, this study demonstrates underutilization of genetics services at the end of life continues to be problematic, despite high patient interest.

  8. Evaluation of the Prostate Cancer Prevention Trial Risk Calculator in a High-Risk Screening Population

    Science.gov (United States)

    Kaplan, David J.; Boorjian, Stephen A.; Ruth, Karen; Egleston, Brian L.; Chen, David Y.T.; Viterbo, Rosalia; Uzzo, Robert G.; Buyyounouski, Mark K.; Raysor, Susan; Giri, Veda N.

    2009-01-01

    Introduction Clinical factors in addition to PSA have been evaluated to improve risk assessment for prostate cancer. The Prostate Cancer Prevention Trial (PCPT) risk calculator provides an assessment of prostate cancer risk based on age, PSA, race, prior biopsy, and family history. This study evaluated the risk calculator in a screening cohort of young, racially diverse, high-risk men with a low baseline PSA enrolled in the Prostate Cancer Risk Assessment Program. Patients and Methods Eligibility for PRAP include men ages 35-69 who are African-American, have a family history of prostate cancer, or have a known BRCA1/2 mutation. PCPT risk scores were determined for PRAP participants, and were compared to observed prostate cancer rates. Results 624 participants were evaluated, including 382 (61.2%) African-American men and 375 (60%) men with a family history of prostate cancer. Median age was 49.0 years (range 34.0-69.0), and median PSA was 0.9 (range 0.1-27.2). PCPT risk score correlated with prostate cancer diagnosis, as the median baseline risk score in patients diagnosed with prostate cancer was 31.3%, versus 14.2% in patients not diagnosed with prostate cancer (p<0.0001). The PCPT calculator similarly stratified the risk of diagnosis of Gleason score ≥7 disease, as the median risk score was 36.2% in patients diagnosed with Gleason ≥7 prostate cancer versus 15.2% in all other participants (p<0.0001). Conclusion PCPT risk calculator score was found to stratify prostate cancer risk in a cohort of young, primarily African-American men with a low baseline PSA. These results support further evaluation of this predictive tool for prostate cancer risk assessment in high-risk men. PMID:19709072

  9. The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency.

    Science.gov (United States)

    Cressman, Sonya; Peacock, Stuart J; Tammemägi, Martin C; Evans, William K; Leighl, Natasha B; Goffin, John R; Tremblay, Alain; Liu, Geoffrey; Manos, Daria; MacEachern, Paul; Bhatia, Rick; Puksa, Serge; Nicholas, Garth; McWilliams, Annette; Mayo, John R; Yee, John; English, John C; Pataky, Reka; McPherson, Emily; Atkar-Khattra, Sukhinder; Johnston, Michael R; Schmidt, Heidi; Shepherd, Frances A; Soghrati, Kam; Amjadi, Kayvan; Burrowes, Paul; Couture, Christian; Sekhon, Harmanjatinder S; Yasufuku, Kazuhiro; Goss, Glenwood; Ionescu, Diana N; Hwang, David M; Martel, Simon; Sin, Don D; Tan, Wan C; Urbanski, Stefan; Xu, Zhaolin; Tsao, Ming-Sound; Lam, Stephen

    2017-08-01

    Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited. Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency. Use of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non-lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention. Non-lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and

  10. Well-directed inclusion of hematology in African national cancer control plans.

    Science.gov (United States)

    Weaver, Meaghann; Yao, Atteby J J; Renner, Lorna; Harif, Mhamed; Lam, Catherine G

    2017-07-01

    In the context of a convergent call for noncommunicable disease integration in the global agenda, recognizing cross-cutting needs and opportunities in national strategies across disease fields with shared priorities in low- and middle-income settings can enhance sustainable development approaches. We reviewed publicly available cancer control plans in Africa to evaluate for inclusion of hematology needs and shared service priorities. Pediatric data remain sparse in cancer control plans. While continental Africa represents incredible diversity, recognizing shared priorities and opportunity for collaboration between oncology and hematology services and across age groups may guide prioritized cancer control efforts and reduce programmatic redundancies in resource-limited settings. © 2017 Wiley Periodicals, Inc.

  11. Compliance with adjuvant treatment guidelines in endometrial cancer: room for improvement in high risk patients.

    Science.gov (United States)

    Eggink, F A; Mom, C H; Boll, D; Ezendam, N P M; Kruitwagen, R F P M; Pijnenborg, J M A; van der Aa, M A; Nijman, H W

    2017-08-01

    Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014. While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Radiotherapy after high-dose chemotherapy and peripheral blood stem cell support in high-risk breast cancer

    International Nuclear Information System (INIS)

    Hoeller, Ulrike; Heide, Juergen; Kroeger, Nicolaus; Krueger, William; Jaenicke, Fritz; Alberti, Winfried

    2002-01-01

    Purpose: To assess the toxicity and efficacy of radiotherapy with respect to locoregional control after adjuvant high-dose chemotherapy for patients with breast cancer. At first, radiotherapy was withheld because of toxicity concerns, but it was introduced in 1995 because of reported high locoregional relapse rates. Methods and Materials: Between 1992 and 1998, 40 patients with Stage II-III high-risk breast cancer received adjuvant high-dose chemotherapy consisting of thiotepa, mitoxantrone, and cyclophosphamide and peripheral blood stem cell support after four cycles of induction chemotherapy. The chest wall or breast, as well as the supraclavicular nodes, were irradiated with electrons and photons to a median dose of 50.4 Gy in 20 patients. Six additional patients received only supraclavicular irradiation to a median dose of 50.4 Gy. Acute toxicity was scored clinically. Pulmonary function tests were performed in 14 irradiated patients before high-dose chemotherapy and 1.1-4.4 years (median 1.6) after irradiation. The median follow-up time of living patients was 33 vs. 67 months in irradiated (n=26) and nonirradiated (n=14) patients, respectively. Results: G2 and G3 hematologic toxicity occurred in 1 patient each. No clinical pneumonitis or clinical impairment of lung function was observed. After 1-2 years, the lung function tests showed only minor changes in 4 patients. The 3-year locoregional control rate was 92% in the irradiated patients vs. 58% in the nonirradiated patients (p=0.049, actuarial analysis). Conclusion: In this series, adjuvant radiotherapy after adjuvant chemotherapy for breast cancer appeared well tolerated, with improved local regional control and without significant side effects. Longer follow-up and more patient accrual, as well as Phase III trials, are necessary for confirmation

  13. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

    Science.gov (United States)

    Cha, Eugene K; Eastham, James A

    2015-05-01

    Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review

    Science.gov (United States)

    2011-01-01

    Background Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history. Methods We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk. Results Of 1028 titles identified, 53 articles met our criteria. Most (92%) used an observational design and focused on women (70%) with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups) and few employed theory-driven analytic strategies to decipher interrelationships of factors. Conclusions Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although evolving, is still

  15. Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Tilburt Jon C

    2011-05-01

    Full Text Available Abstract Background Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history. Methods We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk. Results Of 1028 titles identified, 53 articles met our criteria. Most (92% used an observational design and focused on women (70% with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups and few employed theory-driven analytic strategies to decipher interrelationships of factors. Conclusions Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although

  16. Male Oncology Research and Education program for men at high risk for prostate cancer.

    Science.gov (United States)

    Lorentz, J; Liu, S K; Vesprini, D

    2018-04-01

    Three groups of men are at high risk of developing prostate cancer: men with a strong family history of prostate cancer, men of West African or Caribbean ancestry, and men with a germline pathogenic variant in a prostate cancer-associated gene. Despite the fact that those men constitute a significant portion of the male population in North America, few recommendations for prostate cancer screening specific to them have been developed. For men at general population risk for prostate cancer, screening based on prostate-specific antigen (psa) has remained controversial despite the abundance of literature on the topic. As a result, recommendations made by major screening authorities are inconsistent (ranging from no psa screening to baseline psa screening at age 45), allowing physicians to pick and choose how to screen their patients. The Male Oncology Research and Education (more) program is an observational research program that serves as an academic platform for multiple research foci. For its participants, serum and dna are biobanked, medical information is collected, and contact for relevant research-related opportunities is maintained. This research program is paired with a specialized clinic called the more clinic, where men at high risk are regularly screened for prostate cancer in a standard approach that includes physical examination and serum psa measurement. In this article, we describe the goals, participant accrual to date, and projects specific to this unique program.

  17. Role of robot-assisted radical prostatectomy in the management of high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Akshay Sood

    2014-01-01

    Full Text Available We aimed to evaluate the role of robot-assisted radical prostatectomy (RARP in the management of high-risk prostate cancer (PCa, with a focus on oncological, functional and perioperative outcomes. Further, we also aimed to briefly describe our novel modification to conventional RARP that allows immediate organ retrieval and examination for intra-operative surgical margin assessment. A literature search of PubMed was performed for articles on the management of high-risk PCa. Papers written in English and concerning clinical outcomes following RARP for locally advanced and high-risk PCa were selected. Outcomes data from our own center were also included. A total of 10 contemporary series were evaluated. Biopsy Gleason score ≥ 8 was the most common cause for classification of patients into the high-risk PCa group. Biochemical failure rate, in the few series that looked at long-term follow-up, varied from 9% to 26% at 1 year. The positive surgical margin rate varied from 12% to 53.3%. Urinary continence rates varied from 78% to 92% at 1 year. The overall complication rates varied from 2.4% to 30%, with anastomotic leak and lymphocele being the most common complications. Long-term data on oncological control following RARP in high-risk patients is lacking. Short-term oncological outcomes and functional outcomes are equivalent to open radical prostatectomy (RP. Safety outcomes are better in patients undergoing RARP when compared with open RP. Improved tools for predicting the presence of organ-confined disease (OCD are available. High-risk patients with OCD would be ideal candidates for RARP and would benefit most from surgery alone.

  18. Value of breast MRI as supplement to mammography and sonography for high risk breast cancer patients

    International Nuclear Information System (INIS)

    Schlossbauer, T.; Hellerhoff, K.; Reiser, M.

    2008-01-01

    The aim of this study is to give an overview on early detection of breast cancer in patients with an increased risk of breast cancer. Sensitivities and diagnostic accuracies of breast MRI, mammography and ultrasound were compared. A systematic literature search of the past 3 years was performed. Studies which compared breast imaging modalities and used image-guided biopsy results as standard of reference were included. Patients included had to have had an increased lifetime risk for breast cancer (>15%). Regarding sensitivity and diagnostic accuracy, breast MRI performed best in comparison to the other modalities within this collective of patients. Sensitivities ranged from 71-100%, 0-78%, and 13-65%, for MRI, mammography, and ultrasound, respectively Breast MRI is a well established tool for screening in patients at high risk for developing breast cancer and is a valuable supplement to mammography and ultrasound within this selected cohort of patients. (orig.) [de

  19. Endocrine therapy for breast cancer prevention in high-risk women: clinical and economic considerations.

    Science.gov (United States)

    Groom, Amy G; Younis, Tallal

    2016-01-01

    The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their "value for money" in various health care jurisdictions.

  20. HDR Brachytherapy in the Management of High-Risk Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Susan Masson

    2012-01-01

    Full Text Available High-dose-rate (HDR brachytherapy is used with increasing frequency for the treatment of prostate cancer. It is a technique which allows delivery of large individual fractions to the prostate without exposing adjacent normal tissues to unacceptable toxicity. This approach is particularly favourable in prostate cancer where tumours are highly sensitive to dose escalation and to increases in radiotherapy fraction size, due to the unique radiobiological behaviour of prostate cancers in contrast with other malignancies. In this paper we discuss the rationale and the increasing body of clinical evidence for the use of this technique in patients with high-risk prostate cancer, where it is combined with external beam radiotherapy. We highlight practical aspects of delivering treatment and discuss toxicity and limitations, with particular reference to current practice in the United Kingdom.

  1. Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Zieger, Karsten; Wiuf, Carsten; Jensen, Klaus Møller-Ernst; Ørntoft, Torben Falck; Dyrskjøt, Lars

    2009-01-01

    Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1) or high grade of dysplasia are at 'high risk' of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI) is associated with high tumor stage and grade, and possibly with the risk of progression. To investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with 'high-risk' non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical) resections and full prospective clinical follow-up (> 5 years). We investigated primary lesions in 59, and recurrent lesions in 66 cases. We used Affymetrix GeneChip ® Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes) in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays). Chromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a 'high-risk' tumor). However, about 25% of the 'high-risk' tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes. Chromosomal instability (CI) was associated with 'high risk' tumors

  2. Screening women at high risk of breast cancer on the basis of evidence

    International Nuclear Information System (INIS)

    Warren, Ruth

    2001-01-01

    Geneticists are able to identify the risk of breast cancer. Strategies on offer include prevention, early diagnosis by screening, and prophylactic surgery. This paper analyses the evidence for offering screening. The radiation dose of mammography has been measured, but the risk is not fully known. Mammography screening of women of 40-50 years in the normal population has known effect. Little evidence is available for women under 40 years or for women with genetic susceptibility to breast cancer. Dense parenchymal pattern is associated with high grade cancers, and is both a risk factor and a reason for impaired screening sensitivity. Whether this applies to younger women or women at high risk is speculative. The pathological features of the cancers in gene carriers show differences from those occurring in normal women. This work should be correlated with imaging features. There is no literature to support the use of newer imaging methods in these women. Ultrasound and MRI avoid radiation and may be useful in dense breasts. SestaMIBI and PET scanning are not yet mature enough for screening, and may never have such a role. Any newer modality must be subjected to a formal randomised trial before being offered to screen women at high risk

  3. Sun-protective behaviors in populations at high risk for skin cancer

    Science.gov (United States)

    Diao, Diana Y; Lee, Tim K

    2014-01-01

    Over 3 million new cases of skin cancer are diagnosed in the US annually. Melanoma, a subtype of skin cancer that can be fatal if the disease is not detected and treated at an early stage, is the most common cancer for those aged 25–29 years and the second most common cancer in adolescents and young adults aged 15–29 years. The primary carcinogen for the genesis of skin cancers is ultraviolet light from solar radiation and tanning beds. In spite of massive health campaigns to raise public awareness on ultraviolet radiation, sun-protective practices still fall behind. A plausible explanation is the lack of behavioral change in the populations at risk; in this review article, we examine sun-protective behavior in the four high-risk skin cancer groups: skin cancer survivors, individuals with a family history of melanoma, individuals with physical characteristics associated with skin cancer risk, and organ transplantation patients. Findings in the literature demonstrate that increased knowledge and awareness does not consequently translate into behavioral changes in practice. Behavior can differ as a result of different attitudes and beliefs, depending on the population at risk. Thus, intervention should be tailored to the population targeted. A multidisciplinary health team providing consultation and education is required to influence these much needed changes. PMID:24379732

  4. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

    Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

  5. Should a Sentinel Node Biopsy Be Performed in Patients with High-Risk Breast Cancer?

    International Nuclear Information System (INIS)

    Westover, K.D.; Westover, M.B.; Winer, E.P.; Richardson, A.L.; Iglehart, J.D.; Punglia, R.S.

    2011-01-01

    A negative sentinel lymph node (SLN) biopsy spares many breast cancer patients the complications associated with lymph node irradiation or additional surgery. However, patients at high risk for nodal involvement based on clinical characteristics may remain at unacceptably high risk of axillary disease even after a negative SLN biopsy result. A Bayesian nomogram was designed to combine the probability of axillary disease prior to nodal biopsy with customized test characteristics for an SLN biopsy and provides the probability of axillary disease despite a negative SLN biopsy. Users may individualize the sensitivity of an SLN biopsy based on factors known to modify the sensitivity of the procedure. This tool may be useful in identifying patients who should have expanded up front exploration of the axilla or comprehensive axillary irradiation

  6. Contemporary management of men with high-risk localized prostate cancer in the United States.

    Science.gov (United States)

    Weiner, A B; Matulewicz, R S; Schaeffer, E M; Liauw, S L; Feinglass, J M; Eggener, S E

    2017-09-01

    Surgery and radiation-based therapies are standard management options for men with clinically localized high-risk prostate cancer (PCa). Contemporary patterns of care are unknown. We hypothesize the use of surgery has steadily increased in more recent years. Using the National Cancer Data Base for 2004-2013, all men diagnosed with high-risk localized PCa were identified using National Comprehensive Cancer Network criteria. Temporal trends in initial management were assessed. Multivariable logistic regression was used to evaluate demographic and clinical factors associated with undergoing radical prostatectomy (RP). In total, 127 391 men were identified. Use of RP increased from 26% in 2004 to 42% in 2013 (adjusted risk ratio (RR) 1.51, 95% CI 1.42-1.60, P<0.001), while external beam radiation therapy (EBRT) decreased from 49% to 42% (P<0.001). African American men had lower odds of undergoing RP (unadjusted rate of 28%, adjusted RR 0.69, 95% CI 0.66-0.72, <0.001) compared to White men (37%). Age was inversely associated with likelihood of receiving RP. Having private insurance was significantly associated with the increased use of RP (vs Medicare, adjusted odds ratio 1.04, 95% CI 1.01-1.08, P=0.015). Biopsy Gleason scores 8-10 with and without any primary Gleason 5 pattern were associated with decreased odds of RP (vs Gleason score ⩽6, both P<0.001). Academic and comprehensive cancer centers were more likely to perform RP compared to community hospitals (both P<0.001). The likelihood of receiving RP for high-risk PCa dramatically increased from 2004 to 2013. By 2013, the use of RP and EBRT were similar. African American men, elderly men and those without private insurance were less likely to receive RP.

  7. High biologically effective dose radiation therapy using brachytherapy in combination with external beam radiotherapy for high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Keisei Okamoto

    2017-02-01

    Full Text Available Purpose : To evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR brachytherapy in combination with external beam radiotherapy (EBRT and short-term androgen deprivation therapy (ADT. Material and methods : From 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT. The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%, 61 patients with 2 high-risk factors (43%, and 22 patients with 3 high-risk factors (15% including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition. Results : Six patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS rate of 97.2%, and an overall survival (OS rate of 95.5%. Conclusions : High-dose (BED ≥ 220 Gy radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further.

  8. Sun-protective behaviors in populations at high risk for skin cancer

    Directory of Open Access Journals (Sweden)

    Diao DY

    2013-12-01

    Full Text Available Diana Y Diao,1 Tim K Lee1,21Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada; 2Cancer Control Research Program, BC Cancer Agency, Vancouver, British Columbia, CanadaAbstract: Over 3 million new cases of skin cancer are diagnosed in the US annually. Melanoma, a subtype of skin cancer that can be fatal if the disease is not detected and treated at an early stage, is the most common cancer for those aged 25–29 years and the second most common cancer in adolescents and young adults aged 15–29 years. The primary carcinogen for the genesis of skin cancers is ultraviolet light from solar radiation and tanning beds. In spite of massive health campaigns to raise public awareness on ultraviolet radiation, sun-protective practices still fall behind. A plausible explanation is the lack of behavioral change in the populations at risk; in this review article, we examine sun-protective behavior in the four high-risk skin cancer groups: skin cancer survivors, individuals with a family history of melanoma, individuals with physical characteristics associated with skin cancer risk, and organ transplantation patients. Findings in the literature demonstrate that increased knowledge and awareness does not consequently translate into behavioral changes in practice. Behavior can differ as a result of different attitudes and beliefs, depending on the population at risk. Thus, intervention should be tailored to the population targeted. A multidisciplinary health team providing consultation and education is required to influence these much needed changes.Keywords: skin cancer, melanoma, risk, prevention, behaviour

  9. Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer.

    Science.gov (United States)

    Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira

    2017-01-01

    Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, pgastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all pgastritis classification may thus be useful for detecting these patients.

  10. End-of-Life Care for Blood Cancers: A Series of Focus Groups With Hematologic Oncologists

    Science.gov (United States)

    Odejide, Oreofe O.; Salas Coronado, Diana Y.; Watts, Corey D.; Wright, Alexi A.; Abel, Gregory A.

    2014-01-01

    Purpose: Hematologic cancers are associated with aggressive cancer-directed care near death and underuse of hospice and palliative care services. We sought to explore hematologic oncologists' perspectives and decision-making processes regarding end-of-life (EOL) care. Methods: Between September 2013 and January 2014, 20 hematologic oncologists from the Dana-Farber/Harvard Cancer Center participated in four focus groups regarding EOL care for leukemia, lymphoma, multiple myeloma, and hematopoietic stem-cell transplantation. Focus groups employed a semistructured format with case vignettes and open-ended questions and were followed by thematic analysis. Results: Many participants felt that identifying the EOL phase for patients with hematologic cancers was challenging as a result of the continuing potential for cure with advanced disease and the often rapid pace of decline near death. This difficulty was reported to result in later initiation of EOL care. Barriers to high-quality EOL care were also reported to be multifactorial, including unrealistic expectations from both physicians and patients, long-term patient-physician relationships resulting in difficulty conducting EOL discussions, and inadequacy of existing home-based EOL services. Participants also expressed concern that some EOL quality measures developed for solid tumors may be unacceptable for patients with blood cancers given their unique needs at the EOL (eg, palliative transfusions). Conclusion: Our analysis suggests that hematologic oncologists need better clinical markers for when to initiate EOL care. In addition, current quality measures may be inappropriate for identifying overly aggressive care for patients with blood cancers. Further research is needed to develop effective interventions to improve EOL care for this patient population. PMID:25294393

  11. The risk of melanoma and hematologic cancers in patients with psoriasis.

    Science.gov (United States)

    Reddy, Shivani P; Martires, Kathryn; Wu, Jashin J

    2017-04-01

    The risk of melanoma and hematologic cancers in patients with psoriasis is controversial. We sought to assess the risk of melanoma and hematologic cancers in patients with psoriasis, and the association with different treatments. We used case-control and retrospective cohort designs to determine melanoma or hematologic cancer risk in patients with psoriasis. Risk with treatment type was assessed using Fisher exact test. Patients with psoriasis had 1.53 times greater risk of developing a malignancy compared with patients without psoriasis (P < .01). There were no significant differences in malignancy risk among patients treated with topicals, phototherapy, systemics, or biologic agents. Patients with psoriasis and malignancy did not have significantly worse survival than patients without psoriasis. It is possible that patients developed malignancy subsequent to the follow-up time included in the study. Patients with psoriasis may experience an elevated risk of melanoma and hematologic cancers, compared with the general population. The risk is not increased by systemic or biologic psoriasis therapies. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Colorectal cancer screening of high-risk populations: A national survey of physicians

    Directory of Open Access Journals (Sweden)

    White Pascale M

    2012-01-01

    Full Text Available Abstract Background The incidence of colorectal cancer can be decreased by appropriate use of screening modalities. Patients with a family history of colon cancer and of African-American ethnicity are known to be at higher risk of developing colorectal cancer. We aimed to determine if there is a lack of physician knowledge for colorectal cancer screening guidelines based on family history and ethnicity. Between February and April 2009 an anonymous web-based survey was administered to a random sample selected from a national list of 25,000 internists, family physicians and gastroenterologists. A stratified sampling strategy was used to include practitioners from states with high as well as low CRC incidence. All data analyses were performed following data collection in 2009. Results The average knowledge score was 37 ± 18% among the 512 respondents. Gastroenterologists averaged higher scores compared to internists, and family physicians, p = 0.001. Only 28% of physicians correctly identified the screening initiation point for African-Americans while only 12% of physicians correctly identified the screening initiation point and interval for a patient with a family history of CRC. The most commonly cited barriers to referring high-risk patients for CRC screening were "patient refusal" and "lack of insurance reimbursement." Conclusions There is a lack of knowledge amongst physicians of the screening guidelines for high-risk populations, based on family history and ethnicity. Educational programs to improve physician knowledge and to reduce perceived barriers to CRC screening are warranted to address health disparities in colorectal cancer.

  13. Capecitabine and Oxaliplatin Before, During, and After Radiotherapy for High-Risk Rectal Cancer.

    Science.gov (United States)

    Larsen, Finn Ole; Markussen, Alice; Jensen, Benny V; Fromm, Anne L; Vistisen, Kirsten K; Parner, Vibeke K; Linnemann, Dorte; Hansen, Rasmus H; Johannesen, Helle H; Schou, Jakob V

    2017-06-01

    To evaluate the effect of capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer. Patients with rectum cancer T4 or T3 involving the mesorectal fascia was included in a prospective phase 2 trial. Liver or lung metastases were accepted if the surgeons found them resectable. The patients received 6 weeks of capecitabine and oxaliplatin before chemoradiotherapy (CRT), continued capecitabine and oxaliplatin during radiotherapy, and received 4 weeks of capecitabine and oxaliplatin after CRT. The patients received radiotherapy as intensity-modulated radiotherapy. Total mesorectal excision was planned 8 weeks after CRT. The patients were evaluated with magnetic resonance imaging (MRI) before start of treatment, after 6 weeks of chemotherapy, and again just before the operation. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR29 scoring system was used to evaluate adverse events. Fifty-two patients were enrolled between 2009 and 2012. The treatment was well tolerated, with only one death during treatment. Eighty percent of assessable patients experienced response to chemotherapy alone as evaluated by MRI, which increased to 94% after complete oncologic treatment. Forty-nine patients had a total mesorectal excision performed, all with a R0 resection and with a pathologic complete response of 20% for patients with T3 tumor and 7% for patients with T4 tumor. Five patients had metastases at study entry, while 47 patients had locally advanced rectal cancer without metastases. Of these 47 patients, overall survival and progression-free survival at 5 years was 72% and 62%, respectively, with a median follow-up of 60 months. This aggressive approach with capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer is safe and feasible; it also has an impressive response rate as measured by MRI and a promising 5-year overall survival. Copyright © 2016 Elsevier Inc. All rights

  14. Radiotherapy and androgen ablation for clinically localized high-risk prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pollack, Alan; Zagars, Gunar K; Kopplin, Susan

    1995-04-30

    Purpose: The response of patients with clinical stages T1-4 prostate cancer to radiotherapy is variable. A particularly poor prognostic group has been found to be comprised of those with pretreatment prostate specific antigen (PSA) levels above 30 ng/ml with any tumor grade, or PSA levels > 10 and {<=} 30 with tumors grade 3 or 4. These patients have over an 80% actuarial risk of biochemical failure 3 years after definitive external beam radiotherapy. Thus, patients with these high-risk features require more aggressive therapy. During the last 3-4 years, the policy to treat such patients with radiotherapy and androgen ablation (XRT/HORM) was instituted. A retrospective comparison was made between high-risk patients treated with radiotherapy alone (XRT) vs. XRT/HORM. Methods and Materials: Between 1987 and 1991, there were 81 high-risk patients treated with XRT. There were 38 high-risk patients treated with XRT/HORM between 1990 and 1992. The median follow-up was 37 months for the XRT group and 22 months for the XRT/HORM group. No patient had clinical, radiographic, or pathologic evidence of lymph node involvement. The median dose to the prostate was 66 Gy for the XRT group and 68 Gy for the XRT/HORM group. Results: The distributions of several potential prognostic factors were analyzed. Significant differences between the groups were observed for tumor grade, pretreatment prostatic acid phosphatase, and age. The XRT/HORM group was composed of patients with worse features, including a greater proportion of patients with grade 4 tumors, more with abnormal acid phosphatase levels, and more under 60 years of age. The actuarial incidence of a rising PSA at 3 years for the XRT group was 81% vs. 15% for the XRT/HORM group (p < 0.0001). In addition, local relapse at 3 years was 34% for the XRT group and 15% for the XRT/HORM group (p < 0.02). There was no difference between the groups in terms of survival. Cox proportional hazards analyses were performed using several

  15. Selection of high risk groups among prognostically favorable patients with breast cancer.

    Science.gov (United States)

    Andersen, J A; Fischermann, K; Hou-Jensen, K; Henriksen, E; Andersen, K W; Johansen, H; Brincker, H; Mouridsen, H T; Castberg, T; Rossing, N; Rørth, M

    1981-01-01

    In a prospective, nationwide, decentralized breast cancer project conducted by The Danish Breast Cancer Cooperative Group (DBCG) the recurrence rate within the first year after surgery was analysed in relation to tumor anaplasia. One thousand forty-eight patients met the requirements of eligibility, i.e. tumor size less than or equal to 5 cm with negative axillary nodes, and no skin or deep invasion. The recurrence rates in tumors with anaplasia Grades I, II, and III were 4, 9, and 14%, respectively (p = 0.001). Therefore, it seems possible, prospectively, among otherwise prognostically favorable patients, to select a group with high risk of recurrence which might benefit from adjuvant systemic therapy. PMID:7247527

  16. Capecitabine and Oxaliplatin Before, During, and After Radiotherapy for High-Risk Rectal Cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Markussen, Alice; Jensen, Benny V

    2017-01-01

    PURPOSE: To evaluate the effect of capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer. PATIENTS AND METHODS: Patients with rectum cancer T4 or T3 involving the mesorectal fascia was included in a prospective phase 2 trial. Liver or lung metastases were...... accepted if the surgeons found them resectable. The patients received 6 weeks of capecitabine and oxaliplatin before chemoradiotherapy (CRT), continued capecitabine and oxaliplatin during radiotherapy, and received 4 weeks of capecitabine and oxaliplatin after CRT. The patients received radiotherapy...... as intensity-modulated radiotherapy. Total mesorectal excision was planned 8 weeks after CRT. The patients were evaluated with magnetic resonance imaging (MRI) before start of treatment, after 6 weeks of chemotherapy, and again just before the operation. The European Organization for Research and Treatment...

  17. Identification of patients with cancer with a high risk to develop delirium.

    Science.gov (United States)

    Neefjes, Elisabeth C W; van der Vorst, Maurice J D L; Verdegaal, Bertha A T T; Beekman, Aartjan T F; Berkhof, Johannes; Verheul, Henk M W

    2017-08-01

    Delirium deteriorates the quality of life in patients with cancer, but is frequently underdiagnosed and not adequately treated. In this study, we evaluated the occurrence of delirium and its risk factors in patients admitted to the hospital for treatment or palliative care in order to develop a prediction model to identify patients at high risk for delirium. In a period of 1.5 years, we evaluated the risk of developing delirium in 574 consecutively admitted patients with cancer to our academic oncology department with the Delirium Observation Screening Scale. Risk factors for delirium were extracted from the patient's chart. A delirium prediction algorithm was constructed using tree analysis, and validated with fivefold cross-validation. A total of 574 patients with cancer were acutely (42%) or electively (58%) admitted 1733 times. The incidence rate of delirium was 3.5 per 100 admittances. Tree analysis revealed that the predisposing factors of an unscheduled admittance and a metabolic imbalance accurately predicted the development of delirium. In this group the incidence rate of delirium was 33 per 100 patients (1:3). The AUC of the model was 0.81, and 0.65 after fivefold cross-validation. We identified that especially patients undergoing an unscheduled admittance with a metabolic imbalance do have a clinically relevant high risk to develop a delirium. Based on these factors, we propose to evaluate preventive treatment of these patients when admitted to the hospital in order to improve their quality of life. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  18. Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

    International Nuclear Information System (INIS)

    Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe; Rubin, Daniel L.; Napel, Sandy; Diehn, Maximilian; Loo, Billy W.; Li, Ruijiang

    2016-01-01

    Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from "1"8F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust intratumor

  19. Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study.

    Science.gov (United States)

    Wu, Jia; Gensheimer, Michael F; Dong, Xinzhe; Rubin, Daniel L; Napel, Sandy; Diehn, Maximilian; Loo, Billy W; Li, Ruijiang

    2016-08-01

    To develop an intratumor partitioning framework for identifying high-risk subregions from (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. In this institutional review board-approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). We propose a robust intratumor partitioning method to identify clinically relevant, high-risk

  20. Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Rubin, Daniel L. [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California (United States); Napel, Sandy [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Li, Ruijiang, E-mail: rli2@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

    2016-08-01

    Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust

  1. Identifying women with dense breasts at high risk for interval cancer: a cohort study.

    Science.gov (United States)

    Kerlikowske, Karla; Zhu, Weiwei; Tosteson, Anna N A; Sprague, Brian L; Tice, Jeffrey A; Lehman, Constance D; Miglioretti, Diana L

    2015-05-19

    Twenty-one states have laws requiring that women be notified if they have dense breasts and that they be advised to discuss supplemental imaging with their provider. To better direct discussions of supplemental imaging by determining which combinations of breast cancer risk and Breast Imaging Reporting and Data System (BI-RADS) breast density categories are associated with high interval cancer rates. Prospective cohort. Breast Cancer Surveillance Consortium (BCSC) breast imaging facilities. 365,426 women aged 40 to 74 years who had 831,455 digital screening mammography examinations. BI-RADS breast density, BCSC 5-year breast cancer risk, and interval cancer rate (invasive cancer ≤12 months after a normal mammography result) per 1000 mammography examinations. High interval cancer rate was defined as more than 1 case per 1000 examinations. High interval cancer rates were observed for women with 5-year risk of 1.67% or greater and extremely dense breasts or 5-year risk of 2.50% or greater and heterogeneously dense breasts (24% of all women with dense breasts). The interval rate of advanced-stage disease was highest (>0.4 case per 1000 examinations) among women with 5-year risk of 2.50% or greater and heterogeneously or extremely dense breasts (21% of all women with dense breasts). Five-year risk was low to average (0% to 1.66%) for 51.0% of women with heterogeneously dense breasts and 52.5% with extremely dense breasts, with interval cancer rates of 0.58 to 0.63 and 0.72 to 0.89 case per 1000 examinations, respectively. The benefit of supplemental imaging was not assessed. Breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient-provider discussions about alternative screening strategies. National Cancer Institute.

  2. Neoadjuvant Treatment of High-Risk, Clinically Localized Prostate Cancer Prior to Radical Prostatectomy.

    Science.gov (United States)

    Pietzak, Eugene J; Eastham, James A

    2016-05-01

    Multimodal strategies combining local and systemic therapy offer the greatest chance of cure for many with men with high-risk prostate cancer who may harbor occult metastatic disease. However, no systemic therapy combined with radical prostatectomy has proven beneficial. This was in part due to a lack of effective systemic agents; however, there have been several advancements in the metastatic and castrate-resistant prostate cancer that might prove beneficial if given earlier in the natural history of the disease. For example, novel hormonal agents have recently been approved for castration-resistant prostate cancer with some early phase II neoadjuvant showing promise. Additionally, combination therapy with docetaxel-based chemohormonal has demonstrated a profound survival benefit in metastatic hormone-naïve patients and might have a role in eliminating pre-existing ADT-resistant tumor cells in the neoadjuvant setting. The Cancer and Leukemia Group B (CALGB)/Alliance 90203 trial has finished accrual and should answer the question as to whether neoadjuvant docetaxel-based chemohormonal therapy provides an advantage over prostatectomy alone. There are also several promising targeted agents and immunotherapies under investigation in phase I/II trials with the potential to provide benefit in the neoadjuvant setting.

  3. Communication and information-giving in high-risk breast cancer consultations: influence on patient outcomes.

    Science.gov (United States)

    Lobb, E A; Butow, P N; Barratt, A; Meiser, B; Gaff, C; Young, M A; Haan, E; Suthers, G; Gattas, M; Tucker, K

    2004-01-26

    This longitudinal study aimed to document (i) the information-giving and patient-communication styles of clinical geneticists and genetic counsellors (consultants) in familial breast cancer clinics and (ii) assess the effect of these styles on women's knowledge, whether their expectations were met, satisfaction, risk perception and psychological status. A total of 158 women from high-risk breast cancer families completed self-report questionnaires at 2 weeks preconsultation and 4 weeks postconsultation. The consultations were audiotaped, transcribed and coded. Multivariate logistic regressions showed that discussing prophylactic mastectomy (P=0.00) and oophorectomy (P=0.01) led to women having significantly more expectations met; discussing genetic testing significantly decreased anxiety (P=0.03) and facilitating understanding significantly decreased depression (P=0.05). Receiving a summary letter of the consultation significantly lowered anxiety (P=0.01) and significantly increased the accuracy of perceived risk (P=0.02). Women whose consultant used more supportive communications experienced significantly more anxiety about breast cancer at the 4 weeks follow-up (P=0.00). These women were not significantly more anxious before genetic counselling. In conclusion, this study found that consultants vary in the amount of information they give and the way they communicate; and this variation can result in better or worse psychosocial outcomes. Greater use of supportive and counselling communications appeared to increase anxiety about breast cancer. Identifying methods to assist consultants to address emotional issues effectively may be helpful.

  4. High-risk older smokers' perceptions, attitudes, and beliefs about lung cancer screening

    International Nuclear Information System (INIS)

    Cataldo, Janine K.

    2016-01-01

    The US Preventive Services Task Force recommends that smokers aged 55–80 should be screened annually with low-dose computed tomography (LDCT). This study identified demographics, smoking history, health risk perceptions, knowledge, and attitudes factors of older smokers (≥55 years) related to LDCT agreement. Using binary logistic regression, a predictive model of factors to explain LDCT agreement was produced. This is a cross-sectional, national, online survey of 338 older smokers (≥55 years) with a ≥30 pack-year smoking history. Over 82% of the sample believed that a person who continues to smoke after the age of 40 has at least a 25% chance of developing lung cancer and 77.3% would “agree to a LDCT today”. Using chi-square analyses, six variables that were significant at the 0.10 level were selected for inclusion in model development. Four of the independent variables made a unique statistically significant contribution to the model: perceives accuracy of the LDCT as an important factor in the decision to have a LDCT scan; believes that early detection of LC will result in a good prognosis; believes that they are at high risk for lung cancer; and is not afraid of CT scans. Of note, only 10.9% believed that a negative CT scan result would mean that they could continue to smoke. Older smokers are aware of the risks of smoking, are interested in smoking cessation, and most are interested in and positive about LDCT. Cognitive aspects of participation in screening are key to increasing the uptake of lung cancer screening among high-risk smokers

  5. Androgenic alopecia is not useful as an indicator of men at high risk of prostate cancer.

    Science.gov (United States)

    Cremers, Ruben G; Aben, Katja K; Vermeulen, Sita H; den Heijer, Martin; van Oort, Inge M; Kiemeney, Lambertus A

    2010-12-01

    Androgens are assumed to play a central role in the pathophysiology of both prostate cancer (PC) and androgenic alopecia (AA). A correlation between the two phenotypes may be relevant for identification of men at high risk of PC. We evaluated the association between AA at different ages and PC in a large case-control study. The case group comprised 938 PC patients recruited from a population-based cancer registry. The controls (n = 2160) were a random sample of the male general population. All subjects completed a questionnaire on risk factors for cancer, including questions on hair pattern at different ages using an adapted version of the Hamilton-Norwood scale, race and family history of PC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression. Baldness at early age appeared to be associated with a lower risk of PC (baldness at age 20: OR = 0.86; 95% CI 0.69-1.07 and baldness at age 40: OR = 0.81; 95% CI 0.70-0.96). Baldness at completion of the questionnaire was not associated with PC: OR = 1.10; 95% CI 0.89-1.34. An isolated 'frontal baldness' or 'vertex baldness' pattern was not significantly associated with PC at any age. Presence of a combined 'frontal and vertex' baldness pattern at age 40 was associated with a decreased risk of PC (OR = 0.62; 95% CI 0.45-0.86). There were no significant associations between AA and aggressive PC. We did not find consistent positive associations between AA at different ages and PC. Surprisingly, if anything, baldness at early age is inversely related to PC in this study. Androgenic alopecia is not useful as an indicator of men at high risk of PC. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy?

    International Nuclear Information System (INIS)

    Wan, Juefeng; Liu, Kaitai; Li, Kaixuan; Li, Guichao; Zhang, Zhen

    2015-01-01

    To identify dosimetric parameters associated with acute hematologic toxicity (HT) in rectal cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. Ninety-three rectal cancer patients receiving concurrent capecitabine and pelvic intensity-modulated radiation therapy (IMRT) were analyzed. Pelvic bone marrow (PBM) was contoured for each patient and divided into three subsites: lumbosacral spine (LSS), ilium, and lower pelvis (LP). The volume of each site receiving 5–40 Gy (V 5, V10, V15, V20, V30, and V40, respectively) as well as patient baseline clinical characteristics was calculated. The endpoint for hematologic toxicity was grade ≥ 2 (HT2+) leukopenia, neutropenia, anemia or thrombocytopenia. Logistic regression was used to analyze correlation between dosimetric parameters and grade ≥ 2 hematologic toxicity. Twenty-four in ninety-three patients experienced grade ≥ 2 hematologic toxicity. Only the dosimetric parameter V40 of lumbosacral spine was correlated with grade ≥ 2 hematologic toxicity. Increased pelvic lumbosacral spine V40 (LSS-V40) was associated with an increased grade ≥ 2 hematologic toxicity (p = 0.041). Patients with LSS-V40 ≥ 60 % had higher rates of grade ≥ 2 hematologic toxicity than did patients with lumbosacral spine V40 < 60 % (38.3 %, 18/47 vs.13 %, 6/46, p =0.005). On univariate and multivariate logistic regression analysis, lumbosacral spine V40 and gender was also the variable associated with grade ≥ 2 hematologic toxicity. Female patients were observed more likely to have grade ≥ 2 hematologic toxicity than male ones (46.9 %, 15/32 vs 14.8 %, 9/61, p =0.001). Lumbosacral spine -V40 was associated with clinically significant grade ≥ 2 hematologic toxicity. Keeping the lumbosacral spine -V40 < 60 % was associated with a 13 % risk of grade ≥ 2 hematologic toxicity in rectal cancer patients undergoing concurrent chemoradiotherapy

  7. Complementary and alternative medicine use in patients with hematological cancers in Malaysia.

    Science.gov (United States)

    Gan, G G; Leong, Y C; Bee, P C; Chin, E; Teh, A K H

    2015-08-01

    Complementary and alternative medicine (CAM) is often used by cancer patients, but not many studies had been published on the prevalence of CAM use in patients with hematological cancers. This study aims to determine the prevalence of CAM and type of CAM used in this group of patients in a multiracial and multicultural country. This is a cross-sectional survey carried out in two hospitals in Malaysia. Patients with underlying hematological cancers were asked to complete the questionnaires on CAM and the Hospital Anxiety and Depression Scale. A total of 245 patients participated. The prevalence of CAM use was 70.2 %. The most common types of CAM used are biological-based therapies (90.2 %) and mind-body interventions (42 %). Vitamin and diet supplements (68.6 %) and folk/herb remedies (58 %) are the most common biological-based therapies used. There is no significant association of CAM use with age, gender, education level, and household income. Female patients are more likely to use more than one CAM therapies. The most common reason reported for CAM use was to boost immunity (57 %) and cure (24 %). Majority of patients (65 %) felt CAM was effective, and 60 % did not inform their physicians regarding CAM usage. In view of the high prevalence of CAM use in patients with hematological cancers, it is important that the physicians play an active role in seeking information from patients and to monitor possible drug-vitamin-herbal interactions.

  8. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    NARCIS (Netherlands)

    Gast, M.C.; van Tinteren, H.; Bontenbal, M.; van Hoesel, R.Q.; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; de Vries, E.G.; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

    2008-01-01

    Background: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods: Two

  9. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    NARCIS (Netherlands)

    M.C.W. Gast; H. van Tinteren (Harm); M. Bontenbal (Marijke); R.Q.G.C.M. van Hoesel (René); M.A. Nooij; S. Rodenhuis (Sjoerd); P.N. Span (Paul); V.C.G. Tjan-Heijnen (Vivianne); E. de Vries (Esther); N. Harris (Nathan); J.W.R. Twisk (Jos); J.H.M. Schellens (Jan); J.H. Beijnen (Jos)

    2008-01-01

    textabstractBackground: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

  10. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    NARCIS (Netherlands)

    Gast, Marie-Christine W.; van Tinteren, Harm; Bontenbal, Marijke; van Hoesel, Rene Q. G. C. M.; Nooij, Marianne A.; Rodenhuis, Sjoerd; Span, Paul N.; Tjan-Heijnen, Vivianne C. G.; de Vries, Elisabeth G. E.; Harris, Nathan; Twisk, Jos W. R.; Schellens, Jan H. M.; Beijnen, Jos H.

    2008-01-01

    ABSTRACT: BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

  11. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients.

    NARCIS (Netherlands)

    Gast, M.C.; Tinteren, H. van; Bontenbal, M.; Hoesel, R.Q. van; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; Vries, E.G.F. de; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

    2008-01-01

    BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two

  12. Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Koontz, Bridget F.; Quaranta, Brian P.; Pura, John A.; Lee, W.R.; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S.; Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W.

    2013-01-01

    Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes

  13. Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Koontz, Bridget F., E-mail: Bridget.Koontz@duke.edu [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Quaranta, Brian P. [21st Century Oncology, Asheville, North Carolina (United States); Pura, John A. [Division of Biostatistics, Duke Cancer Institute, Durham, North Carolina (United States); Lee, W.R.; Vujaskovic, Zeljko [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Gerber, Leah [Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Haake, Michael [Southeast Radiation Oncology, Charlotte, North Carolina (United States); Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W. [Department of Surgery, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States)

    2013-09-01

    Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

  14. Neoadjuvant treatment and adjuvant radiotherapy for patients with high risk prostate cancer and radical prostatectomy

    International Nuclear Information System (INIS)

    Scorticati, Carlos; Aguilar, Jorge A.; Gonzalez Granda, Pablo; Mendez, Fernando; Montiel, Raul; Rege, Eduardo; Alvarez, Patricio; Lopez, Miguel A.; Rizzi, Alfredo; Mazza, Osvaldo

    2009-01-01

    Introduction and Objectives: To analyze the results of the treatment in patients with cancer of prostate of high risk. Material and Method: Retrospective and observational analysis of 130 patients operated by CAP of high risk (criteria of D'Amico) average 41,48 months, divided in form nonrandomized in three groups 1: radical prostatectomy, 2: neoadjuvant hormonoterapy (BAC) + PR, 3: BAC + PR + x-ray (RT). Statistical analysis: multivaried, test of curved Chi2 and p statistical and of Kaplan Meier. Results: Biochemical relapse 68 patients (52.3%), average 23,37 months. Without differences according to therapeutic modality (p: 0.043). In the multivaried analysis of the 3 factors of presurgical, single risk we found a statistically significant relation in the coexistence of the 3 factors with the presence of positive margin in the PR piece. (p: 0,002). The analysis to make or not, neoadjuvant BAC without significant difference (p: 0,403) evaluating in such the rate of M+, actuarial global survival according to curves of Kaplan Meier to 5 and 10 years (P: 0,5257) and survival 5 actuarial specific cancer to and 10a (P: 0,2165). Conclusions: Without significant differences in: RB, clinical progression, pathological relapse, global and specific survival, rate of positive surgical margins. The 3 criteria of D'Amico were predictive of positive surgical margins and RB, the patients with RB in group 2 presented/displayed greater risk of clinical progression, the PR demonstrated a global survival and specify actuarial to 10 years greater to 50%, considering it therapeutic an option been worth. (authors) [es

  15. The validation and clinical implementation of BRCAplus: a comprehensive high-risk breast cancer diagnostic assay.

    Directory of Open Access Journals (Sweden)

    Hansook Kim Chong

    Full Text Available Breast cancer is the most commonly diagnosed cancer in women, with 10% of disease attributed to hereditary factors. Although BRCA1 and BRCA2 account for a high percentage of hereditary cases, there are more than 25 susceptibility genes that differentially impact the risk for breast cancer. Traditionally, germline testing for breast cancer was performed by Sanger dideoxy terminator sequencing in a reflexive manner, beginning with BRCA1 and BRCA2. The introduction of next-generation sequencing (NGS has enabled the simultaneous testing of all genes implicated in breast cancer resulting in diagnostic labs offering large, comprehensive gene panels. However, some physicians prefer to only test for those genes in which established surveillance and treatment protocol exists. The NGS based BRCAplus test utilizes a custom tiled PCR based target enrichment design and bioinformatics pipeline coupled with array comparative genomic hybridization (aCGH to identify mutations in the six high-risk genes: BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11. Validation of the assay with 250 previously characterized samples resulted in 100% detection of 3,025 known variants and analytical specificity of 99.99%. Analysis of the clinical performance of the first 3,000 BRCAplus samples referred for testing revealed an average coverage greater than 9,000X per target base pair resulting in excellent specificity and the sensitivity to detect low level mosaicism and allele-drop out. The unique design of the assay enabled the detection of pathogenic mutations missed by previous testing. With the abundance of NGS diagnostic tests being released, it is essential that clinicians understand the advantages and limitations of different test designs.

  16. Galactomannan and Polymerase Chain Reaction-Based Screening for Invasive Aspergillosis Among High-Risk Hematology Patients: A Diagnostic Meta-analysis.

    Science.gov (United States)

    Arvanitis, Marios; Anagnostou, Theodora; Mylonakis, Eleftherios

    2015-10-15

    Screening of high-risk patients for invasive aspergillosis (IA) has the potential to decrease the use of empiric antifungal agents. However, the performance of different screening methods has not been studied. We performed a meta-analysis of published studies to assess the diagnostic performance of galactomannan (GM) and polymerase chain reaction (PCR) as weekly screening tests in high-risk populations. The sensitivity and specificity of 6 approaches combining GM and PCR were estimated using the bivariate model. Thirteen studies with 1670 patients met our inclusion criteria. Single positive test results had modest sensitivity and specificity for screening (respectively, 92% and 90% for GM; 84% and 76% for PCR). The screening approach with the highest sensitivity was the one that used at least 1 GM- or PCR-positive result to define a positive episode, achieving a sensitivity of 99%, significantly higher than any single test (P = .0018 compared with GM and P value of 100%, whereas the presence of at least 2 positive results is highly suggestive of an active infection with a positive predictive value of 88%. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

    Science.gov (United States)

    Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena

    2015-01-01

    Objective Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Methods Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Results Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Conclusion Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III. PMID:26197768

  18. High risk men's perceptions of pre-implantation genetic diagnosis for hereditary breast and ovarian cancer.

    Science.gov (United States)

    Quinn, Gwendolyn P; Vadaparampil, Susan T; Miree, Cheryl A; Lee, Ji-Hyun; Zhao, Xiuhua; Friedman, Susan; Yi, Susan; Mayer, James

    2010-10-01

    Pre-implantation genetic diagnosis (PGD) is an assisted reproductive technology procedure which provides parents with the option of conducting genetic analyses to determine if a mutation is present in an embryo. Though studies have discussed perceptions of PGD from a general population, couples or high-risk women, no studies to date have specifically examined PGD usage among men. This study sought to explore perceptions and attitudes towards PGD among males who either carry a BRCA mutation or have a partner or first degree relative with a BRCA mutation. A cross-sectional survey was conducted among 228 men visiting the Facing Our Risk of Cancer Empowered or Craigslist website. Eligibility criteria included men who self-reported they had been tested for a BRCA mutation or had a partner or first degree relative tested for a BRCA mutation. A 41-item survey assessed socio-demographic, clinical characteristics, PGD knowledge and attitudinal factors and consideration of the use of PGD. Differences in proportions of subgroups were tested using the Monte Carlo exact test for categorical data. A multiple logistic regression model was then built through a backward elimination procedure. Although 80% of men reported being previously unfamiliar with PGD, after learning the definition of PGD, 34% of the 228 respondents then said they would 'ever consider the use of PGD'. Respondents who thought of PGD only in terms of 'health and safety' were almost three times more likely (OR = 2.82; 95% 1.19-6.71) to 'ever consider the use of PGD' compared with respondents who thought of PGD in terms of both 'health and safety', and 'religion and morality'. As with other anonymous web-based surveys, we cannot verify clinical characteristics that may impact consideration of PGD use. Our findings indicate high-risk men need more information about PGD and may benefit from educational materials to assist them in reproductive decision-making.

  19. Incidence and survival of stomach cancer in a high-risk population of Chile

    Science.gov (United States)

    Heise, Katy; Bertran, Enriqueta; Andia, Marcelo E; Ferreccio, Catterina

    2009-01-01

    AIM: To study the incidence and survival rate of stomach cancer (SC) and its associated factors in a high risk population in Chile. METHODS: The population-based cancer registry of Valdivia, included in the International Agency for Research on Cancer system, covers 356 396 residents of Valdivia Province, Southern Chile. We studied all SC cases entered in this Registry during 1998-2002 (529 cases). Population data came from the Chilean census (2002). Standardized incidence rates per 100 000 inhabitants (SIR) using the world population, cumulative risk of developing cancer before age 75, and rate ratios by sex, age, ethnicity and social factors were estimated. Relative survival (Ederer II method) and age-standardized estimates (Brenner method) were calculated. Specific survival rates (Kaplan-Meier) were measured at 3 and 5 years and survival curves were analyzed with the Logrank and Breslow tests. Survival was studied in relation to demographics, clinical presentation, laboratory results and medical management of the cases. Those variables significantly associated with survival were later included in a Cox multivariate model. RESULTS: Between 1998 and 2002, 529 primary gastric cancers occurred in Valdivia (crude incidence rate 29.2 per 100 000 inhabitants). Most cases were male (69.0%), residents of urban areas (57.5%) and Hispanic (83.2%), with a low education level (84.5% Mapuche ethnicity only significant for women (RR 2.2, 95% CI: 1.2-3.7). Of all cases, 76.4% were histologically confirmed, 11.5% had a death certificate only (DCO), 56.1% were TNM stage IV; 445 cases (84.1%) were eligible for survival analysis, all completed five years follow-up; 42 remained alive, 392 died of SC and 11 died from other causes. Specific 5-year survival, excluding cases with DCO, was 10.6% (95% CI: 7.7-13.5); 5-year relative survival rate was 12.3% (95% CI: 9.1-16.1), men 10.9% (95% CI: 7.4-15.2) and women 16.1% (95% CI: 9.5-24.5). Five-year specific survival was higher for patients

  20. Optimal management of high-risk T1G3 bladder cancer: a decision analysis.

    Directory of Open Access Journals (Sweden)

    Girish S Kulkarni

    2007-09-01

    Full Text Available BACKGROUND: Controversy exists about the most appropriate treatment for high-risk superficial (stage T1; grade G3 bladder cancer. Immediate cystectomy offers the best chance for survival but may be associated with an impaired quality of life compared with conservative therapy. We estimated life expectancy (LE and quality-adjusted life expectancy (QALE for both of these treatments for men and women of different ages and comorbidity levels. METHODS AND FINDINGS: We evaluated two treatment strategies for high-risk, T1G3 bladder cancer using a decision-analytic Markov model: (1 Immediate cystectomy with neobladder creation versus (2 conservative management with intravesical bacillus Calmette-Guérin (BCG and delayed cystectomy in individuals with resistant or progressive disease. Probabilities and utilities were derived from published literature where available, and otherwise from expert opinion. Extensive sensitivity analyses were conducted to identify variables most likely to influence the decision. Structural sensitivity analyses modifying the base case definition and the triggers for cystectomy in the conservative therapy arm were also explored. Probabilistic sensitivity analysis was used to assess the joint uncertainty of all variables simultaneously and the uncertainty in the base case results. External validation of model outputs was performed by comparing model-predicted survival rates with independent published literature. The mean LE of a 60-y-old male was 14.3 y for immediate cystectomy and 13.6 y with conservative management. With the addition of utilities, the immediate cystectomy strategy yielded a mean QALE of 12.32 y and remained preferred over conservative therapy by 0.35 y. Worsening patient comorbidity diminished the benefit of early cystectomy but altered the LE-based preferred treatment only for patients over age 70 y and the QALE-based preferred treatment for patients over age 65 y. Sensitivity analyses revealed that patients

  1. Hormone Therapy in Breast Cancer Survivors and Those at High Risk for Breast Cancer.

    Science.gov (United States)

    Reid, Robert L

    2018-05-10

    Women and health care providers are often fearful of using hormone therapy to deal with distressing menopausal symptoms in circumstances where there is a perceived or real increased risk of breast cancer. This paper examines the evidence for and against hormone therapy use in 3 common clinical situations: the woman with a positive family history in a first-degree relative, the woman who has undergone risk-reducing salpingo-oophorectomy due to a known genetic mutation, and the woman in whom treatment of breast cancer has induced premature menopause.

  2. Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort

    Energy Technology Data Exchange (ETDEWEB)

    Teras, Lauren R., E-mail: lauren.teras@cancer.org [Epidemiology Research Program, American Cancer Society, Atlanta, GA (United States); Diver, W. Ryan [Epidemiology Research Program, American Cancer Society, Atlanta, GA (United States); Turner, Michelle C. [Centre for Research in Environmental Epidemiology (CREAL), Barcelona (Spain); Universitat Pompeu Fabra (UPF), Barcelona (Spain); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid (Spain); McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa (Canada); Krewski, Daniel [McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa (Canada); School of Epidemiology, Public Health and Disease Prevention, University of Ottawa, Ottawa, Ontario (Canada); Sahar, Liora [Statistics and Evaluation Center, American Cancer Society, Atlanta, GA (United States); Ward, Elizabeth [Intramural Research, American Cancer Society, Atlanta, GA (United States); Gapstur, Susan M. [Epidemiology Research Program, American Cancer Society, Atlanta, GA (United States)

    2016-07-15

    Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer. The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148 Bq/m{sup 3}) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74 Bq/m{sup 3}) radon levels (HR=1.63, 95% CI:1.23–2.18), and there was evidence of a dose-response relationship (HR{sub continuous}=1.38, 95% CI:1.15–1.65 per 100 Bq/m{sup 3}; p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. - Highlights: • This is the first prospective, general population study of residential radon and risk of hematologic cancer. • Findings from this study suggest that residential radon exposure may be a risk factor

  3. Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort

    International Nuclear Information System (INIS)

    Teras, Lauren R.; Diver, W. Ryan; Turner, Michelle C.; Krewski, Daniel; Sahar, Liora; Ward, Elizabeth; Gapstur, Susan M.

    2016-01-01

    Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer. The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148 Bq/m 3 ) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74 Bq/m 3 ) radon levels (HR=1.63, 95% CI:1.23–2.18), and there was evidence of a dose-response relationship (HR continuous =1.38, 95% CI:1.15–1.65 per 100 Bq/m 3 ; p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. - Highlights: • This is the first prospective, general population study of residential radon and risk of hematologic cancer. • Findings from this study suggest that residential radon exposure may be a risk factor for lymphoid

  4. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    Science.gov (United States)

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered.

  5. Breast MR imaging in women at high-risk of breast cancer. Is something changing in early breast cancer detection?

    International Nuclear Information System (INIS)

    Sardanelli, Francesco; Podo, Franca

    2007-01-01

    In the last few years, several papers have addressed the introduction of contrast-enhanced MR imaging for screening women at high risk for breast cancer. Taking in consideration five prospective studies, on 3,571 screened women with hereditary predisposition to the disease and 9,652 rounds, we found that 168 patients were diagnosed with breast cancer (155 screen-detected, eight interval, and five cancers excluded from analysis) with a detection rate per year of 1.7%. These cancers were small (49% equal to or less than 10 mm in diameter) but aggressive, 82% being invasive and 49% with histologic grade 3; however, only 19% of these invasive cancers were associated with nodal involvement. The pooled sensitivity was 16% for clinical breast examination, 40% for mammography, 43% for ultrasound, and 81% for MR. The positive predictive value (calculated on the basis of the number of invasive diagnostic procedures due to false positives) was 33%, 47%, 18%, and 53%, respectively. Aim of the present article is to present the historical development of MR imaging of breast tumors that made this application theoretically and technically possible, to explain what strategic problems we face in the presence of a hereditary predisposition to the disease, to review the main results of the published studies, and to outline open problems and future perspectives. (orig.)

  6. PET/CT in staging of the high risk prostate cancer

    International Nuclear Information System (INIS)

    Bergero, M.A.; David, C.; Dipatto, F.; Popeneciu, V.; Ríos, L.; Faccio, F.

    2016-01-01

    Objectives: In the last decade multimodal management of the high risk prostate cancer (HRPC) is a therapeutic option in selected patients and the staging of these patients depends on the current diagnostic methods (DM) which have low diagnostic accuracy for detecting metastasis (MTS). The positron emission tomography/computed tomography (PET/CT) would have a greater diagnostic accuracy and it is presented as a better DM for staging prostate cancer (PC). The aim of this article is present 2 patients in whom PET/CT modified the therapeutic decision and conduct a literature review. Materials and methods: 2 patients with HRPC who performed PET/CT and it modified the therapeutic behavior were described and a systematic review of the literature was conducted using PubMed, Embase, SciELO and Cochrane answering the question: has PET/CT a place in HRPC staging? Results: TPET/CT has a sensitivity and specificity between 19% to 100% and 67% to 98,5 %, respectively, in assessing nodal involvement by PC and between 84% to 96% and 92.3% to 100%, respectively, in assessing bone involvement by PC. Besides PET/CT allowed to modify the therapeutic behavior between 20% to 40% of the patients with PC. Conclusions: PET/CT has good specificity and moderate sensitivity for detecting lymph node MTS and good sensitivity and specificity for detecting bone MTS. Besides PET/CT modified the therapeutic behavior in 1/3 of cases and it allowed us to modify the therapeutic behavior in our series. (authors) [es

  7. An audit of referral and treatment patterns of high-risk prostate cancer patients in Alberta.

    Science.gov (United States)

    Alghamdi, Majed; Taggar, Amandeep; Tilley, Derek; Kerba, Marc; Kostaras, Xanthoula; Gotto, Geoffrey; Sia, Michael

    2016-01-01

    We aimed to determine the impact of clinical practice guidelines (CPG) on rates of radiation oncologist (RO) referral, androgen-deprivation therapy (ADT), radiation therapy (RT), and radical prostatectomy (RP) in patients with high-risk prostate cancer (HR-PCa). All men >18 years, diagnosed with PCa in 2005 and 2012 were identified from the Alberta Cancer Registry. Patient age, aggregated clinical risk group (ACRG) score, Gleason score (GS), pre-treatment prostate-specific antigen (PSA), RO referral, and treatment received were extracted from electronic medical records. Logistic regression modelling was used to examine associations between RO referral rates and relevant factors. HR-PCa was diagnosed in 261 of 1792 patients in 2005 and 435 of 2148 in 2012. Median age and ACRG scores were similar in both years (p>0.05). The rate of patients with PSA >20 were 67% and 57% in 2005 and 2012, respectively (p=0.004). GS ≤6 was found in 13% vs. 5% of patients, GS 7 in 27% vs. 24%, and GS ≥8 in 59% vs. 71% in 2005 and 2012, respectively (p<0.001). In 2005, RO referral rate was 68% compared to 56% in 2012 (p=0.001), use of RT + ADT was 53% compared to 32% (p<0.001), and RP rate was 9% vs. 17% (p=0.002). On regression analysis, older age, 2012 year of diagnosis and higher PSA were associated with decreased RO referral rates (odds ratios [OR] 0.49, 95% confidence interval [CI] 0.39-0.61; OR 0.51, 95% CI 0.34-0.76; and OR 0.64, 95% CI 0.39-0.61), respectively [p<0.001]). Since CPG creation in 2005, RO referral rates and ADT + RT use declined and RP rates increased, which demonstrates a need to improve adherence to CPG in the HR-PCa population.

  8. Cispaltino in radiotherapy and treatment of cancer advanced cervical and high risk

    International Nuclear Information System (INIS)

    Santini, A.; Mara, C.; Terradas, M.; Ferreira, V.; Torres, M.

    2010-01-01

    Fulltext: Uterine cervix cancer (CCU) is a frequent disease Uruguay, killing more than 100 women per year. The standard treatment CCU for patients with locoregionally advanced cataloged as (LRA), stages IIB-IVA and operated and in those patients with high risk factors relapse (AFR) was until 1999 the radiotherapy (RT) exclusive. in February that year the National Cancer Institute USA underwent a medical alert recommending the use of chemotherapy (CT) with concomitant RT (mainly cisplatin) in this group of patients. This alert was due to the publication of 5 randomized work showing an improvement in both the locoregional control and overall survival. In June 2000, both the RT Service ospital and Clinics in INDO, I modified the standard treatment of these patients by adding cisplatin 40mg/m2 weekly for the treatment of external RT. From that date until January 2003, 36 patients were included with CCU LRA or operated with AFR. the risk factors were: tumors larger than 4cm, parametrial invasion, lymph positive, involved margins, suboptimal surgery or deep infiltration stroma. 18 patients had stage IIIB or IV and of which 6 had failure obstructive acute renal (acute obstructive renal failure). Tolerance was acceptable, only one patient not tolerated treatment for severe leucopenia continuing exclusive RT; 68% had leukopenia grade - 2 and there was no increase in toxicity gastrointestinal or urinary. There were no treatment related deaths. When comparing historical results verified an improvement in complete answers to all stages primarily for advanced in the second period with the addition of cisplatin. Stage IB2-IIB: 52% (RT-CT) - 45% RT (historical) ns. Stage IIB: 22% (RT-CT) - 15% RT (historical) sl. In those patients with acute obstructive renal failure in any complete response was not achieved. Due to the short track differences still not tested for the surviving whole or survive disease-free

  9. Does Specialty Bias Trump Evidence in the Management of High-risk Prostate Cancer?

    Science.gov (United States)

    Kishan, Amar U; Duchesne, Gillian; Wang, Pin-Chieh; Rwigema, Jean-Claude M; Saigal, Christopher; Rettig, Matthew; Steinberg, Michael L; King, Christopher R

    2018-06-01

    The objective was to query how specialty influences treatment recommendations for high-risk prostate cancer in 3 clinical settings: upfront management, postoperative management, and management of biochemical recurrences (BCRs) after radiotherapy (RT). We hypothesized that specialty bias would manifest in all settings, trumping available evidence. A survey of practicing urologists and radiation oncologists was distributed through electronic mail. Questions pertained to upfront management, postoperative treatment, and local salvage for postradiation BCRs. The associations between 26 selected categorical responses and specialty were assessed using multivariate logistic regression. Training level/expertise, practice setting, percentage of consultation caseload consisting of prostate cancer, and nationality were set as effect modifiers. One thousand two hundred fifty-three physicians (846 radiation oncologists and 407 urologists) completed the survey. Radiation oncologists were more likely to recommend adjuvant RT and consider it to be underutilized, and more likely to recommend salvage RT at lower prostate-specific antigen thresholds (P<0.0001). Urologists were more likely to recommend salvage radical prostatectomy or cryoablation for local salvage after RT, whereas radiation oncologists were more likely to recommend RT-based modalities and more likely to report that local salvage was underutilized after RT (P<0.0001). Urologists were more likely to report that upfront radical prostatectomy was a better definitive treatment (P<0.0001), whereas radiation oncologists were more likely to report the opposite (P=0.005). Specialty biases permeate recommendations for upfront management and management in the postoperative and post-RT BCR setting, irrespective of available evidence. These data reveal the critical need for multidisciplinary clinics and cross-specialty training as potential solutions for overcoming specialty bias.

  10. American Brachytherapy Society Task Group Report: Combination of brachytherapy and external beam radiation for high-risk prostate cancer.

    Science.gov (United States)

    Spratt, Daniel E; Soni, Payal D; McLaughlin, Patrick W; Merrick, Gregory S; Stock, Richard G; Blasko, John C; Zelefsky, Michael J

    To review outcomes for high-risk prostate cancer treated with combined modality radiation therapy (CMRT) utilizing external beam radiation therapy (EBRT) with a brachytherapy boost. The available literature for high-risk prostate cancer treated with combined modality radiation therapy was reviewed and summarized. At this time, the literature suggests that the majority of high-risk cancers are curable with multimodal treatment. Several large retrospective studies and three prospective randomized trials comparing CMRT to dose-escalated EBRT have demonstrated superior biochemical control with CMRT. Longer followup of the randomized trials will be required to determine if this will translate to a benefit in metastasis-free survival, disease-specific survival, and overall survival. Although greater toxicity has been associated with CMRT compared to EBRT, recent studies suggest that technological advances that allow better definition and sparing of critical adjacent structures as well as increasing experience with brachytherapy have improved implant quality and the toxicity profile of brachytherapy. The role of androgen deprivation therapy is well established in the external beam literature for high-risk disease, but there is controversy regarding the applicability of these data in the setting of dose escalation. At this time, there is not sufficient evidence for the omission of androgen deprivation therapy with dose escalation in this population. Comparisons with surgery remain limited by differences in patient selection, but the evidence would suggest better disease control with CMRT compared to surgery alone. Due to a series of technological advances, modern combination series have demonstrated unparalleled rates of disease control in the high-risk population. Given the evidence from recent randomized trials, combination therapy may become the standard of care for high-risk cancers. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All

  11. Intratumoural evolutionary landscape of high-risk prostate cancer: The PROGENY study of genomic and immune parameters

    DEFF Research Database (Denmark)

    Linch, M.; Goh, G.; Hiley, C.

    2017-01-01

    Background: Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-...

  12. Impact of screening for breast cancer in high-risk women on health-related quality of life

    NARCIS (Netherlands)

    Rijnsburger, A. J.; Essink-Bot, M. L.; van Dooren, S.; Borsboom, G. J. J. M.; Seynaeve, C.; Bartels, C. C. M.; Klijn, J. G. M.; Tibben, A.; de Koning, H. J.

    2004-01-01

    The effectiveness of intensive surveillance in women at high risk for breast cancer due to a familial or genetic predisposition is uncertain and is currently being evaluated in a Dutch magnetic resonance imaging (MRI) screening (MRISC) study, in which annual imaging consists of mammography and MRI.

  13. Management of women at high risk of hereditary breast cancer in the Veneto Regional Program for Prevention.

    Science.gov (United States)

    Del Sole, Annamaria; Cinquetti, Sandro; Fedato, Chiara; Montagna, Marco; Russo, Francesca; Sbrogiò, Luca Gino; Zorzi, Manuel

    2015-01-01

    Today it is well-known that high risk of genetic breast cancer concerns a very limited part of the population: no more than 2-3 women are affected every thousand and this condition as a whole accounts for no more than 3%-5% of all breast cancers. Following the directions contained in the 2014-2018 National Prevention Plan, Veneto's 2014-2018 Regional Program of Prevention (PRP), approved by Regional Council Resolution (DGR) No. 749 of 14.5.2015, consolidation of a pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma is thus proposed. The principal activities of this policy will be the following: creation of a regional working group, survey of currently existing pathways for the identification of women at risk of hereditary breast cancer and adoption of the same, approval and consolidation of a structured regional pathway for women at high risk of hereditary breast and/or ovarian cancer, from paths of oncogenetic consultation and genetic testing to management of disease risk. Subsequent to the recognition of the pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma, the Veneto region undertakes to develop a co-ordinated program of information and training on this pathway directed at the population and healthcare workers. It is firmly hoped that with the inclusion of a program for the management of women at high risk of hereditary breast cancer within the Veneto PRP this topic may become more defined and structured in terms of sustainability, integration with the existing regional networks (mammography network, Breast Unit), contrasting inequality, monitoring and evaluation, in this way pursuing the objectives of a reduction of cause-specific mortality and improvement of quality of life.

  14. HIV-associated hematologic malignancies: Experience from a Tertiary Cancer Center in India.

    Science.gov (United States)

    Reddy, Rakesh; Gogia, Ajay; Kumar, Lalit; Sharma, Atul; Bakhshi, Sameer; Sharma, Mehar C; Mallick, Saumyaranjan; Sahoo, Ranjit

    2016-01-01

    Data on HIV associated hematologic malignancies is sparse from India. This study attempts to analyze the spectrum and features of this disease at a tertiary cancer center in India. Retrospective study from case records of patients registered with a diagnosis of hematologic malignancy and HIV infection between January 2010 and June 2015. Thirteen cases of HIV associated hematologic malignancies were identified, six of them pediatric. HIV diagnosis was concurrent to diagnosis of cancer in 12 and preceded it in one of them. ECOG PS at presentation was >1 in all of them. All patients, except one, had B symptoms. Six of the patients had bulky disease and six are stage 4. Predominant extranodal disease was seen in 67% of them. NHL accounted for 10 of 13 patients and DLBCL-Germinal center was the most common subtype. Mean CD4+ cell count was 235/μL (range, 32-494). HAART could be given along with chemotherapy to 11 patients. Two-thirds of patients received standard doses of therapy. Chemo-toxicity required hospitalization in 58%. CR was achieved in 45% and 36% had progressive disease with first-line therapy. At the time of last follow up, 3 patients were alive with responsive disease, 2 in CR and 1 in PR. None of the pediatric patients were long time responders. These malignancies were of advanced stage and higher grade. Goal of therapy, in the HAART era, is curative. Pediatric patients had dismal outcome despite good chemotherapy and HAART. There is an urgent need to improve data collection for HIV related cancers in India.

  15. Confirmation of the reported association of clonal chromosomal mosaicism with an increased risk of incident hematologic cancer.

    Directory of Open Access Journals (Sweden)

    Ursula M Schick

    Full Text Available Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS. The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE and the Women's Health Initiative (WHI. We detected clonal mosaicism in 169 individuals (1.4% and large clonal mosaic events (>2 mb in 117 (1.0% individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia, the carriers had a 5.5-fold increased risk (95% CI: 3.3-9.3; p-value = 7.5×10(-11 of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9-41.6; p-value = 7.3×10(-14. Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications.

  16. Long-Term Trends in Hematological and Nutritional Status After Gastrectomy for Gastric Cancer.

    Science.gov (United States)

    Kim, Ji-Hyun; Bae, You-Jin; Jun, Kyong-Hwa; Chin, Hyung-Min

    2017-08-01

    This study investigated long-term trends in hematological and nutritional parameters after gastrectomy for gastric cancer and evaluated the influence of the reconstruction type on these trends. The medical records of 558 patients who underwent curative gastrectomy with standard lymph node dissection for stage I gastric cancer between January 2006 and December 2013 were reviewed. The hematological and nutritional parameters evaluated included hemoglobin, ferritin, vitamin B 12 , total protein, albumin, total cholesterol, triglyceride, and calcium. The patients were followed up for 6 months postoperatively and then annually until death, cancer recurrence, or follow-up loss. In the long term, ferritin and triglyceride gradually decreased after gastrectomy, while the other parameters decreased slightly or were stable. In the comparisons according to reconstruction type, the Roux-en-Y group had the lowest levels of hemoglobin, ferritin, vitamin B12, total protein, albumin, and total cholesterol beginning 6 months postoperatively compared with the Billroth I and II groups. However, only ferritin and vitamin B 12 had significant differences in the 5-year cumulative incidences of deficiency/reduction according to the reconstruction type, whereas albumin, triglyceride, total cholesterol, and calcium did not. Although malabsorption and malnutrition are common in patients after a gastrectomy, most nutritional parameters were stable or decreased slightly in the long-term and were not markedly influenced by the reconstruction type or extent of gastrectomy. Therefore, for more accurate nutritional assessment after gastrectomy, multidirectional monitoring should be considered rather than simply measuring biochemical parameters.

  17. [Sport coaching for psychological and social recovery after hematological cancer: An innovative perspective].

    Science.gov (United States)

    Calvin, Sarah; Blaise, Didier; Ben Soussan, Patrick; Cuvelier, Sarah; Cicut, Nicolas; Caymaris, Laurence; Arnault, Yolande; Onesta, Claude; Dantin, Pierre; Viens, Patrice

    2017-10-01

    This study is a first step towards the transfer of knowledge and practices between psychological support and performance in elite sport and a patient's "social recovery" in oncology. This proposal brings together people engaged in a variety of healthcare and relationship support roles, and aims to set up a support system beyond the hospital context. It questions the ability of elite sport management and its main actors, the "Great Coaches", to contribute to the support of patients in cancer remission through an onco-coaching approach. This innovative proposal is initiated by a life coaching pilot study designed for hematologic cancer patients in remission after a hematopoietic stem cell transplantation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  18. High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2014-01-01

    OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid......-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up...... cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types. LEVEL OF EVIDENCE: II....

  19. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    Directory of Open Access Journals (Sweden)

    Shakespeare TP

    2016-05-01

    Full Text Available Thomas P Shakespeare,1,2 Shea W Wilcox,1 Noel J Aherne1,2 1Department of Radiation Oncology, North Coast Cancer Institute, 2Rural Clinical School, Faculty of Medicine, University of New South Wales, Coffs Harbour, NSW, Australia Aim: Both dose-escalated external beam radiotherapy (DE-EBRT and androgen deprivation therapy (ADT improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods: Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results: In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion: There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. Keywords: radiotherapy, IMRT, dose

  20. High-risk populations identified in Childhood Cancer Survivor Study investigations: implications for risk-based surveillance.

    Science.gov (United States)

    Hudson, Melissa M; Mulrooney, Daniel A; Bowers, Daniel C; Sklar, Charles A; Green, Daniel M; Donaldson, Sarah S; Oeffinger, Kevin C; Neglia, Joseph P; Meadows, Anna T; Robison, Leslie L

    2009-05-10

    Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.

  1. Dosimetric Study of Pelvic Proton Radiotherapy for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Chera, Bhishamjit S.; Vargas, Carlos; Morris, Christopher G.; Louis, Debbie; Flampouri, Stella; Yeung, Daniel; Duvvuri, Srividya; Li Zuofeng; Mendenhall, Nancy Price

    2009-01-01

    Purpose: To compare dose distributions in targeted tissues (prostate, seminal vesicles, pelvic regional nodes) and nontargeted tissues in the pelvis with intensity-modulated radiotherapy (IMRT) and forward-planned, double-scattered, three-dimensional proton radiotherapy (3D-PRT). Methods and Materials: IMRT, IMRT followed by a prostate 3D-PRT boost (IMRT/3D-PRT), and 3D-PRT plans were created for 5 high-risk prostate cancer patients (n = 15 plans). A 78-CGE/Gy dose was prescribed to the prostate and proximal seminal vesicles and a 46-CGE/Gy was prescribed to the pelvic nodes. Various dosimetric endpoints were compared. Results: Target coverage of the prostate and nodal planning target volumes was adequate for all three plans. Compared with the IMRT and IMRT/3D-PRT plans, the 3D-PRT plans reduced the mean dose to the rectum, rectal wall, bladder, bladder wall, small bowel, and pelvis. The relative benefit of 3D-PRT (vs IMRT) at reducing the rectum and rectal wall V5-V40 was 53% to 71% (p < 0.05). For the bladder and bladder wall, the relative benefit for V5 to V40 CGE/Gy was 40% to 63% (p < 0.05). The relative benefit for reducing the volume of small bowel irradiated from 5 to 30 CGE/Gy in the 3D-PRT ranged from 62% to 69% (p < 0.05). Use of 3D-PRT did not produce the typical low-dose 'bath' of radiation to the pelvis seen with IMRT. Femoral head doses were higher for the 3D-PRT. Conclusions: Use of 3D-PRT significantly reduced the dose to normal tissues in the pelvis while maintaining adequate target coverage compared with IMRT or IMRT/3D-PRT. When treating the prostate, seminal vesicles, and pelvic lymph nodes in prostate cancer, proton therapy may improve the therapeutic ratio beyond what is possible with IMRT.

  2. Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    International Nuclear Information System (INIS)

    Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

    2011-01-01

    Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving ≥10 and 20 Gy (V 10 and V 20 ) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V 10 (regression coefficient (β) = -0.060, p = 0.009) and V 20 (β = -0.044, p = 0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V 10 and V 20 were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V 10 ≥ 95% were more likely to experience Grade ≥3 leukopenia (68.8% vs. 24.6%, p 20 > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V 10 20 < 76% may reduce HT.

  3. Cervical cancer screening by high risk HPV testing in routine practice: results at one year recall of high risk HPV-positive and cytology-negative women.

    Science.gov (United States)

    Del Mistro, Annarosa; Frayle, Helena; Ferro, Antonio; Callegaro, Susanna; Del Sole, Annamaria; Stomeo, Anna; Cirillo, Emanuela; Fedato, Chiara; Pagni, Silvana; Barzon, Luisa; Zorzi, Manuel

    2014-03-01

    Cervical cancer screening by human papillomavirus (HPV) testing requires the use of additional triage and follow-up analyses. We evaluated women's compliance with and the performance of this strategy in a routine setting. Five cervical service screening programmes in North-East Italy. Eligible women aged 25-64 invited for a new screening episode underwent HPV testing for high risk types (hrHPV by Hybrid Capture 2) and cytology triage. Women with positive HPV and cytology results were referred for colposcopy; women with positive HPV but negative cytology results were referred to 1-year repeat hrHPV testing. Of 46,694 women screened by HPV testing up to December 2011, 3,211 (6.9%) tested hrHPV positive; 45% of these had a positive triage cytology. Those with negative cytology were invited for 1-yr repeat testing. Compliance with invitation was 61.6% at baseline and 85.3% at 1-yr repeat. Rate of persistent hrHPV positivity was 58% (830/1,435). Colposcopy performed in women with a positive hrHPV test at 1-yr repeat accounted for 36% of all colposcopies performed within the screening programmes. Cumulatively, a histological high-grade lesion was detected in 276 women (5.9‰ detection rate), 234 at baseline (85%), and 42 (15%) at 1-yr repeat. Compliance with hrHPV-based screening programmes was high both at baseline and at 1-yr repeat. Compared with the randomized trials, a higher proportion of triage cytology was read as positive, and only a small number of high-grade lesions were detected among the group of hrHPV positive cytology negative women who repeated testing 1-yr after baseline.

  4. Validation of Association of Genetic Variants at 10q with PSA Levels in Men at High Risk for Prostate Cancer

    Science.gov (United States)

    Chang, Bao-Li; Hughes, Lucinda; Chen, David Y. T.; Gross, Laura; Ruth, Karen; Giri, Veda N.

    2013-01-01

    Objectives Men with a family history of prostate cancer and African American men are at increased risk for prostate cancer and stand to benefit from individualized interpretation of PSA to guide screening strategies. The purpose of this study was to validate six previously identified markers among high-risk men enrolled in the Prostate Cancer Risk Assessment Program - a prostate cancer screening study. Patients and Methods Eligibility for PRAP includes men ages 35–69 years with a family history of prostate cancer, any African American male regardless of family history, and men with known BRCA gene mutations. GWAS markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12), and rs17632542 (19q13.33). Genotyping methods included either Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders. Results 707 participants (37% Caucasian, 63% African American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) strongly associated with PSA levels among high-risk Caucasian participants (p<0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) demonstrated an association to PSA level (p=0.03) in high-risk Caucasian men, with a 15% increase in PSA with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 is proposed specific to high-risk Caucasian men. Conclusion Genetic variation at 10q may be particularly important in personalizing interpretation of PSA for high-risk Caucasian men. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for high-risk Caucasian men. Further study is warranted. PMID:23937305

  5. [Nutritional status in patients first hospital admissions service hematology National Cancer Institute].

    Science.gov (United States)

    Baltazar Luna, E; Omaña Guzmán, L I; Ortiz Hernández, L; Ñamendis-Silva, S A; De Nicola Delfin, L

    2013-01-01

    To determine the nutritional status of patients admitted to hospital for the first time the hematology service and who have not received treatment for cancer, to know if the nutritional status assessed by the EGS-GP and serum albumin related mortality of patients A longitudinal, prospective, analytical. EGS-Through GP assessed the nutritional status of patients, we used SPSS 19.0 for data analysis. Evaluaron 119 patients, 52.1% female and 47.9% male. The most common diagnosis was non-Hodgkin lymphoma in 43.7%. According to the EGS-GP 50.4% of patients had some degree of malnutrition or was at risk of suffering of which: 31.1% had moderate and 19.3% had severe malnutrition. The 49.6% of patients had an adequate nutritional status. 30.3% of the patients who died, 37% had severe malnutrition and 50% severe decrease in albumin concentration. The prevalence of malnutrition in hematological patients treated at the National Cancer Institute of Mexico that have not received medical treatment was high. There is an association between nutritional status and mortality in this patient group. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  6. Body Image Discomfort of Adolescent and Young Adult Hematologic Cancer Survivors.

    Science.gov (United States)

    Zucchetti, Giulia; Bellini, Simona; Bertolotti, Marina; Bona, Francesca; Biasin, Eleonora; Bertorello, Nicoletta; Tirtei, Elisa; Fagioli, Franca

    2017-06-01

    This study focuses on body image discomfort (BID) of 50 adolescent and young adult (AYA) hematologic cancer survivors (age range 15-23; 52% males). The study results were obtained through data from a self-report questionnaire: the Body Uneasiness Test. Findings differed according to gender: a greater proportion of females were in the Risk category of impaired body image than males (χ 2  = 5.258, p < 0.05). No significant body image differences were found according to the type of diagnosis or to the length of survival. To manage survivors' BIDs and to improve their quality of life, assessing BID in AYA cancer survivors is important for identifying those who might be in need of additional supportive care or a program.

  7. Mortality and recurrence rates among systemically untreated high risk breast cancer patients included in the DBCG 77 trials

    DEFF Research Database (Denmark)

    Jensen, Maj Britt; Nielsen, Torsten O.; Knoop, Ann S.

    2018-01-01

    Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient characte......Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient...... and EGFR positive. Multivariate categorical and fractional polynomials (MFP) models were used to construct prognostic subsets by clinicopathologic characteristics. Results: In a multivariate model, mortality rate was significantly associated with age, tumor size, nodal status, invasion, histological type...

  8. Histological evaluation of patients with gastritis at high risk of developing gastric cancer using a conventional index.

    Science.gov (United States)

    Tanaka, Aki; Kamada, Tomoari; Inoue, Kazuhiko; Shiotani, Akiko; Kusunoki, Hiroaki; Manabe, Noriaki; Ito, Masanori; Hata, Jiro; Haruma, Ken

    2011-06-15

    Although gastric cancer (GCa) is strongly associated with Helicobacter pylori infection, only some H. pylori-positive subjects develop gastric cancer. The aim of this study is to identify H. pylori-positive subjects at high risk of developing GCa by assessment of the histopathological findings in the non-cancer-containing mucosa of patients with and without GCa. The subjects were 35 patients with diffuse-type gastric cancer (D-GCa), 55 with intestinal-type gastric cancer (I-GCa), and 99 H. pylori-positive controls without GCa. Two specimens were taken from the greater curvature of the antrum and the middle body. Histopathological gradings were evaluated using the updated Sydney System, and the risk of GCa was evaluated using a modified Meining's gastric cancer risk index (GCRI). Among the H. pylori-positive controls, corpus gastritis was seen in 98.0% (97/99) and corpus atrophic gastritis in 78.8% (78/99). The mean GCRI for the D-GCa (5.514±2.03) and I-GCa (6.836±2.08) groups was significantly greater than that for the H. pylori-positive controls (4.071±2.07; p=0.0005, pcancer. However, H. pylori-positive patients at high risk of developing GCa (not only intestinal-type but also diffuse-type) may be detected using a simple GCRI. Copyright © 2011 Elsevier GmbH. All rights reserved.

  9. Clinical outcomes of image guided radiation therapy (IGRT) with gold fiducial vaginal cuff markers for high-risk endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Monroe, Alan T.; Peddada, Anuj V. [Dept. of Radiation Oncology, Penrose Cancer Center, Colorado Springs (United States); Pikaart, Dirk [Dept. of Gynecologic Oncology, Penrose Cancer Center, Colorado Springs (United States)

    2013-06-15

    Objective. To report two year clinical outcomes of image guided radiation therapy (IGRT) to the vaginal cuff and pelvic lymph nodes in a series of high-risk endometrial cancer patients. Methods . Twenty-six consecutive high-risk endometrial cancer patients requiring adjuvant radiation to the vaginal cuff and regional lymph nodes were treated with vaginal cuff fiducial-based IGRT. Seventeen (65%) received sequential chemotherapy, most commonly with a sandwich technique. Brachytherapy followed external radiation in 11 patients to a median dose of 18 Gy in 3 fractions. The median external beam dose delivered was 47.5 Gy in 25 fractions. Results. All 656 fractions were successfully imaged and treated. The median overall translational shift required for correction was 9.1 mm (standard deviation, 5.2 mm) relative to clinical set-up with skin tattoos. Shifts of 1 cm, 1.5 cm, and 2 cm or greater were performed in 43%, 14%, and 4% of patients, respectively. Acute grade 2 gastrointestinal (GI) toxicity occurred in eight patients (30%) and grade 3 toxicity occurred in one. At two years, there have been no local or regional failures and actuarial overall survival is 95%. Conclusion. Daily image guidance for high-risk endometrial cancer results in a low incidence of acute GI/genitourinary (GU) toxicity with uncompromised tumor control at two years. Vaginal cuff translations can be substantial and may possibly result in underdosing if not properly considered.

  10. Clinical outcomes of image guided radiation therapy (IGRT) with gold fiducial vaginal cuff markers for high-risk endometrial cancer

    International Nuclear Information System (INIS)

    Monroe, Alan T.; Peddada, Anuj V.; Pikaart, Dirk

    2013-01-01

    Objective. To report two year clinical outcomes of image guided radiation therapy (IGRT) to the vaginal cuff and pelvic lymph nodes in a series of high-risk endometrial cancer patients. Methods . Twenty-six consecutive high-risk endometrial cancer patients requiring adjuvant radiation to the vaginal cuff and regional lymph nodes were treated with vaginal cuff fiducial-based IGRT. Seventeen (65%) received sequential chemotherapy, most commonly with a sandwich technique. Brachytherapy followed external radiation in 11 patients to a median dose of 18 Gy in 3 fractions. The median external beam dose delivered was 47.5 Gy in 25 fractions. Results. All 656 fractions were successfully imaged and treated. The median overall translational shift required for correction was 9.1 mm (standard deviation, 5.2 mm) relative to clinical set-up with skin tattoos. Shifts of 1 cm, 1.5 cm, and 2 cm or greater were performed in 43%, 14%, and 4% of patients, respectively. Acute grade 2 gastrointestinal (GI) toxicity occurred in eight patients (30%) and grade 3 toxicity occurred in one. At two years, there have been no local or regional failures and actuarial overall survival is 95%. Conclusion. Daily image guidance for high-risk endometrial cancer results in a low incidence of acute GI/genitourinary (GU) toxicity with uncompromised tumor control at two years. Vaginal cuff translations can be substantial and may possibly result in underdosing if not properly considered

  11. Image-guided intensity modulated radiotherapy with helical tomotherapy for postoperative treatment of high-risk oral cavity cancer

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    Chen Yu-Jen

    2011-01-01

    Full Text Available Abstract Background The aim of this study was to assess the treatment results and toxicity profiles of helical tomotherapy (HT for postoperative high-risk oral cavity cancer. Methods From December 6, 2006 through October 9, 2009, 19 postoperative high-risk oral cavity cancer patients were enrolled. All of the patients received HT with (84% or without (16% chemotherapy. Results The median follow-up time was 17 months. The 2-year overall survival, disease-free survival, locoregional control, and distant metastasis-free rates were 94%, 84%, 92%, and 94%, respectively. The package of overall treatment time > 13 wk, the interval between surgery and radiation ≤ 6 wk, and the overall treatment time of radiation ≤ 7 wk was 21%, 84%, and 79%, respectively. The percentage of grade 3 mucositis, dermatitis, and leucopenia was 42%, 5% and 5%, respectively. Conclusions HT achieved encouraging clinical outcomes for postoperative high-risk oral cavity cancer patients with high compliance. A long-term follow-up study is needed to confirm these preliminary findings.

  12. Image-guided intensity modulated radiotherapy with helical tomotherapy for postoperative treatment of high-risk oral cavity cancer

    International Nuclear Information System (INIS)

    Hsieh, Chen-Hsi; Hsieh, Yen-Ping; Lin, Shoei Long; Chen, Chun-Yi; Chen, Chien-An; Shueng, Pei-Wei; Kuo, Ying-Shiung; Liao, Li-Jen; Hu, Kawang-Yu; Lin, Shih-Chiang; Wu, Le-Jung; Lin, Yu-Chin; Chen, Yu-Jen; Wang, Li-Ying

    2011-01-01

    The aim of this study was to assess the treatment results and toxicity profiles of helical tomotherapy (HT) for postoperative high-risk oral cavity cancer. From December 6, 2006 through October 9, 2009, 19 postoperative high-risk oral cavity cancer patients were enrolled. All of the patients received HT with (84%) or without (16%) chemotherapy. The median follow-up time was 17 months. The 2-year overall survival, disease-free survival, locoregional control, and distant metastasis-free rates were 94%, 84%, 92%, and 94%, respectively. The package of overall treatment time > 13 wk, the interval between surgery and radiation ≤ 6 wk, and the overall treatment time of radiation ≤ 7 wk was 21%, 84%, and 79%, respectively. The percentage of grade 3 mucositis, dermatitis, and leucopenia was 42%, 5% and 5%, respectively. HT achieved encouraging clinical outcomes for postoperative high-risk oral cavity cancer patients with high compliance. A long-term follow-up study is needed to confirm these preliminary findings

  13. Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer.

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    Jia-Min B Pang

    Full Text Available To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31 slides and correlated to mammographic density.Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22 = 0.5226, p = 0.0088 and significantly inversely associated with adipose tissue proportion (rs (22 = -0.5409, p = 0.0064. Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%. There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026.The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.

  14. Prevalence of High risk Human Papillomavirus in cervical dysplasia and cancer samples from twin cities in Pakistan.

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    Gul, Sana; Murad, Sheeba; Javed, Aneela

    2015-05-01

    Human Papilloma Virus (HPV) is small DNA virus mostly infecting mucosa and cutaneous keratinocytes. So far, more than 200 Human papillomaviruses are known. HPV have been divided into high- and low-risk on the basis of their oncogenic potential. High risk HPV is considered to be the main etiological cause for cervical cancer. The current study was designed to screen the local cervical cancer patients from the twin cities of Pakistan for the occurance of high risk HPV. A total of 67 formalin fixed paraffin-embedded samples of cervical cancer biopsies were obtained from the government hospitals in Islamabad and Rawalpindi. Cervical cancer biopsies were examined for the presence of HPV DNA. Polymerase chain reaction (PCR) was used for the amplification of a region in the HPV-L1 gene for the general detection of the Papilloma virus and for the genotype specific detection of high risk HPV 16 and 18 using the GP5/GP6 primers and genotype specific primers, respectively. HPV DNA was detected in 59 out of 67 samples analyzed. 30 samples showed the presence of HPV16 while 22 samples were positive for HPV18. HPV subtype could not be determined in 7 samples. Our results show a strong association between HPV infection and cervical cancer among women in twin cities of Pakistan. One way to minimize the disease burden in relation to HPV infection in Pakistani population is the use of prophylactic vaccines and routine screening. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Association of the p53 codon 72 polymorphism to gastric cancer risk in a high risk population of Costa Rica

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    Alpizar-Alpizar, Warner; Sierra, Rafaela; Cuenca, Patricia; Une, Clas; Mena, Fernando; Perez-Perez, Guillermo Ignacio

    2005-01-01

    Gastric cancer is the second most common cancer associated death cause worldwide. Several factors have been associated with higher risk to develop gastric cancer, among them genetic predisposition. The p53 gene has a polymorphism located at codon 72, which has been associated with higher risk of several types of cancer, including gastric cancer. The aim of this study was to determine the association of p53, codon 72 polymorphism, with the risk of gastric cancer and pre-malignant lesions in a high-risk population from Costa Rica. The genotyping was carried out by PCR-RFLP in a sample of 58 gastric cancer patients, 99 control persons and 41 individuals classified as group I and II, according to the Japanese histological classification. No association was found for p53, codon 72 polymorphism with neither the risk of gastric cancer nor the risk of less severe gastric lesions in the studied sample. Based on this study and taking into account other studies carried out with p53, codon 72 polymorphism, the role of this polymorphism in the development of gastric cancer remains unclear. De novo mutations on p53 gene produced during neoplastic development of this disease might play a greater role than germinal polymorphisms of this same gene. Other polymorphic genes have been associated with higher risk to develop gastric cancer. (author) [es

  16. Use of a combination of CEA and tumor budding to identify high-risk patients with stage II colon cancer.

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    Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Peng, Yifan; Yao, Yunfeng; Zhao, Jun; Gu, Jin

    2017-07-24

    High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

  17. Seasonal clustering of sinopulmonary mucormycosis in patients with hematologic malignancies at a large comprehensive cancer center

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    Shobini Sivagnanam

    2017-12-01

    Full Text Available Abstract Background Invasive Mucorales infections (IMI lead to significant morbidity and mortality in immunocompromised hosts. The role of season and climatic conditions in case clustering of IMI remain poorly understood. Methods Following detection of a cluster of sinopulmonary IMIs in patients with hematologic malignancies, we reviewed center-based medical records of all patients with IMIs and other invasive fungal infections (IFIs between January of 2012 and August of 2015 to assess for case clustering in relation to seasonality. Results A cluster of 7 patients were identified with sinopulmonary IMIs (Rhizopus microsporus/azygosporus, 6; Rhizomucor pusillus, 1 during a 3 month period between June and August of 2014. All patients died or were discharged to hospice. The cluster was managed with institution of standardized posaconazole prophylaxis to high-risk patients and patient use of N-95 masks when outside of protected areas on the inpatient service. Review of an earlier study period identified 11 patients with IMIs of varying species over the preceding 29 months without evidence of clustering. There were 9 total IMIs in the later study period (12 month post-initial cluster with 5 additional cases in the summer months, again suggesting seasonal clustering. Extensive environmental sampling did not reveal a source of mold. Using local climatological data abstracted from National Centers for Environmental Information the clusters appeared to be associated with high temperatures and low precipitation. Conclusions Sinopulmonary Mucorales clusters at our center had a seasonal variation which appeared to be related to temperature and precipitation. Given the significant mortality associated with IMIs, local climatic conditions may need to be considered when considering center specific fungal prevention and prophylaxis strategies for high-risk patients.

  18. The Early Result of Whole Pelvic Radiotherapy and Stereotactic Body Radiotherapy Boost for High Risk Localized Prostate Cancer

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    Yu-Wei eLin

    2014-10-01

    Full Text Available PurposeThe rationale for hypofractionated radiotherapy in the treatment of prostate cancer is based on the modern understanding of radiobiology and advances in stereotactic body radiotherapy (SBRT techniques. Whole-pelvis irradiation combined with SBRT boost for high-risk prostate cancer might escalate biologically effective dose without increasing toxicity. Here, we report our 4-year results of SBRT boost for high-risk localized prostate cancer.Methods and MaterialsFrom October 2009 to August 2012, 41 patients of newly diagnosed, high-risk or very high-risk (NCCN definition localized prostate cancer patients were treated with whole-pelvis irradiation and SBRT boost. The whole pelvis dose was 45Gy (25 fractions of 1.8Gy. The SBRT boost dose was 21 Gy (three fractions of 7 Gy. Ninety percent of these patients received hormone therapy. The toxicities of gastrointestinal (GI and genitourinary (GU tracts were scored by Common Toxicity Criteria Adverse Effect (CTCAE v3.0. Biochemical failure was defined by Phoenix definition.ResultsMedian follow-up was 42 months. Mean PSA before treatment was 44.18 ng/ml. Mean PSA level at 3, 6, 12, 18, and 24 months was 0.94, 0.44, 0.13, 0.12, and 0.05 ng/ml, respectively. The estimated 4-year biochemical failure-free survival was 91.9%. Three biochemical failures were observed. GI and GU tract toxicities were minimal. No grade 3 acute GU or GI toxicity was noted. During radiation therapy, 27% of the patient had grade 2 acute GU toxicity and 12% had grade 2 acute GI toxicity. At 3 months, most toxicity scores had returned to baseline. At the last follow up, there was no grade 3 late GU or GI toxicity.ConclusionsWhole-pelvis irradiation combined with SBRT boost for high-risk localized prostate cancer is feasible with minimal toxicity and encouraging biochemical failure-free survival. Continued accrual and follow-up would be necessary to confirm the biochemical control rate and the toxicity profiles.

  19. Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Tendulkar, Rahul D.; Hunter, Grant K.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Abdel-Wahab, May; Stephenson, Andrew J.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2013-01-01

    Purpose: Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. Methods and Materials: A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. Results: The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). Conclusions: Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not

  20. Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.

    Science.gov (United States)

    Panagopoulou, Maria; Lambropoulou, Maria; Balgkouranidou, Ioanna; Nena, Evangelia; Karaglani, Makrina; Nicolaidou, Christina; Asimaki, Anthi; Konstantinidis, Theocharis; Constantinidis, Theodoros C; Kolios, George; Kakolyris, Stylianos; Agorastos, Theodoros; Chatzaki, Ekaterini

    2017-04-01

    Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.

  1. Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer.

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    Juozas Kupcinskas

    Full Text Available BACKGROUND AND AIMS: MicroRNAs (miRNAs are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 and the presence of GC or high risk atrophic gastritis (HRAG in European population. METHODS: Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281 of European descent. MiR-27a T>C (rs895819, miR-146a G>C (rs2910164, miR-196a-2 C>T (rs11614913, miR-492 G>C (rs2289030 and miR-608 C>G (rs4919510 SNPs were genotyped by RT-PCR. RESULTS: Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR - 1.46, 95% confidence interval (CI 1.03-2.07, P = 0.032. MiR-608 GG genotype was more frequent in GC when compared to controls (OR -2.34, 95% CI 1.08-5.04, but significance remained marginal (P = 0.029. A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14-5.22, P = 0.021. The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC. CONCLUSIONS: Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European

  2. Conformal Brachytherapy Boost To External Beam Irradiation For Clinically Localized High Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Dattoli, Michael J.; Wasserman, Stuart G.; Koval, John M.; Sorace, Richard A.; Cash, Jennifer; Wallner, Kent E.

    1995-01-01

    Purpose: To evaluate the efficacy of using a Pd-103 implant as a boost in conjunction with external beam radiotherapy (EBRT) in patients having prostate cancer associated with adverse features. Materials and Methods: 114 consecutive high risk patients have been treated with combination EBRT and Pd-103 implant. 70 patients with follow-up range of 12-42 months (median 24 months) form the basis of this report. Each patient had at least one of the following risk factors for extra-capsular disease extension: Stage T2b or greater ((66(70))), Gleason score ≥ 7 ((38(70))), significantly elevated PSA (typically > 15 ng/ml)((30(70))) or elevated serum prostatic acid phosphatase (SPAP)((17(70))). Patients received median 4140 cGy EBRT to a limited pelvic field followed by a Pd-103 boost (median prescription dose: 8000 cGy). All patients have been followed in a prospective fashion with respect to PSA response, clinical evidence of disease progression and complications. Criteria for biochemical failure was relatively strict, and was analyzed using both, PSA > 2.0 and PSA > 1.0 as end points. Patients whose PSA was still decreasing at last follow-up were censored at that time. Freedom from failure rates were calculated by the method of Kaplan and Meier. Differences between groups were determined by the Log-rank method. Sexual potency was defined as the ability to attain and maintain an erection sufficient for intercourse. Results: Actuarial freedom from biochemical failure at 3 years after treatment was 90% and 78%, when PSA > 2 and PSA > 1 were used, respectively. There are no documented local relapses. 4 patients failed distantly, and all other failures are based solely on rising PSA values. Biochemical failure was higher in patients having Gleason score ≥ 7 (p=0.001), those with PSA >20 (p=0.014) and in those with elevated SPAP (p=0.007). The primary treatment related morbity was temporary, Grade 1-2 urinary symptoms. No patient developed rectal ulceration or prostatic

  3. Conformal Brachytherapy Boost To External Beam Irradiation For Clinically Localized High Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dattoli, Michael J; Wasserman, Stuart G; Koval, John M; Sorace, Richard A; Cash, Jennifer; Wallner, Kent E

    1995-07-01

    Purpose: To evaluate the efficacy of using a Pd-103 implant as a boost in conjunction with external beam radiotherapy (EBRT) in patients having prostate cancer associated with adverse features. Materials and Methods: 114 consecutive high risk patients have been treated with combination EBRT and Pd-103 implant. 70 patients with follow-up range of 12-42 months (median 24 months) form the basis of this report. Each patient had at least one of the following risk factors for extra-capsular disease extension: Stage T2b or greater ((66(70))), Gleason score {>=} 7 ((38(70))), significantly elevated PSA (typically > 15 ng/ml)((30(70))) or elevated serum prostatic acid phosphatase (SPAP)((17(70))). Patients received median 4140 cGy EBRT to a limited pelvic field followed by a Pd-103 boost (median prescription dose: 8000 cGy). All patients have been followed in a prospective fashion with respect to PSA response, clinical evidence of disease progression and complications. Criteria for biochemical failure was relatively strict, and was analyzed using both, PSA > 2.0 and PSA > 1.0 as end points. Patients whose PSA was still decreasing at last follow-up were censored at that time. Freedom from failure rates were calculated by the method of Kaplan and Meier. Differences between groups were determined by the Log-rank method. Sexual potency was defined as the ability to attain and maintain an erection sufficient for intercourse. Results: Actuarial freedom from biochemical failure at 3 years after treatment was 90% and 78%, when PSA > 2 and PSA > 1 were used, respectively. There are no documented local relapses. 4 patients failed distantly, and all other failures are based solely on rising PSA values. Biochemical failure was higher in patients having Gleason score {>=} 7 (p=0.001), those with PSA >20 (p=0.014) and in those with elevated SPAP (p=0.007). The primary treatment related morbity was temporary, Grade 1-2 urinary symptoms. No patient developed rectal ulceration or prostatic

  4. Offering lung cancer screening to high-risk medicare beneficiaries saves lives and is cost-effective: an actuarial analysis.

    Science.gov (United States)

    Pyenson, Bruce S; Henschke, Claudia I; Yankelevitz, David F; Yip, Rowena; Dec, Ellynne

    2014-08-01

    By a wide margin, lung cancer is the most significant cause of cancer death in the United States and worldwide. The incidence of lung cancer increases with age, and Medicare beneficiaries are often at increased risk. Because of its demonstrated effectiveness in reducing mortality, lung cancer screening with low-dose computed tomography (LDCT) imaging will be covered without cost-sharing starting January 1, 2015, by nongrandfathered commercial plans. Medicare is considering coverage for lung cancer screening. To estimate the cost and cost-effectiveness (ie, cost per life-year saved) of LDCT lung cancer screening of the Medicare population at high risk for lung cancer. Medicare costs, enrollment, and demographics were used for this study; they were derived from the 2012 Centers for Medicare & Medicaid Services (CMS) beneficiary files and were forecast to 2014 based on CMS and US Census Bureau projections. Standard life and health actuarial techniques were used to calculate the cost and cost-effectiveness of lung cancer screening. The cost, incidence rates, mortality rates, and other parameters chosen by the authors were taken from actual Medicare data, and the modeled screenings are consistent with Medicare processes and procedures. Approximately 4.9 million high-risk Medicare beneficiaries would meet criteria for lung cancer screening in 2014. Without screening, Medicare patients newly diagnosed with lung cancer have an average life expectancy of approximately 3 years. Based on our analysis, the average annual cost of LDCT lung cancer screening in Medicare is estimated to be $241 per person screened. LDCT screening for lung cancer in Medicare beneficiaries aged 55 to 80 years with a history of ≥30 pack-years of smoking and who had smoked within 15 years is low cost, at approximately $1 per member per month. This assumes that 50% of these patients were screened. Such screening is also highly cost-effective, at <$19,000 per life-year saved. If all eligible Medicare

  5. Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography.

    Science.gov (United States)

    Ohata, Hiroshi; Oka, Masashi; Yanaoka, Kimihiko; Shimizu, Yasuhito; Mukoubayashi, Chizu; Mugitani, Kouichi; Iwane, Masataka; Nakamura, Hideya; Tamai, Hideyuki; Arii, Kenji; Nakata, Hiroya; Yoshimura, Noriko; Takeshita, Tetsuya; Miki, Kazumasa; Mohara, Osamu; Ichinose, Masao

    2005-10-01

    With the aim of developing more efficient gastric cancer screening programs for use in Japan, we studied a new screening program that combines serum pepsinogen (PG) testing and barium digital radiography (DR). A total of 17 647 middle-aged male subjects underwent workplace screening over a 7-year period using a combination of PG testing and DR. This program's effectiveness, as well as other characteristics of the program, was analyzed. Forty-nine cases of gastric cancer were detected (comprising 88% early cancer cases). The detection rate was 0.28%, and the positive predictive value was 0.85%. The PG test detected 63.3% of cases, DR detected 69.4% of cases, and both tests were positive in 32.7% of cancer cases. The two methods were almost equally effective, and were considerably more effective than conventional screening using photofluorography. Each screening method detected a distinct gastric cancer subgroup; the PG test efficiently detected asymptomatic small early cancer with intestinal type histology, while DR was efficient at detecting cancers with depressed or ulcerated morphology and diffuse type histology. The cost for the detection of a single cancer was much less than that for conventional screening. In fact, it is possible to further reduce the cost of detecting a single cancer to a cost comparable to that of surgically resecting a single gastric cancer. Thus, it is probable that a highly efficient gastric cancer screening system can be implemented by combining the two screening methods. Such a screening program would be beneficial in a population at high risk for gastric cancer.

  6. Mouth self-examination to improve oral cancer awareness and early detection in a high-risk population.

    Science.gov (United States)

    Elango, Kalavathy Jayapal; Anandkrishnan, Nitin; Suresh, Amritha; Iyer, Subramania K; Ramaiyer, Sundaram Karimassery; Kuriakose, Moni Abraham

    2011-07-01

    Oral cancer is a potentially preventable disease due to its association with well-known risk factors and easy detectability. There is a significant deficiency in the awareness of oral cancer and its risk factors among the public. Raising public awareness could effectively contribute to achieving a significant reduction in the incidence of oral cancer. The objective of this study was to evaluate the effectiveness of mouth self-examination (MSE) in improving the awareness of oral cancer and its risk factors as well as test its feasibility as an oral cancer-screening tool. The study was carried out in a high-risk population of 57,704 from India, of which, 34,766 individuals who have met the eligibility criteria formed the study population. MSE brochures and trained health workers were employed for the purpose of health education and cancer screening. The present study compared their efficacy to detect oral lesions. Subjects with suspicious lesions were referred to the trained oral cancer specialist for confirmation. A questionnaire to assess the awareness of oral cancer and its risk factors was developed and validated. SPSS (v.11.0) was used for data analysis. The program identified 216 cases of potentially malignant lesions as well as three cases of oral cancer. The findings of MSE and health workers showed 72% concordance, while that of health workers and oral cancer specialist showed 100% concordance. MSE had a low sensitivity of 18%, while the specificity was 99.9%. Though the technique identified high-risk lesions such as red patches (66.7%) and non-healing ulcers (42.9%), the detection rate of white patches was low (12.7%). Overall awareness of oral cancer and its risk factors after introduction of MSE program was over 80%; but the compliance to seek treatment was poor (32%). Mouth self-examination may be used as an effective tool to improve the awareness of oral cancer and for the early detection of lesions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Adjuvant chemoradiotherapy instead of revision radical resection after local excision for high-risk early rectal cancer.

    Science.gov (United States)

    Jeong, Jae-Uk; Nam, Taek-Keun; Kim, Hyeong-Rok; Shim, Hyun-Jeong; Kim, Yong-Hyub; Yoon, Mee Sun; Song, Ju-Young; Ahn, Sung-Ja; Chung, Woong-Ki

    2016-09-05

    After local excision of early rectal cancer, revision radical resection is recommended for patients with high-risk pathologic stage T1 (pT1) or pT2 cancer, but the revision procedure has high morbidity rates. We evaluated the efficacy of adjuvant concurrent chemoradiotherapy (CCRT) for reducing recurrence after local excision in these patients. Eighty-three patients with high-risk pT1 or pT2 rectal cancer underwent postoperative adjuvant CCRT after local excision. We defined high-risk features as pT1 having tumor size ≤3 cm, and/or resection margin (RM) ≤3 mm, and/or lymphovascular invasion (LVI), and/or non-full thickness excision such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), or unknown records regarding those features, or pT2 cancer. Radiotherapy was administered with a median dose of 50.4 Gy in 1.8 Gy fraction size over 5-7 weeks. Concurrent 5-fluorouracil and leucovorin were administered for 4 days in the first and fifth weeks of radiotherapy. The median interval between local excision and radiotherapy was 34 (range, 11-104) days. Fifteen patients (18.1 %) had stage pT2 tumors, 22 (26.5 %) had RM of ≥3 mm, and 21 (25.3 %) had tumors of ≥3 cm in size. Thirteen patients (15.7 %) had LVI. Transanal excision was performed in 58 patients (69.9 %) and 25 patients (30.1 %) underwent EMR or ESD. The median follow-up was 61 months. The 5-year overall survival (OS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS) rates for all patients were 94.9, 91.0, and 89.8 %, respectively. Multivariate analysis did not identify any significant factors for OS or LRFS, but the only significant factor affecting DFS was the pT stage (p = 0.027). In patients with high-risk pT1 rectal cancer, adjuvant CCRT after local excision could be an effective alternative treatment instead of revision radical resection. However, patients with pT2 stage showed inferior DFS compared to pT1.

  8. Impact of Bone Marrow Radiation Dose on Acute Hematologic Toxicity in Cervical Cancer: Principal Component Analysis on High Dimensional Data

    International Nuclear Information System (INIS)

    Yun Liang; Messer, Karen; Rose, Brent S.; Lewis, John H.; Jiang, Steve B.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2010-01-01

    Purpose: To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods and Materials: The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results: We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R 2 , 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions: We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing.

  9. Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klopp, Ann H., E-mail: aklopp@mdanderson.org [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Moughan, Jennifer [RTOG Statistical Center, Philadelphia, Pennsylvania (United States); Portelance, Lorraine [Sylvester Comprehensive Cancer Center, Miami, Florida (United States); Miller, Brigitte E. [Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina (United States); Salehpour, Mohammad R.; Hildebrandt, Evangeline; Nuanjing, Jenny [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); D' Souza, David [London Regional Cancer Center, University of Western Ontario, London, Ontario (Canada); Souhami, Luis [Sylvester Comprehensive Cancer Center, Miami, Florida (United States); Small, William [Northwestern Memorial Hospital, Chicago, Illinois (United States); Gaur, Rakesh [St. Luke' s Cancer Institute, Kansas City, Missouri (United States); Jhingran, Anuja [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-05-01

    Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m{sup 2}). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is

  10. Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

    International Nuclear Information System (INIS)

    Klopp, Ann H.; Moughan, Jennifer; Portelance, Lorraine; Miller, Brigitte E.; Salehpour, Mohammad R.; Hildebrandt, Evangeline; Nuanjing, Jenny; D'Souza, David; Souhami, Luis; Small, William; Gaur, Rakesh; Jhingran, Anuja

    2013-01-01

    Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m 2 ). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is

  11. Childhood cancer survivorship educational resources in North American pediatric hematology/oncology fellowship training programs: a survey study.

    Science.gov (United States)

    Nathan, Paul C; Schiffman, Joshua D; Huang, Sujuan; Landier, Wendy; Bhatia, Smita; Eshelman-Kent, Debra; Wright, Jennifer; Oeffinger, Kevin C; Hudson, Melissa M

    2011-12-15

    Childhood cancer survivors require life-long care by clinicians with an understanding of the specific risks arising from the prior cancer and its therapy. We surveyed North American pediatric hematology/oncology training programs to evaluate their resources and capacity for educating medical trainees about survivorship. An Internet survey was sent to training program directors and long-term follow-up clinic (LTFU) directors at the 56 US and Canadian centers with pediatric hematology/oncology fellowship programs. Perceptions regarding barriers to and optimal methods of delivering survivorship education were compared among training program and LTFU clinic directors. Responses were received from 45/56 institutions of which 37/45 (82%) programs require that pediatric hematology/oncology fellows complete a mandatory rotation focused on survivorship. The rotation is 4 weeks or less in 21 programs. Most (36/45; 80%) offer didactic lectures on survivorship as part of their training curriculum, and these are considered mandatory for pediatric hematology/oncology fellows at 26/36 (72.2%). Only 10 programs (22%) provide training to medical specialty trainees other than pediatric hematology/oncology fellows. Respondents identified lack of time for trainees to spend learning about late effects as the most significant barrier to providing survivorship teaching. LTFU clinic directors were more likely than training program directors to identify lack of interest in survivorship among trainees and survivorship not being a formal or expected part of the fellowship training program as barriers. The results of this survey highlight the need to establish standard training requirements to promote the achievement of basic survivorship competencies by pediatric hematology/oncology fellows. Copyright © 2011 Wiley Periodicals, Inc.

  12. Preventative therapies for healthy women at high risk of breast cancer

    International Nuclear Information System (INIS)

    Sestak, Ivana

    2014-01-01

    Tamoxifen has been shown to reduce the risk of developing estrogen receptor (ER)-positive breast cancer by at least 50%, in both pre- and postmenopausal women. The current challenge is to find new agents with fewer side effects and to find agents that are specifically suitable for premenopausal women with ER-negative breast cancer. Other selective estrogen receptor modulators (SERMs), such as raloxifene, arzoxifene, and lasofoxifene, have been shown to reduce the incidence of breast cancer by 50%–80%. SERMs are interesting agents for the prevention of breast cancer, but longer follow-up is needed for some of them for a complete risk–benefit profile of these drugs. Aromatase inhibitors have emerged as new drugs in the prevention setting for postmenopausal women. In the Mammary Prevention 3 (MAP3) trial, a 65% reduction in invasive breast cancer with exemestane was observed, and the Breast Cancer Intervention Study-II trial, which compared anastrozole with placebo, reported a 60% reduction in those cancers. Although SERMs and aromatase inhibitors have been proven to be excellent agents in the preventive setting specifically for postmenopausal women and ER-positive breast cancer, newer agents have to be found specifically for ER-negative breast cancers, which mostly occur in premenopausal women

  13. Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions

    NARCIS (Netherlands)

    Tersmette, A. C.; Offerhaus, G. J.; Tersmette, K. W.; Giardiello, F. M.; Moore, G. W.; Tytgat, G. N.; Vandenbroucke, J. P.

    1990-01-01

    Controversy about gastric cancer risk after partial gastrectomy exists, especially in the United States. Therefore, we performed a meta-analysis to determine overall relative risk and weighted mean relative risk for subsets of postgastrectomy patients, define possible high risk patients suitable for

  14. Night-shift work and hematological cancers: a population based case-control study in three Nordic countries.

    Science.gov (United States)

    Talibov, Madar; Pukkala, Eero; Martinsen, Jan Ivar; Tryggvadottir, Laufey; Weiderpass, Elisabete; Hansen, Johnni

    2018-05-01

    Objective The aim of this case-control study was to assess the effect of night-shift work on the risk of hematological cancers. Methods The study included 39 371 leukemia, 56 713 non-Hodgkin lymphoma, 9322 Hodgkin lymphoma, and 26 188 multiple myeloma cases diagnosed between 1961 and 2005 in Finland, Sweden, and Iceland. Five controls for each case were selected from the Nordic Occupational Cancer Study (NOCCA) cohort, matched by year of birth, sex and country. Night-shift exposure was assessed by using the NOCCA job-exposure matrix (JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated from conditional logistic regression models. Results Overall, night work was not associated with a risk of hematological cancers. We observed a small but non-significantly increased risk for leukemia (OR 1.07, 95% CI 0.99-1.16), especially for acute myeloid leukemia (OR 1.15, 95% CI 0.97-1.36) among workers exposed to a high level of cumulative night work exposure. Night work exposure was not associated with lymphatic cancers and multiple myeloma. Conclusion This study did not support associations between night-shift work and hematological cancers.

  15. Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1.

    Science.gov (United States)

    Spans, Lien; Van den Broeck, Thomas; Smeets, Elien; Prekovic, Stefan; Thienpont, Bernard; Lambrechts, Diether; Karnes, R Jeffrey; Erho, Nicholas; Alshalalfa, Mohammed; Davicioni, Elai; Helsen, Christine; Gevaert, Thomas; Tosco, Lorenzo; Haustermans, Karin; Lerut, Evelyne; Joniau, Steven; Claessens, Frank

    2016-04-26

    The clinical heterogeneity of prostate cancer (PCa) makes it difficult to identify those patients that could benefit from more aggressive treatments. As a contribution to a better understanding of the genomic changes in the primary tumor that are associated with the development of high-risk disease, we performed exome sequencing and copy number determination of a clinically homogeneous cohort of 47 high-risk PCas. We confirmed recurrent mutations in SPOP, PTEN and TP53 among the 850 point mutations we detected. In seven cases, we discovered genomic aberrations in the TET1 (Ten-Eleven Translocation 1) gene which encodes a DNA hydroxymethylase than can modify methylated cytosines in genomic DNA and thus is linked with gene expression changes. TET1 protein levels were reduced in tumor versus non-tumor prostate tissue in 39 of 40 cases. The clinical relevance of changes in TET1 levels was demonstrated in an independent PCa cohort, in which low TET1 mRNA levels were significantly associated with worse metastases-free survival. We also demonstrate a strong reduction in hydroxymethylated DNA in tumor tissue in 27 of 41 cases. Furthermore, we report the first exploratory (h)MeDIP-Seq analyses of eight high-risk PCa samples. This reveals a large heterogeneity in hydroxymethylation changes in tumor versus non-tumor genomes which can be linked with cell polarity.

  16. Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients.

    Science.gov (United States)

    Hu, Xiang; Li, Ya-Qi; Li, Qing-Guo; Ma, Yan-Lei; Peng, Jun-Jie; Cai, Sanjun

    2018-05-22

    Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma. © 2018 The Author(s). Published by S. Karger AG, Basel.

  17. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-01-01

    Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR] 0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

  18. Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Pinkawa, Michael; Djukic, Victoria; Klotz, Jens; Holy, Richard; Eble, Michael J. [RWTH Aachen University, Department of Radiation Oncology, Aachen (Germany); Ribbing, Carolina [RWTH Aachen University, Department of Diagnostic and Interventional Radiology, Aachen (Germany)

    2015-10-15

    The primary objective of the study was to identify early hematologic changes predictive for radiotherapy (RT)-associated genitourinary and gastrointestinal toxicity. In a group of 91 prostate cancer patients presenting for primary (n = 51) or postoperative (n = 40) curative RT, blood samples (blood count, acute phase proteins, and cytokines) were analyzed before (T1), three times during (T2-T4), and 6-8 weeks after (T5) radiotherapy. Before RT (baseline), on the last day (acute toxicity), a median of 2 months and 16 months (late toxicity) after RT, patients responded to a validated questionnaire (Expanded Prostate Cancer Index Composite). Acute score changes > 20 points and late changes > 10 points were considered clinically relevant. Radiotherapy resulted in significant changes of hematologic parameters, with the largest effect on lymphocytes (mean decrease of 31-45 %) and significant dependence on target volume. C-reactive protein (CRP) elevation > 5 mg/l and hemoglobin level decrease ≥ 5 G/1 at T2 were found to be independently predictive for acute urinary toxicity (p < 0.01, respectively). CRP elevation was predominantly detected in primary prostate RT (p = 0.02). Early lymphocyte level elevation ≥ 0.3G/l at T2 was protective against late urinary and bowel toxicity (p = 0.02, respectively). Other significant predictive factors for late bowel toxicity were decreasing hemoglobin levels (cut-off ≥ 5 G/l) at T2 (p = 0.04); changes of TNF-α (tumor necrosis factor; p = 0.03) and ferritin levels (p = 0.02) at T5. All patients with late bowel toxicity had interleukin (IL)-6 levels < 1.5 ng/l at T2 (63 % without; p = 0.01). Early hematologic changes during prostate cancer radiotherapy are predictive for late urinary and bowel toxicity. (orig.) [German] Das primaere Ziel der Studie war die Identifikation von fruehen haematologischen Veraenderungen mit praediktiver Bedeutung fuer radiotherapieassoziierte genitourinale und gastrointestinale Toxizitaet. In einer

  19. One-unit versus two-unit cord-blood transplantation for hematologic cancers.

    Science.gov (United States)

    Wagner, John E; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R; Wall, Donna A; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R; Walters, Mark; Horowitz, Mary M; Kurtzberg, Joanne

    2014-10-30

    Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the

  20. Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling

    DEFF Research Database (Denmark)

    M. W. Wille, Mathilde; Dirksen, Asger; Ashraf, Haseem

    2016-01-01

    , lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P...... cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively......; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly...

  1. Magnetic Resonance Imaging as an Adjunct to Mammography for Breast Cancer Screening in Women at Less Than High Risk for Breast Cancer: A Health Technology Assessment

    Science.gov (United States)

    Nikitovic-Jokic, Milica; Holubowich, Corinne

    2016-01-01

    Background Screening with mammography can detect breast cancer early, before clinical symptoms appear. Some cancers, however, are not captured with mammography screening alone. Among women at high risk for breast cancer, magnetic resonance imaging (MRI) has been suggested as a safe adjunct (supplemental) screening tool that can detect breast cancers missed on screening mammography, potentially reducing the number of deaths associated with the disease. However, the use of adjunct screening tests may also increase the number of false-positive test results, which may lead to unnecessary follow-up testing, as well as patient stress and anxiety. We investigated the benefits and harms of MRI as an adjunct to mammography compared with mammography alone for screening women at less than high risk (average or higher than average risk) for breast cancer. Methods We searched Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD) Health Technology Assessment Database, and National Health Service (NHS) Economic Evaluation Database, from January 2002 to January 2016, for evidence of effectiveness, harms, and diagnostic accuracy. Only studies evaluating the use of screening breast MRI as an adjunct to mammography in the specified populations were included. Results No studies in women at less than high risk for breast cancer met our inclusion criteria. Conclusions It remains uncertain if the use of adjunct screening breast MRI in women at less than high risk (average or higher than average risk) for breast cancer will reduce breast cancer–related mortality without significant increases in unnecessary follow-up testing and treatment. PMID:27990198

  2. Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer.

    Science.gov (United States)

    Meiser, Bettina; Price, Melanie A; Butow, Phyllis N; Karatas, Janan; Wilson, Judy; Heiniger, Louise; Baylock, Brandi; Charles, Margaret; McLachlan, Sue-Anne; Phillips, Kelly-Anne

    2013-03-01

    Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one's mutation positive status (OR 2.9, p cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.

  3. A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

    International Nuclear Information System (INIS)

    Cho, Hanbyoul; Nam, Byung-Ho; Kim, Seok Mo; Cho, Chi-Heum; Kim, Byoung Gie; Ryu, Hee-Sug; Kang, Soon Beom; Kim, Jae-Hoon

    2014-01-01

    Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m 2 was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study

  4. A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Hanbyoul [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, Byung-Ho [Cancer Biostatistics Branch, Research Institute for National Cancer Control and Evaluation, National Cancer Center, Goyang (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University School of Medicine, Gwangju (Korea, Republic of); Cho, Chi-Heum [Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu (Korea, Republic of); Kim, Byoung Gie [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ryu, Hee-Sug [Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon (Korea, Republic of); Kang, Soon Beom [Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Kim, Jae-Hoon, E-mail: jaehoonkim@yuhs.ac [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-01

    Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m{sup 2} was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.

  5. Study Shows Aspirin Reduces Colorectal Cancer in Those at High Risk

    Science.gov (United States)

    Findings from the first large clinical trial of its kind indicate that taking high doses of aspirin daily for at least 2 years substantially reduces the risk of colorectal cancer among people at increased risk of the disease.

  6. Recruitment Methods and Show Rates to a Prostate Cancer Early Detection Program for High-Risk Men: A Comprehensive Analysis

    Science.gov (United States)

    Giri, Veda N.; Coups, Elliot J.; Ruth, Karen; Goplerud, Julia; Raysor, Susan; Kim, Taylor Y.; Bagden, Loretta; Mastalski, Kathleen; Zakrzewski, Debra; Leimkuhler, Suzanne; Watkins-Bruner, Deborah

    2009-01-01

    Purpose Men with a family history (FH) of prostate cancer (PCA) and African American (AA) men are at higher risk for PCA. Recruitment and retention of these high-risk men into early detection programs has been challenging. We report a comprehensive analysis on recruitment methods, show rates, and participant factors from the Prostate Cancer Risk Assessment Program (PRAP), which is a prospective, longitudinal PCA screening study. Materials and Methods Men 35–69 years are eligible if they have a FH of PCA, are AA, or have a BRCA1/2 mutation. Recruitment methods were analyzed with respect to participant demographics and show to the first PRAP appointment using standard statistical methods Results Out of 707 men recruited, 64.9% showed to the initial PRAP appointment. More individuals were recruited via radio than from referral or other methods (χ2 = 298.13, p < .0001). Men recruited via radio were more likely to be AA (p<0.001), less educated (p=0.003), not married or partnered (p=0.007), and have no FH of PCA (p<0.001). Men recruited via referrals had higher incomes (p=0.007). Men recruited via referral were more likely to attend their initial PRAP visit than those recruited by radio or other methods (χ2 = 27.08, p < .0001). Conclusions This comprehensive analysis finds that radio leads to higher recruitment of AA men with lower socioeconomic status. However, these are the high-risk men that have lower show rates for PCA screening. Targeted motivational measures need to be studied to improve show rates for PCA risk assessment for these high-risk men. PMID:19758657

  7. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent Laursen; Mouridsen, Henning T; Jensen, Maj-Britt

    2010-01-01

    BACKGROUND: The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single-agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) against no adjuvant systemic therapy in high-risk breast...... cancer patients. The authors report the results from that trial after a potential follow-up of 25 years. METHODS: Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly...... for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) intravenously on Days 1 and 8 every 4 weeks for 12 cycles...

  8. Role of high-risk human papillomavirus in the etiology of oral and oropharyngeal cancers in Thailand: A case-control study.

    Science.gov (United States)

    Chotipanich, Adit; Siriarechakul, Surattaya; Mungkung, On-Ong

    2018-01-01

    Among developing countries, Thailand shows no increase in the incidence of human papillomavirus-driven oropharyngeal cancer. The causal role of human papillomavirus infection in this pathology has not been researched thoroughly. A hospital-based, case-control study was performed which included 104 patients with newly diagnosed oral and oropharyngeal squamous cell carcinomas and 104 individuals without cancer. The Cervista high-risk human papillomavirus and 16/18 assays were used to detect human papillomavirus. Odds ratios were used to assess the association between high-risk genotypes of human papillomavirus and the cancers. High-risk human papillomavirus was detected in 4 of 52 (7.7%) oral cancer cases, 6 of 52 (11.5%) oropharyngeal cancer cases, and 1 of 104 (0.96%) control subjects. Of 104 cancer patients in the study, 83 were smokers. High-risk human papillomavirus was significantly associated with oropharyngeal cancer (odds ratio = 13.44, 95% confidence interval = 1.6-114.8) but was nonsignificantly associated with oral cancer (odds ratio = 8.58, 95% confidence interval = 0.9-78.9). However, after adjustment for smoking, high-risk human papillomavirus was determined to be nonsignificantly associated with oropharyngeal cancer (adjusted odds ratio = 5.83, 95% confidence interval = 0.8-43.5). Although low human papillomavirus prevalence was observed, the rate of high-risk human papillomavirus infection in the cancer group was still higher than that in the control group. Smoking may have an influence on the etiology of human papillomavirus-related cancers. However, the study is underpowered to clarify the role of human papillomavirus as the independent risk factor for oral and oropharyngeal cancers in the Thai population.

  9. 10-Year Survival and Quality of Life in Patients With High-Risk PN0 Prostate Cancer Following Definitive Radiotherapy

    International Nuclear Information System (INIS)

    Berg, Arne; Lilleby, Wolfgang; Bruland, Oyvind Sverre; Fossa, Sophie Dorothea

    2007-01-01

    Purpose: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T 1-4p N 0 M 0 prostate cancer patients provided by a single institution between 1989 and 1996. Methods and Materials: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. Results: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T 3-4 or Gleason score (GS) ≥7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T 1-2 and GS ≤7A [3+4]) were 79%, 95%, and 73%, respectively. Both CSS and cPFS were predicted by GS and T-classification; OS was associated with GS only. High-risk, but not low-risk, patients had reduced OS compared with the general population (p p N 0 , RT with dosage 3-4 or GS ≥7B

  10. Treatment options for high-risk T1 bladder cancer. Status quo and future perspectives of radiochemotherapy

    International Nuclear Information System (INIS)

    Weiss, C.; Roedel, C.; Ott, O.J.; Wittlinger, M.; Fietkau, R.; Sauer, R.; Krause, S.F.

    2008-01-01

    Purpose: to review the standards and new developments in diagnosis and management of high-risk T1 bladder cancer with emphasis on the role of radiotherapy (RT) and radiochemotherapy (RCT). Material and methods: a systematic review of the literature on developments in diagnosis and management of high-risk T1 bladder cancer was performed. Results: first transurethral resection (TUR), as radical as safely possible, supported by fluorescence cystoscopy, shows higher detection and decreased recurrence rates. An immediate single postoperative instillation with a chemotherapeutic drug reduces the relative risk of recurrence by 40%. A second TUR is recommended to assess residual tumor. For adjuvant intravesical therapy, bacille Calmette-Guerin (BCG) demonstrated the highest efficacy. Early cystectomy should be reserved for selected patients. A recent phase III trial comparing RT versus conservative treatment in T1 G3 tumors could not show any advantage for RT. Data from Erlangen, Germany, using combined RCT in 80% of the patients, compare favorably with most of the contemporary BCG series. Conclusion: results of intravesical therapy are still unsatisfying and early cystectomy is associated with morbidity and mortality. RT alone proved not superior to other conservative treatment strategies. However, data on RCT are promising and demonstrate an alternative to intravesical therapy and radical cystectomy. (orig.)

  11. Quality of life in survivors of hematological malignancies stratified by cancer type, time since diagnosis and stem cell transplantation.

    Science.gov (United States)

    Esser, Peter; Kuba, Katharina; Mehnert, Anja; Johansen, Christoffer; Hinz, Andreas; Lordick, Florian; Götze, Heide

    2018-06-01

    Quality of life (QoL) has become an important tool to guide decision making in oncology. Given the heterogeneity among hematological cancer survivors, however, clinicians need comparative data across different subsets. This study recruited survivors of hematological malignancies (≥ 2.5 years after diagnosis) from two German cancer registries. QoL was assessed with the EORTC QLQ-C30. The sample was stratified by cancer type, time since diagnosis, treatment with stem cell transplantation (SCT) and type of SCT. First, levels of QoL were compared across subsamples when controlling for several covariates. Second, we contrasted subsamples with gender- and age-matched population controls obtained from the general population. Of 2001 survivors contacted by mail, 922 (46%) participated in the study. QoL did not significantly differ between the subsamples. All subsamples scored significantly lower in functioning and significantly higher in symptom burden compared to population controls (all p < .001). Almost all of these group effects reached clinically meaningful sizes (Cohen's d ≥ .5). Group differences in global health/QoL were mostly non-significant. Hematological cancer survivors are associated with practically relevant impairments irrespective of differences in central medical characteristics. Nevertheless, survivors seem to evaluate their overall situation as relatively well. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Hereditary gynaecologic cancers in Nepal: a proposed model of care to serve high risk populations in developing countries.

    Science.gov (United States)

    Pokharel, Hanoon P; Hacker, Neville F; Andrews, Lesley

    2017-01-01

    Endometrial, ovarian and breast cancers are paradigms for global health disparity. Women living in the developing world continue to present in later stages of disease and have fewer options for treatment than those in developed countries. Risk reducing surgery is of proven benefit for women at high risk of gynaecological cancer. There is no specific model for identification and management of such women in the developing world. We have integrated data from our published audit of a major gynaecological oncology centre at Royal Hospital for Women in Australia, with data from our survey and a focus group discussion of Nepalese gynaecological health care professionals regarding genetic testing, and findings from the literature. These data have been used to identify current barriers to multidisciplinary gynaecological oncology care in developing nations, and to develop a model to integrate hereditary cancer services into cancer care in Nepal, as a paradigm for other developing nations. The ability to identify women with hereditary gynaecological cancer in developing nations is influenced by their late presentation (if active management is declined or not appropriate), limited access to specialised services and cultural and financial barriers. In order to include genetic assessment in multidisciplinary gynaecological cancer care, education needs to be provided to all levels of health care providers to enable reporting of family history, and appropriate ordering of investigations. Training of genetic counsellors is needed to assist in the interpretation of results and extending care to unaffected at-risk relatives. Novel approaches will be required to overcome geographic and financial barriers, including mainstreaming of genetic testing, telephone counselling, use of mouth swabs and utilisation of international laboratories. Women in Nepal have yet to receive benefits from the advances in early cancer diagnosis and management. There is a potential of extending the benefits

  13. Breast Density and Benign Breast Disease: Risk Assessment to Identify Women at High Risk of Breast Cancer.

    Science.gov (United States)

    Tice, Jeffrey A; Miglioretti, Diana L; Li, Chin-Shang; Vachon, Celine M; Gard, Charlotte C; Kerlikowske, Karla

    2015-10-01

    Women with proliferative breast lesions are candidates for primary prevention, but few risk models incorporate benign findings to assess breast cancer risk. We incorporated benign breast disease (BBD) diagnoses into the Breast Cancer Surveillance Consortium (BCSC) risk model, the only breast cancer risk assessment tool that uses breast density. We developed and validated a competing-risk model using 2000 to 2010 SEER data for breast cancer incidence and 2010 vital statistics to adjust for the competing risk of death. We used Cox proportional hazards regression to estimate the relative hazards for age, race/ethnicity, family history of breast cancer, history of breast biopsy, BBD diagnoses, and breast density in the BCSC. We included 1,135,977 women age 35 to 74 years undergoing mammography with no history of breast cancer; 17% of the women had a prior breast biopsy. During a mean follow-up of 6.9 years, 17,908 women were diagnosed with invasive breast cancer. The BCSC BBD model slightly overpredicted risk (expected-to-observed ratio, 1.04; 95% CI, 1.03 to 1.06) and had modest discriminatory accuracy (area under the receiver operator characteristic curve, 0.665). Among women with proliferative findings, adding BBD to the model increased the proportion of women with an estimated 5-year risk of 3% or higher from 9.3% to 27.8% (P<.001). The BCSC BBD model accurately estimates women's risk for breast cancer using breast density and BBD diagnoses. Greater numbers of high-risk women eligible for primary prevention after BBD diagnosis are identified using the BCSC BBD model. © 2015 by American Society of Clinical Oncology.

  14. RAD51C germline mutations in breast and ovarian cancer cases from high-risk families.

    Directory of Open Access Journals (Sweden)

    Jessica Clague

    Full Text Available BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5' UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001. Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene.

  15. Risk perception among Brazilian individuals with high risk for colorectal cancer and colonoscopy

    Directory of Open Access Journals (Sweden)

    Santos Erika M

    2011-07-01

    Full Text Available Abstract Background Risk perception is considered a motivating factor for adopting preventive behaviors. This study aimed to verify the demographic characteristics and cancer family history that are predictors of risk perception and to verify if risk perception is a predictor of colonoscopy adherence. Methods Individuals with a family colorectal cancer history as indicated by a proband with cancer were interviewed by telephone. They responded to a questionnaire covering demographic characteristics, colonoscopy history and four questions on risk perception. Tests of multiple linear regression and logistic regression were used to identify associations between dependent and independent variables. Results The 117 participants belonged to 62 families and had a mean age of 45.2 years. The majority of these individuals were female (74.4% and from families who met the Amsterdam Criteria (54.7%. The average risk perception was 47.6%, with a median of 50%. The average population perception of individual risk was 55.4%, with a median of 50%. Variables associated with a higher risk perception were age, gender, religion, school level, income, and death of a family member. The variable predicting colonoscopy was receiving medical information regarding risk (odds ratio OR 8.40. Conclusions We found that family cancer history characteristics (number of relatives with cancer, risk classification are associated with adequate risk perception. Risk perception does not predict colonoscopy in this sample. The only variable that predicted colonoscopy was receiving medical information recommending screening.

  16. Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Andrew Y.; Golden, Daniel W. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Bazan, Jose G. [Department of Radiation Oncology, The Ohio State University, Columbus, Ohio (United States); Kopec, Malgorzata; Pelizzari, Charles A. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Aggarwal, Sonya; Chang, Daniel T. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

    2017-02-01

    Purpose: Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. Methods and Materials: Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs. Results: Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P=.02), grade 3+ neutropenia (33% vs 8%, P=.04), and grade 2+ thrombocytopenia (32% vs 7%, P=.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 (P<.1). Conclusions: Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total “marrow reserve” can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.

  17. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    Directory of Open Access Journals (Sweden)

    Harris Nathan

    2008-12-01

    Full Text Available Abstract Background Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63 were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS for biomarker finding. Initial results were validated by analysis of sample set II (n = 371, using one-dimensional gel-electrophoresis. Results In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20, identified as haptoglobin (Hp alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014. Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2, of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221 and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966 for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive

  18. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II)

    DEFF Research Database (Denmark)

    Cuzick, Jack; Sestak, Ivana; Forbes, John F

    2014-01-01

    of the disease. METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific...

  19. Regional radiotherapy in high-risk breast cancer: is the issue solved?

    DEFF Research Database (Denmark)

    Krause, M; Petersen, C; Offersen, B V

    2015-01-01

    Adjuvant radiotherapy is the treatment standard for breast cancer with lymph node metastases after breast-conserving surgery or mastectomy. The inclusion of regional lymph nodes into the treatment volumes has been a question in recent clinical trials. Their impact on treatment standards and open...

  20. Is screening for pancreatic cancer in high-risk groups cost-effective?

    DEFF Research Database (Denmark)

    Jørgensen, Maiken Thyregod; Gerdes, Anne-Marie; Sørensen, Jan

    2016-01-01

    OBJECTIVE: Pancreatic cancer (PC) is the fourth leading cause of cancer death worldwide, symptoms are few and diffuse, and when the diagnosis has been made only 10-15% would benefit from resection. Surgery is the only potentially curable treatment for pancreatic cancer, and the prognosis seems to......$ per QALY. CONCLUSIONS: With a threshold value of 50,000 US$ per QALY this screening program appears to constitute a cost-effective intervention although screening of HP patients appears to be less cost-effective than FPC patients....... with Hereditary pancreatitis or with a disposition of HP and 40 first-degree relatives of patients with Familial Pancreatic Cancer (FPC) were screened for development of Pancreatic Ductal Adenocarcinoma (PDAC) with yearly endoscopic ultrasound. The cost-effectiveness of screening in comparison with no......-screening was assessed by the incremental cost-utility ratio (ICER). RESULTS: By screening the FPC group we identified 2 patients with PDAC who were treated by total pancreatectomy. One patient is still alive, while the other died after 7 months due to cardiac surgery complications. Stratified analysis of patients...

  1. Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer

    Directory of Open Access Journals (Sweden)

    Shirish Shukla

    2014-01-01

    Full Text Available Background & objectives: High-risk human papilloma virus (HR-HPV infection and its integration in host genome is a key event in malignant transformation of cervical cells. HPV16 being a dominant HR-HPV type, we undertook this study to analyze if viral load and physical state of the virus correlated with each other in the absence of other confounding variables and examined their potential as predictors of progressive cervical lesions. Methods: Both, viral load and integration status of HPV16 were determined by real time URR PCR and estimation of E2:E6 ratio in a total of 130 PGMY-RLB -confirmed, monotypic HPV16-infected cervical DNA samples from biopsies of cytology-confirmed low grade (LSIL, 30 and high grade (HSIL, 30, and invasive carcinoma, (squamous cell carcinoma SCC, 70 cases. Results: Investigation of DNA samples revealed a gradual increase in HPV16 viral load over several magnitudes and increased frequency of integration from LSIL to HSIL and HSIL to invasive cancer in relation to the severity of lesions in monotypic HPV16-infected cervical tissues. In a substantial number of precancer (11/60 and cancer cases (29/70, HPV16 was detected in concomitant mixed form. The concomitant form of HPV16 genome carried significantly higher viral load. Interpretation & conclusions: Overall, viral load and integration increased with disease severity and could be useful biomarkers in disease progression, at least, in HPV16-infected cervical pre-cancer and cancer lesions.

  2. Occupational risk factors have to be considered in the definition of high-risk lung cancer populations.

    Science.gov (United States)

    Wild, P; Gonzalez, M; Bourgkard, E; Courouble, N; Clément-Duchêne, C; Martinet, Y; Févotte, J; Paris, C

    2012-03-27

    The aim of this study was to compute attributable fractions (AF) to occupational factors in an area in North-Eastern France with high lung cancer rates and a past of mining and steel industry. A population-based case-control study among males aged 40-79 was conducted, including confirmed primary lung cancer cases from all hospitals of the study region. Controls were stratified by broad age-classes, district and socioeconomic classes. Detailed occupational and personal risk factors were obtained in face-to-face interviews. Cumulative occupational exposure indices were obtained from the questionnaires. Attributable fractions were computed from multiple unconditional logistic regression models. A total of 246 cases and 531 controls were included. The odds ratios (ORs) adjusted on cumulative smoking and family history of lung cancer increased significantly with the cumulative exposure indices to asbestos, polycyclic aromatic hydrocarbons and crystalline silica, and with exposure to diesel motor exhaust. The AF for occupational factors exceeded 50%, the most important contributor being crystalline silica and asbestos. These AFs are higher than most published figures. This can be because of the highly industrialised area or methods for exposure assessments. Occupational factors are important risk factors and should not be forgotten when defining high-risk lung cancer populations.

  3. MRI screening for breast cancer in women at high risk; is the Australian breast MRI screening access program addressing the needs of women at high risk of breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Schenberg, Tess [Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Mitchell, Gillian [Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria (Australia); Taylor, Donna [School of Surgery, University of Western Australia, Perth, Western Australia (Australia); Department of Radiology, Royal Perth Hospital, Perth, Western Australia (Australia); BreastScreen Western Australia, Adelaide Terrace, Perth, Western Australia (Australia); Saunders, Christobel [School of Surgery, University of Western Australia, Perth, Western Australia (Australia); Department of General Surgery, St John of God Hospital, Perth, Western Australia (Australia); Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)

    2015-09-15

    Breast magnetic resonance imaging (MRI) screening of women under 50 years old at high familial risk of breast cancer was given interim funding by Medicare in 2009 on the basis that a review would be undertaken. An updated literature review has been undertaken by the Medical Services Advisory Committee but there has been no assessment of the quality of the screening or other screening outcomes. This review examines the evidence basis of breast MRI screening and how this fits within an Australian context with the purpose of informing future modifications to the provision of Medicare-funded breast MRI screening in Australia. Issues discussed will include selection of high-risk women, the options for MRI screening frequency and measuring the outcomes of screening.

  4. MRI screening for breast cancer in women at high risk; is the Australian breast MRI screening access program addressing the needs of women at high risk of breast cancer?

    International Nuclear Information System (INIS)

    Schenberg, Tess; Mitchell, Gillian; Taylor, Donna; Saunders, Christobel

    2015-01-01

    Breast magnetic resonance imaging (MRI) screening of women under 50 years old at high familial risk of breast cancer was given interim funding by Medicare in 2009 on the basis that a review would be undertaken. An updated literature review has been undertaken by the Medical Services Advisory Committee but there has been no assessment of the quality of the screening or other screening outcomes. This review examines the evidence basis of breast MRI screening and how this fits within an Australian context with the purpose of informing future modifications to the provision of Medicare-funded breast MRI screening in Australia. Issues discussed will include selection of high-risk women, the options for MRI screening frequency and measuring the outcomes of screening

  5. Biomarkers of Tobacco Smoke Exposure in Racial/Ethnic Groups at High Risk for Lung Cancer

    Science.gov (United States)

    Moolchan, Eric T.; Pokhrel, Pallav; Herzog, Thaddeus; Cassel, Kevin D.; Pagano, Ian; Franke, Adrian A.; Kaholokula, Joseph Keawe’aimoku; Sy, Angela; Alexander, Linda A.; Trinidad, Dennis R.; Sakuma, Kari-Lyn; Johnson, C. Anderson; Antonio, Alyssa; Jorgensen, Dorothy; Lynch, Tania; Kawamoto, Crissy; Clanton, Mark S.

    2015-01-01

    Objectives. We examined biomarkers of tobacco smoke exposure among Native Hawaiians, Filipinos, and Whites, groups that have different lung cancer risk. Methods. We collected survey data and height, weight, saliva, and carbon monoxide (CO) levels from a sample of daily smokers aged 18–35 (n = 179). Mean measures of nicotine, cotinine, cotinine/cigarettes per day ratio, trans 3′ hydroxycotinine, the nicotine metabolite ratio (NMR), and expired CO were compared among racial/ethnic groups. Results. The geometric means for cotinine, the cotinine/cigarettes per day ratio, and CO did not significantly differ among racial/ethnic groups in the adjusted models. After adjusting for gender, body mass index, menthol smoking, Hispanic ethnicity, and number of cigarettes smoked per day, the NMR was significantly higher among Whites than among Native Hawaiians and Filipinos (NMR = 0.33, 0.20, 0.19, P ≤ .001). The NMR increased with increasing White parental ancestry. The NMR was not significantly correlated with social–environmental stressors. Conclusions. Racial/ethnic groups with higher rates of lung cancer had slower nicotine metabolism than Whites. The complex relationship between lung cancer risk and nicotine metabolism among racial/ethnic groups needs further clarification. PMID:25880962

  6. Clinical Trial of Acolbifene in Premenopausal Women at High Risk for Breast Cancer.

    Science.gov (United States)

    Fabian, Carol J; Kimler, Bruce F; Zalles, Carola M; Phillips, Teresa A; Metheny, Trina; Petroff, Brian K; Havighurst, Thomas C; Kim, KyungMann; Bailey, Howard H; Heckman-Stoddard, Brandy M

    2015-12-01

    The purpose of this study was to assess the feasibility of using the selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women. To do so, we assessed change in proliferation in benign breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) as a primary endpoint, along with changes in other risk biomarkers and objective and subjective side effects as secondary endpoints. Twenty-five women with cytologic hyperplasia ± atypia and ≥2% of breast epithelial cells staining positive for Ki-67, received 20 mg acolbifene daily for 6-8 months, and then had benign breast tissue and blood risk biomarkers reassessed. Ki-67 decreased from a median of 4.6% [interquartile range (IQR), 3.1%-8.5%] at baseline to 1.4% (IQR, 0.6%-3.5%) after acolbifene (P breast density. Subjective side effects were minimal with no significant increase in hot flashes, muscle cramps, arthralgias, or fatigue. Objective measures showed a clinically insignificant decrease in lumbar spine bone density (DEXA) and an increase in ovarian cysts but no change in endometrial thickness (sonography). In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen-inducible gene expression but minimal side effects, suggesting a phase IIB placebo-controlled trial evaluating it further for breast cancer prevention. ©2015 American Association for Cancer Research.

  7. Anti-cancer vaccine therapy for hematologic malignancies: An evolving era.

    Science.gov (United States)

    Nahas, Myrna R; Rosenblatt, Jacalyn; Lazarus, Hillard M; Avigan, David

    2018-02-15

    The potential promise of therapeutic vaccination as effective therapy for hematologic malignancies is supported by the observation that allogeneic hematopoietic cell transplantation is curative for a subset of patients due to the graft-versus-tumor effect mediated by alloreactive lymphocytes. Tumor vaccines are being explored as a therapeutic strategy to re-educate host immunity to recognize and target malignant cells through the activation and expansion of effector cell populations. Via several mechanisms, tumor cells induce T cell dysfunction and senescence, amplifying and maintaining tumor cell immunosuppressive effects, resulting in failure of clinical trials of tumor vaccines and adoptive T cell therapies. The fundamental premise of successful vaccine design involves the introduction of tumor-associated antigens in the context of effective antigen presentation so that tolerance can be reversed and a productive response can be generated. With the increasing understanding of the role of both the tumor and tumor microenvironment in fostering immune tolerance, vaccine therapy is being explored in the context of immunomodulatory therapies. The most effective strategy may be to use combination therapies such as anti-cancer vaccines with checkpoint blockade to target critical aspects of this environment in an effort to prevent the re-establishment of tumor tolerance while limiting toxicity associated with autoimmunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Y.H.; Zeng, Z.F. [State Key Laboratory of Oncology in South China, Guangzhou (China); Sun Yat-sen University Cancer Center, Departments of Radiation Oncology, Guangzhou (China); Zhang, X. [State Key Laboratory of Oncology in South China, Guangzhou (China); Sun Yat-sen University Cancer Center, Departments of Thoracic Surgery, Guangzhou (China); An, X. [State Key Laboratory of Oncology in South China, Guangzhou (China); Sun Yat-sen University Cancer Center, Departments of Medical Oncology, Guangzhou (China); Cai, M.Y. [State Key Laboratory of Oncology in South China, Guangzhou (China); Sun Yat-sen University Cancer Center, Departments of Pathology, Guangzhou (China); Chen, G.; Kong, L.H.; Lin, J.Z.; Wan, D.S.; Pan, Z.Z.; Ding, P.R. [State Key Laboratory of Oncology in South China, Guangzhou (China); Sun Yat-sen University Cancer Center, Departments of Colorectal Surgery, Guangzhou (China)

    2014-02-15

    Conventional neoadjuvant chemoradiotherapy (CRT) is suboptimal for systemic control in locally advanced rectal cancer (LARC). To improve systemic control, we developed an alternative approach in which an intensified oxaliplatin and capecitabine (XELOX) chemotherapy regimen was administered concomitantly with radiation and extended to the resting period (consolidation chemotherapy) for high-risk LARC. The aim of the current study was to evaluate the short-term efficacy and toxicity of this strategy. Patients with high-risk LARC were treated with CRT. Two cycles of XELOX were administered concomitantly with radiation. Thereafter, an additional cycle of the same regimen was administered during the resting period after completion of CRT. Tumor response, toxicities and surgical complications were recorded. This study includes 36 patients treated with the above strategy. All patients completed the planned concurrent CRT. Because of grade 3 toxicities, 2 patients were unable to complete the additional chemotherapy. Grade 3 toxicities were leucopenia (2.8 %), diarrhea (2.8 %) and radiodermatitis (2.8 %). All patients underwent optimal surgery with total mesorectal excision (TME) and a sphincter-saving procedure was performed in 27 patients (75 %). There was no perioperative mortality. Postoperative complications developed in 7 patients (19.4 %). Pathologic complete regression (pCR),''nearly pCR'' (major regression), and moderate or minimal regression were achieved in 13 (36.1 %), 16 (44.4 %), and 7 patients (19.5 %), respectively. The preliminary results suggest that a XELOX regimen initially administered concomitantly with radiotherapy and then extended to the resting period in high-risk LARC patients is well tolerated. The strategy is highly effective in terms of pCR and nearly pCR rates, and thus warrants further investigation. (orig.)

  9. The value of FDG-PET/CT in assessing single pulmonary nodules in patients at high risk of lung cancer

    International Nuclear Information System (INIS)

    Kagna, Olga; Solomonov, Anna; Fruchter, Oren; Keidar, Zohar; Bar-Shalom, Rachel; Israel, Ora; Yigla, Mordechai; Guralnik, Luda

    2009-01-01

    To evaluate whether PET/low-dose CT (ldCT) using 18 F-fluorodeoxyglucose (FDG) improves characterization of indeterminate single pulmonary nodules (SPNs) in patients at high risk of lung cancer. Retrospective analysis of 307 patients who underwent FDG-PET/CT for indeterminate SPNs identified 93 (70 men, age range 46-90 years) at high risk of lung cancer (age >40 years, minimum 10 pack-year smokers). SPNs were evaluated for the presence and intensity of FDG avidity and ldCT patterns. The performance of visual and semiquantitative FDG-PET/ldCT algorithms for characterization of SPNs was compared to that of ldCT. Incongruent FDG-PET and ldCT patterns were analyzed for significance in further patient management. Malignancy was diagnosed in 38% patients. FDG avidity defined 33 SPNs as true-positive (TP) and 2 as false-negative (FN) (malignant), and 41 as true-negative (TN) and 17 as false-positive (FP) (benign). For SUVmax of 2.2 (by ROC analysis) there were 27 TP, 8 FN, 48 TN and 10 FP SPNs. LdCT defined 34 TP, 1 FN, 28 TN and 30 FP lesions. Of the FP lesions on ldCT, 60% were FDG-negative. Visual PET/ldCT analysis had a sensitivity of 94%, a specificity of 70%, an accuracy of 80%, a positive predictive value (PPV) of 66%, and a negative predictive value (NPV) of 95% as compared to 77%, 83%, 81%, 73%, 86% for semiquantitative PET/ldCT and 97%, 48%, 66%, 53%, 96% for ldCT, respectively. Both PET/ldCT algorithms had statistically significantly higher specificity and accuracy than ldCT. Semiquantitative analysis showed significantly higher PPV and lower sensitivity and NPV than found with ldCT. A single screening procedure encompassing FDG-PET and ldCT may improve screening for lung cancer in high-risk patients. The significantly improved specificity may potentially reduce FP ldCT results and further unnecessary invasive procedures. (orig.)

  10. Concurrent cisplatin-based chemoradiotherapy versus exclusive radiotherapy in high-risk cervical cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Meng XY

    2016-03-01

    Full Text Available Xiang-Yu Meng,1,* Yi Liao,2,* Xiao-Ping Liu,3 Sheng Li,1 Ming-Jun Shi,4 Xian-Tao Zeng11Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 2Department of Oncology, Nanfang Hospital, Southern Medical University, GuangZhou Province, People’s Republic of China; 3Department of Hematology and Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 4Institut Curie, Paris Sciences et Lettres Research University, Le Centre National de la Recherche Scientifique, Les Unités Mixtes de Recherche 144, F-75005, Paris, France*These authors contributed equally to this workObjective: To evaluate the efficacy and safety of cisplatin-based concurrent chemoradiotherapy (DDP-CCRT in patients with high-risk cervical carcinoma (CC compared with exclusive radiotherapy (RT.Materials and methods: Databases were searched for randomized controlled trials (RCTs and cohort studies comparing DDP-CCRT with RT alone. Risk of bias assessment for RCTs was performed using the Cochrane Collaboration’s tool, and the Newcastle–Ottawa quality scale was used to perform quality assessment for cohort studies. Meta-analysis was conducted using Review Manager 5 and Stata 12.0 software.Results: Finally, eight RCTs and three cohort studies containing 2,130 subjects were included. Analysis on total failures revealed a statistically significant difference in favor of DDP-CCRT (risk ratio =0.77, 95% confidence intervals [CIs]: 0.67–0.89. No significant heterogeneity was detected for pooled analysis concerning overall survival; the result of which demonstrated the superiority of DDP-CCRT over RT alone (hazard ratio =0.68, 95% CI: 0.57–0.80, and stable and established accumulative effects were observed in cumulative meta-analysis. Similar results were observed for progression-free survival (hazard ratio =0.63, 95% CI: 0.50–0.76. In terms of

  11. Comparison of primary radiation versus robotic surgery plus adjuvant radiation in high-risk prostate cancer: A single center experience

    Directory of Open Access Journals (Sweden)

    Prabhsimranjot Singh

    2015-01-01

    Full Text Available Objective: The objective of this study was to compare robotic-prostatectomy plus adjuvant radiation therapy (RPRAT versus primary RT for high-risk prostate cancer (HRPCa. Materials and Methods: A retrospective chart review was performed for the HRPCa patients treated in our institution between 2000 and 2010. One hundred and twenty-three patients with high-risk disease were identified. The Chi-square test and Fisher′s exact test were used to compare local control and distant failure rates between the two treatment modalities. For prostate-specific antigen comparisons between groups, Wilcoxon rank-sum test was used. Results: The median follow-up was 49 months (range: 3-138 months. Local control, biochemical recurrence rate, distant metastasis, toxicity, and disease-free survival were similar in the two groups. Conclusions: Primary RT is an excellent treatment option in patients with HRPCa, is equally effective and less expensive treatment compared with RPRAT. A prospective randomized study is required to guide treatment for patients with HRPCa.

  12. Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy

    International Nuclear Information System (INIS)

    Yang, T. Jonathan; Oh, Jung Hun; Apte, Aditya; Son, Christina H.; Deasy, Joseph O.; Goodman, Karyn A.

    2014-01-01

    Background and purpose: To identify clinical and dosimetric factors associated with hematologic toxicity (HT) during chemoradiotherapy for rectal cancer. Materials and methods: We analyzed 120 rectal cancer patients treated with neoadjuvant pelvic radiotherapy (PRT) with concurrent 5-fluorouracil-based chemotherapy. The coxal (ilium, ischium, and pubis) bone marrow (BM), sacral BM, and femoral BM were contoured and dose-volume parameters were extracted. Associations between cell count trend and clinical predictors were tested using repeated-measures analysis of variance (ANOVA) test. Associations between clinical variables, Vx (percentage volume receiving x Gy), and cell count ratio at nadir were tested using linear regression models. Results: Nadirs for white blood cell count (WBC), absolute neutrophil count (ANC), and platelets (PLT) occurred in the second week of PRT and the fifth week for hemoglobin and absolute lymphocyte count (ALC). Using cell count ratio, patients treated with 3DCRT had a lower WBC ratio trend during PRT compared to patients treated with IMRT (p = 0.04), and patients ⩾59 years of age had a lower hemoglobin ratio trend during PRT (p = 0.02). Using absolute cell count, patients treated with 3DCRT had lower ANC cell count trend (p = 0.03), and women had lower hemoglobin cell count trend compared to men (p = 0.03). On univariate analysis, use of 3DCRT was associated with a lower WBC ratio at nadir (p = 0.02). On multiple regression analysis using dosimetric variables, coxal BM V45 (p = 0.03) and sacral BM V45 (p = 0.03) were associated with a lower WBC and ANC ratio at nadir, respectively. Conclusions: HT trends during PRT revealed distinct patterns: WBC, ANC, and PLT cell counts reach nadirs early and recover, while hemoglobin and ALC decline steadily. Patients who were treated with 3DCRT and older patients experienced lower cell count ratio trend during PRT. Dosimetric constraints using coxal BM V45 and sacral BM V45 can be considered

  13. Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone.

    Science.gov (United States)

    Agarwal, Harsh K; Mertan, Francesca V; Sankineni, Sandeep; Bernardo, Marcelino; Senegas, Julien; Keupp, Jochen; Daar, Dagane; Merino, Maria; Wood, Bradford J; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

    2017-01-01

    To retrospectively determine the optimal b-value(s) of diffusion-weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate. Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm 2 ) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b-value of 4000 s/mm 2 were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm 2 ) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system. The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm 2 (0.74) with no statistically significant different AUC of DWI with b-values 1067-2000 s/mm 2 . The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm 2 . There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI. The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm 2 . The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm 2 . 4 J. Magn. Reson. Imaging 2017;45:125-131. © 2016 International Society for Magnetic Resonance in Medicine.

  14. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S.A.; Neft, R.E.; Lechner, J.F. [and others

    1995-12-01

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This {open_quotes}field cancerization{close_quotes} theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in {open_quotes}normal{close_quotes} bronchial epithelial cells.

  15. An association between Trichomonas vaginalis and high-risk human papillomavirus in rural Tanzanian women undergoing cervical cancer screening.

    Science.gov (United States)

    Lazenby, Gweneth B; Taylor, Peyton T; Badman, Barbara S; McHaki, Emil; Korte, Jeffrey E; Soper, David E; Young Pierce, Jennifer

    2014-01-01

    The goal of this study was to determine the prevalence of vaginitis and its association with high-risk human papillomavirus (HR HPV) in women undergoing cervical cancer screening in rural Tanzania. For the purpose of cervical cancer screening, cytology and HR HPV polymerase chain reaction data were collected from 324 women aged between 30 and 60 years. Microscopy and gram stains were used to detect yeast and bacterial vaginosis. Cervical nucleic acid amplification test specimens were collected for the detection of Trichomonas vaginalis (TV), Chlamydia trachomatis, and Neisseria gonorrhoeae. The majority of women were married (320 of 324) and reported having a single sexual partner (270 of 324); the median age of participants was 41 years. HR HPV was detected in 42 participants. Forty-seven percent of women had vaginitis. Bacterial vaginosis was the most common infection (32.4%), followed by TV (10.4%), and yeast (6.8%). In multivariable logistic regression analysis, TV was associated with an increased risk of HR HPV (odds ratio, 4.2 [95% CI, 1.7-10.3]). Patients with TV were 6.5 times more likely to have HPV type 16 than patients negative for TV (50% vs 13.3%) (odds ratio, 6.5 [95% CI, 1.1-37]). Among rural Tanzanian women who presented for cervical cancer screening, Trichomonas vaginitis was significantly associated with HR HPV infection (specifically type 16). © 2014 Published by Elsevier HS Journals, Inc.

  16. Lack of Evidence for a Relationship between High Risk Human Papillomaviruses and Breast Cancer in Iranian Patients.

    Science.gov (United States)

    Doosti, Masoud; Bakhshesh, Mehran; Zahir, Shokouh Taghipour; Shayestehpour, Mohammad; Karimi-Zarchi, Mojgan

    2016-01-01

    Whether there is any relationship between human papilloma virus (HPV) and breast carcinoma is not clear. Some previous studies have indicated a possible role in oncogenesis in the breast. In this study, we therefore analyzed the presence of HPV infection in breast tissues of Iranian women from Yazd city. In a cross-sectional study, formalin-fixed paraffin-embedded tissues from 87 patients with breast cancer and 84 cases with breast fibrocystic lesions (control group) were selected from a tissue archive. Grade of tumors and fibrocystic tissues were determined by two pathologists. The nested-PCR method was performed for detection of HPVs in samples. HPV genotypes were determined by sequencing and the phylogenetic tree depicted by MEGA software. Of the 87 women with breast cancer, 22.9% (20 isolates) had positive results for HPV DNA. In the control group no HPV was detected. The HPV genotypes in positive samples were HPV-16 (35%) HPV-18 (15%), HPV-6 (45%) and HPV-11 (5%). The data did not approved a significant correlation between tissue pathology of breast cancer and the HPV genotype frequency. The data did not provide any evidence for a role of high risk HPV types in oncogenesis in the breast.

  17. Opportunities for Skin Cancer Prevention Education among Individuals Attending a Community Skin Cancer Screening in a High-Risk Catchment Area.

    Science.gov (United States)

    Parsons, Bridget Grahmann; Gren, Lisa H; Simonsen, Sara E; Harding, Garrett; Grossman, Douglas; Wu, Yelena P

    2018-04-01

    Despite the highly preventable nature of skin cancer, it remains the most commonly diagnosed form of cancer in the United States. Recommendations for a complete skin cancer prevention regimen include engaging in photoprotection (e.g., sunscreen use), avoiding skin cancer risk behaviors (e.g., tanning), and receiving total body skin exams from a health care provider. The current study examined reported engagement in these behaviors among participants attending a community skin cancer screening (N = 319) in a high-risk catchment area to assess the need for increased health education on skin cancer prevention. Participants' responses indicate a history of suboptimal avoidance of skin cancer risk behaviors. Over half of participants (52%) reported four or more blistering sunburns before age 20, and 46% reported indoor tanning at least one during their lifetime. There is a need among this population for education regarding a complete skin cancer prevention regimen, which could improve adherence to photoprotection and avoidance of skin cancer risk behaviors, thereby reducing morbidity and mortality due to skin cancer.

  18. Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in a region at high risk of gastric cancer.

    Science.gov (United States)

    Wang, Ming-yi; Chen, Cheng; Gao, Xiao-zhong; Li, Jie; Yue, Jing; Ling, Feng; Wang, Xiao-chun; Shao, Shi-he

    2013-01-01

    Helicobacter pylori (H. pylori) is a major human pathogen that is responsible for various gastroduodenal diseases. We investigated the prevalence of H. pylori virulence markers in a region at high risk of gastric cancer. One hundred and sixteen H. pylori strains were isolated from patients with gastroduodenal diseases. cagA, the cagA 3' variable region, cagPAI genes, vacA, and dupA genotypes were determined by PCR, and some amplicons of the cagA 3' variable region, cagPAI genes and dupA were sequenced. cagA was detected in all strains. The cagA 3' variable region of 85 strains (73.3%) was amplified, and the sequences of 24 strains were obtained including 22 strains possessing the East Asian-type. The partial cagPAI presented at a higher frequency in chronic gastritis (44.4%) than that of the severe clinical outcomes (9.7%, p dupA and sequencing of dupA revealed an ORF of 2449-bp. The prevalence of dupA was significantly higher in strains from patients with the severe clinical outcomes (40.3%) than that from chronic gastritis (20.4%, p = 0.02). The high rate of East Asian-type cagA, intact cagPAI, virulent vacA genotypes, and the intact long-type dupA may underlie the high risk of gastric cancer in the region. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Barriers to uptake among high-risk individuals declining participation in lung cancer screening: a mixed methods analysis of the UK Lung Cancer Screening (UKLS) trial.

    Science.gov (United States)

    Ali, Noor; Lifford, Kate J; Carter, Ben; McRonald, Fiona; Yadegarfar, Ghasem; Baldwin, David R; Weller, David; Hansell, David M; Duffy, Stephen W; Field, John K; Brain, Kate

    2015-07-14

    The current study aimed to identify the barriers to participation among high-risk individuals in the UK Lung Cancer Screening (UKLS) pilot trial. The UKLS pilot trial is a randomised controlled trial of low-dose CT (LDCT) screening that has recruited high-risk people using a population approach in the Cambridge and Liverpool areas. High-risk individuals aged 50-75 years were invited to participate in UKLS. Individuals were excluded if a LDCT scan was performed within the last year, if they were unable to provide consent, or if LDCT screening was unable to be carried out due to coexisting comorbidities. Statistical associations between individual characteristics and UKLS uptake were examined using multivariable regression modelling. In those who completed a non-participation questionnaire (NPQ), thematic analysis of free-text data was undertaken to identify reasons for not taking part, with subsequent exploratory linkage of key themes to risk factors for non-uptake. Comparative data were available from 4061 high-risk individuals who consented to participate in the trial and 2756 who declined participation. Of those declining participation, 748 (27.1%) completed a NPQ. Factors associated with non-uptake included: female gender (OR=0.64, pemotional barriers. Smokers were more likely to report emotional barriers to participation. A profile of risk factors for non-participation in lung screening has emerged, with underlying reasons largely relating to practical and emotional barriers. Strategies for engaging high-risk, hard-to-reach groups are critical for the equitable uptake of a potential future lung cancer screening programme. The UKLS trial was registered with the International Standard Randomised Controlled Trial Register under the reference 78513845. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Gallbladder cancer: incidence and survival in a high-risk area of Chile.

    Science.gov (United States)

    Bertran, Enriqueta; Heise, Katy; Andia, Marcelo E; Ferreccio, Catterina

    2010-11-15

    We assessed population incidence rates 1998-2002 and 5-year survival rates of 317 primary gallbladder cancer (GBC) entered in the population-based cancer registry in Valdivia. We analyzed GBC incidence (Poisson regression) and GBC survival (Cox regression). Cases were identified by histology (69.4%), clinical work-up (21.8%), or death certificate only (8.8%). Main symptoms were abdominal pain (82.8%), jaundice (53.6%) nausea (42.6%), and weight loss (38.2%); at diagnosis, 64% had Stage TNM IV. In the period, 4% of histopathological studies from presumptively benign cholecystectomies presented GBC. GBC cases were mainly females (76.0%), urban residents (70.3%), Hispanic (83.7%) of low schooling Mapuche 25.0, Hispanic 16.2 (p = 0.09). The highest SIRs were in Mapuche (269.2) and Hispanic women (199.6) with 8 years of schooling. Low schooling, female and urban residence were independent risk factors. By December 31, 2007, 6 (1.9%) cases were living, 280 (88.3%) died from GBC, 32 (10.1%) were lost of follow-up. Kaplan Meier Global 5-year survival was: 10.3%, 85% at stage I and 1.9% at stage IV; median survival: 3.4 months. Independent poor prognostic factors were TNM IV, jaundice and nonincidental diagnoses. Our results suggest that women of Mapuche ancestry with low schooling (>50 years) are at the highest risk of presenting and dying from GBC and should be the target for early detection programs.

  1. Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer

    Directory of Open Access Journals (Sweden)

    L. Stewart Massad

    2015-04-01

    Conclusion: Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding.

  2. Comparison of the clinical performances of the AdvanSure HPV Screening Real-Time PCR, the Abbott Real-Time High-Risk HPV Test, and the Hybrid Capture High-Risk HPV DNA Test for Cervical Cancer Screening.

    Science.gov (United States)

    Chung, Hae-Sun; Hahm, Chorong; Lee, Miae

    2014-09-01

    The clinical performance of three human papillomavirus (HPV) DNA commercial assays for cervical cancer screening was evaluated; the AdvanSure HPV Screening Real-Time PCR (AdvanSure PCR; LG Life Sciences) that was developed recently for the detection of both high-risk and low-risk genotypes, the Abbott RealTime High-Risk HPV Test (Abbott PCR; Abbott Molecular) and the Hybrid Capture High-Risk HPV DNA test (HC2; Qiagen). The three different HPV DNA tests were compared using cytology samples obtained from 619 women who underwent routine cervical cancer screening. The gold-standard assay was histopathological confirmation of cervical intraepithelial neoplasia of grade 2 or worse. The clinical sensitivities of the AdvanSure PCR, the Abbott PCR and the HC2 for the detection of cervical intraepithelial neoplasia of grade 2 or worse were 95.5%, 95.5% and 100%, respectively, while the clinical specificities were 61.6%, 86.4% and 83.3%, respectively. There were no significant differences in the clinical sensitivities of the Abbott PCR and the AdvanSure PCR compared to the HC2. The clinical specificities of the Abbott PCR and the AdvanSure PCR for the detection of HPV types 16/18 were 97.8% and 98.5%, respectively. For cervical cancer screening, all three tests showed relatively good clinical sensitivities, but the AdvanSure PCR had lower clinical specificity than the Abbott PCR and the HC2. The AdvanSure PCR and the Abbott PCR assays have the advantage of being automated and the ability to distinguish between HPV types 16/18 and other HPV types. The two real-time PCR assays could be useful tools in HPV testing for cervical cancer screening. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cancer

    International Nuclear Information System (INIS)

    Mattes, Malcolm D.; Zhou, Ying; Berry, Sean L.; Barker, Christopher A.

    2016-01-01

    Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards relatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung V 20 (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum D max (13.6 vs. 38.9 Gy), bowel D 200cc (7.3 vs. 23.1 Gy), femur D 50 (34.6 vs. 57.2 Gy), and genitalia D max (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus D mean (16.9 vs. 22.4 Gy), brachial plexus D 5 (57.4 vs. 61.3 Gy), bladder D 5 (26.8 vs. 36.5 Gy), and femur D 50 (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients

  4. Dosimetric impact of mixed-energy volumetric modulated arc therapy plans for high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Shyam Pokharel

    2013-10-01

    Full Text Available Purpose: This study investigated the dosimetric impact of mixing low and high energy treatment plans for prostate cancer treated with volumetric modulated arc therapy (VMAT technique in the form of RapidArc.Methods: A cohort of 12 prostate cases involving proximal seminal vesicles and lymph nodes was selected for this retrospective study. For each prostate case, the single-energy plans (SEPs and mixed-energy plans (MEPs were generated.  First, the SEPs were created using 6 mega-voltage (MV energy for both the primary and boost plans. Second, the MEPs were created using 16 MV energy for the primary plan and 6 MV energy for the boost plan. The primary and boost MEPs used identical beam parameters and same dose optimization values as in the primary and boost SEPs for the corresponding case. The dosimetric parameters from the composite plans (SEPs and MEPs were evaluated. Results: The dose to the target volume was slightly higher (on average <1% in the SEPs than in the MEPs. The conformity index (CI and homogeneity index (HI values between the SEPs and MEPs were comparable. The dose to rectum and bladder was always higher in the SEPs (average difference up to 3.7% for the rectum and up to 8.4% for the bladder than in the MEPs. The mean dose to femoral heads was higher by about 0.8% (on average in the MEPs than in the SEPs. The number of monitor units and integral dose were higher in the SEPs compared to the MEPs by average differences of 9.1% and 5.5%, respectively.Conclusion: The preliminary results from this study suggest that use of mixed-energy VMAT plan for high-risk prostate cancer could potentially reduce the integral dose and minimize the dose to rectum and bladder, but for the higher femoral head dose.-----------------------------------------------Cite this article as:Pokharel S. Dosimetric impact of mixed-energy volumetric modulated arc therapy plans for high-risk prostate cancer. Int J Cancer Ther Oncol 2013;1(1:01011.DOI: http

  5. Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mattes, Malcolm D.; Zhou, Ying; Berry, Sean L.; Barker, Christopher A. [Memorial Sloan Kettering Cancer Center, New York (United States)

    2016-06-15

    Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards relatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung V{sub 20} (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum D{sub max} (13.6 vs. 38.9 Gy), bowel D{sub 200cc} (7.3 vs. 23.1 Gy), femur D{sub 50} (34.6 vs. 57.2 Gy), and genitalia D{sub max} (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus D{sub mean} (16.9 vs. 22.4 Gy), brachial plexus D{sub 5} (57.4 vs. 61.3 Gy), bladder D{sub 5} (26.8 vs. 36.5 Gy), and femur D{sub 50} (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients.

  6. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

    International Nuclear Information System (INIS)

    Belinsky, S.A.; Neft, R.E.; Lechner, J.F.

    1995-01-01

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This open-quotes field cancerizationclose quotes theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in open-quotes normalclose quotes bronchial epithelial cells

  7. Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer.

    Science.gov (United States)

    Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa N; Perry, Antoinette S; de Llorens, Rafael; Peracaula, Rosa

    2017-07-01

    The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children.

    Science.gov (United States)

    Sawada, Akihisa; Inoue, Masami; Kondo, Osamu; Yamada-Nakata, Kayo; Ishihara, Takashi; Kuwae, Yuko; Nishikawa, Masanori; Ammori, Yasuhiro; Tsuboi, Akihiro; Oji, Yusuke; Koyama-Sato, Maho; Oka, Yoshihiro; Yasui, Masahiro; Sugiyama, Haruo; Kawa, Keisei

    2016-02-01

    Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times. Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission. WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned. © 2015 Wiley Periodicals, Inc.

  9. Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer.

    Science.gov (United States)

    Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Gerullis, Holger; Otto, Thomas; Roth, Emanuel; Volkert, Frank; Ovsiannikov, Daniel; Moormann, Oliver; Banfi, Gergely; Nyirady, Peter; Vermeulen, Sita H; Garcia-Closas, Montserrat; Figueroa, Jonine D; Johnson, Alison; Karagas, Margaret R; Kogevinas, Manolis; Malats, Nuria; Schwenn, Molly; Silverman, Debra T; Koutros, Stella; Rothman, Nathaniel; Kiemeney, Lambertus A; Hengstler, Jan G; Golka, Klaus

    2017-12-07

    Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case-control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case-control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93-3.47; P = 1.87 × 10-10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10-2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer

  10. Double demonstration of oncogenic high risk human papilloma virus DNA and HPV-E7 protein in oral cancers.

    Science.gov (United States)

    Pannone, G; Santoro, A; Carinci, F; Bufo, P; Papagerakis, S M; Rubini, C; Campisi, G; Giovannelli, L; Contaldo, M; Serpico, R; Mazzotta, M; Lo Muzio, L

    2011-01-01

    Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.

  11. Postoperative Intensity Modulated Radiation Therapy in High Risk Prostate Cancer: A Dosimetric Comparison

    International Nuclear Information System (INIS)

    Digesu, Cinzia; Cilla, Savino; De Gaetano, Andrea; Massaccesi, Mariangela; Macchia, Gabriella; Ippolito, Edy; Deodato, Francesco; Panunzi, Simona; Iapalucci, Chiara; Mattiucci, Gian Carlo; D'Angelo, Elisa; Padula, Gilbert D.A.; Valentini, Vincenzo; Cellini, Numa

    2011-01-01

    The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal technique (3D-CRT), with respect to target coverage and irradiation of organs at risk for high dose postoperative radiotherapy (PORT) of the prostate fossa. 3D-CRT and IMRT treatment plans were compared with respect to dose to the rectum and bladder. The dosimetric comparison was carried out in 15 patients considering 2 different scenarios: (1) exclusive prostate fossa irradiation, and (2) pelvic node irradiation followed by a boost on the prostate fossa. In scenario (1), a 3D-CRT plan (box technique) and an IMRT plan were calculated and compared for each patient. In scenario (2), 3 treatment plans were calculated and compared for each patient: (a) 3D-CRT box technique for both pelvic (prophylactic nodal irradiation) and prostate fossa irradiation (3D-CRT only); (b) 3D-CRT box technique for pelvic irradiation followed by an IMRT boost to the prostatic fossa (hybrid 3D-CRT and IMRT); and (c) IMRT for both pelvic and prostate fossa irradiation (IMRT only). For exclusive prostate fossa irradiation, IMRT significantly reduced the dose to the rectum (lower Dmean, V50%, V75%, V90%, V100%, EUD, and NTCP) and the bladder (lower Dmean, V50%, V90%, EUD and NTCP). When prophylactic irradiation of the pelvis was also considered, plan C (IMRT only) performed better than plan B (hybrid 3D-CRT and IMRT) as respect to both rectum and bladder irradiation (reduction of Dmean, V50%, V75%, V90%, equivalent uniform dose [EUD], and normal tissue complication probability [NTCP]). Plan (b) (hybrid 3D-CRT and IMRT) performed better than plan (a) (3D-CRT only) with respect to dose to the rectum (lower Dmean, V75%, V90%, V100%, EUD, and NTCP) and the bladder (Dmean, EUD, and NTCP). Postoperative IMRT in prostate cancer significantly reduces rectum and bladder irradiation compared with 3D-CRT.

  12. Combined 18F-Fluciclovine PET/MRI Shows Potential for Detection and Characterization of High-Risk Prostate Cancer.

    Science.gov (United States)

    Elschot, Mattijs; Selnæs, Kirsten M; Sandsmark, Elise; Krüger-Stokke, Brage; Størkersen, Øystein; Giskeødegård, Guro F; Tessem, May-Britt; Moestue, Siver A; Bertilsson, Helena; Bathen, Tone F

    2018-05-01

    The objective of this study was to investigate whether quantitative imaging features derived from combined 18 F-fluciclovine PET/multiparametric MRI show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight patients diagnosed with high-risk prostate cancer underwent simultaneous 18 F-fluciclovine PET/MRI before radical prostatectomy. Volumes of interest (VOIs) for prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images, using histology as a reference. Tumor VOIs were marked as high-grade (≥Gleason grade group 3) or not. MRI and PET features were extracted on the voxel and VOI levels. Partial least-squared discriminant analysis (PLS-DA) with double leave-one-patient-out cross-validation was performed to distinguish tumors from benign tissue (BPH, prostatitis, or healthy tissue) and high-grade tumors from other tissue (low-grade tumors or benign tissue). The performance levels of PET, MRI, and combined PET/MRI features were compared using the area under the receiver-operating-characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor VOIs (26 high-grade), 36 BPH VOIs, 6 prostatitis VOIs, and 37 healthy-tissue VOIs. PET/MRI performed better than MRI and PET alone for distinguishing tumors from benign tissue (AUCs of 87%, 81%, and 83%, respectively, at the voxel level and 96%, 93%, and 93%, respectively, at the VOI level) and high-grade tumors from other tissue (AUCs of 85%, 79%, and 81%, respectively, at the voxel level and 93%, 93%, and 91%, respectively, at the VOI level). T2-weighted MRI, diffusion-weighted MRI, and PET features were the most important for classification. Conclusion: Combined 18 F-fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone. © 2018 by the Society of Nuclear Medicine and Molecular

  13. Technique for axillary radiotherapy using computer-assisted planning for high-risk skin cancerΤ

    International Nuclear Information System (INIS)

    Fogarty, G.B.; Martin, J.M.; Fay, M.; Ainslie J; Cassumbhoy, R.

    2007-01-01

    High-risk skin cancer arising on the upper limb or trunk can cause axillary nodal metastases. Previous studies have shown that axillary radiotherapy improves regional control. There is little published work on technique. Technique standardization is important in quality assurance and comparison of results especially for trials. Our technique, planned with CT assistance, is presented. To assess efficacy, an audit of patients treated in our institution over a 15-month period was conducted. Of 24 patients treated, 13 were treated with radical intent, 11 with this technique. With a follow up of over 2 years, the technique had more than a 90% (10/11) regional control in this radical group. Both of the radical patients who were not treated according to the technique had regional failure. One case of late toxicity was found, of asymptomatic lymphoedema in a radically treated patient. This technique for axillary radiotherapy for regional control of skin cancer is acceptable in terms of disease control and toxicity as validated by audit at 2 years

  14. Four cycles of adriamycin and cyclophosphamide followed by four cycles of docetaxel (NSABP-B27 with concomitant trastuzumab as neoadjuvant therapy for high-risk, early-stage, HER2-positive breast cancer patients

    Directory of Open Access Journals (Sweden)

    Abdel-Razeq H

    2018-04-01

    Full Text Available Hikmat Abdel-Razeq,1,2 Salwa S Saadeh,1 Mahmoud Abu-Nasser,1 Hazem Abdulelah,1 Lina Marie,1 Murad Salam,1 Basel Al-Haj Ali,1 Mohammad Ibrahim,1 Dalia Rimawi3 1Department of Internal Medicine, Section of Hematology and Medical Oncology, King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, University of Jordan, Amman, Jordan; 3Office of Scientific Affairs and Research, King Hussein Cancer Center, Amman, Jordan Background: The majority of breast cancer patients in Jordan are diagnosed at a young age and present with metastatic or locally advanced disease. The National Surgical Adjuvant Breast and Bowel Project Protocol B27 (NSABP-B27 (four cycles of adriamycin and cyclophosphamide [AC] followed by four cycles of docetaxel is a standard neoadjuvant regimen in our institution. In this study, we report the efficacy of adding trastuzumab to docetaxel in this regimen for high-risk human epidermal growth factor receptor 2 (HER2-positive early-stage disease. Patients and methods: Consecutive HER2-positive breast cancer patients treated with this regimen were included. Treatment was given at standard doses and schedules as reported in NSABP-B27. Trastuzumab was given with docetaxel and then continued for 1 year. Results: A total of 121 patients (mean age 45.4 years were included. The majority had high-risk features including large tumor size, positive axillary lymph nodes, and grade III disease. Three patients did not complete the planned cycles of AC due to a lack of response. Eight (6.6% patients missed at least one cycle of docetaxel. Following neoadjuvant therapy, 119 patients underwent surgery, of whom 59 (49.6% patients achieved pathological complete response. The response was higher in node-negative patients (64.0 vs 45.7%; P=0.03 and in hormone receptor-negative disease patients (69.7 vs 41.9%; P=0.018. Breast-conserving surgery was performed in 21.5% of the patients. The median disease-free survival (DFS for the whole group was not

  15. The Prognostic Role of Circulating Tumor Cells (CTC) in High-risk Non-muscle-invasive Bladder Cancer.

    Science.gov (United States)

    Busetto, Gian Maria; Ferro, Matteo; Del Giudice, Francesco; Antonini, Gabriele; Chung, Benjamin I; Sperduti, Isabella; Giannarelli, Diana; Lucarelli, Giuseppe; Borghesi, Marco; Musi, Gennaro; de Cobelli, Ottavio; De Berardinis, Ettore

    2017-08-01

    The purpose of this study was to evaluate the impact of circulating tumor cells (CTCs) as a prognostic marker in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) and assess the efficacy and reliability of 2 different CTC isolation methods. Globally, 155 patients with a pathologically confirmed diagnosis of high-risk NMIBC were included (pT1G3 with or without carcinoma in situ) and underwent transurethral resection of bladder tumor (TURB) after a blood withdrawal for CTC evaluation. A total of 101 patients (Group A) had their samples analyzed with the CellSearch automated system, and 54 (Group B) had their samples analyzed with the CELLection Dynabeads manual system. Patients were followed for 28 months, and during this interval, there were a total of 65 (41.9%) recurrences, 27 (17.4%) disease progressions, and 9 (5.8%) lymph node and/or bone metastasis. In our CTC analysis, there were 20 (19.8%) positive patients in Group A and 24 in Group B (44.4%). In our analysis, we found a strong correlation between CTC presence and time to first recurrence; in Group A, we observed an incidence of recurrence in 75% of CTC-positive patients and in Group B of 83% of CTC-positive patients. The time to progression was also strongly correlated with CTCs: 65% and 29%, respectively, of those patients who progressed in those with CTCs in Group A and B. The study demonstrates the potential role of CTCs as a prognostic marker for risk stratification in patients with NMIBC, to predict both recurrence and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade in high-risk prostate cancer

    Science.gov (United States)

    Mellado, B; Font, A; Alcaraz, A; Aparicio, L A; Veiga, F J G; Areal, J; Gallardo, E; Hannaoui, N; Lorenzo, J R M; Sousa, A; Fernandez, P L; Gascon, P

    2009-01-01

    Background: The low probability of curing high-risk prostate cancer (PC) with local therapy suggests the need to study modality of therapeutic approaches. To this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete androgen blockade (CAB) was carried out in high-risk PC patients. The primary end point was to detect at least 10% of pCRs after chemohormonal treatment. Methods: Patients with T1c–T2 clinical stage with prostate-specific antigen (PSA) >20 ng ml−1 and/or Gleason score ⩾7 (4+3) and T3 were included. Treatment consisted of three cycles of D 36 mg m−2 on days 1, 8 and 15 every 28 days concomitant with CAB, followed by radical prostatectomy (RP). Results: A total of 57 patients were included. Clinical stage was T1c, 11 patients (19.3%); T2, 30 (52.6%) and T3, 16 (28%) patients. Gleason score was ⩾7 (4+3) in 44 (77%) patients and PSA >20 ng ml−1 in 15 (26%) patients. Treatment was well tolerated with 51 (89.9%) patients completing neoadjuvant therapy together with RP. The rate of pCR was 6% (three patients). Three (6%) additional patients had microscopic residual tumour (near pCR) in prostate specimen. With a median follow-up of 35 months, 18 (31.6%) patients presented PSA relapse. Conclusion: Short-term neoadjuvant D and CAB induced a 6% pCR rate, which is close to what would be expected with ADT alone. The combination was generally well tolerated. PMID:19755998

  17. Reporting of coronary artery calcification on chest CT studies in breast cancer patients at high risk of cancer therapy related cardiac events

    Directory of Open Access Journals (Sweden)

    William J. Phillips

    2018-03-01

    Full Text Available Background: The identification of coronary artery calcification (CAC detected coincidentally on chest CT exams could assist in cardiovascular risk assessment but may not be reported consistently on clinical studies. Cardiovascular risk factor stratification is important to predict short term cardiac events during cancer therapy and long term cardiac event free survival in cancer patients. We sought to determine the prevalence of CAC and clinical reporting rates in a cohort of cancer patients at high risk of cancer therapy related cardiac events. Methods: 408 Breast cancer patients who were referred to a cardiac oncology clinic were screened. Inclusion criteria included having had a CT chest and the absence of known coronary disease. Among those screened 263 patients were included in the study. Results: CAC was identified in 70 patients (26%. CAC was reported in 18% of studies. The reporting rates of CAC increased with the extent of coronary calcification (p < 0.01 and increased during the period of the study (p < 0.05. Conclusions: CAC was commonly detected on chest CT studies in this observational study of breast cancer patients at high risk of cardiac oncology events. The presence of CAC was often not reported clinically but reporting rates have increased over time. Recent SCCT/STR guidelines recommend reporting the presence of CAC on routine chest CT scans in recognition of the importance of CAC as a predictor of cardiovascular events. Reporting of CAC on chest CTs may help to further risk stratify breast cancer patients and improve cardiovascular outcomes in this vulnerable population. Keywords: Cardiac oncology, Coronary calcification and chest CT

  18. Healing environments in cancer treatment and care. Relations of space and practice in hematological cancer treatment

    DEFF Research Database (Denmark)

    Høybye, Mette Terp

    2013-01-01

    of the individual patient ’ s needs, values and experiences is key to developing the environment to support the patient quality of life. The present study holds implications for practice to inform design of future hospital environments for cancer treatment. The study points to the importance for being attentive...... these concepts, the study demonstrates how the hospital environment is a fl ow of relations between space and practice that changes and challenges a structural idea of design and healing. Patients ’ sense of healing changes with the experience of progression in treatment and the capacity of the hospital space...... to incite an experience of homeliness and care. Furthermore, cancer patients continuously challenge the use and limits of space by individual objects and practices of privacy and home. Discussion. Healing environments are complex relations between practices, space and care, where recognition...

  19. Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Petereit, Daniel G. [Department of Radiation Oncology, John T. Vucurevich Regional Cancer Care Institute, Rapid City Regional Hospital, Rapid City, SD (United States); Hong, Theodore S.; Tome, Wolfgang [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Ritter, Mark A., E-mail: ritter@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States)

    2012-01-01

    Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

  20. Hand-Assisted Robotic Surgery for Staging of Ovarian Cancer and Uterine Cancers With High Risk of Peritoneal Spread: A Retrospective Cohort Study.

    Science.gov (United States)

    Fornalik, Hubert; Brooks, Hannah; Moore, Elizabeth S; Flanders, Nicole L; Callahan, Michael J; Sutton, Gregory P

    2015-10-01

    This study aimed to determine surgical outcomes related to hand-assisted robotic surgery (HARS) for staging of ovarian cancer and uterine cancers with high risk of peritoneal spread and compare them to laparotomy and standard robotic-assisted surgery. A retrospective cohort study of women undergoing staging for uterine and ovarian cancer between January 2011 and July 2013 at a major metropolitan teaching hospital was reviewed. Patients undergoing HARS were matched with patients undergoing staging laparotomy [exploratory laparotomy (XLAP)] for the same indications and with patients undergoing traditional robotic surgery (RS) for staging of endometrioid endometrial cancer. In HARS, a longer incision is used to allow palpation of the peritoneal surfaces, to exteriorize the small bowel, to examine the mesentery, and to perform omentectomy. One hundred five patients were analyzed (15 HARS, 45 RS, 45 XLAP). Compared with XLAP, HARS was associated with decreased blood loss (200 vs 400 mL, P = 0.011) and shorter hospital stay (1 vs 4 days, P < 0.001). Patients who had undergone HARS had fewer major complications, but those results did not reach statistical significance (0% vs 27%, P = 0.063). Hand-assisted robotic surgery was associated with higher blood loss and length of stay as compared to robotic staging of endometrioid endometrial cancer (RS). Minor wound complications were also more common (27% vs 2%, P = 0.012). Hand-assisted robotic surgery allows for thorough visual and tactile assessment of peritoneal surfaces. It represents a safe alternative to laparotomy for staging of ovarian and uterine cancers with high risk of peritoneal spread. Long-term follow-up study is needed to determine oncologic adequacy of HARS.

  1. Hematologic emergencies

    Directory of Open Access Journals (Sweden)

    Daniele Vallisa

    2012-01-01

    Full Text Available In recent years, the surprising progress made in other areas of hematology (advances in the understanding of leukemogenesis, improved transplant techniques has been conspicuously absent in the management of hematologic emergencies. And yet, every step toward greater knowledge, every new treatment option will be of little value unless we are able to manage the acute complications of hematologic diseases. These complications are better defined as hematologic emergencies, and they are characterized by a high rate of mortality. This review is based on a search of the literature that was initially confined to articles published in the journal Hematology from 2000 to 2009. The search was then extended to the Cochrane Library and to Pub Med in February 2010 with the following Keywords emergencies; urgencies; hematology. The same key words were employed in a search of the archives of Blood and the New England Journal of Medicine from 2000 to 2010. The results confirm that hematologic emergencies can be caused by hematologic malignancies as well as by non-neoplastic hematologic diseases. Within the former category; this review examines the causes; manifestations; treatment and prevention of disseminated intravascular coagulation; superior vena caval syndrome; spinal cord compression; tumor lysis syndrome; hyperleukocytosis; and hypercalcemia. We also review emergency situations associated with non-neoplatic haematological diseases; such as thrombotic thrombocytopenic purpura; drug-induced hemolytic anemia; and acute sickle-cell crisis.

  2. Do HMO market level factors lead to racial/ethnic disparities in colorectal cancer screening? A comparison between high-risk Asian and Pacific Islander Americans and high-risk whites.

    Science.gov (United States)

    Ponce, Ninez A; Huh, Soonim; Bastani, Roshan

    2005-11-01

    Few studies have explored health care market structure and colorectal cancer (CRC) screening test use, and little is known whether market factors contribute to racial/ethnic screening disparities. We investigated whether HMO market level factors, controlling for individual covariates, differentially impact Asian American and Pacific Islander (AAPI) subjects' access to CRC screening compared with white subjects. We used random intercept hierarchical models to predict CRC test use. Individual-level survey data was linked to market data by metropolitan statistical areas from InterStudy. Insured first-degree relatives, ages 40-80, of a random sample of colorectal cancer cases identified from the California Cancer Registry: 515 white subjects and 396 AAPI subjects residing in 36 metropolitan statistical areas (MSAs). Dependent variables were receipt of (1) annual fecal occult blood test only; (2) sigmoidoscopy in the past 5 years; (3) colonoscopy in the past 10 years; and (4) any of these tests over the recommended time interval. Market characteristics were HMO penetration, HMO competition, and proportion of staff/group/network HMOs. Market characteristics were as important as individual-level characteristics for AAPI but not for white subjects. Among AAPI subjects, a 10% increase in the percent of group/staff/network model HMO was associated with a reduction in colonoscopy use (28.9% to 20.5%) and in receipt of any of the CRC tests (53.2% to 45.4%). The prevailing organizational structure of a health care market confers a penalty on access to CRC test use among high-risk AAPI subjects but not among high-risk white subjects. Identifying the differential effect of market structure on race/ethnicity can potentially reduce the cancer burden among disadvantaged racial groups.

  3. Practicalities of developing a breast magnetic resonance imaging screening service for women at high risk for breast cancer.

    Science.gov (United States)

    Kiely, Belinda E; Hossack, Lucinda K; Shadbolt, Clair L; Davis, Anna; Cassumbhoy, Robin; Moodie, Kate; Antill, Yoland; Mitchell, Gillian

    2011-10-01

    Demand for screening breast magnetic resonance imaging (MRI) for women with a hereditary predisposition to breast cancer has increased since the introduction of a medicare item number. To aid future service planning, we examined the practicalities of establishing and running a breast MRI screening programme for high risk women and to describe the early outcomes of our screening programme. We undertook a retrospective audit of prospectively collected data. Women detection rate; and patient satisfaction via questionnaire. From 2006 to 2009, 82 women completed a round one screening MRI and 45, 21 and one women completed second, third and fourth round annual MRI studies, respectively. Median MRI process times were: booking 20 min; attendance in radiology department 90 min; imaging duration 45 min; reporting by one radiologist 30 min. Of the 82 round one studies, 23 (28%) were reported as ≥Breast Imaging Reporting and Data System three requiring further investigation. Of the round two and three studies completed, 13/45 (28%) and 2/21 (9%) have been recalled, respectively. Seven malignancies were detected. Questionnaires revealed women were satisfied with the service. Significant time, staff and equipment is required to run an effective breast MRI screening programme and this must be considered by future service providers.

  4. Contemporary management of patients with high-risk non-muscle-invasive bladder cancer who fail intravesical BCG therapy.

    Science.gov (United States)

    Yates, D R; Rouprêt, M

    2011-08-01

    It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery.

  5. Biomarkers for screening of lung cancer and pre-neoplastic lesions in a high risk Chilean population

    Directory of Open Access Journals (Sweden)

    Marta I Adonis

    2014-01-01

    Full Text Available BACKGROUND: The mortality of lung cancer (LC, increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 μg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70 and Auto Fluorescence Bronchoscopy (AFB might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL and neoplastic lesions (NL. RESULTS: Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8% and specificity (91.9% than AQC. However, for PNL AQC showed a higher sensitivity (91.9% than DR70 (27.3%, although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%. CONCLUSION: This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC

  6. Risk factor assessment in high-risk, bacillus Calmette–Guérin-treated, non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Holz S

    2017-09-01

    Full Text Available Serge Holz,* Simone Albisinni,* Jacques Gilsoul, Michel Pirson, Véronique Duthie, Thierry Quackels, Marc Vanden Bossche, Thierry Roumeguère Department of Urology, Erasme Hospital, Université libre de Bruxelles, Belgium *These authors contributed equally to this work Objective: To assess the risk factors associated with recurrence, progression and survival in high-risk non-muscle-invasive bladder cancer (NMIBC patients treated with bacillus Calmette–Guérin (BCG and validate the European Organization for Research and Treatment of Cancer (EORTC and Spanish Urological Club for Oncological Treatment (CUETO scores.Patients and methods: We retrospectively analyzed all BCG-treated NMIBC patients from 1998 to 2012. Multiple variables were tested as risk factors for recurrence-free survival and progression-free survival (PFS. Variables included age, sex, grade, stage, tumor size, number of tumors, carcinoma in situ (CIS, recurrence status, BCG strain used, smoking status, use of re-staging transurethral resection and use of single immediate postoperative instillation. We also tested the accuracy of EORTC and CUETO scores in predicting recurrence and progression.Results: Overall, 123 patients were analyzed. Median (interquartile range follow-up was 49 months. The 5-year overall survival, cancer-specific survival, recurrence-free survival and PFS were 75.0%, 89.3%, 59.4% and 79.2%, respectively. On univariate analysis, multiple tumors (≥3, concomitant CIS and smoking influenced recurrence. Regarding progression, multiple tumors, concomitant CIS and Connaught strain (vs Tice negatively influenced PFS on univariate and multivariate analyses were independent prognostic factors. CUETO scores were accurate, with a slight overestimation, while EORTC score was not predictive of recurrence or progression.Conclusion: In this study, CIS and tumor multiplicity were unfavorable predictors of recurrence and progression in patients with NMIBC receiving BCG

  7. Quality of Life After Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Quon, Harvey; Cheung, Patrick C.F.; Loblaw, D. Andrew; Morton, Gerard; Pang, Geordi; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Kiss, Alex; Mamedov, Alexandre; Deabreu, Andrea

    2012-01-01

    Purpose: To evaluate the change in health-related quality of life (QOL) of patients with high-risk prostate cancer treated using hypofractionated radiotherapy combined with long-term androgen deprivation therapy. Methods and Materials: A prospective Phase I–II study enrolled patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥20 ng/mL, or Gleason score 8–10. Radiotherapy consisted of 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes with a concomitant 22.5 Gy intensity-modulated radiotherapy boost to the prostate, for a total of 67.5 Gy (2.7 Gy per fraction) in 25 fractions over 5 weeks. Daily image guidance was performed using three gold seed fiducials. Quality of life was measured using the Expanded Prostate Cancer Index Composite (EPIC), a validated tool that assesses four primary domains (urinary, bowel, sexual, and hormonal). Results: From 2004 to 2007, 97 patients were treated. Median follow-up was 39 months. Compared with baseline, at 24 months there was no statistically significant change in the mean urinary domain score (p = 0.99), whereas there were decreases in the bowel (p < 0.01), sexual (p < 0.01), and hormonal (p < 0.01) domains. The proportion of patients reporting a clinically significant difference in EPIC urinary, bowel, sexual, and hormonal scores at 24 months was 27%, 31%, 55%, and 60%, respectively. However, moderate and severe distress related to these symptoms was minimal, with increases of only 3% and 5% in the urinary and bowel domains, respectively. Conclusions: Hypofractionated radiotherapy combined with long-term androgen deprivation therapy was well tolerated. Although there were modest rates of clinically significant patient-reported urinary and bowel toxicity, most of this caused only mild distress, and moderate and severe effects on QOL were limited. Additional follow-up is ongoing to characterize long-term QOL.

  8. Evaluation of a new solid media specimen transport card for high risk HPV detection and cervical cancer prevention.

    Science.gov (United States)

    Maurer, Kathryn; Luo, Hongxue; Shen, Zhiyong; Wang, Guixiang; Du, Hui; Wang, Chun; Liu, Xiaobo; Wang, Xiamen; Qu, Xinfeng; Wu, Ruifang; Belinson, Jerome

    2016-03-01

    Solid media transport can be used to design adaptable cervical cancer screening programs but currently is limited by one card with published data. To develop and evaluate a solid media transport card for use in high-risk human papillomavirus detection (HR-HPV). The Preventative Oncology International (POI) card was constructed using PK 226 paper(®) treated with cell-lysing solution and indicating dye. Vaginal samples were applied to the POI card and the indicating FTA (iFTA) elute card. A cervical sample was placed in liquid media. All specimens were tested for HR-HPV. Color change was assessed at sample application and at card processing. Stability of the POI card and iFTA elute card was tested at humidity. 319 women were enrolled. Twelve women had at least one insufficient sample with no difference between media (p=0.36). Compared to liquid samples, there was good agreement for HR-HPV detection with kappa of 0.81 (95% CI 0.74-0.88) and 0.71 (95% CI 0.62-0.79) for the POI and iFTA elute card respectively. Sensitivity for ≥CIN2 was 100% (CI 100-100%), 95.1% (CI 92.7-97.6%), and 93.5% (CI 90.7-96.3%) for the HR-HPV test from the liquid media, POI card, and iFTA elute card respectively. There was no color change of the POI card noted in humidity but the iFTA elute card changed color at 90% humidity. The POI card is suitable for DNA transport and HR-HPV testing. This card has the potential to make cervical cancer screening programs more affordable worldwide. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Healing environments in cancer treatment and care. Relations of space and practice in hematological cancer treatment.

    Science.gov (United States)

    Høybye, Mette Terp

    2013-02-01

    Given the growing attention to the importance of design in shaping healing hospital environments this study extends the understanding of healing environments, beyond causal links between environmental exposure and health outcome by elucidating how environments and practices interrelate. The study was conducted as an ethnographic fieldwork from March 2011 to September 2011 at the Department of Haematology at Odense University Hospital, Denmark, systematically using participant observation and interviews as research strategies. It included 20 patients, four of who were followed closely over an extended time period. Through thematic analysis five key concepts emerged about the social dynamics of hospital environments: practices of self; creating personal space; social recognition; negotiating space; and ambiguity of space and care. Through these concepts, the study demonstrates how the hospital environment is a flow of relations between space and practice that changes and challenges a structural idea of design and healing. Patients' sense of healing changes with the experience of progression in treatment and the capacity of the hospital space to incite an experience of homeliness and care. Furthermore, cancer patients continuously challenge the use and limits of space by individual objects and practices of privacy and home. Healing environments are complex relations between practices, space and care, where recognition of the individual patient's needs, values and experiences is key to developing the environment to support the patient quality of life. The present study holds implications for practice to inform design of future hospital environments for cancer treatment. The study points to the importance for being attentive to the need for flexible spaces in hospitals that recognize the dynamics of healing, by providing individualized care, relating to the particular and changing needs of patients supporting their potential and their challenged condition with the best

  10. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3) : final results of an international, open-label, multicentre, randomised, phase 3 trial

    NARCIS (Netherlands)

    de Boer, Stephanie M.; Powell, Melanie E.; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B.; Ledermann, Jonathan A.; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie-Helene; Jurgenliemk-Schulz, Ina M.; Kitchener, Henry C.; Nijman, Hans W.; Wilson, Godfrey; Brooks, Susan; Carinelli, Silvestro; Provencher, Diane; Hanzen, Chantal; Lutgens, Ludy C. H. W.; Smit, Vincent T. H. B. M.; Singh, Naveena; Do, Viet; D'Amico, Romerai; Nout, Remi A.; Feeney, Amanda; Verhoeven-Adema, Karen W.; Putter, Hein; Creutzberg, Carien L.

    Background Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy)

  11. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3) : final results of an international, open-label, multicentre, randomised, phase 3 trial

    NARCIS (Netherlands)

    de Boer, Stephanie M.; Powell, Melanie E.; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B.; Ledermann, Jonathan A.; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie Helene; Jürgenliemk-Schulz, Ina M.; Kitchener, Henry C.; Nijman, Hans W.; Wilson, Godfrey; Brooks, Susan; Carinelli, Silvestro; Provencher, Diane; Hanzen, Chantal; Lutgens, Ludy C.H.W.; Smit, Vincent T.H.B.M.; Singh, Naveena; Do, Viet; D'Amico, Romerai; Nout, Remi A.; Feeney, Amanda; Verhoeven-Adema, Karen W.; Putter, Hein; Creutzberg, Carien L.; McCormack, Mary; Whitmarsh, Karen; Allerton, Rozenn; Gregory, Deborah; Symonds, Paul; Hoskin, Peter J.; Adusumalli, Madhavi; Anand, Anjana; Wade, Robert; Stewart, Alexandra; Taylor, Wendy; Kruitwagen, Roy F.P.M.; Hollema, Harry; Pras, Elizabeth; Snyers, An; Stalpers, Lukas; Jobsen, Jan J.; Slot, Annerie; Mens, Jan Willem M.; Stam, Tanja C.; Van Triest, Baukelien; Van der Steen - Banasik, Elzbieta M.; De Winter, Karin A.J.; Quinn, Michael A.; Kolodziej, Ilka; Pyman, Jan; Johnson, Carol; Capp, Anne; Fossati, Roldano; Gribaudo, Sergio; Lissoni, Andrea A.; Ferrero, Annamaria; Artioli, Grazia; Davidson, Cathy; McLachlin, C. Meg; Ghatage, Prafull; Rittenberg, Paula V.C.; Souhami, Luis; Thomas, Gillian; Duvillard, Pierre; Berton-Rigaud, Dominique; Tubiana-Mathieu, Nicole

    2018-01-01

    Background: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy)

  12. Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib.

    Science.gov (United States)

    Zhao, Bin; Zhao, Hong

    2017-11-07

    Regorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase inhibitor, has been approved for the treatment of several malignancies. As a non-traditional cytotoxic chemotherapeutic agent, regorafenib is often associated with hematologic toxicities. Here we searched PubMed and Embase up to June 2017 for relevant clinical trials. Eligible studies include trials in which subjects treated with 160 mg of regorafenib daily during the first 21 days of each 28-day cycle, and adequate safety data profile reporting thrombocytopenia, anemia, neutropenia and leucopenia. Statistical analyses were conducted to calculate the overall incidences, relative risks (RRs) and their 95% confidence intervals (CIs). A total of 2,341 subjects from 16 trials were included in the present studies. The incidences of regorafenib associated all-grade and high-grade hematologic toxicities were: thrombocytopenia, 22% and 3%; anemia, 20% and 3%; neutropenia, 10% and 2%, and leucopenia, 13% and 2%, respectively. Regorafenib-treated subjects had a significant increased risk of all-grade (RR=6.35; 95% CI, 3.19-12.64) and high-grade (RR=6.27; 95% CI, 1.69-23.26) thrombocytopenia, all-grade (RR=2.76; 95% CI, 1.63-4.68) and high-grade (RR=5.38; 95% CI, 1.60-18.06) anemia. Our results suggested that regorafenib therapy was associated with significantly increased risks of hematological toxicities, and hematologic monitoring at regular intervals should be advised to clinician.

  13. Establishing the distribution of satellite lesions in intermediate- and high-risk prostate cancer: implications for focused radiotherapy.

    Science.gov (United States)

    Hegde, J V; Margolis, D J; Wang, P-C; Reiter, R E; Huang, J; Steinberg, M L; Kamrava, M

    2017-06-01

    In focused radiotherapy for prostate cancer (PC), a full dose of radiation is delivered to the index lesion while reduced dose is delivered to the remaining prostate to reduce morbidity. As PC is commonly multifocal, we investigated whether baseline clinical characteristics or multiparametric magnetic resonance imaging (mpMRI) may be useful to predict the actual pathologic distribution of PC in men with intermediate- or high-risk PC, which may better inform how to deliver focused radiotherapy. A retrospective single-institutional study was performed on 71 consecutive men with clinically localized, intermediate- or high-risk PC who underwent mpMRI followed by radical prostatectomy (RP) from January 2012 to December 2012. Logistic regression analysis was performed to evaluate preoperative predictors for satellite lesions. Performance characteristics of mpMRI to detect satellite lesions and the extent of prostate disease (one hemi-gland vs both) were also evaluated. In all, 50.7% had satellite lesions on mpMRI. On RP specimen analysis, 66.2% had satellite lesions and 55.3% of these satellite lesions had pathologic Gleason score (pGS)⩾3+4. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for mpMRI detecting a satellite lesion being present in the RP specimen were 59.6%, 66.7%, 77.8%, 45.7% and 62.0%, respectively. The presence of MRI satellite lesions was the only preoperative predictor significantly associated with finding satellite lesions on final pathology (hazard ratio (HR), 2.95, P=0.040). There was agreement in 76.1% of the entire cohort for unilateral vs bilateral disease when incorporating both biopsy and mpMRI information and comparing with the RP specimen. In intermediate risk or greater PC, only the presence of mpMRI satellite lesions could predict for pathologic satellite lesions. While combining biopsy and mpMRI information may improve preoperative disease localization, the relatively high incidence of

  14. Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

    International Nuclear Information System (INIS)

    Kaidar-Person, Orit; Roach, Mack; Créhange, Gilles

    2013-01-01

    Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have a high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer

  15. Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

    Energy Technology Data Exchange (ETDEWEB)

    Kaidar-Person, Orit [Division of Oncology, Rambam Health Care Campus, Haifa (Israel); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Créhange, Gilles, E-mail: gcrehange@cgfl.fr [Department of Radiation Oncology, Georges-François Leclerc Cancer Center, Dijon (France)

    2013-07-15

    Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have a high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer.

  16. Associations between dyadic coping and supportive care needs: findings from a study with hematologic cancer patients and their partners.

    Science.gov (United States)

    Weißflog, Gregor; Hönig, Klaus; Gündel, Harald; Lang, Dirk; Niederwieser, Dietger; Döhner, Hartmut; Vogelhuber, Martin; Mehnert, Anja; Ernst, Jochen

    2017-05-01

    The way couples mutually cope with hematologic cancer is likely to influence their levels of supportive care needs (SCN). Therefore, this study evaluated the levels of dyadic coping (DC) and SCN and the concurrent associations between both variables. Three hundred thirty patients with a hematologic malignancy (63% male) and their partners completed the dyadic coping inventory (DCI) and the supportive care needs survey (SCNS-SF-34-G). The levels of dyadic coping (DC) and supportive care needs (SCN) were compared with representative validation samples. Correlational analyses and actor-partner interdependence models (APIM) were calculated to estimate the association between DC and SCN. Partners' stress communication of cancer patients (as part of DC) was decreased in contrast to that of a non-cancer sample. The perception of partners' delegated DC was higher (both with a moderate effect size of g ≥ |0.50|). SCN of patients and partners were lower in the dimensions health system/information and physical problems/daily living in contrast to those of a cancer patients' validation sample (both with a small effect of g ≥ |0.20|). Higher perceptions of partners' negative DC were associated with higher SCN for both patients and partners. The same was true for patients' own stress communication and SCN, but only for the patients. Sociodemographic and illness-related factors were only partially related with the SCN of patients and partners. In order to diminish SCN of patients and partners, a possible way is to strengthen the quality of the dyadic relation. Due to its associations with elevated SCN, stress communication and negative dyadic coping behaviours may be useful targets for psychosocial interventions.

  17. Are HPV vaccination services accessible to high-risk communities? A spatial analysis of HPV-associated cancer and Chlamydia rates and safety-net clinics.

    Science.gov (United States)

    Tsui, Jennifer; Rodriguez, Hector P; Gee, Gilbert C; Escobedo, Loraine A; Kominski, Gerald F; Bastani, Roshan

    2013-12-01

    While HPV vaccines can greatly benefit adolescents and young women from high-risk areas, little is known about whether safety-net immunization services are geographically accessible to communities at greatest risk for HPV-associated diseases. We explore the spatial relationship between areas with high HPV risk and proximity to safety-net clinics from an ecologic perspective. We used cancer registry data and Chlamydia surveillance data to identify neighborhoods within Los Angeles County with high risk for HPV-associated cancers. We examined proximity to safety-net clinics among neighborhoods with the highest risk. Proximity was measured as the shortest distance between each neighborhood center and the nearest clinic and having a clinic within 3 miles of each neighborhood center. The average 5-year non-age-adjusted rates were 1,940 cases per 100,000 for Chlamydia and 60 per 100,000 for HPV-associated cancers. A large majority, 349 of 386 neighborhoods with high HPV-associated cancer rates and 532 of 537 neighborhoods with high Chlamydia rates, had a clinic within 3 miles of the neighborhood center. Clinics were more likely to be located within close proximity to high-risk neighborhoods in the inner city. High-risk neighborhoods outside of this urban core area were less likely to be near accessible clinics. The majority of high-risk neighborhoods were geographically near safety-net clinics with HPV vaccination services. Due to low rates of vaccination, these findings suggest that while services are geographically accessible, additional efforts are needed to improve uptake. Programs aimed to increase awareness about the vaccine and to link underserved groups to vaccination services are warranted.

  18. Is less more? Comparing chemotherapy alone with chemotherapy and radiation for high-risk grade 2 glioma: An analysis of the National Cancer Data Base.

    Science.gov (United States)

    Jhaveri, Jaymin; Liu, Yuan; Chowdhary, Mudit; Buchwald, Zachary S; Gillespie, Theresa W; Olson, Jeffrey J; Voloschin, Alfredo D; Eaton, Bree R; Shu, Hui-Kuo G; Crocker, Ian R; Curran, Walter J; Patel, Kirtesh R

    2018-03-15

    The addition of chemotherapy to adjuvant radiotherapy (chemotherapy and radiation therapy [CRT]) improves overall survival (OS) for patients with high-risk grade 2 gliomas; however, the impact of chemotherapy alone (CA) is unknown. This study compares the OS of patients with high-risk grade 2 gliomas treated with CA versus CRT. Patients with high-risk grade 2 gliomas (subtotal resection or age ≥ 40 years) with oligodendrogliomas, astrocytomas, or mixed tumors were identified with the National Cancer Data Base. Patients were grouped into CA and CRT cohorts. Univariate analyses and multivariate analyses (MVAs) were performed. Propensity score (PS) matching was also implemented. The Kaplan-Meier method was used to analyze OS. A total of 1054 patients with high-risk grade 2 gliomas were identified: 496 (47.1%) received CA, and 558 (52.9%) received CRT. Patients treated with CA were more likely (all P values  6 cm, astrocytoma histology, and older age were predictors for worse OS (all P values < .05). After 1:1 PS matching (n = 331 for each cohort), no OS difference was seen (P = .696) between the CA and CRT cohorts at 5 (69.3% vs 67.4%) and 8 years (52.8% vs 56.7%). No long-term OS difference was seen in patients with high-risk grade 2 gliomas treated with CA versus CRT. These findings are hypothesis-generating, and prospective clinical trials comparing these treatment paradigms are warranted. Cancer 2018;124:1169-78. © 2017 American Cancer Society. © 2017 American Cancer Society.

  19. Limitations of widely used high-risk human papillomavirus laboratory-developed testing in cervical cancer screening

    Directory of Open Access Journals (Sweden)

    Naryshkin S

    2012-11-01

    Full Text Available Sonya Naryshkin,1 R Marshall Austin21Department of Pathology, Mercy Health System, Janesville, WI; 2Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, USAObjective: To increase awareness of the limitations of high-risk human papillomavirus (hrHPV laboratory-developed testing (LDT widely used in US cervical cancer screening.Methods and results: A young woman in her 30s was diagnosed and treated for stage 1B1 cervical squamous cell carcinoma in which HPV 16 DNA was detected using polymerase chain reaction testing. Both 1 month before and 42 months before cervical cancer diagnosis, the patient had highly abnormal cytology findings; however, residual SurePath™ (Becton, Dickson and Company, Franklin Lakes, NJ vial fluid yielded negative Hybrid Capture 2 (HC2; Qiagen NV, Hilden, Germany hrHPV LDT results from each of the two specimens. This prompted questions to be asked concerning the performance characteristics of hrHPV LDT. A review of the available data indicates that (1 purification of DNA from SurePath specimens requires complex sample preparation due to formaldehyde crosslinking of proteins and nucleic acids, (2 HC2–SurePath hrHPV testing had not been Food and Drug Administration-approved after multiple premarket approval submissions, (3 detectible hrHPV DNA in the SurePath vial decreases over time, and (4 US laboratories performing HC2–SurePath hrHPV LDT testing are not using a standardized manufacturer-endorsed procedure.Conclusion: Recently updated cervical screening guidelines in the US recommend against the use of hrHPV LDT in cervical screening, including widely used HC2 testing from the SurePath vial. The manufacturer recently issued a technical bulletin specifically warning that use of SurePath samples with the HC2 hrHPV test may provide false negative results and potentially compromise patient safety. Co-collection using a Food and Drug Administration-approved hrHPV test

  20. Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

    Science.gov (United States)

    Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

    2011-01-01

    Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

  1. REPTILE HEMATOLOGY

    Directory of Open Access Journals (Sweden)

    Nejra Hadžimusić

    2013-03-01

    Full Text Available Determination of the number of circulating blood cells is of a great importance in clinical diagnosis. However, in some species, such as birds and reptiles, it is not possible to determine the number of individual blood cells using standard automated equipment, because of the specific morphological characteristics. For this reason, recognition of individual cell elements is crucial during hematological examination. Key words: Hematology, reptiles, blood cell morphology

  2. Adjuvant chemotherapy and risk of gastrointestinal, hematologic, and cardiac toxicities in elderly patients with stage III colon cancer.

    Science.gov (United States)

    Hu, Chung-Yuan; Chan, Wenyaw; Delclos, George P; Du, Xianglin L

    2012-06-01

    Randomized trials have established the effectiveness of 5-fluorouracil-based adjuvant chemotherapy for stage III resectable colon cancer but the toxicity has not been well established outside the trial setting. The objective of this study was to estimate the risk of various toxicity-related endpoints among the elderly patients. Patients diagnosed with stage III colon cancer in 1991 to 2005 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Chemotherapy use within 3 months after tumor resection was identified from submitted claims. We reported the 3-month cumulative incidence rate (CIR) for gastrointestinal and hematologic toxicities. The risk of ischemic heart disease in relation to chemotherapy use and length was assessed using Cox regression models, stratified by age and comorbidity subgroups. Of the 12,099 patients, 63.9% (n=7740) received adjuvant chemotherapy. Common gastrointestinal and hematologic toxicities among chemotherapy group include volume depletion disorder (CIR=9.1%), agranulocytosis (CIR=3.4%), diarrhea (CIR=2.4%), nausea and vomiting (CIR=2.3%). Chemotherapy use was significantly associated with the onset of these toxicities [hazard ratio (HR)=2.76; 95% confidence interval (95% CI)=2.42-3.15]. The risk of ischemic heart disease was slightly associated with chemotherapy use (HR=1.08, 95% CI=0.96-1.22), but significant only among patients aged colon cancer. On account of the effects of these side effects on treatment discontinuation, rehospitalization, and overall health status, some close monitoring and preventive measures may be emphasized to maximize the benefits of adjuvant chemotherapy.

  3. Evolution of human cytomegalovirus-seronegative donor/-seropositive recipient high-risk combination frequency in allogeneic hematopoietic stem cell transplantations at Institute of Hematology and Blood Transfusion during 1995-2014.

    Science.gov (United States)

    Nemeckova, S; Sroller, V; Stastna-Markova, M

    2016-04-01

    Human cytomegalovirus (HCMV) establishes lifelong latent infection that can result in severe life-threatening disease in immunosuppressed patients after hematopoietic stem cell transplantation (HSCT). An HCMV-seropositive transplant recipient who receives a graft from a seronegative donor (R+/D-) is at high risk of recurrent HCMV reactivation. To assess the incidence of R+/D- combination, we retrospectively evaluated HCMV-seronegative donors for 746 allogeneic HSCT treatments carried out at our center during 1995-2014. In our cohort, 20% HCMV-seronegative HSCT recipients, 21% HCMV-seronegative related graft donors, and 52% HCMV-seronegative unrelated graft donors were included. Analyses of the HCMV serostatus of hematopoietic stem cell donors during 2 consecutive calendar periods (1995-2005 and 2006-2014) showed a significant increase in the proportion of seronegative donors (odds ratio [OR] = 1.947). In addition, the number of HSCT treatments using an unrelated donor increased (OR = 2.376). Finally, the use of grafts from countries with a very low HCMV prevalence increased. This increase in HCMV seronegativity in unrelated donors and the increased proportion of unrelated donors were responsible for the increased occurrence of the high-risk combination R+/D- (OR = 1.680). If the reduction in the rate of HCMV-seropositive graft donors continues, an increased frequency of HCMV reactivation events in our transplant recipients can be expected, because of the increasing occurrence of the high-risk R+/D- combination. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Predictive value of pretreatment lymphocyte count in stage II colorectal cancer and in high-risk patients treated with adjuvant chemotherapy.

    Science.gov (United States)

    Liang, Lei; Zhu, Ji; Jia, Huixun; Huang, Liyong; Li, Dawei; Li, Qingguo; Li, Xinxiang

    2016-01-05

    Pretreatment lymphocyte count (LC) has been associated with prognosis and chemotherapy response in several cancers. The predictive value of LC for stage II colorectal cancer (CRC) and for high-risk patients treated with adjuvant chemotherapy (AC) has not been determined. A retrospective review of prospectively collected data from 1332 consecutive stage II CRC patients who underwent curative tumor resection was conducted. A pretreatment LC value risk, 459 (62.2%) of whom received AC. Patients with low LCs had significantly worse 5-year OS (74.6% vs. 90.2%, p risk patients with low LCs had the poorest DFS (p value or combined with high-risk status were both independent prognostic factors(p risk, AC-treated patients with high LCs had significantly longer DFS than untreated patients (HR, 0.594; 95% CI, 0.364-0.970; p = 0.035). There was no difference or trend for DFS or OS in patients with low LCs, regardless of the use of AC (DFS, p = 0.692; OS, p = 0.522). Low LC was also independently associated with poorer DFS in high-risk, AC-treated patients (HR, 1.885; 95% CI, 1.112-3.196; p = 0.019). Pretreatment LC is an independent prognostic factor for survival in stage II CRC. Furthermore, pretreatment LC reliably predicts chemotherapeutic efficacy in high-risk patients with stage II CRC.

  5. Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Deek, Matthew P.; Benenati, Brian [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Kim, Sinae [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Biometrics Division, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting; Ahmed, Inaya; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

    2016-01-01

    Purpose: To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). Methods and Materials: We included 52 patients with NSCLC treated with definitive concurrent carboplatin–paclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage of the total organ volume exceeding x radiation dose. Results: Grade ≥3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥3 leukopenia across multiple DVH parameters, including TV V{sub 20} (TVV) (odds ratio [OR] 1.06; P=.025), TVV{sub 30} (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV{sub 30} (β = −0.004; P=.018) and TVV{sub 20} (β = −0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥3 leukopenia was associated with a MVD of 13.5 Gy and a TTV{sub 30} of 28%. Cutoff values to avoid grade ≥3 leukopenia were MVD ≤23.9 Gy, TVV{sub 20} ≤56.0%, and TVV{sub 30} ≤52.1%. Conclusions: Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.

  6. {sup 18}F-FDG PET/contrast enhanced CT in the standard surveillance of high risk colorectal cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Jiménez Londoño, Germán Andrés, E-mail: gjimenez91@yahoo.com [Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); García Vicente, Ana María [Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Sánchez Pérez, Victoria [Department of Oncology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Jiménez Aragón, Fátima [Department of Radiology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); León Martin, Alberto [Investigation Unit, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Cano Cano, Juana María [Department of Oncology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Domínguez Ferreras, Esther [Department of Radiology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Gómez López, Ober Van [Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Espinosa Arranz, Javier [Department of Oncology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Soriano Castrejón, Ángel María [Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain)

    2014-12-15

    Highlights: • We assessed the accuracy of FDG-PET/contrast enhanced CT (FDG-PET/ceCT) in the detection of unsuspected recurrence of colorectal cancer. In regard to our knowledge, no previous experience has been reported about the combined acquisition and interpretation of a FDG-PET/ceCT in the surveillance of colorectal cancer. • We designed a prospective study and performed an individual and combined assessment of both techniques (PET and ceCT), in a patient-based analysis and a lesion-based analysis. • The value of PET and ceCT was found to be similar in the detection of unsuspected recurrence of CRC in a patient-based analysis. The most interesting of our result, is that the combined assessment of PET/ceCT improves the accuracy in the lesion-based analysis. - Abstract: Objective: To assess the accuracy of FDG-PET/contrast enhanced CT (FDG-PET/ceCT) in the detection of unsuspected recurrence of colorectal cancer (CRC) in patients with high risk of relapse. Methods: Thirty-three patients (14 females and 19 males, mean age: 62, range: 41–78), with CRC in complete remission, were prospectively included. All patients underwent FDG-PET/ceCT (58 studies). FDG-PET/ceCT was requested in the surveillance setting, and performed following a standardized protocol. A portal venous phase CT scan was performed after the injection of iodinated contrast agent. An individual and combined assessment of both techniques (PET and ceCT) was performed. Concordant and discordant findings of PET, ceCT and FDG-PET/ceCT were compared in a patient-based and a lesion-based analysis. The final diagnosis, recurrence or disease free status (DFS), were established by histopathology or clinical/radiological follow-up of at least 6 months. Results: Seven out of 33 patients had a confirmed recurrence and the rest of patients had a DFS. In a patient-based analysis the sensitivity and specificity of PET, ceCT and PET/ceCT was of 86% and 88%, 86% and 92%, 86% and 85%, respectively. Attending to

  7. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler; Sandler, Howard M.; Feng, Felix Y.; Hamstra, Daniel A.

    2011-01-01

    Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11–33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer–specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8–3.9, p < 0.0001), salvage ADT use (HR 3.9–6.3, p < 0.0001), metastasis (HR 3.7–6.6, p < 0.0001), and PCSM (HR 3.7–16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19–0.38, p < 0.001) and PCSM (HR 0.38–0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3–4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25–0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

  8. Reflections on the Implementation of Low-Dose Computed Tomography Screening in Individuals at High Risk of Lung Cancer in Spain.

    Science.gov (United States)

    Garrido, Pilar; Sánchez, Marcelo; Belda Sanchis, José; Moreno Mata, Nicolás; Artal, Ángel; Gayete, Ángel; Matilla González, José María; Galbis Caravajal, José Marcelo; Isla, Dolores; Paz-Ares, Luis; Seijo, Luis M

    2017-10-01

    Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals. This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM). Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b&c

    DEFF Research Database (Denmark)

    Kyndi, Marianne; Sørensen, Flemming Brandt; Knudsen, Helle

    2008-01-01

    -Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2......PURPOSE: To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). PATIENTS AND METHODS: The present analysis included 1 000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b&c studies. Tissue...... tests, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. RESULTS: p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan...

  10. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b

    DEFF Research Database (Denmark)

    Kyndi, M.; Sorensen, F.B.; Alsner, J.

    2008-01-01

    -Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2......Purpose. To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). Patients and methods. The present analysis included 1000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b&c studies. Tissue microarray......, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. Results. p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots...

  11. Oncological outcomes of high-risk prostate cancer patients between robot-assisted laparoscopic radical prostatectomy and laparoscopic radical prostatectomy in Taiwan

    Directory of Open Access Journals (Sweden)

    Chieh-Chun Liao

    2018-01-01

    Full Text Available Objective: To compare pathological and oncological outcomes between robotic-assisted laparoscopic radical prostatectomy (RaLRP and laparoscopic radical prostatectomy (LRP among high-risk prostate cancer patient in a tertiary center in Taiwan. Materials and methods: From November 2003 to October 2013, 129 high-risk prostate cancer patients receiving minimally-invasive radical prostatectomy were included. The Kaplan–Meier analysis was used for measuring biochemical recurrence-free survival (BFS. Multivariate logistic regression models and Cox proportional hazards regression models were used to determine predictors of positive surgical margin and BFS. Results: Among the 129 high-risk prostate cancer patients included, 80 (62% patients received LRP and 49 (38% patients received RaLRP. There was no significant difference of positive surgical margin and biochemical recurrence rate between RaLRP and LRP group (P = 0.802 and 0.292. Higher pathological T stage predicted an increased likelihood of positive margins (OR = 3.44, 95% CI [1.45, 8.18], P = 0.005. Higher initial PSA level (HR = 2.88, 95% CI [1.04, 7.94], P = 0.041 and positive surgical margin (HR = 2.55, 95% CI [1.20, 5.44], P = 0.015 were poor prognostic factors for BFS. Conclusion: RaLRP can be considered among high-risk prostate cancer in Asian people with comparable oncological outcomes to LRP. Higher pathological T stage was associated with increased likelihood of positive margins, patients with higher iPSA level and positive surgical margin had worsen biochemical recurrence-free survival.

  12. Utility of supplemental screening with breast ultrasound in asymptomatic women with dense breast tissue who are not at high risk for breast cancer

    OpenAIRE

    Klevos, Geetika A; Collado-Mesa, Fernando; Net, Jose M; Yepes, Monica M

    2017-01-01

    Objective: To assess the results of an initial round of supplemental screening with hand-held bilateral breast ultrasound following a negative screening mammogram in asymptomatic women with dense breast tissue who are not at high risk for breast cancer. Materials and Methods: A retrospective, Health Insurance Portability and Accountability Act compliant, Institutional Research Board approved study was performed at a single academic tertiary breast center. Informed consent was waived. A system...

  13. Role of P53 and BCL-2 in high-risk breast cancer patients treated with adjuvant anthracycline-based chemotherapy.

    Science.gov (United States)

    Mottolese, M; Benevolo, M; Del Monte, G; Buglioni, S; Papaldo, P; Nisticò, C; Di Filippo, F; Vasselli, S; Vici, P; Botti, C

    2000-12-01

    Adjuvant therapy has become an integral component of the managment of primary high-risk breast cancer patients. However, a considerable fraction of women receive no benefit from this treatment. This study investigates whether a number of biopathological factors can influence the outcome of patients submitted to adjuvant chemotherapy involving the use of high-dose epirubicin and cyclophosphamide. One hundred and fifty-seven primary breast cancer patients, considered at high risk according to the St. Gallen Meeting Consensus Conference, were evaluated immunohistochemically for estrogen, progesterone receptors, p53, bcl-2, HER-2/neu, and Ki-67, of which the results were correlated with patient outcome. Results obtained demonstrated that p53 is a significant predictor of disease-free survival (DFS P < 0.0001) and overall survival (OS P = 0.0002) both in ductal and lobular carcinomas, whereas bcl-2 expression seems to be of prognostic value only in lobular carcinomas (DFS P = 0.01; OS P = 0.02). This data indicates that in high-risk breast cancer patients the immunohistochemical evaluation of p53 and bcl-2 may be of clinical value in distinguishing different responses to adjuvant anthracycline-based chemotherapy.

  14. Radiation Therapy and Late Mortality From Second Sarcoma, Carcinoma, and Hematological Malignancies After a Solid Cancer in Childhood

    International Nuclear Information System (INIS)

    Tukenova, Markhaba; Guibout, Catherine; Hawkins, Mike; Quiniou, Eric; Mousannif, Abddedahir; Pacquement, Helene; Winter, David; Bridier, Andre; Lefkopoulos, Dimitri; Oberlin, Odile; Diallo, Ibrahima; Vathaire, Florent de

    2011-01-01

    Purpose: To compare patterns of long-term deaths due to secondary carcinomas, sarcomas, and hematological malignancies occurring after childhood cancer in a cohort of patients followed over a median of 28 years. Methods and Materials: The study included 4,230 patients treated at eight institutions, who were at least 5-year survivors of a first cancer, representing 105,670 person-years of observation. Complete clinical, chemotherapeutic, and radiotherapeutic data were recorded, and the integral radiation dose was estimated for 2,701 of the 2,948 patients who had received radiotherapy. The integral dose was estimated for the volume inside the beam edges. The causes of death obtained from death certificates were validated. Results: In total, 134 events were due to second malignant neoplasm(s) (SMN). We found that the standardized mortality ratio decreased with increasing follow-up for second carcinomas and sarcomas, whereas the absolute excess risk (AER) increased for a second carcinoma but decreased for second sarcomas. There was no clear variation in SMN and AER for hematological malignancies. We found a significant dose-response relationship between the radiation dose received and the mortality rate due to a second sarcoma and carcinoma. The risk of death due to carcinoma and sarcoma as SMN was 5.2-fold and 12.5-fold higher, respectively, in patients who had received a radiation dose exceeding 150 joules. Conclusions: Among patients who had received radiotherapy, only those having received the highest integral radiation dose actually had a higher risk of dying of a second carcinoma or sarcoma.

  15. An exercise trial targeting African-American women with metabolic syndrome and at high risk for breast cancer: Rationale, design, and methods.

    Science.gov (United States)

    Dash, Chiranjeev; Makambi, Kepher; Wallington, Sherrie F; Sheppard, Vanessa; Taylor, Teletia R; Hicks, Jennifer S; Adams-Campbell, Lucile L

    2015-07-01

    Metabolic syndrome and obesity are known risk factors for breast cancers. Exercise interventions can potentially modify circulating biomarkers of breast cancer risk but evidence in African-Americans and women with metabolic syndrome is lacking. The Focused Intervention on Exercise to Reduce CancEr (FIERCE) trial is a prospective, 6-month, 3-arm, randomized controlled trial to examine the effect of exercise on obesity, metabolic syndrome components, and breast cancer biomarkers among African-American women at high risk of breast cancer. Two hundred-forty inactive women with metabolic syndrome and absolute risk of breast cancer ≥ 1.40 will be randomized to one of the three trial arms: 1) a supervised, facility-based exercise arm; 2) a home-based exercise arm; and 3) a control group that maintains physical activity levels through the course of the trial. Assessments will be conducted at baseline, 3 months, and 6 months. The primary outcome variables are anthropometric indicators of obesity, metabolic syndrome components, and inflammatory, insulin-pathway, and hormonal biomarkers of breast cancer risk. The FIERCE trial will provide evidence on whether a short-term exercise intervention might be effective in reducing breast cancer risk among African-American women with comorbidities and high breast cancer risk--a group traditionally under-represented in non-therapeutic breast cancer trials. NCT02103140. Copyright © 2015. Published by Elsevier Inc.

  16. Life-Style Habits in a High-Risk Area for Upper Gastrointestinal Cancers: a Population-Based Study from Shanxi, China.

    Science.gov (United States)

    Cheng, Yi-Kun; Yao, Shang-Man; Xu, Yi-Ran; Niu, Run-Gui

    2016-01-01

    Cancer is a burden on humanity and ranks as a leading cause of morbidity and mortality in China. Shanxi province has its unique cancer patterns and the burden is increasing. In this study, we aimed to assess the pattern of dietary habits and life-style in Shanxi, a high-risk area for upper gastrointestinal cancers in China and further evaluate the trends in cancer incidence and mortality based on registered data. Data on lifestyle, diet, physical activity were obtained from the household health survey at Zhongyang from 2013 to 2015. Cancer diagnoses were reported to Shanxi Center for Disease Control and Prevention (SCDCP). Population-based cancer incidence data and mortality data of 2012 were collected from the SCDCP. All incidence and death rates were expressed per 100,000 populations. Univariate analysis was performed using the Chi-squared test or Fisherandapos;s exact test. Overall, deficiencies in fresh fruits and vegetable food, and intake of hot food, salted food, or pickled food are serious problems in Shanxi, especially in rural areas. Upper gastrointestinal cancers were the most commonly diagnosed cancers, and the incidence in rural areas is higher than those in urban areas. Cervical cancer is the most common cancer for females. Moreover, the agespecific incidence exhibited an increased trend before 40 years old. Consistent with the previous literature, our epidemiological investigation results suggest that lifestyle, nutrition deficient, and infections were major risk factors for upper gastrointestinal cancers or cervical cancer in Shanxi. Facing a serious situation, we further explored defensible recommendations for the general public in order to promote changes in environments that support healthful eating and physical activity habits, to reduce cancer risk. Our results present the current cancer trends in Shanxi and its related etiologic risk factors and provide a theoretical basis to guide public health efforts to prevent and control cancers in the

  17. Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Wei [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nezolosky, Michelle [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Beard, Clair J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Den, Robert B. [Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States)

    2016-03-15

    Purpose: Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials: We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results: A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95-0.98; P<.0001) after adjusting for known confounders. For illustrative purposes, when RCV was dichotomized at the 80th percentile (43 patients/year), high RCV was associated with improved OS (7-year overall survival 76% vs 74%, log-rank test P=.0005; AHR: 0.91, 95% CI: 0.86-0.96, P=.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions: Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate

  18. A new hereditary colorectal cancer network in the Middle East and eastern mediterranean countries to improve care for high-risk families.

    Science.gov (United States)

    Ghorbanoghli, Zeinab; Jabari, Carol; Sweidan, Walid; Hammoudeh, Wail; Cortas, George; Sharara, Ala I; Abedrabbo, Amal; Hourani, Ijad; Mahjoubi, Bahareh; Majidzadeh, Keivan; Tözün, Nurdan; Ziada-Bouchaar, Hadia; Hamoudi, Waseem; Diab, Osama; Khorshid, Hamid Reza Khorram; Lynch, Henry; Vasen, Hans

    2018-04-01

    Colorectal cancer (CRC) has a very high incidence in the western world. Data from registries in the Middle East showed that the incidence of CRC is relatively low in these countries. However, these data also showed that CRC incidence has increased substantially over the past three decades and that a high proportion of cases are diagnosed at an early age (Middle East was discussed and the idea was conceived to establish a network on hereditary colorectal cancer (HCCN-ME) with the goal of improving care for high-risk groups in the Middle East and (Eastern) Mediterranean Countries.

  19. Occult Breast Cancer: Scintimammography with High-Resolution Breast-specific Gamma Camera in Women at High Risk for Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rachel F. Brem; Jocelyn A. Rapelyea; , Gilat Zisman; Kevin Mohtashemi; Joyce Raub; Christine B. Teal; Stan Majewski; Benjamin L. Welch

    2005-08-01

    To prospectively evaluate a high-resolution breast-specific gamma camera for depicting occult breast cancer in women at high risk for breast cancer but with normal mammographic and physical examination findings. MATERIALS AND METHODS: Institutional Review Board approval and informed consent were obtained. The study was HIPAA compliant. Ninety-four high-risk women (age range, 36-78 years; mean, 55 years) with normal mammographic (Breast Imaging Reporting and Data System [BI-RADS] 1 or 2) and physical examination findings were evaluated with scintimammography. After injection with 25-30 mCi (925-1110 MBq) of technetium 99m sestamibi, patients were imaged with a high-resolution small-field-of-view breast-specific gamma camera in craniocaudal and mediolateral oblique projections. Scintimammograms were prospectively classified according to focal radiotracer uptake as normal (score of 1), with no focal or diffuse uptake; benign (score of 2), with minimal patchy uptake; probably benign (score of 3), with scattered patchy uptake; probably abnormal (score of 4), with mild focal radiotracer uptake; and abnormal (score of 5), with marked focal radiotracer uptake. Mammographic breast density was categorized according to BI-RADS criteria. Patients with normal scintimammograms (scores of 1, 2, or 3) were followed up for 1 year with an annual mammogram, physical examination, and repeat scintimammography. Patients with abnormal scintimammograms (scores of 4 or 5) underwent ultrasonography (US), and those with focal hypoechoic lesions underwent biopsy. If no lesion was found during US, patients were followed up with scintimammography. Specific pathologic findings were compared with scintimammographic findings. RESULTS: Of 94 women, 78 (83%) had normal scintimammograms (score of 1, 2, or 3) at initial examination and 16 (17%) had abnormal scintimammograms (score of 4 or 5). Fourteen (88%) of the 16 patients had either benign findings at biopsy or no focal abnormality at US; in two

  20. Occult Breast Cancer: Scintimammography with High-Resolution Breast-specific Gamma Camera in Women at High Risk for Breast Cancer

    International Nuclear Information System (INIS)

    Rachel F. Brem; Jocelyn A. Rapelyea; , Gilat Zisman; Kevin Mohtashemi; Joyce Raub; Christine B. Teal; Stan Majewski; Benjamin L. Welch

    2005-01-01

    To prospectively evaluate a high-resolution breast-specific gamma camera for depicting occult breast cancer in women at high risk for breast cancer but with normal mammographic and physical examination findings. MATERIALS AND METHODS: Institutional Review Board approval and informed consent were obtained. The study was HIPAA compliant. Ninety-four high-risk women (age range, 36-78 years; mean, 55 years) with normal mammographic (Breast Imaging Reporting and Data System [BI-RADS] 1 or 2) and physical examination findings were evaluated with scintimammography. After injection with 25-30 mCi (925-1110 MBq) of technetium 99m sestamibi, patients were imaged with a high-resolution small-field-of-view breast-specific gamma camera in craniocaudal and mediolateral oblique projections. Scintimammograms were prospectively classified according to focal radiotracer uptake as normal (score of 1), with no focal or diffuse uptake; benign (score of 2), with minimal patchy uptake; probably benign (score of 3), with scattered patchy uptake; probably abnormal (score of 4), with mild focal radiotracer uptake; and abnormal (score of 5), with marked focal radiotracer uptake. Mammographic breast density was categorized according to BI-RADS criteria. Patients with normal scintimammograms (scores of 1, 2, or 3) were followed up for 1 year with an annual mammogram, physical examination, and repeat scintimammography. Patients with abnormal scintimammograms (scores of 4 or 5) underwent ultrasonography (US), and those with focal hypoechoic lesions underwent biopsy. If no lesion was found during US, patients were followed up with scintimammography. Specific pathologic findings were compared with scintimammographic findings. RESULTS: Of 94 women, 78 (83%) had normal scintimammograms (score of 1, 2, or 3) at initial examination and 16 (17%) had abnormal scintimammograms (score of 4 or 5). Fourteen (88%) of the 16 patients had either benign findings at biopsy or no focal abnormality at US; in two

  1. Reptile Hematology.

    Science.gov (United States)

    Sykes, John M; Klaphake, Eric

    2015-09-01

    The basic principles of hematology used in mammalian medicine can be applied to reptiles. The appearances of the blood cells are significantly different from those seen in most mammals, and vary with taxa and staining method used. Many causes for abnormalities of the reptilian hemogram are similar to those for mammals, although additional factors such as venipuncture site, season, hibernation status, captivity status, and environmental factors can also affect values, making interpretation of hematologic results challenging. Values in an individual should be compared with reference ranges specific to that species, gender, and environmental conditions when available. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. [(18)F]Fluorodeoxyglucose - positron emission tomography/computed tomography improves staging in patients with high-risk muscle-invasive bladder cancer scheduled for radical cystectomy.

    Science.gov (United States)

    Kollberg, Petter; Almquist, Helen; Bläckberg, Mats; Cronberg, Carin; Garpered, Sabine; Gudjonsson, Sigurdur; Kleist, Jakob; Lyttkens, Kerstin; Patschan, Oliver; Liedberg, Fredrik

    2015-01-01

    The aim of this study was to evaluate the clinical use of [(18)F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in addition to conventional preoperative radiological investigations in a defined group of patients with high-risk muscle-invasive bladder cancer. In total, 103 patients with high-risk muscle-invasive bladder cancer defined as stage T3/T4 disease or as stage T2 with hydronephrosis or high-risk histological features, who were provisionally scheduled to undergo cystectomy, were prospectively recruited to the study. The patients were referred to FDG-PET/CT in addition to standard preoperative investigation with computed tomography (CT). The final treatment decision was reached at a multidisciplinary conference based on all available information including the FDG-PET/CT findings. Compared to CT alone, FDG-PET/CT provided more supplemental findings suggesting malignant manifestations in 48 (47%) of the 103 patients. The additional FDG-PET/CT findings led to an altered provisional treatment plan in 28 out of 103 patients (27%), detection of disseminated bladder cancer and subsequent cancellation of the initially intended cystectomy in 16 patients, and identification of disseminated disease and treatment with induction chemotherapy before radical cystectomy in 12 patients. Preoperative FDG-PET/CT changed the treatment plan for a considerable proportion (27%) of the present patients. Accordingly, such examination can potentially improve the preoperative staging of cystectomy patients with high-risk features, and may also reduce the number of futile operations in patients with advanced disease who are beyond cure.

  3. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.

    Science.gov (United States)

    Cuzick, Jack; Sestak, Ivana; Forbes, John F; Dowsett, Mitch; Knox, Jill; Cawthorn, Simon; Saunders, Christobel; Roche, Nicola; Mansel, Robert E; von Minckwitz, Gunter; Bonanni, Bernardo; Palva, Tiina; Howell, Anthony

    2014-03-22

    Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, pbreast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in

  4. Under-utilisation of high-dose-rate brachytherapy boost in men with intermediate-high risk prostate cancer treated with external beam radiotherapy.

    Science.gov (United States)

    Ong, Wee Loon; Evans, Sue M; Millar, Jeremy L

    2018-04-01

    The aim of this study was to evaluate the use of high-dose-rate brachytherapy (HDR-BT) boost with definitive external beam radiotherapy (EBRT) in prostate cancer (CaP) management. The study population comprised men with intermediate-high risk CaP captured in the population-based Prostate Cancer Outcome Registry Victoria (PCOR-Vic), treated with EBRT from January 2010 to December 2015. The primary outcome is the proportion of men who received HDR-BT boost. Multivariate logistic regressions were used to evaluate the effect of patient-, tumour- and treatment-factors on the likelihood of HDR-BT use. Medicare Benefit Schedule (MBS) data was accessed to evaluate the Australia-wide pattern of HDR-BT use. One thousand eight hundred and six patients were included in this study - 886 (49%) intermediate-risk, and 920 (51%) high-risk CaP patients. Overall, only 124 (7%) patients had EBRT + HDR-BT - 47 (5%) intermediate-risk and 77 (8%) high-risk CaP patients (P = 0.01). There is higher proportion of patients who had HDR-BT in public institutions (7% public vs. 3% private, P = 0.005) and in metropolitan centres (9% metropolitan vs. 2% regional, P Victorian men with CaP. The decline in HDR-BT use was also observed nationally. © 2017 The Royal Australian and New Zealand College of Radiologists.

  5. Radiation hematology

    International Nuclear Information System (INIS)

    Zherbin, E.A.; Chukhlovin, A.B.

    1989-01-01

    State-of-the-Art ofl radiation hematology and review of the problems now facing this brauch of radiobiology and nuclear medicine are presented. Distortion of division and maturation of hemopoiesis parent cells is considered as main factor of radiopathology for hematopoetic system. Problems of radiation injury and functional variation of hematopoetic microenvironment cell populations are discussed. 176 figs.; 23 figs.; 18 tabs

  6. DOC-2/DAB2 Interacting Protein Status in High-Risk Prostate Cancer Correlates With Outcome for Patients Treated With Radiation Therapy

    International Nuclear Information System (INIS)

    Jacobs, Corbin; Tumati, Vasu; Kapur, Payal; Yan, Jingsheng; Hong, David; Bhuiyan, Manzerul; Xie, Xian-Jin; Pistenmaa, David; Yu, Lan; Hsieh, Jer-Tsong; Saha, Debabrata; Kim, D. W. Nathan

    2014-01-01

    Purpose: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy. Methods and Materials: Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance–free survival (CRFS), and distant metastasis–free survival (DMFS). Log-rank test and Cox regression were used to determine significance of biomarker levels with clinical outcome. Results: Fifty-four patients with high-risk prostate cancer (stage ≥T3a, or Gleason score ≥8, or prostate-specific antigen level ≥20 ng/mL) treated with radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2 study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%, P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%, P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04) compared with the control group. Conclusion: Loss of DAB2IP is a potent biomarker that portends worse outcome despite definitive radiation therapy for patients with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most high-risk tumors and is a less potent discriminator of outcome in this study. The DAB2IP status in combination with degree of EZH2 expression may be useful for

  7. Low-dose-rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse.

    Science.gov (United States)

    Laing, Robert; Uribe, Jennifer; Uribe-Lewis, Santiago; Money-Kyrle, Julian; Perna, Carla; Chintzoglou, Stylianos; Khaksar, Sara; Langley, Stephen E M

    2018-04-01

    To report clinical outcomes of 125 I low-dose-rate prostate brachytherapy (LDR-PB) as monotherapy or combined with androgen-deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high-risk localised prostate cancer. Analysis of clinical outcomes from a prospective cohort of patients treated with LDR-PB alone or combined treatment in a single institution. Men with a high risk of disease relapse were identified by the National Institute for Health and Care Excellence (NICE) criteria or by the National Comprehensive Cancer Network (NCCN) criteria. Relapse-free survival (RFS), overall survival (OS), prostate cancer-specific survival (PCSS), and metastases-free survival (MFS), were analysed together with patient-reported symptom scores and physician-reported adverse events. The NICE and NCCN criteria identified 267 and 202 high-risk patients, respectively. NICE-defined patients had significantly lower pre-treatment PSA levels, Gleason scores LDR-PB monotherapy. At 9 years after implantation RFS was 89% and 87% in the NICE and NCCN groups, respectively (log-rank P = 0.637), and OS 93% and 94%, respectively (log-rank P = 0.481). All of the survival estimates were similar between LDR-PB monotherapy and combined therapies. Cox proportional hazards regression confirmed RFS was similar between the treatment types. Treatment-related toxicity was also similar between the treatment methods. LDR-PB is effective at controlling localised prostate cancer in patients with a high risk of disease relapse. As the present study was not randomised, it is not possible to define those patients who need the addition of ADT and/or EBRT. However, the NICE criteria appear suitable to define treatment options where patients could benefit from LDR-PB as monotherapy or combined treatment. This choice should be discussed with the patient taking into account comorbidities and presence of multiple high-risk factors. © 2018 The Authors BJU International © 2018 BJU International

  8. DOC-2/DAB2 Interacting Protein Status in High-Risk Prostate Cancer Correlates With Outcome for Patients Treated With Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Corbin; Tumati, Vasu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Kapur, Payal [Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Yan, Jingsheng [Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hong, David; Bhuiyan, Manzerul [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Xie, Xian-Jin [Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Pistenmaa, David [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States); Yu, Lan [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong [Simmons Cancer Center, Dallas, Texas (United States); Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Saha, Debabrata [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States); Kim, D. W. Nathan, E-mail: Nathan.Kim@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States)

    2014-07-15

    Purpose: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy. Methods and Materials: Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance–free survival (CRFS), and distant metastasis–free survival (DMFS). Log-rank test and Cox regression were used to determine significance of biomarker levels with clinical outcome. Results: Fifty-four patients with high-risk prostate cancer (stage ≥T3a, or Gleason score ≥8, or prostate-specific antigen level ≥20 ng/mL) treated with radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2 study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%, P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%, P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04) compared with the control group. Conclusion: Loss of DAB2IP is a potent biomarker that portends worse outcome despite definitive radiation therapy for patients with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most high-risk tumors and is a less potent discriminator of outcome in this study. The DAB2IP status in combination with degree of EZH2 expression may be useful for

  9. Efficacy of modest dose irradiation in combination with long-term endocrinal treatment for high-risk prostate cancer. A preliminary report

    International Nuclear Information System (INIS)

    Sasaki, Tomonari; Nakamura, Katsumasa; Shioyama, Yoshiyuki

    2004-01-01

    Although radiotherapy in combination with endocrinal manipulation has been identified as an effective treatment for patients with high-risk prostate cancer, the optimal dose for locoregional control of prostate cancer in combination with hormonal therapy has not yet been determined. The efficacy of modest doses of irradiation (60-62 Gy) combined with long-term endocrinal treatment for patients with high-risk prostate cancer (defined as a pretreatment prostate-specific antigen (PSA) level greater than 20 ng/ml or a Gleason's score of 8-10 or T3-T4 disease) was analyzed in 60 Japanese patients. The patients included in this study had received radical radiotherapy with long-term endocrinal manipulation in the period between 1993 and 2000. The median age of the patients was 70 years (range, 56-83). Neoadjuvant hormonal therapy with a median duration of 3.9 months was performed prior to radiotherapy, and hormonal therapy was continued until recurrence. A median dose of 61.4 Gy (range, 44-71.4) was delivered to the prostate. Pelvic node irradiation was performed in 49 patients (81.6%). After a median follow-up period of 28.5 months, the overall survival, cause-specific survival and biochemical relapse-free survival at 3 years were 94.4%, 96% and 89.8%, respectively. Local failure was observed in one patient, distant metastases were observed in three patients and a late toxic effect greater than Grade 2 was not observed in any patients. This study, though preliminary due to a short-term follow-up period, reveals the possibility that modest doses of irradiation combined with long-term endocrinal treatment could be an effective means of achieving excellent local control of high-risk prostate cancer. (author)

  10. Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial.

    Science.gov (United States)

    Blanchard, Pierre; Faivre, Laura; Lesaunier, François; Salem, Naji; Mesgouez-Nebout, Nathalie; Deniau-Alexandre, Elisabeth; Rolland, Frédéric; Ferrero, Jean-Marc; Houédé, Nadine; Mourey, Loïc; Théodore, Christine; Krakowski, Ivan; Berdah, Jean-François; Baciuchka, Marjorie; Laguerre, Brigitte; Davin, Jean-Louis; Habibian, Muriel; Culine, Stéphane; Laplanche, Agnès; Fizazi, Karim

    2016-01-01

    The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (PENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy.

    Science.gov (United States)

    Ross, Ashley E; Hughes, Robert M; Glavaris, Stephanie; Ghabili, Kamyar; He, Ping; Anders, Nicole M; Harb, Rana; Tosoian, Jeffrey J; Marchionni, Luigi; Schaeffer, Edward M; Partin, Alan W; Allaf, Mohamad E; Bivalacqua, Trinity J; Chapman, Carolyn; O'Neal, Tanya; DeMarzo, Angelo M; Hurley, Paula J; Rudek, Michelle A; Antonarakis, Emmanuel S

    2017-11-28

    To determine the pharmacodynamic effects of Sonidegib (LDE-225) in prostate tumor tissue from men with high-risk localized prostate cancer, by comparing pre-surgical core-biopsy specimens to tumor tissue harvested post-treatment at prostatectomy. We conducted a prospective randomized (Sonidegib vs. observation) open-label translational clinical trial in men with high-risk localized prostate cancer undergoing radical prostatectomy. The primary endpoint was the proportion of patients in each arm who achieved at least a two-fold reduction in GLI1 mRNA expression in post-treatment versus pre-treatment tumor tissue. Secondary endpoints included the effect of pre-surgical treatment with Sonidegib on disease progression following radical prostatectomy, and safety. Fourteen men were equally randomized (7 per arm) to either neoadjuvant Sonidegib or observation for 4 weeks prior to prostatectomy. Six of seven men (86%) in the Sonidegib arm (and none in the control group) achieved a GLI1 suppression of at least two-fold. In the Sonidegib arm, drug was detectable in plasma and in prostatic tissue; and median intra-patient GLI1 expression decreased by 63-fold, indicating potent suppression of Hedgehog signaling. Sonidegib was well tolerated, without any Grade 3-4 adverse events observed. Disease-free survival was comparable among the two arms (HR = 1.50, 95% CI 0.26-8.69, P = 0.65). Hedgehog pathway activity (as measured by GLI1 expression) was detectable at baseline in men with localized high-risk prostate cancer. Sonidegib penetrated into prostatic tissue and induced a >60-fold suppression of the Hedgehog pathway. The oncological benefit of Hedgehog pathway inhibition in prostate cancer remains unclear.

  12. The accuracy of {sup 68}Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oebek, Can; Doganca, Tuenkut [Acibadem Taksim Hospital, Department of Urology, Istanbul (Turkey); Demirci, Emre [Sisli Etfal Training and Research Hospital, Department of Nuclear Medicine, Istanbul (Turkey); Ocak, Meltem [Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul (Turkey); Kural, Ali Riza [Acibadem University, Department of Urology, Istanbul (Turkey); Yildirim, Asif [Istanbul Medeniyet University, Department of Urology, Istanbul (Turkey); Yuecetas, Ugur [Istanbul Training and Research Hospital, Department of Urology, Istanbul (Turkey); Demirdag, Cetin [Istanbul University, Cerrahpasa School of Medicine, Department of Urology, Istanbul (Turkey); Erdogan, Sarper M. [Istanbul University, Cerrahpasa School of Medicine, Department of Public Health, Istanbul (Turkey); Kabasakal, Levent [Istanbul University, Cerrahpasa School of Medicine, Department of Nuclear Medicine, Istanbul (Turkey); Collaboration: Members of Urooncology Association, Turkey

    2017-10-15

    To assess the diagnostic accuracy of {sup 68}Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging. This was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included. Either MRI or CT was used for morphological imaging. PSMA PET/CT was performed and evaluated at a single centre. Sensitivity, specificity and accuracy were calculated for the detection of lymphatic metastases by PSMA PET/CT and morphological imaging. Kappa values were calculated to evaluate the correlation between the numbers of LN metastases detected by PSMA PET/CT and by histopathology. Data on 51 eligible patients are presented. The sensitivity, specificity and accuracy of PSMA PET in detecting LN metastases in the primary setting were 53%, 86% and 76%, and increased to 67%, 88% and 81% in the subgroup with of patients with ≥15 LN removed. Kappa values for the correlation between imaging and pathology were 0.41 for PSMA PET and 0.18 for morphological imaging. PSMA PET/CT is superior to morphological imaging for the detection of metastatic LNs in patients with primary prostate cancer. Surgical dissection remains the gold standard for precise lymphatic staging. (orig.)

  13. Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy.

    Science.gov (United States)

    Chen, Xin; Bernemann, Christof; Tolkach, Yuri; Heller, Martina; Nientiedt, Cathleen; Falkenstein, Michael; Herpel, Esther; Jenzer, Maximilian; Grüllich, Carsten; Jäger, Dirk; Sültmann, Holger; Duensing, Anette; Perner, Sven; Cronauer, Marcus V; Stephan, Carsten; Debus, Jürgen; Schrader, Andres Jan; Kristiansen, Glen; Hohenfellner, Markus; Duensing, Stefan

    2018-04-01

    Overexpression of the androgen receptor (AR) splice variant 7 (AR-V7) has recently been reported to be associated with resistance to antihormonal therapy. Herein, we address the question whether tumor cells with AR-V7 expression can be detected at the time of radical prostatectomy, that is, before long-term hormonal manipulation and castration resistance, and what the potential prognostic impact on the biochemical recurrence (BCR)-free survival may be. An anti-AR-V7 antibody was first validated in a training set of prostate cancer specimens by a comparison of AR-V7 protein to AR-V7 mRNA expression. We then analyzed nuclear AR-V7 protein expression in the primary tumors and lymph node metastases from 163 predominantly high-risk patients (cohort I) as well as the primary tumors from patients of a second, consecutive patient cohort (n = 238, cohort II) not selected for any clinicopathological features. Staining results were correlated to patient characteristics and BCR-free patient survival. High nuclear AR-V7 protein expression was detected in approximately 30%-40% of patients in cohort I and II at the time of radical prostatectomy. High baseline expression of nuclear AR-V7 protein was associated with an unfavorable BCR-free survival in the high-risk patient cohort I but not in the unselected consecutive cohort II. Remarkably, AR-V7 was an independent negative prognostic factor in high-risk prostate cancer patients of cohort I who were selected to receive adjuvant treatment. Prostate cancer cells with high nuclear AR-V7 protein expression can be detected in a substantial proportion of tumors at the time of radical prostatectomy. The presence of AR-V7-positive tumor cells is associated with an unfavorable prognosis for BCR-free survival in a high-risk patient cohort including a subgroup of patients selected to receive adjuvant therapy, in which AR-V7 was an independent negative prognosticator. Overexpression of nuclear AR-V7 protein hence identifies a subset of tumors

  14. Long term results of a prospective dose escalation phase-II trial: Interstitial pulsed-dose-rate brachytherapy as boost for intermediate- and high-risk prostate cancer

    International Nuclear Information System (INIS)

    Lettmaier, Sebastian; Lotter, Michael; Kreppner, Stephan; Strnad, Annedore; Fietkau, Rainer; Strnad, Vratislav

    2012-01-01

    Purpose: We reviewed our seven year single institution experience with pulsed dose rate brachytherapy dose escalation study in patients with intermediate and high risk prostate cancer. Materials and methods: We treated a total of 130 patients for intermediate and high risk prostate cancer at our institution between 2000 and 2007 using PDR-brachytherapy as a boost after conformal external beam radiation therapy to 50.4 Gy. The majority of patients had T2 disease (T1c 6%, T2 75%, T3 19%). Seventy three patients had intermediate-risk and 53 patients had high-risk disease according to the D’Amico classification. The dose of the brachytherapy boost was escalated from 25 to 35 Gy – 33 pts. received 25 Gy (total dose 75 Gy), 63 pts. 30 Gy (total dose 80 Gy) and 34 pts. 35 Gy, (total dose 85 Gy) given in one session (dose per pulse was 0.60 Gy or 0.70 Gy/h, 24 h per day, night and day, with a time interval of 1 h between two pulses). PSA-recurrence-free survival according to Kaplan–Meier using the Phoenix definition of biochemical failure was calculated and also late toxicities according to Common Toxicity Criteria scale were assessed. Results: At the time of analysis with a median follow-up of 60 months biochemical control was achieved by 88% of patients – only 16/130 patients (12.3%) developed a biochemical relapse. Biochemical relapse free survival calculated according to Kaplan–Meier for all patients at 5 years was 85.6% (83.9% for intermediate-risk patients and 84.2% for high-risk patients) and at 9 years’ follow up it was 79.0%. Analysing biochemical relapse free survival separately for different boost dose levels, at 5 years it was 97% for the 35 Gy boost dose and 82% for the 25 and 30 Gy dose levels. The side effects of therapy were negligible: There were 18 cases (15%) of grade 1/2 rectal proctitis, one case (0.8%) of grade 3 proctitis, 18 cases (15%) of grade 1/2 cystitis, and no cases (0%) with dysuria grade 3. No patient had a bulbourethral

  15. Is there light at the end of the tunnel; symptoms and chest x-ray help identify patients at high risk of lung cancer

    International Nuclear Information System (INIS)

    Toori, K.U.; Nomani, A.Z.; Winson, M.; Rehman, M.U.

    2015-01-01

    Objectives: Late recognition of lung cancer is the major factor contributing towards its unsuccessful treatment. We conducted a prospective study to define any significant relationship of presenting symptoms with the diagnosis of lung cancer with a view to develop a model to identify those at high risk. Methods: A consecutive series of 587 patients referred to our rapid access chest clinic with the suspicion of lung cancer were included. The presenting symptoms, chest x-ray findings and final diagnosis of all the patients were recorded. Chi-square and t-test were used for univariate analysis. A model was generated from logistic regression analysis and the discriminatory power of the model was assessed using area under receiver operator characteristic curve. Results: Univariate analysis demonstrated that smoking, anorexia, weight loss and voice change were significantly more common in patients with lung cancer (p<0.05). Cough, expectoration and hemoptysis were significantly less common (p<0.05). Regression analysis qualified age, weight loss and smoking as significant predictors of lung cancer. Conclusion: Only few of the historically accepted symptoms demonstrated a strong association with lung cancer and the model developed on these can form basis for a scoring tool that can perhaps help identify those at higher risk of cancer. Further refinement of the tool is required to accommodate cases presenting at primary care level. (author)

  16. Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families

    Directory of Open Access Journals (Sweden)

    Pichette Roxane

    2006-09-01

    Full Text Available Abstract Background Ataxia telangiectasia-mutated and Rad3-related (ATR is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. Methods ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD, haplotype analyses, and tagging SNP (tSNP identification. Expression analyses were carried out using real-time PCR. Results The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. Conclusion Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association

  17. Survivin Expression as a Predictive Marker for Local Control in Patients With High-Risk T1 Bladder Cancer Treated With Transurethral Resection and Radiochemotherapy

    International Nuclear Information System (INIS)

    Weiss, Christian; Roemer, Felix von; Capalbo, Gianni; Ott, Oliver J.; Wittlinger, Michael; Krause, Steffen F.; Sauer, Rolf; Roedel, Claus; Roedel, Franz

    2009-01-01

    Purpose: The objectives of this study were to investigate the expression of survivin in tumor samples from patients with high-risk T1 bladder cancer and to correlate its expression with clinicopathologic features as well as clinical outcomes after initial transurethral resection (TURBT) followed by radiotherapy (RT) or radiochemotherapy (RCT). Methods and Materials: Survivin protein expression was evaluated by immunohistochemistry on tumor specimen (n = 48) from the initial TURBT, and was correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure, tumor progression, and death from urothelial cancer after primary bladder sparring treatment with RT/RCT. Results: Survivin was not expressed in normal bladder urothelium but was overexpressed in 67% of T1 tumors. No association between survivin expression and clinicopathologic factors (age, gender, grading, multifocality, associated carcinoma in situ) could be shown. With a median follow-up of 27 months (range, 3-140 months), elevated survivin expression was significantly associated with an increased probability of local failure after TURBT and RCT/RT (p = 0.003). There was also a clear trend toward a higher risk of tumor progression (p = 0.07) and lower disease-specific survival (p = 0.10). Conclusions: High survivin expression is a marker of tumor aggressiveness and may help to identify a subgroup of patients with T1 bladder cancer at a high risk for recurrence when treated with primary organ-sparing approaches such as TURBT and RCT.

  18. Prognostic significance of several histological features in intermediate and high-risk endometrial cancer patients treated with curative intent using surgery and adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Narayan, K.; Bernshaw, D.; Quinn, M.; Allen, D.; Rejeki, V.; Herschtal, A.; Jobling, T.

    2009-01-01

    Full text: The purpose of the present study was to explore the prognostic significance of several histological features with respect to lymph node metastasis, failure-free survival (FeS), and overall survival (Os) in intermediate and high-risk endometrial cancer patients treated with curative intent. One hundred and eighty patients with endometrial cancer were treated with hysterectomy with or without lymphadenectomy and received external beam radiotherapy (EBRT). The mean follow-up period was 4.25 years (range 0.44-10.45 years). In multifactor analysis, fractional myometrial invasion (MI) (P = 0.047), histology (P < 0.001) and lymph-vascular space invasion (LVSI) (P = 0.025) were significant predictors for FFS when nodal status was not included. When lymph node status was known, histology (P - 0.007) and LVSI (P = 0.014) remained significant factors for FFS. For OS, histology (P < 0.001) and fractional MI (P = 0.004) were the significant factors. Lymph node status could be predicted by tumour grading (P = 0.016) and absolute MI (P 0.002). Histology type and the presence of LVSI were the most important prognostic factors in high-risk endometrial cancer patients treated by surgery and postoperative radiotherapy. Absolute MI and tumour grading were useful predictors of nodal spread.

  19. [Comparison of screening performance between primary high-risk HPV screening and high-risk HPV screening plus liquid-based cytology cotesting in diagnosis of cervical precancerous or cancerous lesions].

    Science.gov (United States)

    Zhao, X L; Remila, Rezhake; Hu, S Y; Zhang, L; Xu, X Q; Chen, F; Pan, Q J; Zhang, X; Zhao, F H

    2018-05-06

    Objective: To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+). Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups. Results: Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ(2)=19.00, PHPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z= 6.16, PHPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ(2)=132.00, PHPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting. Conclusion: Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

  20. Chemoradiation With Paclitaxel and Carboplatin in High-Risk Cervical Cancer Patients After Radical Hysterectomy: A Korean Gynecologic Oncology Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Taek Sang [Department of Obstetrics and Gynecology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Soon Beom, E-mail: tslee70@gmail.com [Department of Obstetrics and Gynecology, Konkuk University Medical Center, Seoul (Korea, Republic of); Kim, Young Tak [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Park, Byung Joo [Department of Preventive Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Man [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jong Min [Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Young Tae [Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Jae Hoon [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung Tai [Department of Obstetrics and Gynecology, Hanyang University Medical Center, Seoul (Korea, Republic of)

    2013-06-01

    Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Methods and Materials: Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m{sup 2}, carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. Results: This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Conclusions: Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.

  1. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b and c

    International Nuclear Information System (INIS)

    Kyndi, M.; Alsner, J.; Nielsen, H.M.; Overgaard, J.; Soerensen, F.B.; Knudsen, H.; Overgaard, M.

    2008-01-01

    Purpose. To examine p53 and BCL2 expression in high-risk breast cancer patients randomized to postmastectomy radiotherapy (PMRT). Patients and methods. The present analysis included 1 000 of 3 083 high-risk breast cancer patients randomly assigned to PMRT in the DBCG82 b and c studies. Tissue microarray sections were stained with immunohistochemistry for p53 and BCL2. Median potential follow-up was 17 years. Clinical endpoints were locoregional recurrence (LRR), distant metastases (DM), overall mortality, and overall survival (OS). Statistical analyses included Kappa statistics, χ2 or exact tests, Kaplan-Meier probability plots, Log-rank test, and Cox univariate and multivariate regression analyses. Results. p53 accumulation was not significantly associated with increased overall mortality, DM or LRR probability in univariate or multivariate Cox regression analyses. Kaplan-Meier probability plots showed reduced OS and improved DM and LRR probabilities after PMRT within subgroups of both p53 negative and p53 positive patients. Negative BCL2 expression was significantly associated with increased overall mortality, DM and LRR probability in multivariate Cox regression analyses. Kaplan-Meier probability plots showed a significantly improved overall survival after PMRT for the BCL2 positive subgroup, whereas practically no survival improvement was seen after PMRT for the BCL2 negative subgroup. In multivariate analysis of OS, however, no significant interaction was found between BCL2 and randomization status. Significant reductions in LRR probability after PMRT were recorded within both the BCL2 positive and BCL2 negative subgroups. Conclusion. p53 was not associated with survival after radiotherapy in high-risk breast cancer, but BCL2 might be

  2. Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

    Directory of Open Access Journals (Sweden)

    Zhen-Yu He

    Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

  3. Role of hormonal therapy in the management of intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation

    International Nuclear Information System (INIS)

    Lee, Lucille N.; Stock, Richard G.; Stone, Nelson N.

    2002-01-01

    Purpose: To study the impact of hormonal therapy (HTx) on intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation. Methods and Materials: Patients with Stage T1b-T3bN0 prostate cancer, and Gleason score ≥7 or prostate-specific antigen (PSA) level >10 ng/mL were treated with seed implantation with or without HTx. Their disease was defined as intermediate risk (PSA 10-20, Gleason score 7, or Stage T2b) or high risk (two or more intermediate criteria, or PSA >20 ng/mL, Gleason score 8-10, or Stage T2c-T3). The median follow-up for 201 eligible patients was 42 months (range 18-110). Biochemical failure was defined as a rising PSA >1.0 ng/mL. Pretreatment disease characteristics, implant dose, and HTx were evaluated using univariate and multivariate analyses. Results: HTx significantly improved 5-year actuarial freedom from biochemical failure rate, 79% vs. 54% without HTx. In addition, high-dose, PSA ≤15 ng/mL, intermediate risk, and Stage T2a or lower significantly improved outcome in the univariate analyses. HTx was the most significant predictor of 5-year actuarial freedom from biochemical failure (p <0.0001) in a multivariate analysis. The best outcome was in the intermediate-risk patients treated with a high implant dose and HTx, resulting in a 4-year actuarial freedom from biochemical failure rate of 94%. Conclusion: In this retrospective review, HTx improved outcome in intermediate- to high-risk prostate cancer patients treated with brachytherapy. HTx was the most important prognostic factor in the univariate and multivariate analyses

  4. Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Nanda, Akash; Chen, M.-H.; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2010-01-01

    Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score ≥8, or clinical category ≥T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

  5. Hematological dosimetry

    International Nuclear Information System (INIS)

    Fluery-Herard, A.

    1991-01-01

    The principles of hematological dosimetry after acute or protracted whole-body irradiation are reviewed. In both cases, over-exposure is never homogeneous and the clinical consequences, viz medullary aplasia, are directly associated with the mean absorbed dose and the seriousness and location of the overexposure. The main hematological data required to assess the seriousness of exposure are the following: repeated blood analysis, blood precursor cultures, as indicators of whole-body exposure; bone marrow puncture, medullary precursor cultures and medullary scintigraphy as indicators of the importance of a local over-exposure and capacity for spontaneous repair. These paraclinical investigations, which are essential for diagnosis and dosimetry, are also used for surveillance and for the main therapeutic issues [fr

  6. Phase 1b Food Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer.

    Science.gov (United States)

    2018-03-05

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage 0 Hypopharyngeal Cancer; Stage 0 Laryngeal Cancer; Stage 0 Lip and Oral Cavity Cancer; Stage 0 Nasopharyngeal Cancer; Stage 0 Oropharyngeal Cancer; Stage 0 Paranasal Sinus and Nasal Cavity Cancer; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Nasal Cavity and Paranasal Sinus Cancer; Stage IVA

  7. Whole-Pelvis Radiotherapy in Combination With Interstitial Brachytherapy: Does Coverage of the Pelvic Lymph Nodes Improve Treatment Outcome in High-Risk Prostate Cancer?

    International Nuclear Information System (INIS)

    Bittner, Nathan; Merrick, Gregory S.; Wallner, Kent E.; Butler, Wayne M.; Galbreath, Robert; Adamovich, Edward

    2010-01-01

    Purpose: To compare biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) rates among high-risk prostate cancer patients treated with brachytherapy and supplemental external beam radiation (EBRT) using either a mini-pelvis (MP) or a whole-pelvis (WP) field. Methods and Materials: From May 1995 to October 2005, 186 high-risk prostate cancer patients were treated with brachytherapy and EBRT with or without androgen-deprivation therapy (ADT). High-risk prostate cancer was defined as a Gleason score of ≥8 and/or a prostate-specific antigen (PSA) concentration of ≥20 ng/ml. Results: With a median follow-up of 6.7 years, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 91.7% vs. 84.4% (p = 0.126), 95.5% vs. 92.6% (p = 0.515), and 79.5% vs. 67.1% (p = 0.721), respectively. Among those patients who received ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 93.6% vs. 90.1% (p = 0.413), 94.2% vs. 96.0% (p = 0.927), and 73.7% vs. 70.2% (p = 0.030), respectively. Among those patients who did not receive ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 82.4% vs. 75.0% (p = 0.639), 100% vs. 88% (p = 0.198), and 87.5% vs. 58.8% (p = 0.030), respectively. Based on multivariate analysis, none of the evaluated parameters predicted for CSS, while bPFS was best predicted by ADT and percent positive biopsy results. OS was best predicted by age and percent positive biopsy results. Conclusions: For high-risk prostate cancer patients receiving brachytherapy, there is a nonsignificant trend toward improved bPFS, CSS, and OS rates when brachytherapy is given with WPRT. This trend is most apparent among ADT-naive patients, for whom a significant improvement in OS was observed.

  8. High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer in Patients at Moderate or High Risk of Biochemical Recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Hoskin, Peter [Cancer Centre, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom); Rojas, Ana, E-mail: arc03@btconnect.com [Cancer Centre, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom); Lowe, Gerry; Bryant, Linda; Ostler, Peter; Hughes, Rob; Milner, Jessica; Cladd, Helen [Cancer Centre, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom)

    2012-03-15

    Purpose: To evaluate genitourinary (GU) and gastrointestinal (GI) morbidity and biochemical control of disease in patients with localized prostate adenocarcinoma treated with escalating doses per fraction of high-dose rate brachytherapy alone. Methods and Materials: A total of 197 patients were treated with 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in three fractions, or 26 Gy in two fractions. Median follow-up times were 60, 54, 36, and 6 months, respectively. Results: Incidence of early Grade {>=} 3 GU morbidity was 3% to 7%, and Grade 4 was 0% to 4%. During the first 12 weeks, the highest mean International Prostate Symptom Score (IPSS) value was 14, and between 6 months and 5 years it was 8. Grade 3 or 4 early GI morbidity was not observed. The 3-year actuarial rate of Grade 3 GU was 3% to 16%, and was 3% to 7% for strictures requiring surgery (4-year rate). An incidence of 1% Grade 3 GI events was seen at 3 years. Late Grade 4 GU or GI events were not observed. At 3 years, 99% of patients with intermediate-risk and 91% with high-risk disease were free of biochemical relapse (log-rank p = 0.02). Conclusions: There was no significant difference in urinary and rectal morbidity between schedules. Biochemical control of disease in patients with intermediate and high risk of relapse was good.

  9. Prevalence of High risk Human Papillomavirus in cervical dysplasia and cancer samples from twin cities in Pakistan

    Directory of Open Access Journals (Sweden)

    Sana Gul

    2015-05-01

    Conclusion: Our results show a strong association between HPV infection and cervical cancer among women in twin cities of Pakistan. One way to minimize the disease burden in relation to HPV infection in Pakistani population is the use of prophylactic vaccines and routine screening. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer.

  10. Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection.

    Science.gov (United States)

    Ferrer-Batallé, Montserrat; Llop, Esther; Ramírez, Manel; Aleixandre, Rosa Núria; Saez, Marc; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2017-04-17

    Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors. For that, new diagnostic methods are being developed, such as PCA-3, PSA isoforms that have resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms. In the present study, we have compared the PHI with our recently developed PSA glycoform assay, based on the determination of the α2,3-sialic acid percentage of serum PSA (% α2,3-SA), in a cohort of 79 patients, which include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH) patients. The % α2,3-SA could distinguish high-risk PCa patients from the rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs. 0.840), although the PHI correlated better with the Gleason score than the % α2,3-SA. The combination of both markers increased the AUC up to 0.985 resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk PCa from the other low and intermediate-risk PCa and BPH patients. These results suggest that both serum markers complement each other and offer an improved diagnostic tool to identify high-risk PCa, which is an important requirement for guiding treatment decisions.

  11. Understanding strength exercise intentions and behavior in hematologic cancer survivors: an analysis of the intention-behavior gap.

    Science.gov (United States)

    Vallerand, James R; Rhodes, Ryan E; Walker, Gordon J; Courneya, Kerry S

    2016-12-01

    Strength exercise improves many health outcomes in cancer survivors but the prevalence and correlates of strength exercise have not been well-described. Moreover, no study has examined the critical intention-behavior gap for exercise in cancer survivors. The aims of this study are to quantify the intention-behavior gap for strength exercise in hematologic cancer survivors (HCS) and examine correlates of both intention formation and translation using the multi-process action control framework (M-PAC). A random sample of 2100 HCS in Alberta, Canada, were mailed a survey assessing strength exercise behavior, the M-PAC, and demographic/medical variables. Separate logistic regressions were used to analyze the relationships between the correlates and intention formation and translation. Surveys were completed by 606 HCS with 58 % (n = 353) intending to do strength exercise. HCS who were not retired (OR = 1.56, p = 0.001), were highly educated (OR = 1.32, p = 0.001), and had a favorable attitude (OR = 1.56, p exercise intention. Of those with an exercise intention, 51 % (n = 181) reported regular strength exercise. HCS with a detailed plan (OR = 1.86, p attitude (OR = 1.68, p = 0.001), sense of obligation (OR = 1.38, p = 0.010), and self-regulated their affinity for competing activities (OR = 1.35, p = 0.012), were more likely to translate their intention into behavior. Just over half of HCS intended to do strength exercise and only half of intenders translated that intention into behavior. Interventions targeting both intention formation and translation may provide the best approach for increasing strength exercise in HCS.

  12. FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy

    International Nuclear Information System (INIS)

    Ghebeh, Hazem; Barhoush, Eman; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Dermime, Said

    2008-01-01

    Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T regs ). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T regs as a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated in vitro and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease. Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease. A co-existence of B7-H1 + T lymphocytes and FOXP3 + T regs was evidenced by the highly significant correlation of these molecules (P < .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3 + T regs , B7-H1 + and PD-1 + TIL synergistically correlated with high histological grade (III) (P < .001), estrogen receptor negative status (P = .017), and the presence of severe lymphocytic infiltration (P = .022). Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T regs and B7-H1/PD-1 molecules

  13. Postoperative Chemoradiation Therapy in High-Risk Cervical Cancer: Re-evaluating the Findings of Gynecologic Oncology Group Study 109 in a Large, Population-Based Cohort

    Energy Technology Data Exchange (ETDEWEB)

    Trifiletti, Daniel M. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Swisher-McClure, Samuel [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Hegarty, Sarah E. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Grover, Surbhi, E-mail: Surbhi.grover@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2015-12-01

    Purpose: To review the National Cancer Database (NCDB) to evaluate postoperative high-risk cervical cancer patients for factors associated with a benefit from chemoradiation therapy (CRT) over external beam radiation therapy alone (EBRT). Methods and Materials: The National Cancer Database was queried for women with cervical cancer treated with hysterectomy and adjuvant EBRT from 2002 to 2012. Only patients with pathologic lymph node involvement (LN+), positive surgical margins, and/or parametrial invasion were included in our analysis (on the basis of Peter's criteria). Univariable and multivariable analyses (MVA) were performed, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate for factors associated with of CRT utilization and overall survival (OS). Results: A total of 3053 patients met inclusion criteria, and 2479 received adjuvant CRT (81%), whereas 574 (19%) received EBRT alone. Factors associated with increased CRT utilization on MVA included age <69 years, year of diagnosis ≥2008, non-adenocarcinoma histology, and LN+. Use of CRT improved OS among the entire cohort on MVA (HR 0.76, CI 0.601-0.962; P=.022). On MVA, CRT improved OS in patients with LN+ as their sole Peter's criteria (HR 0.58, CI 0.413-0.814; P=.002). Chemoradiation therapy did not improve OS in patients with only positive margins (P=.73), only parametrial invasion (P=.95), or any combination of these 2 factors without LN+ (P=.63). Conclusions: The use of adjuvant CRT after hysterectomy improves OS in patients with high-risk cervical cancer compared with EBRT alone, but this benefit seems to be restricted to patients with LN+. The benefits of adjuvant CRT over EBRT alone in patients with parametrial invasion and/or positive margins (without nodal involvement) are unknown.

  14. Influence of Androgen Deprivation Therapy on All-Cause Mortality in Men With High-Risk Prostate Cancer and a History of Congestive Heart Failure or Myocardial Infarction

    International Nuclear Information System (INIS)

    Nguyen, Paul L.; Chen, Ming-Hui; Beckman, Joshua A.; Beard, Clair J.; Martin, Neil E.; Choueiri, Toni K.; Hu, Jim C.; Hoffman, Karen E.; Dosoretz, Daniel E.; Moran, Brian J.; Salenius, Sharon A.; Braccioforte, Michelle H.; Kantoff, Philip W.; D’Amico, Anthony V.; Ennis, Ronald D.

    2012-01-01

    Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c–T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32–2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17–5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13–2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96–2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.

  15. Influence of Androgen Deprivation Therapy on All-Cause Mortality in Men With High-Risk Prostate Cancer and a History of Congestive Heart Failure or Myocardial Infarction

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu [Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Chen, Ming-Hui [Department of Statistics, University of Connecticut, Storrs, CT (United States); Beckman, Joshua A. [Department of Cardiology, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Beard, Clair J.; Martin, Neil E. [Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Choueiri, Toni K. [Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA (United States); Hu, Jim C. [Division of Urologic Surgery, Brigham and Women' s/Faulkner Hospital, Harvard Medical School, Boston, MA (United States); Hoffman, Karen E. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Dosoretz, Daniel E. [21st Century Oncology, Fort Myers, FL (United States); Moran, Brian J. [Chicago Prostate Center, Westmont, IL (United States); Salenius, Sharon A. [21st Century Oncology, Fort Myers, FL (United States); Braccioforte, Michelle H. [Chicago Prostate Center, Westmont, IL (United States); Kantoff, Philip W. [Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA (United States); D' Amico, Anthony V. [Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Ennis, Ronald D. [Department of Radiation Oncology, St. Luke' s-Roosevelt and Beth Israel Hospitals, Continuum Cancer Centers of New York, Albert Einstein College of Medicine, New York, NY (Israel)

    2012-03-15

    Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c-T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32-2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17-5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13-2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96-2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.

  16. Elucidating the underlying causes of oral cancer through spatial clustering in high-risk areas of Taiwan with a distinct gender ratio of incidence

    Directory of Open Access Journals (Sweden)

    Chi-Ting Chiang

    2010-05-01

    Full Text Available This study aimed to elucidate whether or not high-risk clusters of oral cancer (OC incidence spatially correlate with the prevalence rates of betel quid chewing (BQC and cigarette smoking (CS in Taiwan. The spatial autocorrelation and potential clusters of OC incidence among the 307 townships and heavy metal content of soil throughout Taiwan were identified using the Anselin’s local Moran test. Additionally, the spatial correlations among the incidence of OC, the prevalence of BQC and CS and heavy metal content of soil were determined based on a comparison of spatial clusters. High-risk OC (Moran’s I = 0.638, P <0.001 clusters were located in central and eastern Taiwan, while “hot spots” of BQC and CS prevalence were located mainly in eastern Taiwan. The distributions of BQC and CS lifestyle factors (P <0.001 were spatially autocorrelated. The “hot spots” of OC largely coincided with the “hot spots” of BQC, except for the Changhua and Yunlin counties, which are located in central Taiwan. However, high soil contents of nickel and chromium (P <0.001 in central Taiwan also coincided with the high-risk areas of OC incidence. In particular, Changhua county has incurred several decades of serious heavy-metal pollution, with inhabitants living in polluted areas having high-risk exposure to these metals. Results of this study suggest that, in addition to BQC and CS, anthropogenic pollution may profoundly impact the complexity of OC aetiology in central Taiwan.

  17. High-Risk Premenopausal Luminal A Breast Cancer Patients Derive no Benefit from Adjuvant Cyclophosphamide-based Chemotherapy

    DEFF Research Database (Denmark)

    Nielsen, Torsten O; Jensen, Maj-Brit; Burugu, Samantha

    2017-01-01

    Purpose: Luminal A breast cancers have better prognosis than other molecular subtypes. Luminal A cancers may also be insensitive to adjuvant chemotherapy, although there is little high-level evidence to confirm this concept. The primary hypothesis in this formal prospective-retrospective analysis...... was to assess interaction between subtype (Luminal A vs. other) and treatment (chemotherapy vs. not) for the primary endpoint (10-year invasive disease-free survival) of a breast cancer trial randomizing women to adjuvant chemotherapy, analyzed in multivariate Cox proportional hazards models using the Wald...... interval (CI), 0.53-2.14; P = 0.86], whereas patients with non-luminal A subtypes did (HR, 0.50; 95% CI, 0.38-0.66; P breast cancers did not benefit from adjuvant...

  18. Prophylactic bilateral salpingectomy as a prevention strategy in women at high risk of ovarian cancer: a mini-review

    Directory of Open Access Journals (Sweden)

    Tess eSchenberg

    2014-02-01

    Full Text Available Risk-reducing bilateral salpingo-oophorectomy is a proven strategy to reduce the risk of serous ovarian cancer associated with germline BRCA mutations. It is most effective when performed before natural menopause but it will render a woman prematurely menopausal. The tubal hypothesis of serous ovarian cancer brings with it the possibility of the alternative surgical approach in younger women comprising of risk-reducing bilateral salpingectomy while conserving their ovaries until nearer the age of natural menopause when a delayed bilateral oophorectomy can be performed. This article will review the evidence behind the tubal hypothesis of serous ovarian cancer and explore the opportunities for translating this into clinical cancer prevention practice.

  19. SUVmax of 18FDG PET/CT as a predictor of high-risk endometrial cancer patients

    DEFF Research Database (Denmark)

    Antonsen, Sofie Leisby; Loft, Annika; Fisker, Rune Vincents

    2013-01-01

    OBJECTIVE: To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS: A total of 268 women with endometrial cancer or atypical...... endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS: SUVmax was significantly higher in patients with high FIGO stages (p...

  20. Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

    Energy Technology Data Exchange (ETDEWEB)

    Zapatero, Almudena, E-mail: azapatero.hlpr@salud.madrid.org [Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid (Spain); Garcia-Vicente, Feliciano [Department of Medical Physics, Hospital Universitario de la Princesa, Madrid (Spain); Martin de Vidales, Carmen; Cruz Conde, Alfonso; Ibanez, Yamile [Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid (Spain); Fernandez, Inmaculada; Rabadan, Mariano [Department of Urology, Hospital Universitario de la Princesa, Madrid (Spain)

    2011-12-01

    Purpose: To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. Methods and Materials: A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). Results: The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score >7 (p = 0.001), pretreatment prostate-specific antigen (PSA) level >20 ng/mL (p = 0.037), higher radiation dose (p = 0.005), and the use of adjuvant LTAD vs. STAD (p = 0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose >78 Gy was 97%. Conclusions: For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum >7 and pretreatment PSA level >20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with

  1. Lack of benefit for the addition of androgen deprivation therapy to dose-escalated radiotherapy in the treatment of intermediate- and high-risk prostate cancer.

    LENUS (Irish Health Repository)

    Krauss, Daniel

    2012-02-01

    PURPOSE: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). METHODS AND MATERIALS: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng\\/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA >\\/=20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. RESULTS: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason >\\/=8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. CONCLUSION: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.

  2. HER2,TOP2A, and TIMP-1 and responsiveness to adjuvant anthracycline-containing chemotherapy in high-risk breast cancer patients

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Jensen, Maj-Britt; Nielsen, Kirsten V.

    2010-01-01

    analyzed individually. PATIENTS AND METHODS The Danish Breast Cancer Cooperative Group (DBCG) 89D trial randomly assigned 980 high-risk Danish breast cancer patients to CMF or CEF. Archival tumor tissue was analyzed TIMP-1, and HER2-negative and TIMP-1 immunoreactive tumors were classified as HT...... nonresponsive and otherwise HT responsive. Similarly, the 2T panel was constructed by combining TOP2A and TIMP-1; tumors with normal TOP2A status and TIMP-1 immunoreactivity were classified as 2T-nonresponsive and otherwise 2T-responsive. Results In total, 623 tumors were available for analysis, of which 154......(interaction) containing chemotherapy than HER2, TIMP-1, or TOP2A individually, and compared with these, 2T classifies a larger proportion of patients as sensitive to anthracyclines....

  3. Comparison of clinical and analytical performance of the Abbott Realtime High Risk HPV test to the performance of hybrid capture 2 in population-based cervical cancer screening.

    Science.gov (United States)

    Poljak, Mario; Ostrbenk, Anja; Seme, Katja; Ucakar, Veronika; Hillemanns, Peter; Bokal, Eda Vrtacnik; Jancar, Nina; Klavs, Irena

    2011-05-01

    The clinical performance of the Abbott RealTime High Risk HPV (human papillomavirus) test (RealTime) and that of the Hybrid Capture 2 HPV DNA test (hc2) were prospectively compared in the population-based cervical cancer screening setting. In women >30 years old (n = 3,129), the clinical sensitivity of RealTime for detection of cervical intraepithelial neoplasia of grade 2 (CIN2) or worse (38 cases) and its clinical specificity for lesions of less than CIN2 (3,091 controls) were 100% and 93.3%, respectively, and those of hc2 were 97.4% and 91.8%, respectively. A noninferiority score test showed that the clinical specificity (P laboratories. RealTime can be considered to be a reliable and robust HPV assay clinically comparable to hc2 for the detection of CIN2+ lesions in a population-based cervical cancer screening setting.

  4. HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors

    International Nuclear Information System (INIS)

    Jong, Monique C. de; Pramana, Jimmy; Knegjens, Joost L.; Balm, Alfons J.M.; Brekel, Michiel W.M. van den; Hauptmann, Michael; Begg, Adrian C.; Rasch, Coen R.N.

    2010-01-01

    Purpose: The purpose of this study was to combine gene expression profiles and clinical factors to provide a better prediction model of local control after chemoradiotherapy for advanced head and neck cancer. Material and methods: Gene expression data were available for a series of 92 advanced stage head and neck cancer patients treated with primary chemoradiotherapy. The effect of the Chung high-risk and Slebos HPV expression profiles on local control was analyzed in a model with age at diagnosis, gender, tumor site, tumor volume, T-stage and N-stage and HPV profile status. Results: Among 75 patients included in the study, the only factors significantly predicting local control were tumor site (oral cavity vs. Pharynx, hazard ratio 4.2 [95% CI 1.4-12.5]), Chung gene expression status (high vs. Low risk profile, hazard ratio 4.4 [95% CI 1.5-13.3]) and HPV profile (negative vs. Positive profile, hazard ratio 6.2 [95% CI 1.7-22.5]). Conclusions: Chung high-risk expression profile and a negative HPV expression profile were significantly associated with increased risk of local recurrence after chemoradiotherapy in advanced pharynx and oral cavity tumors, independent of clinical factors.

  5. Large Prospective Study of Ovarian Cancer Screening in High-risk Women: CA125 Cut-point Defined by Menopausal Status

    Science.gov (United States)

    Skates, Steven J.; Mai, Phuong; Horick, Nora K.; Piedmonte, Marion; Drescher, Charles W.; Isaacs, Claudine; Armstrong, Deborah K.; Buys, Saundra S.; Rodriguez, Gustavo C.; Horowitz, Ira R.; Berchuck, Andrew; Daly, Mary B.; Domchek, Susan; Cohn, David E.; Van Le, Linda; Schorge, John O.; Newland, William; Davidson, Susan A.; Barnes, Mack; Brewster, Wendy; Azodi, Masoud; Nerenstone, Stacy; Kauff, Noah D.; Fabian, Carol J.; Sluss, Patrick M.; Nayfield, Susan G.; Kasten, Carol H.; Finkelstein, Dianne M.; Greene, Mark H.; Lu, Karen

    2011-01-01

    Background Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, while the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Methods Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the NCI-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this pre-planned analysis. Due to the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points based on the 98th percentile. Results The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. Conclusions To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (~ 50 for premenopausal women, 40 for premenopausal on OC, 35 for postmenopausal women). PMID:21893500

  6. Androgen Deprivation Therapy Does Not Impact Cause-Specific or Overall Survival in High-Risk Prostate Cancer Managed With Brachytherapy and Supplemental External Beam

    International Nuclear Information System (INIS)

    Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A.; Adamovich, Edward; Lief, Jonathan

    2007-01-01

    Purpose: To determine cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in high-risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and July 2002, 204 patients with high-risk prostate cancer (Gleason score ≥8 or prostate-specific antigen [PSA] >20 ng/mL or clinical stage ≥T2c) underwent brachytherapy. Median follow-up was 7.0 years. The bPFS was defined by a PSA ≤0.40 ng/mL after nadir. Multiple clinical, treatment, and dosimetric parameters were evaluated for the impact on survival. Results: The 10-year CSS, bPFS, and OS were 88.9%, 86.6%, and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naive, ADT ≤6 months, and ADT >6 month cohorts (79.7% vs. 95.% vs. 89.9%, p = 0.032). Androgen deprivation therapy (ADT) did not impact CSS or OS. For bPFS patients, the median posttreatment PSA was <0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS, whereas percent positive biopsies and duration of ADT best predicted for bPFS. The OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died, with 26 of the deaths from cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: The ADT improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact OS

  7. Progress of dendritic cell-based cancer vaccines for patients with hematological malignancies.

    Science.gov (United States)

    Ni, Ming; Hoffmann, Jean-Marc; Schmitt, Michael; Schmitt, Anita

    2016-09-01

    Dendritic cells (DCs) are the most professional antigen-presenting cells eliciting cellular and humoral immune responses against cancer cells by expressing these antigens on MHC class I/II complexes to T cells. Therefore, they have been employed in many clinical trials as cancer vaccines for patients with cancer. This review focuses on the use of DCs in leukemia patients expressing leukemia-associated antigens (LAAs). The contribution of both stimulating vs. tolerogenic DCs as well as of other factors to the milieu of anti-leukemia immune responses are discussed. Several DC vaccination strategies like leukemia lysate, proteins and peptides have been developed. Next generation DC vaccines comprise transduction of DCs with retroviral vectors encoding for LAAs, cytokines and costimulatory molecules as well as transfection of DCs with naked RNA encoding for LAAs. Published as well as ongoing clinical trials are reported and critically reviewed. Future results will demonstrate whether next-generation DCs are really superior to conventional pulsing with peptide, protein or tumor lysate. However, currently available methods based on nucleic acid transfection/transduction are tempting in terms of material production costs and time for clinical application according to good manufacturing practice (GMP).

  8. Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, Pierre, E-mail: pierre.blanchard@gustaveroussy.fr [Radiation Oncology, Gustave Roussy Cancer Center, Villejuif (France); University of Paris-Sud, Cancer Campus, Villejuif (France); Faivre, Laura [Biostatistics, Gustave Roussy Cancer Center, Villejuif (France); Lesaunier, François [Radiation Oncology, Centre Francois Baclesse, Caen (France); Salem, Naji [Radiation Oncology, Institut Paoli Calmette, Marseille (France); Mesgouez-Nebout, Nathalie [Radiation Oncology, Institut de Cancérologie de l' Ouest, Angers (France); Deniau-Alexandre, Elisabeth [Centre Hospitalier La Roche sur Yon, La Roche sur Yon (France); Rolland, Frédéric [Medical Oncology, Institut de Cancérologie de l' Ouest, Nantes (France); Ferrero, Jean-Marc [Medical Oncology, Centre Antoine Lacassagne, Nice (France); Houédé, Nadine [Medical Oncology, Institut Bergonié, Bordeaux (France); Mourey, Loïc [Institut Claudius Regaud, Toulouse (France); Théodore, Christine [Hospital Foch, Suresnes (France); Krakowski, Ivan [Centre Alexis Vautrin, Vandoeuvre-lès-Nancy (France); Berdah, Jean-François [Clinique Sainte Marguerite, Hyeres (France); Baciuchka, Marjorie [Centre Hospitalier de la Timone, Marseille (France); Laguerre, Brigitte [Centre Eugène Marquis, Rennes (France); Davin, Jean-Louis [Clinique Sainte Catherine, Avignon (France); Habibian, Muriel [R& D UNICANCER, Paris (France); UNICANCER, Paris (France); Culine, Stéphane [Department of Medical Oncology, Hopital Saint-Louis, APHP, Paris (France); and others

    2016-01-01

    Purpose: The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Methods and Materials: Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). Results: A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. Conclusions: This unplanned analysis of

  9. Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

    International Nuclear Information System (INIS)

    Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.; Reddy, Chandana A.; Thousand, Richard A.; Vassil, Andrew; Stovsky, Mark; Berglund, Ryan K.; Klein, Eric A.; Stephans, Kevin L.

    2016-01-01

    Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

  10. SU-D-207B-05: Robust Intra-Tumor Partitioning to Identify High-Risk Subregions for Prognosis in Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wu, J; Gensheimer, M; Dong, X; Rubin, D; Napel, S; Diehn, M; Loo, B; Li, R [Stanford University, Palo Alto, CA (United States)

    2016-06-15

    Purpose: To develop an intra-tumor partitioning framework for identifying high-risk subregions from 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and CT imaging, and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods: In this institutional review board-approved retrospective study, we analyzed the pre-treatment FDG-PET and CT scans of 44 lung cancer patients treated with radiotherapy. A novel, intra-tumor partitioning method was developed based on a two-stage clustering process: first at patient-level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor, which were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI = 0.66–0.67. When restricting the analysis to patients with stage III disease (n = 32), the same subregion achieved an even higher CI = 0.75 (HR = 3.93, logrank p = 0.002) for predicting OS, and a CI = 0.76 (HR = 4.84, logrank p = 0.002) for predicting OFP. In comparison, conventional imaging markers including tumor volume, SUVmax and MTV50 were not predictive of OS or OFP, with CI mostly below 0.60 (p < 0.001). Conclusion: We propose a robust intra-tumor partitioning method to identify clinically relevant, high-risk subregions in lung cancer. We envision that this approach will be applicable to identifying useful

  11. Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.; Reddy, Chandana A.; Thousand, Richard A.; Vassil, Andrew [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stovsky, Mark; Berglund, Ryan K.; Klein, Eric A. [Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stephans, Kevin L., E-mail: stephak@ccf.org [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States)

    2016-07-01

    Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

  12. Fertility considerations in young women with hematological malignancies

    DEFF Research Database (Denmark)

    Jadoul, Pascale; Kim, S Samuel; Andersen, Claus Yding

    2012-01-01

    The need for practice guidelines for fertility preservation in young women with hematological malignancies has been increased. To develop recommendations, publications relevant to fertility preservation and hematological cancers were identified through a PubMed database search and reviewed...

  13. Comparison of global gene expression of gastric cardia and noncardia cancers from a high-risk population in china.

    Directory of Open Access Journals (Sweden)

    Gangshi Wang

    Full Text Available To profile RNA expression in gastric cancer by anatomic subsites as an initial step in identifying molecular subtypes and providing targets for early detection and therapy.We performed transcriptome analysis using the Affymetrix GeneChip U133A in gastric cardia adenocarcinomas (n = 62 and gastric noncardia adenocarcinomas (n = 72 and their matched normal tissues from patients in Shanxi Province, and validated selected dysregulated genes with additional RNA studies. Expression of dysregulated genes was also related to survival of cases.Principal Component Analysis showed that samples clustered by tumor vs. normal, anatomic location, and histopathologic features. Paired t-tests of tumor/normal tissues identified 511 genes whose expression was dysregulated (P<4.7E-07 and at least two-fold difference in magnitude in cardia or noncardia gastric cancers, including nearly one-half (n = 239, 47% dysregulated in both cardia and noncardia, one-fourth dysregulated in cardia only (n = 128, 25%, and about one-fourth in noncardia only (n = 144, 28%. Additional RNA studies confirmed profiling results. Expression was associated with case survival for 20 genes in cardia and 36 genes in noncardia gastric cancers.The dysregulated genes identified here represent a comprehensive starting point for future efforts to understand etiologic heterogeneity, develop diagnostic biomarkers for early detection, and test molecularly-targeted therapies for gastric cancer.

  14. Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

    DEFF Research Database (Denmark)

    Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders

    2009-01-01

    BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovaria...

  15. Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

    Science.gov (United States)

    Donnelly, L S; Evans, D G; Wiseman, J; Fox, J; Greenhalgh, R; Affen, J; Juraskova, I; Stavrinos, P; Dawe, S; Cuzick, J; Howell, A

    2014-04-02

    Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. All eligible women between 33 and 46 years at ≥17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a 'cancer drug', and daily reminder of cancer risk. Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.

  16. CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers.

    Science.gov (United States)

    Vedeld, Hege Marie; Merok, Marianne; Jeanmougin, Marine; Danielsen, Stine A; Honne, Hilde; Presthus, Gro Kummeneje; Svindland, Aud; Sjo, Ole H; Hektoen, Merete; Eknaes, Mette; Nesbakken, Arild; Lothe, Ragnhild A; Lind, Guro E

    2017-09-01

    The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5-markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni- and multivariate analyses. Subgroup analyses were conducted according to MSI and BRAF mutation status, disease stage, and also age at time of diagnosis (CIMP positive tumors demonstrated significantly shorter TTR and worse OS compared to those with CIMP negative tumors (multivariate hazard ratio [95% CI] 1.86 [1.31-2.63] and 1.89 [1.34-2.65], respectively). In stratified analyses, CIMP tumors showed significantly worse outcome among patients with microsatellite stable (MSS, P CIMP is significantly associated with inferior outcome for colorectal cancer patients, and can stratify the poor prognostic patients with MSS BRAF mutated tumors. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  17. Awareness of preventive medication among women at high risk for breast cancer and their willingness to consider transdermal or oral tamoxifen: a focus group study

    International Nuclear Information System (INIS)

    Karavites, Lindsey C.; Allu, Subhashini; Khan, Seema A.; Kaiser, Karen

    2015-01-01

    Despite demonstrated efficacy, acceptance of selective estrogen receptor modulators (SERMs), such as tamoxifen, for breast cancer risk reduction remains low. Delivering SERMs via local transdermal therapy (LTT) could significantly reduce systemic effects and therefore may increase acceptance. We aim to assess women’s knowledge of breast cancer prevention medications and views on LTT of SERMs. Focus groups were conducted with healthy women identified through the comprehensive breast center of a large urban cancer institution. Group discussions covered risk perceptions, knowledge of and concerns about risk reducing medications. Participants reported their perceived risk for breast cancer (average, below/above average), preference for SERMs in a pill or gel form, risk factors, and prior physician recommendations regarding risk-reducing medicines. Participants’ breast cancer risk was estimated using tools based on the Gail Model. Trained personnel examined all qualitative results systematically; risk perceptions and preferred method of medication delivery were tallied quantitatively. Four focus groups (N = 32) were conducted. Most participants had at least a college degree (78.2 %) and were of European (50 %) or African ancestry (31 %). The majority (72 %) were at elevated risk for breast cancer; approximately half of these women perceived themselves to be at elevated risk. Few participants had prior knowledge of preventive medications. The women noted a number of concerns about LTT, including dosage, impact on day-to-day life, and side effects; nonetheless, over 90 % of the women stated they would prefer LTT to a pill. Awareness of preventive medications was low even in a highly educated sample of high-risk women. If given a choice in the route of administration, most women preferred a gel to a pill, anticipating fewer side effects. Future work should focus on demonstrating equivalent efficacy and reduced toxicity of topical over oral medications and on raising

  18. The long-term spatial-temporal trends and burden of esophageal cancer in one high-risk area: A population-registered study in Feicheng, China.

    Directory of Open Access Journals (Sweden)

    Xiubin Sun

    Full Text Available Feicheng County is a high-risk area for esophageal cancer in Shandong province, China. It is important to determine the long-term spatio-temporal trends in epidemiological characteristics and the burden of esophageal cancer, especially since the implementation of the national esophageal cancer screening program for early detection and treatment in 2005.The data collected in Feicheng County from 2001 to 2012 was extracted from the whole-population cancer registry system. The incidence, mortality, disability-adjusted life years (DALY and changing trends in esophageal cancer according to age and sex were calculated and described.The incidence rate of esophageal cancer in Feicheng was consistently high, and increased significantly for male, but not for female from 2001 to 2012, according to the joinpoint regression analysis. The highest and lowest yearly crude incidence rates were 160.78 and 95.97 per 100000 for males, and 81.36 and 52.17 per 100000 for females. The highest and lowest crude yearly mortality rates were 122.26 and 94.40 per 100000 for males, and 60.75 and 49.35 per 100000for females. Esophageal squamous cell carcinoma was the main pathology type and the tumor location changed significantly from 2001 to 2012. Overall, the DALY remained roughly stable and was estimated as 11.50 for males and 4.90 for females per 1000 people. The burden was mainly caused by premature death. There is an obvious spatial pattern in the distribution of incidence density and burden.Esophageal cancer remains a public health issue in Feicheng County with a high incidence, mortality and disease burden. The incidence and burden have obvious spatial heterogeneity, and further studies should be conducted to identify geographical risk factors for precise local prevention and control measures.

  19. Awareness of preventive medication among women at high risk for breast cancer and their willingness to consider transdermal or oral tamoxifen: a focus group study.

    Science.gov (United States)

    Karavites, Lindsey C; Allu, Subhashini; Khan, Seema A; Kaiser, Karen

    2015-11-09

    Despite demonstrated efficacy, acceptance of selective estrogen receptor modulators (SERMs), such as tamoxifen, for breast cancer risk reduction remains low. Delivering SERMs via local transdermal therapy (LTT) could significantly reduce systemic effects and therefore may increase acceptance. We aim to assess women's knowledge of breast cancer prevention medications and views on LTT of SERMs. Focus groups were conducted with healthy women identified through the comprehensive breast center of a large urban cancer institution. Group discussions covered risk perceptions, knowledge of and concerns about risk reducing medications. Participants reported their perceived risk for breast cancer (average, below/above average), preference for SERMs in a pill or gel form, risk factors, and prior physician recommendations regarding risk-reducing medicines. Participants' breast cancer risk was estimated using tools based on the Gail Model. Trained personnel examined all qualitative results systematically; risk perceptions and preferred method of medication delivery were tallied quantitatively. Four focus groups (N = 32) were conducted. Most participants had at least a college degree (78.2 %) and were of European (50 %) or African ancestry (31 %). The majority (72 %) were at elevated risk for breast cancer; approximately half of these women perceived themselves to be at elevated risk. Few participants had prior knowledge of preventive medications. The women noted a number of concerns about LTT, including dosage, impact on day-to-day life, and side effects; nonetheless, over 90 % of the women stated they would prefer LTT to a pill. Awareness of preventive medications was low even in a highly educated sample of high-risk women. If given a choice in the route of administration, most women preferred a gel to a pill, anticipating fewer side effects. Future work should focus on demonstrating equivalent efficacy and reduced toxicity of topical over oral medications and on raising

  20. Physicians involved in the care of patients with high risk of skin cancer should be trained regarding sun protection measures: evidence from a cross sectional study.

    Science.gov (United States)

    Thomas, M; Rioual, E; Adamski, H; Roguedas, A-M; Misery, L; Michel, M; Chastel, F; Schmutz, J-L; Aubin, F; Marguery, M-C; Meyer, N

    2011-01-01

    Knowledge, regarding sun protection, is essential to change behaviour and to reduce sun exposure of patients at risk for skin cancer. Patient education regarding appropriate or sun protection measures, is a priority to reduce skin cancer incidence. The aim of this study was to evaluate the knowledge about sun protection and the recommendations given in a population of non-dermatologists physicians involved in the care of patients at high risk of skin cancer. This study is a cross-sectional study. Physicians were e-mailed an anonymous questionnaire evaluating the knowledge about risk factors for skin cancer, sun protection and about the role of the physician in providing sun protection recommendations. Of the responders, 71.4% considered that the risk of skin cancer of their patients was increased when compared with the general population. All the responders knew that UV-radiations can contribute to induce skin cancers and 71.4% of them declared having adequate knowledge about sun protection measures. A proportion of 64.2% of them declared that they were able to give sun protection advices: using sunscreens (97.8%), wearing covering clothes (95.5%), performing regular medical skin examination (91.1%), to avoid direct sunlight exposure (77.8%), avoiding outdoor activities in the hottest midday hours (73.3%) and practising progressive exposure (44.4%). Non-dermatologist physicians reported a correct knowledge of UV-induced skin cancer risk factors. The majority of responders displayed adequate knowledge of sun protection measures and declared providing patients with sun protection recommendation on a regular basis. Several errors persisted. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

  1. Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population.

    Science.gov (United States)

    Gawron, Andrew J; Fought, Angela J; Lissowska, Jolanta; Ye, Weimin; Zhang, Xiao; Chow, Wong-Ho; Beane Freeman, Laura E; Hou, Lifang

    2011-03-01

    To examine if genetic variations in chemokine receptor and ligand genes are associated with gastric cancer risk and survival. The study included 298 cases and 417 controls from a population-based study of gastric cancer conducted in Warsaw, Poland in 1994-1996. We investigated seven single nucleotide polymorphisms in a chemokine ligand (CXCL12) and chemokine receptor (CCR2, CCR5, CX3CR1) genes and one frameshift deletion (CCR5) in blood leukocyte DNA in relation to gastric cancer risk and survival. Genotyping was conducted at the NCI Core Genotyping Facility. Odds ratios and 95% confidence intervals were computed using univariate and multivariate logistic regression models. Survival analysis was performed using Cox proportional hazards models. Gastric cancer risk was not associated with single chemokine polymorphisms. A CCR5 haplotype that contained the common alleles of IVS1+151 G>T (rs2734648), IVS2+80 C>T (rs1800024) and minor allele of IVS1+246 A>G (rs1799987) was associated with a borderline significantly increased risk (OR = 1.5, 95% CI: 1.0?2.2). For gastric cancer cases, there was a greater risk of death for carriers of the minor alleles of CCR2 Ex2+241 G>A (rs1799864) (HR = 1.5, 95% CI: 1.1-2.1) and CCR5 IVS2+80 C>T (rs1800024) (HR = 1.5, 95% CI: 1.1-2.1). Carriers of the CCR5 minor allele of IVS1+151 G>T (rs2734648) had a decreased risk of death compared to homozygote carriers of the common allele (HR = 0.8, 95% CI: 0.6-1.0). Our findings do not support an association between gastric cancer risk and single chemokine genetic variation. The observed associations between cancer risk and a CCR5 haplotype and between survival and polymorphisms in CCR2 and CCR5 need replication in future studies.

  2. The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.

    Science.gov (United States)

    Omenn, G S; Goodman, G; Thornquist, M; Grizzle, J; Rosenstock, L; Barnhart, S; Balmes, J; Cherniack, M G; Cullen, M R; Glass, A

    1994-04-01

    CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

  3. Mouth self-examination as a screening tool for oral cancer in a high-risk group of patients with Fanconi anemia.

    Science.gov (United States)

    Furquim, Camila Pinheiro; Pivovar, Allana; Cavalcanti, Laura Grein; Araújo, Renata Fuentes; Sales Bonfim, Carmem Maria; Torres-Pereira, Cassius Carvalho

    2014-10-01

    Oral cancer usually occurs at accessible sites, enabling early detection by visual inspection. Fanconi anemia (FA) is a recessive disorder associated with a high risk of developing head and neck solid tumors. The aim of this study was to assess the ability to perform mouth self-examination (MSE) in these patients. A total of 44 patients with FA, aged ≥ 18 years, were given a self-reported questionnaire to collect sociodemographic data and information about health-related behaviors and oral cancer awareness. They were asked to perform MSE, which was evaluated using criteria for mucosal visualization and retracting ability. Subsequently, an oral medicine specialist clinically examined all participants, and these findings were considered to be the gold standard. The sensitivity and specificity values of MSE were 43% and 44%, respectively. The MSE accuracy was 43%. Most patients (73%) reported that MSE was easy or very easy, although 75% showed insufficient performance. The accuracy of MSE alone is not sufficient to indicate whether MSE should be recommended as a strategy to prevent oral cancer in patients with FA. Nevertheless, the present results indicate that this inexpensive technique could be used as a tool for early detection of cancer in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Utility of supplemental screening with breast ultrasound in asymptomatic women with dense breast tissue who are not at high risk for breast cancer.

    Science.gov (United States)

    Klevos, Geetika A; Collado-Mesa, Fernando; Net, Jose M; Yepes, Monica M

    2017-01-01

    To assess the results of an initial round of supplemental screening with hand-held bilateral breast ultrasound following a negative screening mammogram in asymptomatic women with dense breast tissue who are not at high risk for breast cancer. A retrospective, Health Insurance Portability and Accountability Act compliant, Institutional Research Board approved study was performed at a single academic tertiary breast center. Informed consent was waived. A systematic review of the breast imaging center database was conducted to identify and retrieve data for all asymptomatic women, who were found to have heterogeneously dense or extremely dense breast tissue on screening bilateral mammograms performed from July 1, 2010 through June 30, 2012 and who received a mammographic final assessment American College of Radiology's (ACR) Breast Imaging Reporting and Data System (BI-RADS) category 1 or BI-RADS category 2. Hand-held screening ultrasound was performed initially by a technologist followed by a radiologist. Chi-square and t -test were used and statistical significance was considered at P ultrasound. BI-RADS category 1 or 2 was assigned to 323 women (81.9%). BI-RADS category 3 was assigned to 50 women (12.9%). A total of 26 biopsies/aspirations were recommended and performed in 26 women (6.6%). The most common finding for which biopsy was recommended was a solid mass (88.5%) with an average size of 0.9 cm (0.5-1.7 cm). Most frequent pathology result was fibroadenoma (60.8%). No carcinoma was found. Our data support the reported occurrence of a relatively high number of false positives at supplemental screening with breast ultrasound following a negative screening mammogram in asymptomatic women with dense breast tissue, who are not at a high risk of developing breast cancer, and suggests that caution is necessary in establishing wide implementation of this type of supplemental screening for all women with dense breast tissue without considering other risk factors for

  5. Cost-effectiveness analysis of cervical cancer prevention based on a rapid human papillomavirus screening test in a high-risk region of China.

    Science.gov (United States)

    Levin, Carol E; Sellors, John; Shi, Ju-Fang; Ma, Li; Qiao, You-lin; Ortendahl, Jesse; O'Shea, Meredith K H; Goldie, Sue J

    2010-09-01

    This study assessed the cost-effectiveness of a new, rapid human papillomavirus (HPV)-DNA screening test for cervical cancer prevention in the high-risk region of Shanxi, China. Using micro-costing methods, we estimated the resources needed to implement preventive strategies using cervical cytology or HPV-DNA testing, including the Hybrid Capture 2 (hc2) test (QIAGEN Corp., Gaithersburg, MD) and the rapid HPV-DNA careHPV test (QIAGEN). Data were used in a previously published model and empirically calibrated to country-specific epidemiological data. Strategies differed by initial test, targeted age, frequency of screening, number of clinic visits required (1, 2 or 3) and service delivery setting (national, county and township levels). Outcomes included lifetime risk of cancer, years of life saved (YLS), lifetime costs and incremental cost-effectiveness ratios (cost per YLS). For all screening frequencies, the most efficient strategy used 2-visit rapid HPV-DNA testing at the county level, including screening and diagnostics in the first visit, and treatment in the second visit. Screening at ages 35, 40 and 45 reduced cancer risk by 50% among women compliant with all 3 screening rounds, and was US$ 150 per YLS, compared with this same strategy applied twice per lifetime. This would be considered very cost-effective evaluated against China's per-capita gross domestic product (US$ 1,702). By enhancing the linkage between screening and treatment through a reduced number of visits, rapid HPV-DNA testing 3 times per lifetime is more effective than traditional cytology, and is likely to be cost-effective in high-risk regions of China.

  6. [Prevalence of high-risk HPV and its distribution in cervical precancerous lesions among 35-64 years old women who received cervical cancer screening in Beijing].

    Science.gov (United States)

    Shen, J; Gao, L L; Zhang, Y; Han, L L; Wang, J D

    2018-05-06

    Objective: To study the prevalence of high-risk HPV (HR HPV) in women who accepted cervical cancer screening in Beijing and its distribution in cervical precancerous lesions. Methods: From January 2014 to March 2015, all women aged 35-64 years old and received free screening in institutions of cervical cancer in Beijing were recruited. Stratified cluster random sampling method was used in selecting 31 091 women for gynecological examination and genotyping of HR-HPV. Those positive for HR-HPV (except for HPV 16/18) were examined for cervical cell. For those atypical squamous cells of uncertain significance (ASCUS) and above, who were positive for HPV 16/18 and with uncertain results for cervical cell, were transferred for colposcopy examination. For those with suspicious or abnormal results for colposcopy, were transferred for histopathology. The prevalence of HR-HPV, cervical cancer and precancerous lesions among the participants were analyzed. Results: Totally 31 091 women aged from 35-year-old to 64-year-old, with 44.3% (13 780 women) in the 35-49 age group and 55.7% (17 311 women) in the 50-64 age group. 66.1% (20 536 women) were rural women. The infection rate of HR-HPV was 7.4%(2 305 cases) among the women. High-risk infection rates of HPV except HPV 16/18 were 5.7% (1 758 cases), and multi-infection rate was 1.5% (477 cases). The highest infection rate was 7.9% (1 044 cases) among the 45-49 year-old and 50-54 year-old age groups (χ(2)=14.07, P= 0.015). The rate in rural women was significantly higher than that of the urban women (6.2%, 507 cases; 7.9%, 1 798 cases) (χ(2)=25.75, Page group.

  7. Stents in patients with esophageal cancer before chemoradiotherapy: high risk of complications and no impact on the nutritional status.

    Science.gov (United States)

    Mão-de-Ferro, S; Serrano, M; Ferreira, S; Rosa, I; Lage, P; Alexandre, D P; Freire, J; Mirones, L; Casaca, R; Bettencourt, A; Pereira, A D

    2016-03-01

    Preoperative chemoradiotherapy is the standard of care for locally advanced esophageal cancer, causing persistent deterioration in the nutritional status. We performed a prospective study to evaluate the safety and efficacy of esophageal double-covered self-expandable metal stents in patients with esophageal cancer before chemoradiotherapy. The nutritional status and dysphagia were prospectively recorded. Eleven patients were included: eight were moderate and three were severely malnourished. After stent placement, dysphagia improved in all patients. With regard to complications, one patient developed an esophageal perforation that required urgent esophagectomy. Four patients presented stent migration. Three of these patients required enteral nutrition and none was submitted to surgery because of poor nutritional status. Of the other six patients, only four were operated upon. Stent placement presented a high complication rate and did not prevent weight loss or malnutrition. Other alternatives, including naso-gastric tube placement or endoscopic percutaneous gastrostomy or jejunostomy, should be considered.

  8. First pregnancy characteristics, postmenopausal breast density, and salivary sex hormone levels in a population at high risk for breast cancer

    Directory of Open Access Journals (Sweden)

    Mary Mockus

    2015-06-01

    Conclusions and general significance: While reproductive characteristics, in particular parity, generally demonstrated independent associations with postmenopausal breast density and E, P and DHEA levels, T levels showed concordant inverse associations with age-at-first birth and breast density. These findings suggest that reproductive effects and later life salivary sex steroid hormone levels may have independent effects on later life breast density and cancer risk.

  9. Neoplasms of the Stomach, Liver & Pancreas: Prevention, Diagnosis, and Treatment among High-Risk Populations | Division of Cancer Prevention

    Science.gov (United States)

    Agenda - Day 1, September 18, 2015 08:00 am - Registration 08:30 am - Welcome remarks and overview of the Conference Dr. Leslie Ford (NCI) – 5 min Dr. Edgar Colon (RCM and UPRCCC) - 5 min Luz Maria Rodriguez – Conference objectives & structure  Global Cancer Burden: An Overview and State of the Problem Moderators: Dr. Luz Maria Rodriguez and Dr. Victor Jose Carlo (PR

  10. Adherence to cervical cancer screening varies by human papillomavirus vaccination status in a high-risk population

    Directory of Open Access Journals (Sweden)

    Christopher A. Paynter

    2015-01-01

    Full Text Available Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14–26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00. Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35. Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population.

  11. Humoral leukocyte adherence inhibition (H-LAI) test in screening of high risk group for lung cancer

    International Nuclear Information System (INIS)

    Kubasova, T.; Koeteles, G.J.; Horvath, M.; Bank, J.

    1990-01-01

    In screening 150 ore miners a positive humoral immune response to the lung tumor antigen was found in 30 serum samples. Repeated testing of the positive sera (after 1-3 years) was only possible in 15 cases. The reaction of 12 serum samples again was positive, while 2 persons died of lung cancer. The results obtained in these follow-up investigations are discussed. (author). 2 figs., 2 tabs., 11 refs

  12. High-Risk List

    Science.gov (United States)

    2017-01-01

    economy. The World Bank has said that “corruption creates an unfavorable business environment by undermining the operation efficiency of firms and... Bank Began as ‘Ponzi Scheme,’” 11/27/2012. 64 Independent Joint Anti-Corruption Monitoring and Evaluation Committee, Unfinished Business : The Follow...HIGH RISK AREA 7: Oversight 51 HIGH-RISK AREA 8: Strategy and Planning 55 CONCLUSION HIGH RISK LIST I JANUARY 11, 2017 2 EXECUTIVE SUMMARY

  13. The predictive value of endorectal 3 Tesla multiparametric magnetic resonance imaging for extraprostatic extension in patients with low, intermediate and high risk prostate cancer.

    Science.gov (United States)

    Somford, D M; Hamoen, E H; Fütterer, J J; van Basten, J P; Hulsbergen-van de Kaa, C A; Vreuls, W; van Oort, I M; Vergunst, H; Kiemeney, L A; Barentsz, J O; Witjes, J A

    2013-11-01

    We determined the positive and negative predictive values of multiparametric magnetic resonance imaging for extraprostatic extension at radical prostatectomy for different prostate cancer risk groups. We evaluated a cohort of 183 patients who underwent 3 Tesla multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted magnetic resonance imaging and dynamic contrast enhanced sequences, with an endorectal coil before radical prostatectomy. Pathological stage at radical prostatectomy was used as standard reference for extraprostatic extension. The cohort was classified into low, intermediate and high risk groups according to the D'Amico criteria. We recorded prevalence of extraprostatic extension at radical prostatectomy and determined sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging for extraprostatic extension in each group. Univariate and multivariate analyses were performed to identify predictors of extraprostatic extension at radical prostatectomy. The overall prevalence of extraprostatic extension at radical prostatectomy was 49.7% ranging from 24.7% to 77.1% between low and high risk categories. Overall staging accuracy of multiparametric magnetic resonance imaging for extraprostatic extension was 73.8%, with sensitivity, specificity, positive predictive value and negative predictive value of 58.2%, 89.1%, 84.1% and 68.3%, respectively. Positive predictive value of multiparametric magnetic resonance imaging for extraprostatic extension was best in the high risk cohort with 88.8%. Negative predictive value was highest in the low risk cohort with 87.7%. With an odds ratio of 10.3 multiparametric magnetic resonance imaging is by far the best preoperative predictor of extraprostatic extension at radical prostatectomy. For adequate patient counseling, knowledge of predictive values of multiparametric magnetic resonance imaging for extraprostatic extension is

  14. The influence of selected factors on the attendance of the high-risk population in the early lung cancer detection program.

    Science.gov (United States)

    Zakrzewska, Agata; Szczepanowska, Magdalena; Książek, Janina; Biadacz, Iwona; Dziedzic, Robert; Jelitto-Górska, Małgorzata; Rzyman, Witold

    2014-01-01

    Lung cancer is the most common cause of cancer-related death worldwide, killing almost 22,000 people in Poland every year. Low-dose computed tomography (LDCT) is the most promising tool of secondary prophylaxis leading to early detection and thus successful treatment of this malignancy. Knowledge about socio-demographic factors that affect participation in lung cancer early detection programs is essential for the future design and implementation of such programs. Among the 8649 participants of the Pomeranian Lung Cancer Screening Program (PLCSP), 1619 individuals responded to a questionnaire that had been designed to assess socio-demographic data of participants at high risk of developing lung cancer. The survey was conducted on-site after reception of results by the program participants. Among the survey participants, 777 (48%) were current cigarette smokers. The majority of them represented low or medium level of wealth status. The respondents positively evaluated the promotional campaign during the PLCSP, although 43% of them indicated family and friends as a source of information about the program. As the most important action that stimulated the participation, 46% of the respondents indicated the awareness campaign involving a celebrity, and 45% of them indicated the presence of cancer in the family. The influence of healthcare employees on the participation in the screening program was minimal. More than half of the respondents (53%) declared a willingness to co-finance a similar prophylactic program in the future in an amount not exceeding 100 PLN. An effective promotional campaign in the media, the influence of family and a campaign involving a celebrity promoted attendance at the screening program. The influence of healthcare employees on the participation in the program was minimal. The majority of the screened population declared a willingness to actively participate in the costs of LDCT examination.

  15. Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study.

    Science.gov (United States)

    Canlorbe, Geoffroy; Bendifallah, Sofiane; Raimond, Emilie; Graesslin, Olivier; Hudry, Delphine; Coutant, Charles; Touboul, Cyril; Bleu, Géraldine; Collinet, Pierre; Darai, Emile; Ballester, Marcos

    2015-08-01

    Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups. Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables. Distribution of the 729 women with EC according to BMI was BMI women with a BMI ≥ 35 (72 %) than for those with a BMI obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group. Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women.

  16. Creation of RTOG compliant patient CT-atlases for automated atlas based contouring of local regional breast and high-risk prostate cancers.

    Science.gov (United States)

    Velker, Vikram M; Rodrigues, George B; Dinniwell, Robert; Hwee, Jeremiah; Louie, Alexander V

    2013-07-25

    Increasing use of IMRT to treat breast and prostate cancers at high risk of regional nodal spread relies on accurate contouring of targets and organs at risk, which is subject to significant inter- and intra-observer variability. This study sought to evaluate the performance of an atlas based deformable registration algorithm to create multi-patient CT based atlases for automated contouring. Breast and prostate multi-patient CT atlases (n = 50 and 14 respectively) were constructed to be consistent with RTOG consensus contouring guidelines. A commercially available software algorithm was evaluated by comparison of atlas-predicted contours against manual contours using Dice Similarity coefficients. High levels of agreement were demonstrated for prediction of OAR contours of lungs, heart, femurs, and minor editing required for the CTV breast/chest wall. CTVs generated for axillary nodes, supraclavicular nodes, prostate, and pelvic nodes demonstrated modest agreement. Small and highly variable structures, such as internal mammary nodes, lumpectomy cavity, rectum, penile bulb, and seminal vesicles had poor agreement. A method to construct and validate performance of CT-based multi-patient atlases for automated atlas based auto-contouring has been demonstrated, and can be adopted for clinical use in planning of local regional breast and high-risk prostate radiotherapy.

  17. Creation of RTOG compliant patient CT-atlases for automated atlas based contouring of local regional breast and high-risk prostate cancers

    International Nuclear Information System (INIS)

    Velker, Vikram M; Rodrigues, George B; Dinniwell, Robert; Hwee, Jeremiah; Louie, Alexander V

    2013-01-01

    Increasing use of IMRT to treat breast and prostate cancers at high risk of regional nodal spread relies on accurate contouring of targets and organs at risk, which is subject to significant inter- and intra-observer variability. This study sought to evaluate the performance of an atlas based deformable registration algorithm to create multi-patient CT based atlases for automated contouring. Breast and prostate multi-patient CT atlases (n = 50 and 14 respectively) were constructed to be consistent with RTOG consensus contouring guidelines. A commercially available software algorithm was evaluated by comparison of atlas-predicted contours against manual contours using Dice Similarity coefficients. High levels of agreement were demonstrated for prediction of OAR contours of lungs, heart, femurs, and minor editing required for the CTV breast/chest wall. CTVs generated for axillary nodes, supraclavicular nodes, prostate, and pelvic nodes demonstrated modest agreement. Small and highly variable structures, such as internal mammary nodes, lumpectomy cavity, rectum, penile bulb, and seminal vesicles had poor agreement. A method to construct and validate performance of CT-based multi-patient atlases for automated atlas based auto-contouring has been demonstrated, and can be adopted for clinical use in planning of local regional breast and high-risk prostate radiotherapy

  18. The outcome of I-131 ablation therapy for intermediate and high-risk differentiated thyroid cancer using a strict definition of successful ablation.

    Science.gov (United States)

    Watanabe, Ken; Uchiyama, Mayuki; Fukuda, Kunihiko

    2017-09-01

    This article examines the outcome of radioactive iodine ablation therapy for thyroid cancer in high-risk patients and investigates background factors influencing ablation failure. We included 91 patients in this retrospective analysis and evaluated the ablation success rate. Successful ablation was defined as the absence of visible iodine-131 (I-131) accumulation in the thyroid bed after whole-body scans and thyroglobulin levels sex, I-131 dose, pathology, resection stump findings, tumor T category and thyroglobulin levels, which could affect ablation outcome. Successful ablation was achieved in only 14 patients (15.4%). Pre-ablation serum thyroglobulin levels were significantly higher in the ablation failure group than in the success group (P 10 ng/ml were significantly related to ablation failure after multivariate analysis (odds ratio 27.2; 95% confidence interval 2.469-299.7; P = 0.007). The ablation success rate was very low because of high thyroglobulin levels, even with high-dose I-131. High-risk patients, especially those with high thyroglobulin levels (>10 ng/ml), are unlikely to reach levels low enough to meet successful ablation criteria.

  19. Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation.

    Science.gov (United States)

    Sini, Carla; Fiorino, Claudio; Perna, Lucia; Noris Chiorda, Barbara; Deantoni, Chiara Lucrezia; Bianchi, Marco; Sacco, Vincenzo; Briganti, Alberto; Montorsi, Francesco; Calandrino, Riccardo; Di Muzio, Nadia; Cozzarini, Cesare

    2016-01-01

    To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. Significant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20 Gy) and smaller receiving 40-50 Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p ⩽ 0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively. Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Comparison of hematological toxicities between innovator and generic cisplatin formulations in cervical cancer patients treated with concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    Oike, Takahiro; Ohno, Tatsuya; Noda, Shin-ei; Sato, Hiro; Tamaki, Tomoaki; Kiyohara, Hiroki; Ando, Ken; Nakano, Takashi

    2013-01-01

    To compare the incidence and degree of hematological toxicity between innovator and generic cisplatin formulations, decreases in white blood cell (WBC) count (leukopenia) and platelet counts (thrombocytopenia) were retrospectively examined, using the Common Toxicity Criteria for Adverse Events ver. 4.0, in patients with uterine cervical cancer treated with concurrent chemoradiotherapy using innovator (innovator group, n = 22) or generic (generic group, n = 22) cisplatin formulations. There were no significant differences in patient characteristics except in the technique of external irradiation; larger numbers of patients in the innovator and generic groups were irradiated using the parallel-opposed two-field technique and the four-field box technique, respectively (P = 0.00012), which is in line with the historical progress of external beam radiation therapy. The numbers of patients showing Grade 1, 2, 3 and 4 leukopenia were 1 (4.5%), 14 (64%), 7 (32%) and 0 (0.0%) in the innovator group, and 1 (4.5%), 6 (27%), 13 (59%) and 2 (9.0%) in the generic group, respectively. The number of patients showing Grade 3–4 leukopenia was significantly greater in the generic group than in the innovator group (P = 0.034). There was no significant relationship between the incidence of Grade 3–4 leukopenia and the technique of external irradiation. There were no significant differences in the incidence and degree of thrombocytopenia between the two groups. These results indicate the possibility that the generic cisplatin formulation may have a different toxicity profile compared to the innovator formulation in terms of the incidence of leukopenia

  1. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer

    DEFF Research Database (Denmark)

    Jensen, Maj-Britt; Krarup, Jens Fabricius; Palshof, Torben

    2018-01-01

    randomly assigned to two years of daily placebo or tamoxifen. Survival statistics was collected from the Danish Civil Registration System. RESULTS: The five-year invasive breast cancer recurrence (BCR) rate was 43.2% in the placebo arm and 31.9% in the tamoxifen arm. Compared with the placebo arm...... the hazard ratio for a BCR event was 0.73 in the tamoxifen arm (p = .07). With an estimated median follow-up on overall survival of 40.9 years, 154 and 145 patients had died in the placebo and tamoxifen arm, respectively. After adjustment for baseline characteristics a significant reduction in mortality...

  2. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3) : an open-label, multicentre, randomised, phase 3 trial

    NARCIS (Netherlands)

    de Boer, Stephanie M.; Powell, Melanie E.; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B.; Ledermann, Jonathan A.; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie-Helene; Kitchener, Henry C.; Nijman, Hans W.; Kruitwagen, Roy F.; Nout, Remi A.; Verhoeven-Adema, Karen W.; Smit, Vincent T.; Putter, Hein; Creutzberg, Carien L.

    Background About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women

  3. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial

    NARCIS (Netherlands)

    Boer, S.M. de; Powell, M.E.; Mileshkin, L.; Katsaros, D.; Bessette, P.; Haie-Meder, C.; Ottevanger, P.B.; Ledermann, J.A.; Khaw, P.; Colombo, A.; Fyles, A.; Baron, M.H.; Kitchener, H.C.; Nijman, H.W.; Kruitwagen, R.F.; Nout, R.A.; Verhoeven-Adema, K.W.; Smit, V.T.; Putter, H.; Creutzberg, C.L.

    2016-01-01

    BACKGROUND: About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women

  4. Discovery and validation of a colorectal cancer classifier in a new blood test with improved performance for high-risk subjects

    DEFF Research Database (Denmark)

    Croner, Lisa J; Dillon, Roslyn; Kao, Athit

    2017-01-01

    BACKGROUND: The aim was to improve upon an existing blood-based colorectal cancer (CRC) test directed to high-risk symptomatic patients, by developing a new CRC classifier to be used with a new test embodiment. The new test uses a robust assay format-electrochemiluminescence immunoassays......, the indeterminate rate of the new panel was 23.2%, sensitivity/specificity was 0.80/0.83, PPV was 36.5%, and NPV was 97.1%. CONCLUSIONS: The validated classifier serves as the basis of a new blood-based CRC test for symptomatic patients. The improved performance, resulting from robust concentration measures across......-to quantify protein concentrations. The aim was achieved by building and validating a CRC classifier using concentration measures from a large sample set representing a true intent-to-test (ITT) symptomatic population. METHODS: 4435 patient samples were drawn from the Endoscopy II sample set. Samples were...

  5. Dermoscopy, Digital Dermoscopy and Other Diagnostic Tools in the Early Detection of Melanoma and Follow-up of High-risk Skin Cancer Patients.

    Science.gov (United States)

    Thomas, Luc; Puig, Susana

    2017-07-05

    Early detection is a key strategy for reducing the mortality and economic burden associated with melanoma. Dermoscopy is a non-invasive and cost-effective tool for melanoma diagnosis, which has been shown to be a reliable and sensitive method for detecting early-stage skin cancer and reducing the number of unnecessary excisions. Patients at high risk of developing melanoma require long-term surveillance. Use of digital dermoscopy follow-up of these patients has led to improved outcomes. Combined follow-up programmes using total-body photography and digital dermoscopy have led to further improvements in early diagnosis and diagnostic accuracy. Dermoscopy is now widely used by dermatologists, but the public health impact of this tool is yet to be evaluated. Despite the clear advantages of dermoscopy and digital follow-up meth-ods, dermoscopy training and access to digital dermoscopy among dermatologists and general practitioners needs to be improved.

  6. Improving subjective perception of personal cancer risk: systematic review and meta-analysis of educational interventions for people with cancer or at high risk of cancer.

    Science.gov (United States)

    Dieng, Mbathio; Watts, Caroline G; Kasparian, Nadine A; Morton, Rachael L; Mann, Graham J; Cust, Anne E

    2014-06-01

    Newly diagnosed patients with cancer require education about the disease, the available treatments and potential consequences of treatment. Greater understanding of cancer risk has been found to be associated with greater health-related quality of life, improved psychological adjustment and greater health-related behaviours. The aim of this sytematic review was to assess the effectiveness of educational interventions in improving subjective cancer risk perception and to appraise the quality of the studies. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies. Eligible studies were identified via Medline, PsycINFO, AMED, CINAHL and Embase databases. After screening titles and abstracts, two reviewers independently assessed the eligibility of 206 full-text articles. Forty papers were included in the review; the majority of studies were conducted among breast cancer patients (n = 29) and evaluated the effect of genetic counselling on personal perceived risk (n = 25). Pooled results from RCTs (n = 12) showed that, both in the short and long term, educational interventions did not significantly influence risk perception level (standardised mean difference 0.05, 95% CI -0.24-0.34; p = 0.74) or accuracy (odds ratio = 1.96, 95% CI: 0.61-6.25; p = 0.26). Only one RCT reported a short-term difference in risk ratings (p = 0.01). Of prospective observational studies (n = 28), many did demonstrate changes in the level of perceived risk and improved risk accuracy and risk ratings in both the short and long term. However, only one (of three) observational studies reported a short-term difference in risk ratings (p < = 0.003). Further development and investigation of educational interventions using good quality, RCTs are warranted. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Effects of education based on the health belief model on screening behavior in high risk women for breast cancer, Tehran, Iran.

    Science.gov (United States)

    Hajian, Sepideh; Vakilian, Katayon; Najabadi, Khadijeh Mirzaii; Hosseini, Jalil; Mirzaei, Hamid Reza

    2011-01-01

    Breast cancer is the most common malignancy in women. Early diagnosis allows efficient treatment and increases survival, but the efficacy of breast self examination (BSE) is not sufficiently well established. The American Cancer Society aims to give women the opportunity to recognize the utility, limitations and adverse effects of breast cancer screening through education models based on psychological theories. With the Health Belief Model, people's health perceptions and attitudes influence their practices, for example with screening. The purpose of this randomized controlled clinical trial was to determine the effect of education based on this model on breast cancer screening in high risk Iranian women. Participants were women with a family history of breast cancer (mother, sister, and daughter). After explanation of the study objectives to participants, they were recruited on obtaining oral consent and each filled out the study questionnaire based on the Health Belief Model. Allocation was into two groups by computerized randomization, control and intervention, receiving education on breast cancer screening. Perceived susceptibility to and seriousness of breast cancer, perceived usefulness of and barriers to BSE, clinical breast examination, and mammography, and self-efficacy in the ability to perform these, were assessed, with comparison of scores for BSE practice before and after education and doing mammography and clinical examination by a physician in intervention and control group. The mean age was 37.8 ± 11.7 (range 19-60). The mean rank in the intervention group significantly differed before and after the education, but except for " perceived threat" and "perceived usefulness of breast self examination", we did not find any significant differences from the control group. After educational sessions, breast self examination and clinical examination practice rates were elevated. Health education based on well known psychological theories for breast cancer

  8. Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer.

    Science.gov (United States)

    Ong, Wee Loon; Foroudi, Farshad; Evans, Sue; Millar, Jeremy

    2017-11-01

    To evaluate the pattern of use of androgen deprivation therapy (ADT) with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a population-based study in Australia. This is a prospective cohort of men with intermediate- and high-risk PCa, captured in the population-based Prostate Cancer Outcome Registry Victoria, who were treated with definitive prostate RT between January 2010 and December 2015. The primary outcome of interest was ADT utilization. Chi-squared test for trend was used to evaluate the temporal trend in the use of ADT over the study period. Multivariate logistic regressions were used to evaluate the effects of patient-, tumour- and treatment-related factors, and treatment institutions (public/ private and metropolitan/ regional) on the likelihood of ADT utilization. A total of 1806 men were included in the study, 199 of whom (11%) had favourable National Comprehensive Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk feature, primary Gleason grade 3, and variation in the use of ADT between public vs private and metropolitan vs regional institutions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  9. High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node.

    Science.gov (United States)

    Tvedskov, Tove Filtenborg; Jensen, Maj-Britt; Lisse, Ida Marie; Ejlertsen, Bent; Balslev, Eva; Kroman, Niels

    2012-11-15

    Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002-2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases. Copyright © 2012 UICC.

  10. Single-port versus conventional multiport access prophylactic laparoscopic bilateral salpingo-oophorectomy in high-risk patients for ovarian cancer: a comparison of surgical outcomes.

    Science.gov (United States)

    Angioni, Stefano; Pontis, Alessandro; Sedda, Federica; Zampetoglou, Theodoros; Cela, Vito; Mereu, Liliana; Litta, Pietro

    2015-01-01

    Bilateral salpingo-oophorectomy (BSO) in carriers of BRCA1 and BRCA2 mutations is widely recommended as part of a risk-reduction strategy for ovarian or breast cancer due to an underlying genetic predisposition. BSO is also performed as a therapeutic intervention for patients with hormone-positive premenopausal breast cancer. BSO may be performed via a minimally invasive approach with the use of three to four 5 mm and/or 12 mm ports inserted through a skin incision. To further reduce the morbidity associated with the placement of multiple port sites and to improve cosmetic outcomes, single-port laparoscopy has been developed with a single access point from the umbilicus. The purpose of this study was to evaluate the surgical outcomes associated with reducing the risks of salpingo-oophorectomy performed in a single port, while comparing multiport laparoscopy in women with a high risk for ovarian cancer. Single-port laparoscopy-BSO is feasible and safe, with favorable surgical and cosmetic outcomes when compared to conventional laparoscopy.

  11. Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

    International Nuclear Information System (INIS)

    Lim, Tee S.; Cheung, Patrick; Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

    2008-01-01

    Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score ≥8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity

  12. Comparison study of intensity modulated arc therapy using single or multiple arcs to intensity modulated radiation therapy for high-risk prostate cancer

    International Nuclear Information System (INIS)

    Ashamalla, Hani; Tejwani, Ajay; Parameritis, Loannis; Swamy, Uma; Luo, Pei Ching; Guirguis, Adel; Lavaf, Amir

    2013-01-01

    Intensity modulated arc therapy (IMAT) is a form of intensity modulated radiation therapy (IMRT) that delivers dose in single or multiple arcs. We compared IMRT plans versus single-arc field (1ARC) and multi-arc fields (3ARC) IMAT plans in high-risk prostate cancer. Sixteen patients were studied. Prostate (PTV P ), right pelvic (PTV RtLN ) and left pelvic lymph nodes (PTV LtLN ), and organs at risk were contoured. PTVP, PTV RtLN , and PTV LtLN received 50.40 Gy followed by a boost to PTV B of 28.80 Gy. Three plans were per patient generated: IMRT, 1ARC, and 3ARC. We recorded the dose to the PTV, the mean dose (D MEAN ) to the organs at risk, and volume covered by the 50% isodose. Efficiency was evaluated by monitor units (MU) and beam on time (BOT). Conformity index (CI), Paddick gradient index, and homogeneity index (HI) were also calculated. Average Radiation Therapy Oncology Group CI was 1.17, 1.20, and 1.15 for IMRT, 1ARC, and 3ARC, respectively. The plans' HI were within 1% of each other. The D MEAN of bladder was within 2% of each other. The rectum D MEAN in IMRT plans was 10% lower dose than the arc plans (p < 0.0001). The GI of the 3ARC was superior to IMRT by 27.4% (p = 0.006). The average MU was highest in the IMRT plans (1686) versus 1ARC (575) versus 3ARC (1079). The average BOT was 6 minutes for IMRT compared to 1.3 and 2.9 for 1ARC and 3ARC IMAT (p < 0.05). For high-risk prostate cancer, IMAT may offer a favorable dose gradient profile, conformity, MU and BOT compared to IMRT.

  13. Racial Differences in Prediction of Time to Prostate Cancer Diagnosis in a Prospective Screening Cohort of High-Risk Men: Effect of TMPRSS2 Met160Val

    Science.gov (United States)

    Giri, Veda N.; Ruth, Karen; Hughes, Lucinda; Uzzo, Robert G.; Chen, David Y.T.; Boorjian, Stephen A.; Viterbo, Rosalia; Rebbeck, Timothy R.

    2011-01-01

    Introduction The TMPRSS2-ERG gene fusion occurs in >50% of prostate tumors and has been associated with poor outcomes. The T-allele (Valine) of the Met160Val (rs12329760) in TMPRSS2 has been associated with this fusion. We evaluated this polymorphism with respect to self-identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high-risk men. Patients and Methods 631 men ages 35-69 years were studied. “High-risk” was defined as ≥ one first degree or two second degree relatives with PCA, any African American (AA) man regardless of familial PCA, and men with BRCA1/2 mutations. Men with elevated PSA or other indications for PCA underwent biopsy. Men were followed from time of study entry to PCA diagnosis. Cox models were used to evaluate time to PCA diagnosis by genotype. Results Genotype distribution differed significantly by SIRE (CT/TT vs. CC, p<0.0001). Among 183 Caucasian men with at least one follow-up visit, PCA was more than doubled in men carrying CT/TT vs CC genotypes (HR= 2.55, 95% CI=1.14-5.70) after controlling for age and PSA. No association was seen among AA men by TMPRSS2 genotype. Conclusions The T-allele of the Met160Val variant in TMPRSS2, which has been associated with the TMPRSS2-ERG fusion, may be informative of time to PCA diagnosis for a subset of high-risk Caucasian men who are undergoing regular PCA screening. This variant along with other genetic markers warrant further study for personalizing PCA screening. PMID:20735386

  14. Long-term oncological outcomes of a phase II trial of neoadjuvant chemohormonal therapy followed by radical prostatectomy for patients with clinically localised, high-risk prostate cancer.

    Science.gov (United States)

    Silberstein, Jonathan L; Poon, Stephen A; Sjoberg, Daniel D; Maschino, Alexandra C; Vickers, Andrew J; Bernie, Aaron; Konety, Badrinath R; Kelly, W Kevin; Eastham, James A

    2015-07-01

    To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer. In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only. In all, 34 patients were enrolled and followed for a median of 13.1 years. Within 10 years most patients had biochemical recurrence (BCR-free probability 22%; 95% confidence interval [CI] 10-37%). However, the probability of disease-specific survival at 10 years was 84% (95% CI 66-93%) and overall survival was 78% (95% CI 60-89%). The CHT group had higher-risk features than the comparison group (123 patients), with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, P < 0.01). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (hazard ratio [HR] 0.76, 95% CI 0.43-1.34; P = 0.3) and metastasis-free survival (HR 0.55, 95% CI 0.24-1.29; P = 0.2) although these were not statistically significant. Neoadjuvant CHT followed by RP was associated with lower rates of BCR and metastasis compared with the RP-only group; however, these results were not statistically significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

  15. HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy

    Directory of Open Access Journals (Sweden)

    Fountzilas George

    2012-01-01

    Full Text Available Abstract Background HER2 and TOP2A parameters (gene status, mRNA and protein expression have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy. Methods In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization, mRNA expression (quantitative reverse transcription PCR, as well as HER2 and TopoIIa protein expression (immunohistochemistry. Results HER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values Conclusions This study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611000506998.

  16. Boost first, eliminate systematic error, and individualize CTV to PTV margin when treating lymph nodes in high-risk prostate cancer

    International Nuclear Information System (INIS)

    Rossi, Peter J.; Schreibmann, Eduard; Jani, Ashesh B.; Master, Viraj A.; Johnstone, Peter A.S.

    2009-01-01

    Purpose: The purpose of this report is to evaluate the movement of the planning target volume (PTV) in relation to the pelvic lymph nodes (PLNs) during treatment of high-risk prostate cancer. Patients and methods: We reviewed the daily treatment course of ten consecutively treated patients with high-risk prostate cancer. PLNs were included in the initial PTV for each patient. Daily on-board imaging of gold fiducial markers implanted in the prostate was used; daily couch shifts were made as needed and recorded. We analyzed how the daily couch shifts impacted the dose delivered to the PLN. Results: A PLN clinical target volume was identified in each man using CT-based treatment planning. At treatment planning, median minimum planned dose to the PLN was 95%, maximum 101%, and mean 97%. Daily couch shifting to prostate markers degraded the dose slightly; median minimum dose to the PLN was 92%, maximum, 101%, and mean delivered, 96%. We found two cases, where daily systematic shifts resulted in an underdosing of the PLN by 9% and 29%, respectively. In other cases, daily shifts were random and led to a mean 2.2% degradation of planned to delivered PLN dose. Conclusions: We demonstrated degradation of the delivered dose to PLN PTV, which may occur if daily alignment only to the prostate is considered. To improve PLN PTV, it maybe preferable to deliver the prostate/boost treatment first, and adapt the PTV of the pelvic/nodal treatment to uncertainties documented during prostate/boost treatment

  17. The Dose-Response Effects of Aerobic Exercise on Body Composition and Breast Tissue among Women at High Risk for Breast Cancer: A Randomized Trial.

    Science.gov (United States)

    Brown, Justin C; Kontos, Despina; Schnall, Mitchell D; Wu, Shandong; Schmitz, Kathryn H

    2016-07-01

    Observational data indicate that behaviors that shift energetic homeostasis, such as exercise, may decrease the risk of developing breast cancer by reducing the amount of energy-dense, metabolically active adipose tissue. Between December 2008 and April 2013, we conducted a single-blind, 5-month, clinical trial that randomized premenopausal women at high risk of developing breast cancer to one of three groups: 150 min/wk of aerobic exercise (low dose), 300 min/wk of aerobic exercise (high dose), or control. Body composition was assessed using dual-energy x-ray absorptiometry. Background parenchymal enhancement (BPE) was quantified using computerized algorithms on breast dynamic contrast-enhanced MRI. Over 5 months, compared with the control group: the low-dose and high-dose groups lost -1.5 ± 0.5 and -1.3 ± 0.5 kg of body mass (linear Ptrend = 0.032); -1.5 ± 0.4 and -1.4 ± 0.3 kg of fat mass (linear Ptrend = 0.003); -1.3 ± 0.3 and -1.4 ± 0.3% of body fat (linear Ptrend body composition outcomes did not significantly correlate with changes in BPE. These mechanistic data support observational evidence that shifting energetic homeostasis through exercise may alter the risk of developing breast cancer. Additional adequately powered studies are needed to confirm and expand upon our findings that changes in body composition are associated with changes in BPE. Cancer Prev Res; 9(7); 581-8. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Guy, Stephen D.; Tramontana, Adrian R. [Western Health, Department of Infectious Diseases, Private Bag, Footscray, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia); Worth, Leon J.; Thursky, Karin A.; Slavin, Monica A. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Department of Infectious Diseases, Melbourne, Victoria (Australia); Lau, Eddie; Hicks, Rodney J. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, Victoria (Australia); Seymour, John F. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Department of Haematology, Melbourne, Victoria (Australia)

    2012-08-15

    Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [{sup 18} F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature {>=}38 C and neutrophil count <500 cells/{mu}l for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/{mu}l (range 0-730 cells/{mu}l). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as ''true positives'' by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required. (orig.)

  19. Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients

    International Nuclear Information System (INIS)

    Guy, Stephen D.; Tramontana, Adrian R.; Worth, Leon J.; Thursky, Karin A.; Slavin, Monica A.; Lau, Eddie; Hicks, Rodney J.; Seymour, John F.

    2012-01-01

    Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [ 18 F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature ≥38 C and neutrophil count <500 cells/μl for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/μl (range 0-730 cells/μl). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as ''true positives'' by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required. (orig.)

  20. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial

    International Nuclear Information System (INIS)

    Klaver, Charlotte E L; Musters, Gijsbert D; Bemelman, Willem A; Punt, Cornelis J A; Verwaal, Victor J

    2015-01-01

    The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay. The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 °C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy

  1. After low and high dose-rate interstitial brachytherapy followed by IMRT radiotherapy for intermediate and high risk prostate cancer

    International Nuclear Information System (INIS)

    Nakamura, Satoshi; Murakami, Naoya; Inaba, Koji; Wakita, Akihisa; Kobayashi, Kazuma; Takahashi, Kana; Okamoto, Hiroyuki; Umezawa, Rei; Morota, Madoka; Sumi, Minako; Igaki, Hiroshi; Ito, Yoshinori; Itami, Jun

    2016-01-01

    The study aimed to compare urinary symptoms in patients with clinically localized prostate cancer after a combination of either low-dose-rate or high-dose-rate interstitial brachytherapy along with intensity-modulated radiation therapy (LDR-ISBT + IMRT or HDR-ISBT + IMRT). From June 2009 to April 2014, 16 and 22 patients were treated with LDR-ISBT + IMRT and HDR-ISBT + IMRT, respectively. No patient from these groups was excluded from this study. The prescribed dose of LDR-ISBT, HDR-ISBT, and IMRT was 115 Gy, 20 Gy in 2 fractions, and 46 Gy in 23 fractions, respectively. Obstructive and irritative urinary symptoms were assessed by the International Prostate Symptom Score (IPSS) examined before and after treatments. After ISBT, IPSS was evaluated in the 1st and 4th weeks, then every 2–3 months for the 1st year, and every 6 months thereafter. The median follow-up of the patients treated with LDR-ISBT + IMRT and HDR-ISBT + IMRT was 1070.5 days and 1048.5 days, respectively (p = 0.321). The IPSS-increment in the LDR-ISBT + IMRT group was greater than that in the HDR-ISBT + IMRT between 91 and 180 days after ISBT (p = 0.015). In the LDR-ISBT + IMRT group, the IPSS took longer time to return to the initial level than in the HDR-ISBT + IMRT group (in LDR-ISBT + IMRT group, the recovery time was 90 days later). The dose to urethra showed a statistically significant association with the IPSS-increment in the irritative urinary symptoms (p = 0.011). Clinical outcomes were comparable between both the groups. Both therapeutic modalities are safe and well suited for patients with clinically localized prostate cancer; however, it took patients longer to recover from LDR-ISBT + IMRT than from HDR-ISBT + IMRT. It is possible that fast dose delivery induced early symptoms and early recovery, while gradual dose delivery induced late symptoms and late recovery. Urethral dose reductions were associated with small increments in IPSS

  2. Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

    International Nuclear Information System (INIS)

    Mamuris, Z.; Dumont, J.; Dutrillaux, B.; Aurias, A.

    1989-01-01

    A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients

  3. Cigarette smoking, physical activity, and alcohol consumption as predictors of cancer incidence among women at high risk of breast cancer in the NSABP P-1 trial.

    Science.gov (United States)

    Land, Stephanie R; Liu, Qing; Wickerham, D Lawrence; Costantino, Joseph P; Ganz, Patricia A

    2014-05-01

    NSABP P-1 provides an opportunity to examine the association of behavioral factors with prospectively monitored cancer incidence and interactions with tamoxifen. From 1992 to 1997, 13,388 women with estimated 5-year breast cancer risk greater than 1.66% or a history of lobular carcinoma in situ (87% younger than age 65; 67% postmenopausal) were randomly assigned to tamoxifen versus placebo. Invasive breast cancer, lung cancer, colon cancer, and endometrial cancer were analyzed with Cox regression. Predictors were baseline cigarette smoking, leisure-time physical activity, alcohol consumption, and established risk factors. At median 7 years follow-up, we observed 395, 66, 35, and 74 breast cancer, lung cancer, colon cancer, and endometrial cancer, respectively. Women who had smoked were at increased risk of breast cancer (P = 0.007; HR = 1.3 for 15-35 years smoking, HR = 1.6 for ≥ 35 years), lung cancer (P cancer (P breast cancer risk only among women assigned to placebo (P = 0.021 activity main effect, P = 0.013 activity-treatment interaction; HR = 1.4 for the placebo group) and endometrial cancer among all women (P = 0.026, HR = 1.7). Moderate alcohol (>0-1 drink/day) was associated with decreased risk of colon cancer (P = 0.019; HR = 0.35) versus no alcohol. There were no other significant associations between these behaviors and cancer risk. Among women with elevated risk of breast cancer, smoking has an even greater impact on breast cancer risk than observed in past studies in the general population. Women who smoke or are inactive should be informed of the increased risk of multiple types of cancer. ©2014 AACR.

  4. Dosimetric analysis of urethral strictures following HDR 192Ir brachytherapy as monotherapy for intermediate- and high-risk prostate cancer

    International Nuclear Information System (INIS)

    Díez, Patricia; Mullassery, Vinod; Dankulchai, Pittaya; Ostler, Peter; Hughes, Robert; Alonzi, Roberto; Lowe, Gerry; Hoskin, Peter J.

    2014-01-01

    Background and purpose: To evaluate dosimetric parameters related to urethral strictures following high dose-rate brachytherapy (HDRBT) alone for prostate cancer. Material and methods: Ten strictures were identified in 213 patients treated with HDRBT alone receiving 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in 3 fractions or 26 Gy in 2 fractions. A matched-pair analysis used 2 controls for each case matched for dose fractionation schedule, pre-treatment IPSS score, number of needles used and clinical target volume. The urethra was divided into membranous urethra and inferior, mid and superior thirds of the prostatic urethra. Results: Stricture rates were 3% in the 34 Gy group, 4% in the 36 Gy group, 6% in the 31.5 Gy group and 4% in the 26 Gy group. The median time to stricture formation was 26 months (range 8–40). The dosimetric parameters investigated were not statistically different between cases and controls. No correlation was seen between stricture rate and fractionation schedule. Conclusions: Urethral stricture is an infrequent complication of prostate HDRBT when used to deliver high doses as sole treatment, with an overall incidence in this cohort of 10/213 (4.7%). In a matched pair analysis no association with dose schedule or urethral dosimetry was identified, but the small number of events limits definitive conclusions

  5. [Acceptance and willingness-to-pay for colorectal colonoscopy screening among high-risk populations for colorectal cancer in urban China].

    Science.gov (United States)

    Shi, Jufang; Huang, Huiyao; Guo, Lanwei; Ren, Jiansong; Ren, Ying; Lan, Li; Zhou, Qi; Mao, Ayan; Qi, Xiao; Liao, Xianzhen; Liu, Guoxiang; Bai, Yana; Cao, Rong; Liu, Yuqin; Wang, Yuanzheng; Gong, Jiyong; Li, Ni; Zhang, Kai; He, Jie; Dai, Min

    2015-05-01

    To survey the acceptance and willingness-to-pay for colorectal cancer colonoscopy screening among high risk populations in urban China. From 2012 to 2013, a Cancer Screening Program in Urban China (CanSPUC) was initiated in 9 provinces, the current survey was conducted among those participants who were evaluated as "high risk for colorectal cancer" by a risk-factor-evaluation-model (community-based) and then went through a colonoscopy screening procedure (hospital-based). All the data were obtained through a questionnaire-based interview (face-to-face or self-completed), mainly focusing on the acceptance and willingness-to-pay of the participants for colorectal colonoscopy screening. The current analysis included a total of 1 624 participants, with an median age of 55.0 years (P25 = 49.0, P75 = 61.0 years) and an annual income per capita of 17 thousand (range: 10-25 thousand) Chinese Yuan (CNY), 42.8% (695/1 624) of whom were males. Of all the participants, 87.0% (1 414/1 624) could totally or substantially accept the colonoscopy screening, particularly in those at higher education level (junior high school: OR = 0.34, 95% CI: 0.22-0.52; high school OR = 0.41, 95% CI: 0.26-0.66; college or over OR = 0.35, 95% CI: 0.20-0.59). Of all the participants, 13.0% (210/1 624) could not or hardly accept it, particularly in those with older age (60-69 years) (OR = 1.48, 95% CI: 1.06-2.07), not in marriage (OR = 2.15, 95% CI: 1.25-3.70) or with family member(s) to raise (OR = 1.60, 95% CI: 1.17-2.20). 1 388 (85.5%) of all the participants had willingness-to-pay for a long-term colonoscopy screening service, particularly in those working in public (OR = 0.61, 95% CI: 0.44-0.84) or enterprise sectors (OR = 0.60, 95% CI: 0.38-0.94), but 82.3% (1 141/1 386) of whom would only pay less than 100 CNY; 14.5% (236/1 624) of total had no willingness-to-pay, particularly in those living in areas with moderate (OR = 4.08, 95% CI: 2.75-6.33) or high GDP per capita (OR = 3.26, 95% CI: 2

  6. Rates and predictors of consideration for adjuvant radiotherapy among high-risk breast cancer patients: a cohort study.

    Science.gov (United States)

    Krotneva, Stanimira; Reidel, Kristen; Nassif, Mohammed; Trabulsi, Nora; Mayo, Nancy; Tamblyn, Robyn; Meguerditchian, Ari N

    2013-07-01

    Radiotherapy (RT) after breast conserving surgery (BCS) represents the standard for local control of breast cancer (BC). However, variations in practice persist. We aimed to characterize the rate of RT consideration (or referral) after BCS and identify predictors in Quebec, Canada, where universal health insurance is in place. A historical prospective cohort study using the provincial hospital discharge and medical services databases was conducted. All women with incident, non-metastatic BC (stages I-III) undergoing BCS (1998-2005) were identified. Odds ratios (ORs) and 95 % confidence intervals (CIs) for RT consideration were estimated with a generalized estimating equations regression model, adjusting for clustering of patients within physicians. Of the 27,483 women selected, 90 % were considered for RT and 84 % subsequently received it. Relative to women 50-69 years old, younger and older women were less likely to be considered: ORs of 0.82 (95 % CI 0.73-0.93) and 0.10 (0.09-0.12), respectively. Emergency room visits and hospitalizations unrelated to BC were associated with decreased odds of RT consideration: 0.85 (0.76-0.94) and 0.83 (0.71-0.97). Women with regional BC considered for chemotherapy were more likely to be considered for RT: 3.41 (2.83-4.11). RT consideration odds increased by 7 % (OR of 1.07, 95 % CI 1.03-1.10) for every ten additional BCSs performed by the surgeon in the prior year. Social isolation, comorbidities, and greater distance to a referral center lowered the odds. Demographic and clinical patient-related risk factors, health service use, gaps in other aspects of BC management, and surgeon's experience predicted RT consideration.

  7. The distribution of high-risk human papillomaviruses is different in young and old patients with cervical cancer.

    Directory of Open Access Journals (Sweden)

    Mariano Guardado-Estrada

    Full Text Available Despite numerous human papillomavirus (HPV frequency studies in women with cervical cancer (CC, little is known of HPV frequency trends according to patient age. In this work, we compare the mean age and frequency distribution by age of CC patients positive for different HPVs. This study included 462 CC patients. HPVs were detected by PCR and typed using DNA sequencing. A total of 456 patients (98.7% were positive for HPV: 418 (90.5% had single and 38 (8.2% had double HPV infections. HPV16 (46.5%, HPV18 (10.4%, HPV45 (6.7%, and HPV31 (4.1% were the most frequent viral types in single-infected patients. The mean ages of single-infected patients with HPV16 (49.2±13.3, HPV18 (47.9±12.2, HPV45 (47.9±11.7, or HPV39 (42.6±8.9 were significantly lower than the mean ages of patients singly (53.9±12.7; p70 years; 12.8% women. In contrast, the trend for the remaining HPVs increased from the youngest (15.8% to the oldest (46.2% women. Unlike other life-style factors, low-risk sexual behavior was associated with late onset of CC independent of low-oncogenic HPV types (p<0.05, Wald chi-square statistic. The data indicate that most CCs in young women depend on the presence of high-oncogenic HPVs. In contrast, almost half of CCs in older patients had low-oncogenic HPVs, suggesting they could depend on the presence of other factors.

  8. Qidong hepatitis B virus infection cohort: a 25-year prospective study in high risk area of primary liver cancer.

    Science.gov (United States)

    Chen, Taoyang; Qian, Gengsun; Fan, Chunsun; Sun, Yan; Wang, Jinbing; Lu, Peixin; Xue, Xuefeng; Wu, Yan; Zhang, Qinan; Jin, Yan; Wu, Yiqian; Gan, Yu; Lu, Jianquan; Kensler, Thomas W; Groopman, John D; Tu, Hong

    2018-01-01

    Qidong hepatitis B virus (HBV) infection cohort (QBC) is a prospective community-based study designed to investigate causative factors of primary liver cancer (PLC) in Qidong, China, where both PLC and HBV infection are highly endemic. Residents aged 20-65 years, living in seven townships of Qidong, were surveyed using hepatitis B surface antigen (HBsAg) serum test and invited to participate in QBC from June 1991 to December 1991. A total of 852 and 786 participants were enrolled in HBsAg-positive and HBsAg-negative sub-cohorts in May 1992, respectively. All participants were actively followed up in person, received HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP) tests and upper abdominal ultrasonic examination, and donated blood and urine samples once or twice a year. The total response rate was 99.6%, and the number of incident PLC was 201 till the end of February 2017. The ratio of incidence rates was 12.32 (95% confidence interval[CI]=7.16-21.21, P PLC was 13.25 (95% CI=6.67-26.33, P PLC-related mutations including A2159G, A2189C and G2203W at the C gene, A799G, A987G and T1055A at the P gene of HBV genome were identified by using samples from the cohort. The mutation in hepatitis B virus (HBV) basal core promoter region of HBV genome has an accumulative effect on the occurrence of PLC. In addition, the tripartite relationship of aflatoxin exposure, P53 mutation and PLC was also investigated. Dynamic prediction model for PLC risk by using its long-term follow-up information and serial blood samples for QBC was developed. This model is expected to improve the efficiency of PLC screening in HBV infection individuals.

  9. Biochemical Control With Radiotherapy Improves Overall Survival in Intermediate and High-Risk Prostate Cancer Patients Who Have an Estimated 10-Year Overall Survival of >90%

    International Nuclear Information System (INIS)

    Herbert, Christopher; Liu, Mitchell; Tyldesley, Scott; Morris, W. James; Joffres, Michel; Khaira, Mandip; Kwan, Winkle; Moiseenko, Vitali; Pickles, Thomas

    2012-01-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51–176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%–94.1%) and 62.1% (95% CI 52.9%–71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%–100%) and 79.8% (95% CI 68.0%–91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p 90%.

  10. Utility of supplemental screening with breast ultrasound in asymptomatic women with dense breast tissue who are not at high risk for breast cancer

    Directory of Open Access Journals (Sweden)

    Geetika A Klevos

    2017-01-01

    Full Text Available Objective: To assess the results of an initial round of supplemental screening with hand-held bilateral breast ultrasound following a negative screening mammogram in asymptomatic women with dense breast tissue who are not at high risk for breast cancer. Materials and Methods: A retrospective, Health Insurance Portability and Accountability Act compliant, Institutional Research Board approved study was performed at a single academic tertiary breast center. Informed consent was waived. A systematic review of the breast imaging center database was conducted to identify and retrieve data for all asymptomatic women, who were found to have heterogeneously dense or extremely dense breast tissue on screening bilateral mammograms performed from July 1, 2010 through June 30, 2012 and who received a mammographic final assessment American College of Radiology's (ACR Breast Imaging Reporting and Data System (BI-RADS category 1 or BI-RADS category 2. Hand-held screening ultrasound was performed initially by a technologist followed by a radiologist. Chi-square and t-test were used and statistical significance was considered at P< 0.05. Results: A total of 1210 women were identified. Of these, 394 underwent the offered supplemental screening ultrasound. BI-RADS category 1 or 2 was assigned to 323 women (81.9%. BI-RADS category 3 was assigned to 50 women (12.9%. A total of 26 biopsies/aspirations were recommended and performed in 26 women (6.6%. The most common finding for which biopsy was recommended was a solid mass (88.5% with an average size of 0.9 cm (0.5–1.7 cm. Most frequent pathology result was fibroadenoma (60.8%. No carcinoma was found. Conclusion: Our data support the reported occurrence of a relatively high number of false positives at supplemental screening with breast ultrasound following a negative screening mammogram in asymptomatic women with dense breast tissue, who are not at a high risk of developing breast cancer, and suggests that caution

  11. Long-Term Results after Treatment of Very Low-, Low-, and High-Risk Thyroid Cancers in a Combined Setting of Thyroidectomy and Radio Ablation Therapy in Euthyroidism

    Directory of Open Access Journals (Sweden)

    Nikos Emmanouilidis

    2013-01-01

    Full Text Available Introduction. Differentiated thyroid cancer treatment usually consists of thyroidectomy and radio ablation in hypothyroidism 4-6 weeks after surgery. Replacing hypothyroidism by recombinant human thyroid stimulating hormone can facilitate radio ablation in euthyroidism within one week after surgery. The outcome of this approach was investigated. Methods. This is a prospective randomized trial to compare thyroidectomy and radio ablation within a few days after preconditioning with recombinant human thyroid stimulating hormone versus thyroidectomy and radio ablation separated by four weeks of L-T4 withdrawal. Tumors were graded into very low-, low- , or high-risk tumors. Recurrence-free survival was confirmed at follow-up controls by neck ultrasound and serum thyroglobulin. Suspected tumor recurrence was treated by additional radio ablation or surgery. Quality-of-life questionnaires with additional evaluation of job performance and sick-leave time were used in all patients. Results. Radio ablation in euthyroidism in quick succession after thyroidectomy did not lead to higher tumor recurrence rates of differentiated thyroid cancers in any risk category and was significantly advantageous with respect to quality-of-life (P<0.001, sick-leave time (P<0.001, and job performance (P=0.002. Conclusion. Recombinant human thyroid stimulating hormone can be used safely and with good efficacy to allow radio ablation under sustained euthyroidism within one week after thyroidectomy.

  12. Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk non-metastatic prostate cancer: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Frederico; Figueiredo, Maximiliano Augusto Novis de; Sasse, Andre Deeke, E-mail: sasse@cevon.com.br [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

    2015-05-15

    Objectives: to investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. Materials and Methods: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. Results: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 - 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. Conclusions: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted. (author)

  13. Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort

    DEFF Research Database (Denmark)

    Hansen, T F; Kjær-Frifeldt, S; Christensen, R D

    2014-01-01

    Background:The aim of the present study was to analyse the prognostic value of microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk index for this group of patients.Methods:A population-based cohort of 554 patients was included. MicroRNA-21 was analysed by qPCR based...... on tumour tissue. An index was created using the coefficients obtained from a collective multiple Cox regression. The entire procedure was cross-validated (10-fold). The performance of the index was quantified by time-dependent receiver operating characteristics curves.Results:High miRNA-21 expression...... was associated with an unfavourable recurrence-free cancer-specific survival (RF-CSS), hazard ratio 1.35 (95% confidence interval, 1.03-1.76) (P=0.028). The generated RF-CSS index divided the traditional high-risk patients into subgroups with 5-year RF-CSS rates of 87% and 73%, respectively (P...

  14. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance.

    Science.gov (United States)

    Sveistrup, Joen; af Rosenschöld, Per Munck; Deasy, Joseph O; Oh, Jung Hun; Pommer, Tobias; Petersen, Peter Meidahl; Engelholm, Svend Aage

    2014-02-04

    Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.

  15. Polymorphic variations in the FANCA gene in high-risk non-BRCA1/2 breast cancer individuals from the French Canadian population.

    Science.gov (United States)

    Litim, Nadhir; Labrie, Yvan; Desjardins, Sylvie; Ouellette, Geneviève; Plourde, Karine; Belleau, Pascal; Durocher, Francine

    2013-02-01

    The majority of genes associated with breast cancer susceptibility, including BRCA1 and BRCA2 genes, are involved in DNA repair mechanisms. Moreover, among the genes recently associated with an increased susceptibility to breast cancer, four are Fanconi Anemia (FA) genes: FANCD1/BRCA2, FANCJ/BACH1/BRIP1, FANCN/PALB2 and FANCO/RAD51C. FANCA is implicated in DNA repair and has been shown to interact directly with BRCA1. It has been proposed that the formation of FANCA/G (dependent upon the phosphorylation of FANCA) and FANCB/L sub-complexes altogether with FANCM, represent the initial step for DNA repair activation and subsequent formation of other sub-complexes leading to ubiquitination of FANCD2 and FANCI. As only approximately 25% of inherited breast cancers are attributable to BRCA1/2 mutations, FANCA therefore becomes an attractive candidate for breast cancer susceptibility. We thus analyzed FANCA gene in 97 high-risk French Canadian non-BRCA1/2 breast cancer individuals by direct sequencing as well as in 95 healthy control individuals from the same population. Among a total of 85 sequence variants found in either or both series, 28 are coding variants and 19 of them are missense variations leading to amino acid change. Three of the amino acid changes, namely Thr561Met, Cys625Ser and particularly Ser1088Phe, which has been previously reported to be associated with FA, are predicted to be damaging by the SIFT and PolyPhen softwares. cDNA amplification revealed significant expression of 4 alternative splicing events (insertion of an intronic portion of intron 10, and the skipping of exons 11, 30 and 31). In silico analyzes of relevant genomic variants have been performed in order to identify potential variations involved in the expression of these spliced transcripts. Sequence variants in FANCA could therefore be potential spoilers of the Fanconi-BRCA pathway and as a result, they could in turn have an impact in non-BRCA1/2 breast cancer families. Copyright

  16. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

    2013-01-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10

  17. Treatment Results of PDR Brachytherapy Combined With External Beam Radiotherapy in 106 Patients With Intermediate- to High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Pieters, Bradley R.; Geijsen, Elisabeth D.; Koedooder, Kees; Blank, Leo E.C.M.; Rezaie, Elisa; Grient, Johan N.B. van der; Reijke, Theo M. de; Koning, Caro C.E.

    2011-01-01

    Purpose: To evaluate treatment outcome of pulsed dose-rate brachytherapy (PDR) combined with external-beam radiotherapy (EBRT) for the treatment of prostate cancer. Methods and Materials: Between 2002 and 2007, 106 patients were treated by EBRT combined with PDR and followed prospectively. Two, 38, and 66 patients were classified as low-, intermediate-, and high-risk disease respectively according to the National Comprehensive Cancer Network criteria. EBRT dose was 46 Gy in 2.0-Gy fractions. PDR dose was increased stepwise from 24.96 to 28.80 Gy. Biochemical disease free survival and overall survival were determined by the Kaplan-Meier method. Cumulative incidence of late gastrointestinal (GI) and genitourinary (GU) toxicity were scored, according to the Common Terminology Criteria for Adverse Events. Results: The 3- and 5-year biochemical nonevidence of disease (bNED) were 92.8% (95% confidence interval [CI], 87.1-98.5) and 89.5% (95% CI, 85.2-93.8), respectively. Overall survival at 3 and 5 years was 99% (95% CI, 96-100) and 96% (95% CI, 90-100), respectively. The 3- and 5-year Grade 2 GI toxicity was 5.3% (95% CI, 0-10.6) and 12.0% (95% CI, 1.4-22.6), respectively. No Grade 3 or higher GI toxicity was observed. The 3- and 5-year Grade 2 or higher GU toxicity was 18.7% (95% CI, 10.3-27.1) and 26.9% (95% CI, 15.1-38.7), respectively. Conclusion: Results on tumor control and late toxicity of EBRT combined with PDR are good and comparable to results obtained with EBRT combined with high-dose-rate brachytherapy for the treatment of prostate cancer.

  18. High Chromosome Number in hematological cancer cell lines is a Negative Predictor of Response to the inhibition of Aurora B and C by GSK1070916

    Directory of Open Access Journals (Sweden)

    Hardwicke Mary

    2011-07-01

    Full Text Available Abstract Background Aurora kinases play critical roles in mitosis and are being evaluated as therapeutic targets in cancer. GSK1070916 is a potent, selective, ATP competitive inhibitor of Aurora kinase B and C. Translation of predictive biomarkers to the clinic can benefit patients by identifying the tumors that are more likely to respond to therapies, especially novel inhibitors such as GSK1070916. Methods 59 Hematological cancer-derived cell lines were used as models for response where in vitro sensitivity to GSK1070916 was based on both time and degree of cell death. The response data was analyzed along with karyotype, transcriptomics and somatic mutation profiles to determine predictors of response. Results 20 cell lines were sensitive and 39 were resistant to treatment with GSK1070916. High chromosome number was more prevalent in resistant cell lines (p-value = 0.0098, Fisher Exact Test. Greater resistance was also found in cell lines harboring polyploid subpopulations (p-value = 0.00014, Unpaired t-test. A review of NOTCH1 mutations in T-ALL cell lines showed an association between NOTCH1 mutation status and chromosome number (p-value = 0.0066, Fisher Exact Test. Conclusions High chromosome number associated with resistance to the inhibition of Aurora B and C suggests cells with a mechanism to bypass the high ploidy checkpoint are resistant to GSK1070916. High chromosome number, a hallmark trait of many late stage hematological malignancies, varies in prevalence among hematological malignancy subtypes. The high frequency and relative ease of measurement make high chromosome number a viable negative predictive marker for GSK1070916.

  19. Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2 French Canadian families with high risk of breast cancer

    International Nuclear Information System (INIS)

    Desjardins, Sylvie; Beauparlant, Joly Charles; Labrie, Yvan; Ouellette, Geneviève; INHERIT BRCAs; Durocher, Francine

    2009-01-01

    The Nijmegen Breakage Syndrome is a chromosomal instability disorder characterized by microcephaly, growth retardation, immunodeficiency, and increased frequency of cancers. Familial studies on relatives of these patients indicated that they also appear to be at increased risk of cancer. In a candidate gene study aiming at identifying genetic determinants of breast cancer susceptibility, we undertook the full sequencing of the NBN gene in our cohort of 97 high-risk non-BRCA1 and -BRCA2 breast cancer families, along with 74 healthy unrelated controls, also from the French Canadian population. In silico programs (ESEfinder, NNSplice, Splice Site Finder and MatInspector) were used to assess the putative impact of the variants identified. The effect of the promoter variant was further studied by luciferase gene reporter assay in MCF-7, HEK293, HeLa and LNCaP cell lines. Twenty-four variants were identified in our case series and their frequency was further evaluated in healthy controls. The potentially deleterious p.Ile171Val variant was observed in one case only. The p.Arg215Trp variant, suggested to impair NBN binding to histone γ-H2AX, was observed in one breast cancer case and one healthy control. A promoter variant c.-242-110delAGTA displayed a significant variation in frequency between both sample sets. Luciferase reporter gene assay of the promoter construct bearing this variant did not suggest a variation of expression in the MCF-7 breast cancer cell line, but indicated a reduction of luciferase expression in both the HEK293 and LNCaP cell lines. Our analysis of NBN sequence variations indicated that potential NBN alterations are present, albeit at a low frequency, in our cohort of high-risk breast cancer cases. Further analyses will be needed to fully ascertain the exact impact of those variants on breast cancer susceptibility, in particular for variants located in NBN promoter region

  20. Efficacy and toxicity of conventionally fractionated pelvic radiation with a hypo fractionated simultaneous versus conventionally fractionated sequential boost for patients with high-risk prostate cancer

    International Nuclear Information System (INIS)

    McDonald, Andrew M.; Jacob, Rojymon; Dobelbower, Michael C.; Kim, Robert Y.; Fiveash, John B.

    2013-01-01

    Purpose: To determine if high-risk prostate cancer responds differently to hypo fractionation. Material and methods: One hundred and fifty-seven men with NCCN high-risk (T3, PSA 20, or Gleason 8) clinically localized prostate cancer treated between 1998 and 2010 met the inclusion criteria for the analysis. Eighty-two were treated with conventional WPRT with a conventionally fractionated sequential boost to the prostate (cRT), with the prostate receiving 75-77 Gy in 1.8 - 2.0 Gy fractions. Seventy-five were treated with pelvic IMRT with a hypo fractionated simultaneous boost to the prostate (hRT), with the prostate receiving 70 Gy in 2.5 Gy fractions. The dose to the pelvic lymph nodes was 45 Gy in the cRT group and 50.4 Gy in the hRT group, both at 1.8 Gy per fraction. Ninety-two percent received neoadjuvant hormonal ablation therapy, typically beginning two months prior to the start of RT. Results: Median follow-up was 6.5 years for men receiving cRT and 3.7 years for those receiving hRT. The actuarial rate of biochemical control at four years was 88% for cRT and 94% for hRT (p=0.82). The rates of early rectal and urinary grade ≥2 toxicities were 35% (29 of 82) and 49% (40 of 82) for the cRT group and 36% (27 of 75) and 44% (33 of 75) for the hRT group. The actuarial rate of late grade 2 rectal toxicity at four years was 25% for the cRT group and 13% for the hRT group (p=0.037). The rate of late grade 3 rectal complications was 4% (3 of 82) for patients receiving cRT and 1% (1 of 75) for patients receiving hRT. Conclusion: Initial follow-up indicates equivalent biochemical control between regimens. Patients receiving hRT experienced fewer late rectal complications

  1. Postoperative inspiratory muscle training in addition to breathing exercises and early mobilization improves oxygenation in high-risk patients after lung cancer surgery: a randomized controlled trial.

    Science.gov (United States)

    Brocki, Barbara Cristina; Andreasen, Jan Jesper; Langer, Daniel; Souza, Domingos Savio R; Westerdahl, Elisabeth

    2016-05-01

    The aim was to investigate whether 2 weeks of inspiratory muscle training (IMT) could preserve respiratory muscle strength in high-risk patients referred for pulmonary resection on the suspicion of or confirmed lung cancer. Secondarily, we investigated the effect of the intervention on the incidence of postoperative pulmonary complications. The study was a single-centre, parallel-group, randomized trial with assessor blinding and intention-to-treat analysis. The intervention group (IG, n = 34) underwent 2 weeks of postoperative IMT twice daily with 2 × 30 breaths on a target intensity of 30% of maximal inspiratory pressure, in addition to standard postoperative physiotherapy. Standard physiotherapy in the control group (CG, n = 34) consisted of breathing exercises, coughing techniques and early mobilization. We measured respiratory muscle strength (maximal inspiratory/expiratory pressure, MIP/MEP), functional performance (6-min walk test), spirometry and peripheral oxygen saturation (SpO2), assessed the day before surgery and again 3-5 days and 2 weeks postoperatively. Postoperative pulmonary complications were evaluated 2 weeks after surgery. The mean age was 70 ± 8 years and 57.5% were males. Thoracotomy was performed in 48.5% (n = 33) of cases. No effect of the intervention was found regarding MIP, MEP, lung volumes or functional performance at any time point. The overall incidence of pneumonia was 13% (n = 9), with no significant difference between groups [IG 6% (n = 2), CG 21% (n = 7), P = 0.14]. An improved SpO2 was found in the IG on the third and fourth postoperative days (Day 3: IG 93.8 ± 3.4 vs CG 91.9 ± 4.1%, P = 0.058; Day 4: IG 93.5 ± 3.5 vs CG 91 ± 3.9%, P = 0.02). We found no association between surgical procedure (thoracotomy versus thoracoscopy) and respiratory muscle strength, which was recovered in both groups 2 weeks after surgery. Two weeks of additional postoperative IMT, compared with standard physiotherapy alone, did not preserve

  2. A Dosimetric Comparison of Tomotherapy and Volumetric Modulated Arc Therapy in the Treatment of High-Risk Prostate Cancer With Pelvic Nodal Radiation Therapy

    International Nuclear Information System (INIS)

    Pasquier, David; Cavillon, Fabrice; Lacornerie, Thomas; Touzeau, Claire; Tresch, Emmanuelle; Lartigau, Eric

    2013-01-01

    Purpose: To compare the dosimetric results of volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in the treatment of high-risk prostate cancer with pelvic nodal radiation therapy. Methods and Materials: Plans were generated for 10 consecutive patients treated for high-risk prostate cancer with prophylactic whole pelvic radiation therapy (WPRT) using VMAT and HT. After WPRT, a sequential boost was delivered to the prostate. Plan quality was assessed according to the criteria of the International Commission on Radiation Units and Measurements 83 report: the near-minimal (D98%), near-maximal (D2%), and median (D50%) doses; the homogeneity index (HI); and the Dice similarity coefficient (DSC). Beam-on time, integral dose, and several organs at risk (OAR) dosimetric indexes were also compared. Results: For WPRT, HT was able to provide a higher D98% than VMAT (44.3 ± 0.3 Gy and 43.9 ± 0.5 Gy, respectively; P=.032) and a lower D2% than VMAT (47.3 ± 0.3 Gy and 49.1 ± 0.7 Gy, respectively; P=.005), leading to a better HI. The DSC was better for WPRT with HT (0.89 ± 0.009) than with VMAT (0.80 ± 0.02; P=.002). The dosimetric indexes for the prostate boost did not differ significantly. VMAT provided better rectum wall sparing at higher doses (V70, V75, D2%). Conversely, HT provided better bladder wall sparing (V50, V60, V70), except at lower doses (V20). The beam-on times for WPRT and prostate boost were shorter with VMAT than with HT (3.1 ± 0.1 vs 7.4 ± 0.6 min, respectively; P=.002, and 1.5 ± 0.05 vs 3.7 ± 0.3 min, respectively; P=.002). The integral dose was slightly lower for VMAT. Conclusion: VMAT and HT provided very similar and highly conformal plans that complied well with OAR dose-volume constraints. Although some dosimetric differences were statistically significant, they remained small. HT provided a more homogeneous dose distribution, whereas VMAT enabled a shorter delivery time.

  3. A Dosimetric Comparison of Tomotherapy and Volumetric Modulated Arc Therapy in the Treatment of High-Risk Prostate Cancer With Pelvic Nodal Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pasquier, David, E-mail: d-pasquier@o-lambret.fr [Departement Universitaire de Radiotherapie, Centre O. Lambret, Lille (France); Universite Lille Nord de France, Lille (France); Centre Galilee, Clinique de la Louviere, Lille (France); Cavillon, Fabrice [Universite Lille Nord de France, Lille (France); Faculte Libre de Medecine, Lille (France); Lacornerie, Thomas [Departement Universitaire de Radiotherapie, Centre O. Lambret, Lille (France); Universite Lille Nord de France, Lille (France); Touzeau, Claire [Centre Galilee, Clinique de la Louviere, Lille (France); Tresch, Emmanuelle [Unite de Methodologie et Biostatistique, Centre O. Lambret, Lille (France); Lartigau, Eric [Departement Universitaire de Radiotherapie, Centre O. Lambret, Lille (France); Universite Lille Nord de France, Lille (France)

    2013-02-01

    Purpose: To compare the dosimetric results of volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in the treatment of high-risk prostate cancer with pelvic nodal radiation therapy. Methods and Materials: Plans were generated for 10 consecutive patients treated for high-risk prostate cancer with prophylactic whole pelvic radiation therapy (WPRT) using VMAT and HT. After WPRT, a sequential boost was delivered to the prostate. Plan quality was assessed according to the criteria of the International Commission on Radiation Units and Measurements 83 report: the near-minimal (D98%), near-maximal (D2%), and median (D50%) doses; the homogeneity index (HI); and the Dice similarity coefficient (DSC). Beam-on time, integral dose, and several organs at risk (OAR) dosimetric indexes were also compared. Results: For WPRT, HT was able to provide a higher D98% than VMAT (44.3 {+-} 0.3 Gy and 43.9 {+-} 0.5 Gy, respectively; P=.032) and a lower D2% than VMAT (47.3 {+-} 0.3 Gy and 49.1 {+-} 0.7 Gy, respectively; P=.005), leading to a better HI. The DSC was better for WPRT with HT (0.89 {+-} 0.009) than with VMAT (0.80 {+-} 0.02; P=.002). The dosimetric indexes for the prostate boost did not differ significantly. VMAT provided better rectum wall sparing at higher doses (V70, V75, D2%). Conversely, HT provided better bladder wall sparing (V50, V60, V70), except at lower doses (V20). The beam-on times for WPRT and prostate boost were shorter with VMAT than with HT (3.1 {+-} 0.1 vs 7.4 {+-} 0.6 min, respectively; P=.002, and 1.5 {+-} 0.05 vs 3.7 {+-} 0.3 min, respectively; P=.002). The integral dose was slightly lower for VMAT. Conclusion: VMAT and HT provided very similar and highly conformal plans that complied well with OAR dose-volume constraints. Although some dosimetric differences were statistically significant, they remained small. HT provided a more homogeneous dose distribution, whereas VMAT enabled a shorter delivery time.

  4. A dosimetric comparison of tomotherapy and volumetric modulated arc therapy in the treatment of high-risk prostate cancer with pelvic nodal radiation therapy.

    Science.gov (United States)

    Pasquier, David; Cavillon, Fabrice; Lacornerie, Thomas; Touzeau, Claire; Tresch, Emmanuelle; Lartigau, Eric

    2013-02-01

    To compare the dosimetric results of volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in the treatment of high-risk prostate cancer with pelvic nodal radiation therapy. Plans were generated for 10 consecutive patients treated for high-risk prostate cancer with prophylactic whole pelvic radiation therapy (WPRT) using VMAT and HT. After WPRT, a sequential boost was delivered to the prostate. Plan quality was assessed according to the criteria of the International Commission on Radiation Units and Measurements 83 report: the near-minimal (D98%), near-maximal (D2%), and median (D50%) doses; the homogeneity index (HI); and the Dice similarity coefficient (DSC). Beam-on time, integral dose, and several organs at risk (OAR) dosimetric indexes were also compared. For WPRT, HT was able to provide a higher D98% than VMAT (44.3 ± 0.3 Gy and 43.9 ± 0.5 Gy, respectively; P=.032) and a lower D2% than VMAT (47.3 ± 0.3 Gy and 49.1 ± 0.7 Gy, respectively; P=.005), leading to a better HI. The DSC was better for WPRT with HT (0.89 ± 0.009) than with VMAT (0.80 ± 0.02; P=.002). The dosimetric indexes for the prostate boost did not differ significantly. VMAT provided better rectum wall sparing at higher doses (V70, V75, D2%). Conversely, HT provided better bladder wall sparing (V50, V60, V70), except at lower doses (V20). The beam-on times for WPRT and prostate boost were shorter with VMAT than with HT (3.1 ± 0.1 vs 7.4 ± 0.6 min, respectively; P=.002, and 1.5 ± 0.05 vs 3.7 ± 0.3 min, respectively; P=.002). The integral dose was slightly lower for VMAT. VMAT and HT provided very similar and highly conformal plans that complied well with OAR dose-volume constraints. Although some dosimetric differences were statistically significant, they remained small. HT provided a more homogeneous dose distribution, whereas VMAT enabled a shorter delivery time. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node–Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Müller, Arndt-Christian, E-mail: arndt-christian.mueller@med.uni-tuebingen.de [Department of Radiation Oncology, Eberhard Karls University, Tübingen (Germany); Eckert, Franziska; Paulsen, Frank; Zips, Daniel [Department of Radiation Oncology, Eberhard Karls University, Tübingen (Germany); Stenzl, Arnulf; Schilling, David [Department of Urology, Eberhard Karls University, Tübingen (Germany); Alber, Markus [Department of Oncology, Aarhus University, Aarhus (Denmark); Bares, Roland [Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University, Tübingen (Germany); Martus, Peter [Institute for Clinical Epidemiology and Applied Biometry, Eberhard Karls University, Tübingen (Germany); Weckermann, Dorothea [Department of Urology, Klinikum Augsburg, Augsburg (Germany); Belka, Claus; Ganswindt, Ute [Department of Radiation Oncology, Ludwig-Maximilians-University, Munich (Germany)

    2016-02-01

    Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.

  6. Improved health perception after genetic counselling for women at high risk of breast and/or ovarian cancer: construction of new questionnaires--an Italian exploratory study.

    Science.gov (United States)

    Catania, Chiara; Feroce, Irene; Barile, Monica; Goldhirsch, Aron; De Pas, Tommaso; de Braud, Filippo; Boselli, Sabrina; Adamoli, Laura; Radice, Davide; Rossi, Alessandra; Spitaleri, Gianluca; Noberasco, Cristina; Bonanni, Bernardo

    2016-03-01

    Subjects referred to genetic counselling for cancer may have heightened perceptions of illness and death, even though they are healthy and this may cause anxiety and reluctance to follow through with consultation. We investigated such perceptions before and after counselling and genetic testing for cancer in a cohort of Italian women. We sought to understand the situation of the women referred by designing questionnaires administered to women at high risk of breast and/or ovarian cancer (those who had had a pathogenic mutation identified in a family member via diagnostic testing). We also assessed women after the diagnosis of breast cancers, but free of disease, to help determine risks in their families. The first questionnaires were administered before initial counselling, and the second were completed within 20 days after the counselling. When a genetic test was proposed, the individual was asked to fill in a third questionnaire; the final questionnaire was administered after the person had received the results of the genetic test. We evaluated 204 subjects. Before counselling, 89 % of the subjects were worried about their risk of disease, 52 % felt "different" because of their personal and family history, and 39 % declared that their life choices were influenced by their fear of cancer. After counselling, 82 % of the subjects felt more relived about their pre-existing fears and stated that this process of being seen in a clinic with genetic expertise had clarified the meaning of disease risk for them, and for 50 %, this experience had positively influenced their life choices. Thirty percentage of the subjects had a positive test; all of them felt safer in being cared for by specifically trained staff. Fifty percentage had a less informative test (e.g. "wild-type" gene found); 84 % of them were not worried by the uncertainty, and overall, 96 % considered counselling to be very useful. Candidates for genetic counselling frequently had heightened their perception

  7. XRAYS (eXamining Relevance of Articles to Young Survivors) Program Survey of Information Needs and Media Use by Young Breast Cancer Survivors and Young Women at High-Risk for Breast Cancer.

    Science.gov (United States)

    Yi, Robin H Pugh; Rezende, Lisa F; Huynh, Julie; Kramer, Karen; Cranmer, Melissa; Schlager, Lisa; Dearfield, Craig T; Friedman, Susan J

    2017-09-28

    Women age 45 years or younger with breast cancer, or who are at high-risk for breast cancer due to previously having the disease or to genetic risk, have distinct health risks and needs from their older counterparts. Young women frequently seek health information through the Internet and mainstream media, but often find it does not address their particular concerns, that it is difficult to evaluate or interpret, or even misleading. To help women better understand media coverage about new research, Facing Our Risk of Cancer Empowered (FORCE) developed the CDC-funded XRAYS (eXamining Relevance of Articles to Young Survivors) program. To assure that the XRAYS program is responsive to the community's needs, FORCE launched a web-based survey to assess where young women seek information about breast cancer, and to learn their unmet information needs. A total of 1,178 eligible women responded to the survey. In general, the breast cancer survivors and high-risk women between ages 18-45 years who responded to this survey, are using multiple media sources to seek information about breast cancer risk, prevention, screening, and treatment. They place trust in several media sources and use them to inform their medical decisions. Only about one-third of respondents to this survey report discussing media sources with their health care providers. Current survey results indicate that, by providing credible information on the quality of evidence and reporting in media reports on cancer, XRAYS is addressing a key need for health information. Results suggest that it will be useful for XRAYS to offer reviews of articles on a broad range of topics that can inform decisions at each stage of risk assessment and treatment.

  8. Correlation Between Radiation Dose to 18F-FDG-PET Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    International Nuclear Information System (INIS)

    Rose, Brent S.; Liang Yun; Lau, Steven K.; Jensen, Lindsay G.; Yashar, Catheryn M.; Hoh, Carl K.; Mell, Loren K.

    2012-01-01

    Purpose: To test the hypothesis that radiation dose to 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET)-defined active bone marrow (BM ACT ) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Methods and Materials: The conditions of 26 women with cervical cancer who underwent 18 F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM ACT was defined as the subregion of total bone marrow (BM TOT ) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM INACT ) was defined as BM TOT − BM ACT . Generalized linear modeling was used to test the correlation between BM ACT and BM INACT dose–volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). Results: Increased BM ACT mean dose was significantly associated with decreased log(WBC) nadir (β = −0.04; 95% CI, −0.07to −0.01; p = 0.009), decreased log(ANC) nadir (β = −0.05; 95% CI, −0.08 to −0.02; p = 0.006), decreased hemoglobin nadir (β = −0.16; 95% CI, −0.27 to −0.05; p = 0.010), and decreased platelet nadir (β = −6.16; 95% CI, −9.37 to −2.96; p INACT mean dose and log(WBC) nadir (β = −0.01; 95% CI, −0.06 to 0.05; p = 0.84), log(ANC) nadir (β = −0.03; 95% CI, −0.10 to 0.04; p = 0.40), hemoglobin nadir (β = −0.09; 95% CI, −0.31 to 0.14; p = 0.452), or platelet nadir (β = −3.47; 95% CI, −10.44 to 3.50; p = 0.339). Conclusions: Irradiation of BM subregions with higher 18 F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM ACT subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify optimal SUV thresholds to define BM ACT .

  9. The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Fei Zhou

    Full Text Available BACKGROUND AND OBJECTIVE: Overexpression of COX-2 is proved to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum treatment. This study aimed at investigating the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Two hundred and twelve patients with inoperable stage IIIB-IV NSCLC received first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP methods. RESULTS: The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 rs689466 (-1195G/A polymorphism compared with wild-type homozygotes AA (P value = 0.008; odds ratio, 2.47; 95% confidence internal, 1.26-4.84 and the significance still existed after the Bonferroni correction. Statistically significant difference was also found in grade 3 or 4 leukopenia (P value = 0.010; OR = 2.82; 95%CI = 1.28-6.20. No other significant association was observed between genotype and toxicity in the study. The haplotype analysis showed that the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 0.59; 95%CI = 0.39-0.88 and P value = 0.025; OR = 0.61; 95%CI = 0.39-0.94, respectively while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 1.71; 95%CI = 1.14-2.56 and P value = 0.025; OR = 1.65; 95%CI  = 1.06-2.57, respectively. CONCLUSION: This investigation for the first time

  10. High-dose chemotherapy for patients with high-risk breast cancer: a clinical and economic assessment using a quality-adjusted survival analysis.

    Science.gov (United States)

    Marino, Patricia; Roché, Henri; Moatti, Jean-Paul

    2008-04-01

    The benefit of high-dose chemotherapy (HDC) has not been clearly demonstrated. It may offer disease-free survival improvement at the expense of major toxicity and increasing cost. We evaluated the trade-offs between toxicity, relapse, and costs using a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis. The analysis was conducted in the context of a randomized trial (PEGASE 01) evaluating the benefit of HDC for 314 patients with high-risk breast cancer. A Q-TWiST analysis was first performed to compare HDC with standard chemotherapy. We then used the results of this Q-TWiST analysis to inform a cost per quality-adjusted life-year (QALY) comparison between treatments. Q-TWiST durations were in favor of HDC, whatever the weighting coefficients used for the analysis. This benefit was significant when the weighting coefficient related to the time spent after relapse was low (0.78), HDC offered no benefit. For intermediate values, the results depended on the weighting coefficient attributed to the toxicity period. The incremental cost per QALY ranged from 12,691euro/QALY to 26,439euro/QALY, according to the coefficients used to weight toxicity and relapse. The benefits of HDC outweigh the burdens of treatment for a wide range of utility coefficients. Economic impact is not a barrier to HDC diffusion in this situation. Nevertheless, no significant benefit was demonstrated for a certain range of utility values.

  11. The outcome of I-131 ablation therapy for intermediate and high-risk differentiated thyroid cancer using a strict definition of successful ablation

    International Nuclear Information System (INIS)

    Watanabe, Ken; Uchiyama, Mayuki; Fukuda, Kunihiko

    2017-01-01

    This article examines the outcome of radioactive iodine ablation therapy for thyroid cancer in nigh-risk patients and investigates background factors influencing ablation failure. We included 91 patients in this retrospective analysis and evaluated the ablation success rate. Successful ablation was defined as the absence of visible iodine-131 (I-131) accumulation in the thyroid bed after whole-body scans and thyroglobulin levels <2 ng/ml in a TSH-stimulated state after ablation. We extracted data on patients' age, sex, I-131 dose, pathology, resection stump findings, tumor T category and thyroglobulin levels, which could affect ablation outcome. Successful ablation was achieved in only 14 patients (15.4%). Pre-ablation serum thyroglobulin levels were significantly higher in the ablation failure group than in the success group (P < 0.001), while no significant differences were found for other factors between the groups. Furthermore, thyroglobulin levels >10 ng/ml were significantly related to ablation failure after multivariate analysis (odds ratio 27.2; 95% confidence interval 2.469-299.7; P = 0.007). The ablation success rate was very low because of high thyroglobulin levels, even with high-dose I-131. High-risk patients, especially those with high thyroglobulin levels (>10 ng/ml), are unlikely to reach levels low enough to meet successful ablation criteria. (author)

  12. Cognitive and emotional factors predicting decisional conflict among high-risk breast cancer survivors who receive uninformative BRCA1/2 results.

    Science.gov (United States)

    Rini, Christine; O'Neill, Suzanne C; Valdimarsdottir, Heiddis; Goldsmith, Rachel E; Jandorf, Lina; Brown, Karen; DeMarco, Tiffani A; Peshkin, Beth N; Schwartz, Marc D

    2009-09-01

    To investigate high-risk breast cancer survivors' risk reduction decision making and decisional conflict after an uninformative BRCA1/2 test. Prospective, longitudinal study of 182 probands undergoing BRCA1/2 testing, with assessments 1-, 6-, and 12-months postdisclosure. Primary predictors were health beliefs and emotional responses to testing assessed 1-month postdisclosure. Main outcomes included women's perception of whether they had made a final risk management decision (decision status) and decisional conflict related to this issue. There were four patterns of decision making, depending on how long it took women to make a final decision and the stability of their decision status across assessments. Late decision makers and nondecision makers reported the highest decisional conflict; however, substantial numbers of women--even early and intermediate decision makers--reported elevated decisional conflict. Analyses predicting decisional conflict 1- and 12-months postdisclosure found that, after accounting for control variables and decision status, health beliefs and emotional factors predicted decisional conflict at different timepoints, with health beliefs more important 1 month after test disclosure and emotional factors more important 1 year later. Many of these women may benefit from decision making assistance. Copyright 2009 APA, all rights reserved.

  13. A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer.

    Science.gov (United States)

    Kelly, Karen; Kittelson, John; Franklin, Wilbur A; Kennedy, Timothy C; Klein, Catherine E; Keith, Robert L; Dempsey, Edward C; Lewis, Marina; Jackson, Mary K; Hirsch, Fred R; Bunn, Paul A; Miller, York E

    2009-05-01

    No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without alpha tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus alpha tocopherol (13-cis RA/alpha toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to observations/13-cis RA/13-cis RA/alpha toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/alpha toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36-2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, -0.18; 95% confidence interval, -1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The

  14. A Randomized Phase II Chemoprevention Trial of 13-CIS Retinoic Acid with Or without α Tocopherol or Observation in Subjects at High Risk for Lung Cancer

    Science.gov (United States)

    Kelly, Karen; Kittelson, John; Franklin, Wilbur A.; Kennedy, Timothy C.; Klein, Catherine E.; Keith, Robert L.; Dempsey, Edward C.; Lewis, Marina; Jackson, Mary K.; Hirsch, Fred R.; Bunn, Paul A.; Miller, York E.

    2011-01-01

    No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without α tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus α tocopherol (13-cis RA/α toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment “failure” defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to obervations/13-cis RA/13-cis RA/α toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/α toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36–2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, −0.18; 95% confidence interval, −1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The addition of

  15. 'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example

    International Nuclear Information System (INIS)

    Rosewall, Tara; Alasti, Hamideh; Bayley, Andrew; Yan, Jing

    2017-01-01

    Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2 = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were −0.4 to 1.8 mm (LR), −1.2 to 5.2 mm (SI) and −1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer.

  16. Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

    International Nuclear Information System (INIS)

    Corn, Paul G.; Song, Danny Y.; Heath, Elisabeth; Maier, Jordan; Meyn, Raymond; Kuban, Deborah; DePetrillo, Thomas A.; Mathew, Paul

    2013-01-01

    Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily

  17. Diagnostic values of serum levels of pepsinogens and gastrin-17 for screening gastritis and gastric cancer in a high risk area in northern Iran.

    Science.gov (United States)

    Nejadi-Kelarijani, Fatemeh; Roshandel, Gholamreza; Semnani, Shahryar; Ahmadi, Ali; Faghani, Behzad; Besharat, Sima; Akhavan-Tabib, Atefeh; Amiriani, Taghi

    2014-01-01

    Gastric cancer (GC) is the second cause of cancer related death in the world. It may develop by progression from its precancerous condition, called gastric atrophy (GA) due to gastritis. The aim of this study was to evaluate the accuracy of serum levels of pepsinogens (Pg) and gastrin-17 (G17) as non-invasive methods to discriminate GA or GC (GA/GC) patients. Subjects referred to gastrointestinal clinics of Golestan province of Iran during 2010 and 2011 were invited to participate. Serum levels of PgI, PgII and G17 were measured using a GastroPanel kit. Based on the pathological examination of endoscopic biopsy samples, subjects were classified into four groups: normal, non-atrophic gastritis, GA, and GC. Receiver operating curve (ROC) analysis was used to determine cut-off values. Indices of validity were calculated for serum markers. Study groups were normal individuals (n=74), non-atrophic gastritis (n=90), GA (n=31) and GC patients (n=30). The best cut-off points for PgI, PgI/II ratio, G17 and HP were 80 μg/L, 10, 6 pmol/L, and 20 EIU, respectively. PgI could differentiate GA/GC with high accuracy (AUC=0.83; 95%CI: 0.76-0.89). The accuracy of a combination of PgI and PgI/II ratio for detecting GA/GC was also relatively high (AUC=0.78; 95%CI: 0.70-0.86). Our findings suggested PgI alone as well as a combination of PgI and PgI/II ratio are valid markers to differentiate GA/GC. Therefore, Pgs may be considered in conducting GC screening programs in high-risk areas.

  18. 'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example.

    Science.gov (United States)

    Rosewall, Tara; Yan, Jing; Alasti, Hamideh; Cerase, Carla; Bayley, Andrew

    2017-04-01

    Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer. © 2016 The Royal Australian and New Zealand College of Radiologists.

  19. Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

    Energy Technology Data Exchange (ETDEWEB)

    Corn, Paul G., E-mail: pcorn@mdanderson.org [Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Song, Danny Y. [Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland (United States); Heath, Elisabeth; Maier, Jordan [Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (United States); Meyn, Raymond [Department of Experimental Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Kuban, Deborah [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); DePetrillo, Thomas A. [Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts (United States); Mathew, Paul, E-mail: pmathew@tuftsmedicalcenter.org [Department of Hematology-Oncology, Tufts Medical Center, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

    2013-07-01

    Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

  20. Superior metastasis-free survival for patients with high-risk prostate cancer treated with definitive radiation therapy compared to radical prostatectomy: A propensity score-matched analysis

    Directory of Open Access Journals (Sweden)

    Stephanie Markovina, MD, PhD

    2018-04-01

    Full Text Available Purpose: For high-risk prostate cancer (HR-PCa in men with a life expectancy of at least 10 years, the National Comprehensive Cancer Network recommends radiation therapy (RT plus androgen deprivation therapy (ADT with category 1 evidence or radical prostatectomy (RP as an acceptable initial therapy. Randomized evidence regarding which therapy is optimal for disease control is lacking for men with HR-PCa. We performed a propensity-score-matched comparison of outcomes for men with localized HR-PCa treated with primary RT or RP. Methods and materials: The medical records of patients with localized HR-PCa who were treated at our institution between 2002 and 2011 were reviewed. Patient and disease characteristics, treatment details, and outcomes were collected. A combination of nearest-neighbor propensity score matching on age, Adult Comorbidity Evaluation-27 comorbidity index, prostate-specific antigen, biopsy Gleason scores, and clinical T-stage as well as exact matching on prostate-specific antigen, biopsy Gleason scores, and clinical T-stage was performed. Outcomes were measured from diagnosis. Multivariate Cox proportional hazards regression was used to compare metastasis-free and overall survival. Results: A total of 246 patients were identified with 62 propensity-score-matched pairs. ADT was administered to 6.5% and 80.6% of patients receiving RP and RT, respectively. Five-year rates of metastasis for RP and RT were 33% and 8.9%, respectively (P = .003. Overall survival was not different. Delay of salvage therapy was longer for patients undergoing primary RT (P < .001. Findings were similar when only those patients who did not receive ADT were compared. Conclusions: At our institution, treatment with primary RT resulted in superior metastasis-free survival over RP. This was not accompanied by an improvement in OS.

  1. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS)

    NARCIS (Netherlands)

    Witjes, J.A.; Palou, J.; Soloway, M.; Lamm, D.; Kamat, A.M.; Brausi, M.; Persad, R.; Buckley, R.; Colombel, M.; Bohle, A.

    2013-01-01

    OBJECTIVES: To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guerin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU)

  2. Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: results of monotherapy and combination therapy trials

    Directory of Open Access Journals (Sweden)

    Alecu I

    2018-02-01

    Full Text Available Iulian Alecu, Tsveta Milenkova, Simon R Turner Research and Development, AstraZeneca UK Limited, Cambridge, UKThe tolerability profile of PARP inhibitors often includes hematologic toxicities, and the characterization of these adverse events is important to allow effective management by clinicians. Zhou et al1 recently carried out a meta-analysis of the incidence and relative risks of severe neutropenia, thrombocytopenia, and anemia events in 12 randomized controlled trials of PARP inhibitors, either as monotherapy or in combination with chemotherapy or radiotherapy. The authors concluded that olaparib resulted in a higher incidence of severe (common terminology criteria for adverse events [CTCAE] grade $3 neutropenia when compared with niraparib and veliparib; however, these conclusions are based on inappropriate and incomplete comparisons of hematologic toxicity with olaparib or veliparib in combination with myelotoxic chemotherapy versus niraparib monotherapy. While both monotherapy and combination therapy olaparib studies are discussed in the paper, the neutropenia analysis is based on olaparib data solely from studies in combination with paclitaxel or paclitaxel plus carboplatin. In order to inform the practicing clinician of the relative risk of hematologic toxicity associated with different PARP inhibitors, direct comparison needs to be conducted based on monotherapy, where applicable, as per the approved drug indication, otherwise the reader is given misleading information.View the original paper by Zhou et al.