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  1. Metastatic Cancer

    Science.gov (United States)

    Metastatic cancer is cancer that spreads from its site of origin to another part of the body. Learn how cancer spreads, possible symptoms, common sites where cancer spreads, and how to find out about treatment options.

  2. Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance

    Directory of Open Access Journals (Sweden)

    Lindkær-Jensen S

    2015-03-01

    Full Text Available Steen Lindkær-Jensen,1 Stig Larsen,2 Nina Habib-Lindkær-Jensen,1 Hans E Fagertun3 1Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London, UK; 2Center of Epidemiology and Biostatistics, Faculty of Veterinary Medicine, University of Life Science, Oslo, Norway; 3Meddoc Research AS, Skjetten, Norway Abstract: A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life.Methods: The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose–response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design.Results: Hemoglobin (Hb and hematocrit (Hct increased significantly (P<0.01 during BP-C1 treatment, while red blood cell (RBC count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC was in anemic patients (P≤0.01. WBC count and neutrophils increased significantly (P=0.01 in the overall data. WBCs and neutrophils (P<0.01, eosinophils (P=0.05 and monocytes (P<0.01 increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04. An increase in K+, Ca2+, and PO43- was most pronounced in patients with low baseline levels (P≤0.02. A similar pattern detected for Mg2+, prothrombin

  3. Ziv-aflibercept in metastatic colorectal cancer

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    Patel A

    2013-12-01

    Full Text Available Anuj Patel, Weijing Sun Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: The combination of cytotoxic chemotherapy and antiangiogenic agents has become a conventional treatment option for patients with metastatic colorectal cancer. Ziv-aflibercept is a fusion protein which acts as a decoy receptor for vascular endothelial growth factor (VEGF-A, VEGF-B, and placental growth factor (PlGF; it was approved in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing fluoropyrimidine-based regimen. Herein we review the role of tumor angiogenesis as the rationale for antiangiogenic therapy, the clinical data associated with ziv-aflibercept, and its current role as a treatment option compared to other antiangiogenic agents, such as bevacizumab and regorafenib. Keywords: aflibercept, angiogenesis, colorectal cancer

  4. Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

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    Kunos, Charles A., E-mail: charles.kunos@UHhospitals.org [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Debernardo, Robert [Department of Obstetrics and Gynecology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Radivoyevitch, Tomas [Department of Epidemiology and Biostatistics, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Fabien, Jeffrey; Dobbins, Donald C.; Zhang Yuxia; Brindle, James [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States)

    2012-09-01

    Purpose: To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. Methods and Materials: A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile, 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. Results: In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. Conclusions: Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.

  5. Sorafenib for Metastatic Thyroid Cancer

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    A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

  6. 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.

  7. Chemotherapy of metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Colorectal cancer is one of the leading causes of cancer incidence and mortality. In 2008 inRussian Federation55 719 new cases of colorectal cancer were diagnosed and 37 911 patients died of this disease. A significant progress was achieved in metastatic colorectal cancer treatment during the last decades. A lot of treatment options became available: from 5-fluoruracil monotherapy to combined treatment treatment schemes including surgery. A group of patients with isolated liver metastases was distinguished, who can achieve 5-year survival rate of 40 % after systemic treatment and surgery. Today, based on clinical data and molecular analysis, we come close to individualized treatment of this patient group. In this literature review results of metastatic colorectal cancer chemotherapy are being analyzed and rational treatment tactic is proposed based on therapy goals. 

  8. A Metastatic Ovarian Angiosarcoma Mimicking Hematologic Neoplasia at Diagnosis

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    Rafael Dezen Gaiolla

    2014-04-01

    Full Text Available Angiosarcomas are rare aggressive neoplasms of vascular endothelial origin with a high metastatic rate and poor prognosis. Involvement of the bone marrow by the angiosarcoma is exceedingly uncommon, and there have only been a few cases reported in the literature to date. Clinical manifestations and common laboratory findings of bone marrow involvement can mimic other more common bone marrow-replacing neoplasias such as lymphomas and acute leukemia. A definitive diagnosis is difficult to make from cytologic material, probably due to an associated bone marrow fibrosis, and requires bone marrow trephine biopsy with an immunohistochemical profile. Here we had the opportunity to study a case of metastatic angiosarcoma with positive cytologic findings and an unusual presentation that challenged its primary diagnosis.

  9. A Metastatic Ovarian Angiosarcoma Mimicking Hematologic Neoplasia at Diagnosis

    Science.gov (United States)

    Gaiolla, Rafael Dezen; Duarte, Ívison Xavier; Bacchi, Carlos Eduardo; Paiva, Carlos Eduardo

    2014-01-01

    Angiosarcomas are rare aggressive neoplasms of vascular endothelial origin with a high metastatic rate and poor prognosis. Involvement of the bone marrow by the angiosarcoma is exceedingly uncommon, and there have only been a few cases reported in the literature to date. Clinical manifestations and common laboratory findings of bone marrow involvement can mimic other more common bone marrow-replacing neoplasias such as lymphomas and acute leukemia. A definitive diagnosis is difficult to make from cytologic material, probably due to an associated bone marrow fibrosis, and requires bone marrow trephine biopsy with an immunohistochemical profile. Here we had the opportunity to study a case of metastatic angiosarcoma with positive cytologic findings and an unusual presentation that challenged its primary diagnosis. PMID:24847252

  10. Regulation of Metastatic Breast Cancer Dormancy

    Science.gov (United States)

    2015-09-01

    to begin to unravel the complex resistance seen with metastatic breast cancer , particularly the fear of recurrence 5-10 years after apparent cure...AWARD NUMBER: W81XWH-14-1-0062 TITLE: Regulation of Metastatic Breast Cancer Dormancy PRINCIPAL INVESTIGATOR: Sarah Wheeler CONTRACTING...Metastatic Breast Cancer Dormancy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0062 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sarah Wheeler 5d

  11. General Information about Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... Head and Neck Cancer Patient Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ... Oropharyngeal Cancer Screening Health Professional Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ...

  12. Stages of Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... Head and Neck Cancer Patient Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ... Oropharyngeal Cancer Screening Health Professional Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ...

  13. Treatment Option Overview (Metastatic Squamous Neck Cancer with Occult Primary)

    Science.gov (United States)

    ... Head and Neck Cancer Patient Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ... Oropharyngeal Cancer Screening Health Professional Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ...

  14. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Science.gov (United States)

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  15. [Role of surgery in metastatic breast cancer].

    Science.gov (United States)

    Medina-Franco, Heriberto; Suárez-Bobadilla, Yoli Lizbeth

    2012-01-01

    Breast cancer is the most common malignant tumor in Mexican women and very often patients present with advanced stages. Patients with metastatic breast cancer have limited therapeutic options and the mainstay of treatment in this disease stage is systemic chemotherapy Traditionally, the role of surgery in this context is limited to symptom palliation. The increase in efficiency of chemotherapy drugs and the new endocrine and molecular targeted therapy has prolonged the life expectancy of this group of patients and has expanded surgical indications beyond palliation. Some recent institutional reports suggest increasing survival of patients who undergo resection of limited metastatic disease. On another hand, there are reports of survival benefit when the primary tumor is removed even in presence of metastatic disease. We conducted a systematic review of the literature with the objective to analyze the role of surgery in the multidisciplinary management of metastatic breast cancer in order to improve the prognosis of this increasing group of patients.

  16. Metastatic urachal cancer responding to FOLFOX chemotherapy.

    Science.gov (United States)

    Tran, Ben; McKendrick, Joe

    2010-04-01

    Metastatic urachal cancer is a rare disease and subsequently, does not have a defined systemic treatment. Although urachal cancer is most commonly adenocarcinoma and histologically similar to colon cancer, treatment selection is usually based upon location (the proximity of the urachus to the bladder) with bladder cancer regimens the most commonly prescribed. We report a case of metastatic urachal cancer where the immunohistochemical profile's similarities to colon cancer led to treatment with colon cancer specific chemotherapy. Our case is the first to report urachal cancer treated with and responding to modified FOLFOX6. In the age of targeted therapy, where molecular biology drives treatment selection, our case highlights that in rare tumors, when evidence is often lacking, a common sense approach can often prevail.

  17. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E

    2014-01-01

    BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have...... the most common clinically relevant adverse events associated with enzalutamide treatment. CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas...... skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P

  18. Targeting metastatic colorectal cancer – present and emerging treatment options

    Directory of Open Access Journals (Sweden)

    Ciombor KK

    2014-07-01

    Full Text Available Kristen K Ciombor,1 Jordan Berlin21Division of Medical Oncology, Department of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 2Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USAAbstract: Metastatic colorectal cancer is a significant cause of morbidity and mortality in the US and around the world. While several novel cytotoxic and biologic therapies have been developed and proven efficacious in the past two decades, their optimal use in terms of patient selection, drug combinations, and regimen sequences has yet to be defined. Recent investigations regarding anti-epidermal growth factor receptor therapies include the comparison of single-agent panitumumab and cetuximab, the benefit of adding cetuximab to chemotherapy in the conversion therapy setting, the comparison of cetuximab and bevacizumab when added to first-line chemotherapy, and predictive biomarkers beyond KRAS exon 2 (codons 12 and 13 mutations. With respect to anti-vascular endothelial growth factor therapies, new data on continuing bevacizumab beyond disease progression on a bevacizumab-containing chemotherapy regimen, the addition of bevacizumab to triplet chemotherapy in the first-line setting, maintenance therapy with bevacizumab plus either capecitabine or erlotinib, the addition of aflibercept to chemotherapy, and regorafenib as monotherapy have emerged. Recent scientific and technologic advances in the field of metastatic colorectal cancer promise to elucidate the biological underpinnings of this disease and its therapies for the goal of improving personalized treatments for patients with metastatic colorectal cancer.Keywords: cetuximab, panitumumab, bevacizumab, aflibercept, regorafenib, biomarker

  19. Sorafenib makes headway on metastatic thyroid cancer.

    Science.gov (United States)

    2013-07-01

    In a randomized phase III clinical trial, patients with metastatic differentiated cancer of the thyroid who were treated with sorafenib achieved median progression-free survival of 10.8 months, compared with 5.8 months among patients treated with placebo.

  20. An Unusual Course of Metastatic Gastroesophageal Cancer

    Directory of Open Access Journals (Sweden)

    William H. Smith

    2015-01-01

    Full Text Available We are reporting on a case of a 41-year-old woman who presented with metastatic gastroesophageal junction cancer and who achieved prolonged survival with a multimodal treatment approach. After initially experiencing robust response to chemotherapy, she was treated for distant recurrence with palliative radiation to the gastrohepatic and supraclavicular lymph nodes and subsequently, given her unusual near-complete response, with reirradiation to the abdomen with curative intent for residual disease. The case presented is unique due to the patient’s atypical treatment course, including technically difficult reirradiation to the abdomen, and the resulting prolonged survival despite metastatic presentation.

  1. Paclitaxel and doxorubicin in metastatic breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T

    1996-01-01

    For the past decades the anthracyclines have been regarded as among the most active drugs for the treatment of metastatic breast cancer. However, the 5-year survival rate in patients with stage IV breast cancer continues to be below 20%, and new active drugs and drug combinations clearly must...... be explored. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be highly effective in treating patients with advanced breast cancer, including those with anthracycline-resistant breast cancer, a fact that has led to efforts to combine paclitaxel and anthracyclines...

  2. Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer?

    Science.gov (United States)

    Lobbezoo, D J A; van Kampen, R J W; Voogd, A C; Dercksen, M W; van den Berkmortel, F; Smilde, T J; van de Wouw, A J; Peters, F P J; van Riel, J M G H; Peters, N A J B; de Boer, M; Peer, P G M; Tjan-Heijnen, V C G

    2015-04-28

    We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients. Consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy. Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI 24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI 24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI 24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy. Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI 24 months, patients with de novo metastatic breast cancer had similar outcome.

  3. Metastatic breast cancer: The Odyssey of personalization.

    Science.gov (United States)

    Sonnenblick, A; Pondé, N; Piccart, M

    2016-10-01

    Metastatic breast cancer is the most frequent cause of cancer death for women worldwide. In the last 15 years, a large number of new agents have entered clinical use, a result of the dramatic increase in our understanding of the molecular underpinnings of metastatic breast cancer. However, while these agents have led to better outcomes, they are also at the root cause of increasing financial pressure on healthcare systems. Moreover, decision making in an era where every year new agents are added to the therapeutic armamentarium has also become a significant challenge for medical oncologists. In the present article, we will provide an ample review on the most recent developments in the field of treatment of the different subtypes of metastatic breast cancer with a critical discussion on the slow progress made in identifying response biomarkers. New hopes in the form of ctDNA monitoring and functional imaging will be presented. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Colon Cancer Metastatic to the Biliary Tree

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    Strauss, Alexandra T.; Clayton, Steven B.; Markow, Michael; Mamel, Jay

    2016-01-01

    Metastasis of colon adenocarcinoma is commonly found in the lung, liver, or peritoneum. Common bile duct (CBD) tumors related to adenomas from familial adenomatous polyposis metastasizing from outside of the gastrointestinal tract have been reported. We report a case of biliary colic due to metastatic colon adenocarcinoma to the CBD. Obstructive jaundice with signs of acalculous cholecystitis on imaging in a patient with a history of colon cancer should raise suspicion for metastasis to CBD.

  5. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie

    2012-01-01

    Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC...... and presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along...

  6. Radioisotopes in management of metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Amar Raval

    2016-01-01

    Full Text Available Introduction: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. Methods: Medline publications from 1990 to 2016 were searched and reviewed to assess the use of currently approved radioisotopes in the management of prostate cancer including emerging data regarding integration with novel systemic therapies. New positron emission tomography-based radiotracers for advanced molecular imaging of prostate cancer were also queried. Results: Radioisotopes play a crucial role in the diagnosis and treatment of prostate cancer in the definitive and metastatic setting. Molecular imaging of prostate cancer and theranostics are currently being investigated in the clinical arena. Conclusions: The use of modern radioisotopes in selected patients with mCRPC is associated with improvements in overall survival, pain control, and quality of life.

  7. Metastatic Prostate Cancer of Hand

    Directory of Open Access Journals (Sweden)

    Akihito Nagano

    2016-01-01

    Full Text Available Soft tissue metastases of prostate cancer to other sites are extremely rare, and, to our best knowledge, there have been no reports of metastasis to soft tissue of the hand. A 63-year-old man was diagnosed with prostatic cancer. During treatment, bone and soft tissue metastases to the right hand, appearing in the first web space, were observed. The tumor was resected, along with both the first and second metacarpal bones. The thumb was reconstructed by pollicization of the remaining index finger, enabling the patient to use the pollicized thumb for activities of daily living. This is the first case report of prostate cancer metastasizing to the soft tissue in hand. After wide resection, pollicization was able to reconstruct a functional hand and thumb.

  8. Clinical holistic medicine: metastatic cancer.

    Science.gov (United States)

    Ventegodt, Søren; Solheim, Elin; Saunte, Mads E; Morad, Mohammed; Kandel, Isack; Merrick, Joav

    2004-10-28

    We believe that the consciousness-based/holistic medical toolbox has a serious additional offer to cancer patients and, as a consequence, designed a treatment for the patient with metastasized cancer. From a holistic perspective, cancer can be understood as a simple disturbance of the cells, arising from the tissue holding on to a trauma with strong emotional content. This is called "a blockage", where the function of the cells is allocated from their original function in the tissue to a function of holding emotions. We hope to be able not only to improve the quality of life, but also to improve survival and in some cases even induce spontaneous remission of the metastasized cancer. This paper describes how work with a patient with metastasized cancer can be done in the holistic clinical practice in 14 days on an individual basis, helping the patient to recover her human character, purpose of life, coherence, and will to live, thus improving quality of life and possibly also survival time. The holistic therapeutic work includes (1) teaching existential theory, (2) working with life perspective and philosophy of life, (3) helping the patient to acknowledge the state of the disease and the feelings connected to it, and finally (4) getting the patient into the holistic state of healing: (a) feeling old repressed emotions, (b) understanding why she got sick from a holistic point of view, and finally (c) letting go of the negative beliefs and decisions that made her sick according to the holistic theory of nongenetic diseases. The theory of the human character, the quality of life theories, the holistic theory of cancer, the holistic process theory of healing, the theory of (Antonovsky) coherence, and the life mission theory are the most important theories for the patient to find hope and mobilize the will to fight the cancer and survive. The patient went through the following phases: (1) finding the purpose of life and hidden resources; (2) confronting denial; (3

  9. Clinical Holistic Medicine: Metastatic Cancer

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2004-01-01

    Full Text Available We believe that the consciousness-based/holistic medical toolbox has a serious additional offer to cancer patients and, as a consequence, designed a treatment for the patient with metastasized cancer. From a holistic perspective, cancer can be understood as a simple disturbance of the cells, arising from the tissue holding on to a trauma with strong emotional content. This is called “a blockage”, where the function of the cells is allocated from their original function in the tissue to a function of holding emotions. We hope to be able not only to improve the quality of life, but also to improve survival and in some cases even induce spontaneous remission of the metastasized cancer. This paper describes how work with a patient with metastasized cancer can be done in the holistic clinical practice in 14 days on an individual basis, helping the patient to recover her human character, purpose of life, coherence, and will to live, thus improving quality of life and possibly also survival time. The holistic therapeutic work includes (1 teaching existential theory, (2 working with life perspective and philosophy of life, (3 helping the patient to acknowledge the state of the disease and the feelings connected to it, and finally (4 getting the patient into the holistic state of healing: (a feeling old repressed emotions, (b understanding why she got sick from a holistic point of view, and finally (c letting go of the negative beliefs and decisions that made her sick according to the holistic theory of nongenetic diseases. The theory of the human character, the quality of life theories, the holistic theory of cancer, the holistic process theory of healing, the theory of (Antonovsky coherence, and the life mission theory are the most important theories for the patient to find hope and mobilize the will to fight the cancer and survive. The patient went through the following phases: (1 finding the purpose of life and hidden resources; (2 confronting

  10. Metastatic Breast Cancer and Hormonal Receptor Status among a ...

    African Journals Online (AJOL)

    Background: Breast cancer is the third commonest cancer in women in Uganda. The majority of breast cancer patients in Uganda present with advanced disease. Many studies show that metastatic lesions frequently lodge in bones, lung and liver. Tumour hormone receptor status correlates with site of metastatic lesions and ...

  11. Duodenal Obstruction as First Presentation of Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sami Khairy

    2015-01-01

    Full Text Available The metastatic breast cancer to the duodenum is rare in spite of common breast cancer. In this paper, we are reporting a rare case of 50-year-old lady who presented with intestinal obstruction as result of metastatic breast cancer which completely responds to chemotherapy. The tumor presents again as brain metastasis after stop of Herceptin due to cardiac toxicity.

  12. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. Meryem Aitelhaj, Siham Lkhoyaali, Ghizlane Rais, Saber Boutayeb, Hassan Errihani ...

  13. Intra-abdominal splenosis mimicking metastatic cancer.

    Science.gov (United States)

    Short, Nicholas J; Hayes, Teresa G; Bhargava, Peeyush

    2011-03-01

    Splenosis, the heterotopic autotransplantion of splenic tissue, is a common benign condition among patients with a history of splenic trauma. Most cases of splenosis are intra-abdominal due to direct seeding of surrounding structures, although these ectopic rests may occur almost anywhere in the body, and its diffuse nature may raise the suspicion of metastatic cancer. Confirmation of splenic tissue can be made by technetium-99m (Tc-99m) sulfur colloid scintigraphy or with Tc-99m heat-damaged red blood cells; however, in some cases, biopsy may be required for definitive diagnosis. Here, the authors present a patient with a remote history of posttraumatic splenectomy who was discovered to have multiple intra-abdominal nodules by CT scan. A diagnosis of diffuse metastatic disease was initially considered before a diagnosis of intraabdominal splenosis was ultimately made with the aid of Tc-99m sulfur colloid single-positron emission computed tomography (SPECT) and computed tomography imaging.

  14. Durable response using regorafenib in an elderly patient with metastatic colorectal cancer: case report

    Directory of Open Access Journals (Sweden)

    Tang R

    2015-11-01

    Full Text Available Ronald Tang,1 Tatiana Kain,2 June Herman,2 Tara Seery1 1Division of Hematology-Oncology, 2Division of Nuclear Medicine and Molecular Imaging, University of California, Irvine, Orange, CA, USA Abstract: Regorafenib, an oral multikinase inhibitor, was approved in September 2012 by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer. Since this time, however, few case reports outlining real-world usage have been published in the literature. Here, we detail the clinical history of an elderly woman with KRAS wild-type colon cancer who received regorafenib after prior treatment with other agents. We show that by employing dose modification strategies to address adverse events, this patient was able to remain on therapy for 11 months and achieve stable disease. Keywords: regorafenib, metastatic colorectal cancer, oral multikinase inhibitor

  15. Cetuximab in treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Guren, Tormod Kyrre; Thomsen, Maria Morandi; Kure, Elin H

    2017-01-01

    BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival......, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy. CONCLUSIONS: Adding cetuximab to Nordic FLOX did not provide any clinical...

  16. 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.

  17. Organtropic Metastatic Secretomes and Exosomes in Breast Cancer

    Science.gov (United States)

    2016-10-01

    breast cancer cell lines. We also plan to isolate miRNAs from the 4T1 series of mouse mammary tumor cell lines with progressively higher lung metastatic...identified distinct protein profiles (Lyden) of breast cancer cell lines with differential lung metastatic capabilities whose pathological relevance

  18. Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer

    Science.gov (United States)

    2017-09-07

    Carcinoma of the Collecting Ducts of Bellini; Chromophobe Renal Cell Carcinoma; Kidney Medullary Carcinoma; Kidney Oncocytoma; Metastatic Renal Cell Cancer; Papillary Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage IV Renal Cell Cancer

  19. Molecularly targeted drugs for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Cheng YD

    2013-11-01

    Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

  20. Advancing Immunotherapy in Metastatic Breast Cancer.

    Science.gov (United States)

    Mansour, Mariam; Teo, Zhi Ling; Luen, Stephen J; Loi, Sherene

    2017-06-01

    Despite many advances in the treatment of breast cancer, the development of metastatic disease remains an incurable and frequent cause of cancer death for women worldwide. An improved understanding of the role of host immunosurveillance in modulating breast cancer disease biology, as well as impressive survival benefits seen to checkpoint blockade in other malignancies have provided great hope for an expanding role of immunotherapies in breast cancer management. While these novel therapies are currently being investigated in clinical trials, signals of efficacy, and tolerability in early phase studies suggest these will eventually make their way into standard practice algorithms. Ongoing research has highlighted a high degree of intertumoural heterogeneity in tumour lymphocytic infiltrates, suggesting some tumours or subtypes are more immunogenic than others. Furthermore, tumour intrinsic mechanisms of immune evasion are beginning to be uncovered, potentially representing key therapeutic targets to use in combination with checkpoint blockade, exemplifying the emerging concept of personalised medicine approaches to immune therapies. Subsequently, different immunotherapeutic strategies may be required based on stratification by these factors-for the minority of tumours with a high level of pre-existing immunity, immune checkpoint blockade monotherapy may be sufficient. However, for the majority of tumours with lower levels of pre-existing immunity, combination approaches will likely be required to achieve maximal therapeutic effect. Results of ongoing clinical trials including combinations with chemotherapy, radiation therapy, and targeted therapies are eagerly awaited.

  1. Metastatic Breast Cancer and Hormonal Receptor Status among a ...

    African Journals Online (AJOL)

    hormone receptor status correlates with site of metastatic lesions and survival among breast cancer patients. Objective: To determine the sites of metastatic breast lesions and how they relate to the hormonal receptor status. Methods: In this cross sectional descriptive study, 71 women with histologically confirmed incident ...

  2. Hematological issues in critically ill patients with cancer.

    Science.gov (United States)

    Carlson, Karen S; DeSancho, Maria T

    2010-01-01

    Patients with solid and hematologic malignancies presenting with major bleeding or thrombotic complications, potentially life-ending events in a cancer patient's clinical course, usually require admission to an intensive care unit (ICU), making their diagnosis and management even more important for the intensivist. Given the significant advances in the diagnosis and treatment of almost all types of cancers in recent years, the intensivist is likely to encounter an ever-increasing number of cancer patients in the ICU setting with these complications. Abnormal hemostasis can occur as a consequence of both the pathology and treatment of cancer. Because cancer can have multiple effects on hemostatic equilibrium, treatment of these complications can be more complex than in the general population. This article reviews the physiology of coagulation and fibrinolysis, with special attention to those aspects that are most frequently altered in the setting of malignancy. The pathophysiology of bleeding and thrombotic complications specific to critically ill cancer patients are then detailed, and the diagnostic and therapeutic strategies are discussed. Special emphasis is placed on new cancer medications that have an effect on hemostasis, and on novel clotting and anticoagulant agents that are available to the intensivist for the management of these patients.

  3. Cytoreductive surgery for men with metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Nikolas Katelaris

    2016-09-01

    Conclusions: This data supports recent findings demonstrating that radical prostatectomy for metastatic prostate cancer is feasible. Further studies are needed to explore the role of cytoreductive surgery with regards to the potential oncological benefit.

  4. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer

    NARCIS (Netherlands)

    Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.M.; Schrama, J.G.; Erdkamp, F.L.G.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.M.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.J.M.; Dalesio, O.; Punt, C.J.A.

    2009-01-01

    Background: Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor (EGFR) antibody cetuximab to

  5. General Information about Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... lymph nodes in the neck or around the collarbone , it is called metastatic squamous neck cancer. The ... of the neck between the jawbone and the collarbone , including the following: All lymph nodes . The jugular ...

  6. Dyadic Coping in Metastatic Breast Cancer

    Science.gov (United States)

    Badr, Hoda; Carmack, Cindy L.; Kashy, Deborah A.; Cristofanilli, Massimo; Revenson, Tracey A.

    2011-01-01

    Objective Couples facing metastatic breast cancer (MBC) must learn to cope with stressors that can affect both partners' quality of life as well as the quality of their relationship. Common dyadic coping involves taking a “we” approach, whereby partners work together to maintain their relationship while jointly managing their shared stress. This study prospectively evaluated whether common dyadic coping was associated with less cancer-related distress and greater dyadic adjustment for female MBC patients and their male partners. Design Couples (N = 191) completed surveys at the start of treatment for MBC (baseline), and 3 and 6 months later. Main Outcome Measures Cancer-related distress was assessed with the Impact of Events Scale; dyadic adjustment was assessed using the short-form of the Dyadic Adjustment Scale. Results Multilevel models using the couple as the unit of analysis showed that the effects of common positive dyadic coping on cancer-related distress significantly differed for patients and their partners. Whereas partners experienced slightly lower levels of distress, patients experienced slightly higher levels of distress. Although patients and partners who used more common negative dyadic coping experienced significantly greater distress at all times, the association was stronger for patients. Finally, using more common positive dyadic coping and less common negative dyadic coping was mutually beneficial for patients and partners in terms of greater dyadic adjustment. Conclusion Our findings underscore the importance of couples working together to manage the stress associated with MBC. Future research may benefit from greater focus on the interactions between patients and their partners to address ways that couples can adaptively cope together. PMID:20230090

  7. Apparent diffusion coefficient for discriminating metastatic from non-metastatic lymph nodes in primary rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Een Young, E-mail: seirosera@naver.com; Kim, Seung Ho, E-mail: radiresi@gmail.com; Yoon, Jung-Hee, E-mail: radyjh@hanmail.net; Lee, Yedaun, E-mail: chosai@hanmail.net; Lim, Yun-Jung, E-mail: iihiye@hanmail.net; Kim, Seon-Jeong, E-mail: bluesingirl@naver.com; Baek, Hye Jin, E-mail: sartre81@gmail.com; Eun, Choong Ki, E-mail: ilovegod@chollian.net

    2013-11-01

    Objective: To investigate whether the apparent diffusion coefficient (ADC) could be used to discriminate metastatic from non-metastatic lymph nodes (LNs) in patients with primary rectal cancer. Methods: This study investigated 34 patients (male: 12, female: 22, mean: 62.7, range: 37–82) who underwent 1.5-T MRI with diffusion-weighted imaging (DWI) and subsequent surgical resection. A blinded radiologist measured the ADC value in each regional LN after referring to the T2-weighted images and DWI. The t-test was used to compare the mean ADC values of the metastatic and non-metastatic LNs. A ROC analysis was performed to calculate the diagnostic performance and obtain the optimal cut-off. The histopathological results were used as the reference standard. Results: 114 LNs (46 metastatic and 68 non-metastatic) were matched and analyzed. The mean ADC of the metastatic LNs was significantly lower than that of the non-metastatic LNs (0.9 ± 0.15 × 10{sup −3} mm{sup 2}/s; 1.1 ± 0.22 × 10{sup −3} mm{sup 2}/s, P < 0.0001). The area under the ROC curve was 0.734 (95% confidence interval, 0.644–0.812). When an ADC value of 1.0 × 10{sup −3} mm{sup 2}/s was used as the cut-off, a maximum accuracy of 72% was calculated (sensitivity, 78%; specificity, 67%). Conclusions: Although ADC could be used to discriminate metastatic from non-metastatic LNs, the diagnostic accuracy is approximately 70%.

  8. Metastatic Breast Cancer to the Stomach Resembling Early Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Fumikata Hara

    2010-04-01

    Full Text Available Breast cancer metastases to the stomach are very rare. As characteristics of breast cancer metastases to the stomach, metastases of lobular carcinoma, mainly with signet ring cells, are frequently observed, and they are often difficult to distinguish from a primary gastric cancer with signet ring cells. Moreover, because no characteristic symptoms are shown and they involve a submucosal lesion, it is difficult to make a radiographic diagnosis. However, if a gastric lesion is observed after breast carcinoma surgery, differentiation between a gastric primary lesion and a metastatic lesion is very important in order to determine treatment. We encountered a case that was diagnosed as early gastric cancer discovered using an endoscope 2 years after surgery and which was found to be breast cancer metastasis to the stomach by gross cystic disease fluid protein (GCDFP and cytokeratin (CK 7/20 immunostaining of the biopsy tissue. Here, we report our findings of this unique case.

  9. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2016-10-01

    Mary Bowen Project Role: Research Assistance on animal work Researcher Identifier: Nearest person month worked: 2 Contributions to Project: Ms...AD______________ AWARD NUMBER: W81XWH-14-1-0552 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0552 5c. PROGRAM ELEMENT NUMBER

  10. Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

    Science.gov (United States)

    2017-09-05

    Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

  11. Indirect costs associated with metastatic breast cancer.

    Science.gov (United States)

    Wan, Yin; Gao, Xin; Mehta, Sonam; Wang, Zhixiao; Faria, Claudio; Schwartzberg, Lee

    2013-10-01

    To compare the indirect costs of productivity loss between metastatic breast cancer (MBC) and early stage breast cancer (EBC) patients, as well as their respective family members. The MarketScan Health and Productivity Management database (2005-2009) was used. Adult BC patients eligible for employee benefits of sick leave and/or short-term disability were identified with ICD-9 codes. Difference in sick leave and short-term disability days was calculated between MBC patients and their propensity score matched EBC cohort and general population (controls) during a 12-month follow-up period. Generalized linear models were used to examine the impact of MBC on indirect costs to patients and their families. A total of 139 MBC, 432 EBC, and 820 controls were eligible for sick leave and 432 MBC, 1552 EBC, and 4682 controls were eligible for short-term disability (not mutually exclusive). After matching, no statistical difference was found in sick leave days and the associated costs between MBC and EBC cohorts. However, MBC patients had significantly higher short-term disability costs than EBC patients and controls (MBC: $6166 ± $9194 vs. EBC: $3690 ± $6673 vs. $558 ± $2487, both p indirect costs compared to EBC patients' families after controlling for key covariates. Productivity loss and associated costs in MBC patients are substantially higher than EBC patients or the general population. These findings underscore the economic burden of MBC from a US societal perspective. Various treatment regimens should be evaluated to identify opportunities to reduce the disease burden from the societal perspective.

  12. Vectors for Treatment of Metastatic Breast Cancer

    Science.gov (United States)

    2006-08-01

    Medicine, Ankara, Turkey ; and 4Yale University, New Haven, Connecticut Abstract S.c. injection of the Ad-sig-tumor-associated antigen (TAA)/ecdCD40L vector...hMUC1 is over- expressed. (Blood. 2004;104:2704-2713) © 2004 by The American Society of Hematology Introduction We previously reported that subcutaneous...The American Society of Hematology 2704 BLOOD, 1 NOVEMBER 2004 VOLUME 104, NUMBER 9 disrupting the regulation of anchorage-dependent growth, which

  13. Evaluation of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Huanhuan [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Department of Radiology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine (China); Yan, Fuhua; Pan, Zilai; Lin, Xiaozhu; Luo, Xianfu; Shi, Cen [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Chen, Xiaoyan [Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Wang, Baisong [Department of Biomedical Statistics, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Zhang, Huan, E-mail: huanzhangy@126.com [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China)

    2015-02-15

    Highlights: • Colorectal cancer is the third most prevalent cancer and the status of the regional lymph nodes in rectal cancer is considered to be one of the most powerful prognostic factor in the absence of distant metastatic disease. Detecting LNs metastasis is still a challenging problem due to the presence of microscopic metastasis or inflammatory swelling of LNs. • We investigated the value of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Our study demonstrated that the quantitative normalized iodine concentration (nIC) could be useful for differentiating metastatic and non-metastatic lymph nodes. The combination of nIC in portal venous phase and conventional size criterion could improve the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of rectal cancer. - Abstract: Objectives: To investigate the value of dual energy spectral CT (DEsCT) imaging in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Methods: Fifty-five patients with rectal cancer underwent the arterial phase (AP) and portal venous phase (PP) contrast-enhanced DEsCT imaging. The virtual monochromatic images and iodine-based material decomposition images derived from DEsCT imaging were interpreted for lymph nodes (LNs) measurement. The short axis diameter and the normalized iodine concentration (nIC) of metastatic and non-metastatic LNs were measured. The two-sample t test was used to compare the short axis diameters and nIC values of metastatic and non-metastatic LNs. ROC analysis was performed to assess the diagnostic performance. Results: One hundred and fifty two LNs including 92 non-metastatic LNs and 60 metastatic LNs were matched using the radiological-pathological correlation. The mean short axis diameter of metastatic LNs was significantly larger than that of the non-metastatic LNs (7.28 ± 2.28 mm vs. 4.90 ± 1.64 mm, P < 0.001). The mean n

  14. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    OpenAIRE

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were conside...

  15. Ixabepilone: a new chemotherapeutic option for refractory metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Shannon Puhalla

    2008-09-01

    Full Text Available Shannon Puhalla, Adam BrufskyUPMC Magee-Womens Cancer Program, University of Pittsburgh, Pittsburgh, Pennsylvania, USAAbstract: Taxane therapy is commonly used in the treatment of metastatic breast cancer. However, most patients will eventually become refractory to these agents. Ixabepilone is a newly approved chemotherapeutic agent for the treatment of metastatic breast cancer. Although it targets microtubules similarly to docetaxel and paclitaxel, ixabepilone has activity in patients that are refractory to taxanes. This review summarizes the pharmacology of ixapebilone and clinical trials with the drug both as a single agent and in combination. Data were obtained using searches of PubMed and abstracts of the annual meetings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium from 1995 to 2008. Ixapebilone is a semi-synthetic analog of epothilone B that acts to induce apoptosis of cancer cells via the stabilization of microtubules. Phase I clinical trials have employed various dosing schedules ranging from daily to weekly to 3-weekly. Dose-limiting toxicites included neuropathy and neutropenia. Responses were seen in a variety of tumor types. Phase II studies verified activity in taxane-refractory metastatic breast cancer. The FDA has approved ixabepilone for use as monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer. Ixabepilone is an efficacious option for patients with refractory metastatic breast cancer. The safety profile is similar to that of taxanes, with neuropathy and neutropenia being dose-limiting. Studies are ongoing with the use of both iv and oral formulations and in combination with other chemotherapeutic and biologic agents.Keywords: ixabepilone, epothilone, metastatic breast cancer, taxane-refractory

  16. Intrahepatic therapy for liver-dominant metastatic colorectal cancer

    OpenAIRE

    De Groote, Kerlijne; Prenen, Hans

    2015-01-01

    In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for loco...

  17. A surprising diagnosis: metastatic prostate cancer causing cervical lymphadenopathy.

    Science.gov (United States)

    Lad, Meher; Sharma, Anita; Patten, Darren K

    2014-02-11

    Cervical lymphadenopathy as an initial presentation for metastatic prostate cancer has been rarely described. Less than 30 cases have been published in medical literature whereby a lymph node biopsy revealed immunoreactivity for prostate-specific antigen (PSA) diagnosing metastatic prostate cancer. We present a unique scenario whereby an asymptomatic patient with previous high-risk gastric cancer presented to clinic with cervical lymphadenopathy. A hunt for a recurrence ensued to no avail and imaging of the head and neck showed no hint of a primary malignancy in those regions. A lymph node biopsy was undertaken which showed elements suggesting metastatic prostate cancer. The patient developed symptoms of urinary outflow obstruction shortly afterwards. Blood tests revealed a very high PSA and a bone scan showed widespread bony metastasis. He was started on androgen deprivation therapy with an improvement of his PSA and symptoms. A regular clinic follow-up has shown stable disease.

  18. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-14-1-0553 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Martin Gleave...Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0553 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Martin Gleave 5d...goal of this project was to develop a novel means to inhibit prostate cancer development and progression. The development of Siah1/2 inhibitors to the

  19. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-14-1-0551 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Ze’ev Ronai...CONTRACT NUMBER Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0551 5c. PROGRAM ELEMENT NUMBER 6... cancer development and progression. The development of Siah1/2 inhibitors to the ubiquitin ligase Siah1/2 was advanced by the ability to develop a Siah1/2

  20. Laser immunotherapy for metastatic pancreatic cancer (Conference Presentation)

    Science.gov (United States)

    Zhou, Feifan

    2017-02-01

    Pancreatic cancer is an extremely malignant disease with high mortality rate. Currently there is no effective therapeutic strategy for highly metastatic pancreatic cancers. Laser immunotherapy (LIT) is a combination therapeutic approach of targeted phototherapy and immunotherapy, which could destroy treated primary tumors with elimination of untreated metastases. LIT affords a remarkable efficacy in suppressing tumor growth in pancreatic tumors in mice, and results in complete tumor regression in many cases. LIT could synergize targeted phototherapy and immunological effects of immunoadjuvant, which represent a promising treatment modality to induce systemic antitumor response through a local intervention, paving the way for the treatment of highly metastatic pancreatic cancers.

  1. Trends in hematological cancer in the elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Ocias, Lukas F; Larsen, Thomas S; Vestergaard, Hanne

    2016-01-01

    BACKGROUND: The number of hematological malignancies is expected to increase as the Danish population ages within the next few decades. Despite this, data on the course of hematological cancers among the oldest patients are sparse with many intervention studies focusing on younger age groups...

  2. Syndecan-1 expression in locally invasive and metastatic prostate cancer.

    Science.gov (United States)

    Chen, David; Adenekan, Bosede; Chen, Lu; Vaughan, E Darracott; Gerald, William; Feng, Ziding; Knudsen, Beatrice S

    2004-02-01

    To determine the significance of syndecan-1 expression, a cell-surface heparan sulfate proteoglycan in localized and metastatic prostate cancer. We performed a retrospective analysis of 76 men with Gleason sum 6 or 7 prostate cancer treated by radical prostatectomy and a separate cohort of 75 men with metastatic prostate cancer. Syndecan-1 immunoreactivity was measured in primary prostate specimens or in samples from metastatic sites and correlated with patient outcome. Syndecan-1 was expressed in normal basal and secretory epithelial cells, 26% of radical prostatectomy specimens, and 35% of metastatic disease. No association was found between syndecan-1 positivity and prostate-specific antigen recurrence in the collective cohort of Gleason sum 6 and 7 cancers. However, when stratified by Gleason sum, syndecan-1 immunoreactivity (immunoreactivity score 150 or greater) was associated with a greater recurrence rate in Gleason sum 7 cancers. Expression of syndecan-1 was significantly greater in soft tissue than in bone metastasis (P = 0.048, Fisher's exact test). Consistent with a possible biochemical role for syndecan-1 in prostate cancer progression and metastasis, syndecan-1 expression correlated with serologic recurrence in Gleason sum 7 prostate cancer and was highly expressed in soft-tissue metastases.

  3. Volume-outcome relation in palliative systemic treatment of metastatic oesophagogastric cancer

    NARCIS (Netherlands)

    Haj Mohammad, N; Bernards, N; van Putten, M; Lemmens, V E P P; van Oijen, M G H; van Laarhoven, H W M

    INTRODUCTION: Palliative systemic therapy has been shown to improve survival in metastatic oesophagogastric cancer. Administration of palliative systemic therapy in metastatic oesophagogastric cancer varies between hospitals. We aimed to explore the association between the annual hospital volume of

  4. Breast cancer metastatic to the kidney with renal vein involvement.

    Science.gov (United States)

    Nasu, Hatsuko; Miura, Katsutoshi; Baba, Megumi; Nagata, Masao; Yoshida, Masayuki; Ogura, Hiroyuki; Takehara, Yasuo; Sakahara, Harumi

    2015-02-01

    The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

  5. Phase II trial of gemcitabine as prolonged infusion in metastatic breast cancer.

    Science.gov (United States)

    Schmid, P; Akrivakis, K; Flath, B; Grosse, Y; Sezer, O; Mergenthaler, H G; Possinger, K

    1999-08-01

    Gemcitabine is an active agent in the treatment of metastatic breast cancer. The phosphorylation of gemcitabine into the active gemcitabine triphosphate (dFdCTP) is catalyzed by deoxycytidine kinase. This enzyme is saturated at plasma concentrations achieved after an infusion over 30 min. Therefore accumulation of higher intracellular dFdCTP concentrations, which may result in an enhanced antineoplastic activity, cannot be achieved by higher dosage, but only by prolonged infusion time. In a previous phase I trial the maximum tolerated dose of gemcitabine given as a 6 h i.v. infusion was 250 mg/m2. The objective of this phase II trial was to determine the efficacy and safety of gemcitabine as prolonged infusion in patients with metastatic breast cancer. Twenty patients [median age 50.4 years, range 35-63 years; performance status EORTC 0 (17 patients), 1 (two patients), 2 (one patient)] with metastatic breast cancer were treated with 250 mg/m2 gemcitabine as infusion over 6 h on days 1, 8 and 15 q3 weeks for up to six courses (median 3.9 courses). Treatment was first line for four patients, second line for five patients and third line or higher for 11 patients. Metastatic sites were liver in 14 patients, bone in 12 patients, lung in eight patients and lymph nodes in nine patients. Nine patients presented two metastatic sites, three patients three and five patients four. All patients were evaluable for response and toxicity. One patient (5%) achieved a complete remission (CR) and four patients (20%) a partial remission (PR) (one patient with CR of visceral metastases but stable bone metastases), for an overall response rate of 25% (five of 20). In addition, six patients (30%) had stable disease and nine (45%) failed to respond to the treatment. Time to progression ranged from 2 to 23 months with a median of 6.3 months. Hematologic toxicity was mild with leukopenia grade 3 in only three patients (15%) and no grade 3 thrombocytopenia. Moderate elevations of liver

  6. [Role of surgery for metastatic breast cancer at diagnosis].

    Science.gov (United States)

    Vlastos, Georges; Rapiti, Elisabetta; Verkooijen, Helena M; Bouchardy, Christine

    2007-10-24

    Metastatic breast cancer is considered as incurable. Treatments of choice are systemic and palliative. Surgery of the primary tumor is usually indicated for palliation of local complications. However recently published studies seem to demonstrate that the surgical excision of the primary tumor increase survival, in particular for patients with negative surgical margins or with only bone metastases. As these studies have been adjusted for factors that may induce biais, only a prospective clinical randomized trial may confirm the role of surgery in the management of metastatic breast cancer.

  7. Chemotherapeutic Treatment of Priapism in Metastatic Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Y. Kitai

    2008-12-01

    Full Text Available A 65-year-old man was admitted with penile tenderness and dysuria due to priapism. Enhanced computed tomography revealed metastatic tumors in the liver, lung, sacrum and lymph nodes. Advanced rectal cancer, detected by colonoscopy as a primary tumor, was treated with chemotherapy (FOLFOX4. Although the rectal cancer showed no change, five months of chemotherapy improveid the priapism, suggesting that chemotherapy can improve rare symptoms of rectal cancer.

  8. 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 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.

  9. Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer?

    Science.gov (United States)

    Mita, Alain C; Figlin, Robert; Mita, Monica M

    2012-12-15

    The taxanes are recognized as a major class of chemotherapeutic agents; however, mechanisms of innate and acquired resistance can limit their usefulness. Cabazitaxel, a novel taxane with microtubule-stabilizing potency similar to docetaxel, exhibits activity against tumor cell lines resistant to paclitaxel and docetaxel. Cabazitaxel showed linear pharmacokinetics and a terminal elimination half-life comparable with that of docetaxel, findings which support dosing as a single infusion in three-week treatment cycles. Dose-ranging studies recommended doses of 20 or 25 mg/m(2) every three weeks. Antitumor activity was shown in patients with advanced cancer and chemotherapy failure (including taxane failure). Other early studies investigated the efficacy of cabazitaxel in pretreated metastatic breast cancer, either as a single agent or in combination with capecitabine. Objective antitumor response rates of up to 24% and sustained tumor stabilizations were also observed. The TROPIC phase III study, conducted in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel, established cabazitaxel as the first chemotherapeutic agent to offer a survival advantage in this patient population. Across these studies, the dose-limiting hematologic toxicity was neutropenia (including febrile neutropenia), usually controllable with colony-stimulating factor/granulocyte-colony stimulating factor support. ©2012 AACR.

  10. Non-invasive actionable biomarkers for metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Jun Luo

    2016-10-01

    Full Text Available In the current clinical setting, many disease management options are available for men diagnosed with prostate cancer. For metastatic prostate cancer, first-line therapies almost always involve agents designed to inhibit androgen receptor (AR signaling. Castration-resistant prostate cancers (CRPCs that arise following first-line androgen deprivation therapies (ADT may continue to respond to additional lines of AR-targeting therapies (abiraterone and enzalutamide, chemotherapies (docetaxel and cabazitaxel, bone-targeting Radium-223 therapy, and immunotherapy sipuleucel-T. The rapidly expanding therapies for CRPC is expected to transform this lethal disease into one that can be managed for prolonged period of time. In the past 3 years, a number of promising biomarkers that may help to guide treatment decisions have been proposed and evaluated, including androgen receptor splice variant-7 (AR-V7, a truncated AR lacking the ligand-binding domain (LBD and mediate constitutively-active AR signaling. Putative treatment selection markers such as AR-V7 may further improve survival benefit of existing therapies and help to accelerate development of new agents for metastatic prostate cancer. In the metastatic setting, it is important to consider compatibility between the putative biomarker with non-invasive sampling. In this review, biomarkers relevant to the setting of metastatic prostate cancer are discussed with respect to a number of key attributes critical for clinical development of non-invasive, actionable markers. It is envisioned that biomarkers for metastatic prostate cancer will continue to be discovered, developed, and refined to meet the unmet needs in both standard-of-care and clinical trial settings.

  11. Actomyosin tension as a determinant of metastatic cancer mechanical tropism

    Science.gov (United States)

    McGrail, Daniel J.; Kieu, Quang Minh N.; Iandoli, Jason A.; Dawson, Michelle R.

    2015-04-01

    Despite major advances in the characterization of molecular regulators of cancer growth and metastasis, patient survival rates have largely stagnated. Recent studies have shown that mechanical cues from the extracellular matrix can drive the transition to a malignant phenotype. Moreover, it is also known that the metastatic process, which results in over 90% of cancer-related deaths, is governed by intracellular mechanical forces. To better understand these processes, we identified metastatic tumor cells originating from different locations which undergo inverse responses to altered matrix elasticity: MDA-MB-231 breast cancer cells that prefer rigid matrices and SKOV-3 ovarian cancer cells that prefer compliant matrices as characterized by parameters such as tumor cell proliferation, chemoresistance, and migration. Transcriptomic analysis revealed higher expression of genes associated with cytoskeletal tension and contractility in cells that prefer stiff environments, both when comparing MDA-MB-231 to SKOV-3 cells as well as when comparing bone-metastatic to lung-metastatic MDA-MB-231 subclones. Using small molecule inhibitors, we found that blocking the activity of these pathways mitigated rigidity-dependent behavior in both cell lines. Probing the physical forces exerted by cells on the underlying substrates revealed that though force magnitude may not directly correlate with functional outcomes, other parameters such as force polarization do correlate directly with cell motility. Finally, this biophysical analysis demonstrates that intrinsic levels of cell contractility determine the matrix rigidity for maximal cell function, possibly influencing tissue sites for metastatic cancer cell engraftment during dissemination. By increasing our understanding of the physical interactions of cancer cells with their microenvironment, these studies may help develop novel therapeutic strategies.

  12. Visualising and quantifying angiogenesis in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Jakobsen, Anders

    2013-01-01

    Angiogenesis plays an important role in tumour growth and dissemination. We have recently shown that blood vessel density, determined by image analysis based on microRNA-126 (miRNA-126) in situ hybridization (ISH) in the primary tumours of metastatic colorectal cancers (mCRC), is predictive...

  13. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    Science.gov (United States)

    2012-09-01

    and the well-known devastating side effects of chemotherapy [4, 5]. Metastatic prostate cancer is a death sentence as it is infeasible to remove... radioactive thymidine to each co-culture. Proliferation is directly correlated to the suppressive capacity of Tregs; increased proliferation equates to

  14. Metastatic breast cancer in a Nigerian tertiary hospital | Adisa ...

    African Journals Online (AJOL)

    Metastatic breast cancer in a Nigerian tertiary hospital. ... Background: Late presentation of breast carcinoma is common in resource-limited countries with attendant poor outcome. Objective: To describe the pattern of clinical ... resource limitations. Improved awareness of the disease is advocated to reduce late presentation.

  15. Assessment of cognitive function in patients with metastatic cancer

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Sandvad, Marlene; Lundorff, Lena

    2017-01-01

    OBJECTIVE: This study aimed at analyzing the validity and reliability of the continuous reaction time (CRT) test, the finger-tapping test (FTT), the Digit Span Test (DST), the Trail Making Test - part B (TMTB), and the Mini-Mental State Examination (MMSE) in patients with metastatic cancer. METHO...

  16. Abiraterone in metastatic prostate cancer without previous chemotherapy

    NARCIS (Netherlands)

    Ryan, C.J.; Smith, M.R.; Bono, J. De; Molina, A.; Logothetis, C.J.; Souza, P. de; Fizazi, K.; Mainwaring, P.; Piulats, J.M.; Ng, S.; Carles, J.; Mulders, P.F.A.; Basch, E.; Small, E.J.; Saad, F.; Schrijvers, D.; Poppel, H. van; Mukherjee, S.D.; Suttmann, H.; Gerritsen, W.R.; Flaig, T.W.; George, D.J.; Yu, E.Y.; Efstathiou, E.; Pantuck, A.; Winquist, E.; Higano, C.S.; Taplin, M.E.; Park, Y.; Kheoh, T.; Griffin, T.; Scher, H.I.; Rathkopf, D.E.

    2013-01-01

    BACKGROUND: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. METHODS: In this double-blind study, we

  17. Optimal duration of systemic treatment in metastatic colorectal cancer

    NARCIS (Netherlands)

    Simkens, Lieke H. J.; Koopman, Miriam; Punt, Cornelis J. A.

    2014-01-01

    With the currently available cytotoxic and targeted drugs, metastatic colorectal cancer (mCRC) may be controlled by systemic treatment for a significant period of time. However, many questions remain about the optimal use of drugs and duration of treatment. We reviewed the data from clinical trials

  18. Metastatic breast cancer - age has a significant effect on survival ...

    African Journals Online (AJOL)

    The data on 217 elderly (aged ≥ 65 years) and 209 middleaged postmenopausal patients with metastatic breast cancer treated in the Department of Medical Oncology, University of Pretoria, from 1976 to 1985 were analysed to determine the effect of age on survival. When considered as a group, the elderly have a more ...

  19. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    Science.gov (United States)

    2017-08-23

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  20. Radium-223 therapy of advanced metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Fosbøl, Marie Øbro; Petersen, Peter Meidahl; Kjaer, Andreas

    2018-01-01

    ratio 2.65 [95% CI: 1.5-4.71];P= 0.001). Likewise, baseline BSI was prognostic for occurrence of hematological toxicity and patients with BSI > 5 had an odds ratio of 3.02 (95% CI: 1.2-7.8;P= 0.02) for toxicity. BSI declined during therapy in 44% of patients who completed three cycles of223RaCl2(n= 52......Aim: To investigate the prognostic value of quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC) receiving Radium-223-dichloride (223RaCl2). We hypothesize that Bone Scan Index (BSI...

  1. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with (177)Lu-DOTATATE.

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium ((177)Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with (177)Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites

  2. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites of

  3. Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, R.G.; Blake, G.M.; Preston, D.F.; McEwan, A.J.; Spicer, J.A.; Martin, N.L.; Wegst, A.V.; Ackery, D.M.

    1989-03-01

    Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

  4. New Epigenetic Therapeutic Intervention for Metastatic Breast Cancer

    Science.gov (United States)

    2017-04-01

    AWARD NUMBER: W81XWH-15-1-0043 TITLE:New Epigenetic Therapeutic Intervention for Metastatic Breast Cancer PRINCIPAL INVESTIGATOR: Ming-Ming Zhou... Nutritional Sciences, The University of Kentucky, College of Medicine, Lexington, Kentucky 40506, USA. 2Markey Cancer Center, The University of Kentucky...40506, USA. 9 Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education , Shanghai Jiao Tong University School of Medicine

  5. Microenvironment -Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

    Science.gov (United States)

    2016-10-01

    mPCSCs)” PI : Dean Tang 1. INTRODUCTION: The main goal of this IDEA project is to help elucidate the cellular and molecular mechanisms underlying...metastatic prostate cancer stem cells 3. ACCOMPLISHMENTS: Dr. Tang, the PI of this grant, together with most lab members, moved from the M.D...repressing CD44. Nat Med 17, 211-215 (2011). 5. Qin, J. et al. The PSA -/lo prostate cancer cell population harbors self-renewing long-term tumor

  6. Gemcitabine and mitoxantrone in metastatic breast cancer: a phase-I-study.

    Science.gov (United States)

    Schmid, Peter; Flath, Bernd; Akrivakis, Konstantin; Heilmann, Volker; Mergenthaler, Hans-Günther; Sezer, Orhan; Kreienberg, Rolf; Possinger, Kurt

    2005-08-01

    Gemcitabine and mitoxantrone are active agents for the treatment of metastatic breast cancer. Due to different modes of action and a favorable toxicity profile they are suitable for combination therapy. This phase I trial was initiated to determine the optimal doses for the combination in patients with metastatic breast cancer. Secondary objectives included the evaluation of the safety and efficacy of the regimen. Patients with metastatic breast cancer were treated with gemcitabine (1000-1400 mg/m(2)) on days 1, 8 and 15 and mitoxantrone (10-14 mg/m(2)) on day 8. Treatment was repeated every 4 weeks for a maximum of 8 cycles. Doses were assigned at registration according to the escalation scheme. Twenty-six patients received a total of 93 cycles at 5 different dose levels. The maximum tolerated doses were 1200 mg/m(2) gemcitabine and 14 mg/m(2) mitoxantrone with grade 4 neutropenia being the dose limiting toxicity. Recommended phase II doses, however, are gemcitabine 1200 mg/m(2) and mitoxantrone 12 mg/m(2) based on a similar median dose intensity and a more favorable toxicity profile. Predominant toxicity was myelosuppression. Most common non-hematological toxicities were nausea, vomiting, alopecia and elevation of liver enzymes. Twenty-one patients were assessable for response. Four patients achieved a partial response accounting for an overall response rate of 19%. In addition, 12 patients (57%) had stable disease and 5 patients (24%) failed to response to the treatment. Median duration of response and duration of clinical benefit were 14 and 9 months, respectively. In this phase I study of gemcitabine and mitoxantrone, the DLT was neutropenia. Recommended phase II doses are gemcitabine 1200 mg/m(2) and mitoxantrone 12 mg/m(2).

  7. Gemcitabine as prolonged infusion and vinorelbine in anthracycline and/or taxane pretreated metastatic breast cancer: a phase II study.

    Science.gov (United States)

    Schmid, Peter; Heilmann, Volker; Schulz, Carsten-Oliver; Dieing, Annette; Lehenbauer-Dehm, Silvia; Jehn, Christian; Sezer, Orhan; Possinger, Kurt; Flath, Bernd

    2005-09-01

    Gemcitabine and vinorelbine are active agents for the treatment of metastatic breast cancer. Prolonged infusion of gemcitabine can result in higher levels of active metabolites compared to shorter administration. This phase II trial was initiated to evaluate the efficacy and tolerability of gemcitabine as prolonged infusion in combination with vinorelbine in anthracycline and/or taxane pretreated patients with metastatic breast cancer. Patients who had received one prior line of chemotherapy for metastatic disease were treated with gemcitabine (350 mg/m2 as 4 h infusion) and vinorelbine (25 mg/m2 on days 1 and 8. Treatment was repeated every 3 weeks for a maximum of six cycles. Of 26 patients enrolled, 84% had received prior anthracycline treatment and 50% prior taxane therapy. In total, one complete and six partial responses were achieved, accounting for an overall response rate of 30.4%. The clinical benefit rate was 47.8%. Median duration of response and median time to progression were 7.3 months and 4.6 months, respectively. Median overall survival was 14.5 months. Although the predominant toxicity was myelosuppression with grade 3/4 neutropenia in 42% of patients, few neutropenic complications resulted. Non-hematological toxicity was generally moderate. Most common non-hematologic toxicities were nausea, vomiting, alopecia, peripheral neuropathy and elevation of liver enzymes. Gemcitabine as prolonged infusion and vinorelbine are a safe and effective combination treatment in anthracycline and/or taxane pretreated patients. Approximately 47.8% of patients derived clinical benefit from treatment. This regimen represents a therapeutic option for patients receiving second-line therapy for metastatic breast cancer.

  8. [Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer].

    Science.gov (United States)

    Lheureux, Stéphanie; Joly, Florence

    2012-09-01

    The management of patients with metastatic castration-resistant prostate cancer is a real challenge. Indeed, after a first line chemotherapy with docetaxel, there was no standard because the treatments were ineffective. Today, several therapeutic options are available with the development of new therapies. Among them, cabazitaxel, semi-synthetic derivative of a natural taxoid, has been developed to its low recognition by the MDR system and power distribution including brain. This new chemotherapy was assessed in patients with metastatic castration-resistant prostate cancer whose disease has progressed during or after docetaxel-based therapy. Treatment with cabazitaxel plus prednisone has improved overall survival of 2.4 months compared to mitoxantrone in the TROPIC phase III. However, hematologic toxicity may be limiting with a risk of febrile neutropenia; hematopoietic growth factors are advised in case of significant neutropenia. The cabazitaxel, Jevtana(®), has been approved in second line after docetaxel. Its position in relation to new types of hormone therapy, as abiraterone acetate, in the same indication requires further investigations, including predictive factors of response. Studies are on going in first line indication (compared to docetaxel) and associated to other new hormone therapies.

  9. Advances in diagnosis and treatment of metastatic cervical cancer.

    Science.gov (United States)

    Li, Haoran; Wu, Xiaohua; Cheng, Xi

    2016-07-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.

  10. Metastatic breast cancer 42 years after bilateral subcutaneous mastectomies.

    Science.gov (United States)

    Jameson, M B; Roberts, E; Nixon, J; Probert, J C; Braatvedt, G D

    1997-01-01

    Subcutaneous mastectomy has a possible role as prophylaxis in patients at high risk of developing breast cancer. A case history is presented of a woman who developed metastatic breast carcinoma 42 years after bilateral subcutaneous mastectomies for non-malignant disease. This case is presented to draw attention to the persistent risk of developing breast cancer even decades after subcutaneous mastectomy and to point out that the role of such surgery in preventing breast cancer has still not been clarified. The appropriateness of prophylactic mastectomy for an individual is better assessed on the absolute risk of breast cancer developing over a defined period rather than the relative risk.

  11. Quantitative mitochondrial redox imaging of breast cancer metastatic potential

    Science.gov (United States)

    Xu, He N.; Nioka, Shoko; Glickson, Jerry D.; Chance, Britton; Li, Lin Z.

    2010-05-01

    Predicting tumor metastatic potential remains a challenge in cancer research and clinical practice. Our goal was to identify novel biomarkers for differentiating human breast tumors with different metastatic potentials by imaging the in vivo mitochondrial redox states of tumor tissues. The more metastatic (aggressive) MDA-MB-231 and less metastatic (indolent) MCF-7 human breast cancer mouse xenografts were imaged with the low-temperature redox scanner to obtain multi-slice fluorescence images of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp). The nominal concentrations of NADH and Fp in tissue were measured using reference standards and used to calculate the Fp redox ratio, Fp/(NADH+Fp). We observed significant core-rim differences, with the core being more oxidized than the rim in all aggressive tumors but not in the indolent tumors. These results are consistent with our previous observations on human melanoma mouse xenografts, indicating that mitochondrial redox imaging potentially provides sensitive markers for distinguishing aggressive from indolent breast tumor xenografts. Mitochondrial redox imaging can be clinically implemented utilizing cryogenic biopsy specimens and is useful for drug development and for clinical diagnosis of breast cancer.

  12. Tumor-infiltrating lymphocytes for the treatment of metastatic cancer

    DEFF Research Database (Denmark)

    Geukes Foppen, M H; Donia, M; Svane, I M

    2015-01-01

    Over the past few years melanoma incidence has been rising steadily, resulting in an increase in melanoma related mortality. Until recently, therapeutic options for metastatic melanoma were scarce. Chemotherapy and, in some countries, IL-2 were the only registered treatment modalities. In the last...... five years, treatment with immunotherapy (anti CTLA-4, anti PD-1, or the combination of these antibodies) has shown very promising results and was able to improve survival in patients with metastatic melanoma. Adoptive cell therapy using tumor-infiltrating lymphocytes is yet another, but highly...... promising, immunotherapeutic strategy for patients with metastatic melanoma. This review will discuss the development of TIL as a treatment option for melanoma, its mode of action and simplification over time, and the possibilities to expand this therapy to other types of cancer. Also, the future directions...

  13. Hardware failure in patients with metastatic cancer to the spine.

    Science.gov (United States)

    Pedreira, Rachel; Abu-Bonsrah, Nancy; Karim Ahmed, A; De la Garza-Ramos, Rafael; Rory Goodwin, C; Gokaslan, Ziya L; Sacks, Justin; Sciubba, Daniel M

    2017-11-01

    The spine is the most common site of skeletal metastases, affecting approximately 30% of individuals with cancer. The aim of surgical treatment for metastatic spine disease is generally palliative to address pain and/or neurologic compromise, significantly improving patients' quality of life. Patients with metastatic spine disease, however, represent a vulnerable cohort and may have comorbidities or previous treatments that impair the structural integrity of spinal hardware. As such, identifying factors that may contribute to hardware failure is an essential component in treating individuals with metastatic spine disease. The aim of this study was to identify pre-operative risk factors associated with hardware failure in patients undergoing surgical treatment for metastatic spine disease. A retrospective cohort study was conducted to include patients surgically treated for metastatic spine tumors between 2003 and 2013, at a single institution. A univariate analysis was initially performed to identify associated factors. Any associated factor with a p-value failure of the spine instrumentation. 1 patient had metastatic prostate cancer, and 2 had metastatic breast cancer. Patient demographics, co-morbidities, tumor location, and primary tumor etiology were not found to be statistically significant, with respect to hardware failure. Predictive factors included in the multivariate model were other bone metastasis, visceral metastasis, brain metastasis, Modified Rankin scale, previous systemic chemotherapy, previous radiation to the spine, and mean survival. Previous radiation to the spine was the only factor to be significantly associated (p=0.029), present in all three patients with hardware failure. Of note, there was a trend indicating that patients with longer life expectancies were more likely to experience hardware failure (mean survival of 16.7months in non-failure cohort vs. 33months in failure cohort), though this did not achieve statistical significance due

  14. Therapeutic effects of HESA-A in patients with end-stage metastatic cancers.

    Science.gov (United States)

    Ahmadi, Amrollah; Mohagheghi, Mohammadali; Karimi, Mehrdad; Golestanha, Seyed Ali; Naseri, Mohsen; Faghihzadeh, Soghrat; Habibi, Gholamreza

    2010-03-01

    After cardiovascular disease, cancer is the most common cause of death. HESA-A is a natural product of herbal and marine origin. The aim of this study was to investigate the beneficial effects of HESA-A in patients with end-stage metastatic cancers. In this clinical trial, 30 consecutive patients (18 men, 12 women) with end-stage cancers and liver metastasis at the Cancer Research Center of Tehran University of Medical Sciences were studied. Patients received HESA-A 50 mg/kg/d orally in 2 to 3 divided doses for 3 months. At the start and end of the 1st, 4th, 8th, and 12th weeks of the study, the patients were assessed and hematological and hepatic biochemical indices were measured. Also, the Karnofsky Performance Scale questionnaire was completed for each patient. The mean age of patients was 56.23 +/- 12.10 years. Mean Karnofsky Performance Scale scores of the patients increased from 48 +/- 14.36 to 78.42 +/- 15.37 after 12 weeks of treatment. A total of 90.4% of the patients who remained in the study were alive for 12 weeks. No significant hepatic or hematologic adverse effect was seen during the study. HESA-A appears to be an effective and safe anticancer compound that may increase survival of end-stage patients and can be used in selected cases. Further prospective controlled clinical trials with large sample size and longer follow-up period are warranted to understand the mechanisms of action of HESA-A and evaluate its long-term effects on the survival and quality of life of patients with cancer and as well as its unfavorable side effects.

  15. An in vivo mouse model of metastatic human thyroid cancer.

    Science.gov (United States)

    Zhang, Lisa; Gaskins, Kelli; Yu, Zhiya; Xiong, Yin; Merino, Maria J; Kebebew, Electron

    2014-04-01

    Mouse models of metastatic human cancers are important tools in preclinical studies for testing new systematic therapies and studying effectors of cancer metastasis. The major drawbacks of current mouse models for metastatic thyroid cancer are that they have low metastasis rates and do not allow in vivo tumor detection. Here, we report and characterize an in vivo detectable metastasis mouse model of human thyroid cancer using multiple thyroid cancer cell lines. Human anaplastic thyroid cancer cell lines 8505C, C-643, SW-1736, and THJ-16T; follicular thyroid cancer cell lines FTC-133, FTC-236, and FTC-238; and Hürthle cell carcinoma cell line XTC-1 were transfected with a linearized pGL4.51[luc2/CMV/Neo] vector or transduced with lentivirus containing Luc2-eGFP reporter genes. The stably transfected cells were injected intravenously into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Tumors were detected with an in vivo imaging system-Xenogen IVIS. Vemurafenib, a BRAF inhibitor, was used to treat lung metastases generated from 8505C-Luc2 cells with a BRAF(V600E) mutation to test the accuracy of the model to evaluate response to therapy. Intravenous injection of as few as 30,000 8505C-Luc2 cells produced lung metastases in 100% of the injected mice, and many of these mice also developed bone metastases at a later stage of the disease. Similarly, metastatic tumors also developed in all mice injected with C-643-Luc2, THJ-16T-Luc2, FTC-133-Luc2, FTC-236-Luc2, FTC-238-Luc2, and XTC-1-Luc2 cells. The metastases were easily detectable in vivo, and tumor progression could be dynamically and accurately followed and correlated with the actual tumor burden. Furthermore, disease progression could be easily controlled by adjusting the number of injected cells. The in vivo treatment of 8505C xenograft lung metastases with vemurafenib dramatically reduced the growth and signal intensity with good correlation with actual tumor burden. Herein we report an in vivo detectable mouse model

  16. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    Science.gov (United States)

    2017-06-05

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  17. 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.

  18. Biweekly Pegylated Liposomal Doxorubicin (Caelyx) in Heavily Pretreated Metastatic Breast Cancer: A Phase 2 Study.

    Science.gov (United States)

    Jehn, Christian F; Hemmati, Philipp; Lehenbauer-Dehm, Silvia; Kümmel, Sherko; Flath, Bernd; Schmid, Peter

    2016-12-01

    Pegylated liposomal doxorubicin (PLD) has shown to be as effective as conventional doxorubicin in the treatment of metastatic breast cancer but provides a lower risk of cardiotoxicity. This phase 2 study in heavily pretreated patients with metastatic breast cancer was initiated to evaluate a biweekly instead of a 4-week schedule of PLD in order to obtain a more flexible and tolerable regimen. A total of 25 patients with 2 or more prior lines of chemotherapy for metastatic disease were treated with PLD (25 mg/m2) at 2-week intervals for a maximum of 12 courses. Pretreatment with anthracyclines was allowed as long as the cumulative doxorubicin dose at study entry was below 400 mg/m2. Most patients were pretreated with anthracyclines, taxanes, vinorelbine, alkylating agents, and capecitabine. The clinical benefit rate, ie, objective response or stable disease, for at least 6 months was 22.7% for all patients and 22.2% in anthracycline- and taxane-pretreated patients, respectively. Median duration of clinical benefit and median time to progression were 12.5 months (95% confidence interval [CI], 10.1-32.3) and 7 weeks (95% CI, 5.4-8.6), respectively. Median overall survival was 9.6 months (95% CI, 5.4-13.9). One- and 2-year survival rates were 38% and 4%, respectively. Myelosuppression was low, with no grade 3 or 4 neutropenia or thrombocytopenia. Most common nonhematologic toxicities were nausea, alopecia, asthenia, and hand-foot syndrome. The low rate of hematologic toxicity and hand-foot syndrome is clinically noteworthy. Biweekly PLD is an easily manageable schedule with a favorable toxicity profile. Efficacy was moderate in heavily pretreated patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Unusual presentation of metastatic gall bladder cancer

    Directory of Open Access Journals (Sweden)

    Piyush Shukla

    2014-01-01

    Full Text Available To report the first case of rare isolated breast metastasis from carcinoma gall bladder. Single patient case report. A 35-year-old pre-menopausal female presented with 2 FNx01 2 cm right upper outer quadrant breast lump. Post-mastectomy, histology confirmed it to be metastatic adenocarcinoma positive for both Cytokeratin (CK 7 and CK20. Past history as told by the patient revealed that 2 years back, cholecystectomy was performed for gall stones, of which no histology reports were present; she had a port site scar recurrence which showed it to be adenocarcinoma. Adjuvant chemotherapy and radiotherapy was advised which the patient did not complete. This is probably the first case reported of isolated breast metastasis from gall bladder carcinoma, diagnosed retrospectively. It also highlights the importance of adjuvant treatment in gall bladder malignancy.

  20. Metastatic Breast Cancer to the Common Bile Duct Presenting as Obstructive Jaundice

    Directory of Open Access Journals (Sweden)

    Justin Cochrane

    2015-07-01

    Full Text Available Metastatic breast cancer is typically identified in the bones, lymph nodes, lungs and liver. Rarely does metastatic breast cancer involve the common bile duct (CBD without direct extension from liver metastasis into the CBD. We present a woman diagnosed with metastatic breast cancer in the CBD after presenting with obstructive jaundice. Patients with a history of primary breast cancer who present with obstructive jaundice secondary to CBD mass need identification of the mass in order to provide appropriate treatment.

  1. Trastuzumab in Treating Patients With Previously Treated, Locally Advanced, or Metastatic Cancer of the Urothelium

    Science.gov (United States)

    2013-05-01

    Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

  2. Adrenal Insufficiency in Metastatic Lung Cancer

    OpenAIRE

    Carvalho, F.; Louro, F; Zakout, R

    2015-01-01

    We report a case of adrenal insufficiency in patient with lung cancer. Although adrenal metastases are common in cancer patients, adrenal insufficiency is a rare occurrence. Diagnosis and treatment of adrenal insufficiency will improve the physical status and the quality of life in those patients.

  3. Adrenal Insufficiency in Metastatic Lung Cancer.

    Science.gov (United States)

    Carvalho, Filipe; Louro, Fernanda; Zakout, Raed

    2015-06-01

    We report a case of adrenal insufficiency in patient with lung cancer. Although adrenal metastases are common in cancer patients, adrenal insufficiency is a rare occurrence. Diagnosis and treatment of adrenal insufficiency will improve the physical status and the quality of life in those patients.

  4. Cytoreductive prostatectomy in metastatic prostate cancer

    DEFF Research Database (Denmark)

    Becker, Joachim Aidt; Berg, Kasper Drimer; Røder, Martin Andreas

    2017-01-01

    The impact of cytoreductive radical prostatectomy on oncological outcome in patients with prostate cancer and limited number of bone metastases is unclear. Data from cancer registries, multi-institutional databases and a single institutional case-control study indicate a possible benefit...

  5. Targeted treatment of advanced and metastatic breast cancer with lapatinib

    Directory of Open Access Journals (Sweden)

    Brendan Corkery

    2008-09-01

    Full Text Available Brendan Corkery1,2, Norma O’Donovan2, John Crown1,21St. Vincent’s University Hospital, Dublin, Ireland; 2National Institute for Cellular Biotechnology, Dublin City University, Dublin, IrelandAbstract: Improved molecular understanding of breast cancer in recent years has led to the discovery of important drug targets such as HER-2 and EGFR. Lapatinib is a potent dual inhibitor of HER-2 and EGFR. Preclinical and phase I studies have shown activity with lapatinib in a number of cancers, including breast cancer, and the drug is well tolerated. The main known drug interactions are with paclitaxel and irinotecan. The most significant side-effects of lapatinib are diarrhea and adverse skin events. Rates of cardiotoxicity compare favorably with trastuzumab, a monoclonal antibody against HER-2. This paper focuses on lapatinib in advanced and metastatic breast cancer, which remains an important therapeutic challenge. Phase II and III studies show activity as monotherapy, and in combination with chemotherapy or hormonal agents. Results from these studies suggest that the main benefit from lapatinib is in the HER-2 positive breast cancer population. Combinations of lapatinib and trastuzumab are also being studied and show encouraging results, particularly in trastuzumab-refractory metastatic breast cancer. Lapatinib may have a specific role in treating HER-2 positive CNS metastases. The role of lapatinib as neoadjuvant therapy and in early breast cancer is also being evaluated.Keywords: HER-2, EGFR, erbB, lapatinib, Tykerb®, tyrosine kinase

  6. Metastatic Breast Cancer or Multiple Myeloma? Camouflage by Lytic Lesions

    Directory of Open Access Journals (Sweden)

    Bruce Hough

    2010-01-01

    Full Text Available We report a case of a female with stage I infiltrating ductal carcinoma who received adjuvant therapy including trastuzumab. One year later she developed lytic lesions and was retreated with trastuzumab that was held after she developed symptomatic heart failure. Lytic lesions were attributed to relapse of breast cancer, and cardiac failure attributed to prior trastuzumab therapy. After complications necessitated multiple hospitalizations, a further workup revealed that the lytic lesions were not metastatic breast cancer but multiple myeloma. Her advanced multiple myeloma was associated with systemic amyloidosis involving gut and heart, which ultimately led to her demise. This report addresses the pitfalls of overlapping symptoms and the question of which patients with suspected metastatic disease should undergo a biopsy.

  7. Combination Drug Delivery Approaches in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun H. Lee

    2012-01-01

    Full Text Available Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms.

  8. Management of metastatic thyroid cancer in pregnancy: risk and uncertainty

    Directory of Open Access Journals (Sweden)

    Christopher W Rowe

    2016-12-01

    Full Text Available Metastatic thyroid cancer is an uncommon condition to be present at the time of pregnancy, but presents a challenging paradigm of care. Clinicians must balance the competing interests of long-term maternal health, best achieved by iatrogenic hyperthyroidism, regular radioiodine therapy and avoidance of dietary iodine, against the priority to care for the developing foetus, with inevitable compromise. Additionally, epidemiological and cellular data support the role of oestrogen as a growth factor for benign and malignant thyrocytes, although communicating the magnitude of this risk to patients and caregivers, as well as the uncertain impact of any pregnancy on long-term prognosis, remains challenging. Evidence to support treatment decisions in this uncommon situation is presented in the context of a case of a pregnant teenager with known metastatic papillary thyroid cancer and recent radioiodine therapy.

  9. OPTIMIZATION OF METASTATIC COLORECTAL CANCER TREATMENT WITH RAS MUTATIONS

    Directory of Open Access Journals (Sweden)

    L. V. Bolotina

    2013-01-01

    Full Text Available Current knowledge concerning impact of certain mutations on targeted therapy efficacy underlines the necessity to perform genetical analysis in order to choose appropriate treatment. Panitumumab addition to 1st line metastatic colorectal cancer chemotherapy in patients with wild-type RAS allows to achieve median progression-free survival up to 13 months and median overall survival of 41,3 months.

  10. Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer

    Science.gov (United States)

    2014-01-01

    Introduction Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR) inhibitor) and carboplatin may have activity in metastatic triple-negative breast cancer (TNBC). Methods The primary objective of this study was to determine clinical benefit rate (CBR), that is (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting ≥6 months) and the toxicity of everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was allowed. Treatment consisted of intravenous carboplatin area under the curve (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with daily 5 mg everolimus. Results We enrolled 25 patients in this study. Median age was 58 years. There were one CR, six PRs, seven SDs and eight PDs (progression of disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%). One SD was achieved in a patient progressing on single agent carboplatin. The median progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There were seven patients (28%) with ≥ grade 3 thrombocytopenia; three (12%) with grade 3 neutropenia (no bleeding/febrile neutropenia) and one (4%) with grade 3 anemia. Greater hematological toxicity was seen in the first seven patients treated with carboplatin AUC5/6. After the amendment for starting dose of carboplatin to AUC 4, the regimen was well tolerated with only one out of 18 patients with grade 3 neutropenia and two patients with grade 3 thrombocytopenia. There was only one case of mucositis. Conclusion Everolimus-carboplatin was efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed when AUC5/6 of carboplatin was combined with everolimus. However, carboplatin AUC 4 was well tolerated in

  11. Liver-directed therapy in metastatic colorectal cancer.

    Science.gov (United States)

    Kelly, Ciara M; Kemeny, Nancy E

    2017-08-01

    Colorectal cancer is a significant global health issue with over 1 million cases diagnosed annually throughout the world. 15% of patients diagnosed with colorectal cancer will have liver metastases and 60% will develop liver metastases if they have metastatic disease. Oligometastatic colorectal cancer confined to the liver represents an intermediate state in the evolution of metastatic capacity that opens the opportunity for local interventions. Areas covered: The literature supports long-term survival if patients undergo liver resection of colorectal metastases. This article reviews the liver-directed therapeutic strategies available for the management of metastatic liver disease including hepatic arterial infusion therapy, radiofrequency ablation, radiation therapy and transarterial chemoembolization. Expert commentary: Great advances have been made with the use of liver directed therapies. In the USA using hepatic arterial infusions with FUDR and Decadron along with systemic therapy, 5 year survivals after liver resection have improved. In Europe with the use of HAI of Oxaliplatin, more patients have been able to get to resection and have obtained higher survival rates, even in second line therapy. New advances in ablative therapy have improved results to get all disease treated at resection for the treatment of reccurrence.

  12. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen

    2001-01-01

    .... Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines...

  13. Attitudes of patients with metastatic cancer towards research biopsies.

    Science.gov (United States)

    Robinson, Danielle H; Churilov, Leonid; Lin, Nancy U; Lim, Elgene; Seah, Davinia

    2017-11-06

    To evaluate the attitudes of patients with different cancers towards research biopsies outside a clinical trial. Patients with metastatic cancer completed a questionnaire that assessed patients' willingness to consider research biopsies. Research biopsies were divided into two groups: biopsies performed as stand-alone procedures (research purposes only biopsy, RPOB) or performed during a clinically indicated biopsy (additional pass biopsy, APB). Factors analyzed included biopsy timing, biopsy site, sociodemographic information and information about prior trial participation. Univariate and multivariable analyses were conducted using random-effects logistic regression. One hundred and sixty-five patients with cancer (40 melanoma, 37 colorectal, 32 breast, 30 lung, 26 prostate) completed the questionnaire. Patients with melanoma demonstrated the greatest willingness to consider a research biopsy compared to patients with other cancer types (P biopsies, time since metastatic diagnosis, and previous trial enrolment were all statistically significant for willingness to consider a research biopsy on univariate analysis. When adjusting for statistically significant variables on univariate analysis, the odds of patients considering APBs were 14.6 times greater than RPOBs (P biopsies. Patients with cancer show a greater willingness to consider APBs compared to RPOBs, and biopsies performed at less invasive body sites. There are differences in the attitudes of patients with different cancers towards research biopsies. Further research addressing motivations and barriers to research biopsies should be considered to increase the availability of this important resource. © 2017 John Wiley & Sons Australia, Ltd.

  14. [Multidisciplinary tailoring of therapy of metastatic colon cancer].

    Science.gov (United States)

    Österlund, Pia; Isoniemi, Helena; Scheinin, Tom; Ristimäki, Ari; Lantto, Eila

    2016-01-01

    Treatment of colon cancer requires multidisciplinary team work. The multitude of therapies in metastatic colon cancer have led to longer overall survival with fewer symptoms. Median survival has increased from 5 months with the best supportive care to 30-40 months in randomized studies, even with curative treatment in some patients. Tailoring of the treatment is best done by a multidisciplinary team considering radiotherapy and operation of the primary tumor, resection of liver, lung and peritoneal metastases, medical treatment alternatives, palliative care, ablative methods etc. Without skillful surgeons, oncologists, pathologists, geneticists, radiologists etc. the best treatment opportunities may be missed.

  15. miR-345 in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Schou, Jakob V; Rossi, Simona; Jensen, Benny V

    2014-01-01

    INTRODUCTION: MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic...... for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. METHODS: From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood...

  16. A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

    Science.gov (United States)

    2017-08-11

    CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Marginal Zone B Cell Lymphoma); Any T-cell Malignancy; Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma; Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer; Colorectal Adenocarcinoma, Non-small Cell Lung Cancer); Burkett's Lymphoma; Primary Lymphoma of the Central Nervous System

  17. Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

    Science.gov (United States)

    Singer, Adam; Tresley, Jonathan; Velazquez-Vega, Jose; Yepes, Monica

    2013-02-01

    For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

  18. Phytochemicals potently inhibit migration of metastatic breast cancer cells†

    Science.gov (United States)

    Ham, Stephanie Lemmo; Nasrollahi, Samila; Shah, Kush N.; Soltisz, Andrew; Paruchuri, Sailaja; Yun, Yang H.; Luker, Gary D.; Bishayee, Anupam; Tavana, Hossein

    2017-01-01

    Cell migration is a major process that drives metastatic progression of cancers, the major cause of cancer death. Existing chemotherapeutic drugs have limited efficacy to prevent and/or treat metastasis, emphasizing the need for new treatments. We focus on triple negative breast cancer (TNBC), the subtype of breast cancer with worst prognosis and no standard chemotherapy protocols. Here we demonstrate that a group of natural compounds, known as phytochemicals, effectively block migration of metastatic TNBC cells. Using a novel cell micropatterning technology, we generate consistent migration niches in standard 96-well plates where each well contains a cell-excluded gap within a uniform monolayer of cells. Over time, cells migrate into and occupy the gap. Treating TNBC cells with non-toxic concentrations of phytochemicals significantly blocks motility of cells. Using a molecular analysis approach, we show that anti-migratory property of phytochemicals is partly due to their inhibitory effects on phosphorylation of ERK1/2. This study provides a framework for future studies to understand molecular targets of phytochemicals and evaluate their effectiveness in inhibiting metastasis in animal models of cancer. PMID:26120051

  19. A Rare Case of Endometrial Cancer Metastatic to the Sigmoid Colon and Small Bowel

    Directory of Open Access Journals (Sweden)

    Jeffrey A. Hubers

    2017-01-01

    Full Text Available Metastatic endometrial cancer to the small bowel or colon has been described but is quite rare. We present a case of metastatic endometrial cancer with synchronous metastases to the colon and jejunum identified three years after surgical treatment of early stage endometrial cancer.

  20. [Standards, Options and Recommendations for non metastatic breast cancer patients].

    Science.gov (United States)

    Mauriac, Louis

    2002-02-01

    The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. To develop clinical practice guidelines for non metastatic breast cancer patients according to the definitions of the Standards, Options and Recommendations project. Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 148 independent reviewers. This article is an update of the version published in 1996. The modified 2001 version of the standards, options and recommendations takes into account new information published. Important changes have been made in terms of clinical practice. They concern loco-regional and general therapy. Regarding loco-regional treatment, a increased dose to the tumor bed should be needs to be systematically delivered to the tumor bed for women under 50 years. The analysis of margin involvement is essential and constitutes an important factor for therapeutic decision. Regarding general therapy, hormone therapy with tamoxifen appeared, in 2001, as one of the standards in non-menopausal and oestrogen receptor-positive patients. Concerning patients with N- tumors, the standards and therapeutic options were refined with regard to the notion of metastatic relapse risk. Chemotherapy constitutes one of the standard treatments for non-menopausal women with one or more factor(s) predictive of metastatic relapse.

  1. Treatment of locally advanced and metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Makarand V Khochikar

    2008-01-01

    Full Text Available Background: There is a significant variation in the treatment strategies adopted for the treatment of locally advanced T3b, T4a, N1-3 and metastatic bladder cancer. There is increasing evidence that we would be able to offer them some benefit in terms of disease-free survival and improving the quality of life. This article is aimed at reviewing the current literature on the treatment strategies in locally advanced and metastatic bladder cancer. Materials and Methods: Extensive literature search was done on Medline/Pubmed from 1980-2007 using the key words - treatment of locally advanced, metastatic bladder cancer. Standard textbooks on urology, urologic oncology and monograms were reviewed. Guidelines such as National Comprehensive Cancer Network guidelines, European Urology Association guidelines and American Urology Association guidelines were also studied. Results and Conclusions: There is a place for radical cystectomy in locally advanced T3b-T4 and N1-3 bladder cancer. Radical cystectomy alone rarely cures this subgroup of patients. There is increasing evidence that meticulous surgical clearance and extended lymphadenectomy has significant impact on disease-free survival. Adjuvant chemotherapy has been found to be effective in terms of recurrence-free survival and better than cystectomy alone. Neoadjuvant chemotherapy followed by radical cystectomy also has beneficial effects in terms of downstaging the disease and improving recurrence-free survival. This perioperative chemotherapy (adjuvant/neoadjuvant has 5-7% survival benefit and 10% reduction in the death due to cancer disease. Excellent five-year survival rates have been achieved in patients achieving pT0 stage at surgery following chemotherapy (around 80% and overall 40% five-year survival in node positive patients, which is promising. Though practiced widely, perioperative chemotherapy is not considered as a standard of care as yet. Current ongoing trials are likely to help us in

  2. Pembrolizumab and Ruxolitinib Phosphate in Treating Patients With Metastatic Stage IV Triple Negative Breast Cancer

    Science.gov (United States)

    2017-08-28

    Breast Carcinoma Metastatic in the Bone; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  3. Comparative effectiveness of early-line nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer: a US community-based real-world analysis

    Directory of Open Access Journals (Sweden)

    Mahtani RL

    2018-02-01

    Full Text Available Reshma L Mahtani,1 Monika Parisi,2 Stefan Glück,3 Quanhong Ni,2 Siyeon Park,4 Corey Pelletier,2 Claudio Faria,2 Fadi Braiteh5,6 1Division of Hematology/Oncology, University of Miami, Miami, FL, 2Health Economics and Outcomes Research, Celgene Corporation, Summit, NJ, 3Global Medical Affairs, Celgene Corporation, Summit, NJ, 4School of Pharmacy, The Ohio State University, Columbus, OH, 5Department of Hematology/Oncology, University of Nevada School of Medicine, Las Vegas, NV, 6Department of Hematology/Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA Background: Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA.Methods: We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab-paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014. The clinical efficacy objectives were time to treatment discontinuation (TTD and time to next treatment (TTNT. Subgroup analyses were performed in patients with 2 types of metastatic breast cancer as follows: 1 hormone receptor-positive and human epidermal growth factor receptor 2 negative, and 2 triple-negative disease. Results: This analysis included 925 patients. Patients receiving nab-paclitaxel vs. paclitaxel had significantly longer TTD (median 4.2 vs. 2.8 months, P<0.0001 and TTNT (median 6.0 vs. 4.2 months, P<0.0001; similar outcomes were observed for patients with hormone receptor-positive/human epidermal growth factor receptor 2 negative disease. Compared with paclitaxel, nab-paclitaxel was associated with significantly longer TTD in patients with triple

  4. Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination.

    Science.gov (United States)

    Hallou, Adrien; Jennings, Joel; Kabla, Alexandre J

    2017-08-01

    Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo, such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes.

  5. Combination of TB lymphadenitis and metastatic LAP in breast cancer

    Directory of Open Access Journals (Sweden)

    Abdolhassan Talaiezadeh

    2015-06-01

    Full Text Available Tuberculosis (TB may present as pulmonary and extra-pulmonary. TB lymphadenitis is the most common presentation of extra-pulmonary TB. TB lymphadenitis should be taken into account in the differential diagnosis of different disorders such as metastatic lymphadenopathy. The reported patient was a 65-year-old lady with breast cancer and conglomerated and matted axillary lymphadenopathy who received chemotherapy. She presented with more extensive axillary LAP contrary to our expectation. Modified radical mastectomy was done and pathology analysis reported TB lymphadenitis associated with metastatic LAP. Under cover of anti-TB therapy adjuvant chemoradiation therapy was started. Accordingly, we recommend TB be ruled out in every patient who needs chemotherapy in the endemic region because chemotherapy may cause the extension of TB in the body.

  6. Metastatic pancreatic cancer presenting as linitis plastica of the stomach.

    Science.gov (United States)

    Garg, Shivani; Mulki, Ramzi; Sher, Daniel

    2016-03-08

    Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas. 2016 BMJ Publishing Group Ltd.

  7. Evaluation of metastatic potential of prostate cancer

    Directory of Open Access Journals (Sweden)

    Yoshitomo Chihara

    2011-06-01

    Full Text Available We aimed to establish a method for evaluating malignant potential of prostate cancer using prostatic core needle biopsy (PCNB before prostatectomy. If we can know the final pathological stage before treatment, we can select the most suitable therapeutic tactics. We then examined the expression of E-cadherin and type IV collagenase (MMP-9/-2, which play essential role in cancer cell invasion and metastasis. The expression ratio of MMP-9/-2 to E-cadherin (MER is revealed as the relevant marker correlated with the final pathological stage and Gleason score by prostatectomy specimens. We next confirmed the significance of MER in PCNB, which means PCNB MER enables the prediction of the final pathologic stage at the cancer diagnosis. However, the methodology measuring MER is complicated to produce an observer-to-observer deviation. We then establish a bicolor fluorescent ISH (bicolor FISH with a computerized fluorescence detector- based system. By this method, we can reduce an observer-to-observer deviation and a slide-to-slide deviation. The bicolor FISH-based MER is a useful tool for the preoperative evaluation of the final pathologic stage, by which we can assure a decision of prostatectomy indication.

  8. A review on metastatic breast cancer in Iran

    Directory of Open Access Journals (Sweden)

    Hamidreza Alizadeh Otaghvar

    2015-06-01

    Full Text Available Metastatic breast cancer is a disease of early breast cancer that usually occurs several years after the early breast cancer. Breast cancer is the most common cancer among Iranian women. According to the new statistics in Iran 6160 breast cancers are diagnosed in the country each year and 1063 cases lead to death. In this paper, epidemiology, diagnosis and treatment have been investigated. In this study, case–control clinical trials and open studies with adequate data were collected. Due to the higher risk of age group 40–49 years and the advent of advanced breast cancer in Iranian women, the early diagnosis and determination of the exact size of the tumor before surgery is important in choosing a therapy plan. The decision on the therapy of invasive breast cancer depends on several factors such as cancer stage, tumor size and type, pathological and cytological status of the tumor, the patient's opinion, the presence or absence of estrogen and progesterone receptors in the cytoplasm of tumor cells and so on.

  9. Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer.

    Science.gov (United States)

    Matsunaga, Shigeo; Shuto, Takashi; Sato, Mitsuru

    2016-05-01

    The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Hormone therapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Jebelameli P

    1997-09-01

    Full Text Available Only orchiectomy is still commonly used today either as a single therapy or in combination regimens. Hypophysectomy & adrenalectomy showed such devastating effects on the endocrine equilibrium as to be inconsistent with an acceptable quality of life or even with survival. Chemical adrenalectomy was also tried with drugs (eg. aminoglutethmide, spironolactone leading to consequences superimposable to those of surgical adrenalectomy. Along with orchiectomy, three groups of substances are commonly used today for the hormonal therapy of prostate cancer: estrogens, LHRH agonists & anti androgens. Bilateral orchiectomy removes 90-95% of circulating testosterone. Clinical studies document 60-80% of positive responders to castration, on continued evaluation, relapse occurs usually within 6-24 months in responders, with a death rate of 50% within 6 months. The androgenic activity still remaining after castration may explain the partial & progressively decreasing effectiveness of this & other testosterone reducing therapies. Antiandrogens define substances that act directly at the target site, where interacting with steroid hormone receptors, they impede the binding of androgens. A trend towards the combination of testosterone-reducing & androgen-blocking treatment is developing in modern therapy of prostate cancer. This is due to the complementary characteristics of the two different pharmacological mechanisms that are involved. In this study castration+antiandrogen is compared to castration alone. The results demonstrate a significantly greater percentage of positive objective & subjective responses with antiandrogen than with placebo. In addition survival time was increased in patients treated with castration+antiandrogen than castration+placebo.

  11. Functionalization of nanotextured substrates for enhanced identification of metastatic breast cancer cells

    Science.gov (United States)

    Mansur, Nuzhat; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

    2017-09-01

    Metastasis is the major cause of low survival rates among cancer patients. Once cancer cells metastasize, it is extremely difficult to contain the disease. We report on a nanotextured platform for enhanced detection of metastatic cells. We captured metastatic (MDA-MDB-231) and non-metastatic (MCF-7) breast cancer cells on anti-EGFR aptamer modified plane and nanotextured substrates. Metastatic cells were seen to change their morphology at higher rates when captured on nanotextured substrates than on plane substrates. Analysis showed statistically different morphological behaviors of metastatic cells that were very pronounced on the nanotextured substrates. Several distance matrices were calculated to quantify the dissimilarity of cell shape change. Nanotexturing increased the dissimilarity of the metastatic cells and as a result the contrast between metastatic and non-metastatic cells increased. Jaccard distance measurements found that the shape change ratio of the non-metastatic and metastatic cells was enhanced from 1:1.01 to 1:1.81, going from plane to nanotextured substrates. The shape change ratio of the non-metastatic to metastatic cells improved from 1:1.48 to 1:2.19 for the Hausdorff distance and from 1:1.87 to 1:4.69 for the Mahalanobis distance after introducing nanotexture. Distance matrix analysis showed that nanotexture increased the shape change ratios of non-metastatic and metastatic cells. Hence, the detectability of metastatic cells increased. These calculated matrices provided clear and explicit measures to discriminate single cells for their metastatic state on functional nanotextured substrates.

  12. Thyroid Cancer Presenting with Concomitant Metastatic Breast Cancer in the Thyroid

    Directory of Open Access Journals (Sweden)

    Chung-Chen Wang

    2014-12-01

    Full Text Available The thyroid is an unusual site to find cancer metastasis. When it does occur, such cancer spread is often manifested in multiple metastases and generally suggests a poor prognosis. We presented here a 49-year-old woman recently diagnosed with thyroid cancer, who had been treated for stage IIA breast cancer 8 years ago. After radical right thyroidectomy and left subtotal thyroidectomy, her pathological report showed papillary thyroid carcinoma, right thyroid, with concomitant metastatic breast carcinoma. This is the first case of which we are aware involving coexisting thyroid cancer and metastatic breast cancer in the ipsilateral lobe. Moreover, the circumstances of this case show a very unique clinical course compared with previous studies. Given the unusual circumstances of our case, we further discuss the relationship between thyroid cancer and breast cancer.

  13. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Gundgaard, M.G.; Ehrnrooth, E.; Sørensen, Jens Benn

    2008-01-01

    , panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). MATERIALS AND METHODS: We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data......BACKGROUND: The past years' therapy for colorectal cancer has evolved rapidly with the introduction of novel cytotoxic agents such as irinotecan, capecitabine and oxaliplatin. Further advances have been achieved with the integration of targeted agents such as bevacizumab, cetuximab and recently......OS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. CONCLUSION: Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted...

  14. Subacute liver failure by pseudocirrhotic metastatic breast cancer infiltration.

    Science.gov (United States)

    Jüngst, Christoph; Krämer, Jens; Schneider, Günther; Lammert, Frank; Zimmer, Vincent

    2013-01-01

    Hepatic metastases are common in the clinical course of breast cancer and typically appear as mass lesions. This report describes the case of a 70-year-old woman with a history of breast cancer and no previously known liver disease presenting with the first episode of variceal bleeding and subacute hepatic failure. Imaging studies indicated liver cirrhosis without signs of malignant focal lesions. Comprehensive diagnostic work-up was negative for specific causes of liver disease and provided no evidence for tumor recurrence. Finally transjugular liver biopsy revealed a marked diffuse desmoplastic infiltration by breast cancer cells. Malignant pseudocirrhosis is an unusual pattern of metastatic, tumor spread representing a rare but important differential diagnosis of progressive liver failure. Liver biopsy is the key procedure to establish the diagnosis as imaging studies may mimic cirrhosis.

  15. HER-2-positive metastatic breast cancer: new possibilities for therapy

    Directory of Open Access Journals (Sweden)

    E. V. Artamonova

    2013-01-01

    Full Text Available This article is devoted to modern approaches in HER-2-positive metastatic breast cancer therapy. Recently treatment algorithm for this type of cancer included trastuzumab plus cytostatic in first line, continuation of trastuzumab with another chemotherapy regimen in second line, further switch to lapatinib and eventual return to trastuzumab after progression. Nowadays our options are broader owing to new anti-HER-2 agents which are pertruzumab and T-DM1. Now the most effective therapy regimen in first line is double HER-2 blockade (trastuzumab + pertuzumab in combination with docetaxel. Benefit of new agent T-DM1 versus combination of lapatinib and capecitabin is proved in patients progressed on trastuzumab and taxanes. T-DM1 also showed high efficacy as salvage therapy in intensively pretreated patients with meta- static HER-2-positive breast cancer who progressed on taxanes, trastuzumab and lapatinib.

  16. Radioembolization for primary and metastatic liver cancer.

    Science.gov (United States)

    Memon, Khairuddin; Lewandowski, Robert J; Kulik, Laura; Riaz, Ahsun; Mulcahy, Mary F; Salem, Riad

    2011-10-01

    The incidence of hepatocellular carcinoma is increasing. Most patients present beyond potentially curative options and are usually affected by underlying cirrhosis. In this scenario, transarterial therapies, such as radioembolization, are rapidly gaining acceptance as a potential therapy for hepatocellular carcinoma and liver metastases. Radioembolization is a catheter-based liver-directed therapy that involves the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous transarterial techniques. Cancer cells are preferentially supplied by arterial blood and normal hepatocytes by portal venous blood; therefore, radioembolization specifically targets tumor cells with a high dose of lethal radiation and spares healthy hepatocytes. The antitumor effect mostly comes from radiation rather than embolization. The most commonly used radioisotope is yttrium-90. The commercially available devices are TheraSphere (glass based; MDS Nordion, Ottawa, Canada) and SIR-Sphere (resin based; Sirtex, Lane Cove, Australia). The procedure is performed on an outpatient basis. The incidence of complications is comparatively less than other locoregional therapies and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, gastrointestinal ulcers, and vascular injury. However, these complications can be avoided by meticulous pretreatment assessment, careful patient selection, and adequate dosimetry. This article focuses on both the technical and clinical aspects of radioembolization with emphasis on patient selection, uses and complications. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Modified FOLFOX6 chemotherapy in patients with metastatic urachal cancer.

    Science.gov (United States)

    Yanagihara, Yutaka; Tanji, Nozomu; Miura, Noriyoshi; Shirato, Akitomi; Nishimura, Kenichi; Fukumoto, Tetsuya; Azuma, Koji; Miyauchi, Yuki; Kikugawa, Tadahiko; Yokoyama, Masayoshi

    2013-01-01

    To improve the prognosis of patients with urachal cancer and establish an effective chemotherapeutic regimen for distant metastases. We conducted a retrospective study to evaluate the efficacy and safety of a modified combination of 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) therapy in patients with metastatic urachal cancer. Five patients were treated with mFOLFOX6. Their median age was 65 years (range 41-80). The median follow-up time was 42 months (range 18-46). Two of the 5 patients (40%) showed an objective response: 1 achieved a clinically complete response and 1 a partial response. The grade 3/4 toxicity associated with this regimen was primarily neutropenia, but febrile neutropenia was not observed. Oxaliplatin treatment was discontinued because of a grade 2 allergic reaction in 1 patient. Grade 2 peripheral sensory neuropathy caused by oxaliplatin was observed in 2 patients, and the OPTIMOX (stop and go) approach had to be adopted. mFOLFOX6 appears to be effective for the treatment of metastatic urachal cancer. © 2014 S. Karger AG, Basel.

  18. Abiraterone in metastatic prostate cancer without previous chemotherapy.

    Science.gov (United States)

    Ryan, Charles J; Smith, Matthew R; de Bono, Johann S; Molina, Arturo; Logothetis, Christopher J; de Souza, Paul; Fizazi, Karim; Mainwaring, Paul; Piulats, Josep M; Ng, Siobhan; Carles, Joan; Mulders, Peter F A; Basch, Ethan; Small, Eric J; Saad, Fred; Schrijvers, Dirk; Van Poppel, Hendrik; Mukherjee, Som D; Suttmann, Henrik; Gerritsen, Winald R; Flaig, Thomas W; George, Daniel J; Yu, Evan Y; Efstathiou, Eleni; Pantuck, Allan; Winquist, Eric; Higano, Celestia S; Taplin, Mary-Ellen; Park, Youn; Kheoh, Thian; Griffin, Thomas; Scher, Howard I; Rathkopf, Dana E

    2013-01-10

    Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; Pchemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone. Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.).

  19. The changing natural history of metastatic prostate cancer.

    Science.gov (United States)

    Alva, Ajjai; Hussain, Maha

    2013-01-01

    Since 1941, the understanding of prostate cancer pathogenesis and therapy has undergone a significant transformation. Rigorous translational research has identified multiple mechanisms underlying castration resistance, the fatal clinical state of the disease. Therapeutic approaches targeting these mechanisms in metastatic castration-resistant prostate cancer have now been clinically validated in the clinic including high-potency androgen signaling inhibition, novel cytotoxic chemotherapy, and bone-targeted therapies. Despite these advances, cure remains an elusive goal. The natural history of metastatic prostate cancer has evolved particularly in the last 2 decades in step with improved management of age-associated comorbidities, improved imaging, and the expansion of novel therapies, thus providing new opportunities and challenges. It is also important to note that the advent of prostate-specific antigen testing caused a stage shift in the disease spectrum, thus leading to earlier interventions and potentially positively impacting survival. The optimal sequencing and combinations of available therapies, predictive biomarkers, and better understanding of mechanisms of resistance remain high priority. Further refinement of the clinical niche for novel therapies in hormone-sensitive and castration-resistant disease through rationally designed clinical trials incorporating molecular, clinical, and imaging biomarkers and quality-of-life correlatives is of paramount importance.

  20. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

    OpenAIRE

    Yo-Han Han; Ji-Ye Kee; Dae-Seung Kim; Jeong-geon Mun; Mi-Young Jeong; Sang-Hyun Park; Byung-Min Choi; Sung-Joo Park; Hyun-Jung Kim; Jae-Young Um; Seung-Heon Hong

    2016-01-01

    Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mese...

  1. Gemcitabine for palliative treatment in metastatic breast cancer.

    Science.gov (United States)

    Lüftner, D; Flath, B; Akrivakis, C; Grunewald, R; Mergenthaler, H G; Possinger, K

    1998-01-01

    Gemcitabine is one of the recently developed drugs with a high efficacy in various malignant tumours and a mild toxicity profile. As monochemotherapy in metastatic breast cancer, gemcitabine yielded response rates up to 46% as first- and second-line treatment. Neutropenia is the clinically most relevant unwanted effect. Haematological and nonhaematological toxicities are mild, making dose reductions, delays of treatment or withdrawal from treatment very rare. The first phase I and phase II studies of gemcitabine in combination with anthracyclines have shown a good toxicity profile and promising remission rates. Phase I experiences with long-time infusion schedules reveal good feasibility and high patient acceptance.

  2. Perspectives on Treatment of Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Bellmunt, Joaquim; Jenkins, Cheryl; Parker, Chris; Fitzpatrick, John M.

    2013-01-01

    The arrival of several new agents—cabazitaxel, abiraterone acetate, enzalutamide, and radium-223—is changing the treatment options and management of patients with metastatic castration-resistant prostate cancer (mCRPC). Many other novel agents are also being investigated. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. This review article is a summary of a European Treatment Practices Meeting, which was convened to discuss these latest data on novel agents and current treatment strategies in the mCRPC setting. PMID:23671006

  3. Improvement in survival for patients with synchronous metastatic esophageal cancer in the south of the Netherlands from 1994 to 2013

    NARCIS (Netherlands)

    Bernards, N.; Haj Mohammad, N.; Creemers, G. J.; Rozema, T.; Roukema, J. A.; Nieuwenhuijzen, G. A. P.; van Laarhoven, H. W. M.; van der Sangen, M.; Lemmens, V. E. P. P.

    2016-01-01

    Background: We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival.Methods: We included all patients diagnosed with synchronous metastatic esophageal cancer in the

  4. Improvement in survival for patients with synchronous metastatic esophageal cancer in the south of the Netherlands from 1994 to 2013

    NARCIS (Netherlands)

    Bernards, N.; Mohammed, N.H.; Creemers, G.J.; Rozema, T.; Roukema, J.A.; Nieuwenhuijzen, G.A.P.; van Laarhoven, M.; van der Sangen, M.J.C.; Lemmens, V.E.P.P.

    2016-01-01

    Background: We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival. Methods: We included all patients diagnosed with synchronous metastatic esophageal cancer in the

  5. High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

    National Research Council Canada - National Science Library

    Donald A. Berry; Naoto T. Ueno; Marcella M. Johnson; Xiudong Lei; Jean Caputo; Dori A. Smith; Linda J. Yancey; Michael Crump; Edward A. Stadtmauer; Pierre Biron; John P. Crown; Peter Schmid; Jean-Pierre Lotz; Giovanni Rosti; Marco Bregni; Taner Demirer

    2011-01-01

    ... to evaluate its effect in the treatment of metastatic breast cancer. We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support...

  6. A stochastic model for cancer stem cell origin in metastatic colon cancer.

    Science.gov (United States)

    Odoux, Christine; Fohrer, Helene; Hoppo, Toshitaka; Guzik, Lynda; Stolz, Donna Beer; Lewis, Dale W; Gollin, Susanne M; Gamblin, T Clark; Geller, David A; Lagasse, Eric

    2008-09-01

    Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.

  7. Profile of palbociclib in the treatment of metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Ehab M

    2016-05-01

    treatment of postmenopausal women with ERα+/HER2− locally advanced or metastatic breast cancer. In this review, we discuss the potential role of CDK inhibition in breast cancer treatment, and focus on palbociclib progress from preclinical studies to clinical trials with mentioning the most recent ongoing as well as planned Phase II and Phase III trials of palbociclib in advanced breast cancer.Keywords: cyclin-dependent kinases, cell cycle, metastatic breast cancer, PD0332991

  8. Targeted treatment of metastatic castration-resistant prostate cancer with sipuleucel-T immunotherapy

    NARCIS (Netherlands)

    Mulders, P.F.; Santis, M. de; Powles, T.; Fizazi, K.

    2015-01-01

    CONTEXT: Prostate cancer remains highly prevalent and has a poor clinical outcome once metastatic. Sipuleucel-T is an autologous cellular immunotherapy approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T treatment extends survival but is independent of

  9. Serum HER-2: Sensitivity, specificity, and predictive values for detecting metastatic recurrence in breast cancer patients

    DEFF Research Database (Denmark)

    Sørensen, Patricia Diana; Jakobsen, Erik Hugger; Madsen, Jonna Skov

    2013-01-01

    The aim of this study was to determine the sensitivity, specificity, and predictive values of serum HER-2 for detecting metastatic recurrence in breast cancer patients.......The aim of this study was to determine the sensitivity, specificity, and predictive values of serum HER-2 for detecting metastatic recurrence in breast cancer patients....

  10. Proteolysis-a characteristic of tumor-initiating cells in murine metastatic breast cancer

    Science.gov (United States)

    Hillebrand, Larissa E.; Bengsch, Fee; Hochrein, Jochen; Hülsdünker, Jan; Bender, Julia; Follo, Marie; Busch, Hauke; Boerries, Melanie; Reinheckel, Thomas

    2016-01-01

    Tumor initiating cells (TICs) have been identified and functionally characterized in hematological malignancies as well as in solid tumors such as breast cancer. In addition to their high tumor-initiating potential, TICs are founder cells for metastasis formation and are involved in chemotherapy resistance. In this study we explored molecular pathways which enable this tumor initiating potential for a cancer cell subset of the transgenic MMTV-PyMT mouse model for metastasizing breast cancer. The cell population, characterized by the marker profile CD24+CD90+CD45−, showed a high tumorigenicity compared to non-CD24+CD90+CD45− cancer cells in colony formation assays, as well as upon orthotopic transplantation into the mammary fat pad of mice. In addition, these orthotopically grown CD24+CD90+CD45− TICs metastasized to the lungs. The transcriptome of TICs freshly isolated from primary tumors by cell sorting was compared with that of sorted non-CD24+CD90+CD45− cancer cells by RNA-seq. In addition to more established TIC signatures, such as epithelial-to-mesenchymal transition or mitogen signaling, an upregulated gene set comprising several classes of proteolytic enzymes was uncovered in the TICs. Accordingly, TICs showed high intra- and extracellular proteolytic activity. Application of a broad range of protease inhibitors to TICs in a colony formation assay reduced anchorage independent growth and had an impact on colony morphology in 3D cell culture assays. We conclude that CD24+CD90+CD45− cells of the MMTV- PyMT mouse model possess an upregulated proteolytic signature which could very well represent a functional hallmark of metastatic TICs from mammary carcinomas. PMID:27542270

  11. To adhere or not to adhere: Rates and reasons of medication adherence in hematological cancer patients.

    Science.gov (United States)

    Hall, Alix E; Paul, Chris; Bryant, Jamie; Lynagh, Marita C; Rowlings, Philip; Enjeti, Anoop; Small, Hannah

    2016-01-01

    To conduct a comprehensive review to examine among hematological cancer patients: (1) rates of adherence to self-administered cancer treatments; and (2) factors impacting on their adherence. Fifty two eligible publications were identified. The majority focused on Chronic Myeloid Leukaemia (CML) (n=40) and Acute Lymphoid Leukaemia (ALL) (n=11) patients. Adherence rates varied and depended on the definition and measures used. Patient understanding about their disease and treatment, and forgetting to take their medication impacted on patients' level of adherence; while the use of reminders reduced forgetfulness. There is a lack of valid and reliable information relating to medication adherence of hematological cancer patients. Based on the limited data available we provide a profile of CML and ALL patients at potential risk of medication non-adherence, as well as a proposed checklist that can be used by health care providers in assessing and supporting patients in adhering to their medication. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Metastatic Spinal Cord Compression Secondary to Liver Cancer

    Directory of Open Access Journals (Sweden)

    Daniel Gams Massi

    2017-01-01

    Full Text Available Metastatic spinal cord compression (MSCC is a medical emergency that requires rapid diagnosis and treatment to reduce pain, to preserve neurological functioning, and to prolong survival. The diagnosis of liver cancer is often neglected in the differential diagnosis of MSCC. Treatment is usually palliative and evolution is often fatal. This is a case report of a 28-year-old patient living in Mauritania hospitalized in November 2014 at the neurology department of Fann national teaching hospital in Dakar, for the management of a chronic dorsal spinal cord compression. The radiological and laboratory investigations done revealed the metastatic compression originating from a liver cancer with elevated alpha-fetoprotein and aspartate transaminase, positive hepatitis B surface antigen, and multiple metastasis in the lungs, mediastinum, ribs, iliac, and peritoneum. The hip joint X-ray showed a spontaneous fracture of the right femoral neck. The multidisciplinary treatment was palliative and the evolution was fatal within the month of hospitalization. Earlier diagnosis and treatment of MSCC may not have saved the life of the patient but may have prevented much suffering and would likely have prolonged the life of a young man.

  13. Tolerability of Capecitabine Monotherapy in Metastatic Colorectal Cancer: A Real-World Study.

    Science.gov (United States)

    Leicher, Laura W; de Graaf, Jacques C; Coers, Wilko; Tascilar, Metin; de Groot, Jan Willem B

    2017-03-01

    Capecitabine monotherapy is a treatment option for selected patients with metastatic colorectal cancer (mCRC) and is administered to up to 17% of patients. Data are limited with regard to adverse events and dosing practices associated with capecitabine monotherapy in real-world situations. The aim of this study was to provide real-world data on adverse event rates and dose adjustments/discontinuations associated with capecitabine monotherapy in patients with mCRC. This retrospective study analyzed data from CRC patients scheduled to receive up to eight planned cycles of capecitabine monotherapy between 2009 and 2013 at a single large community hospital in The Netherlands. Data on adverse events (hand-foot syndrome [HFS], gastrointestinal (GI) events, hematological adverse events, and cardiotoxicity), as well as relative dose intensities (RDIs), dose reductions, and discontinuations, were evaluated. Data from 86 patients (45 females; mean age at the start of treatment, 69 years) were included. A total of 46.5% of patients experienced HFS and 44.2% experienced a GI event at some time during treatment. Hematological events and cardiotoxicity were rare. Most patients (77%) started at below the recommended dose, and patients at the lowest dose also had the lowest median RDIs. Dose reductions and discontinuations occurred in 15-25% of patients who experienced HFS or GI event over the course of eight cycles. HFS and GI events were very common in patients treated with capecitabine monotherapy in a real-world clinical setting. Most patients started treatment at below the recommended dose, and 15-25% of patients who had HFS or a GI event had a dose reduction or discontinuation.

  14. Radical prostatectomy for locally advanced and metastatic prostate cancer.

    Science.gov (United States)

    Veeratterapillay, R; Goonewardene, S S; Barclay, J; Persad, R; Bach, C

    2017-04-01

    The management of advanced prostate cancer remains challenging. Traditionally, radical prostatectomy was discouraged in patients with locally advanced or node positive disease owing to the increased complication rate and treatment related morbidity. However, technical advances and refinements in surgical techniques have enabled the outcomes for patients with high risk prostate cancer to be improved. More recently, the concept of cytoreductive prostatectomy has been described where surgery (often Combined with an extended lymph node dissection) is performed in the setting of metastatic disease. Indirect evidence suggests an advantage using the cytoreductive approach. Hypothetical explanations for this observed benefit include decreased tumour burden, immune modulation, improved response to secondary treatment and avoidance of secondary complications attributable to local tumour growth. Nevertheless, prospective trials are required to investigate this further.

  15. Vinflunine treatment in patients with metastatic urothelial cancer

    DEFF Research Database (Denmark)

    Holmsten, Karin; Dohn, Line; Jensen, Niels Viggo

    2016-01-01

    of evaluating treatment patterns, response, survival parameters and side-effects. Data were collected retrospectively from the first 100 mUC patients treated with vinflunine at three Nordic cancer centers associated with the Nordic Urothelial Cancer Oncology Group. The overall response rate was 23% and complete.......6 vs. 6.0 months, P=0.008). The median number of cycles of vinflunine was 3 (range, 1-28). The current data confirms that vinflunine is an active agent for second-line treatment in an unselected clinical cohort of patients with mUC. ECOG PS and presence of visceral metastases were significant......In 2009, vinflunine was introduced as a second-line treatment to be used after the failure of platinum therapy in patients with metastatic urothelial carcinoma (mUC). The present study investigated the administered vinflunine to patients with mUC in standard clinical practice with the aim...

  16. Bevacizumab maintenance in metastatic colorectal cancer: How long?

    Science.gov (United States)

    De Stefano, Alfonso; Moretto, Roberto; Cella, Chiara Alessandra; Romano, Francesco Jacopo; Raimondo, Lucia; Fiore, Giovanni; Di Pietro, Francesca; Pepe, Stefano; De Placido, Sabino; Carlomagno, Chiara

    2014-11-16

    The management of patients with non-progressive metastatic colorectal cancer after six months of treatment has not yet been codified. The most relevant concerns are the effectiveness of maintenance vs discontinuation, and the tolerability of prolonged treatment. Here we report the case of a 72-year-old man affected by colorectal cancer with lung metastases who achieved a complete response after receiving capecitabine, oxaliplatin and bevacizumab for six months, and bevacizumab alone for six months. Bevacizumab was continued as maintenance regimen for more than three years. It was discontinued because of an arthroplasty. Fifty-eight months after beginning first-line treatment, the patient remains free from relapse. Adverse effects were minimal and easily controlled.

  17. Metastatic castration-resistant prostate cancer: changing landscape with cabazitaxel.

    Science.gov (United States)

    Fernández, Ovidio; Afonso, Javier; Vázquez, Sergio; Campos, Begoña; Lázaro, Matín; León, Luis; Antón Aparicio, Luis M

    2014-03-01

    Docetaxel is the standard first-line chemotherapy for men with metastatic castration-resistant prostate cancer. Until recently, there was no standard therapy after failure of docetaxel treatment. Cabazitaxel has been shown to improve overall survival in this setting. As a result, the treatment paradigm for mCRPC is changing rapidly. The improved survival shown with cabazitaxel provides an important new opportunity to treat men with mCRPC after docetaxel treatment. Despite the toxicity recorded in the pivotal study, subsequent trials have shown that cabazitaxel is a safe drug. Patient selection and the optimal interval between prior docetaxel treatment and cabazitaxel remain the critical issues. According to a subanalysis of the various studies discussed in this review, there is a patient profile that will probably benefit from use of cabazitaxel after docetaxel failure. Cabazitaxel represents a new treatment option for patients with prostate cancer.

  18. Profile of palbociclib in the treatment of metastatic breast cancer.

    Science.gov (United States)

    Ehab, Moataz; Elbaz, Mohamad

    2016-01-01

    Breast cancer is the most common cancer diagnosed in women. Each year, thousands die either because of disease progression or failure of treatment. Breast cancer is classified into different subtypes based on the molecular expression of estrogen receptor (ER), progesterone receptor, and/or human epidermal growth factor receptor 2 (HER2). These receptors represent important therapeutic targets either through monoclonal antibodies or through small-molecule inhibitors directed toward them. However, up to 40% of patients develop either a primary or a secondary resistance to the current treatments. Therefore, there is an urgent need for investigating new targets in order to overcome the resistance and/or enhance the current therapies. Cell cycle is altered in many human cancers, especially in breast cancer. Cyclin-dependent kinases (CDKs), especially CDK4 and CDK6, play a pivotal role in cell cycle progression that makes them potential targets for new promising therapies. CDK inhibition has shown strong antitumor activities, ranging from cytostatic antiproliferative effects to synergistic effects in combination with other antitumor drugs. In order to overcome the drawbacks of the first-generation CDK inhibitors, recently, new CDK inhibitors have emerged that are more selective to CDK4 and CDK6 such as palbociclib, which is the most advanced CDK4/6 inhibitor in trials. In preclinical studies, palbociclib has shown a very promising antitumor activity, especially against ERα+ breast cancer subtype. Palbociclib has gained world attention, and US the Food and Drug Administration has accelerated its approval for first-line treatment in combination with letrozole for the first-line systematic treatment of postmenopausal women with ERα+/HER2- locally advanced or metastatic breast cancer. In this review, we discuss the potential role of CDK inhibition in breast cancer treatment, and focus on palbociclib progress from preclinical studies to clinical trials with mentioning the

  19. Increased expression and aberrant localization of mucin 13 in metastatic colon cancer.

    Science.gov (United States)

    Gupta, Brij K; Maher, Diane M; Ebeling, Mara C; Sundram, Vasudha; Koch, Michael D; Lynch, Douglas W; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E; Jaggi, Meena; Chauhan, Subhash C

    2012-11-01

    MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer.

  20. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells

    Science.gov (United States)

    Lawson, Devon A.; Bhakta, Nirav R.; Kessenbrock, Kai; Prummel, Karin D.; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-01-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality1. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours2–5. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown2. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are

  1. Metastatic gastric cancer – focus on targeted therapies

    Directory of Open Access Journals (Sweden)

    Meza-Junco J

    2012-06-01

    Full Text Available Judith Meza-Junco, Michael B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta, CanadaAbstract: Gastric cancer (GC is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.Keywords: gastric cancer, targeted therapy, antiangiogenesis drugs, anti-EGFR drugs

  2. Local tumour hyperthermia as immunotherapy for metastatic cancer.

    Science.gov (United States)

    Toraya-Brown, Seiko; Fiering, Steven

    2014-12-01

    Abstract Local tumour hyperthermia for cancer treatment is currently used either for ablation purposes as an alternative to surgery or less frequently, in combination with chemotherapy and/or radiation therapy to enhance the effects of those traditional therapies. As it has become apparent that activating the immune system is crucial to successfully treat metastatic cancer, the potential of boosting anti-tumour immunity by heating tumours has become a growing area of cancer research. After reviewing the history of hyperthermia therapy for cancer and introducing methods for inducing local hyperthermia, this review describes different mechanisms by which heating tumours can elicit anti-tumour immune responses, including tumour cell damage, tumour surface molecule changes, heat shock proteins, exosomes, direct effects on immune cells, and changes in the tumour vasculature. We then go over in vivo studies that provide promising results showing that local hyperthermia therapy indeed activates various systemic anti-tumour immune responses that slow growth of untreated tumours. Finally, future research questions that will help bring the use of local hyperthermia as systemic immunotherapy closer to clinical application are discussed.

  3. Early palliative care for patients with metastatic cancer.

    Science.gov (United States)

    Gaertner, Jan; Wolf, J; Voltz, R

    2012-07-01

    At present, clinicians and healthcare providers are increasingly urged to advance the provision of state-of-the-art palliative care for patients with incurable cancer. This review provides an overview about the recent findings and practical suggestions. In the last decade, the awareness about the logistic and personal resources needed to meet the somatic and psychological needs of patients with progressive and life-threatening diseases has increased and in parallel, palliative care concepts and expertise have evolved substantially. Care concepts for patients with metastatic cancer emphasized the potential of interdisciplinary care. For example, in 2010, a randomized trial reported a benefit for patients with lung cancer who received early palliative care in addition to routine care. It is discussed that this was because of increased quality of life and detailed exploration of patient preferences. Patients, families and physicians benefit from shared care concepts of oncology and specialized palliative care. Although this concept is already becoming increasingly implemented in tertiary (comprehensive cancer-) care settings, the potential of this approach should be explored for other clinical settings such as office-based oncology.

  4. Survival of metastatic colorectal cancer patients treated with chemotherapy in Alberta (1995?2004)

    OpenAIRE

    Chen, Yiqun; Qiu, Zhenguo; Kamruzzaman, Anmmd; Snodgrass, Tom; Scarfe, Andrew; Bryant, Heather E.

    2009-01-01

    Goals of work Clinical trials have suggested that advances in chemotherapy significantly improve the survival of patients with metastatic colorectal cancer. Comparable evidence from clinical practice is scarce. This study aims to investigate the survival of patients with metastatic colorectal cancer treated with chemotherapy in Alberta, Canada. Patients and methods Trends of relative survival of patients diagnosed in 1994?2003 were assessed using Alberta Cancer Registry (ACR) data. The median...

  5. Sequencing of Cabazitaxel in Metastatic Castrate-Resistant Prostate Cancer: A Case Report

    OpenAIRE

    Donald Colbourn

    2012-01-01

    Prostate cancer is a common cancer in men; for metastatic disease, it has a 5-year survival rate of 30%. No FDA-approved therapy for castrate-resistant prostate cancer (CRPC) known to improve survival was available until 2004, when based on a significant survival benefit over mitoxantrone, docetaxel in combination with prednisone was approved. In combination with prednisone, cabazitaxel, which was approved in the United States in 2010, is indicated for patients with metastatic CRPC previously...

  6. Cell-Free DNA in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Boysen, Anders K; Pallisgård, Niels

    2017-01-01

    of tumor-specific mutations, whereas the use of total cell-free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta...... independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed, and meta-analysis applied on both aggregate data extraction...... therapy. Small fragments of circulating cell-free DNA (cfDNA) can be measured in a simple blood sample. This report presents the first meta-analysis of the prognostic value of total cfDNA measurement in patients with metastatic colorectal cancer. Data from 1,076 patients confirmed that patients...

  7. Treatment advances in liver-limited metastatic colorectal cancer.

    Science.gov (United States)

    Alberts, Steven R; Poston, Graeme J

    2011-12-01

    Over the last several decades advances in the management and treatment of patients with liver metastases from colorectal cancer (CRC) has changed a disease with a dismal prognosis to one with a potential for cure in some patients. Advances have been made through coordinated management of patients by surgeons, medical oncologists, radiologists, and other health care professionals coupled with advances in treatment options. Although these advances have clearly impacted patient outcomes, it is clear that the benefit of traditional surgical approaches and the use of cytoxic chemotherapy are reaching a plateau. Continued research to develop new and more active therapies, including targeted or biologic agents, is needed. This review discusses the advances made in management of patients with liver-limited metastatic disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Raltitrexed combined with bevacizumab in heavily pretreated metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ke Cheng

    2013-01-01

    Full Text Available No standard chemotherapy regimen has been established for metastatic colorectal cancer (mCRC after progression on 5-fluorouracil, oxaliplatin, and irinotecan. Here, we report the combination of raltitrexed and bevacizumab as a salvage regimen for the treatment of three heavily pretreated patients with KRAS mutant mCRC. All three patients had stable disease (SD according to response evaluation criteria in solid tumors (RECIST criteria, progression free survival (PFS were 3.0, 3.2 months for the first two patients and have not been reached for over 5 months for the third patient and no severe adverse effect was observed. The combination of raltitrexed plus bevacizumab in mCRC seems worthy of further investigation.

  9. FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Geva, Ravit; Vecchione, Loredana; Kalogeras, Konstantinos T

    2015-01-01

    of 0.6 in progression-free survival (PFS) for FCGR2A-HH versus the rest and FCGR3A-VV versus the rest, with an 80% power, 80 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type (KRAS-WT) and 52 KRAS-WT patients are required, respectively. This leads to a total sample size of 952 and 619......OBJECTIVE: We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled. DESIGN: To show a HR advantage...

  10. Cabazitaxel in metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Yap, Timothy A; Pezaro, Carmel J; de Bono, Johann S

    2012-09-01

    Metastatic castration-resistant prostate cancer (CRPC) has a poor prognosis and remains a significant therapeutic challenge. Prior to 2010, docetaxel chemotherapy was the only treatment shown to improve overall survival, symptom control and quality of life in patients with CRPC. Research efforts focused on overcoming chemoresistance to taxanes eventually led to the development of multiple novel anti-tumor agents, including cabazitaxel. Cabazitaxel has recently been shown to significantly improve overall survival compared with mitoxantrone in a large multicenter Phase III study. This article details the preclinical and clinical development of cabazitaxel and discusses the importance of this novel chemotherapy in CRPC. The authors also discuss the challenges now facing the future use of cabazitaxel in CRPC, including the determination of the optimal dose of cabazitaxel in patients with advanced CRPC, the ideal sequencing of cabazitaxel relative to other anti-tumor treatments, appropriate patient selection and novel strategies for the assessment of treatment response.

  11. Metastatic Prostate Cancer and the Bone: Significance and Therapeutic Options.

    Science.gov (United States)

    Gartrell, Benjamin A; Coleman, Robert; Efstathiou, Eleni; Fizazi, Karim; Logothetis, Christopher J; Smith, Matthew R; Sonpavde, Guru; Sartor, Oliver; Saad, Fred

    2015-11-01

    Skeletal involvement is common in metastatic prostate cancer (PCa) and is associated with skeletal-related events (SREs). The interaction of PCa with the bone microenvironment contributes to self-perpetuating progression of cancer in bone. Bone-targeted agents (BTAs) are available for use in metastatic castration-resistant prostate cancer (mCRPC). To review the biology of bone metastases in PCa and to review the clinical trial data for BTAs in PCa. A literature search was conducted in October 2014. Keywords included clinical trial, prostate cancer, denosumab, bisphosphonates, zoledronic acid, radium-223, bone turnover markers, skeletal-related events, and symptomatic skeletal events. The biology of bone metastases in PCa is summarized. Data supporting the use of BTAs in PCa are reviewed, and issues related to the combination and sequencing of available agents are discussed. The osteoclast-targeted agents zoledronic acid and denosumab decrease SREs in mCRPC, and the α-emitting radiopharmaceutical agent radium-223 improves survival and decreases symptomatic skeletal events. Limited data are available to guide the sequence and combination of BTAs with disease-modifying agents, although data support the use of osteoclast-targeted drugs with chemotherapy, androgen-targeted agents, and radium-223. Zoledronic acid does not reduce SREs when started prior to castration resistance, although osteoclast-targeted agents do improve outcomes when used in patients with asymptomatic to minimally symptomatic chemotherapy-naive mCRPC. The optimal sequence of radium-223 with chemotherapy is uncertain, although data suggest the efficacy and tolerability of radium-223 is similar with either sequence. Clinical trials evaluating the combination of BTAs with other agents are under way. The optimization of sequence and combination strategies will guide the best use of available agents. The literature pertaining to bone metastases in prostate cancer (PCa) was reviewed, and the current

  12. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

    Science.gov (United States)

    2017-12-04

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  13. A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

    Science.gov (United States)

    2017-06-28

    TYPE 08/ 03/20 17 Publ ication/Journal 4. TITLE AND SUBTITLE A unique case of muscle-invasive metastatic breast cancer mimicking myositis 6...Rev. 8/98) Prescnbed by ANSI Std Z39. 18 Adobe Profes11on11 7.0 Title: A Unique Case of M uscle-Invasive Metastatic Breast Cancer M imicking...an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid

  14. Primary gastric cancer presenting with a metastatic embolus in the common carotid artery: a case report

    Directory of Open Access Journals (Sweden)

    Zhang Ying

    2012-10-01

    Full Text Available Abstract Although about 30% of gastric cancers have distant metastasis at the time of initial diagnosis, metastatic tumor embolus in the main blood vessels is not common, especially in the main artery. The report presents, for the first time, an extremely rare clinical case of a metastatic embolus in the common carotid artery (CCA from primary gastric cancer. Metastatic embolus from the primary tumor should be considered when patients present with gastric cancer accompanied by intravascular emboli. The patient should be actively examined further so as to allow early detection and treatment.

  15. Immortalizing the Complexity of Cancer Metastasis Genetic Features of Lethal Metastatic Pancreatic Cancer Obtained from Rapid Autopsy

    Science.gov (United States)

    Embuscado, Erlinda E.; Laheru, Daniel; Ricci, Francesca; Yun, Ki Jung; de Boom Witzel, Sten; Seigel, Allison; Flickinger, Katie; Hidalgo, Manuel; Bova, G. Steven; Iacobuzio-Donahue, Christine A.

    2009-01-01

    The virtual lack of well-characterized metastatic pancreatic cancer tissues for study has limited systematic studies of the metastatic process of this deadly disease. To address this important issue, we have instituted a rapid autopsy protocol for the collection of high quality tissues from patients with metastatic pancreatic cancer, called the Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP). At the time of preparation of this manuscript, 20 patients with metastatic pancreatic cancer and one patient with metastatic colon cancer have undergone a rapid autopsy in association with the GICRMDP. The average time interval achieved for these 21 patients was 8.0 hours, with more than 500 individual samples of matched high quality primary and metastatic pancreatic cancer tissues, peritoneal/pleural fluid and blood obtained so far. For the first four patients in which the autopsy was performed in <6 hours, we have successfully xenografted the primary tumor and/or two to four independent matched metastases from a variety of target organ sites, with a take rate of almost 60% for the first 26 xenografted tumors attempted. In an initial survey of KRAS2, TP53 and DPC4 genetic status in lethal metastatic pancreatic cancers, activating KRAS2 mutations were detected in 82% of cases and inactivating TP53 mutations in 55% of cases, consistent with rates of genetic alteration of these genes in early stage pancreatic cancers. However, DPC4 inactivation was found in 75% of patients analyzed, suggesting that genetic inactivation of the DPC4 tumor suppressor gene continues to be selected for with growth at the primary site and metastatic spread to other organs. The invaluable tissue resources generated by the success of the GICRMDP will provide an unparalleled resource for study of metastatic pancreatic cancer and of the metastatic process in general. PMID:15846069

  16. Immortalizing the complexity of cancer metastasis: genetic features of lethal metastatic pancreatic cancer obtained from rapid autopsy.

    Science.gov (United States)

    Embuscado, Erlinda E; Laheru, Daniel; Ricci, Francesca; Yun, Ki Jung; de Boom Witzel, Sten; Seigel, Allison; Flickinger, Katie; Hidalgo, Manuel; Bova, G Steven; Iacobuzio-Donahue, Christine A

    2005-05-01

    The virtual lack of well-characterized metastatic pancreatic cancer tissues for study has limited systematic studies of the metastatic process of this deadly disease. To address this important issue, we have instituted a rapid autopsy protocol for the collection of high quality tissues from patients with metastatic pancreatic cancer, called the Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP). At the time of preparation of this manuscript, 20 patients with metastatic pancreatic cancer and one patient with metastatic colon cancer have undergone a rapid autopsy in association with the GICRMDP. The average time interval achieved for these 21 patients was 8.0 hours, with more than 500 individual samples of matched high quality primary and metastatic pancreatic cancer tissues, peritoneal/pleural fluid and blood obtained so far. For the first four patients in which the autopsy was performed in <6 hours, we have successfully xenografted the primary tumor and/or two to four independent matched metastases from a variety of target organ sites, with a take rate of almost 60% for the first 26 xenografted tumors attempted. In an initial survey of KRAS2, TP53 and DPC4 genetic status in lethal metastatic pancreatic cancers, activating KRAS2 mutations were detected in 82% of cases and inactivating TP53 mutations in 55% of cases, consistent with rates of genetic alteration of these genes in early stage pancreatic cancers. However, DPC4 inactivation was found in 75% of patients analyzed, suggesting that genetic inactivation of the DPC4 tumor suppressor gene continues to be selected for with growth at the primary site and metastatic spread to other organs. The invaluable tissue resources generated by the success of the GICRMDP will provide an unparalleled resource for study of metastatic pancreatic cancer and of the metastatic process in general.

  17. Role of ultrasound in detection of metastatic neck nodes in patients with oral cancer

    Directory of Open Access Journals (Sweden)

    P Sureshkannan

    2011-01-01

    Conclusion: USG is a reliable and valuable tool for metastatic lymph node screening in head and neck cancer patients. It is a cheap, noninvasive, easy-to-handle and cost-effective diagnostic method. USG performed better than clinical palpation in detecting cervical metastatic nodes.

  18. Identification of ovarian cancer metastatic miRNAs.

    Directory of Open Access Journals (Sweden)

    Souriya Vang

    Full Text Available Serous epithelial ovarian cancer (EOC patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2-4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.

  19. Radium-223 dichloride for the treatment of metastatic prostate cancer.

    Science.gov (United States)

    Turner, Philip Geoffrey; O'Sullivan, Joe

    2014-10-01

    Bone metastases are a frequent complication of many malignancies and are particularly common in metastatic prostate cancer, where they are associated with a high degree of morbidity. Until recently, treatments relied on palliative bone targeting measures with no proven survival-prolonging action or on systemic agents with general anti-prostate cancer activity but significant toxicities. Radium-223 dichloride is a bone-seeking, α-emitting, radionuclide that has recently been licensed in the US and Europe for the treatment of men with castration-resistant prostate cancer, bone metastases and no known visceral metastases. Radium-223 is the first bone-seeking radionuclide therapy proven to result in increased overall survival versus placebo. The existing market of bone-targeted agents is reviewed before considering what radium-223 adds by examining its pharmacology, pharmacokinetics and clinical efficacy and safety data. Initial relevant papers were identified by searching PubMed using combinations of the terms, 'Radium', 'Prostatic neoplasms', 'Bone', 'Neoplasm metastasis'. Consideration is given to further preclinical work needed into the mechanism of action of radium-223 and future clinical directions of the drug including combinations with other agents.

  20. Unusual asymptomatic presentation of bladder cancer metastatic to the penis.

    Science.gov (United States)

    Giunchi, Francesca; Vasuri, Francesco; Valerio, Vagnoni; Montagnani, Ilaria; Nelli, Federico; Fiorentino, Michelangelo; Raspollini, Maria Rosaria

    2017-06-01

    Penile metastasis is an extremely rare event and mainly originate from primary pelvic tumor sites such us urinary bladder, gastro-intestinal tract and prostate and more rarely from respiratory system, bone tumors and melanoma. Here we describe the unusual presentation of two bladder urothelial cancer metastatic to the penis with no relevant clinical symptoms. Namely, a 69 years-old man with a warthy lesions of the foreskin and the glans misunderstood for a condylomata that at histological and immunohistochemical analysis showed a bladder urothelial carcinoma; and a 71 years-old man with reddish skin lesion of the glans, a previous history of bladder and urethral carcinoma and histological pagetoid spread of urothelial cancer to the glans. Recurrent bladder urothelial carcinoma is usually a visceral disease that rarely presents as a superficial asymptomatic skin lesion. The two reported cases were asymptomatic superficial penis metastases with a relatively slow growth and a fairy good prognosis after conservative surgical approach. Accurate clinical examination of the penis is mandatory for males with history of bladder cancer. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.

    Science.gov (United States)

    Cejalvo, Juan M; Martínez de Dueñas, Eduardo; Galván, Patricia; García-Recio, Susana; Burgués Gasión, Octavio; Paré, Laia; Antolín, Silvia; Martinello, Rosella; Blancas, Isabel; Adamo, Barbara; Guerrero-Zotano, Ángel; Muñoz, Montserrat; Nucíforo, Paolo; Vidal, María; Pérez, Ramón M; Chacón López-Muniz, José I; Caballero, Rosalía; Peg, Vicente; Carrasco, Eva; Rojo, Federico; Perou, Charles M; Cortés, Javier; Adamo, Vincenzo; Albanell, Joan; Gomis, Roger R; Lluch, Ana; Prat, Aleix

    2017-05-01

    Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We identified 47 genes that were expressed differentially in metastatic versus primary disease. Metastatic tumors were enriched for proliferation-related and migration-related genes and diminished for luminal-related genes. Expression of proliferation-related genes were better at predicting overall survival in metastatic disease (OSmet) when analyzed in metastatic tissue rather than primary tissue. In contrast, a basal-like gene expression signature was better at predicting OSmet in primary disease compared with metastatic tissue. We observed correlations between time to tumor relapse and the magnitude of changes of proliferation, luminal B, or HER2-E signatures in metastatic versus primary disease. Although the intrinsic subtype was largely maintained during metastatic progression, luminal/HER2-negative tumors acquired a luminal B or HER2-E profile during metastatic progression, likely reflecting tumor evolution or acquisition of estrogen independence. Overall, our analysis revealed the value of stratifying gene expression by both cancer subtype and tissue type, providing clinicians more refined tools to evaluate prognosis and treatment. Cancer Res; 77(9); 2213-21. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers

    Directory of Open Access Journals (Sweden)

    Friedenson Bernard

    2007-08-01

    Full Text Available Abstract Background The present study was designed to test the hypothesis that inactivation of virtually any component within the pathway containing the BRCA1 and BRCA2 proteins would increase the risks for lymphomas and leukemias. In people who do not have BRCA1 or BRCA2 gene mutations, the encoded proteins prevent breast/ovarian cancer. However BRCA1 and BRCA2 proteins have multiple functions including participating in a pathway that mediates repair of DNA double strand breaks by error-free methods. Inactivation of BRCA1, BRCA2 or any other critical protein within this "BRCA pathway" due to a gene mutation should inactivate this error-free repair process. DNA fragments produced by double strand breaks are then left to non-specific processes that rejoin them without regard for preserving normal gene regulation or function, so rearrangements of DNA segments are more likely. These kinds of rearrangements are typically associated with some lymphomas and leukemias. Methods Literature searches produced about 2500 epidemiology and basic science articles related to the BRCA pathway. These articles were reviewed and copied to a database to facilitate access. Meta-analyses of statistical information compared risks for hematologic cancers vs. mutations for the components in a model pathway containing BRCA1/2 gene products. Results Deleterious mutations of genes encoding proteins virtually anywhere within the BRCA pathway increased risks up to nearly 2000 fold for certain leukemias and lymphomas. Cancers with large increases in risk included mantle cell lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, and prolymphocytic leukemia. Mantle cell lymphoma is defined by a characteristic rearrangement of DNA fragments interchanged between chromosomes 11 and 14. DNA translocations or rearrangements also occur in significant percentages of the other cancers. Conclusion An important function of the BRCA pathway is to

  3. Metastatic colon cancer from extrahepatic cholangiocarcinoma presenting as painless jaundice: case report and literature review.

    Science.gov (United States)

    Vabi, Benjamin W; Carter, Jeffrey; Rong, Rong; Wang, Minhua; Corasanti, James G; Gibbs, John F

    2016-04-01

    Cholangiocarcinoma (CCA) is a rare cancer of the biliary epithelium comprising only about 3% of all gastrointestinal malignancies. It is a highly aggressive malignancy and confers a dismal prognosis with majority of patients presenting with metastatic disease. Metastatic CCA to the colon is extremely rare with only few cases reported in the literature. We present a 61-year-old patient with incidental synchronous metastatic colonic adenocarcinoma from extra-hepatic CCA. Laboratory data revealed significant indirect hyperbilirubinemia and transaminitis. Imaging study showed intrahepatic bile ducts prominence without mass lesions. Incidentally, there was diffuse colonic thickening without mass lesions or obstruction. Endoscopic retrograde cholangiopancreatography (ERCP) showed a common bile duct stricture. Brushings were consistent with CCA. Screening colonoscopy identified nodularity and biopsy and immunostaining were consistent with CCA metastasis to colon. The patient elected for palliative and comfort care. Metastatic CCA to the colon is a rare pattern of distant spread that may pose a diagnostic challenge. Some salient characteristics may assist in the differentiation of primary colon cancer and metastatic colon cancer from CCA. Little remains known about the pathogenic behavior of metastatic secondary colorectal cancer. And more so, the management approach to such metastatic cancer still remains to be defined. Screening colonoscopy in patients presenting with resectable CCA may alter management. Furthermore, whether patients with history of resected CCA may benefit from a more frequent screening colonoscopy remains to be validated.

  4. Clinical significance of the metastatic lymph-node ratio in early gastric cancer.

    Science.gov (United States)

    Kunisaki, Chikara; Makino, Hirochika; Akiyama, Hirotoshi; Otsuka, Yuichi; Ono, Hidetaka A; Kosaka, Takashi; Takagawa, Ryo; Nagahori, Yutaka; Takahashi, Masazumi; Kito, Fumihiko; Shimada, Hiroshi

    2008-03-01

    The metastatic lymph-node ratio has important prognostic value in gastric cancer; this study focused on its significance in early gastric cancer. In total, 1,472 patients with early gastric cancer underwent curative gastrectomy between 1992 and 2001. Of these, 166 (11.3%) had histologically proven lymph-node metastasis. Prognostic factors were identified by univariate and multivariate analyses. Metastasis was evaluated using the Japanese Classification of Gastric Carcinoma (JGC) and the Union Internationale Contre le Cancer/Tumor, Node, Metastasis (UICC/TNM) Classification. The metastatic lymph-node ratio was calculated using the hazard ratio. The cut-off values for the metastatic lymph-node ratio were set at 0, or=0.15 to or=0.30. The numbers of dissected and metastatic lymph nodes were correlated, but the number of dissected lymph nodes and the metastatic lymph-node ratio was not related. The JGC and UICC/TNM classification demonstrated stage migration and heterogeneous stratification for disease-specific survival. The metastatic lymph-node ratio showed less stage migration and homogenous stratification. The metastatic lymph-node ratio may be a superior method of classification, which provides also accurate prognostic stratification for early gastric cancer patients.

  5. The prognostic importance of metastatic site in men with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Pond, Gregory R; Sonpavde, Guru; de Wit, Ronald; Eisenberger, Mario A; Tannock, Ian F; Armstrong, Andrew J

    2014-01-01

    The presence of visceral metastases is adversely prognostic in men with metastatic castration-resistant prostate cancer (mCRPC), but the prognostic impact of the site of visceral metastasis is unclear. Men with mCRPC in the TAX 327 phase 3 trial receiving docetaxel or mitoxantrone every 3 wk or weekly docetaxel, each with prednisone, were analyzed retrospectively to study the impact of the site of visceral metastasis on overall survival (OS). Patients were assessed for OS by site of metastases: liver with or without other sites, lung with or without bone or lymph nodes, bone plus lymph nodes, bone only, and lymph nodes only. Cox proportional hazards regression, adjusted for treatment and stratification factors, was performed. Men with liver metastases with or without other metastases had shorter median OS (10.0 mo; 95% confidence interval [CI], 5.4-11.5) than men with lung metastases with or without bone or nodal metastases (median OS: 14.4 mo; 95% CI, 11.5-22.4). Men with lymph node-only disease had the best median OS (26.7 mo; 95% CI, 22.3-34.2), followed by men with bone-only metastases (median OS: 19.0 mo; 95% CI, 18.2-20.7) and bone-plus-node disease (median OS: 15.7 mo; 95% CI, 14.4-17.2). Thus, pattern of spread including site of visceral metastasis confers a differential prognostic impact. These data require validation and may inform trial design and therapy. Copyright © 2013. Published by Elsevier B.V.

  6. Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

    Science.gov (United States)

    Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G M; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M

    2014-01-01

    In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66). The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

  7. MTHFR polymorphisms and capecitabine-induced toxicity in patients with metastatic colorectal cancer

    NARCIS (Netherlands)

    van Huis-Tanja, Lieke H.; Gelderblom, Hans; Punt, Cornelis J. A.; Guchelaar, Henk-Jan

    2013-01-01

    Objective The availability of current chemotherapeutic options for metastatic colorectal cancer (mCRC) has increased survival, but it is also accompanied by considerable morbidity. Fluoropyrimidines are the mainstay of systemic therapy. Germline pharmacogenetic markers involved in 5-fluorouracil

  8. The clinical significance of circulating tumor cells in non-metastatic colorectal cancer - A review

    DEFF Research Database (Denmark)

    Thorsteinsson, M; Jess, Per

    2011-01-01

    BACKGROUND: Finding a clinical tool to improve the risk stratification and identifying those colorectal cancer patients with an increased risk of recurrence is of great importance. The presence of circulating tumor cells (CTC) in peripheral blood can be a strong marker of poor prognosis in patients...... with metastatic disease, but the prognostic role of CTC in non-metastatic colorectal cancer is less clear. The aim of this review is to examine the possible clinical significance of circulating tumor cells in non-metastatic colorectal cancer (TNM-stage I-III) with the primary focus on detection methods...... and prognosis. METHODS: The PubMed and Cochrane database and reference lists of relevant articles were searched for scientific literature published in English from January 2000 to June 2010. We included studies with non-metastatic colorectal cancer (TNM-stage I-III) and CTC detected pre- and/or post...

  9. The clinical value of hybrid sentinel lymphoscintigraphy to predict metastatic sentinel lymph nodes in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Na, Cang Ju; Kim, Jeong Hun; Choi, Se Hun; Han, Yeon Hee; Jeong, Hwan Jeong; Sohn, Myung Hee; Youn, Hyun Jo; Lim, Seok Tae [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2015-03-15

    Hybrid imaging techniques can provide functional and anatomical information about sentinel lymph nodes in breast cancer. Our aim in this study was to evaluate which imaging parameters on hybrid sentinel lymphoscintigraphy predicted metastatic involvement of sentinel lymph nodes (SLNs) in patients with breast cancer. Among 56 patients who underwent conventional sentinel lymphoscintigraphy, 45 patients (age, 53.1 ± 9.5 years) underwent hybrid sentinel lymphoscintigraphy using a single-photon emission computed tomography (SPECT)/computed tomography (CT) gamma camera. On hybrid SPECT/CT images, we compared the shape and size (long-to-short axis [L/S] ratio) of the SLN, and SLN/periareolar injection site (S/P) count ratio between metastatic and non-metastatic SLNs. Metastatic involvement of sentinel lymph nodes was confirmed by pathological biopsy. Pathological biopsy revealed that 21 patients (46.7 %) had metastatic SLNs, while 24 (53.3 %) had non-metastatic SLNs. In the 21 patients with metastatic SLNs, the SLN was mostly round (57.1 %) or had an eccentric cortical rim (38.1 %). Of 24 patients with non-metastatic SLNs, 13 patients (54.1 %) had an SLN with a C-shape rim or eccentric cortex. L/S ratio was 2.04 for metastatic SLNs and 2.38 for non-metastatic SLNs. Seven (33 %) patients had T1 primary tumors and 14 (66 %) had T2 primary tumors in the metastatic SLN group. In contrast, 18 (75 %) patients had T1 primary tumors and six (25 %) had T2 tumors in the non-metastatic SLN group. S/P count ratio was significantly lower in the metastatic SLN group than the non-metastatic SLN group for those patients with a T1 primary tumor (p = 0.007). Hybrid SPECT/CT offers the physiologic data of SPECT together with the anatomic data of CT in a single image. This hybrid imaging improved the anatomic localization of SLNs in breast cancer patients and predicted the metastatic involvement of SLNs in the subgroup of breast cancer patients with T1 primary tumors.

  10. A Novel Differentiation Therapy Approach to Reduce the Metastatic Potential of Basal, Highly Metastatic, Triple-Negative Breast Cancers

    Science.gov (United States)

    2012-05-01

    metastases by GATA3 results from the suppression of lysyl oxidase (LOX) expression, a metastasis promoting matrix remodeling protein, via epigenetic changes...TERMS GATA3, Lysyl oxidase , triple-negative breast cancer, metastasis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF...macrophages promoting metastatic progression. Importantly, we demonstrate that the repression of lysyl oxidase (LOX) expression by GATA3 is a key

  11. Disseminated breast cancer cells acquire a highly malignant and aggressive metastatic phenotype during metastatic latency in the bone.

    Directory of Open Access Journals (Sweden)

    Carolyn G Marsden

    Full Text Available BACKGROUND: Disseminated tumor cells (DTCs in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorigenicity and metastatic potential of dormant disseminated breast cancer cells (prior to activation in the bone marrow. METHODOLOGY/PRINCIPAL FINDINGS: Total bone marrow, isolated from mice previously injected with tumorspheres into the mammary fat pad, was injected into the mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were analyzed by H+E staining to detect metastases. The injection of bone marrow isolated from mice previously injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-injection. However, the injection of bone marrow isolated from non-injected mice did not result in tumor formation in the mammary fat pad. The DTC-derived tumors exhibited accelerated development of metastatic lesions within the lung, liver and kidney. The resultant tumors and the majority of metastatic lesions within the lung and liver exhibited a mesenchymal-like phenotype. CONCLUSIONS/SIGNIFICANCE: Dormant DTCs within the bone marrow are highly malignant upon injection into the mammary fat pad, with the accelerated development of metastatic lesions within the lung, liver and kidney. These results suggest the acquisition of a more aggressive phenotype of DTCs during

  12. Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis.

    Directory of Open Access Journals (Sweden)

    Celine Lefebvre

    2016-12-01

    Full Text Available Major advances have been achieved in the characterization of early breast cancer (eBC genomic profiles. Metastatic breast cancer (mBC is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing.Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A were identified as significantly mutated in mBC (false discovery rate [FDR] < 0.1. Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN were more frequently mutated in mBC as compared to eBC (FDR < 0.01. ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI [9-155], p = 1.2e-12 and also presented with focal amplification (n = 9 for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+ and HER2 negative (HER2- mBCs (19%. HR+/HER2- mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR pathway (TSC1 and TSC2 as compared to HR+/HER2- eBC (respectively 6% and 0.7%, p = 0.0004. Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8, NOTCH3 (n = 7, and ALK (n = 7. Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2- metastatic tumors as compared to primary TCGA samples (p < 2e-16. The main limitations of this study include the absence of bone metastases and the size of the cohort, which might

  13. Childhood hematologic cancer and residential proximity to oil and gas development

    Science.gov (United States)

    McKenzie, Lisa M.; Allshouse, William B.; Byers, Tim E.; Bedrick, Edward J.; Serdar, Berrin; Adgate, John L.

    2017-01-01

    Background Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Methods Participants were 0–24 years old, living in rural Colorado, and diagnosed with cancer between 2001–2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Findings Overall, ALL cases 0–24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5–24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0–4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Conclusion Because oil and gas development has potential to expose a large population

  14. Radium-223 in metastatic castration resistant prostate cancer.

    Science.gov (United States)

    Vuong, Winston; Sartor, Oliver; Pal, Sumanta K

    2014-01-01

    In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently) radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89), radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.

  15. Radium-223 in metastatic castration resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Winston Vuong

    2014-06-01

    Full Text Available In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.

  16. DIFFERENTIAL DIAGNOSIS OF PRIMARY AND METASTATIC OVARIAN TUMORS IN PATIENTS WITH COLONIC CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Komarov

    2013-01-01

    Full Text Available This report summarizes existing data on differential diagnosis between primary and metastatic ovarian cancer in patients with colorectal cancer (CRC. The results obtained in N.N. Blokhin Russian Cancer Research Center on the management of this malignancy are also presented. The evidence in favour of the need of genetic counseling and monitoring of the patients with aggravated familial history for early diagnosis of synchronous and metachronous ovarian cancer in patients with CRC is produced. A number of clinical, laboratory and diagnostic methods in addition to immunohistology and molecular genetics should be used for differential diagnosis of primary and metastatic ovarian cancer in patients with CRC.

  17. Estramustine phosphate versus placebo as second line treatment after orchiectomy in patients with metastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Asmussen, C

    1997-01-01

    We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer.......We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer....

  18. Targeted Therapy Combined with Immune Modulation Using Gold Nanoparticles for Treating Metastatic Colorectal Cancer

    Science.gov (United States)

    2017-09-01

    stimulate the body’s immune system to target and attack cancer cells. Another part of our research includes coating these gold nanoparticles with...AWARD NUMBER: W81XWH-16-1-0427 TITLE: Targeted Therapy Combined with Immune Modulation Using Gold Nanoparticles for Treating Metastatic Colorectal... Nanoparticles for Treating Metastatic Colorectal Cancer 5b. GRANT NUMBER W81XWH-16-1-0427 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Branden Moriarity, Tim

  19. Consensus on precision medicine for metastatic cancers: a report from the MAP conference

    OpenAIRE

    Swanton, C.; Soria, J.-C.; Bardelli, A.; Biankin, A.; Caldas, C.; Chandarlapaty, S.; de Koning, L.; Dive, C.; Feunteun, J.; Leung, S.-Y.; Marais, R.; Mardis, E. R.; McGranahan, N.; Middleton, G.; Quezada, S. A.

    2016-01-01

    Recent advances in biotechnologies have led to the development of multiplex genomic and proteomic analyses for clinical use. Nevertheless, guidelines are currently lacking to determine which molecular assays should be implemented in metastatic cancers. The first MAP conference was dedicated to exploring the use of genomics to better select therapies in the treatment of metastatic cancers. Sixteen consensus items were covered. There was a consensus that new technologies like next-generation se...

  20. Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis

    OpenAIRE

    Pollari, Sirkku; Kakonen, Sanna-Maria; Edgren, Henrik; Wolf, Maija; Kohonen, Pekka; Sara, Henri; Guise, Theresa,; Nees, Matthias; Kallioniemi, Olli

    2010-01-01

    Abstract Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, an understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidences for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic...

  1. Molecular markers in circulating tumour cells from metastatic colorectal cancer patients

    OpenAIRE

    Gazzaniga, Paola; Gradilone, Angela; Petracca, Arianna; Nicolazzo, Chiara; Raimondi, Cristina; Iacovelli, Roberto; Naso, Giuseppe; Cortesi, Enrico

    2010-01-01

    Abstract The prognosis of metastatic cancer patients is still largely affected by treatment failure, mainly due to drug resistance. The hypothesis that chemotherapy might miss circulating tumour cells (CTCs) and particularly a subpopulation of more aggressive, stem-like CTCs, characterized by multidrug resistance, has been recently raised. We investigated the prognostic value of drug resistance and stemness markers in CTCs from metastatic colorectal cancer patients treated with oxaliplatin (L...

  2. Resolution of Diffuse Intrahepatic Biliary Strictures after Chemotherapy for Metastatic Ovarian Cancer

    Science.gov (United States)

    Sundaram, Vinay; Barrows, Brad D.; Lo, Simon K.; Gaddam, Srinivas

    2017-01-01

    Sclerosing cholangitis and cholestatic jaundice secondary to metastatic disease is a rare complication. We report a rare case of secondary sclerosing cholangitis (SSC) due to lymphatic spread from ovarian cancer with complete resolution after chemotherapy. The diagnosis of SSC from metastatic ovarian cancer was clinically challenging, as endoscopic retrograde cholangiopancreatography revealed irregular hepatic ducts consistent with sclerosing cholangitis, but it did not identify any malignant cells. The final diagnosis was made with liver biopsy revealing high-grade metastatic Mullerian carcinoma. The patient responded well to chemotherapy and is in remission. A timely diagnosis is important and can lead to complete resolution of the disease. PMID:28620623

  3. CURRENT POSSIBILITIES OF TREATMENT FOR VISCERAL METASTASES IN PATIENTS WITH METASTATIC CASTRATION-REFRACTORY PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-07-01

    Full Text Available Medications increasing the survival of patients with metastatic castration-refractory prostate cancer (CRPC are lacking today. In the past 3 years, in the pharmaceutical market there have been a few novel drugs to treat progressive prostate cancer. Abiraterone acetate is an androgen synthesis inhibitor, which is also used to increase the survival of patients with metastatic CRPC that progresses after chemotherapy. The results of treatment for metastatic CRPC depend on a number of factors. Visceral metastases are poor predictors of the course of the disease. The results of abiraterone acetate treatment were analyzed in CRPC patients with visceral metastases.

  4. The oncologic role of local treatment in primary metastatic prostate cancer.

    Science.gov (United States)

    Ghadjar, Pirus; Briganti, Alberto; De Visschere, Peter J L; Fütterer, Jurgen J; Giannarini, Gianluca; Isbarn, Hendrik; Ost, Piet; Sooriakumaran, Prasanna; Surcel, Christian I; van den Bergh, Roderick C N; van Oort, Inge M; Yossepowitch, Ofer; Ploussard, Guillaume

    2015-06-01

    To determine the oncologic benefit or otherwise of local treatment of the prostate in patients with primary metastatic prostate cancer. A review of the literature was performed in April 2014 using the Medline/PubMed database. Studies were identified using the search terms "prostate cancer," "metastatic," "metastasis," "high risk," "radiation therapy," "radiotherapy" and "prostatectomy" from 1990 until April, 2014. Articles were also identified through searches of references of these articles. Retrospective series and population-based data suggest that the use of local treatment of the prostate in patients with primary metastatic prostate cancer may improve cancer-specific survival and overall survival compared with treating these patients with androgen deprivation therapy alone. The clinical outcome in metastatic prostate cancer is largely determined by the extent of lymph node involvement and overall metastatic burden. Contemporary data are lacking to recommend one alternative of local therapy (radiotherapy or radical prostatectomy) over the other. The primary limitation of this literature review is the lack of published randomized trial assessing the role of local treatment in addition to systemic therapy. Local treatment appears to improve oncologic outcomes in metastatic prostate cancer patients. Nevertheless, due to the lack of high-quality evidence, its role needs to be confirmed in future prospective trials. The selection of ideal candidates and optimal treatment alternative (radiotherapy, radical prostatectomy or other) warrants further investigation.

  5. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with {sup 131}I-MIP-1095

    Energy Technology Data Exchange (ETDEWEB)

    Afshar-Oromieh, Ali; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Zechmann, Christian; Mier, Walter; Spohn, Fabian; Debus, Nils; Kratochwil, Clemens [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Armor, Thomas [Progenics Pharmaceuticals, Inc., New York, NY (United States); Holland-Letz, Tim [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Babich, John [Weill Cornell Medicine, Division of Radiopharmaceutical Sciences, Department of Radiology, New York, NY (United States); Weill Cornell Medicine, Citigroup Biomedical Imaging Center, New York, NY (United States); Weill Cornell Medicine, Meyer Cancer Center, New York, NY (United States)

    2017-06-15

    Prostate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies. Thirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with {sup 131}I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy. The applied doses were separated in three groups: <3.5, 3.5-5.0 and >5.0 GBq. Antitumor and side-effects were analyzed by blood samples and other clinical data. Follow-up was conducted for up to 5 years. The best therapeutic effect was achieved by the first therapy. A PSA decline of ≥50% was achieved in 70.6% of the patients. The second and third therapies were significantly less effective. There was neither an association between the applied activity and PSA response or the time-to-progression. Hematologic toxicities were less prevalent but presented in a higher percentage of patients with increasing number of therapies. After hematologic toxicities, xerostomia was the second most frequent side effect and presented more often and with higher intensity after the second or third therapy. The first dose of RLT with {sup 131}I-MIP-1095 presented with low side effects and could significantly reduce the tumor burden in a majority of patients. The second and third therapies were less effective and presented with more frequent and more intense side effects, especially hematologic toxicities and xerostomia. (orig.)

  6. [Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience].

    Science.gov (United States)

    Takeda, Yutaka; Katsura, Yoshiteru; Ohmura, Yoshiaki; Sakamoto, Takuya; Akiyama, Yasuki; Kuwahara, Ryuichi; Morimoto, Yoshihiro; Ishida, Tomo; Oneda, Yasuo; Murakami, Kouhei; Naito, Atsushi; Kagawa, Yoshinori; Takeno, Atsushi; Kato, Takeshi; Tamura, Shigeyuki

    2016-11-01

    Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan.Albumin -bound paclitaxel (nab-paclitaxel)plus gemcitabine hydrochloride(GEM)combination chemotherapy provided significant improvements in the overall and progression-free survival in a phase III trial in Europe and America and a phase II trial in Japan.As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of nab-paclitaxel plus GEM with metastatic or recurrent pancreatic cancer.Between December 2014 and March 2016, 11 patients received nab-paclitaxel plus GEM as follows: nab-paclitaxel(125mg/m2 of body-surface area)followed by GEM(1,000mg/m2)on days 1, 8, and 15 every 4 weeks.The treatment was continued until disease progression, unacceptable adverse events, discontinuation as decided by the investigators, or patient refusal. The mean age was 65.6 years(range, 48-75 years), and 8 out of 11 patients were men.Ten patients had an Eastern Cooperative Oncology Group(ECOG)performance status(PS)of 0.Ten patients had metastatic disease.Only 4 patients had no prior therapy.The mean duration of treatment was 10.2 weeks(range, 2-41 weeks).The relative dose intensities of nab-paclitaxel and GEM were 90.6%(66.7-100%)and 87.5%(62.9-100%), respectively.The major Grade 3 or 4 hematological toxicities were leucopenia(54.5%), neutropenia(36.4%), anemia (27.3%), and thrombocytopenia(18.2%).The major grade 2 or 3 non-hematological toxicities were fatigue(45.6%), skin rash(27.3%), peripheral sensory neuropathy(9.1%), anorexia(9.1%), and stomatitis(9.1%).There were no treatmentrelated deaths.Interstitial lung disease was not observed.The 6 month progression-free and overall survival rate were 25.7% and 66.7%, respectively. The disease control rate was 90.9%(complete response, n=0; partial response, n=1; stable disease, n=9; progressive disease, n=1). Nab-paclitaxel plus GEM is well tolerated and associated with efficacy and improved survival outcomes.Nab -paclitaxel

  7. PALBOCICLIB IN COMBINATION WITH HORMONE THERAPY FOR LUMINAL HER2-NEGATIVE METASTATIC BREAST CANCER: NEW HIGHLY EFFECTIVE STRATEGY OF DRUG TREATMENT

    Directory of Open Access Journals (Sweden)

    E. V. Artamonova

    2017-01-01

    Full Text Available The review considers a new oral targeted drug palbociclib and its place in treatment of luminal (estrogen receptor-positive HER2– metastatic breast cancer. The results of randomized clinical trials have shown that inclusion of palbociclib in various hormone therapy regimens for treatment of HER2– metastatic breast cancer with expression of estrogen receptors allows to significantly improve clinical outcomes and increase survival, objective response rate and its duration, as well as clinical benefit rate (CBR. Addition of palbociclib to letrozole in the 1st line hormone therapy or to fulvestrant in patients with progression at/after previous endocrine therapy increased progression-free survival in all groups irrespective of clinical characteristics, tumor progression, or expression of molecular markers mediating development of hormone resistance. The main adverse events associated with palbociclib were neutropenia, leukopenia and thrombocytopenia, but overall hematological toxicity was manageable, and the therapy itself was safe. This strategy received a “breakthrough therapy designation” from the experts and combines proven effectiveness and satisfactory tolerability, allows to maintain high quality of life, and should be prescribed to patients with luminal HER2– metastatic breast cancer.

  8. Patient with metastatic breast cancer presenting as acute cholecystitis with one-year survival on hormonotherapy.

    Science.gov (United States)

    Zamkowski, Mateusz; Kąkol, Michał; Makarewicz, Wojciech; Ropel, Jerzy; Bobowicz, Maciej

    2017-08-31

    Breast cancer has high metastatic potential with distant metastases involving mainly lungs, liver and bones. Less frequently it gives distant spread to other organs. Herein we would like to present a very rare case of an acute cholecystitis which turned out to be a metastatic breast cancer in previously healthy woman. A female patient, 64-years old, presented to the emergency department with symptoms of biliary colic and acute abdomen. During the emergency cholecystectomy, we diagnosed the gallbladder empyema with thickened wall. There were also multiple metastatic nodules in the peritoneal cavity and an excessive amount of free fluid. The emergency physicians diagnosing female patient with the acute abdominal symptoms and a breast cancer history might suspect malignant spread into abdominal organs including gallbladder. On the other hand, acute cholecystitis symptoms might be the first symptoms of metastatic process in the gallbladder from the unknown primary source, which may be breast.

  9. 'Cancer changes everything!' Exploring the lived experiences of women with metastatic breast cancer.

    Science.gov (United States)

    Krigel, Susan; Myers, Jamie; Befort, Christie; Krebill, Hope; Klemp, Jennifer

    2014-07-01

    The aim of this study was to further explore the lived experiences of women with metastatic breast cancer (MBC), to inform the development of interventions to enhance survivorship care for women with advanced disease. Four semi-structured focus groups were conducted with women with MBC. The data was analysed using qualitative content analysis. Participants described the challenges of living with uncertainty, as a result of a lack of information regarding treatment options and symptom management, and a sense of the unknown related to prognosis and survival. Of major concern were changes in role functioning, altered relationships, and self-image. Women with metastatic breast cancer must cope with dramatic changes in all aspects of their lives. Clinicians should tailor survivorship care and evidence-based interventions to individuals' concerns with changes in role functioning, fatigue, relationships, and self-image. A multidisciplinary approach should be used to address practical and existential concerns focused on improving quality of life.

  10. Prognostic Impacts of Metastatic Site and Pain on Progression to Castrate Resistance and Mortality in Patients with Metastatic Prostate Cancer.

    Science.gov (United States)

    Koo, Kyo Chul; Park, Sang Un; Kim, Ki Hong; Rha, Koon Ho; Hong, Sung Joon; Yang, Seung Choul; Chung, Byung Ha

    2015-09-01

    To investigate predictors of progression to castration-resistant prostate cancer (CRPC) and cancer-specific mortality (CSM) in patients with metastatic prostate cancer (mPCa). A retrospective analysis was performed on 440 consecutive treatment-naïve patients initially diagnosed with mPCa between August 2000 and June 2012. Patient age, body mass index (BMI), Gleason score, prostate-specific antigen (PSA), PSA nadir, American Joint Committee on Cancer stage, Visual Analogue Scale pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), PSA response to hormone therapy, and metastatic sites were assessed. Cox-proportional hazards regression analyses were used to evaluate survivals and predictive variables of men with bone metastasis stratified according to the presence of pain, compared to men with visceral metastasis. Metastases were most often found in bone (75.4%), followed by lung (16.3%) and liver (8.3%) tissues. Bone metastasis, pain, and high BMI were associated with increased risks of progression to CRPC, and bone metastasis, pain, PSA nadir, and ECOG PS≥1 were significant predictors of CSM. During the median follow-up of 32.0 (interquartile range 14.7-55.9) months, patients with bone metastasis with pain and patients with both bone and visceral metastases showed the worst median progression to CRPC-free and cancer-specific survivals, followed by men with bone metastasis without pain. Patients with visceral metastasis had the best median survivals. Metastatic spread and pain patterns confer different prognosis in patients with mPCa. Bone may serve as a crucial microenvironment in the development of CRPC and disease progression.

  11. [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.

  12. Metastatic Prostate Cancer Diagnosed by Bone Marrow Aspiration in an Elderly Man Not Undergoing PSA Screening

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    Ridwan Alam

    2017-02-01

    Full Text Available Prostate cancer screening by PSA testing remains controversial, particularly in the elderly. Practice guidelines from most clinical societies suggest discontinuing PSA screening at age 70 while the USPSTF recommends against screening at any age. Recent reports have demonstrated an increased incidence of metastatic prostate cancer, with men aged 75 or older accounting for roughly half of those newly diagnosed at an incurable stage. We herein describe the case of an elderly gentleman with no history of prostate cancer screening who presented with anorexia and back pain of unclear etiology. Evaluation with bone marrow aspiration revealed a diagnosis of metastatic prostate cancer.

  13. Severe Hypocalcemia due to Denosumab in Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Mohammed Muqeet Adnan

    2014-01-01

    Full Text Available Denosumab is a monoclonal antibody used for prevention of skeletal-related events (SREs in patients with bone metastases from solid tumors. Hypocalcemia is a rare and dangerous side effect of the drug Denosumab. We present a case of a patient with metastatic prostate cancer who developed severe hypocalcemia after the administration of the drug. The patient’s vitamin D levels were low when checked after administration of the drug, which likely predisposed him to the development of hypocalcemia. He was placed on high doses of oral and intravenous (IV calcium and vitamin D without any appreciable response in the serum calcium level. His ionized calcium remained below 0.71 mmol/L despite very high doses of oral and IV calcium supplements. During the hospital course, he developed hydronephrosis from the spread of a tumor and did not want to undergo percutaneous nephrostomy tube placement; therefore, it was decided to dialyse him for acute renal failure and to correct his hypocalcemia. Checking calcium and vitamin D levels prior to the administration of Denosumab is vital in preventing hypocalcemia. If hypocalcemia is severe and not responsive to high doses of vitamin D, oral and IV calcium, then hemodialysis with a high calcium bath can correct this electrolyte abnormality.

  14. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Oliver Sartor

    2014-06-01

    Full Text Available Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC. Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

  15. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Science.gov (United States)

    Sartor, Oliver; Gillessen, Silke

    2014-01-01

    Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients. PMID:24675654

  16. "Unique trend" and "contradictory trend" in discrimination of primary synchronous lung cancer and metastatic lung cancer.

    Science.gov (United States)

    Shen, Cheng; Xu, Huan; Liu, Lunxu; Zhou, Yubin; Chen, Dali; Du, Heng; Han, Zhaojie; Che, Guowei

    2013-10-09

    Distinguishing between multiple primary lung cancers and metastatic tumors is often difficult when the tumor histology is same. Since genomic instability is a common feature of cancer, we hypothesized that independently arising neoplasms in an individual patient would exhibit measurable genomic variation, enabling discrimination of tumor lineage and relatedness. The feasibility of analyzing genomic instability expression profiles to distinguish multiple primary lung cancers from metastatic tumors was evaluated. This study enrolled 13 patients, with multiple primary lung cancers demonstrating with the histology, who underwent surgery between April 2003 and December 2012 at the Department of the Thoracic Surgery at West China Hospital in Sichuan province of China and 10 patients who were diagnosed as metastasis disease during the same period for comparison purposes. Genomic DNA from lung cancers from individual patients was analyzed by six microsatellites (D2S1363, D6S1056, D7S1824, D10S1239, D15S822, and D22S689) with PCR to identify discordant allelic variation. The experiments were approved by the West China Hospital Ethics committee (No.2013 (33)) and all patients agreed to participate in the study and signed an informed consent form. All of the 10 patients with distant metastasis showed a consistent consequence that we called "unique trend" between primary tumor and distant metastasis. The "trend" is representive in this study, which means that all alleles corresponding to six microsatellite markers were detected in DNA from primary tumors but were reduced or not observed in DNA from metastatic tumors. In the group of synchronous lung tumor with different histological types, the result showed a "contradictory trend". Some alleles were detected in DNA from primary tumors but were reduced or not observed in DNA from metastatic tumors and other alleles corresponding to six microsatellite markers were detected in DNA from metastatic tumors but were reduced or not

  17. Feasibility and response of helical tomotherapy in patients with metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Ho [Dept. of Radiation Oncology, Catholic Kwandong University International St. Mary' s Hospital, Incheon (Korea, Republic of); Bae, Sun yun; Moon, Seong Kwon; Cho, Kwang Hwan; Shin, Eung Jin; Lee, Moon Sung; Ryu, Chang Beom; Ko, Bong Min; Yun, Ji Na [Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2015-12-15

    To investigate the treatment outcome and the toxicity of helical tomotherapy (HT) in patients with metastatic colorectal cancer (mCRC). We retrospectively reviewed 18 patients with 31 lesions from mCRC treated with HT between 2009 and 2013. The liver (9 lesions) and lymph nodes (9 lesions) were the most frequent sites. The planning target volume (PTV) ranged from 12 to 1,110 mL (median, 114 mL). The total doses ranged from 30 to 70 Gy in 10-30 fractions. When the alpha/beta value for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the total doses ranged from 39 to 119 Gy{sub 10} (median, 55 Gy{sub 10}). Nineteen lesions were treated with concurrent chemotherapy (CCRT). With a median follow-up time of 16 months, the median overall survival for 18 patients was 33 months. Eight lesions (26%) achieved complete response. The 1- and 3-year local progression free survival (LPFS) rates for 31 lesions were 45% and 34%, respectively. On univariate analysis, significant parameters influencing LPFS rates were chemotherapy response before HT, aim of HT, CCRT, PTV, BED, and adjuvant chemotherapy. On multivariate analysis, PTV < or =113 mL and BED >48 Gy{sub 10} were associated with a statistically significant improvement in LFPS. During HT, four patients experienced grade 3 hematologic toxicities, each of whom had also received CCRT. The current study demonstrates the efficacy and tolerability of HT for mCRC. To define optimal RT dose according to tumor size of mCRC, further study should be needed.

  18. Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Tomas Pascual

    Full Text Available Metastatic breast cancer (MBC progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs on outcomes from this treatment through a pharmacogenetic analysis.Blood was collected from 90 postmenopausal women with hormone receptor-positive, HER2-negative MBC treated with exemestane-everolimus following progression after prior treatment with a non-steroidal aromatase inhibitor. Everolimus pharmacokinetics was measured in 37 patients. Twelve SNPs in genes involved in everolimus pharmacokinetics and pharmacodynamics were genotyped and associations assessed with drug plasma levels, clinically relevant toxicities (non-infectious pneumonitis, mucositis, hyperglycemia and hematological toxicities, dose reductions or treatment suspensions due to toxicity, progression free survival (PFS and overall survival.We found that CYP3A4 rs35599367 variant (CYP3A4*22 allele carriers had higher everolimus blood concentration compared to wild type patients (P = 0.019. ABCB1 rs1045642 was associated with risk of mucositis (P = 0.031, while PIK3R1 rs10515074 and RAPTOR rs9906827 were associated with hyperglycemia and non-infectious pneumonitis (P = 0.016 and 0.024, respectively. Furthermore, RAPTOR rs9906827 was associated with PFS (P = 0.006.CYP3A4*22 allele influenced plasma concentration of everolimus and several SNPs in PI3K/AKT/mTOR pathway genes were associated with treatment toxicities and prognosis. These results require replication, but suggest that germline variation could influence everolimus outcomes in MBC.

  19. Third-Line Chemotherapy with Irinotecan plus 5-Fluorouracil in Caucasian Metastatic Gastric Cancer Patients.

    Science.gov (United States)

    Pasquini, Giulia; Vasile, Enrico; Caparello, Chiara; Vivaldi, Caterina; Musettini, Gianna; Lencioni, Monica; Petrini, Iacopo; Fornaro, Lorenzo; Falcone, Alfredo

    2016-01-01

    The aim of this study was to evaluate the activity of the combination of 5-fluorouracil/folinic acid and irinotecan (FOLFIRI) as third-line chemotherapy (CT) in metastatic gastric cancer (mGC) patients pretreated with platinum derivatives, fluoropyrimidines, and taxanes. We prospectively collected data of mGC patients treated with third-line FOLFIRI at our institution from 2009 to 2014. Eligible patients should be treated with a fluoropyrimidine-platinum first-line CT and a subsequent taxane-based second-line CT. FOLFIRI consisted of irinotecan 180 mg/m2 and leucovorin 200 mg/m2, followed by 5-fluorouracil 2,800 mg/m2 (administered as 48-hour i.v. continuous infusion from day 1 to 3), with cycles repeated every 2 weeks. Response rate (RR) was evaluated according to RECIST version 1.0, while progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. A total of 33 patients were included. The majority (97%) had good performance status (0-1 according to ECOG), while median PFS after first-line and second-line CT was 5.2 and 4.4 months, respectively. Two patients experienced an objective response (RR: 6%), while 14 patients achieved disease stabilization (disease control rate: 42%). Median PFS and OS from the start of third-line CT were 3.3 and 7.5 months, respectively. Hematological and nonhematological grade 3-4 toxicities were uncommon and included neutropenia (6.1%), diarrhea (9.1%), vomiting (3%), and asthenia (3%). Febrile neutropenia was not reported. Third-line CT with FOLFIRI may be an option in heavily pretreated mGC patients with preserved performance status and organ function. This regimen has a favorable safety profile, and signs of activity have been observed after standard first- and second-line CT. © 2016 S. Karger AG, Basel.

  20. Psychological distress, chronic conditions and quality of life in elderly hematologic cancer patients: study protocol of a prospective study.

    Science.gov (United States)

    Köhler, Norbert; Mehnert, Anja; Götze, Heide

    2017-10-25

    Similar to most solid tumors, the incidence of hematologic malignancies has been rising. Although the median age at diagnosis is about 70 years, little is known about psychosocial aspects and comorbid conditions in elderly patients with hematologic cancers. The main objectives of our study are to assess the prevalence of psychological distress, chronic conditions, functional disabilities, and quality of life in both elderly hematologic cancer patients aged ≥70 years and an age-matched comparison sample of the general population. We conduct a prospective study with three measuring points (t_1: ≥5 years after first time hematologic cancer diagnosis / relapse; t_2 and t_3 six months and 1 year after t_1). In addition, we use a cross sectional study design to recruit a comparison sample of the general population matched by age and sex. Both samples, patients and the comparison group complete validated questionnaires measuring psychological distress, chronic conditions, functional disabilities, and quality of life as well as health care needs and health care utilization. Our study will provide both a data set offering detailed information about elderly hematologic cancer patients' physical, psychological and demographic characteristics, and reference data of the elderly general population. Furthermore, the study will provide important information for the development and implementation of psychooncological support offers and survivorship care plans.

  1. Metastatic Prostate Cancer in Men Initially Treated with Active Surveillance.

    Science.gov (United States)

    Yamamoto, Toshihiro; Musunuru, Bindu; Vesprini, Danny; Zhang, Liying; Ghanem, Gabriella; Loblaw, Andrew; Klotz, Laurence

    2016-05-01

    Active surveillance is an approach to low and low intermediate risk prostate cancer that is designed to decrease overtreatment. Despite close monitoring a small subset of patients progress to metastatic disease. We analyzed the clinical and pathological correlates of surveillance in patients who eventually experienced metastasis. This was a single center, prospective cohort study. Eligible patients were treated with an expectant approach. The main outcome measure was metastasis-free survival. Predictive factors for metastasis were identified. Metastasis developed in 30 of 980 patients, of whom 211 were classified at intermediate risk, including 14 who progressed to metastatic disease. Median followup was 6.3 years, median age was 70 years, median prostate specific antigen was 6.2 ng/ml and median time to metastasis was 8.9 years. Metastases developed in bone in 18 patients (60%) and in lymph nodes in 13 (43%). Prostate specific antigen doubling time less than 3 years (HR 3.7, 95% CI 1.4-9.4, p = 0.0006), Gleason score 7 (HR 3.0, 95% CI 1.2-7.3, p = 0.0018) and a total of 3 or more positive cores (HR 2.7, 95% CI 1.1-6.8, p = 0.0028) were independent predictors of metastasis. Although the intermediate risk group was at higher risk for metastasis, those with Gleason score 6 and prostate specific antigen greater than 10 ng/ml were not at increased risk for metastasis. Metastasis developed in only 2 patients with Gleason score 6 and neither had surgical pathology grading. Active surveillance appears safe in patients at low risk and in select patients at intermediate risk, particularly those with Gleason score 6 and prostate specific antigen greater than 10 ng/ml. Patients with elements of Gleason pattern 4 on diagnostic biopsy are at increased risk for eventual metastasis when treated with an initial conservative approach. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-03-01

    We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer – role of radium-223

    Directory of Open Access Journals (Sweden)

    Mukherji D

    2014-05-01

    Full Text Available Deborah Mukherji,1 Imane El Dika,1 Sally Temraz,1 Mohammed Haidar,2 Ali Shamseddine11Department of Hematology/Oncology, 2Department of Nuclear Medicine, American University of Beirut Medical Center, Beirut, LebanonAbstract: Radium-223 is a first-in-class alpha particle-emitting radiopharmaceutical approved for the treatment of bone metastatic castration-resistant prostate cancer. Radium-223 is administered intravenously with no requirement for complex shielding and specifically targets areas of bone metastasis. In a randomized placebo-controlled Phase III study, treatment with radium-223 was shown to improve overall survival, time to skeletal-related events, and health-related quality of life. Apart from radium-223, the cytotoxic chemotherapy agents docetaxel and cabazitaxel, androgen biosynthesis inhibitor abiraterone acetate, novel anti-androgen enzalutamide, and immunotherapy sipuleucel-T have also been shown to improve survival of men with advanced prostate cancer in Phase III trials. This review will outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 in changing treatment paradigms.Keywords: Alpharadin, alpha-emitting radionuclide, bone metastasis

  4. Improvement in survival for patients with synchronous metastatic esophageal cancer in the south of the Netherlands from 1994 to 2013

    National Research Council Canada - National Science Library

    Bernards, N; Haj Mohammad, N; Creemers, G. J; Rozema, T; Roukema, J. A; Nieuwenhuijzen, G. A. P; van Laarhoven, H. W. M; van der Sangen, M; Lemmens, V. E. P. P

    2016-01-01

    Background: We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival.Methods...

  5. Improvement in survival for patients with synchronous metastatic esophageal cancer in the south of the Netherlands from 1994 to 2013

    National Research Council Canada - National Science Library

    Bernards, N; Mohammed, N.H; Creemers, G.J; Rozema, T; Roukema, J.A; Nieuwenhuijzen, G.A.P; van Laarhoven, M; van der Sangen, M.J.C; Lemmens, V.E.P.P

    2016-01-01

    Background: We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival. Methods...

  6. Adoptive T-cell Therapy Promising for Metastatic Cervical Cancer | Center for Cancer Research

    Science.gov (United States)

    Over 4,000 women in the U.S. die from cervical cancer each year. Nearly all cases of the disease are caused by infection with human papilloma viruses (HPVs), particularly strains 16 and 18. Cervical cancer can be prevented with vaccination against HPVs before the initiation of sexual activity and can be detected early with regular screening via the Pap test and/or HPV DNA testing. If the disease progresses to a metastatic state, however, it is generally incurable and difficult to treat with chemotherapy.

  7. [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.

  8. Consistent expression of guanylyl cyclase-C in primary and metastatic gastrointestinal cancers.

    Directory of Open Access Journals (Sweden)

    Hadi Danaee

    Full Text Available The transmembrane receptor guanylate cyclase-C (GCC has been found to be expressed in colorectal cancers. However, limited data are available on GCC protein expression in non-colorectal gastrointestinal tumors and few studies have reported whether GCC protein expression was consistently preserved in synchronous primary and metastatic cancer tissues.GCC protein status was assessed by immunohistochemistry in tumor specimens from individuals (n = 627 with gastrointestinal tumors, including esophageal (n = 130, gastric (n = 276, pancreatic (n = 136, and colorectal (n = 85 primary and metastatic tumors. Tissue specimens consisted of tissue microarrays containing esophageal, gastric, pancreatic tumors, and whole-slide tissue sections from colorectal cancer patients with matching primary and metastatic tumors.Among the evaluated esophageal, gastric, and pancreatic tumors, the frequency of GCC positivity at the protein level ranged from 59% to 68%. GCC was consistently expressed in primary and matched/synchronous metastatic lesions of colorectal cancer tissues derived from the same patients.This observational study demonstrated the protein expression of GCC across various gastrointestinal malignancies. In all cancer histotypes, GCC protein localization was observed predominantly in the cytoplasm compared to the membrane region of tumor cells. Consistent immunohistochemistry detection of GCC protein expression in primary colorectal cancers and in their matched liver metastases suggests that the expression of GCC is maintained throughout the process of tumor progression and formation of metastatic disease.

  9. Mesenchymal cell interaction with ovarian cancer cells induces a background dependent pro-metastatic transcriptomic profile.

    Science.gov (United States)

    Lis, Raphael; Touboul, Cyril; Halabi, Najeeb M; Madduri, Abishek Sainath; Querleu, Denis; Mezey, Jason; Malek, Joel A; Suhre, Karsten; Rafii, Arash

    2014-03-05

    The cross talk between the stroma and cancer cells plays a major role in phenotypic modulation. During peritoneal carcinomatosis ovarian cancer cells interact with mesenchymal stem cells (MSC) resulting in increased metastatic ability. Understanding the transcriptomic changes underlying the phenotypic modulation will allow identification of key genes to target. However in the context of personalized medicine we must consider inter and intra tumoral heterogeneity. In this study we used a pathway-based approach to illustrate the role of cell line background in transcriptomic modification during a cross talk with MSC. We used two ovarian cancer cell lines as a surrogate for different ovarian cancer subtypes: OVCAR3 for an epithelial and SKOV3 for a mesenchymal subtype. We co-cultured them with MSCs. Genome wide gene expression was determined after cell sorting. Ingenuity pathway analysis was used to decipher the cell specific transcriptomic changes related to different pro-metastatic traits (Adherence, migration, invasion, proliferation and chemoresistance). We demonstrate that co-culture of ovarian cancer cells in direct cellular contact with MSCs induces broad transcriptomic changes related to enhance metastatic ability. Genes related to cellular adhesion, invasion, migration, proliferation and chemoresistance were enriched under these experimental conditions. Network analysis of differentially expressed genes clearly shows a cell type specific pattern. The contact with the mesenchymal niche increase metastatic initiation and expansion through cancer cells' transcriptome modification dependent of the cellular subtype. Personalized medicine strategy might benefit from network analysis revealing the subtype specific nodes to target to disrupt acquired pro-metastatic profile.

  10. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in Breast Cancer

    DEFF Research Database (Denmark)

    Dupont Jensen, Jeanette; Laenkholm, Anne-Vibeke; Knoop, Ann

    2011-01-01

    PURPOSE: PIK3CA mutations are frequent in breast cancer and activate the PI3K/Akt pathway. Unexpectedly, PIK3CA mutation appears in general to be associated with better outcome. In a cohort of patients where both primary and metastatic lesions were available the objective was to assess changes...... recurrence than wild type cases (p=0.03). CONCLUSIONS: PIK3CA mutations occur at high frequency in primary and metastatic breast cancer; these may not necessarily confer increased aggressiveness as mutants had a longer time to recurrence. Because PIK3CA status quite frequently changes between primary...... metastatic breast tumors. Samples were analysed for PIK3CA mutations (exon 9 and 20) as well as immunohistochemical evaluation for PTEN, pAKT, Ki67, ER and HER2. RESULTS: PIK3CA mutation was detected in 45 % of the primary tumors. Overall there was a net gain in mutation in metastatic disease, to 53...

  11. Research progress on genetic heterogeneity between primary and paired metastatic colorectal cancer.

    Science.gov (United States)

    Lu, You-Wang; Wang, Kun-Hua

    2017-06-20

    Colorectal cancer (CRC) is one of the leading causes of cancer deaths in China. A standard practice in treating metastatic CRC (mCRC) is to predict benefits of the anti-EGFR monoclonal antibody treatment based on the somatic mutation spectrum. Because metastatic samples are difficult to obtain clinically, primary tumors are normally used instead. However, due to the genetic heterogeneity between primary and paired metastatic tumors, primary site biopsy always underrepresents the mutational landscape of metastatic sites. Currently, the extent of genetic heterogeneity between primary and paired mCRC is still under debate. Here, we review comparative studies of primary and matched mCRC and discuss the underlying causes and potential strategies.

  12. Knee pain and swelling: An atypical presentation of metastatic colon cancer to the patella

    Directory of Open Access Journals (Sweden)

    Bethany Gasagranda, DO

    2014-01-01

    Full Text Available Knee pain is a common reason for a patient to seek medical evaluation. Of the many causes of knee pain, malignancy is one of the least common. When malignancy is the etiology of the pain, it is usually due to a primary tumor of the osseous structures or soft tissues of the knee joint. Metastatic disease involving the knee joint is uncommon, with few cases reported in the literature. Of these reported cases, metastatic colon cancer is exceedingly rare. However, in a patient with new onset knee pain and the proper clinical history, metastatic disease should be considered as a potential explanation of symptoms. We report a case of knee pain and swelling due to metastatic colon cancer to the patella.

  13. Maintenance therapy with oral etoposide following first-line docetaxel-cisplatin chemotherapy in metastatic non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Meiyu Fang

    2012-08-01

    Full Text Available The present study evaluated the efficacy and safety of maintenance therapy with oral etoposide following first-line docetaxel-cisplatin chemotherapy in patients with metastatic non-small cell lung cancer. The overall response rate in the docetaxel-cisplatin phase was 30.4%, with complete response of 0, partial response of 28, stable disease of 39. Maintenance chemotherapy with oral etoposide was given in 67 patients. No complete response was observed, but 10 patients presented with partial response and 45 with stable disease . The median time to progression was 5.0 months; median overall survival time was 10 months and the 1-year survival rate was 41% during the maintenance therapy. Therapy with oral etoposide was well tolerated with the hematologic toxicities, fatigue and oral mucositis being the most frequent side effects. Docetaxel-cisplatin chemotherapy followed by maintenance therapy with oral etoposide was well tolerated and moderately active against metastatic metastatic non-small cell lung cancer.

  14. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    Science.gov (United States)

    Poff, Angela M; Ari, Csilla; Seyfried, Thomas N; D'Agostino, Dominic P

    2013-01-01

    Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging. KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  15. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    Directory of Open Access Journals (Sweden)

    Angela M Poff

    Full Text Available INTRODUCTION: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. METHODS: We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week. Tumor growth was monitored by in vivo bioluminescent imaging. RESULTS: KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. CONCLUSIONS: KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  16. A qualitative study of women's experiences of healthcare, treatment and support for metastatic breast cancer.

    Science.gov (United States)

    Lewis, Sophie; Yee, Jasmine; Kilbreath, Sharon; Willis, Karen

    2015-06-01

    The purpose of this qualitative research was to identify the healthcare, information and support needs of women living with metastatic breast cancer. Semi-structured qualitative interviews were conducted with 18 women. Women were asked about their experiences of living with metastatic breast cancer and their information and support needs. Women valued relationships with their healthcare professionals, particularly their oncologists. They wanted more attention paid to side-effects of ongoing treatments, which had a negative impact on their health. While oncologists were a primary source of information, women also drew on other sources. There were mixed findings about the value of support groups, with women preferring to seek alternative sources of social support. A diagnosis of metastatic breast cancer brings heightened reliance on healthcare professionals to respond to women's needs in a way that is different to that required with a diagnosis of early breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Prognostic value of serum tetranectin in patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Høgdall, C K; Sölétormos, G; Nielsen, D

    1993-01-01

    To evaluate serum tetranectin as a prognostic marker before first-line chemotherapy, serum levels were studied in 67 patients with metastatic breast cancer. In the Cox analyses, the relative risk (RR) for death of cancer varied with the cut-off level of serum tetranectin. A maximal RR of 5...... prognostic factor in metastatic breast cancer........0 was found for patients with serum tetranectin metastases 2.8, and for a poor performance status 2.0. Testing for the outcome, progressive disease, a maximal RR of 3.8 was found for patients with serum tetranectin...

  18. Sweets for a bitter end: lung cancer cell-surface protein glycosylation mediates metastatic colonization.

    Science.gov (United States)

    Arnal-Estapé, Anna; Nguyen, Don X

    2015-02-01

    Glycosylation is one of the most predominant forms of cell-surface protein modifications, yet its deregulation in cancer and contribution to tumor microenvironment interactions remain poorly understood. In this issue of Cancer Discovery, Reticker-Flynn and Bhatia characterize an enzymatic switch in lung cancer cells that triggers aberrant surface protein glycosylation patterns, adhesion to lectins on the surface of inflammatory cells, and subsequent metastatic colonization of the liver. ©2015 American Association for Cancer Research.

  19. [Cabazitaxel--a next-generation taxane for the treatment of patients with metastatic castration-resistant prostate cancer].

    Science.gov (United States)

    Ecstein-Fraisse, Evelyne; Su, Zhen

    2014-07-01

    Prostate cancer is a heterogeneous disease that responds variably to available agents, particularly androgen receptor(AR)- targeting agents. In preclinical models, cabazitaxel, a second-generation taxane, demonstrated enhanced antitumor activity when compared with docetaxel. In subsequent clinical trials, cabazitaxel was associated with pharmacokinetic, safety, and tolerability profiles consistent with those of previous taxanes. In the pivotal phase III study(TROPIC; NCT00417079), cabazitaxel led to significantly improved overall survival in patients with metastatic castration-resistant prostate cancer(mCRPC), compared with mitoxantrone, when both were administered in combination with prednisone/prednisolone(median survival: 15.1 months[95%confidence interval(CI): 14.1-16.3]vs 12.7 months[95% CI: 11.6-13.7], hazard ratio(HR): 0.70[95% CI: 0.59-0.83], pcabazitaxel was maintained at 2 years, with 60(15.9%)patients in the cabazitaxel group and 31(8.2%)patients in the mitoxantrone group surviving for B2 years(odds ratio: 2.11, 95% CI: 1.33-3.33). Cabazitaxel also provides pain palliation similar to that provided by using mitoxantrone. The safety profile of cabazitaxel is consistent with that of first-generation taxanes, and gastrointestinal(predominantly diarrhea)and hematologic(mainly neutropenia)adverse events are the most frequently reported. Clinical trial data suggest that these events can be managed with careful monitoring and dose reduction where necessary. In addition, treatment with granulocyte colony-stimulating factor(G-CSF)can mitigate hematologic adverse events, whereas supportive treatment with antiemetic and antidiarrheal agents may ameliorate gastrointestinal symptoms. The treatment paradigm for mCRPC is evolving rapidly with the emergence of data for new agents, leading to maximization of patient benefits. The proven efficacy and tolerability profiles of cabazitaxel suggest the promising role of this agent within this paradigm.

  20. Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer

    NARCIS (Netherlands)

    Witjes, J.A.; Lebret, T.; Comperat, E.M.; Cowan, N.C.; Santis, M. de; Bruins, H.M.; Hernandez, V.; Espinos, E.L.; Dunn, J.; Rouanne, M.; Neuzillet, Y.; Veskimae, E.; Heijden, A.G. van der; Gakis, G.; Ribal, M.J.

    2017-01-01

    CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis,

  1. Metastatic Squamous Neck Cancer with Occult Primary Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Metastatic squamous neck cancer with occult primary occurs when squamous cell cancer spreads to lymph nodes in the neck from an undetectable primary tumor. Treatment includes surgery and radiation therapy. Learn about the diagnosis, survival, staging, and treatment of these tumors.

  2. Improving therapy options for patients with metastatic castrate-resistant prostate cancer

    NARCIS (Netherlands)

    Wissing, Michel Daniël

    2014-01-01

    Metastatic castrate-resistant prostate cancer (mCRPC) is the second deadliest cancer in men in the Western world. Therapy options are limited, but expanding. In the current thesis, various aspects of (pre)clinical research are discussed, all sharing the ultimate aim to improve therapy options for

  3. Karnofsky Performance Score Is Predictive of Survival After Palliative Irradiation of Metastatic Bile Duct Cancer.

    Science.gov (United States)

    Rades, Dirk; Bolm, Louisa; Kaesmann, Lukas; Bartscht, Tobias

    2017-02-01

    Palliative irradiation is effective in alleviating symptoms in patients with metastatic cancer in general. However, little data exist regarding irradiation of metastatic bile duct cancer. Selection of the best regimen for such a patient should be based on their survival prognosis. This study included five patients irradiated for metastatic bile duct cancer and aimed to identify predictors of survival by analyzing six factors: age, gender, general condition (Karnofsky performance score), metastatic site receiving palliative irradiation, metastases outside irradiated sites and time between diagnosis of bile duct cancer and palliative irradiation. In the whole series, median survival was 3 months. Survival rates at 3 and 6 months were 40% and 40%, respectively. A Karnofsky performance score >70% had a borderline significant association with better survival (p=0.05). Karnofsky performance score was identified as predictor of survival and should be considered when assigning the radiation regimen to patients with metastatic bile duct cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Clinical and microbiological characteristics of bloodstream infections in hematological cancer patients

    Directory of Open Access Journals (Sweden)

    V. N. Chebotkevich

    2016-01-01

    Full Text Available Introduction. Bloodstream infections (BSI are life-threatening illness for immunocompromised patients with hematological malignancies.The aim of the study was to compare epidemiology, causative pathogens and outcome of hospital-acquired BSI and clarifying the role of herpes group of viruses in their development.Materials and methods. During the period 1991–2013 438 bacterial strains obtained from 360 patients (pts with hematological malignancies wеre studied. All blood cultures were incubated in the continuous monitoring system for 7 days before discard. The real-time PCR was used for human herpesviruses DNA detection: Herpes simplex viruses types 1 and 2 (HSV 1, 2, Cytomegalovirus (CMV, Epstein–Barr virus(EBV and Herpesvirus 6 (HHV-6. In this study 64 hematological cancer patients with infectious complications who fulfilled criteria of systemic inflammatory response syndrome with positive peripheral blood cultures were investigated. All pts received empirical anti-infectious therapy with subsequent correction based on the bacteriological, virological and mycological analyses.Results and discussion. A total Gram-positive (G+ accounted for 69.2 % of BSI, Gram-negative (G– for 30.8 %. Among G+ BSI Coagulase Negative Staphylococci and Staphylococcus aureus were the most frequent pathogens (58.8 %, among G– BSI Escherichia coli (13.0 % was predominant. It is shown that the development of bacteremia were significantly more frequently occurs in the case of cytomegalovirusand the Epstein–Barr virus detection.Conclusion. Further epidemiological surveillance is warranted in order emerging resistant strains and related mortality. Reactivation of CMV and EBV is significantly associated with higher incidence of bacterial BSI.

  5. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  6. Weekly paclitaxel plus trastuzumab in metastatic breast cancer pretreated with anthracyclines--a phase II multipractice study.

    Science.gov (United States)

    John, Matthias; Hinke, Axel; Stauch, Martina; Wolf, Heiner; Mohr, Benno; Hindenburg, Hans-Joachim; Papke, Jens; Schlosser, Joachim

    2012-05-04

    The 3-weekly combination of trastuzumab and paclitaxel has been approved for the treatment of advanced breast cancer based on a large pivotal study. However, mono and combination chemotherapy trials suggest that weekly paclitaxel has a better therapeutic index, especially in the palliative setting. The present trial examined the efficacy and safety of weekly paclitaxel over a limited duration combined with continued trastuzumab in HER2+ patients. Patients with histologically confirmed metastatic breast cancer overexpressing HER2 were eligible if pretreated with anthracycline in either the adjuvant or palliative setting. Treatment consisted of weekly trastuzumab (2 mg/kg/week for up to one year after a loading dose of 4 mg/kg in week 1) and paclitaxel (90 mg/m², administered in weeks 1-6 and 8-13). Twenty-seven German centers enrolled 121 patients. The median number of metastatic sites was two (range 1-5); 38% of patients had received chemotherapy for advanced disease. After a median 42 weeks of trastuzumab treatment, limited by disease progression in roughly half the patients, a best objective response rate (complete response + partial response) of 76% was achieved, including complete remissions in 29%. 74% of patients lived without tumor progression at six months. Median progression-free and overall survival were 9.4 (95% confidence interval [CI]: 8.1-11.3) and 22 months (95% CI: 17-46). After alopecia, Common Toxicity Criteria grade ≥2 toxicity was predominantly hematological (leukopenia [31%] and anemia [41%]); however, thrombocytopenia occurred in only 5%. Neurotoxicity was remarkably low. Two cardiac events (grades 2 and 3) were presumed treatment-related. Weekly paclitaxel plus trastuzumab allows an increased dose density and offers an attractive and effective alternative to the conventional schedule. Limiting the duration of cytotoxic therapy to 3 months seems to be an option to reduce neurotoxicity without impairing long-term outcome.

  7. Weekly paclitaxel plus trastuzumab in metastatic breast cancer pretreated with anthracyclines-a phase II multipractice study

    Directory of Open Access Journals (Sweden)

    John Matthias

    2012-05-01

    Full Text Available Abstract Background The 3-weekly combination of trastuzumab and paclitaxel has been approved for the treatment of advanced breast cancer based on a large pivotal study. However, mono and combination chemotherapy trials suggest that weekly paclitaxel has a better therapeutic index, especially in the palliative setting. The present trial examined the efficacy and safety of weekly paclitaxel over a limited duration combined with continued trastuzumab in HER2+ patients. Methods Patients with histologically confirmed metastatic breast cancer overexpressing HER2 were eligible if pretreated with anthracycline in either the adjuvant or palliative setting. Treatment consisted of weekly trastuzumab (2 mg/kg/week for up to one year after a loading dose of 4 mg/kg in week 1 and paclitaxel (90 mg/m², administered in weeks 1–6 and 8–13. Results Twenty-seven German centers enrolled 121 patients. The median number of metastatic sites was two (range 1–5; 38% of patients had received chemotherapy for advanced disease. After a median 42 weeks of trastuzumab treatment, limited by disease progression in roughly half the patients, a best objective response rate (complete response + partial response of 76% was achieved, including complete remissions in 29%. 74% of patients lived without tumor progression at six months. Median progression-free and overall survival were 9.4 (95% confidence interval [CI]: 8.1–11.3 and 22 months (95% CI: 17–46. After alopecia, Common Toxicity Criteria grade ≥2 toxicity was predominantly hematological (leukopenia [31%] and anemia [41%]; however, thrombocytopenia occurred in only 5%. Neurotoxicity was remarkably low. Two cardiac events (grades 2 and 3 were presumed treatment-related. Conclusions Weekly paclitaxel plus trastuzumab allows an increased dose density and offers an attractive and effective alternative to the conventional schedule. Limiting the duration of cytotoxic therapy to 3 months seems to be an option to

  8. Biopsy confirmation of metastatic sites in breast cancer patients: clinical impact and future perspectives

    Science.gov (United States)

    2014-01-01

    Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome, and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations, the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future, advances in targeted therapy will depend on the availability of metastatic tissue. PMID:25032257

  9. Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

    Directory of Open Access Journals (Sweden)

    Hui Miao

    Full Text Available BACKGROUND: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. MATERIALS AND METHODS: We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic. RESULTS: We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53 to 0.63 (95% CI, 0.60-0.66. CONCLUSION: The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

  10. Outcomes in Patients with Obstructive Jaundice from Metastatic Colorectal Cancer and Implications for Management

    Science.gov (United States)

    Nichols, Shawnn D.; Albert, Scott; Shirley, Lawrence; Schmidt, Carl; Abdel-Misih, Sherif; El-Dika, Samer; Groce, J. Royce; Wu, Christina; Goldberg, Richard M.; Bekaii-Saab, Tanios; Bloomston, Mark

    2016-01-01

    Introduction Patients with metastatic colorectal cancer can develop jaundice from intrahepatic or extrahepatic causes. Currently, there is little data on the underlying causes and overall survival after onset of jaundice. The purpose of this study was to characterize the causes of jaundice and determine outcomes. Methods Six hundred twenty-nine patients treated for metastatic colorectal cancer between 2004 and 2010 were retrospectively reviewed. Those developing jaundice were grouped as having intrahepatic or extrahepatic obstruction. Demographics, clinicopathologic, and outcome data were analyzed. Results Sixty-two patients with metastatic colorectal cancer developed jaundice. Intrahepatic biliary obstruction was most common, occurring in younger patients. Time from metastatic diagnosis to presentation of jaundice was similar between groups, as was the mean number of prior lines of chemotherapy. Biliary decompression was successful 41.7 % of the time and was attempted more commonly for extrahepatic causes. Median overall survival after onset of jaundice was 1.5 months and it was similar between groups, but improved to 9.6 months in patients who were able to receive further chemotherapy. Conclusions Jaundice due to metastatic colorectal cancer is an ominous finding, representing aggressive tumor biology or exhaustion of therapies. Biliary decompression is often difficult and should only be pursued when additional treatment options are available. PMID:25300799

  11. Carbohydrate antigen 549 in metastatic breast cancer during cytostatic treatment and follow-up

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1992-01-01

    This study was designed to investigate whether the serum tumour marker CA 549 gave early and reliable information about disease activity among metastatic breast cancer patients during cytostatic treatment and follow-up. 50 females with metastatic breast cancer were monitored clinically...... among 91% by marker progression. Clinical progression was excluded among 93% without marker progression. In conclusion, monitoring of metastatic breast cancer patients could include CA 549 if standardised criteria for marker evaluation are used....... and with the tumour marker CA 549. Response evaluation was based upon clinical (World Health Organization) and elaborated CA 549 criteria, respectively. In 113 blindly and matched evaluations, concordance appeared in 73/113 and discordance in 40/113 evaluations. In 27, discordance concerned degree of response, in 2...

  12. Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske

    2014-01-01

    BACKGROUND: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final...... analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. METHODS: We did a multicentre, open-label, early......-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression...

  13. Bevacizumab with chemotherapy in patients with KRAS wild-type metastatic colorectal cancer: Czech registry data.

    Science.gov (United States)

    Kubáčková, Kateřina; Bortlíček, Zbyněk; Pikus, Tomáš; Linke, Zdeněk; Pokorná, Petra; Vyzula, Rostislav; Prausová, Jana

    2015-01-01

    This retrospective analysis investigated the effectiveness of combination therapy with bevacizumab and chemotherapy in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer. Patients with KRAS wild-type metastatic colorectal cancer in the CORECT registry who initiated treatment with bevacizumab between 2008 and 2012 were enrolled. Overall survival and progression-free survival were the main effectiveness end points. A total of 981 patients were enrolled. Median progression-free survival was 11.3 months (95% CI: 10.7-11.8) and median overall survival was 28.4 months (95% CI: 26.2-30.6). The most common adverse events were thromboembolic disease (4%) and hypertension (3.5%). This retrospective analysis shows the effectiveness of bevacizumab with chemotherapy in patients with KRAS wild-type metastatic colorectal cancer.

  14. CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2017-08-14

    Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer

  15. Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Pfeiffer, Per; Nielsen, Dorte

    2011-01-01

    The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated.......The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated....

  16. Metabolic Plasticity of Metastatic Breast Cancer Cells: Adaptation to Changes in the Microenvironment

    Directory of Open Access Journals (Sweden)

    Rui V. Simões

    2015-08-01

    Full Text Available Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells, leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehydrogenase subunit A expression according to metastatic potential. Moreover, glucose-derived lactate production was more glutamine dependent in cell lines with higher metastatic potential. These studies show clear differences in TCA cycle metabolism between 4T1 and 67NR breast cancer cells. They indicate that metastases-forming 4T1 cells are more adept at adjusting their metabolism in response to environmental stress than isogenic, nonmetastatic 67NR cells. We suggest that the metabolic plasticity and adaptability are more important to the metastatic breast cancer phenotype than rapid cell proliferation alone, which could 1 provide a new biomarker for early detection of this phenotype, possibly at the time of diagnosis, and 2 lead to new treatment strategies of metastatic breast cancer by targeting mitochondrial metabolism.

  17. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim

    2007-01-01

    chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients with advanced urothelial cancer. A panel of international experts has formulated grade A through D recommendations for the management......To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review...... the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed...

  18. MYC RNAi-Pt Combination Nanotherapy for Metastatic Prostate Cancer Treatment

    Science.gov (United States)

    2017-10-01

    4b and 4c). We further harvested the tumors and major organs at 24 h post injection (Figure 4d and 4e) and the quantification of BioD is shown in...AWARD NUMBER: W81XWH-15-1-0728 TITLE: MYC RNAi-PT Combination Nanotherapy for Metastatic Prostate Cancer Treatment PRINCIPAL INVESTIGATOR: Omid C...MYC RNAi-Pt Combination Nanotherapy for Metastatic Prostate Cancer Treatment 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0728 5c. PROGRAM

  19. Treatment landscape of metastatic prostate cancer: the role of radium-223.

    Science.gov (United States)

    Dermine, Alexandre; Machiels, Jean-Pascal

    2017-02-01

    The landscape of metastatic prostate cancer has changed recently with the availability of six new molecules showing an overall survival benefit. The development of compounds able to decrease the rate of complications from bone metastasis has also led to improvements in overall morbidity associated with this disease. In this paper, we briefly review the currently available drugs indicated in the treatment of metastatic prostate cancer, focusing on the place of the radiopharmaceutical agent radium-223 and its very unique mechanism of action and safety profile.

  20. Should capecitabine replace 5-fluorouracil in the first-line treatment of metastatic colorectal cancer?

    Science.gov (United States)

    Aguado, Carlos; García-Paredes, Beatriz; Sotelo, Miguel Jhonatan; Sastre, Javier; Díaz-Rubio, Eduardo

    2014-01-01

    Fluoropyrimidines play a central role in the first-line treatment of metastatic colorectal cancer. Our aim was to review whether capecitabine was a safer, non-inferior, economically superior and more convenient alternative to 5-fluorouracil. Capecitabine has previously been compared to 5-fluorouracil-either as a monotherapy or in combination with oxaliplatin, irinotecan, or biological drugs-and has been found to have comparable efficacy and safety profiles. Furthermore, pharmacoeconomic data and patients’ preferences for oral chemotherapy further favor capecitabine. Therefore, capecitabine appears to be an effective and safe alternative to fluorouracil in the first-line treatment of metastatic colorectal cancer. PMID:24876731

  1. Selecting patients for gastrectomy in metastatic esophago-gastric cancer: clinics and pathology are not enough.

    Science.gov (United States)

    Fornaro, Lorenzo; Fanotto, Valentina; Musettini, Gianna; Uccello, Mario; Rimassa, Lorenza; Vivaldi, Caterina; Fontanella, Caterina; Leone, Francesco; Giampieri, Riccardo; Rosati, Gerardo; Lencioni, Monica; Santini, Daniele; Donato, Samantha Di; Tomasello, Gianluca; Brunetti, Oronzo; Pietrantonio, Filippo; Bergamo, Francesca; Scartozzi, Mario; Avallone, Antonio; Lutrino, Stefania Eufemia; Melisi, Davide; Antonuzzo, Lorenzo; Pellegrino, Antonio; Gerratana, Lorenzo; Cordio, Stefano; Vasile, Enrico; Aprile, Giuseppe

    2017-10-04

    To evaluate the impact on overall survival (OS) of gastrectomy in asymptomatic metastatic esophago-gastric cancer.  Five hundred and thirteen patients were included. The role of surgery and other clinico-pathological factors was evaluated by univariate and Cox regression analyses. OS was the primary end point. Multivariate analysis confirmed that gastrectomy was a predictor of longer OS (p  0.05). Palliative gastrectomy might play a role in asymptomatic metastatic esophago-gastric cancer patients with good performance status who received benefit from first-line chemotherapy. Future prospective trials integrating tumor biology among inclusion criteria may help defining the optimal candidates.

  2. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy

    Science.gov (United States)

    Turo, Rafal; Jallad, Samer; Prescott, Stephen; Cross, William Richard

    2013-01-01

    The incidence of prostate cancer in transsexual patients is very low with only few reported cases. Many years before presenting with prostate cancer, these patients receive hormone ablation as a part of their gender therapy. Their disease is already defined as castrate resistant, and the treatment and follow-up of such patients remains a challenge. We report a case of a male-to-female transgender woman who was diagnosed with metastatic prostate cancer, 31 years post-feminization. PMID:24032068

  3. CLINICAL CASE OF A MASSIVE ISOLA TED METASTATIC ADRENAL LESION IN COLORECT AL CANCER

    Directory of Open Access Journals (Sweden)

    I. P. Moshurov

    2015-01-01

    Full Text Available AbstractThe liver, lungs, parietal and visceral peritoneum have traditionally been considered to be the main target organs of metastatic colorectal cancer. The isolated adrenal metastasis in colorectal cancer is rare, in the literature there are single observations of clinical cases of successful surgical treatment of such patients. This article presents the clinical observation of successful surgical treatment of patients with colorectal cancer with massive isolated adrenal metastases.

  4. A Near-Complete Response to Treatment with Gemcitabine plus nab®-Paclitaxel in a Patient with Metastatic Pancreatic Cancer and Poor Performance Status: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdur R. Shakir

    2014-10-01

    Full Text Available Patients with metastatic pancreatic adenocarcinoma and poor performance status (PS are typically excluded from clinical trials of new systemic treatments. Due to concerns that such patients cannot tolerate the greater toxicity sometimes associated with combination chemotherapy regimens, the recommended treatment for pancreatic cancer patients with poor PS is gemcitabine monotherapy. We report the case of a 79-year-old female with pancreatic adenocarcinoma metastatic to the lungs, with multiple comorbidities and an Eastern Cooperative Oncology Group PS of 3, who achieved a rapid and prolonged objective response to gemcitabine plus nab®-paclitaxel. The patient received a total of 11 cycles of treatment. Although her disease was well controlled with gemcitabine plus nab-paclitaxel, she died just over 11 months after diagnosis as a result of her comorbid conditions compounded by treatment-related hematologic toxicity. This case suggests that patients with metastatic pancreatic adenocarcinoma and poor PS may benefit from first-line combination therapy with gemcitabine plus nab-paclitaxel. Further study of this regimen in such patients is warranted.

  5. Metastatic breast cancer cells adhere strongly on varying stiffness substrates, initially without adjusting their morphology.

    Science.gov (United States)

    Massalha, Sonbula; Weihs, Daphne

    2017-06-01

    We show that metastatic breast cancer cells are quantitatively identifiable from benign cells during adherence onto soft, elastic gels. We identify differences in time-dependent morphology and strength of adherence of single breast cells that are likely related to their malignancy and metastatic potential (MP). Specifically, we compare high and low MP breast cancer cells with benign cells as a control on collagen-coated, polyacrylamide gels with Young's modulus in the physiological range of 2.4-10.6 kPa. We observe that the evaluated metastatic breast cancer cells remain rounded, with small contact area, up to 6.5 h following seeding. In contrast, the benign cells spread and become more elongated on stiffer gels. We identify measurable differences in the two-dimensional, lateral, traction forces exerted by the cells, where the rounded, metastatic cells apply significantly larger, traction forces, as compared to the benign cells, on gels stiffer than 2.4 kPa. The metastatic cell lines exhibited gel-stiffness-dependent differences in traction forces, strain energies, and morphologies during the initial stages of adhesion, which may relate to their MP or invasiveness.

  6. Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients.

    Science.gov (United States)

    Ogiya, Rin; Niikura, Naoki; Kumaki, Nobue; Bianchini, Giampaolo; Kitano, Shigehisa; Iwamoto, Takayuki; Hayashi, Naoki; Yokoyama, Kozue; Oshitanai, Risa; Terao, Mayako; Morioka, Toru; Tsuda, Banri; Okamura, Takuho; Saito, Yuki; Suzuki, Yasuhiro; Tokuda, Yutaka

    2016-12-01

    The presence of tumor-infiltrating lymphocytes (TILs) is associated with favorable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2 + , n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin-eosin-stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD-L1), PD-L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t-test, P = 0.004) and that of CD8 + and CD4 + T cells significantly decreased from primary to metastatic tumors (paired t-test, P = 0.008 and P = 0.026, respectively). The PD-L1, PD-L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2 + and TN breast cancers have a lower percentage of TILs and CD8 + and CD4 + T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Hematologic safety of breast cancer chemotherapies in patients with hepatitis B or C virus infection.

    Science.gov (United States)

    Shoji, Hirokazu; Hashimoto, Kenji; Kodaira, Makoto; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Tamura, Kenji; Ando, Masashi; Fujiwara, Yasuhiro

    2012-01-01

    Information regarding hematological toxicities in breast cancer chemotherapy patients with hepatitis B (HBV) or C virus (HCV) infection is limited. We retrospectively reviewed the presence of hepatotoxicities (i.e. aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin elevation) and hematotoxicities (i.e. leukopenia and thrombocytopenia) among breast cancer patients with HBV or HCV infection who received chemotherapy from 1999 to 2010. All of the patients included in this analysis were classified as Child-Pugh A. Among 32 patients with HBV infection who underwent chemotherapy (total cycles, 378), 3 experienced grade 3/4 hepatotoxicities, requiring 2 treatment delays and 1 treatment revision. Further, 9 patients experienced grade 3/4 hematotoxicities; of these, 2 required treatment delays and 3 required treatment revisions. Fifty-two HCV patients underwent a total of 570 cycles of chemotherapy. Five patients experienced grade 3/4 hepatotoxicities and required treatment delays, whereas 10 patients experienced grade 3 hematotoxicities; 3 of these patients required treatment delays. Hematotoxicities requiring chemotherapy dose or treatment revision were not highly prevalent among breast cancer chemotherapy patients with HBV or HCV infection and a normal range of liver function. Under careful monitoring, chemotherapy dosage or schedule adjustments may not be necessary in similar patients positive for HBV or HCV. Copyright © 2012 S. Karger AG, Basel.

  8. [Advanced and Metastatic Lung Cancer – What is new in the Diagnosis and Therapy?].

    Science.gov (United States)

    Rothschild, Sacha I

    2015-07-01

    Lung cancer is one of the most common types of malignancies worldwide. The majority of patients are diagnosed with an incurable advanced/metastatic stage disease. Palliative treatment approaches improve the survival and the quality of life of these patients. Lung cancer is subdivided according to histology and molecular biology. The most important classification separates small cell from non-small cell lung cancer. In the subgroup of non-small cell lung cancer novel treatment approaches coming along with an improved prognosis have been established during the last decade. The current manuscript provides an overview on current treatment options for metastatic lung cancer. Furthermore, an outlook on promising future treatment options is provided.

  9. Development of a novel metastatic breast cancer score based on hyaluronic acid metabolism.

    Science.gov (United States)

    El-Mezayen, Hatem A; Toson, El-Shahat A; Darwish, Hossam; Metwally, Fatheya M

    2013-03-01

    Tumor metastasis involves the dissemination of malignant cells into the basement membrane, and the vascular system contributes to the circulating pool of these markers. In this context, our aim has been focused on the development of a non-invasive score based on degradation of the backbone of glycosaminoglycans of the extracellular matrix; namely hyaluronic acid (HA), for the assessment of metastasis in patients with breast cancer. HA level was determined by enzyme-linked immunosorbent assay; CA 15.3 was determined by microparticle enzyme immunoassay; hyaluronidase, N-acetyl-β-D-glucosaminidase, β-glucuronidase, glucuronic acid, and glucosamine were assayed by standard colorimetric techniques in 217 patients with breast cancer. Statistical analyses were performed by logistic regression and receiver-operating characteristic analysis curves. The multivariate discriminant analysis selects a score based on absolute values of the six biochemical markers: metastatic breast cancer score (MBCS) = [1.04 (Numerical constant) + 0.003 × CA 15.3 (U/l) + 0.001 × HA (ng/ml) + 0.004 × hyaluronidase (mg N-acetyl-β-D-glucosamine/ml/18 h) + 0.001 × N-acetyl-β-D-glucosaminidase (μmol/ml/min) + 0.026 × glucuronic acid (ng/ml) + 0.003 × glucosamine (μg/dl)]. This function correctly classified 87 % of metastatic breast cancer at cut-off value = 0.85 (i.e., great than 0.85 indicates patients with metastatic breast cancer and less than 0.85 indicates patients with non-metastatic breast cancer). MBCS is a novel, non-invasive, and simple score which can be applied to discriminate patients with metastatic breast cancer.

  10. 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

  11. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes.

    Science.gov (United States)

    Han, Yo-Han; Kee, Ji-Ye; Kim, Dae-Seung; Mun, Jeong-Geon; Jeong, Mi-Young; Park, Sang-Hyun; Choi, Byung-Min; Park, Sung-Joo; Kim, Hyun-Jung; Um, Jae-Young; Hong, Seung-Heon

    2016-08-27

    Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

  12. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

    Directory of Open Access Journals (Sweden)

    Yo-Han Han

    2016-08-01

    Full Text Available Arctigenin (ARC has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC. In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2 and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

  13. DEGRO practice guidelines for palliative radiotherapy of metastatic breast cancer. Bone metastases and metastatic spinal cord compression (MSCC)

    Energy Technology Data Exchange (ETDEWEB)

    Souchon, Rainer [Dept. of Radiation Oncology, UKT Tuebingen (Germany); Wenz, Frederik [Univ. Hospital Mannheim (Germany); Sedlmayer, Felix [Univ. Hospital, Salzburger Landeskliniken, Salzburg (Austria); Budach, Wilfried [Univ. Hospital Duesseldorf (Germany); Dunst, Juergen [Univ. Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, Petra [Klinikum Neukoelln, Berlin (Germany); Haase, Wulf [St.-Vincentius-Kliniken, Karlsruhe (Germany); Harms, Wolfgang [St. Clara Hospital, Basel (Switzerland); Sautter-Bihl, Marie-Luise [Municipal Hospital, Karlsruhe (Germany); Sauer, Rolf [Univ. Hospital Erlangen (Germany)

    2009-07-15

    To provide practice guidelines and clinical recommendations on preferred standard palliative radiation therapy of bone metastases as well as metastatic spinal cord compression (MSCC) for metastatic breast cancer patients. Methods: The breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials. The literature search encompassed the period 1995-2008 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''breast cancer'', ''bone metastasis'', ''osseous metastasis'', ''metastatic spinal cord compression'' as well as ''radiotherapy'' and ''radiation therapy''. Clinical recommendations were formulated based on the panel's interpretation of the level of evidence referring to the criteria of evidence-based medicine. Results: Different therapeutic goals (pain relief, local tumor control, prevention or improvement of motor deficits, stabilization of the spine or other bones) require complex approaches considering individual factors (i.e. life expectancy, tumor progression at other sites). Best results are achieved by close interdisciplinary cooperation minimizing the interval between diagnosis and onset of treatment. Most important criteria for prognosis and choice of treatment (mostly combined multimodal therapy) are neurologic status at diagnosis of MSCC, time course of duration and progression of the neurologic symptoms. Radiation therapy is effective and regarded as treatment of choice for MSCC with or without motor deficits and/or bone metastases, which do not need immediate surgical intervention. It may be used either postoperatively or as primary treatment in case of inoperability. An optimal dose fractionation schedule or optimal standard dose for treatment of bone

  14. HPMA-Copolymer Nanocarrier Targets Tumor-Associated Macrophages in Primary and Metastatic Breast Cancer.

    Science.gov (United States)

    Zimel, Melissa N; Horowitz, Chloe B; Rajasekhar, Vinagolu K; Christ, Alexander B; Wei, Xin; Wu, Jianbo; Wojnarowicz, Paulina M; Wang, Dong; Goldring, Steven R; Purdue, P Edward; Healey, John H

    2017-12-01

    Polymeric nanocarriers such as N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers deliver drugs to solid tumors and avoid the systemic toxicity of conventional chemotherapy. Because HPMA copolymers can target sites of inflammation and accumulate within innate immune cells, we hypothesized that HPMA copolymers could target tumor-associated macrophages (TAM) in both primary and metastatic tumor microenvironments. We verified this hypothesis, first in preliminary experiments with isolated bone marrow macrophage cultures in vitro and subsequently in a spontaneously metastatic murine breast cancer model generated from a well-established, cytogenetically characterized 4T1 breast cancer cell line. Using our standardized experimental conditions, we detected primary orthotopic tumor growth at 7 days and metastatic tumors at 28 days after orthotopic transplantation of 4T1 cells into the mammary fat pad. We investigated the uptake of HPMA copolymer conjugated with Alexa Fluor 647 and folic acid (P-Alexa647-FA) and HPMA copolymer conjugated with IRDye 800CW (P-IRDye), following their retroorbital injection into the primary and metastatic tumor-bearing mice. A significant uptake of P-IRDye was observed at all primary and metastatic tumor sites in these mice, and the P-Alexa647-FA signal was found specifically within CD11b+ TAMs costained with pan-macrophage marker CD68. These findings demonstrate, for the first time, a novel capacity of a P-Alexa647-FA conjugate to colocalize to CD11b+CD68+ TAMs in both primary and metastatic breast tumors. This underscores the potential of this HPMA nanocarrier to deliver functional therapeutics that specifically target tumor-promoting macrophage activation and/or polarization during tumor development. Mol Cancer Ther; 16(12); 2701-10. ©2017 AACR. ©2017 American Association for Cancer Research.

  15. Efficacy of chemotherapy after hormone therapy for hormone receptor–positive metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Ryutaro Mori

    2014-11-01

    Full Text Available Objective: According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor–positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy–effective and hormone therapy–ineffective cases. Methods: Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. Results: A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+ status, while 7 patients had human epidermal growth factor receptor 2–positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy–ineffective patients (52.6%. A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%. The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085. However, there were no significant differences in the response to or duration of chemotherapy. Conclusion: The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype

  16. Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers.

    Science.gov (United States)

    Wu, Xihai; Miao, Jilan; Jiang, Jingyan; Liu, Fangmei

    2017-10-01

    Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases. STRING database and Cytoscape were used to analyze and visualize protein-protein interactions (PPIs) between DMGs. CytoNCA plugin was utilized to identify key nodes in PPI network. A total of 610, 1076, and 501 DMGs were identified between primary endometrial cancer and hyperplasia, metastatic endometrial cancer and hyperplasia, as well as metastatic and primary endometrial cancers, respectively. For the three DMG sets, 53 common hypermethylated DMGs (e.g. PAX6 and INSR) and 6 common hypomethylated DMGs (e.g. PRDM8, KLHL14, and DUSP6) were found. For primary-hyperplasia DMG set and metastasis-hyperplasia DMG set, 527 common DMGs were found. For these common DMGs, a PPI network involving 692 PPIs was constructed. For DMGs between metastatic and primary endometrial cancers, a PPI network involving 673 PPIs was established, with PAX6 and INSR in the top 20 DMGs in both networks. PRDM8, KLHL14, and DUSP6 had hypomethylated CpG islands. DMGs comparison, PPI network analysis, and analysis of differentially methylated CpG islands indicated that PAX6, INSR, PRDM8, KLHL14, and DUSP6 might participate in the development and metastasis of endometrial cancer. Copyright © 2017. Published by Elsevier B.V.

  17. [Cabazitaxel for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: the TROPIC study in France].

    Science.gov (United States)

    Pouessel, Damien; Oudard, Stéphane; Gravis, Gwenaëlle; Priou, Frank; Shen, Liji; Culine, Stéphane

    2012-01-01

    In 2010, results of the TROPIC study demonstrated that, when compared to mitxantrone, the novel taxane cabazitaxel improved median overall survival of patients with metastatic castration-resistant prostate cancer who progressed on or after docetaxel treatment. We report the data on efficacy and toxicity observed in the subgroup of patients included in the French centers. In this phase III randomized international trial, patients received prednisone and were treated with either 25 mg/m(2) cabazitaxel or 12 mg/m(2) mitoxantrone intravenously every three weeks. The primary endpoint was overall survival. The secondary endpoints included progression-free survival (PFS) and safety. Analyses were performed on the intention-to-treat population. Among the 90 patients enrolled in France, the median overall survival was 18 months for the cabazitaxel arm versus 14.3 months for the mitoxantrone arm. An improvement in PFS was also observed, with a median of 1.4 months for the mitoxatrone arm compared to a median of 2.5 months for the cabazitaxel arm. The most common grade ≥ 3 adverse events were hematologic with neutropenia, usually afebrile and digestive with 4 % of patients reporting diarrhea. These results are comparable to those reported for the overall population and the safety profile remains favorable without any toxic death related to cabazitaxel.

  18. Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

    DEFF Research Database (Denmark)

    Buch-Hansen, Trine Zeeberg; Bentzen, Lise Nørgaard; Hansen, Steinbjoern

    2010-01-01

    DGP, maximum of eight courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m(2) was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m(2) every third week. Patients had castrate refractory metastatic prostate cancer (CRMPC...

  19. Slow accrual of elderly patients with metastatic breast cancer in the Dutch multicentre OMEGA study

    NARCIS (Netherlands)

    Hamaker, M. E.; Seynaeve, C.; Nortier, J. W. R.; Wymenga, M.; Maartense, E.; Boven, E.; van Leeuwen-Stok, A. E.; de Rooij, S. E.; van Munster, B. C.; Smorenburg, C. H.

    2013-01-01

    In a Dutch multicentre study, elderly (65 + year) metastatic breast cancer patients, eligible for first-line chemotherapy, were randomised between two types of single-agent chemotherapy. As accrual was slow, with 78 randomised patients between April 2007 and September 2011, we explored potential

  20. The updated EAU guidelines on muscle-invasive and metastatic bladder cancer.

    NARCIS (Netherlands)

    Stenzl, A.; Cowan, N.C.; Santis, M. de; Jakse, G.; Kuczyk, M.A.; Merseburger, A.S.; Ribal, M.J.; Sherif, A.; Witjes, J.A.

    2009-01-01

    CONTEXT: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION: A

  1. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2013 Guidelines

    NARCIS (Netherlands)

    Witjes, J.A.; Comperat, E.; Cowan, N.C.; Santis, M. de; Gakis, G.; Lebret, T.; Ribal, M.J.; Heijden, A.G. van der; Sherif, A.

    2014-01-01

    CONTEXT: The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments. OBJECTIVE: To provide graded

  2. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer.

    Science.gov (United States)

    Tolaney, Sara M; Tan, Sally; Guo, Hao; Barry, William; Van Allen, Eliezer; Wagle, Nikhil; Brock, Jane; Larrabee, Katherine; Paweletz, Cloud; Ivanova, Elena; Janne, Pasi; Overmoyer, Beth; Wright, John J; Shapiro, Geoffrey I; Winer, Eric P; Krop, Ian E

    2015-10-01

    MET expression and activation appear to be important for initiation and progression of triple-negative breast cancer. Tivantinib (ARQ 197) is an orally administered agent that targets MET, although recent preclinical data suggests the agent may have mechanisms of action that are independent of MET signaling. We conducted a phase 2 study of tivantinib monotherapy in patients with metastatic triple-negative breast cancer. Patients with metastatic triple-negative breast cancer who had received 1 to 3 prior lines of chemotherapy in the metastatic setting were enrolled into this two-stage, single arm phase 2 study. Treatment consisted of twice daily oral dosing of tivantinib (360 mg po bid) during a 21-day cycle. Patients underwent restaging scans at 6 weeks, and then every 9 weeks. Tumor biomarkers that might predict response to tivantinib were explored. 22 patients were enrolled. The overall response rate was 5 % (95 % CI 0-25 %) and the 6-month progression-free survival (PFS) was 5 % (95 % CI 0-25 %), with one patient achieving a partial response (PR). Toxicity was minimal with only 5 grade ≥3 adverse events (one grade 3 anemia, one grade 3 fatigue, and 3 patients with grade 3/4 neutropenia). This study represents the first evaluation of tivantinib for the treatment of metastatic triple-negative breast cancer. These results suggest that single agent tivantinib is well tolerated, but did not meet prespecified statistical targets for efficacy.

  3. A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells.

    Science.gov (United States)

    Lirdprapamongkol, Kriengsak; Sakurai, Hiroaki; Abdelhamed, Sherif; Yokoyama, Satoru; Maruyama, Takeyuki; Athikomkulchai, Sirivan; Viriyaroj, Amornrat; Awale, Suresh; Yagita, Hideo; Ruchirawat, Somsak; Svasti, Jisnuson; Saiki, Ikuo

    2013-11-01

    Tumor hypoxia commonly occurs in solid tumors, and correlates with metastasis. Current cancer therapies are inefficient in curing metastatic disease. Herein, we examined effect of Thai propolis extract and its major constituent, chrysin, on hypoxic survival of 4T1 mouse breast cancer cells in vitro, and investigated its underlying mechanism. In vivo effect of chrysin on metastatic progression of cancer cells was studied, both as a single agent and in combination with another antimetastatic agent, agonistic monoclonal antibody targeting the DR5 TRAIL receptor (DR5 mAb). Thai propolis extract and chrysin decreased survival of 4T1 cells after exposure to hypoxia (1% O2), for 2 days. Immunoblot analysis revealed that chrysin inhibited hypoxia-induced STAT3 phosphorylation without affecting HIF-1α protein level. Chrysin also abrogated hypoxia-induced VEGF gene expression as determined by qRT-PCR. The in vivo effect of chrysin was determined in a spontaneous metastasis mouse model of breast cancer, either alone or in combination with DR5 mAb. Daily oral administration of chrysin in Balb/c mice implanted with 4T1 cells significantly suppressed growth of lung metastatic colonies. Moreover, antimetastatic activity of DR5 mAb was enhanced when given in combination with chrysin. We demonstrate that chrysin has potential in controlling metastatic progression.

  4. Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Oudard, Stéphane; Kramer, Gero; Caffo, Orazio

    2015-01-01

    OBJECTIVE: To evaluate the benefit of docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line docetaxel. PATIENTS AND METHODS: We retrospectively reviewed the records of consecutive patients with mCRPC w...

  5. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Tabernero, Josep; Pfeiffer, Per; Cervantes, Andrés

    2008-01-01

    The primary purpose of this paper is to present the available evidence for the administration of cetuximab on an every-2-weeks basis in combination with irinotecan in metastatic colorectal cancer (mCRC). Cetuximab is an epidermal growth factor receptor-targeted IgG(1) monoclonal antibody that is ...

  6. Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Thomsen, Maria; Kersten, Christian; Sorbye, Halfdan

    2016-01-01

    Objectives: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. Results...

  7. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana

    2017-01-01

    Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated...

  8. Low Number of Detectable Circulating Tumor Cells in Non-metastatic Colon Cancer

    DEFF Research Database (Denmark)

    Thorsteinsson, Morten; Söletormos, György; Jess, Per

    2011-01-01

    The aim of the present study was to detect circulating tumor cells (CTCs) in the peripheral blood of patients with non-metastatic colon cancer and to evaluate whether there is a diurnal variation in the CTC counts. Furthermore, the study aimed to examine the correlation between CTCs and TNM stage...

  9. Cost utility analysis of everolimus in the treatment of metastatic renal cell cancer in the Netherlands

    NARCIS (Netherlands)

    Mihajlović, J.; Minović, I.; Bruinsma, A.; Postma, M.J.

    2013-01-01

    Objectives: Metastatic renal cell cancer (mRCC) is becoming an important part of Dutch health care expenditure due to expensive pharmaceutical options for disease control and lack of adequate prevention methods. New targeted therapeutics, such as sunitinib, sorafenib and everolimus, have recently

  10. Prognostic factors for survival in metastatic breast cancer by hormone receptor status

    NARCIS (Netherlands)

    Kwast, A.B.G.; Voogd, A.C.; Menke-Pluijmers, M.B.E.; Linn, S.C.; Sonke, G.S.; Kiemeney, L.A.; Siesling, Sabine

    2014-01-01

    Hormone receptor (HR) status is an important prognostic factor for patients with metastatic breast cancer (MBC) and is also correlated with other prognostic factors, such as initial lymph node status, HER2-Neu status and age. The prognostic value of these other factors, however, is unknown when

  11. Molecular markers in circulating tumour cells from metastatic colorectal cancer patients

    Science.gov (United States)

    Gazzaniga, Paola; Gradilone, Angela; Petracca, Arianna; Nicolazzo, Chiara; Raimondi, Cristina; Iacovelli, Roberto; Naso, Giuseppe; Cortesi, Enrico

    2010-01-01

    Abstract The prognosis of metastatic cancer patients is still largely affected by treatment failure, mainly due to drug resistance. The hypothesis that chemotherapy might miss circulating tumour cells (CTCs) and particularly a subpopulation of more aggressive, stem-like CTCs, characterized by multidrug resistance, has been recently raised. We investigated the prognostic value of drug resistance and stemness markers in CTCs from metastatic colorectal cancer patients treated with oxaliplatin (L-OHP) and 5-fluoruracil (5-FU) based regimens. Forty patients with metastatic colorectal cancer were enrolled. CTCs were isolated from peripheral blood and analysed for the expression of aldheyde dehydrogenase 1 (ALDH1), CD44, CD133 (used as markers of stemness), multidrug resistance related protein 5 (MRP5 used as marker of resistance to 5-FU and L-OHP) and survivin (used as a marker of apoptosis resistance). CTCs were found in 27/40 (67%) patients. No correlation was found between the expression of either CD44 and CD133 in CTCs and the outcome of patients, while a statistically significant shorter progression-free survival was found in patients with CTCs positive for the expression of ALDH1, survivin and MRP5. These results support the idea that isolating survivin and MRP5+ CTCs may help in the selection of metastatic colorectal cancer patients resistant to standard 5-FU and L-OHP based chemotherapy, for which alternative regimens may be appropriate. PMID:20597995

  12. Survival benefit associated with surgical oophorectomy in patients with colorectal cancer metastatic to the ovary.

    Science.gov (United States)

    Garrett, Christopher R; George, Ben; Viswanathan, Chitra; Bhadkamkar, Nishin A; Wen, Sijin; Baladandayuthapani, Veerarabhadran; You, Y Nancy; Kopetz, Edmund S; Overman, Michael J; Kee, Bryan K; Eng, Cathy

    2012-09-01

    The purpose of this study was to determine the outcome of patients with colorectal cancer metastatic to the ovary and the impact of surgical oophorectomy on the outcome. We conducted a retrospective evaluation of patients with metastatic colorectal cancer to the ovary. Of 3776 female patients with colorectal cancer seen at MD Anderson from 2001-2008, 110 (2.9%) were identified as having metastases to the ovary. The Kaplan-Meier method and log-rank test were used to examine the survival functions. Seventy-one patients (64.5%) had disease metastatic to the ovary at the time of initial presentation; in 39 patients (35.5%) the ovaries were a site of relapse after previous curative colorectal surgical resection. Patients who presented with ovarian relapse after previous colorectal surgery and who underwent oophorectomy had a median survival of 50 months compared with 12 months for those who did not (P cancer metastatic to the ovary may derive a survival benefit from palliative oophorectomy. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Decoy receptor 1 (DCR1) promoter hypermethylation and response to irinotecan in metastatic colorectal cancer

    NARCIS (Netherlands)

    Bosch, Linda J W; Trooskens, Geert; Snaebjornsson, Petur; Coupe, Veerle M. H.; Mongera, Sandra; Haan, Josien C.; Richman, Susan D.; Koopman, Miriam|info:eu-repo/dai/nl/298209640; Tol, Jolien; Meyer, Tim; Louwagie, Joost; Dehaspe, Luc; van Grieken, Nicole C. T.; Ylstra, Bauke; Verheul, Henk M. W.; van Engeland, Manon; Nagtegaal, Iris D; Herman, James G; Quirke, Philip; Seymour, Matthew T; Punt, Cornelis J A; van Criekinge, Wim; Carvalho, Beatriz; Meijer, Gerrit A.

    2017-01-01

    Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate genes were selected from 389 genes involved in

  14. Metastatic castration-resistant prostate cancer: new therapies, novel combination strategies and implications for immunotherapy

    NARCIS (Netherlands)

    Drake, C.G.; Sharma, P.; Gerritsen, W.R.

    2014-01-01

    For the past decade, docetaxel has remained the global standard of care for frontline treatment of metastatic castration-resistant prostate cancer (mCRPC). Until recently, there were limited options for patients with mCRPC following docetaxel failure or resistance, but now the approved treatment

  15. Optimal management of metastatic castration-resistant prostate cancer: Highlights from a European Expert Consensus Panel

    NARCIS (Netherlands)

    J.M. Fitzpatrick (John); J. Bellmunt (Joaquim); K. Fizazi (Karim); A. Heidenreich (Axel); C.N. Sternberg (Cora); B. Tombal (Bertrand); A. Alcaraz (Antonio); A. Bahl (Amit); S. Bracarda (Sergio); G. Di Lorenzo (Giuseppe); E. Efstathiou (Eleni); S.P. Finn (Stephen); S.D. Fossa (Sophie); S. Gillessen (Silke); P.-L. Kellokumpu-Lehtinen (Pirkko-Liisa); F.E. Lecouvet (Frédéric); S. Oudard (Stéphane); T.M. de Reijke (Theo); C.N. Robson (Craig); M. de Santis (Maria); B. Seruga (Bostjan); R. de Wit (Ronald)

    2014-01-01

    textabstractThe exponential growth of novel therapies for the treatment of metastatic castration-resistant prostate cancer (mCRPC) over the last decade has created an acute need for education and guidance of clinicians regarding optimal strategies for patient management. A multidisciplinary panel of

  16. 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

  17. Quantitative method of measuring cancer cell urokinase and metastatic potential

    Science.gov (United States)

    Morrison, Dennis R. (Inventor)

    1993-01-01

    The metastatic potential of tumors can be evaluated by the quantitative detection of urokinase and DNA. The cell sample selected for examination is analyzed for the presence of high levels of urokinase and abnormal DNA using analytical flow cytometry and digital image analysis. Other factors such as membrane associated urokinase, increased DNA synthesis rates and certain receptors can be used in the method for detection of potentially invasive tumors.

  18. Cavernous sinus syndrome associated with metastatic colorectal cancer and perineural spread along the trigeminal nerve.

    Science.gov (United States)

    Nassrallah, Georges; Sun, Vincent; Guiot, Marie-Christine; Mikhail, Mikel; Arthurs, Bryan

    2017-06-01

    We report the case of a patient with cavernous sinus syndrome associated with biopsy-confirmed metastasis from colorectal cancer. A patient known for laryngeal carcinoma and metastatic colorectal carcinoma presented with symptoms of left trigeminal neuralgia and progressive, near-complete ophthalmoplegia. Magnetic resonance imaging (MRI) revealed a mass in the left cavernous sinus, extending into Meckel's cave with perineural spread along the mandibular branch of the left trigeminal nerve. A transsphenoidal biopsy was performed and demonstrated metastatic colon adenocarcinoma. We review the existing literature on colorectal cancer associated cavernous sinus syndrome. Cavernous sinus metastasis from colorectal cancer is exceedingly rare. We report the second case of this entity with histopathologic confirmation, and the first case with concurrent perineural spread involving the trigeminal nerve. Cavernous sinus metastasis may represent a poor prognostic factor in colorectal cancer.

  19. Evolution of DNA aptamers through in vitro metastatic-cell-based systematic evolution of ligands by exponential enrichment for metastatic cancer recognition and imaging.

    Science.gov (United States)

    Li, Xilan; An, Yuan; Jin, Jiang; Zhu, Zhi; Hao, Linlin; Liu, Lu; Shi, Yongquan; Fan, Daiming; Ji, Tianhai; Yang, Chaoyong James

    2015-01-01

    Metastasis, the capability of tumor cells to spread and grow at distant sites, is the primary factor in cancer mortality. Because metastasis in sentinel lymph nodes suggests the original spread of tumors from a primary site, the detection of lymph node involvement with cancer serves as an important prognostic and treatment parameter. Here we have developed a panel of DNA aptamers specifically binding to colon cancer cell SW620 derived from metastatic site lymph node, with high affinity after 14 rounds of selection by the cell-SELEX (systematic evolution of ligands by exponential enrichment) method. The binding affinities of selected aptamers were evaluated by flow cytometry. Aptamer XL-33 with the best binding affinity (0.7 nM) and its truncated sequence XL-33-1 with 45 nt showed excellent selectivity for recognizing target cell SW620. The binding entity of the selected aptamer has been preliminarily determined as a membrane protein on the cell surface. Tissue imaging results showed that XL-33-1 was highly specific to the metastatic tumor tissue or lymph node tissue with corresponding cancer metastasis and displayed an 81.7% detection rate against colon cancer tissue with metastasis in regional lymph nodes. These results suggest that XL-33-1 has great potential to become a molecular imaging agent for early detection of lymph node tissue with colon cancer metastasis. More importantly, this study clearly demonstrates that DNA ligands selectively recognizing metastatic cancer cells can be readily generated by metastatic-cell-based SELEX for potential applications in metastatic cancer diagnosis and treatment.

  20. Oxidative stress may cause metastatic disease in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Søndergaard, Edith Smed; Gögenur, Ismail

    2014-01-01

    Despite surgical treatment of stage II colorectal cancer many patients will experience relapse. Inflammatory and immunologic reactions created due to the surgical stress response result in the production of reactive oxygen species. Oxidative stress in turn, may result in the stimulation of cancer...... cells that have not been cleared by the immune system to metastasize. In this paper we present an overview of studies where oxidative stress in relation to surgery has been linked to the development of metastatic disease....

  1. Infused Therapy and Survival in Older Patients Diagnosed with Metastatic Breast Cancer who Received Trastuzumab

    OpenAIRE

    Griffiths, Robert I.; Lalla, Deepa; Robert J. Herbert; Doan, Justin F; Brammer, Melissa G; Danese, Mark D.

    2011-01-01

    We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [C...

  2. Impact of modern chemotherapy on the survival of women presenting with de novo metastatic breast cancer

    OpenAIRE

    Pal Sumanta K; Dehaven Mary; Nelson Rebecca A; Onami Susan; Hsu JoAnn; Waliany Sarah; Kruper Laura; Mortimer Joanne

    2012-01-01

    Abstract Background Data that directly associate utilization of novel systemic therapies with survival trends in metastatic breast cancer (MBC) are limited. In the setting of de novo MBC, large registry analyses cite positive temporal trends in survival, but the extent to which advances in systemic therapy have contributed to these gains is not clear. Methods The City of Hope Cancer Registry was used to identify a consecutive series of patients with de novo MBC who received their first line o...

  3. High Throughput Sequencing of Germline and Tumor from Men With Early-Onset Metastatic Prostate Cancer

    Science.gov (United States)

    2014-10-01

    laboratory has applied these same approaches to interrogate hundreds of routine FFPE cancer specimens on the Ion Torrent platform, including...START DATE Sept. 01, 2013 Site 1: University of Michigan Site 2: University of Carolina – Chapel Hill 3003 S. State Street Ann Arbor, MI 48109-1274...specified in proposal) Timeline Site 1 Site 2 Major Task 1: To identify and enroll men with de novo metastatic prostate cancer presenting at or before

  4. A Unique Case of Muscle-Invasive Metastatic Breast Cancer Mimicking Myositis

    Directory of Open Access Journals (Sweden)

    Janelle Gyorffy

    2017-01-01

    Full Text Available Breast cancer rarely metastasizes to the muscles, and it is even more unusual for this phenomenon to result in airway compromise. We present a unique case of an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid muscles. After establishing the diagnosis and discussing possible treatment options, the patient elected for antiestrogen therapy, palliative tracheostomy, radiation therapy, and hospice services.

  5. A Randomized Controlled Trial of Emotionally Expressive Writing for Women With Metastatic Breast Cancer

    Science.gov (United States)

    Low, Carissa A.; Stanton, Annette L.; Bower, Julienne E.; Gyllenhammer, Lauren

    2011-01-01

    Objective To test the effects of emotionally expressive writing in a randomized controlled trial of metastatic breast cancer patients and to determine whether effects of the intervention varied as a function of perceived social support or time since metastatic diagnosis. Design Women (N = 62) living with Stage IV breast cancer were randomly assigned to write about cancer-related emotions (EMO; n = 31) or the facts of their diagnosis and treatment (CTL; n = 31). Participants wrote at home for four 20-min sessions within a 3-week interval. Main Outcome Measures Depressive symptoms, cancer-related intrusive thoughts, somatic symptoms, and sleep quality at 3 months postintervention. Results No significant main effects of experimental condition were observed. A significant condition × social support interaction emerged on intrusive thoughts; EMO writing was associated with reduced intrusive thoughts for women reporting low emotional support (η2 = .15). Significant condition × time since metastatic diagnosis interactions were also observed for somatic symptoms and sleep disturbances. Relative to CTL, EMO participants who were more recently diagnosed had fewer somatic symptoms (η2 = .10), whereas EMO participants with longer diagnosis duration exhibited increases in sleep disturbances (η2 = .09). Conclusion Although there was no main effect of expressive writing on health among the current metastatic breast cancer sample, expressive writing may be beneficial for a subset of metastatic patients (including women with low levels of emotional support or who have been recently diagnosed) and contraindicated for others (i.e., those who have been living with the diagnosis for years). PMID:20658835

  6. Critical questions in metastatic castration-resistant prostate cancer: Integrating emerging clinical evidence and guideline recommendations

    Directory of Open Access Journals (Sweden)

    Mohamed Ali

    2016-01-01

    Full Text Available Metastatic castration-resistant prostate cancer (CRPC typically confers a poor prognosis, however, novel advances in treatment options, as well as biomarkers for monitoring disease response and progression, have recently helped improve survival rates. Additionally, new guidelines provide some direction on incorporating these new treatments but some confusion still exists among clinicians about best methods for initiating treatment and the optimal sequencing of agents to prolong survival. In this article, we review the literature and answer some frequently asked questions about treating men with metastatic CRPC, including choosing a first-line treatment, monitoring treatment response, and proceeding to additional lines of therapy.

  7. Radium 223: how can we optimize this new tool for metastatic castration-resistant prostate cancer?

    Science.gov (United States)

    Dorff, Tanya Barauskas; Gross, Mitchell E

    2015-01-01

    Radium 223 is an alpha-emitting intravenous radiotherapy approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). The approved indication covers men with pain from bony metastatic disease and no visceral involvement; however, questions remain as to optimal patient selection and timing of this treatment relative to other life-extending therapies for mCRPC. Limited data exist to guide clinicians on how to position radium 223 in the therapeutic sequence, however, some theoretical considerations and data derived from the ALSYMPCA trial populations pre- and postdocetaxel will be outlined. Subgroup analyses may provide some insight into patient selection.

  8. A Case of Metastatic Bladder Cancer in Both Lungs Treated with Korean Medicine Therapy Alone

    Directory of Open Access Journals (Sweden)

    Dong-Hyun Lee

    2014-07-01

    Full Text Available This case report is aimed to investigate the effects of Korean medicine therapy (KMT including oral herbal medicine and herb nebulizer therapy in treating metastatic bladder cancer in the lungs. A 74-year-old man was diagnosed with metastatic bladder cancer in both lungs in August 2013. He refused any chemotherapy and was admitted to our hospital in a much progressed state on January 11, 2014. Since then, he was treated with KMT until May 17, 2014. The main oral herbal medicines were Hyunamdan made of heat-processed ginseng, Hangamdan S made of Cordyceps militaris, Panax ginseng radix, Commiphora myrrha, calculus bovis, margarita, Boswellia carteri, Panax notoginseng radix and Cremastra appendiculata tuber, and nebulizer therapy with Soram nebulizer solution made of wild ginseng and Cordyceps sinensis distillate. Their effect was evaluated considering the change of the main symptoms and using serial chest X-ray. The size and number of multiple metastatic nodules in both lungs were markedly decreased and the symptoms had disappeared. These results suggest that KMT can be an effective method to treat metastatic bladder cancer in the lungs.

  9. A multicentric observational trial of pegylated liposomal doxorubicin for metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Wischnik Arthur

    2010-01-01

    Full Text Available Abstract Background Pegylated liposomal doxorubicin (PLD is active in metastatic breast cancer. This observational study evaluated the efficacy and safety of PLD in patients treated during routine clinical practice. Methods Eligible patients had metastatic breast cancer and were treated with PLD according to the dose and schedule determined by their physician as part of routine practice. The primary objectives were to analyze the efficacy and toxicity of PLD therapy. Results 125 patients were assessable. Median age was 62 years, 78% had performance status 0-1, and 60% had estrogen-receptor-positive disease. PLD treatment was second- or third-line in 69% of patients. Prior anthracyclines (adjuvant or metastatic had been used in 56% of patients. The majority of patients (79% received PLD every 4 weeks at a median dose of 40 mg/m2. Overall response rate was 43% in all patients and 34% in those previously treated with anthracyclines. The most common grade 3/4 adverse events were skin toxicity/hand-foot syndrome (6%, and leukopenia (3%. Conclusions This observational study supports the activity and tolerability of PLD in metastatic breast cancer as demonstrated in PLD clinical trials.

  10. Bisphosphonate-functionalized coordination polymer nanoparticles for the treatment of bone metastatic breast cancer.

    Science.gov (United States)

    He, Yuanfeng; Huang, Yanjuan; Huang, Ziyuan; Jiang, Yali; Sun, Xiaoqi; Shen, Yifeng; Chu, Weijing; Zhao, Chunshun

    2017-10-28

    Bone is the most common organ affected by metastatic breast cancer. Targeting cancers within the bone remains a great challenge due to the inefficient delivery of therapeutic to bone. In this study, a polyethylene glycol (PEG) coated nanoparticles (NPs) made of a Zn2+ coordination polymer was linked with a bone seeking moiety, alendronate (ALN), to deliver cisplatin prodrug (DSP) to the bone. The particle sizes of this novel system, DSP-Zn@PEG-ALN NPs, were regulated by adjusting the volume ratio of water phase to oil phase in microemulsion. It was small enough (about 55nm) to extravasate through the clefts (80nm) of the bone's sinusoidal capillaries and localize into metastatic bones. DSP-Zn@PEG-ALN NPs showed much higher affinity for hydroxyapatite in vitro and bone in vivo than non-targeted DSP-Zn@PEG NPs and cisplatin. In addition, the in vivo biodistribution studies demonstrated that about 4-fold of platinum was delivered to the bone metastatic lesions than that in healthy bones by DSP-Zn@PEG-ALN NPs intravenously. Finally, DSP-Zn@PEG-ALN NPs not only inhibited the tumor growth efficiently but also reduced the osteocalastic bone destruction. Besides, DSP-Zn@PEG-ALN NPs showed significantly reduced toxicity of cisplatin. These results indicate that the DSP-Zn@PEG-ALN NPs have a great potential in enhancing chemotherapeutic efficacy for the treatment of bone metastatic breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Cancer incidence in France over the 1980-2012 period: Hematological malignancies.

    Science.gov (United States)

    Le Guyader-Peyrou, S; Belot, A; Maynadié, M; Binder-Foucard, F; Remontet, L; Troussard, X; Bossard, N; Monnereau, A

    2016-04-01

    The classification of hematological malignancies (HMs) has changed in recent decades. For the first time, the French network of cancer registries (Francim) provides estimates for incidence and trends of HM in France between 1980 and 2012 for major HM subtypes. Incidence was directly estimated by modeling the incidence rates measured in the cancer registry area. For each HM subtype, a "usable incidence period" was defined a priori, corresponding to the years for which all the registries collected them in a homogeneous way. For both sexes and each HM subtype, age-period-cohort models were used to estimate national incidence trends. Overall in France, there were an estimated 35,000 new HMs in 2012 (19,400 in men and 15,600 in women). Lymphoid malignancies accounted for more than two-thirds of HM incident cases (n=25,136). The incidence sex ratio (M/F) varied from 1.1 for classical Hodgkin lymphoma to 4.0 for mantle-cell lymphoma. The median age at diagnosis ranged from 62 to 81 years according to the major HM subtypes. Overall in both sexes, the top five most frequent HMs in 2012 were plasma cell neoplasm (about 4900 estimated cases), chronic lymphocytic leukemia/small lymphocytic lymphoma (4500 cases), diffuse large B-cell lymphoma and myelodysplastic syndromes (4100 cases), and acute myeloid leukemia (2800 cases). The incidence rates increased for follicular lymphoma and plasma cell neoplasm during the study period in both sexes. Classical Hodgkin lymphoma was relatively stable in men between 1980 and 2012 and increased in both sexes during the most recent period. Chronic myeloproliferative neoplasms, other than chronic myelogenous leukemia, are the only subtype that showed a slightly downward trend in incidence between 2003 and 2012 in both sexes. The striking differences in the incidence patterns by histologic subtype strongly suggest a certain level of etiologic heterogeneity among hematological malignancies and support the pursuit of epidemiologic analysis by

  12. 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.

  13. Novel methylated biomarkers and a robust assay to detect circulating tumor DNA in metastatic breast cancer.

    Science.gov (United States)

    Fackler, Mary Jo; Lopez Bujanda, Zoila; Umbricht, Christopher; Teo, Wei Wen; Cho, Soonweng; Zhang, Zhe; Visvanathan, Kala; Jeter, Stacie; Argani, Pedram; Wang, Chenguang; Lyman, Jaclyn P; de Brot, Marina; Ingle, James N; Boughey, Judy; McGuire, Kandace; King, Tari A; Carey, Lisa A; Cope, Leslie; Wolff, Antonio C; Sukumar, Saraswati

    2014-04-15

    The ability to consistently detect cell-free tumor-specific DNA in peripheral blood of patients with metastatic breast cancer provides the opportunity to detect changes in tumor burden and to monitor response to treatment. We developed cMethDNA, a quantitative multiplexed methylation-specific PCR assay for a panel of ten genes, consisting of novel and known breast cancer hypermethylated markers identified by mining our previously reported study of DNA methylation patterns in breast tissue (103 cancer, 21 normal on the Illumina HumanMethylation27 Beadchip) and then validating the 10-gene panel in The Cancer Genome Atlas project breast cancer methylome database. For cMethDNA, a fixed physiologic level (50 copies) of artificially constructed, standard nonhuman reference DNA specific for each gene is introduced in a constant volume of serum (300 μL) before purification of the DNA, facilitating a sensitive, specific, robust, and quantitative assay of tumor DNA, with broad dynamic range. Cancer-specific methylated DNA was detected in training (28 normal, 24 cancer) and test (27 normal, 33 cancer) sets of recurrent stage IV patient sera with a sensitivity of 91% and a specificity of 96% in the test set. In a pilot study, cMethDNA assay faithfully reflected patient response to chemotherapy (N = 29). A core methylation signature present in the primary breast cancer was retained in serum and metastatic tissues collected at autopsy two to 11 years after diagnosis of the disease. Together, our data suggest that the cMethDNA assay can detect advanced breast cancer, and monitor tumor burden and treatment response in women with metastatic breast cancer. ©2014 AACR.

  14. Primary tumor site and anti-EGFR monoclonal antibody benefit in metastatic colorectal cancer: a meta-analysis.

    Science.gov (United States)

    Li, Dandan; Fu, Qiang; Li, Man; Li, Jun; Yin, Can; Zhao, Jin; Li, Feng

    2017-05-01

    This meta-analysis aimed to document the impact of primary tumor site on anti-EGFR monoclonal antibody (mAb) benefit in metastatic colorectal cancer. Tumors with metastatic left-sided colorectal cancer (LCC) were compared with tumors with metastatic right-sided colon cancer (RCC) with respect to anti-EGFR mAb objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) benefit. Comparing LCC with RCC, LCC was found to have significantly superior anti-EGFR mAb ORR (p analysis demonstrated that LCC had markedly superior anti-EGFR mAb treatment benefit compared with RCC.

  15. Critical appraisal of bevacizumab in the treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Zoratto F

    2012-09-01

    Full Text Available Federica Zoratto,1 Luigi Rossi,1 Angelo Zullo,2 Anselmo Papa,1 Eleonora Zaccarelli,1 Luigi Tomao,3 Erika Giordani,1 Maria Colonna,4 Giovanni Baiano,5 Silverio Tomao11Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University, Oncology Unit, “SM Goretti” Hospital, Latina; 2Gastroenterology and Digestive Endoscopy Unit, “Nuovo Regina Margherita” Hospital, Rome; 3Biology Department, “Regina Elena National Cancer Institute”, Rome; 4Oncology Unit, “Don Luigi di Liegro” Hospital, Gaeta, 5Surgery Unit, “San Giovanni di Dio” Hospital, Fondi, ItalyAbstract: Colorectal cancer is one of the most common cancers worldwide. The prognosis of patients with metastatic colorectal cancer in recent years has increased from 5 months with best supportive care to nearly 2 years with chemotherapy combined with bevacizumab, an antivascular endothelial growth factor monoclonal antibody. New prognostic and predictive biomarkers have been identified to guide chemotherapy in metastatic colorectal cancer, such as KRAS and BRAF oncogenes. However, the status of these oncogenes does not affect the efficacy of bevacizumab, and biomarkers predicting response to treatment with bevacizumab are still lacking. Addition of bevacizumab to regimens based on fluoropyrimidines or irinotecan has been shown to improve overall survival in treatment-naïve patients with metastatic colorectal cancer. Similarly, a significant increase in overall survival rate is achieved by adding bevacizumab to fluoropyrimidines and oxaliplatin in patients with disease progression. Bevacizumab has been found to be effective even when used as third-line therapy and later. In addition, cohort studies have shown that bevacizumab improves survival significantly despite disease progression. Finally, bevacizumab therapy in the neoadjuvant setting for the treatment of liver metastasis is well tolerated, safe, and effective.Keywords: metastatic colorectal cancer

  16. Role of sympathetic nerves in the establishment of metastatic breast cancer cells in bone

    Directory of Open Access Journals (Sweden)

    Florent Elefteriou

    2016-09-01

    Full Text Available The bone marrow microenvironment is characterized by its multicellular nature, and perhaps less obviously by the high mobility of multiple transient and stationary cell lineages present in this environment. The trafficking of hematopoietic and mesenchymal cells between the bone marrow and blood compartments is regulated by a number of bone marrow-derived factors. It is suspected that transformed metastatic cells “hijack” these processes to engraft into the skeleton and eventually cause the skeletal complications associated with metastatic disease. In this short review, experimental and association data supporting the contribution of a less recognized cell type of the bone marrow – the nerves of the sympathetic nervous system – to early events of the breast cancer bone metastatic process, are summarized.

  17. Prospects of 2nd line chemotherapy personalization in patients with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2016-01-01

    Full Text Available Prostate cancer (PC is one of the most challenging and pressing problems of modern oncourology because of high morbidity associated with the disease worldwide. About 1 100 000 new cases are diagnosed each year. The main approach to treatment of locally advanced and/or metastatic PC is hormonal therapy. Androgen deprivation therapy allows to achieve stabilization in more than 90 % of patients, but average time until progression after hormonal therapy in patients with metastatic PC is about 2 years. Then patients with tumor progression accompanied by castration level of testosterone enter the stage of so-called castration-resistant PC (CRPC. Prognosis for regional CRPC is unfavorable, and it substantially lowers patients’ quality of life. Taxane-based chemotherapy remains a standard method of treatment in this patient cohort. The article reviews studies of efficacy of different doses and regimes of 2nd line chemotherapy using cabazitaxel in patients with metastatic CRPC.

  18. Paclitaxel-carboplatin chemotherapy induced hematologic toxicities among epithelial ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Afandi Charles

    2016-11-01

    This study confirmed the hematologic toxicities after paclitaxel-carboplatin chemotherapy in EOC patients treated in Hasan Sadikin General Hospital, West Java. The hemoglobin concentration may serve as prognostic factor. Further studies directed to other factors such as genetic factor for polymorphisms may be encouraged to explore the decrease of the hematologic indices.

  19. Hepatic splenosis diagnosed after inappropriate metastatic evaluation in patient with low-risk prostate cancer.

    Science.gov (United States)

    Li, Hanhan; Snow-Lisy, Devon; Klein, Eric A

    2012-05-01

    A man interested in active surveillance of low-risk prostate cancer sought a second opinion after having undergone an inappropriate metastatic evaluation that demonstrated multiple enhancing liver masses. Because of his history of splenectomy for trauma, hepatic splenosis was suspected. Despite reassurance, the patient desired biopsy of the masses to confirm splenosis. The imaging features and pathophysiology of hepatic splenosis are presented. Owing to the low rates of metastatic disease, the current guidelines do not recommend diagnostic imaging for low-risk prostate cancer. The present case illustrates the dangers of the current widespread practice of inappropriate diagnostic imaging of patients with low-risk prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Metastatic Testicular Cancer to Left Atrium via the Left Inferior Pulmonary Vein: A Case Report

    Directory of Open Access Journals (Sweden)

    Shital Vachhani

    2017-03-01

    Full Text Available Testicular cancer is one of the most common cancers diagnosed in young men. Frequent sites of metastasis include the retroperitoneum, lungs, liver, brain, and bone. Intracardiac metastasis has also been described. An 18-year-old boy with a history of mixed testicular germ cell tumor presented to our institution for surgical resection of his metastatic disease. Intraoperative transesophageal echocardiography during his surgery confirmed a tumor thrombus into the left atrium coming from the left pulmonary vein. We report a case of metastatic testicular cancer with rare tumor extension from the left inferior pulmonary vein into the left atrium. Perioperative transesophageal echocardiography was necessary to aid intraoperative diagnosis and confirmation of the intracardiac tumor, providing data to guide surgical strategy.

  1. Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

    Science.gov (United States)

    Gdowski, Andrew S; Ranjan, Amalendu; Sarker, Marjana R; Vishwanatha, Jamboor K

    2017-09-01

    The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

  2. [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo.

    Science.gov (United States)

    Martin, Ana Carolina B M; Fuzer, Angelina M; Becceneri, Amanda B; da Silva, James Almada; Tomasin, Rebeka; Denoyer, Delphine; Kim, Soo-Hyun; McIntyre, Katherine A; Pearson, Helen B; Yeo, Belinda; Nagpal, Aadya; Ling, Xiawei; Selistre-de-Araújo, Heloisa S; Vieira, Paulo Cézar; Cominetti, Marcia R; Pouliot, Normand

    2017-09-22

    There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo, induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.

  3. The Role of Vascular Endothelial Growth Factor in Metastatic Prostate Cancer to the Skeleton

    Directory of Open Access Journals (Sweden)

    Emma Roberts

    2013-01-01

    Full Text Available Despite the clinical implication and high incidence of bone and spinal metastases, the molecular mechanisms behind prostate cancer metastasis to bone and spine are not well understood. In this review the molecular mechanisms that may contribute to the highly metastatic phenotype of prostate cancer are discussed. Proangiogenic factors such as vascular endothelial growth factor (VEGF have been shown to not only aid in the metastatic capabilities of prostate cancer but also encourage the colonization and growth of prostate tumour cells in the skeleton. The importance of VEGF in the complex process of prostate cancer dissemination to the skeleton is discussed, including its role in the development of the bone premetastatic niche, metastatic tumour cell recognition of bone, and bone remodeling. The expression of VEGF has also been shown to be upregulated in prostate cancer and is associated with clinical stage, Gleason score, tumour stage, progression, metastasis, and survival. Due to the multifaceted effect VEGF has on tumour angiogenesis, tumour cell proliferation, and bone destruction, therapies targeting the VEGF pathways have shown promising clinical application and are being investigated in clinical trials.

  4. PROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnthigh Metastatic Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Simone Ragusa

    2014-09-01

    Full Text Available The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colorectal cancer cells is regulated by the target of oncogenic Wnt signaling, homeobox transcription factor PROX1, expressed by a subpopulation of colon cancer progenitor/stem cells. We identify direct PROX1 target genes and show that repression of a pro-apoptotic member of the BCL2 family, BCL2L15, is important for survival of PROX1+ cells under metabolic stress. PROX1 inactivation after the establishment of metastases prevented further growth of lesions. Furthermore, autophagy inhibition efficiently targeted metastatic PROX1+ cells, suggesting a potential therapeutic approach. These data identify PROX1 as a key regulator of the transcriptional network contributing to metastases outgrowth in colorectal cancer.

  5. Expression of MAGE-A and NY-ESO-1 in Primary and Metastatic Cancers.

    Science.gov (United States)

    Park, Tristen S; Groh, Eric M; Patel, Krishna; Kerkar, Sid P; Lee, Chyi-Chia Richard; Rosenberg, Steven A

    2016-01-01

    Melanoma-associated antigen-A (MAGE-A) and New York esophageal squamous cell cancer-1 (NY-ESO-1) are 2 cancer testis antigens (CTA) demonstrating potential for use in targeted immunotherapy. Clinical trials in melanoma and synovial sarcomas targeting these antigens in immune-based therapies have demonstrated durable tumor regression. Although protein expression of NY-ESO-1 has been assessed in a variety of cancer types, the expression of MAGE-A has not been studied in depth. In this study we analyzed MAGE-A and NY-ESO-1 expression in 314 melanoma specimens from 301 melanoma patients, 38 patients with squamous cell cancers and 111 patients with adenocarcinomas. Our results demonstrated higher expression of MAGE-A compared with NY-ESO-1 in melanomas (32% vs. 13%) and squamous cell carcinomas (45% vs. 7.9%), and higher expression of both CTAs in metastatic versus primary tumors. CTA expression in adenocarcinomas was low (MAGE-A: 10%, NY-ESO-1: 0.9%). In addition, we looked at concordance of expression among metastatic melanoma lesions within the same patient and found concordant expression in 38 of 47 patients for MAGE-A and 43 of 47 patients for NY-ESO-1. Our study demonstrated that the MAGE-A family may be of greater utility than NY-ESO-1 for targeted immunotherapy in a variety of cancer histologies, in particular metastatic melanomas and squamous cell carcinomas.

  6. Exploring correlations between positive psychological resources and symptoms of psychological distress among hematological cancer patients: a cross-sectional study.

    Science.gov (United States)

    Wang, Zi-Yue; Liu, Li; Shi, Meng; Wang, Lie

    2016-07-01

    Hematological cancer patients experience high levels of psychological distress during diagnoses and intensive treatments. The aim of the present study is to explore the effects of positive psychological resources on depressive and anxiety symptoms in hematological cancer patients. This survey was conducted in a hospital during the period from July 2013 to April 2014. A total of 300 inpatients were recruited and finally 227 of them completed the questionnaires. Questionnaires included demographic and clinical variables, the Center for Epidemiologic Studies Depression Scale, the Self-Rating Anxiety Scale, the Life Orientation Scale-Revised, the General Perceived Self-Efficacy Scale, and the Resilience Scale-14. Results showed that the prevalence of depressive and anxiety symptoms was 66.1 and 45.8%, respectively. Both optimism (β = -.479, p optimism (β = -.393, p  .05) was not significantly associated with anxiety symptoms, and self-efficacy was not significantly associated with depressive (β = -.032, p > .05) or anxiety symptoms (β = -.055, p > .05). The results suggest that hematological cancer patients who possess high levels of positive psychological resources may have fewer symptoms of psychological distress. The findings indicate that enhancing positive psychological resources can be considered in developing intervention strategies for decreasing depressive and anxiety symptoms.

  7. Identification of Anti-tumor Cells Carrying Natural Killer (NK Cell Antigens in Patients With Hematological Cancers

    Directory of Open Access Journals (Sweden)

    Ewelina Krzywinska

    2015-10-01

    Full Text Available Natural killer (NK cells, a cytotoxic lymphocyte lineage, are able to kill tumor cells in vitro and in mouse models. However, whether these cells display an anti-tumor activity in cancer patients has not been demonstrated. Here we have addressed this issue in patients with several hematological cancers. We found a population of highly activated CD56dimCD16+ NK cells that have recently degranulated, evidence of killing activity, and it is absent in healthy donors. A high percentage of these cells expressed natural killer cell p46-related protein (NKp46, natural-killer group 2, member D (NKG2D and killer inhibitory receptors (KIRs and a low percentage expressed NKG2A and CD94. They are also characterized by a high metabolic activity and active proliferation. Notably, we found that activated NK cells from hematological cancer patients have non-NK tumor cell antigens on their surface, evidence of trogocytosis during tumor cell killing. Finally, we found that these activated NK cells are distinguished by their CD45RA+RO+ phenotype, as opposed to non-activated cells in patients or in healthy donors displaying a CD45RA+RO− phenotype similar to naïve T cells. In summary, we show that CD45RA+RO+ cells, which resemble a unique NK population, have recognized tumor cells and degranulate in patients with hematological neoplasias.

  8. Retrospective analysis of metastatic behaviour of breast cancer subtypes

    NARCIS (Netherlands)

    Savci-Heijink, C. Dilara; Halfwerk, Hans; Hooijer, Gerrit K. J.; Horlings, Hugo M.; Wesseling, Jelle; van de Vijver, Marc J.

    2015-01-01

    Among breast cancer patients who develop distant metastases, there is marked variability in the clinical course, including metastasis pattern. Here, we present a retrospective study of breast cancer patients who all developed distant metastases focusing on the association between breast cancer

  9. Potential role of pemetrexed in metastatic breast cancer patients pre-treated with anthracycline or taxane

    Directory of Open Access Journals (Sweden)

    Li-Yan Zhou

    2015-03-01

    Full Text Available Objectives: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens. Methods: PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were ‘‘pemetrexed’’ or ‘‘LY231514’’ or “Alimta”, “metastatic breast cancer”, and “advanced breast cancer”. Results: There were 15 studies (n = 1002 meeting our criteria for evaluation. Eight single-agent trials (n = 551 and seven using combinations with other agents (n = 451 were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8% to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B12, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer. Conclusion: Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists. Keywords: Metastatic breast cancer, Chemotherapy, Pemetrexed, Anthracycline, Taxane

  10. Prolonged Pemetrexed Infusion Plus Gemcitabine in Refractory Metastatic Colorectal Cancer: Preclinical Rationale and Phase II Study Results.

    Science.gov (United States)

    Passardi, Alessandro; Fanini, Francesca; Turci, Livia; Foca, Flavia; Rosetti, Paola; Ruscelli, Silvia; Casadei Gardini, Andrea; Valgiusti, Martina; Dazzi, Claudio; Marangolo, Maurizio

    2017-08-01

    Difficulties in translating in vitro results into clinical practice are inevitable.Further efforts to verify the efficacy of alternative schedules of pemetrexed in solid tumors are encouraged. We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedules in three colon cancer cell lines. The best results were obtained with the following schedule: a prolonged pemetrexed exposure followed by a 48-hour wash-out and then gemcitabine. This combination was then advanced to a phase II clinical trial. Patients with metastatic colorectal cancer in progression after standard treatment were included in the study. Adequate bone marrow reserve, normal hepatic and renal function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were required. Treatment consisted of an 8-hour intravenous infusion of pemetrexed 150 mg/m(2) on day 1 and a 30-minute intravenous infusion of gemcitabine 1,000 mg/m(2) on day 3 of each cycle, repeated every 14 days. Fourteen patients were enrolled onto the study (first step). No objective responses were seen, and evidence of stable disease was observed in only one of the 12 evaluable patients. The most important grade 3-4 side effects were hematological toxicity (neutropenia 64.2%, thrombocytopenia 71.4%, anemia 28.7%), fatigue (50.0%), and stomatitis (21.5%). Median overall survival and time to progression were 5.8 months (95% confidence interval [CI]: 3.9-7.1) and 2.1 months (95% CI: 1.7-2.8), respectively. The experimental pemetrexed-gemcitabine combination proved to be inactive and moderately toxic. © AlphaMedPress; the data published online to support this summary is the property of the authors.

  11. Prostate Cancer Metastatic to the Renal Allograft: A Case Report.

    Science.gov (United States)

    Alaini, A; Singh, P; Shah, R; Fischer, E; Ganta, K; Barrett, T; Servilla, K

    Malignancy is a leading cause of morbidity and mortality in organ transplant recipients who receive immunosuppression. Cancers associated with viruses such as nonmelanotic skin cancer and Kaposi sarcoma occur in allograft recipients at rates that far exceed that in the general population. The increased risk and tumor type may depend not only on degree of immune system modulation but also on the type of organ transplanted. In kidney transplant recipients, the risk of cancers such as prostate and breast does not seem to be increased. However, these cancers tend to be advanced and aggressive. The management of these cancers is similar to the general population with the additional consideration for reduction in immunosuppression and conversion to sirolimus. Given the increased survival of both transplanted organs as well as organ recipients along with the increased number of older recipients, the diagnosis of prostate cancer in the older male organ recipient is increasing. The long-term outcomes using current treatment guidelines for prostate cancer in these individuals are not clear. We report a case of known localized prostate cancer in a renal transplant recipient presenting with metastasis diagnosed as tumor infiltration of the allograft. Our patient, upon initial diagnosis of cancer, opted for radiation with eventual androgen-deprivation therapy. This unusual site of prostate cancer spread heightens the need for awareness among providers as well as the need for further studies of the outcomes in these patients undergoing treatments designed using guidelines developed for those with normally functioning immunity. Copyright © 2016. Published by Elsevier Inc.

  12. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer

    NARCIS (Netherlands)

    van Cutsem, Eric; Vervenne, Walter L.; Bennouna, Jaafar; Humblet, Yves; Gill, Sharlene; van Laethem, Jean-Luc; Verslype, Chris; Scheithauer, Werner; Shang, Aijing; Cosaert, Jan; Moore, Malcolm J.

    2009-01-01

    Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the

  13. Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Sørensen, Morten; Pallisgaard, Niels

    2013-01-01

    Background. Patients with chemotherapy refractory metastatic colorectal cancer and KRAS mutations have no effective treatment option. The present study evaluated the efficacy of temsirolimus in chemotherapy refractory mCRC with KRAS mutations. Furthermore, we wanted to investigate if resistance...

  14. Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer ... Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0595 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Dmitri Artemov, Ph.D. 5e...excellent targeting of PSMA- expressing prostate cancer cells both in vitro and in vivo. We investigated details of the mAb and therapeutic complexes

  15. Obstructive uropathy from locally advanced and metastatic prostate cancer: an old problem with new therapies.

    Science.gov (United States)

    Friedlander, Justin I; Duty, Brian D; Okeke, Zeph; Smith, Arthur D

    2012-02-01

    Despite stage migration to more organ-confined disease in the era of prostate-specific antigen, the complications of advanced prostate cancer are still relatively common. Urinary tract obstruction in advanced and metastatic prostate cancer can have a varied presentation, because it may occur in multiple anatomic locations at any point in the natural history of the disease. In all cases, management depends on the current stage of disease, technical feasibility of potential therapeutic interventions, and overall prognosis of the patient. This review highlights a practical approach to the evaluation, diagnosis, and management of obstructive uropathy from prostate cancer.

  16. 10-year survival of a patient with metastatic prostate cancer: Case report and literature review.

    Science.gov (United States)

    Krpina, Kristian; Markić, Dean; Rahelić, Dražen; Ahel, Juraj; Rubinić, Nino; Španjol, Josip

    2015-09-30

    Prostate cancer is the most common malignancy in men. The 5-year relative survival for all stages combined is 98.8%. Patients diagnosed with metastatic prostate cancer have median survival from 2 to 3 years. We describe a case of 64-year old man who clinically presented with inguinal lymphadenopathy. Because of elevated PSA levels biopsy of prostate was done and adenocarcinoma was diagnosed. Biopsy of inguinal lymph nodes confirmed the diagnosis of prostate cancer. Hormonal treatment was started and at the most recent follow-up, 10 years later, the patient is asymptomatic with no clinical signs of disseminated disease.

  17. 10-year survival of a patient with metastatic prostate cancer: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Kristian Krpina

    2015-09-01

    Full Text Available Prostate cancer is the most common malignancy in men. The 5-year relative survival for all stages combined is 98.8%. Patients diagnosed with metastatic prostate cancer have median survival from 2 to 3 years. We describe a case of 64-year old man who clinically presented with inguinal lymphadenopathy. Because of elevated PSA levels biopsy of prostate was done and adenocarcinoma was diagnosed. Biopsy of inguinal lymph nodes confirmed the diagnosis of prostate cancer. Hormonal treatment was started and at the most recent follow-up, 10 years later, the patient is asymptomatic with no clinical signs of disseminated disease.

  18. Complete response of metastatic renal cancer with dendritic cell vaccine

    Directory of Open Access Journals (Sweden)

    Dall'Oglio Marcos

    2003-01-01

    Full Text Available INTRODUCTION: We report a case of metastatic renal cell carcinoma that presented involution following therapy with dendritic cells. CASE REPORT: Male, 51-year old patient underwent left radical nephrectomy in September 1999 due to renal cell carcinoma, evolved with recurrence of the neoplasia in January 2002, confirmed by resection of the lesion. A vaccine therapy based on dendritic cells was then performed during 5 months (4 applications. After this period, there was occurrence of new lesions, whose resection revealed areas of necrosis and inflammatory infiltrate. DISCUSSION: The outcome of renal cell carcinoma is influenced by prognostic factors that confer more aggressive tumor characteristics. However, in cases of recurrence, the systemic therapy with dendritic cells-based vaccine can be associated with a better outcome with regression of disease.

  19. Locally ablative therapies for primary and metastatic liver cancer.

    Science.gov (United States)

    Li, David; Kang, Josephine; Madoff, David C

    2014-08-01

    Locally ablative therapies have an increasing role in the effective multidisciplinary approach towards the treatment of both primary and metastatic liver tumors. In patients who are not considered surgical candidates and have low volume disease, these therapies have now become established into consensus practice guidelines. A large range of therapeutic options exist including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, percutaneous laser ablation (PLA), irreversible electroporation (IRE), stereotactic body radiation therapy (SBRT) and high intensity focused ultrasound (HIFU); each having benefits and drawbacks. The greatest body of evidence supporting clinical utility in the liver currently exists for RFA, with PEI having fallen out of favor. MWA, IRE, SBRT and HIFU are relatively nascent technologies, and outcomes data supporting their use is promising. Future directions of ablative therapies include tandem approaches to improve efficacy in the treatment of liver tumors.

  20. Chemotherapy for recurrent/metastatic head and neck cancers.

    Science.gov (United States)

    Karabajakian, Andy; Toussaint, Philippe; Neidhardt, Eve-Marie; Paulus, Valérie; Saintigny, Pierre; Fayette, Jérôme

    2017-04-01

    Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this protocol in ongoing trials and the association of cisplatin, docetaxel, and cetuximab appears to be the most efficient. The human papilloma virus is very likely a favorable prognostic factor. Immunotherapy with nivolumab or pembrolizumab is now a new standard of treatment in second line after yielding an improvement in overall survival, but predictive markers of efficacy are needed to refine the selection of patients. The combination of paclitaxel and buparlisib appears to be promising.

  1. Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer; Report From the 2016 Coffey-Holden Prostate Cancer Academy Meeting.

    Science.gov (United States)

    Miyahira, Andrea K; Roychowdhury, Sameek; Goswami, Sangeeta; Ippolito, Joseph E; Priceman, Saul J; Pritchard, Colin C; Sfanos, Karen S; Subudhi, Sumit K; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

    2017-02-01

    The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer. The 2016 CHPCA Meeting was attended by 71 investigators from prostate cancer and other fields, who discussed the biology, study methodologies, treatment strategies, and critical unmet needs concerning metastatic prostate cancer, with the ultimate goal of advancing strategies to treat and eliminate this disease. The major topics of discussion included: the molecular landscape and molecular heterogeneity of metastatic prostate cancer, the role of the metastatic microenvironment, optimizing immunotherapy in metastatic prostate cancer, learning from exceptional responders and non-responders, targeting DNA repair deficiency in advanced prostate cancer, developing and applying novel biomarkers and imaging techniques, and potential roles for the microbiome in prostate cancer. This article reviews the topics presented and discussions held at the CHPCA Meeting, with a focus on the unknowns and next steps needed to advance our understanding of the biology and most effective treatment strategies for metastatic prostate cancer. Prostate 77:123-144, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    Science.gov (United States)

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

  3. Optimal screening schedules for prevention of metastatic cancer.

    Science.gov (United States)

    Hanin, Leonid; Pavlova, Lyudmila

    2013-01-30

    We develop methodological, mathematical, statistical, and computational approaches to constructing schedules of cancer screening that maximize the probability that by the time of primary tumor detection it has not yet metastasized. Solving this problem is based on a comprehensive mechanistic model of cancer progression. We apply the model with realistic parameters and the screening optimization methodology to mammographic screening for breast cancer within the American female population. We uncover some general patterns of optimal screening schedules. We show that optimization of screening regimens leads to a significant reduction in the probability of detecting breast cancer that has already disseminated. Copyright © 2012 John Wiley & Sons, Ltd.

  4. A phase II study of lipoplatin (liposomal cisplatin)/vinorelbine combination in HER-2/neu-negative metastatic breast cancer.

    Science.gov (United States)

    Farhat, Fadi S; Temraz, Sally; Kattan, Joseph; Ibrahim, Khaled; Bitar, Nizar; Haddad, Nadine; Jalloul, Rahif; Hatoum, Hassan A; Nsouli, Ghazi; Shamseddine, Ali I

    2011-12-01

    We assessed the efficacy and safety of a liposomal cisplatin (lipoplatin) and vinorelbine combination in metastatic breast cancer (MBC). Thirty-five patients were treated. The objective response rate was 53.1% and the median survival time was 22 months. Grade 3/4 neutropenia was observed in 44% of cycles, and febrile neutropenia was seen in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. This combination is effective and well tolerated in patients with MBC and it warrants investigation as first-line treatment. Liposomal cisplatin (lipoplatin) has a mechanism of action similar to that of cisplatin, with reduced toxicities and enhanced or similar efficacy. We wanted to assess the efficacy and safety of a lipoplatin/vinorelbine combination in a phase II clinical trial in metastatic breast cancer (MBC). Thirty-five patients with HER-2/neu-negative (HER-2/neu(-)) MBC were enrolled. Lipoplatin 120 mg/m(2) (days 1, 8, and 15) and vinorelbine 30 mg/m(2) (days 1 and 8) were administered in a 21-day cycle. Thirty-five patients were included in the intent-to-treat (ITT) analysis; 32 patients were evaluable for response. The objective response rate was 53.1%. Complete response (CR) was achieved in 3 patients (9.4%), partial response (PR) was seen in 14 patients (43.8%), stable disease (SD) was obtained in 12 patients (37.5%), and progressive disease (PD) was seen in 3 patients (9.4%). Median time to disease progression was 8 months (range 6-10 months). After a median follow-up of 15.5 months, 18 patients were still alive; the median survival time was 22 months (95% confidence interval [CI], 14-30). A total of 174 cycles were administered. Neutropenia was the most frequent hematologic toxicity, with grade 3/4 neutropenia observed in 44% of cycles. Febrile neutropenia was observed in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. Grade 1/2 nephrotoxicity occurred in 8 patients (22.9%) and grade 3 vomiting was seen in 3 patients

  5. ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Guadalupe Lorenzatti Hiles

    Full Text Available ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable

  6. Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping, and Monitoring.

    Science.gov (United States)

    Kang, Zhigang; Stevanović, Sanja; Hinrichs, Christian S; Cao, Liang

    2017-11-15

    Purpose: Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making.Experimental Design: In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet PCR (ddPCR). Nine patients had received tumor-infiltrating lymphocyte (TIL) immunotherapy. ccfDNA data were aligned with the tumor HPV genotype, drug treatment, and clinical outcome.Results: In blinded tests, HPV ccfDNA was detected in 19 of 19 (100%) patients with HPV-positive metastatic cervical cancer but not in any of the 45 healthy blood donors. The HPV genotype harbored in the patients' tumors was correctly identified in 87 of 87 (100%) sequential patient serum samples from 9 patients who received TIL immunotherapy. In three patients who experienced objective cancer regression after TIL treatment, a transient HPV ccfDNA peak was detected 2-3 days after TIL infusion. Furthermore, persistent clearance of HPV ccfDNA was only observed in two patients who experienced complete response (CR) after TIL immunotherapy.Conclusions: HPV ccfDNA represents a promising tumor marker for noninvasive HPV genotyping and may be used in selecting patients for HPV type-specific T-cell-based immunotherapies. It may also have value in detecting antitumor activity of therapeutic agents and in the long-term follow-up of cervical cancer patients in remission. Clin Cancer Res; 23(22); 6856-62. ©2017 AACR. ©2017 American Association for Cancer Research.

  7. Resection or cryosurgery relates with pancreatic tumor type: primary pancreatic cancer with previous non-pancreatic cancer or secondary metastatic cancer within the pancreas.

    Science.gov (United States)

    Jin, Peng; Ji, Xiaoyan; Ren, He; Tang, Yong; Hao, Jihui

    2014-01-01

    We investigated the incidence of primary pancreatic cancer with previous non-pancreatic cancer (PPC) and secondary metastatic cancer within the pancreas (SMC) to elucidate the differential diagnosis and treatment of these lesions. The clinical data of 2539 patients with pancreatic mass in Tianjin Cancer Hospital from January 2000 to December 2012 were retrospectively analyzed. All of the 66 patients who showed double or multiple primary cancers or metastatic pancreatic malignancies were included into the PPC group or SMC group, respectively. In addition, PPC patients were compared with 570 patients suffering from pancreatic cancer (PC) alone. For the PPC group (n = 34), the most common previous non-pancreatic cancers were gastric cancer, breast cancer, and thyroid cancer. For the SMC group (n = 32), the most common metastatic tumors were lung cancer, renal cell carcinoma (RCC), and gastric cancer. Multivariate analysis identified age (OR = 1.099; 95% CI, 1.007-1.199), previous tumor type (OR = 1.164; 95% CI, 1.046-1.296), and time interval between two tumors (OR = 1.021; 95% CI, 1.003-1.039) as significant indicators. Significantly better survival times were observed after resection than after cryosurgery in the PPC group (p pancreatic cancers are as common as metastasis to the pancreas in patients with a previous cancer. A longer time interval between two tumors indicates a higher possibility that a new pancreatic cancer will occur. Some cancers (particularly RCC) are more likely to metastasize to the pancreas than other cancers. For metastatic cancers, cryosurgery is as effective as resection as a treatment option. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  8. Upregulation of Glucose-Regulated Protein 78 in Metastatic Cancer Cells Is Necessary for Lung Metastasis Progression

    Directory of Open Access Journals (Sweden)

    Michael M. Lizardo

    2016-11-01

    Full Text Available Metastasis is the cause of more than 90% of all cancer deaths. Despite this fact, most anticancer therapeutics currently in clinical use have limited efficacy in treating established metastases. Here, we identify the endoplasmic reticulum chaperone protein, glucose-regulated protein 78 (GRP78, as a metastatic dependency in several highly metastatic cancer cell models. We find that GRP78 is consistently upregulated when highly metastatic cancer cells colonize the lung microenvironment and that mitigation of GRP78 upregulation via short hairpin RNA or treatment with the small molecule IT-139, which is currently under clinical investigation for the treatment of primary tumors, inhibits metastatic growth in the lung microenvironment. Inhibition of GRP78 upregulation and an associated reduction in metastatic potential have been shown in four highly metastatic cell line models: three human osteosarcomas and one murine mammary adenocarcinoma. Lastly, we show that downmodulation of GRP78 in highly metastatic cancer cells significantly increases median survival times in our in vivo animal model of experimental metastasis. Collectively, our data indicate that GRP78 is an attractive target for the development of antimetastatic therapies.

  9. Tumor markers in metastatic breast cancer subtypes: frequency of elevation and correlation with outcome.

    Science.gov (United States)

    Yerushalmi, R; Tyldesley, S; Kennecke, H; Speers, C; Woods, R; Knight, B; Gelmon, K A

    2012-02-01

    Little is known about the correlations between tumor markers (TMs), breast cancer subtypes, site(s) of metastasis and prognosis. Women diagnosed with metastatic breast cancer were included. Breast cancer subtypes were defined as LuminalA, LuminalB, LuminalHer2, Her2, Basal and non-Basal triple negative (TN). Levels of elevation of TM values [cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA 125)] among the subtypes were analyzed. Site(s) of metastasis and outcomes were captured. Eight hundred and ten patients were included. Luminal subtypes were associated with an elevation in at least one TM: 90.8% of LuminalHer2+, 90% of LuminalB and 88.6% of LuminalA. TMs were less frequently elevated in Basal (74.1%) and non-Basal TN (71.4%) cases (P Breast cancer-specific survival (BCSS) was significantly worse for patients with elevated TMs (P = 0.001). TM elevation of CA 15-3, CEA and/or CA 125 was documented in the majority of patients with metastatic breast cancer with CA 15-3 occurring most commonly. Luminal subtypes expressed elevated TMs significantly more frequently compared with the non-Luminal groups. TM elevation was not different between the different sites of metastasis. Overall, elevated TMs predicted a worse BCSS.

  10. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Van Cutsem, E; Cervantes, A; Adam, R

    2016-01-01

    Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred...... for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team...... environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed...

  11. Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Palshof, Jesper Andreas; Hogdall, Estrid Vilma Solyom; Poulsen, Tim Svenstrup

    2017-01-01

    Background No biomarker exists to guide the optimal choice of chemotherapy for patients with metastatic colorectal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients...... with metastatic colorectal cancer. Methods From a national cohort, we identified 163 patients treated every third week with irinotecan 350 mg/m2 as second-line therapy. Among these 108 were eligible for analyses and thus entered the study. Primary tumors samples were collected and tissue microarray (TMA) blocks...... in search of a biomarker driven patient stratification. Other biomarkers to be paired with TOP1 CN are therefore highly warranted....

  12. Dual Inhibition of EGFR and VEGF in Heavily Pretreated Patients with Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Markussen, Alice; Nielsen, Dorte

    2017-01-01

    Objective: The aim of this study was to evaluate the efficacy and safety of combining irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment in patients with metastatic colorectal cancer. Methods: All patients had KRAS wild-type metastatic colorectal cancer and had previously...... received fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab/panitumumab in a 1st, 2nd, and 3rd line setting. Most patients had previously received bevacizumab as well. All patients had progressed within 3 months after the last given treatment before starting the triple combination therapy every...... second week. Results: Sixty-three patients were evaluated. The triple combination therapy was well tolerated. The median progression-free survival was 6.1 months, and the median overall survival was 11.9 months. Four patients (6%) obtained a partial response, and 40 (63%) had stable disease. Conclusion...

  13. Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer.

    Science.gov (United States)

    Keating, Gillian M

    2013-05-01

    The taxane derivative cabazitaxel (Jevtana(®)) is approved in the USA and the EU for use in combination with prednisone for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. In the pivotal TROPIC trial, overall survival was significantly prolonged with cabazitaxel plus prednisone versus mitoxantrone plus prednisone in patients with metastatic castration-resistant prostate cancer who had progressed during or after docetaxel therapy. In addition, progression-free survival, the times to tumour progression and prostate specific antigen (PSA) progression, and tumour and PSA response rates were improved with cabazitaxel plus prednisone. Intravenous cabazitaxel had an acceptable tolerability profile, with haematological adverse events occurring most commonly, and diarrhoea being the most common nonhaematological adverse event.

  14. The Role of Osteoblast-Derived Cytokines in Bone Metastatic Breast Cancer

    Science.gov (United States)

    2009-01-01

    MDA-MB-231 human metastatic breast cancer cell variants retained a rounded shape , as opposed to a thin, spindle-like shape (Figure 3.1) [5]. Thus...of both cell popu- lations decreased so that the ratio of osteoblasts to osteo- clasts decreased from an average of 40 to only 4 by 4 weeks...bone marrow and lead to osteolysis. Activation of osteo- clasts and bone resorption far exceed bone deposition in this disease. Whether the lesions

  15. Proteinuria with first-line therapy of metastatic renal cell cancer.

    Science.gov (United States)

    Land, Josiah D; Chen, Adrienne H; Atkinson, Bradley J; Cauley, Diana H; Tannir, Nizar M

    2016-04-01

    Vascular endothelial growth factor receptor inhibitors, mammalian target of rapamycin inhibitors, and tyrosine kinase inhibitors are approved for metastatic renal cell cancer. Proteinuria can occur, but there is limited data regarding the incidence, monitoring, and management in metastatic renal cell cancer patients. Our primary objective was to describe the incidence and severity of proteinuria in metastatic renal cell cancer patients treated in the first-line setting with pazopanib, bevacizumab, or everolimus. We conducted a retrospective review of patients with metastatic renal cell cancer enrolled from January 2011-April 2013 in a phase II trial. Baseline and toxicity data were extracted from the electronic medical record. Descriptive statistics were used. In all, 129 patients were eligible for analysis. The overall incidence of proteinuria was 81%, with most events being Grade 1 or 2. The incidence of proteinuria was 80% (n = 35) for pazopanib, 64% (n = 25) for bevacizumab, and 96% (n = 44) for everolimus. At peak proteinuria, 80% (n = 28), 64% (n = 16), and 80% (n = 35) of patients on pazopanib, bevacizumab, and everolimus, respectively, were managed with continued monitoring at the same dose. The overall incidence of Grades 3 and 4 events was 24% (n = 6) and found in the bevacizumab group. A high incidence of proteinuria with minor severity within each class was demonstrated. It may be reasonable to continue therapy at the same dose for Grade 1 or 2 proteinuria. Treatment modification or discontinuation of therapy may be warranted with Grade 3 or 4 proteinuria. © The Author(s) 2014.

  16. Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival.

    Science.gov (United States)

    Kuş, Tülay; Aktaş, Gökmen

    2017-09-01

    To investigate the effects of gemcitabine maintenance treatment on survival in patients with metastatic bladder cancer. Gemcitabine maintenance monotherapy was administered following the standard platinum-gemcitabine therapy in patients with metastatic bladder cancer. Patients who had responded to standard treatment received maintenance gemcitabine therapy as 1000 mg/m2 on days 1 and 8 every three weeks until progression or development of unacceptable toxicity. The following clinical factors were noted: performance status, age, sex, stage, site of metastasis, choice of cisplatin-gemcitabine or carboplatin-gemcitabine, response rates to the initial chemotherapy. Progression-free survival (PFS) and overall survival (OS) for standard treatment, and following gemcitabine monotreatment and for maintenance gemcitabine therapy were calculated using Kaplan-Meier method. A total of 88 patients with metastatic bladder cancer treated between February 2009 to October 2015 were evaluated retrospectively and 23 patients (26.1%) who had responded to six cycles of platinum-gemcitabine treatment were included in this study. Maintenance gamcitabine was administered for a median of 7 times (range 3-14 times). Grade 3 hematotoxicity according to the criteria of the Common Terminology Criteria of Adverse Events was observed in 7 (30.4%) patients. Median PFS of patients was 46 (range: 30-82) weeks for platinum-based treatment plus maintenance gemcitabine therapy. A higher median PFS was obtained in patients who were maintenance therapy in metastatic bladder cancer patients who did not shown progression after the standard platinum-gemcitabine treatment contributes to survival and presents low toxicity profile, when compared to historical controls.

  17. Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.

    Science.gov (United States)

    Del Rio, M; Mollevi, C; Bibeau, F; Vie, N; Selves, J; Emile, J-F; Roger, P; Gongora, C; Robert, J; Tubiana-Mathieu, N; Ychou, M; Martineau, P

    2017-05-01

    Currently, metastatic colorectal cancer is treated as a homogeneous disease and only RAS mutational status has been approved as a negative predictive factor in patients treated with cetuximab. The aim of this study was to evaluate if recently identified molecular subtypes of colon cancer are associated with response of metastatic patients to first-line therapy. We collected and analysed 143 samples of human colorectal tumours with complete clinical annotations, including the response to treatment. Gene expression profiling was used to classify patients in three to six classes using four different molecular classifications. Correlations between molecular subtypes, response to treatment, progression-free and overall survival were analysed. We first demonstrated that the four previously described molecular classifications of colorectal cancer defined in non-metastatic patients also correctly classify stage IV patients. One of the classifications is strongly associated with response to FOLFIRI (P=0.003), but not to FOLFOX (P=0.911) and FOLFIRI + Bevacizumab (P=0.190). In particular, we identify a molecular subtype representing 28% of the patients that shows an exceptionally high response rate to FOLFIRI (87.5%). These patients have a two-fold longer overall survival (40.1 months) when treated with FOLFIRI, as first-line regimen, instead of FOLFOX (18.6 months). Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer and a strong impact of the first-line regimen on the overall survival of some patients. This however remains to be confirmed in a large prospective clinical trial. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Array-based sensing of normal, cancerous, and metastatic cells using conjugated fluorescent polymers.

    Science.gov (United States)

    Bajaj, Avinash; Miranda, Oscar R; Phillips, Ronnie; Kim, Ik-Bum; Jerry, D Joseph; Bunz, Uwe H F; Rotello, Vincent M

    2010-01-27

    A family of conjugated fluorescent polymers was used to create an array for cell sensing. Fluorescent conjugated polymers with pendant charged residues provided multivalent interactions with cell membranes, allowing the detection of subtle differences between different cell types on the basis of cell surface features. Highly reproducible characteristic patterns were obtained from different cell types as well as from isogenic cell lines, enabling the identification of the cell type as well differentiating between normal, cancerous, and metastatic isogenic cell types with high accuracy.

  19. Trials with TALL-1O4 Cells for Treatment of Metastatic Breast Cancer

    Science.gov (United States)

    1999-10-01

    The patients enrolled in this study (Table 1) were required to have histologically proven metastatic breast cancer relapsed after at least two forms...When the mean WBC counts pre-treatment (day 0) were compared to the day 5 counts, a decrease was observed regardless of the dose level. By contrast...conduct histological and/or in situ hybridization studies to definitively document an anti-tumor response. Mild, grade I gastrointestinal toxicity

  20. Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Heidenreich, Axel; Bracarda, Sergio; Mason, Malcolm

    2014-01-01

    BACKGROUND: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access progra......-CSF, especially at cycle 1 and in men aged > or =75 years, is important and improves tolerability in senior adults treated with cabazitaxel....

  1. Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients

    DEFF Research Database (Denmark)

    Fosbøl, Marie Øbro; Petersen, Peter Meidahl; Daugaard, Gedske

    2018-01-01

    BACKGROUND: Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities...... to non-disease related reasons on OS, rPFS or number of completed treatment cycles....

  2. Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor.

    Directory of Open Access Journals (Sweden)

    Ester Rozenblum

    Full Text Available A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY, and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs/mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found. A large number of focal copy number alterations (FCNAs were detected, including homozygous deletions (HDs targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements. Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis.

  3. Identifying Educational Needs of the Multidisciplinary Cancer Team in the Treatment of Metastatic Breast Cancer.

    Science.gov (United States)

    Wanchoo, Priya; Larrison, Chris; Rosenberg, Carol; Ko, Naomi; Cantril, Cynthia; Moeller, Naomi; Parikh, Ruchit; Djordjevic, Ana-Marija

    2017-02-01

    Background: Rapid advancements in the field of metastatic breast cancer (mBC) add to the complexity of managing patients with this disease. An educational needs assessment of multidisciplinary mBC clinicians was executed to identify practice performance gaps and recommend educational strategies aimed at closing these gaps. Methods: To ensure a collection of reliable data for assessment, a systematic process was used to design, develop, and validate the tools that were used. This grounded theory approach included assessment and confirmation by clinical experts and validation testing within the target audiences. A mixed-methods approach was used to identify practice performance gaps in care, using both qualitative in-depth interviews and quantitative surveying. The quantitative survey assessment consisted of 2 main sections: the Clinician Change Readiness Inventory tool and a Clinical Knowledge and Practice Assessment. Results: The study included 42 clinicians in the interview phase and 186 clinicians in the survey phase from 36 different states. Five key practice performance gaps were identified: (1) selecting optimal treatment, (2) personalizing therapy, (3) monitoring mBC, (4) engaging in effective communication, and (5) balancing patient access and time. Most of the gaps overlap and are related to the integral role communication plays in management decision-making in mBC. Conclusions: Awareness of the key practice performance gaps is critical to inform improvements in quality care. Copyright © 2017 by the National Comprehensive Cancer Network.

  4. Androgen receptor expression on circulating tumor cells in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Takeo Fujii

    Full Text Available Androgen receptor (AR is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+ breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer.Blood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK, and biomarkers of interest (AR, estrogen receptor [ER], and HER2 on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms.Of 68 patients, 51 (75% had at least 1 CTC, and 49 of these 51 (96% had hormone-receptor-positive (HR+/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells.CTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their heterogeneity.

  5. Androgen receptor expression on circulating tumor cells in metastatic breast cancer

    Science.gov (United States)

    Fujii, Takeo; Reuben, James M.; Huo, Lei; Espinosa Fernandez, Jose Rodrigo; Gong, Yun; Krupa, Rachel; Suraneni, Mahipal V.; Graf, Ryon P.; Lee, Jerry; Greene, Stephanie; Rodriguez, Angel; Dugan, Lyndsey; Louw, Jessica; Lim, Bora; Barcenas, Carlos H.; Marx, Angela N.; Tripathy, Debu; Wang, Yipeng; Landers, Mark; Dittamore, Ryan

    2017-01-01

    Purpose Androgen receptor (AR) is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+) breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs) can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer. Methods Blood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK), and biomarkers of interest (AR, estrogen receptor [ER], and HER2) on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM) using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms. Results Of 68 patients, 51 (75%) had at least 1 CTC, and 49 of these 51 (96%) had hormone-receptor-positive (HR+)/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells. Conclusions CTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their

  6. Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer.

    Science.gov (United States)

    Soekmadji, Carolina; Corcoran, Niall M; Oleinikova, Irina; Jovanovic, Lidija; Ramm, Grant A; Nelson, Colleen C; Jenster, Guido; Russell, Pamela J

    2017-10-01

    The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation. © 2017 Wiley Periodicals, Inc.

  7. Invasive ductal breast cancer metastatic to the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Zhou Xiao-cong

    2012-11-01

    Full Text Available Abstract The most common sites of breast cancer metastasis are the bone, lung, liver and brain. However, colonic metastases from breast cancer are very rare in the clinic. We describe an unusual case of sigmoid colonic metastasis from invasive ductal breast cancer. With this report, we should increase the clinical awareness that any patient with a colorectal lesion and a history of malignancy should be considered to have a metastasis until proven otherwise. Early diagnosis is very important, which enables prompt initiation of systemic treatment, such as chemotherapy, endocrine therapy or both, thus avoiding unnecessary radical surgical resection and improving the prognosis.

  8. HER-2, ER, PR status concordance in primary breast cancer and corresponding metastatic lesion in lymph node in Chinese women.

    Science.gov (United States)

    Li, Min Hua; Hou, Chuan Ling; Wang, Cheng; Sun, Ai Jing

    2016-04-01

    To compare the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) in the primary site and the metastatic lesion of lymph nodes in invasive breast cancer for investigating whether the expression of these biomarkers in the primary site could act as a surrogate to the lymphatic metastatic lesion in the same patient. In lymphatic metastatic lesion and corresponding primary lesion of 107 cases of invasive breast cancer, ER and PR statuses were assessed by immunohistochemistry (IHC). HER-2 expression level was evaluated by IHC and/or fluorescence in situ hybridization (FISH). In the primary lesions, 43.9% were ER positive; 46.7% were PR positive; 34.6% were HER-2 positive. In corresponding lymphatic metastatic lesions, the HER-2 status was concordant in 90 patients; 9 patients were diagnosed positive in metastatic lesion while negative in primary lesion; 8 patients were negative in metastatic lesion while positive in primary site (agreement, 84.1%; κ=0.647). A change in ER status was observed in 24 cases: 17 cases positive in metastatic site while negative in primary site; 7 cases negative in metastatic site while positive in primary site (agreement, 77.6%; κ=0.534). PR status discordance between the primary lesion and the metastatic regional lymph nodes was reported in 19 cases (agreement, 82.2%; κ=0.640). This study revealed that there was only a moderate concordance of ER, PR and HER-2 status between primary tumors and metastatic lymph nodes. These results indicate that it was inappropriate to predict the status of ER, PR and HER-2 in metastatic lymph nodes based on the results of evaluation of that in primary lesions. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. Clinicoradiologic characteristics and outcomes of metastatic cancer to the pancreas and double primary pancreatic cancer.

    Science.gov (United States)

    Yun, Hwan Sic; Min, Yang Won; Lee, Min Ji; Chang, Woo Ik; Lee, Kwang Hyuck; Lee, Kyu Taek; Lee, Jong Kyun; Kim, Young Kon; Lim, Jae Hoon

    2013-04-01

    The goal of this study was to identify clinicoradiologic characteristics to distinguish metastatic cancer to the pancreas (MCP) from double primary pancreatic cancer (DPPC). From 2000 to 2011, we retrospectively identified MCP and DPPC patients among patients with histories of other primary malignancies. A total of 94 patients with histories of other primary malignancies were histologically confirmed to have pancreatic cancer. Among them, 34 patients had MCP and 60 patients had DPPC, which were ductal adenocarcinomas. The kidney was the most common primary cancer site that metastasized to the pancreas (12, 35.3%). In the DPPC group, the stomach was the most common primary cancer site (11, 18.3%). There were 21 patients (61.8%) with metachronous pancreatic cancer in the MCP group and 29 (48.3%) in the DPPC group (P=0.210). Among the metachronous pancreatic cancer patients, the disease-free interval was 88.3 months in the MCP group, and 49.6 months in the DPPC group (P=0.062). The number of the patients who showed elevated CA 19-9 levels was higher in the DPPC group than in the MCP group (39 (65%) vs. 9 (26.5%); P=0.001). Total bilirubin (P=0.006) and fasting plasma glucose (P=0.050) were also higher in the DPPC group. The numbers of patients who showed pancreatic duct dilatation (P=0.002) and pancreatic atrophy (P=0.008) on radiographs were meaningfully higher in the DPPC group than in the MCP group. On the other hand, the numbers of patients who showed well demarcated tumor margin (P<0.000), tumor necrosis (P=0.002), enhancement (P=0.005) and distant metastasis (P=0.028) were significantly higher in the MCP group than in the DPPC group. We evaluated differences in survival between the two groups. The median survival time in the MCP group (55 months) was significantly longer than that in the DPPC group (20 months). Other than elevated levels of CA 19-9, total bilirubin and fasting glucose, radiologic findings were the most reliable factors for distinguishing the MCP

  10. Circulating Tumor Cells in Metastatic Breast Cancer: A Prognostic and Predictive Marker

    Directory of Open Access Journals (Sweden)

    Sayyed Farshid Moussavi-Harami

    2014-05-01

    Full Text Available The role of circulating tumor cells (CTCs as a marker for disease progression in metastatic cancer is controversial. The current review will serve to summarize the evidence on CTCs as a marker of disease progression in patients with metastatic breast cancer. The immunohistochemistry (IHC-based CellSearch® is the only FDA-approved isolation technique for quantifying CTCs in patients with metastatic breast cancer. We searched PubMed and Web of Knowledge for clinical studies that assessed the prognostic and predictive value of CTCs using IHC-based isolation. The patient outcomes reported include median and Cox-proportional hazard ratios for overall survival (OS and progression-free survival (PFS. All studies reported shorter OS for CTC-positive patients versus CTC-negative. A subset of the selected trials reported significant lower median PFS for CTC-positive patients. The reported trials support the utility of CTC enumeration for patient prognosis. But further studies are required to determine the utility of CTC enumeration for guiding patient therapy. There are three clinical trials ongoing to test this hypothesis. These studies, and others, will further establish the role of CTCs in clinical practice.

  11. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse

    Directory of Open Access Journals (Sweden)

    Rabeah A. Al-Temaimi

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT. Resultant genes were classified based on gene ontology (GO, which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.

  12. Inhibition of metastatic lung cancer in C57BL/6 mice by marine mangrove Rhizophora apiculata.

    Science.gov (United States)

    Prabhu, V Vinod; Guruvayoorappan, C

    2013-01-01

    Metastasis is one of the hallmarks of malignant neoplasms and is the leading cause of death in many cancer patients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastasis. In this study, the anti-metastatic potential of the methanolic extract of Rhizophora apiculata (R.apiculata) was evaluated using the B16F-10 melanoma induced lung metastasis model in C57BL/6 mice. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with R.apiculata extract (10 mg/kg b.wt (intraperitoneal) significantly (p<0.01) inhibited pulmonary tumor nodule formation (41.1 %) and also increased the life span (survival rate) 107.3 % of metastatic tumor bearing animals. The administration of R.apiculata extract significantly (p<0.01) reduced biochemical parameters such as lung collagen hydroxyproline, hexosamine, uronic acid content, serum nitric oxide (NO), γ-glutamyl transpeptidase (GGT) and sialic acid levels when compared to metastasis controls. These results correlated with lung histopathology analysis of R.apiculata extract treated mice showing reduction in lung metastasis and tumor masses. Taken together, our findings support that R.apiculata extract could be used as a potential anti-metastasis agent against lung cancer.

  13. Outcomes After Radio(chemo)therapy for Non-Metastatic Bile Duct Cancer.

    Science.gov (United States)

    Bolm, Louisa; Kaesmann, Lukas; Bartscht, Tobias; Schild, Steven E; Rades, Dirk

    2017-01-02

    The role of radio(chemo) therapy for non-metastatic bile duct cancer is not well defined. This study provides additional data for this rare situation. Data of eight patients receiving radio(chemo)therapy for non-metastatic bile duct cancer were retrospectively analyzed regarding local control, metastases-free survival and overall survival. In addition to the entire cohort, five tumor- or treatment-related factors were investigated: tumor stage, histologic grading, point in time of radio(chemo)therapy, upfront surgery and concurrent chemotherapy. Median overall survival was 37 months. Overall survival rates at 3 and 5 years were 56% and 38%, respectively. Lower histologic grading was significantly associated with better overall survival (p=0.042). Metastases-free survival rates at 3 and 5 years were 38% and 19%, while local control rates were 43% and 21%, respectively. Concurrent radiochemotherapy (vs. radiotherapy alone) resulted in significantly improved local control (p=0.014). Radiochemotherapy can achieve promising results in selected patients with non-metastatic bile duct cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Molecular Mechanisms of Metastatic Progression in Breast Cancer

    National Research Council Canada - National Science Library

    Flanagan, Louise A

    2004-01-01

    .... In our studies, we have focused on determining whether clusterin plays a causative role in the progression of human breast cancer by promoting cell survival, increasing cell motility and resistance to cytotoxic drugs...

  15. Trafficking of Metastatic Breast Cancer Cells in Bone

    National Research Council Canada - National Science Library

    Mastro, Andrea M

    2004-01-01

    ... metaphyses. Human breast cancer cells that express green fluorescent protein (GFP-MDA-MB 231) will be inoculated into athymic mice by intracardiac injection and femurs harvested at various times from 1 hour to 6 weeks later...

  16. Correlation of MMP-9 and p53 protein expression with prognosis in metastatic spinal tumor of lung cancer.

    Science.gov (United States)

    Zhang, Shuquan; Wu, Minfei; Zhao, Yi; Gu, Rui; Peng, Chuangang; Liu, Jiabei; Zhu, Qingsan; Li, Ye

    2017-11-01

    The aim of the study was to compare the protein expression of MMP-9 and p53 and examine their correlation with prognosis in lung cancer metastatic spinal tumor. Tissue samples were obtained from 30 cases of para-cancerous tissue (group I), 75 cases of non-metastatic lung cancer tissue (group II) and 100 cases of metastatic spinal tumor tissue of lung cancer (group III). The protein expression of MMP-9 and p53 was detected by immunohistochemistry and was present in all three groups. The positive rate for MMP-9 was 20, 67 and 83%, respectively. There was a significant difference among the three groups (pp53 was 16.7, 78.7 and 92%, respectively. There was a highly significant difference among the three groups (pp53 (Spearman's correlation coefficient r=0.351, pp53 proteins in metastatic spinal tumors of lung cancer showed increasing trends, and the expression of MMP-9 and p53 proteins was significantly higher compared to non-metastatic lung cancer tissue and para-cancerous tissue samples. This likely was associated with the invasion and metastasis of lung cancer to the spine. Survival analysis suggested that the overexpression of p53 and MMP-9 were correlated with poor prognosis.

  17. Altered Sphingolipid Metabolism in Patients with Metastatic Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Todd E. Fox

    2013-07-01

    Full Text Available Although numerous genetic mutations and amplifications have been identified in pancreatic cancer, much of the molecular pathogenesis of the disease remains undefined. While proteomic and transcriptomic analyses have been utilized to probe and characterize pancreatic tumors, lipidomic analyses have not been applied to identify perturbations in pancreatic cancer patient samples. Thus, we utilized a mass spectrometry-based lipidomic approach, focused towards the sphingolipid class of lipids, to quantify changes in human pancreatic cancer tumor and plasma specimens. Subgroup analysis revealed that patients with positive lymph node metastasis have a markedly higher level of ceramide species (C16:0 and C24:1 in their tumor specimens compared to pancreatic cancer patients without nodal disease or to patients with pancreatitis. Also of interest, ceramide metabolites, including phosphorylated (sphingosine- and sphinganine-1-phosphate and glycosylated (cerebroside species were elevated in the plasma, but not the pancreas, of pancreatic cancer patients with nodal disease. Analysis of plasma level of cytokine and growth factors revealed that IL-6, IL-8, CCL11 (eotaxin, EGF and IP10 (interferon inducible protein 10, CXCL10 were elevated in patients with positive lymph nodes metastasis, but that only IP10 and EGF directly correlated with several sphingolipid changes. Taken together, these data indicate that sphingolipid metabolism is altered in human pancreatic cancer and associated with advanced disease. Assessing plasma and/or tissue sphingolipids could potentially risk stratify patients in the clinical setting.

  18. Long-Time Survival of a Patient with Metastatic Pancreatic Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Željko Soldić

    2011-08-01

    Full Text Available Pancreatic cancer is a malignant neoplasm of the pancreas. It does not cause any symptoms in the early stage, and later symptoms are nonspecific, thus the disease is usually diagnosed when already advanced. In 2008, pancreatic cancer ranked eighth on the list of the 10 most common cancers among men in Croatia and tenth on the list of the most common cancers among Croatian women. Pancreatic cancer has a poor prognosis, with a survival time of only 6–8 months for metastatic disease. Gemcitabine is the standard chemotherapeutic option. Other chemotherapeutic agents include5-fluorouracil and leucovorin. In this paper, we present a case of a patient diagnosed with locally advanced and metastatic pancreatic cancer, who is still alive and currently receives his fourth line of chemotherapy 5 years after the diagnosis. Following disease progression on gemcitabine chemotherapy, he was treated with chemoradiotherapy which, however, had no effect. We then applied cisplatin monochemotherapy which offered excellent disease control, was well tolerated by the patient and, although somewhat obsolete in this form, showed to be a valuable chemotherapeutic option.

  19. The role of Runx2 in facilitating autophagy in metastatic breast cancer cells.

    Science.gov (United States)

    Tandon, Manish; Othman, Ahmad H; Ashok, Vivek; Stein, Gary S; Pratap, Jitesh

    2018-01-01

    Breast cancer metastases cause significant patient mortality. During metastases, cancer cells use autophagy, a catabolic process to recycle nutrients via lysosomal degradation, to overcome nutritional stress for their survival. The Runt-related transcription factor, Runx2, promotes cell survival under metabolic stress, and regulates breast cancer progression and bone metastases. Here, we identify that Runx2 enhances autophagy in metastatic breast cancer cells. We defined Runx2 function in cellular autophagy by monitoring microtubule-associated protein light chain (LC3B-II) levels, an autophagy-specific marker. The electron and confocal microscopic analyses were utilized to identify alterations in autophagic vesicles. The Runx2 knockdown cells accumulate LC3B-II protein and autophagic vesicles due to reduced turnover. Interestingly, Runx2 promotes autophagy by enhancing trafficking of LC3B vesicles. Our mechanistic studies revealed that Runx2 promotes autophagy by increasing acetylation of α-tubulin sub-units of microtubules. Inhibiting autophagy decreased cell adhesion and survival of Runx2 knockdown cells. Furthermore, analysis of LC3B protein in clinical breast cancer specimens and tumor xenografts revealed significant association between high Runx2 and low LC3B protein levels. Our studies reveal a novel regulatory mechanism of autophagy via Runx2 and provide molecular insights into the role of autophagy in metastatic cancer cells. © 2017 Wiley Periodicals, Inc.

  20. Metastatic brain tumor

    Science.gov (United States)

    ... JavaScript. A metastatic brain tumor is cancer that started in another part of the body ... of cancer rarely spread to the brain, such as colon cancer and prostate cancer. In other rare cases, a tumor can ...

  1. Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans With Bone-Metastatic Prostate Cancer

    Science.gov (United States)

    2014-09-01

    Hereditary prostate cancer : epidemiologic and clinical features. J Urol., 150(3):797-802, 1993. 12. Boring, C. C. Cancer StatistiAC. (1991) CA...Ross K, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer . Cancer Res 2006;66(5):2815–2825. [PubMed: 16510604]. 12 ...Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans With Bone-Metastatic Prostate Cancer PRINCIPAL

  2. Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

    DEFF Research Database (Denmark)

    Kaisary, A V; Iversen, P; Tyrrell, C J

    2001-01-01

    Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non...... with a prostate specific antigen (PSA) level 400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203....

  3. Metastatic Spinal Cord Compression: A Survival Score Particularly Developed for Elderly Prostate Cancer Patients.

    Science.gov (United States)

    Rades, Dirk; Conde-Moreno, Antonio J; Cacicedo, Jon; Segedin, Barbara; Veninga, Theo; Schild, Steven E

    2015-11-01

    Metastatic spinal cord compression (MSCC) is an oncological emergency. Many elderly patients cannot tolerate intensive treatment and need individual approaches accounting for a patient's remaining lifetime. The goal of the present study was to develop a survival score for elderly prostate cancer patients with MSCC. Nine characteristics were analyzed in 243 patients: age, performance status, interval from prostate cancer diagnosis until MSCC, affected vertebrae, ambulatory status, further bone lesions, visceral metastases, time developing motor deficits, fractionation schedule. Pre-radiotherapy ambulatory status (ppriorities ranging from symptom control to prolongation of life. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Chemotherapy in the treatment of metastatic prostate cancer: the present state of the problem

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2015-01-01

    Full Text Available The paper reviews the current possibilities of cytostatic chemotherapy in patients with metastatic prostate cancer. It gives the data of studies dealing with the early use of docetaxel in patents with hormone-susceptible tumors and analyzes approaches to sequential therapy with docetaxel, cabazitaxel, and antiandrogens (abiraterone, enzalutamide in patients with castration-refractory prostate cancer. Assessment of the prognostic role of different clinical and biological factors could provide an algorithm for the choice of first- and second-line therapy in patients with castration resistance.

  5. Changes in the gastric potential difference during chemotherapy in patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Fabrin, B; Højgaard, L; Mouridsen, H T

    1991-01-01

    Nausea and vomiting are frequent side-effects of intravenous cancer chemotherapy. How these complications were related to the gastric mucosal function was investigated by measuring the gastric mucosal potential difference (PD). Eight patients with metastatic breast cancer receiving chemotherapy...... were investigated. The liquid junction-corrected gastric PD and pH were measured with a newly developed microelectrode. The measurements started half an hour before chemotherapy and continued for 4-5 hours. Nausea, vomiting, psychological stress and sleeping episodes were registered. The initial PD...

  6. Paclitaxel/oxaliplatin/fluorouracil (TOF) regimen versus S-1/oxaliplatin (SOX) regimen for metastatic gastric cancer patients.

    Science.gov (United States)

    Dai, Xichao; Zhang, Xizhi; Wang, Chaomin; Jiang, Jingting; Wu, Changping

    2017-05-02

    This study was designed to compare the efficacy and safety of paclitaxel/oxaliplatin/fluorouracil (TOF) regimen and S-1/oxaliplatin (SOX) regimen for metastatic gastric cancer (GC) patients. Sixty patients were divided into TOF group and SOX groups randomly. Patients in the TOF group received paclitaxel (135 mg/m2 iv) on day 1, oxaliplatin (100 mg/m2 iv) on day 1, fluorouracil (500 mg/m2 continuous iv) on day 1-5. The patients in the SOX group received oxaliplatin (130 mg/m2 iv) on day 1 and S-1 (40 mg~60mg orally twice/day based on body surface area) on days 1-14. All the treatments were repeated every 21d for 4-6 cycles. The ORR and DCR of TOF group was 43.3% and 60.0%, respectively while that of SOX group was 36.7% and 56.7%. There were no statistical differences between the ORRs (χ2 = 0.278) and the DCRs (χ2 = 0.069) of the 2 groups. The majority of adverse events of two groups were hematological and digestive ones. Most of them were grade I and II. The adverse event rate of TOF group was higher than SOX group. The PFS times of TOF and SOX groups were 6.5 and 5.8 months, respectively. There was no statistical difference between the PFSs of the 2 groups (P = 0.451). The efficacies of TOF and SOX regimens are similar but the safety of SOX regimen better than TOF regimen.

  7. Practical use of capecitabine plus oxaliplatin (CAPEOX) with bevacizumab for patients with metastatic colorectal cancer that cannot expect conversion therapy.

    Science.gov (United States)

    Yokomizo, Hajime; Yoshimatsu, Kazuhiko; Otani, Taisuke; Osawa, Gakuji; Nakayama, Mao; Matsumoto, Atsuo; Yano, Yuki; Okayama, Sachiyo; Naritaka, Yoshihiko

    2013-01-01

    The cytotoxic regimens and bevacizumab (Bev) or anti-EGFR antibody are used for metastatic colorectal cancer (mCRC) that can expect conversion therapy. In this paper, we would present our practical data including the response, survival and toxicity of the capecitabine plus oxaliplatin (CAPEOX) with Bev for mCRC that cannot expect conversion therapy. Nineteen patients with mCRC who were treated with CAPEOX with Bev were enrolled. All the patients had the disseminated hepatic, lung, peritoneal metastases or distant lymph node metastasis assessed as no possibility of R0 resection. The median age was 66 (45-85) years old. Target lesion was liver and lung in 9 patients, peritoneum in 5 patients and distant lymph node in 3 patients. CAPEOX with Bev therapy was administered for a median of 8.0 cycles (range, 4-21 cycles). In the 16 evaluable cases, there were no patient with complete response (CR), 9 patients with partial response (PR), 6 with stable disease (SD), and 1 with progressive disease. The objective response rate (CR plus PR) was 56.3%, and disease control rate (CR, PR plus SD) was 93.8%. The median TTP was 9.3 months and the median OS was 21.1 months. No patients treated with surgery even though the good responses were obtained. No severe hematologic adverse toxicities were observed except only one case with grade 3 platelet decrease. Nonhematologic grade 3 events were observed totally 8 patients including 3 for peripheral neuropathy, 2 for bilirubin, and 1 for nausea/vomiting, amylase and stomatitis. We obtained the quite good results of CAPEOX plus Bev as the first-line treatment practically. This regimen might be useful for mCRC that cannot expect conversion therapy.

  8. 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...

  9. Trafficking of Metastatic Breast Cancer Cells in Bone

    Science.gov (United States)

    2006-08-01

    acids, 5% fetal bovine serum (Atlanta Biologicals, Norcross, GA), without antibiotics or antimycotics (cDME/ F12). All cultures were confirmed to be...32. Fidler IJ. Metastasis: quantitative analysis of distri- bution and fate of tumor emboli labeled with 125I-5- iodo -2V-deoxyuridine. J Natl Cancer

  10. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Nanoparticulate Drug Delivery Systems for Application in Bladder Cancer CIHR Role: Co-Investigator Goals: The major goal of this project is about...new information on mechanisms and processes of drug loaded amine-conjugated nanoparticulate induced urothelial exfoliation and repair, tumor cellular...bladder tissue adhesive nanoparticulate delivery systems for anticancer agents. (2) To determine the factors influencing the interactions of

  11. Treatment Options for Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... that slides through the CT scanner, which takes x-ray pictures of the inside of the head and neck. PET scan (positron emission tomography scan) : ... is a cancer treatment that uses high-energy x-rays or other types of ... External-beam radiation therapy of the head and neck. A machine is used to aim ...

  12. Metastatic breast cancer - age has a significant effect on survival

    African Journals Online (AJOL)

    1991-03-02

    Mar 2, 1991 ... months for patients aged 55 - 64 years (P= 0,08; Cox model). The median survival improves again to 24,6 months ... in the very old (aged 75 - 84 years) (P = 0,52; Cox model). The more favourable prognosis in the elderly ... po Box 667, Pretoria, 0001 RSA. Accepted 18 Ocr 1990. tic breast cancer seen in ...

  13. Current treatment for colorectal cancer metastatic to the liver

    NARCIS (Netherlands)

    Cromheecke, M; de Jong, KP; Hoekstra, HJ

    1999-01-01

    Surgery is currently the only available treatment option which offers the potential for cure for patients with liver metastases from colorectal cancer. Of those who undergo a potentially curative operation for their primary tumour but subsequently recur, almost 80% will develop evidence of

  14. Mitochondrial microsatellite instability in patients with metastatic colorectal cancer

    NARCIS (Netherlands)

    Venderbosch, S.; van Vliet, S.; Craenmehr, M. H C; Simmer, F.; de Haan, A. F J; Punt, C. J A; Koopman, M.; Nagtegaal, I. D.

    2015-01-01

    Mitochondrial microsatellite instability (mtMSI), a change in length in mtDNA microsatellite sequences between normal and tumor tissue, has been described as a frequent occurrence in colorectal cancer (CRC). We evaluated the prevalence and prognostic value of mtMSI and its relation to nuclear

  15. Analysis of autophagic flux in response to sulforaphane in metastatic prostate cancer cells

    Science.gov (United States)

    Watson, Gregory W; Wickramasekara, Samanthi; Fang, Yufeng; Palomera-Sanchez, Zoraya; Maier, Claudia S; Williams, David E; Dashwood, Roderick H; Perez, Viviana I; Ho, Emily

    2015-01-01

    Scope The phytochemical sulforaphane has been shown to decrease prostate cancer metastases in a genetic mouse model of prostate carcinogenesis, though the mechanism of action is not fully known. Sulforaphane has been reported to stimulate autophagy, and modulation of autophagy has been proposed to influence sulforaphane cytotoxicity; however, no conclusions about autophagy can be drawn without assessing autophagic flux, which has not been characterized in prostate cancer cells following sulforaphane treatment. Methods and Results We conducted an investigation to assess the impact of sulforaphane on autophagic flux in two metastatic prostate cancer cell lines at a concentration shown to decrease metastasis in vivo. Autophagic flux was assessed by multiple autophagy related proteins and substrates. We found that sulforaphane can stimulate autophagic flux and cell death only at high concentrations, above what has been observed in vivo. Conclusion These results suggest that sulforaphane does not directly stimulate autophagy or cell death in metastatic prostate cancer cells under physiologically relevant conditions, but instead supports the involvement of in vivo factors as important effectors of sulforaphane- mediated prostate cancer suppression. PMID:26108801

  16. Elucidation of a Conserved Proteomic Pattern of Breast Cancer Tissue and Metastatic Axillary Lymph Node.

    Science.gov (United States)

    Akpinar, Gurler; Simsek, Turgay; Guler, Ata; Kasap, Murat; Canturk, Nuh Zafer

    2017-01-01

    Breast cancer is one of the most devastating cancer types affecting women. For critical decision making regarding the fate of cancerous breast tissue, the assessment of axillary lymph node (ALN) involvement is required. However, such ALN involvement is difficult to predict without surgical intervention. Therefore, an easy predictive test using protein markers may be a desirable approach. In this study, we performed a whole proteome analysis to reveal the presence of a putative biomarker panel using primary breast tumor tissue. Materials and Methods: Proteins were extracted from tumor tissues and were subjected to two dimensional (2D) gel electrophoresis. The resulting gel images were used for inter-gel spot comparisons using PDQuest Advance software. The paterns thus obtained were used for differentiating invasive tumor types from non-invasive ones. Results: The analysis of 2D gel images revealed the presence of 24 conserved protein spots whose intensities were moderately regulated high on the gels. Those protein spots were used to create a conserved 2D pattern spanning a pH range of 4 to 8. Protein spots generating a preserved model among pattern between primary breast cancer and its axillary lymph node indicated that a robust and highly reliable proteomic approach, e.g., 2DE may be used to differentiate metastatic forms of breast cancer from non-metastatic ones. Celsius.

  17. Leptin signals via TGFB1 to promote metastatic potential and stemness in breast cancer.

    Science.gov (United States)

    Mishra, Ameet K; Parish, Christopher R; Wong, Ma-Li; Licinio, Julio; Blackburn, Anneke C

    2017-01-01

    Epidemiological studies have shown obesity to be linked with poorer outcomes in breast cancer patients. The molecular mechanisms responsible for the increased risk of invasive/metastatic disease with obesity are complex, but may include elevated levels of adipokines such as leptin. Using physiological levels of leptin found in obesity in a novel chronic in vitro treatment model (≤200 ng/ml for 14 days), we confirmed the occurrence of leptin-mediated changes in growth, apoptosis and metastatic behavior, and gene expression changes representing epithelial-to-mesenchymal transition (EMT) and a cancer stem cell (CSC) like phenotype in breast epithelial and cancer cell lines (MCF10A, MCF10AT1, MCF7 and MDA-MB-231). Further, we have discovered that these effects were accompanied by increased expression of TGFB1, and could be significantly reduced by co-treatment with neutralizing antibody against TGFB1, indicating that the induction of these characteristics was mediated via TGFB1. Occurring in both MCF7 and MCF10AT1 cells, it suggests these actions of leptin to be independent of estrogen receptor status. By linking leptin signalling to the established TGFB1 pathway of metastasis / EMT, this study gives a direct mechanism by which leptin can contribute to the poorer outcomes of obese cancer patients. Inhibitors of TGFB1 are in currently in phase III clinical trials in other malignancies, thus identifying the connection between leptin and TGFB1 will open new therapeutic opportunities for improving outcomes for obese breast cancer patients.

  18. Vertebral compression fractures after spine irradiation using conventional fractionation in patients with metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ree, Woo Joong; Kim, Kyung Hwan; Chang, Jee Suk; Kim, Hyun Ju; Choi, Seo Hee; Koom, Woong Sub [Dept.of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul (Korea, Republic of)

    2014-12-15

    To evaluate the risk of vertebral compression fracture (VCF) after conventional radiotherapy (RT) for colorectal cancer (CRC) with spine metastasis and to identify risk factors for VCF in metastatic and non-metastatic irradiated spines. We retrospectively reviewed 68 spinal segments in 16 patients who received conventional RT between 2009 and 2012. Fracture was defined as a newly developed VCF or progression of an existing fracture. The target volume included all metastatic spinal segments and one additional non-metastatic vertebra adjacent to the tumor-involved spines. The median follow-up was 7.8 months. Among all 68 spinal segments, there were six fracture events (8.8%) including three new VCFs and three fracture progressions. Observed VCF rates in vertebral segments with prior irradiation or pre-existing compression fracture were 30.0% and 75.0% respectively, compared with 5.2% and 4.7% for segments without prior irradiation or pre-existing compression fracture, respectively (both p < 0.05). The 1-year fracture-free probability was 87.8% (95% CI, 78.2-97.4). On multivariate analysis, prior irradiation (HR, 7.30; 95% CI, 1.31-40.86) and pre-existing compression fracture (HR, 18.45; 95% CI, 3.42-99.52) were independent risk factors for VCF. The incidence of VCF following conventional RT to the spine is not particularly high, regardless of metastatic tumor involvement. Spines that received irradiation and/or have pre-existing compression fracture before RT have an increased risk of VCF and require close observation.

  19. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy.

    Science.gov (United States)

    Kopetz, Scott; Chang, George J; Overman, Michael J; Eng, Cathy; Sargent, Daniel J; Larson, David W; Grothey, Axel; Vauthey, Jean-Nicolas; Nagorney, David M; McWilliams, Robert R

    2009-08-01

    Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified. We performed a retrospective review of patients newly diagnosed with metastatic CRC treated at two academic centers from 1990 through 2006. Landmark analysis evaluated the association of diagnosis year and liver resection with overall survival. Additional survival analysis of the Surveillance Epidemiology and End Results (SEER) database evaluated a similar population from 1990 through 2005. Two thousand four hundred seventy patients with metastatic CRC at diagnosis received their primary treatment at the two institutions during this time period. Median overall survival for those patients diagnosed from 1990 to 1997 was 14.2 months, which increased to 18.0, 18.6, and 29.3 months for patients diagnosed in 1998 to 2000, 2001 to 2003, and 2004 to 2006, respectively. Likewise, 5-year overall survival increased from 9.1% in the earliest time period to 19.2% in 2001 to 2003. Improved outcomes from 1998 to 2004 were a result of an increase in hepatic resection, which was performed in 20% of the patients. Improvements from 2004 to 2006 were temporally associated with increased utilization of new chemotherapeutics. In the SEER registry, overall survival for the 49,459 identified patients also increased in the most recent time period. Profound improvements in outcome in metastatic CRC seem to be associated with the sequential increase in the use of hepatic resection in selected patients (1998 to 2006) and advancements in medical therapy (2004 to 2006).

  20. Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan.

    Science.gov (United States)

    Ko, Andrew H

    2016-01-01

    Nanoliposomal irinotecan (nal-IRI) was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy) trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin) in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in survival.

  1. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease.

    Science.gov (United States)

    Butler, Timothy M; Johnson-Camacho, Katherine; Peto, Myron; Wang, Nicholas J; Macey, Tara A; Korkola, James E; Koppie, Theresa M; Corless, Christopher L; Gray, Joe W; Spellman, Paul T

    2015-01-01

    The identification of the molecular drivers of cancer by sequencing is the backbone of precision medicine and the basis of personalized therapy; however, biopsies of primary tumors provide only a snapshot of the evolution of the disease and may miss potential therapeutic targets, especially in the metastatic setting. A liquid biopsy, in the form of cell-free DNA (cfDNA) sequencing, has the potential to capture the inter- and intra-tumoral heterogeneity present in metastatic disease, and, through serial blood draws, track the evolution of the tumor genome. In order to determine the clinical utility of cfDNA sequencing we performed whole-exome sequencing on cfDNA and tumor DNA from two patients with metastatic disease; only minor modifications to our sequencing and analysis pipelines were required for sequencing and mutation calling of cfDNA. The first patient had metastatic sarcoma and 47 of 48 mutations present in the primary tumor were also found in the cell-free DNA. The second patient had metastatic breast cancer and sequencing identified an ESR1 mutation in the cfDNA and metastatic site, but not in the primary tumor. This likely explains tumor progression on Anastrozole. Significant heterogeneity between the primary and metastatic tumors, with cfDNA reflecting the metastases, suggested separation from the primary lesion early in tumor evolution. This is best illustrated by an activating PIK3CA mutation (H1047R) which was clonal in the primary tumor, but completely absent from either the metastasis or cfDNA. Here we show that cfDNA sequencing supplies clinically actionable information with minimal risks compared to metastatic biopsies. This study demonstrates the utility of whole-exome sequencing of cell-free DNA from patients with metastatic disease. cfDNA sequencing identified an ESR1 mutation, potentially explaining a patient's resistance to aromatase inhibition, and gave insight into how metastatic lesions differ from the primary tumor.

  2. Metastatic Carcinoma Occurring in a Gastric Hyperplastic Polyp Mimicking Primary Gastric Cancer: The First Reported Case

    Directory of Open Access Journals (Sweden)

    Gabriel M. Groisman

    2014-01-01

    Full Text Available Hyperplastic polyps of the stomach are regarded as benign. However, in rare cases they may contain incipient primary carcinomas. To our knowledge, breast carcinoma metastatic to a gastric hyperplastic polyp has not yet been reported. We describe the case of a 69-year-old woman to whom a gastric polyp was endoscopically excised. The patient had previously undergone a right mastectomy for mixed, invasive ductal and lobular carcinoma 5 years earlier. Histological sections from the gastric lesion showed typical features of hyperplastic polyp with foci of poorly differentiated adenocarcinoma including signet ring cells infiltrating the lamina propria. The histologic findings were consistent with a primary gastric cancer. However, the carcinoma cells were immunopositive for estrogen and progesterone receptors and GATA3 and negative for CDX2, Hep Par 1, and MUC5AC. E-cadherin showed membranous reactivity in some of the carcinoma cells while in others it was negative. Accordingly, metastatic mixed, lobular and ductal breast carcinoma was diagnosed. We conclude that metastatic adenocarcinoma mimicking primary gastric cancer can be rarely encountered in hyperplastic gastric polyps.

  3. Subclonal Genomic Architectures of Primary and Metastatic Colorectal Cancer Based on Intratumoral Genetic Heterogeneity.

    Science.gov (United States)

    Kim, Tae-Min; Jung, Seung-Hyun; An, Chang Hyeok; Lee, Sung Hak; Baek, In-Pyo; Kim, Min Sung; Park, Sung-Won; Rhee, Je-Keun; Lee, Sug-Hyung; Chung, Yeun-Jun

    2015-10-01

    The intratumoral heterogeneity (ITH) and the evolution of genomic architectures associated with the development of distant metastases are not well understood in colorectal cancers. We performed multiregion biopsies of primary and liver metastatic regions from five colorectal cancers with whole-exome sequencing and copy number profiling. In addition to a substantial level of genetic ITH, multiregion genetic profiling identifies the subclonal mutational architecture, leading to the region-based or spatial categorization of somatic mutations and the inference of intratumoral evolutionary history of cancers. The universal mutations (those observed in all the regional biopsies) are enriched in known cancer genes such as APC and TP53 with distinct mutational spectra compared with biopsy- or region-specific mutations, suggesting that major operative mutational mechanisms and their selective pressures are not constant across the metastatic progression. The phylogenies inferred from genomic data show branching evolutionary patterns where some primary biopsies are often segregated with metastastic lesions. Our analyses also revealed that copy number changes such as the chromosomal gains of c-MYC and chromothripsis can be region specific and the potential source of genetic ITH. Our data show that the genetic ITH is prevalent in colorectal cancer serving as a potential driving force to generate metastasis-initiating clones and also as a means to infer the intratumoral evolutionary history of cancers. The paucity of recurrent metastasis-clonal events suggests that colorectal cancer distant metastases may not follow a uniform course of genomic evolution, which should be considered in the genetic diagnosis and the selection of therapeutic targets for the advanced colorectal cancer. ©2015 American Association for Cancer Research.

  4. Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology.

    Science.gov (United States)

    Ripperger, Tim; Bielack, Stefan S; Borkhardt, Arndt; Brecht, Ines B; Burkhardt, Birgit; Calaminus, Gabriele; Debatin, Klaus-Michael; Deubzer, Hedwig; Dirksen, Uta; Eckert, Cornelia; Eggert, Angelika; Erlacher, Miriam; Fleischhack, Gudrun; Frühwald, Michael C; Gnekow, Astrid; Goehring, Gudrun; Graf, Norbert; Hanenberg, Helmut; Hauer, Julia; Hero, Barbara; Hettmer, Simone; von Hoff, Katja; Horstmann, Martin; Hoyer, Juliane; Illig, Thomas; Kaatsch, Peter; Kappler, Roland; Kerl, Kornelius; Klingebiel, Thomas; Kontny, Udo; Kordes, Uwe; Körholz, Dieter; Koscielniak, Ewa; Kramm, Christof M; Kuhlen, Michaela; Kulozik, Andreas E; Lamottke, Britta; Leuschner, Ivo; Lohmann, Dietmar R; Meinhardt, Andrea; Metzler, Markus; Meyer, Lüder H; Moser, Olga; Nathrath, Michaela; Niemeyer, Charlotte M; Nustede, Rainer; Pajtler, Kristian W; Paret, Claudia; Rasche, Mareike; Reinhardt, Dirk; Rieß, Olaf; Russo, Alexandra; Rutkowski, Stefan; Schlegelberger, Brigitte; Schneider, Dominik; Schneppenheim, Reinhard; Schrappe, Martin; Schroeder, Christopher; von Schweinitz, Dietrich; Simon, Thorsten; Sparber-Sauer, Monika; Spix, Claudia; Stanulla, Martin; Steinemann, Doris; Strahm, Brigitte; Temming, Petra; Thomay, Kathrin; von Bueren, Andre O; Vorwerk, Peter; Witt, Olaf; Wlodarski, Marcin; Wössmann, Willy; Zenker, Martin; Zimmermann, Stefanie; Pfister, Stefan M; Kratz, Christian P

    2017-04-01

    Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review summarizes the current knowledge of cancer predisposition syndromes in pediatric oncology and provides essential information on clinical situations in which a childhood cancer predisposition syndrome should be suspected. © 2017 Wiley Periodicals, Inc.

  5. Primary hepatic embryonal sarcoma masquerading as metastatic ovarian cancer

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    Praseedom Raaj

    2009-06-01

    Full Text Available Abstract Background Hepatic embryonal sarcoma (HES is a rare but aggressive primary tumor of the liver occurring most frequently in childhood. Case presentation We report a case of a 52 year old woman having previously undergone treatment for ovarian serous papillary carcinoma who subsequently presented with a large solitary mass in the liver. Initially this was presumed to be metastasis from the ovarian primary however, on further examination it was shown to be a primary hepatic embryonal sarcoma. Conclusion Primary liver tumors should be considered in differential diagnoses in patients with ovarian cancer who subsequently present with liver tumors. This is particularly important when there is no direct evidence of recurrence of ovarian cancer.

  6. Metastatic Colorectal Cancer Resembling Severe Preeclampsia in Pregnancy

    Directory of Open Access Journals (Sweden)

    Raminder Kaur Khangura

    2015-01-01

    Full Text Available Although colorectal cancer (CRC is the third most common cancer in women, it is a rare malignancy in pregnancy. Symptoms of CRC such as fatigue, malaise, nausea, vomiting, rectal bleeding, anemia, altered bowel habits, and abdominal mass are often considered typical symptoms of pregnancy. Many cases of CRC are diagnosed in advanced stages due to missed warning signs of CRC, which may be misinterpreted as normal symptoms related to pregnancy. This report reviews 2 cases of CRC diagnosed within a 4-month interval at our institution. Both cases were initially thought to be atypical presentations of preeclampsia. Prenatal history, hospital course, and postpartum course were reviewed for both patients. CRC is often diagnosed at advanced stages in pregnancy. Common physiological symptoms of pregnancy should be scrutinized carefully and worked up appropriately, especially if symptoms remain persistent or increase in intensity or severity.

  7. Metastatic Breast Cancer Cells Collectively Invade Collagen by Following a Glucose Gradient

    Science.gov (United States)

    Sun, Bo; Austin, Robert; Liu, Liyu; Duclos, Guillaume; Lee, Jeongseog; Wu, Amy; Kam, Yooseok; Sontag, Eduardo; Stone, Howard; Sturm, James; Gatenby, Robert

    2013-03-01

    We show that MDA-MB-231 metastatic breast cancer cells collectively invade a three dimensional collagen matrix by following a glucose gradient. We observe that due to the 3D physical deformation of the matrix, as measured by the displacement of reporter beads within the matrix, there exists a long range deformation mechanical field inside the matrix which serves to couple the motions of the invading metastatic cell. The invasion front of the cells is a dynamic one, with different cells assuming the lead on a time scale of 24 hours due to certain cells having higher speeds of penetration, which are not sustained. The front cell leadership is dynamic presumably due to metabolic costs associated with the long range strain field which proceeds the invading cell front, which we have imaged using confocal imaging and marker beads imbedded in the collagen matrix. Sponsored by the NCI/NIH Physical Sciences Oncology Centers

  8. Group support for patients with metastatic cancer. A randomized outcome study.

    Science.gov (United States)

    Spiegel, D; Bloom, J R; Yalom, I

    1981-05-01

    The effects of weekly supportive group meetings for women with metastatic carcinoma of the breast were systematically evaluated in a one-year, randomized, prospective outcome study. The groups focused on the problems of terminal illness, including improving relationships with family, friends, and physicians and living as fully as possible in the face of death. We hypothesized that this invention would lead to improved mood, coping strategies, and self-esteem among those in the treatment group. Eighty-six patients were tested at four-month intervals. The treatment group had significantly lower mood-disturbance scores on the Profile of Mood States scale, had fewer maladaptive coping responses, and were less phobic than the control group. This study provides objective evidence that a supportive group intervention for patients with metastatic cancer results in psychological benefit. Mechanisms underlying the effectiveness of this group intervention are explored.

  9. Mayo Clinic Cancer Center experience of metastatic extramammary Paget disease 1998-2012

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    Leslie Padrnos

    2016-11-01

    Full Text Available Extramammary Paget disease (EMPD is a rare cutaneous malignancy. The most common presentation of EMPD is the vulva followed by perianal involvement. Most cases are localized to the dermis with treatment focused on surgery, topical treatment or radiotherapy. Recurrence is frequent despite therapies utilized. Metastatic extramammary Paget disease is uncommon and, as such, standard treatment guidelines do not exist. This study sought to evaluate the treatment regimens and outcomes of patients treated at a Mayo Clinic Center from 1998-2012. Cancer registry inquiry revealed 261 patients with report advanced Paget disease during these years. Ten cases of metastatic EPMD were identified with sufficient documentation for review. This review reveals support for utilizing localized radiation therapy for bulky disease sequentially with systemic chemotherapy consisting of carboplatin and paclitaxel or irinotecan. Further studies are necessary to define the optimal treatment regimen.

  10. Ureteropelvic Junction Obstruction Secondary to Metastatic Relapse of Breast Cancer

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    Paras H. Shah

    2016-01-01

    Full Text Available We describe the case of a 53-year-old woman with a history of localized breast cancer who presented with flank pain and was found to have new-onset obstruction of the left ureteropelvic junction. Although initially believed to be unrelated to her history of prior malignancy, intraoperative assessment of tissue from the ureteropelvic junction during planned laparoscopic pyeloplasty revealed urothelial infiltration by carcinoma of breast origin.

  11. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2015-10-01

    AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER University of British Columbia 6190 Agronomy Road, Ste 102 Vancouver, BC...0646847,SBI- 0646849, SBI-0646850, SBI-0646-851, SBI-0646852, SBI-0646853). Given that these are natural compound-based structures, the development of...mission pertaining to cancer research and to support shared service facilities, unique resources and recruitment of new staff members for the

  12. New Epigenetic Therapeutic Intervention for Metastatic Breast Cancer

    Science.gov (United States)

    2017-04-01

    migration and metastasis of many types of cancers, including TNBC. Our current study indicates that Twist activation intensifies the inflammatory ATX...microarray screen to identify potential Twist target genes. It was revealed that the mRNA levels of Autotaxin (ATX) and LPAR1 were dramatically increased...Zuber, J., Shi, J., Wang, E., Rappaport, A.R., Herrmann, H., Sison, E.A., Magoon, D., Qi, J., Blatt, K., Wunderlich, M., et al. (2011). RNAi screen iden

  13. Metastatic breast cancer to uterine leiomyoma: case report

    Directory of Open Access Journals (Sweden)

    Hayedeh Haeri

    2015-08-01

    Conclusion: Although metastasis of breast cancer to the genital organs is an uncommon event, breast carcinoma is still considered the second source of extragenital malignant metastasis to the uterus. Overall, the most popular sites for metastasis of breast carcinoma to the female reproductive system include the ovaries and the uterine cervix. The uterine corpus is the least common site involved. In this regard metastasis to a uterine leiomyoma is a rare event.

  14. Expression of glucocorticoid receptor is associated with aggressive primary endometrial cancer and increases from primary to metastatic lesions.

    Science.gov (United States)

    Tangen, Ingvild L; Veneris, Jennifer Taylor; Halle, Mari K; Werner, Henrica M; Trovik, Jone; Akslen, Lars A; Salvesen, Helga B; Conzen, Suzanne D; Fleming, Gini F; Krakstad, Camilla

    2017-12-01

    Glucocorticoid receptor (GR) has emerged as an important steroid nuclear receptor in hormone dependent cancers, however few data are available regarding a potential role of GR in endometrial cancer. The aim of this study was to investigate expression of GR in primary and metastatic endometrial cancer lesions, and to assess the relationship between GR expression and clinical and histopathological variables and survival. Expression of GR was investigated by IHC in 724 primary tumors and 289 metastatic lesions (from 135 patients), and correlations with clinical and histopathological data and survival were explored. Expression of GR was significantly increased in non-endometrioid tumors compared to endometrioid tumors, and was associated with markers of aggressive disease and poor survival both in univariate and multivariate analysis after correcting for age, FIGO stage and histologic grade. Within the subgroups of hormone receptor negative tumors (loss of androgen receptor, estrogen receptor or progesterone receptor) expression of GR was highly significantly associated with poor disease specific survival. There was an overall increase in GR expression from primary to metastatic lesions, and the majority of metastases expressed GR. GR expression in primary endometrial cancer is associated with aggressive disease and poor survival. The majority of metastatic endometrial cancer lesions express GR; therefore GR may represent a therapeutic target in the adjuvant therapy of poor prognosis early-stage as well as metastatic endometrial cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer.

    Science.gov (United States)

    Magnani, Luca; Patten, Darren K; Nguyen, Van T M; Hong, Sung-Pil; Steel, Jennifer H; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Fernandez Garcia, Daniel; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O; Rakha, Emad A; Shousha, Sami; Lam, Eric W-F; Győrffy, Balázs; Lupien, Mathieu; Coombes, R Charles

    2015-09-08

    Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer.

  16. 3D radiation therapy or intensity-modulated radiotherapy for recurrent and metastatic cervical cancer: the Shanghai Cancer Hospital experience.

    Directory of Open Access Journals (Sweden)

    Su-Ping Liu

    Full Text Available We evaluate the outcomes of irradiation by using three-dimensional radiation therapy (3D-RT or intensity-modulated radiotherapy (IMRT for recurrent and metastatic cervical cancer. Between 2007 and 2010, 50 patients with recurrent and metastatic cervical cancer were treated using 3D-RT or IMRT. The median time interval between the initial treatment and the start of irradiation was 12 (6-51 months. Salvage surgery was performed before irradiation in 5 patients, and 38 patients received concurrent chemotherapy. Sixteen patients underwent 3D-RT, and 34 patients received IMRT. Median follow-up for all the patients was 18.3 months. Three-year overall survival and locoregional control were 56.1% and 59.7%, respectively. Three-year progression-free survival and disease-free survival were 65.3% and 64.3%, respectively. Nine patients developed grade 3 leukopenia. Grade 5 acute toxicity was not observed in any of the patients; however, 2 patients developed Grade 3 late toxicity. 3D-RT or IMRT is effective for the treatment of recurrent and metastatic cervical cancer, with the 3-year overall survival of 56.1%, and its complications are acceptable. Long-term follow-up and further studies are needed to confirm the role of 3D-RT or IMRT in the multimodality management of the disease.

  17. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Science.gov (United States)

    Toss, Angela; Venturelli, Marta; Peterle, Chiara; Piacentini, Federico; Cascinu, Stefano; Cortesi, Laura

    2017-01-04

    In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc.) significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  18. Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

    Science.gov (United States)

    Schofield, Penelope E; Stockler, M R; Zannino, D; Tebbutt, N C; Price, T J; Simes, R J; Wong, N; Pavlakis, N; Ransom, D; Moylan, E; Underhill, C; Wyld, D; Burns, I; Ward, R; Wilcken, N; Jefford, M

    2016-01-01

    Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.

  19. Genomic characteristics of trastuzumab-resistant Her2-positive metastatic breast cancer.

    Science.gov (United States)

    de Oliveira Taveira, Mateus; Nabavi, Sheida; Wang, Yuker; Tonellato, Peter; Esteva, Francisco J; Cantley, Lewis C; Wulf, Gerburg M

    2017-07-01

    Resistance to trastuzumab therapy is linked to phosphoinositol 3-kinase (PI3K) pathway activation. One key downstream effector and regulator of this pathway is the mechanistic target of rapamycin (mTOR). In 2011, a phase I/II study evaluated the combination of trastuzumab and everolimus (a mTOR inhibitor) for treatment of Her2-positive metastatic breast cancer (MBC) for patients who had progressed on trastuzumab-based therapy. We retrospectively analyzed GeneChip microarray data from 22 of 47 patients included in the study. Using an unbiased approach, we found that mutations in BRAF, EGFR and KIT are significantly more common in this heavily treated population when compared with the cohort of invasive breast carcinoma patients in The Cancer Genome Atlas (TCGA). Furthermore, 10 out of 22 patients had PIK3CA mutations (45.4%) but PI3KCA status was not predictive of PFS in our cohort. Finally, the use of OncoScan(tm) has allowed us to detected mutations in five genes that have not been shown to be mutated in TCGA subset of Her-2 overexpressing breast cancer: CTNNB1, HRAS, KRAS, NF2 and SMARCB1. Mutational burden in heavily treated trastuzumab-resistant Her2-positive metastatic breast cancer is highly variable and not directly correlated with outcome. Activation of the MAPK/ERK pathway through mutations in EGFR, BRAF or KIT may mediate resistance to trastuzumab.

  20. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2017-01-01

    Full Text Available In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc. significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  1. Palbociclib for the Treatment of Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

    Science.gov (United States)

    Morikawa, Aki; Henry, N Lynn

    2015-08-15

    Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 that acts by reducing phosphorylation of the tumor suppressor gene retinoblastoma. When added to the aromatase inhibitor letrozole in a randomized phase II trial for first-line therapy of estrogen receptor-positive, HER2-negative metastatic breast cancer, palbociclib significantly increased progression-free survival compared with letrozole alone [palbociclib + letrozole: 20.2 months; 95% confidence interval (CI), 13.8-27.5; letrozole: 10.2 months; 95% CI, 5.7-12.6; HR, 0.49; 95% CI, 0.32-0.75; P = 0.0004]. On the basis of these results, the drug was recently granted accelerated approval by the FDA, and confirmatory studies are ongoing. Because this drug has a rational target in an oncologic pathway, concurrent biomarker development is of interest. In breast cancer, the most useful predictive biomarkers identified thus far are estrogen receptor and HER2 receptor status, although additional studies are ongoing. In this article, we review the development of palbociclib and its use in treatment of hormone receptor-positive metastatic breast cancer in the context of other FDA-approved agents in this setting. ©2015 American Association for Cancer Research.

  2. Metastatic breast cancer presenting as a primary hindgut neuroendocrine tumour.

    Science.gov (United States)

    Okines, Alicia F C; Hawkes, Eliza A; Rao, Sheela; VAN As, Nicholas; Marsh, Henry; Riddell, Angela; Wilson, Philip O G; Osin, Peter; Wotherspoon, Andrew C; Wetherspoon, Andrew C

    2010-07-01

    The examination of limited, potentially non-representative fragments of tumour tissue from a core biopsy can be misleading and misdirect subsequent treatment, especially in cases where a primary tumour has not been identified. This case report is of a 65-year-old woman presenting with a destructive sacral mass, diagnosed on radiological imaging and core biopsy as a hindgut neuroendocrine tumour, which on histopathological review of the subsequently resected tumour was found instead to represent a metastasis from an occult hormone-positive breast cancer with neuroendocrine features.

  3. How MMPs Impact Bone Responses to Metastatic Prostate Cancer

    Science.gov (United States)

    2011-04-30

    Washington Note: Sup Cancer Res Correspon and Rehab Tower, Sui Fax: 615-3 doi: 10.115 ©2010 Am www.aacrIn human prostate to bone metastases and in a...threshold. The number of osteolytic lesions that completely penetrated the cortical bone, as seen in the virtual reconstruction, were counted. MicroCT...at the time of their death [1–3]. Bone metastases are often termed as either osteolytic or osteogenic but in reality , the lesions contain areas of

  4. Detecting blood-based biomarkers in metastatic breast cancer : A systematic review of their current status and clinical utility

    NARCIS (Netherlands)

    Berghuis, A.M. Sofie; Koffijberg, Hendrik; Prakash, Jai; Terstappen, Leon W.M.M.; Ijzerman, Maarten J.

    2017-01-01

    Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the

  5. Results from a Phase I Study of Lapatinib with Gemcitabine and Cisplatin in Advanced or Metastatic Bladder Cancer

    DEFF Research Database (Denmark)

    Cerbone, L; Sternberg, C N; Sengeløv, L

    2016-01-01

    BACKGROUND/OBJECTIVE: Lapatinib is a potent HER1 and HER2 inhibitor. Gemcitabine-cisplatin (GC) is a standard chemotherapy regimen for advanced/metastatic bladder cancer. This phase I study examined the safety of lapatinib in combination with GC in patients with bladder cancer. The primary aim...

  6. Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer.

    Science.gov (United States)

    Powles, Thomas; Sarwar, Naveed; Stockdale, Andrew; Sarker, Shah-Jalal; Boleti, Ekaterini; Protheroe, Andrew; Jones, Robert; Chowdhury, Simon; Peters, John; Oades, Grenville; O'Brien, Tim; Sullivan, Mark; Aitchison, Michael; Beltran, Luis; Worth, Daniel; Smith, Kate; Michel, Constance; Trevisan, Giorgia; Harvey-Jones, Elizabeth; Wimalasingham, Akhila; Sahdev, Anju; Ackerman, Charlotte; Crabb, Simon

    2016-10-01

    The role of cytoreductive nephrectomy in patients with metastatic renal cancer in the era of targeted therapy is uncertain. To establish the safety and efficacy of upfront pazopanib therapy prior to cytoreductive nephrectomy in previously untreated patients with metastatic clear cell renal cancer. Single-arm phase 2 study of 104 previously untreated patients with metastatic clear cell renal cancer recruited between June 2008 and October 2012 at cancer treatment centers with access to nephrectomy services. The minimum follow-up was 30 months. Patients received 12 to 14 weeks of preoperative pazopanib therapy prior to planned cytoreductive nephrectomy and continued pazopanib therapy after surgery. Treatment was stopped at disease progression. The primary end point was clinical benefit (using Response Evaluation Criteria in Solid Tumors, version 1.1) prior to surgery (at 12-14 weeks). Secondary end points included surgical complications, progression-free survival (PFS), overall survival (OS), and biomarker analysis. Of 104 patients recruited, 100 patients were assessable for clinical benefit prior to planned nephrectomy; 80 of 104 (76.9%) were men; median [interquartile range] age, 64 [56-71] years). Overall, 84 of 100 (84% [95% CI, 75%-91%]) gained clinical benefit before planned nephrectomy. The median reduction in the size of the primary tumor was 14.4% (interquartile range, 1.4%-21.1%). No patients were unable to undergo surgery as a result of local progression of disease. Nephrectomy was performed in 63 (61%) of patients; 14 (22%) reported surgical complications. The 2 most common reasons for not undergoing surgery were progression of disease (n = 13) and patient choice (n = 9). There was 1 postoperative surgical death. The median PFS and OS for the whole cohort were 7.1 (95% CI, 6.0-9.2) and 22.7 (95% CI, 14.3-not estimable) months, respectively. Patients with MSKCC poor-risk disease or progressive disease prior to surgery had a poor outcome (median OS

  7. Experimental study of the survival of metastatic cancer cells in corneal organ culture.

    Science.gov (United States)

    Deb-Joardar, Nilanjana; Thuret, Gilles; Dumollard, Jean-Marc; Absi, Lena; Campos-Guyotat, Lydia; Peoc'h, Michel; Garraud, Olivier; Gain, Philippe

    2006-04-01

    Transmission of donor malignancy to the recipient could be one of the most disastrous complications of corneal grafting. Because of the scarcity of donor tissue and the lack of sufficient scientific evidence, the harvest of donor tissues from deaths due to systemic malignancy is permitted. This study was conducted to investigate the possible transmission of donor metastatic disease via corneal tissue preserved in organ culture (OC) conditions. The viability of four frequent human cancer cell lines (lung, breast, skin, and colon) was studied in OC. Various inoculums of cancer cells labeled with the membrane marker PKH67 were seeded on donor corneas and preserved in OC, followed by cell-tracking studies, histopathology, and immunohistochemistry. HLA matching of the dissected Descemet's membrane (DM) of preserved corneas was conducted, to demonstrate cell adherence. Primary cell culture was performed to confirm the viability of adherent tumor cells. Viability tests showed a poor but persistent survival of cancer cells after 2 weeks in OC. Cell tracking, histopathology, and immunohistochemistry demonstrated cancer cell adherence to donor endothelium. HLA typing of the DM of preserved corneas revealed the presence of cancer cell alleles. Primary culture of the DM showed cell proliferation that was identical with the original cancer cell line, according to HLA studies. The findings demonstrate that under laboratory conditions, metastatic cancer cells adhere to donor corneal tissue, survive, and retain proliferative capacity during storage in OC. Cell lines differ in their viability potential, as well as the pattern of adherence to donor endothelium. Further in vivo experimentation in laboratory animals is need to determine the safety of such harvests.

  8. Nivolumab in recurrent/metastatic head and neck cancers.

    Science.gov (United States)

    Karabajakian, Andy; Reverdy, Thibaut; Gau, Max; Fayette, Jérôme

    2017-11-13

    Head and neck cancer is an immunosuppressive disease, with a high proportion expressing PD-L1. Until recently, options were lacking in second line. Prognosis is poor especially for patients who progress during chemotherapy with survival often inferior to 6 months. Nivolumab is the only anti-PD1 agent to prolong survival in the second-line setting and is now the standard option since the CheckMate-141 trial. Treatment is generally well tolerated, patients seem to have a better quality of life when compared with chemotherapy. Markers of efficacy are lacking even if some data are emerging. Different combinations of immunotherapy are ongoing. Hyperprogression is a phenomenon associated with poor outcome and might be the consequence of anti-PD1 treatment but this is yet to be proven.

  9. High tumor budding stratifies breast cancer with metastatic properties.

    Science.gov (United States)

    Salhia, Bodour; Trippel, Mafalda; Pfaltz, Katrin; Cihoric, Nikola; Grogg, André; Lädrach, Claudia; Zlobec, Inti; Tapia, Coya

    2015-04-01

    Tumor budding refers to single or small cluster of tumor cells detached from the main tumor mass. In colon cancer high tumor budding is associated with positive lymph nodes and worse prognosis. Therefore, we investigated the value of tumor budding as a predictive feature of lymph node status in breast cancer (BC). Whole tissue sections from 148 surgical resection specimens (SRS) and 99 matched preoperative core biopsies (CB) with invasive BC of no special type were analyzed on one slide stained with pan-cytokeratin. In SRS, the total number of intratumoral (ITB) and peripheral tumor buds (PTB) in ten high-power fields (HPF) were counted. A bud was defined as a single tumor cell or a cluster of up to five tumor cells. High tumor budding equated to scores averaging >4 tumor buds across 10HPFs. In CB high tumor budding was defined as ≥10 buds/HPF. The results were correlated with pathological parameters. In SRS high PTB stratified BC with lymph node metastases (p ≤ 0.03) and lymphatic invasion (p ≤ 0.015). In CB high tumor budding was significantly (p = 0.0063) associated with venous invasion. Pathologists are able, based on morphology, to categorize BC into a high and low risk groups based in part on lymph node status. This risk assessment can be easily performed during routine diagnostics and it is time and cost effective. These results suggest that high PTB is associated with loco-regional metastasis, highlighting the possibility that this tumor feature may help in therapeutic decision-making.

  10. Interleukin-12 in Treating Patients With Hematologic Cancers or Solid Tumors

    Science.gov (United States)

    2014-09-09

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  11. Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer

    Directory of Open Access Journals (Sweden)

    Shen Hu

    2010-09-01

    Full Text Available Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC. A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have performed a serum proteomic analysis of OSCC using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry. One of the down-regulated proteins in OSCC was identified as tetranectin, which is a protein encoded by the CLEC3B gene (C-type lectin domain family 3, member B. We further tested the protein level in serum and saliva from patients with lymph-node metastatic and primary OSCC. Tetranectin was found significantly under-expressed in both serum and saliva of metastatic OSCC compared to primary OSCC. Our results suggest that serum or saliva tetranectin may serve as a potential biomarker for metastatic OSCC. Other candidate serum biomarkers for OSCC included superoxide dismutase, ficolin 2, CD-5 antigen-like protein, RalA binding protein 1, plasma retinol-binding protein and transthyretin. Their clinical utility for OSCC detection remains to be further tested in cancer patients.

  12. Comparable survival outcome of metastatic colorectal cancer in Indigenous and non-Indigenous patients: Retrospective analysis of the South Australian metastatic colorectal cancer registry.

    Science.gov (United States)

    Tomita, Yoko; Karapetis, Christos S; Roder, David; Beeke, Carol; Hocking, Christopher; Roy, Amitesh C; Townsend, Amanda R; Padbury, Rob; Maddern, Guy; Price, Timothy J

    2016-04-01

    This study aims to investigate disparities in demographics, disease characteristics, treatment and overall survival between South Australian (SA) Indigenous and non-Indigenous patients with metastatic colorectal cancer (mCRC). This employs a retrospective population study using the SA mCRC registry. The SA mCRC registry identifies mCRC patients from hospital encounters, histopathology reports, medical oncology letters, clinician notification, attendances at multidisciplinary meetings and death audits by the SA Cancer Registry. A total of 2865 adult mCRC patients including 14 Indigenous patients were identified through the SA mCRC registry between February 2006 and August 2013. Patients were linked to the SA Cancer Registry to obtain Indigenous status. Demographic, disease and treatment characteristics were compared using Chi-squared test and t-test; while overall survival defined as time to any cause of death was analysed using Cox regression. No difference was observed for clinical characteristics, except for a higher proportion of Indigenous patients receiving chemotherapy (85.7% versus 58.5%; P = 0.04). The rate of liver surgery was similar across the two groups (21.0% versus 15.1%; P = 0.40). The median overall survivals were equivalent (11.9 months versus 15.1 months; hazard ratio = 1.00; 95% confidence interval for hazard ratio, 0.54-1.86). Clinical characteristics and survival outcomes were similar between Indigenous and non-Indigenous patients captured on the SA mCRC registry, and outcome of those who have an access to comprehensive cancer care appeared independent of Indigenous status and in line with large clinical trials. Underestimation of Indigenous cases due to their lower utilisation of cancer service could not be excluded and ultimately the accurate reporting of these patients is crucial. © 2015 National Rural Health Alliance Inc.

  13. Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.

    Science.gov (United States)

    Prithviraj, G K; Baksh, K; Fulp, W; Meredith, K; Hoffe, S; Shridhar, R; Almhanna, K

    2015-01-01

    Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we retrospectively present our single center experience. Between 1998 and 2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly area under the curve 5 and paclitaxel predominantly 175 mg/m(2)) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from diagnosis to death or last follow up, and progression-free survival was defined at time from cycle 1 to, progression or last follow up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Of the 134 patients evaluated, the median age at diagnosis was 65 years. Disease control rate was 62.6% (complete response: 11%, partial response: 28%, stable disease: 33%). Median overall survival from date of initial diagnosis was 15.5 months (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 5.3 months (95% CI 0.34-0.5). Grade III or greater toxicity occurred in 26.1% of patients. The most common grade III toxicities were neutropenia and neuropathy, present in 14.2% and 3.7% of the total study population, respectively. In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population. © 2014 International Society for Diseases of the Esophagus.

  14. Neutropenia as a Predictive Factor in Metastatic Colorectal Cancer Treated With TAS-102.

    Science.gov (United States)

    Hamauchi, Satoshi; Yamazaki, Kentaro; Masuishi, Toshiki; Kito, Yosuke; Komori, Azusa; Tsushima, Takahiro; Narita, Yukiya; Todaka, Akiko; Ishihara, Makoto; Yokota, Tomoya; Tanaka, Tsutomu; Machida, Nozomu; Kadowaki, Shigenori; Fukutomi, Akira; Ura, Takashi; Onozawa, Yusuke; Ando, Masashi; Tajika, Masahiro; Muro, Kei; Yasui, Hirofumi; Mori, Keita; Taniguchi, Hiroya

    2017-03-01

    TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common treatment-related adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The potential predictive value of neutropenia caused by cytotoxic drugs has been reported in various types of cancer. We retrospectively analyzed 95 consecutive patients with metastatic colorectal cancer who received TAS-102 at 2 Japanese institutions between May 2014 and May 2015. To evaluate the association between efficacy and neutropenia, patients were divided into 4 categories according to the grade of neutropenia during the first cycle of TAS-102: Category A (grade 0-1), B (grade 2-4), C (grade 0-2), and D (grade 3-4). Patient characteristics were as follows: median age, 64 years; male, 58%; Eastern Cooperative Oncology Group performance status 0 to 1, 91%; primary site colon, 49%; KRAS exon 2 wild, 57%; and number of metastatic site ≥ 3, 55%. The disease control rate was significantly different between Category A and B (29.2% vs. 52.6%; P = .045) and between Category C and D (30.9% vs. 72.2%; P = .002). In multivariate analysis, Category D remained a significant predictive factor for progression-free survival compared with Category C (4.3 vs. 2.0 months; hazard ratio, 0.45; P = .01). Neutropenia caused by TAS-102 during the first cycle was associated with better efficacy. Neutropenia may be a surrogate marker for adequate antitumor doses of TAS-102. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Developing a national database for metastatic colorectal cancer management: perspectives and challenges.

    Science.gov (United States)

    Field, K; Wong, H-L; Shapiro, J; Kosmider, S; Tie, J; Bae, S; Yip, D; McKendrick, J; Nott, L; Desai, J; Harold, M; Lipton, L; Stefanou, G; Lim, L; Parente, P; Gibbs, P

    2013-11-01

    The changing treatment landscape for metastatic colorectal cancer creates multiple potential treatment strategies. An Australian-centric database capturing comprehensive information across a range of treatment locations would create a valuable resource enabling multiple important research questions to be addressed. To establish a collection of a consensus dataset capturing treatment and outcomes at multiple public and private hospitals across Australia. An electronic database was developed by a panel of clinicians, to capture an agreed dataset for patients with newly diagnosed metastatic colorectal cancer. Of particular interest were clinician decision-making, the impact of comorbidities and the frequency of major adverse events. Since July 2009, data collection has been established at six public and eight private hospitals across three Australian states and territories. Successful linkage and analysis, with support from BioGrid Australia, of selected data on the initial 864 patients demonstrates that data can be captured from diverse sites, including public and private practice, that multiple factors impact on treatment delivered and outcomes achieved and that comprehensive data on rare but important adverse events can be captured. As a clinical research tool, the project has been highly successful, generating multiple presentations at national and international conferences related to a diverse range of research questions. Multistate, project-specific data collection involving large numbers of patients is achievable. Providing invaluable insight into the routine clinical management of metastatic colorectal cancer in the era of targeted therapies, this also creates a significant resource for research, including many questions not being addressed by clinical trials. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  16. Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Bryce, A H; Alumkal, J J; Armstrong, A

    2017-01-01

    BACKGROUND: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA...... monitoring alone to determine disease status on therapy. This approach has not been adequately tested. METHODS: Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide...... treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant...

  17. Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond

    Science.gov (United States)

    Mackay, Helen J.; Wenzel, Lari; Mileshkin, Linda

    2016-01-01

    Overview Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease. PMID:25993189

  18. Randomised trial of expressive writing for distressed metastatic breast cancer patients.

    Science.gov (United States)

    Mosher, Catherine E; Duhamel, Katherine N; Lam, Joanne; Dickler, Maura; Li, Yuelin; Massie, Mary Jane; Norton, Larry

    2012-01-01

    Women with metastatic breast cancer and significant psychological distress (N = 87) were assigned randomly to engage in four home-based sessions of expressive writing or neutral writing. Women in the expressive writing group wrote about their deepest thoughts and feelings regarding their cancer, whereas women in the neutral writing group wrote about their daily activities in a factual manner. No statistically significant group differences in existential and psychological well-being, fatigue and sleep quality were found at 8-weeks post-writing. However, the expressive writing group reported significantly greater use of mental health services during the study than the neutral writing group (55% vs. 26%, respectively; p writing may improve the uptake of mental health services among distressed cancer patients, but is not broadly effective as a psychotherapeutic intervention.

  19. Hypertriglyceridemia in patients with metastatic breast cancer and treatment with capecitabine.

    Science.gov (United States)

    Geva, Shahar; Lazarev, Irena; Geffen, David Barry; Ariad, Samuel

    2013-06-01

    Several reports have described hypertriglyceridemia (HTG) in cancer patients, including breast cancer patients treated with capecitabine (CAP). However, the exact range of HTG in patients with metastatic breast cancer (MBC) treated with CAP has clearly not been defined. A retrospective analysis on 54 patients with MBC treated with CAP longer than 2 months was conducted. HTG was defined as triglyceride blood level above 150 mg/dl. Baseline data included age, body mass index (BMI), tumour characteristics, treatment duration, concomitant treatment with lapatinib, diagnosis of dyslipidemia, and diabetes mellitus, as well as antihyperlipidemic therapy. Clinically significant HTG (triglycerides >300 mg/dl) was found in 4/54 (7%) of patients. Post-treatment HTG was associated only with concomitant treatment with lapatinib (PHTG-related complications occurred. Clinically significant HTG in MBC patients treated with CAP may be associated with pre-existing risk factors, such as dyslipidemia or diabetes-mellitus.

  20. Radiotherapy Results of Breast Cancer Patients with Metastatic Bone Disease

    Directory of Open Access Journals (Sweden)

    Ahmet Dirier

    2006-01-01

    Full Text Available Breast cancer patients with bone metastasis who had admitted to Dicle University Department of Radiation Oncology for palliative radiation therapy between September 2001 and December 2003 were evaluated. There were 31 patients (26 female, 5 male. Median age was 43 years (range 23-79. Histopathological subtypes were infiltrating ductal carcinoma (88%, tubulolobuler carcinoma (6% and inflammatory carcinoma (6%. Loci of bone metastasis were vertebra only in twelve patients (39%, non-vertebral bones only in 8 patients (26% and both vertebral and nonvertebral bones in 11 patients (35%. Two patients had refused radiotherapy. Radiation doses were 3000 cGy with 10 fractions in 15 patients, 2000 cGy with 5 fractions in 6 patients and 800 cGy single fraction in eight patients. Complete palliation of pain was achieved in 18 patients (62% and partial palliation was achieved in 11 patients (38%. Treatment related toxicity was grade I-II dermatitis. In conclusion; same respons rates in terms of palliation can be achieved in the three radiotherapy schedules.

  1. Matrix rigidity induces osteolytic gene expression of metastatic breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Nazanin S Ruppender

    Full Text Available Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP. While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung preferentially metastasize to bone.

  2. Numb chin syndrome as a primary presentation of metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Jasjot Sahni

    2017-01-01

    Full Text Available Numb chin syndrome (NCS is characterized by facial neuropathy along the distribution of the mental branch of the trigeminal nerve. We report a case of NCS in a 65 year old woman who initially presented to her dentist with nonspecific symptoms that she thought were related to a tooth infection. The patient was otherwise healthy and her medical history was significant for breast cancer treated 20 years prior; her cancer was thought to be in complete remission. Upon clinical examination and conventional dental radiography, no pathology was seen such as odontogenic, periodontal, or jawbone infection. Only paresthesia and hypoesthesia was noted unilaterally in her left chin, jaw and lower lip. A computed tomography scan was obtained for further evaluation and revealed lytic metastatic disease involving the right mandible at the level of the mandibular foramen; lytic lesions of the thoracic vertebrae and multiple pulmonary nodules were also noted. Oncologic referral was made immediately which confirmed a diagnosis of metastatic breast cancer. Familiarity with NCS is important for oral health care providers in order to identify etiology and differential diagnosis, as well as to provide appropriate referral and management.

  3. Lapatinib plus transtuzumab for HER-2 positiva metastatic breast cancer: Experience of use

    Directory of Open Access Journals (Sweden)

    C. García-Muñoz

    2014-03-01

    Full Text Available Abstract: Objective: To describe the outcomes produced by concomitant use of HER2-receptor inhibitors Lapatinib and Trastuzumab for the treatment of HER 2-positive metastatic breast cancer. Method: Retrospective observational study. Patients treated with Trastuzumab and Lapatinib between January of 2010 and May of 2012 were selected. Demographical and clinical data were gathered. Results: 23 patients with metastatic breast cancer (mean age 59.3 ± 13.3 years were included. All of them had received an average of 5 treatment lines with at least one of them including Trastuzumab. The median progression-free survival rate with combined Lapatinib + Trastuzumab, with or without associated chemotherapy was 7 months (95% CI: 2.78-11.21 and 3 months for the patients only receiving Lapatinib and Trastuzumab. Seven patients experienced adverse events and in four patients the treatment was stopped due to toxicity. Conclusions: The treatment with HER2-receptor inhibitors in our patients resulted in progression-free survival rates similar to those published in clinical trials with patients receiving Lapatinib + Trastuzumab not combined with any other anti-cancer therapy, with good treatment tolerability.

  4. [A case of metastatic pulmonary cancer from urachal carcinoma that required differentiation from primary lung adenocarcinoma].

    Science.gov (United States)

    Tatsuno, Mai; Tamura, Shinobu; Taniguchi, Fumitaka; Yasuoka, Hironao; Nasu, Hideki; Fujimoto, Tokuzo

    2011-11-01

    A 58-year-old man was given a diagnosis of urachal carcinoma and underwent a partial cystectomy with enbloc removal of the tumor and radical lymphadenectomy in 2006. In April 2009 he was admitted to our hospital because of hemoptysis and left chest pain. Chest CT showed a 4-cm mass shadow in the left S3 and nodular shadows in the right S1 and left S10. Flexible bronchoscopy demonstrated a tumorous lesion at the orifice of the left B3 bronchus. Although the cytological diagnosis suggested high-grade adenocarcinoma, the tumor was producing mucin and consisted of cells with anisonucleosis, which is not typical of primary lung adenocarcinoma. We then performed immunohistochemical and histological examination of a transbronchial lung biopsy specimen. The histological findings of the specimen were very similar to those of the previously resected urachal carcinoma. In addition, the tumor cells were negative for thyroid transcription factor-1 and surfactant precursor protein B, which are specific to primary lung adenocarcinoma. We therefore diagnosed metastatic pulmonary cancer from urachal carcinoma, which is a rare manifestation in bladder cancer. We report a rare case of metastatic pulmonary cancer from urachal carcinoma that required differentiation from primary lung adenocarcinoma in addition to a discussion of the literature.

  5. Impact of modern chemotherapy on the survival of women presenting with de novo metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Pal Sumanta K

    2012-09-01

    Full Text Available Abstract Background Data that directly associate utilization of novel systemic therapies with survival trends in metastatic breast cancer (MBC are limited. In the setting of de novo MBC, large registry analyses cite positive temporal trends in survival, but the extent to which advances in systemic therapy have contributed to these gains is not clear. Methods The City of Hope Cancer Registry was used to identify a consecutive series of patients with de novo MBC who received their first line of therapy between 1985 and 2004. Comprehensive clinicopathologic and treatment-related data were collected for each patient. Univariate analyses were conducted via Cox regression to identify factors associated with improved survival. Multivariate analysis was also conducted via Cox regression and the stepwise procedure was used to identify independent predictors of survival. Results A total of 324 patients with de novo MBC were identified. After application of exclusion criteria, including the sole presence of supraclavicular node metastasis, 274 patients were retained in the analysis. The treatment-related characteristics associated with improved survival included: use of endocrine therapy (hazard ratio [HR] 0.60, 95%CI 0.47-0.77; P Conclusions The overall survival of women with de novo metastatic breast cancer has improved over the past 20 years. However, the contribution of conventional cytotoxic agents to this improvement is minimal.

  6. A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Spinelli Gian

    2006-05-01

    Full Text Available Abstract Background Many emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines. Methods A phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines. Results Twenty-five patients received paclitaxel (150 mg/mq by 3-hours infusion, followed by gemcitabine (2000 mg/mq given as a 60 min i.v. infusion (day 1–14 for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16% achieved a complete response, 12 (48% a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20% and progressive disease occurred in 4 patients (16%. Conclusion The schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines.

  7. Focal adhesion kinase inhibitors in the treatment of metastatic cancer: a patent review.

    Science.gov (United States)

    Shanthi, Ekambaram; Krishna, Mudeenahally H; Arunesh, Gubbi M; Venkateswara Reddy, K; Sooriya Kumar, Jegatheesan; Viswanadhan, Vellarkad N

    2014-10-01

    Focal adhesion kinase (FAK) plays a prominent role in integrin signaling. FAK activation increases phosphorylation of Tyr397 and other sites of the protein. FAK-dependent activation of signaling pathways implicated in controlling essential cellular functions including growth, proliferation, survival and migration. FERM (F for the 4.1 protein, ezrin, radixin and moesin) domain-enhanced p53 degradation plays a critical role in proliferation and survival. FAK, overexpressed in metastatic tumors, has emerged as an important therapeutic target for the development of selective inhibitors. FAK inhibitors achieved tumor growth inhibition and induced apoptosis. Strategies targeting FAK inhibition using novel compounds have created an exciting opportunity for anticancer therapy. This review summarizes the current research with available data from early phase clinical trials and discusses the available small-molecule inhibitors of FAK from patents. The importance of inhibiting FAK activity in cancer patients is discussed. Emerging data from clinical trials with orally available small-molecule inhibitors of FAK are promising. Although this approach is appropriate as a targeted therapeutic approach against several metastatic cancer types, several compounds in research are yet to prove their preclinical efficacy. This report lays special emphasis on the available patent data of FAK inhibitors for such targeted molecular therapies. This review summarizes current knowledge about FAK inhibition in cancer therapy.

  8. Potentially resectable metastatic colorectal cancer: an individualized approach to conversion therapy.

    Science.gov (United States)

    Marino, Donatella; Leone, Francesco; D'Avanzo, Francesca; Ribero, Dario; Capussotti, Lorenzo; Aglietta, Massimo

    2014-12-01

    Colorectal cancer is one of the most common cancers worldwide. In recent years, the survival of patients with metastatic disease has improved due to the developments in both medical and surgical care. Patients with technically unresectable metastatic disease could benefit from a multidisciplinary approach for their possible shift toward a technically resectable condition; the choice of the most effective systemic treatment is then crucial to allow conversion to resectability. Systemic conversion therapy may include chemotherapy agents' combinations (fluoropyrimidine, irinotecan and oxaliplatin), with or without targeted agents (cetuximab, panitumumab, bevacizumab). The choice of the best treatment option has to be evaluated by taking into account each patient's baseline characteristics, biological and pathological information and surgical strategy. In particular, the role of some biologic characteristics of the disease, namely the mutational status of EGFR-pathway oncogenes, is emerging as an important predictive factor of response to anti-EGFR targeted agents. Patients presenting with colorectal cancer metastases should be evaluated for multimodal management with curative intent as the appropriate chemotherapy regimen may induce tumor shrinkage, conversion to resectability and improved survival. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Palbociclib for the Treatment of Estrogen Receptor–Positive, HER2-Negative Metastatic Breast Cancer

    Science.gov (United States)

    Morikawa, Aki; Henry, N. Lynn

    2015-01-01

    Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 that acts by reducing phosphorylation of the tumor suppressor gene Retinoblastoma. When added to the aromatase inhibitor letrozole in a randomized phase II trial for first-line therapy of estrogen receptor-positive, HER2-negative metastatic breast cancer, palbociclib significantly increased progression-free survival compared to letrozole alone (palbociclib + letrozole: 20.2 months (95% CI 13.8-27.5), letrozole:10.2 months (95% CI 5.7-12.6); hazard ratio 0.49 (95% CI 0.32-0.75), p=0.0004). Based on these results the drug was recently granted accelerated approval by the FDA, and confirmatory studies are ongoing. Since this drug has a rational target in an oncologic pathway, concurrent biomarker development is of interest. In breast cancer, the most useful predictive biomarkers identified thus far are estrogen receptor and HER2 receptor status, although additional studies are ongoing. In this article, we review the development of palbociclib and its use in treatment of hormone receptor-positive metastatic breast cancer in the context of other FDA-approved agents in this setting. PMID:26100274

  10. Reliability of KRAS mutation testing in metastatic colorectal cancer patients across five laboratories

    Directory of Open Access Journals (Sweden)

    Feigelson Heather

    2012-04-01

    Full Text Available Abstract Background Mutations in the KRAS gene are associated with poor response to epidermal growth factor receptor inhibitors used in the treatment of metastatic colorectal cancer. Factors influencing KRAS test results in tumor specimens include: tumor heterogeneity, sample handling, slide preparation, techniques for tumor enrichment, DNA preparation, assay design and sensitivity. We evaluated comparability and consistency of KRAS test results among five laboratories currently being used to determine KRAS mutation status of metastatic colorectal cancer specimens in a large, multi-center observational study. Findings Twenty formalin-fixed paraffin-embedded human colorectal cancer samples from colon resections previously tested for KRAS mutations were selected based on mutation status (6 wild type, 8 codon 12 mutations, and 6 codon 13 mutations. We found good agreement across laboratories despite differences in mutation detection methods. Eighteen of twenty samples (90% were concordant across all five labs. Discordant results are likely not due to laboratory error, but instead to tumor heterogeneity, contamination of the tumor sample with normal tissue, or analytic factors affecting assay sensitivity. Conclusions Our results indicate commercial and academic laboratories provide reliable results for the common KRAS gene mutations at codons 12 and 13 when an adequate percentage of tumor cells is present in the sample.

  11. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Turner, Natalie [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Pestrin, Marta [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Galardi, Francesca; De Luca, Francesca [Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Malorni, Luca [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Di Leo, Angelo, E-mail: adileo@usl4.toscana.it [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy)

    2014-03-25

    Circulating tumor cell (CTC) count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

  12. Evaluation of KRAS Gene Mutations in Metastatic Colorectal Cancer Patients in Kermanshah Province.

    Science.gov (United States)

    Amirifard, Nasrin; Sadeghi, Edris; Farshchian, Negin; Haghparast, Abbas; Choubsaz, Mansour

    2016-01-01

    Worldwide, colorectal cancer (CRC) is reported to be the fourth most common cancer in men and the third most common in women. KRAS is a protooncogene located on the short arm of chromosome 12. The aim of this study was to evaluate the KRAS oncogene and its relationship it with clinicopathologic features in 33 Kurdish patients. Metastatic CRC between 2012 and 2016 that came to Imam Reza hospital, Kermanshah province, Iran, were analysed for KRAS mutations using allele specific PCR primers and pyrosequencing. Correlations between variables was analyzed in PASW SPSS and overall survival curves were plotted in Graph Pad prism 5. The mean age for them at diagnosis was 51.5±12.6 years (range, 2276 years). Among the 33 patients that were sequenced, 12 samples in the KRAS gene had a nucleotide change, 11 in codon 12 and 1 in codon 13.There was no significant relationship between the mutation and clinical and pathological aspects of the disease. Knowledge of the KRAS status can help in decisionmaking to treat metastatic colorectal cancer patients more efficiently and increase survival. However, many Kurdish people due to economic problems are not able to do this valuable genetic test. In addition, we need more careful research of KRAS oncogene at the molecular level in young populations with more patients.

  13. Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging

    Science.gov (United States)

    Zhang, Jialing; Feider, Clara L.; Nagi, Chandandeep; Yu, Wendong; Carter, Stacey A.; Suliburk, James; Cao, Hop S. Tran; Eberlin, Livia S.

    2017-06-01

    Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed. [Figure not available: see fulltext.

  14. Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    Bisgin Atil

    2012-02-01

    Full Text Available Abstract Background Colorectal cancer is the third most common cancer and the third leading cause of cancer-related death. Bevacizumab is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF for the treatment of metastatic cancer. The parameters of RECIST (Response Evaluation Criteria for Solid Tumors are not adequate to detect important treatment effects and response. Our goal was to evaluate the possibility of using sTRAIL (serum-soluble TNF-related apoptosis-inducing ligand and VEGF as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. Methods sTRAIL and VEGF levels were measured by ELISA in the sera of 16 bevacizumab-treated metastatic colon cancer patients and 10 presumably healthy age-matched controls. The measurements were taken before and after treatment for comparison purposes. Results Elevated levels of sTRAIL were found in seven out of 16 patients after bevacizumab treatment. Although these patients had a median survival time of 20.6 months, the remaining bevacizumab-treated patients who did not show an increase in sTRAIL had a median survival time of 9.4 months. As expected, serum VEGF levels were decreased in all patients who received bevacizumab therapy and showed no correlation between serum VEGF levels and patient survival (data not shown. Conclusions Serum sTRAIL levels might be a useful predictor of prognosis in metastatic colon cancer, in the early evaluation stages following bevacizumab treatment.

  15. Risk factors for brain metastases in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Troels Dreier; Palshof, Jesper Andreas; Larsen, Finn Ole

    2017-01-01

    Background: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict...... patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue. Results: Totally...

  16. The impending financial healthcare burden and ethical dilemma of systemic therapy in metastatic cancer.

    Science.gov (United States)

    Riaz, Muhammad Kashif; Bal, Susan; Wise-Draper, Trisha

    2016-09-01

    Metastatic cancer remains a devastating disease that threatens to disrupt entire family structures creating economic and psychosocial stress. Fortunately, great strides have resulted in improved therapies over the years but at a huge social-economic cost. The economic burden has risen greatly and carries with it new ethical concerns when deciding treatment. Here, we discuss the financial and ethical challenges that oncologists and their patients face in the era of novel treatment strategies. J. Surg. Oncol. 2016;114:323-328. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Array Based Sensing of Normal, Cancerous and Metastatic Cells using Conjugated Fluorescent Polymers

    Science.gov (United States)

    Bajaj, Avinash; Miranda, Oscar R.; Phillips, Ronnie; Kim, Ik-Bum; Jerry, D. Joseph; Bunz, Uwe H. F.; Rotello, Vincent M.

    2010-01-01

    A family of conjugated fluorescent polymers was used to create an array for cell sensing. Fluorescent conjugated polymers with pendant charged residues provided multivalent interactions with cell membranes, allowing the detection of subtle differences between different cell types on the basis of cell surface characteristics. Highly reproducible characteristic patterns were obtained from different cell types as well as from isogenic cell lines, enabling the identification of cell type as well differentiating between normal, cancerous and metastatic isogenic cell types with high accuracy. PMID:20039629

  18. Metastatic adenocarcinoma in a thyroid colloid nodule: a rare presentation of colon cancer.

    Science.gov (United States)

    Osin, P; Shiloni, E; Pikarsky, A J; Okon, E

    1996-08-01

    Colorectal cancer can remain asymptomatic for years. Frequently symptoms develop insidiously and may often remain unnoticed for long periods, even in the presence of disseminated disease. We herein report an unusual case of a patient with carcinoma of the sigmoid colon and multiple liver metastases. The diagnosis was established only after the patient was operated on for a large colloid nodule, a single microscopic metastatic focus being noticed in the histologic sections. The differential diagnosis compared with the columnar type of papillary carcinoma is discussed.

  19. Rapid Translation of a Novel and Potent Vaccine in HER2+ Metastatic Breast Cancer Patients

    Science.gov (United States)

    2013-10-01

    1113:202-216. 17. Modi S, Stopeck A, Linden H, Solit D, Chandarlapaty S, Rosen N, D’Andrea G, Dickler M, Moynahan ME, Sugarman S, Ma W, Patil S, Norton...Integrated Discovery ( DAVID ) by using standard methods (22). MicroRNA (miRNA) arrays were processed from TRI-Reagent cellular extracts as previously...metastatic cancer 1. J Immunol 2004;173:2143–50. 22. Huang dW, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, et al. DAVID bioinformatics resources: expanded

  20. Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer

    DEFF Research Database (Denmark)

    de Lichtenberg, Trine Honnens; Hermann, Gregers G.; Rorth, Mikael

    2014-01-01

    , stage, performance status and white cell blood count were related to poor OS. Using multivariate analyses to adjust for risk predictors the difference in OS disappeared. Median OS before and after introduction of TKIs was 16 months and 14 months, respectively (p = 0.189). Memorial Sloan Kettering Cancer......Abstract Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and forty...

  1. The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential

    Directory of Open Access Journals (Sweden)

    Kun-Chun Chiang

    2016-04-01

    Full Text Available Regarding breast cancer treatment, triple negative breast cancer (TNBC is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl-1α,25(OH2D3, the newly-synthesized 1α,25(OH2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH2D3 induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH2D3 and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9 activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH2D3 and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC.

  2. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

    LENUS (Irish Health Repository)

    Cronin, Patricia A

    2010-05-21

    Abstract Background Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α. Methods Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability. Results CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness. Conclusions CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.

  3. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

    Directory of Open Access Journals (Sweden)

    Redmond H Paul

    2010-05-01

    Full Text Available Abstract Background Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α. Methods Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability. Results CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness. Conclusions CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.

  4. Adverse psychosocial consequences: Compassion fatigue, burnout and vicarious traumatization: Are nurses who provide palliative and hematological cancer care vulnerable?

    Directory of Open Access Journals (Sweden)

    Brenda M Sabo

    2008-01-01

    Full Text Available The work environment significantly affects the physical, psychological, emotional and/or spiritual wellbeing of individuals is unquestionable. Adverse effects have been noted among healthcare professionals working with clients experiencing pain and suffering often associated with cancer, palliative or end-of-life care; however, little is known about how or in which manner the nurse-patient-family relationship may affect the psychosocial health and wellbeing of nurses working in these areas. Three concepts have been highlighted as most frequently associated with the adverse consequences of caring work: these are compassion fatigue (secondary traumatic stress, burnout and vicarious traumatization. The following discussion investigates these concepts and their implications on palliative and hematological cancer nursing practice.

  5. Alpha emitter radium-223 and survival in metastatic prostate cancer.

    Science.gov (United States)

    Parker, C; Nilsson, S; Heinrich, D; Helle, S I; O'Sullivan, J M; Fosså, S D; Chodacki, A; Wiechno, P; Logue, J; Seke, M; Widmark, A; Johannessen, D C; Hoskin, P; Bottomley, D; James, N D; Solberg, A; Syndikus, I; Kliment, J; Wedel, S; Boehmer, S; Dall'Oglio, M; Franzén, L; Coleman, R; Vogelzang, N J; O'Bryan-Tear, C G; Staudacher, K; Garcia-Vargas, J; Shan, M; Bruland, Ø S; Sartor, O

    2013-07-18

    Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; Pradium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).

  6. Cell-Penetrating Peptide-Modified Gold Nanoparticles for the Delivery of Doxorubicin to Brain Metastatic Breast Cancer.

    Science.gov (United States)

    Morshed, Ramin A; Muroski, Megan E; Dai, Qing; Wegscheid, Michelle L; Auffinger, Brenda; Yu, Dou; Han, Yu; Zhang, Lingjiao; Wu, Meijing; Cheng, Yu; Lesniak, Maciej S

    2016-06-06

    As therapies continue to increase the lifespan of patients with breast cancer, the incidence of brain metastases has steadily increased, affecting a significant number of patients with metastatic disease. However, a major barrier toward treating these lesions is the inability of therapeutics to penetrate into the central nervous system and accumulate within intracranial tumor sites. In this study, we designed a cell-penetrating gold nanoparticle platform to increase drug delivery to brain metastatic breast cancer cells. TAT peptide-modified gold nanoparticles carrying doxorubicin led to improved cytotoxicity toward two brain metastatic breast cancer cell lines with a decrease in the IC50 of at least 80% compared to free drug. Intravenous administration of these particles led to extensive accumulation of particles throughout diffuse intracranial metastatic microsatellites with cleaved caspase-3 activity corresponding to tumor foci. Furthermore, intratumoral administration of these particles improved survival in an intracranial MDA-MB-231-Br xenograft mouse model. Our results demonstrate the promising application of gold nanoparticles for improving drug delivery in the context of brain metastatic breast cancer.

  7. Up-regulation of the oligosaccharide sialyl LewisX: a new prognostic parameter in metastatic prostate cancer.

    Science.gov (United States)

    Jørgensen, T; Berner, A; Kaalhus, O; Tveter, K J; Danielsen, H E; Bryne, M

    1995-05-01

    Metastatic prostate cancer has an unpredictable long-term prognosis. At present, there are few specific predictors to indicate the outcome for the individual patient. We have studied immunoreactivity for type-2 carbohydrate structures, known to be involved in various cell adhesion processes, in patients with metastatic prostate cancer. One group of patients (n = 26) did not progress within 3 years after orchiectomy, while another group of patients (n = 33) progressed within 1 year following castration and survived less than 2 years. Among the parameters studied, sialyl LewisX carbohydrate up-regulation was the only variable showing significant association with poor prognosis (P < 0.01). Sialyl LewisX discriminated between these two outcome groups with 71% predictability and 96% specificity. Our results indicate that up-regulation of sialyl LewisX is associated with hormonal-resistant, aggressive disease. This prognostic marker may, therefore, have an important role in selecting proper treatment for patients with metastatic prostate cancer.

  8. [Principles, modalities and indications of the administration of Radium in cancers, focus on metastatic prostate cancer: State of arts].

    Science.gov (United States)

    Bertolaso, Pauline; Leroy, Laura; Gross-Goupil, Marine; Aupee, Olivier; Ravaud, Alain; Roubaud, Guilhem; Cazeau, Anne-Laure; Le Moulec, Sylvestre

    2017-09-01

    Prostate cancer is the first cancer in men and has a specific tropism to bones. This tropism provided the rationale to develop bone targeting radiopharmaceutical agents, such as strontium, samarium and more recently the Radium-223, an alpha-emitter. In a phase III trial, ALSYMPCA, Radium-223 not only improved pain relief, but also impacted on overall survival. Despite an approval by both FDA and EMA, prescription of this agent remains limited by the lack of refund, especially in France. Radium-223 is currently evaluated in several clinical trials (combination with chemotherapy, radiotherapy or hormone therapy) in order to optimize the therapeutic sequences in metastatic bone prostate cancer and argues for being incorporated into the current therapeutic arsenal. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  9. Activating ESR1 mutations in hormone-resistant metastatic breast cancer.

    Science.gov (United States)

    Robinson, Dan R; Wu, Yi-Mi; Vats, Pankaj; Su, Fengyun; Lonigro, Robert J; Cao, Xuhong; Kalyana-Sundaram, Shanker; Wang, Rui; Ning, Yu; Hodges, Lynda; Gursky, Amy; Siddiqui, Javed; Tomlins, Scott A; Roychowdhury, Sameek; Pienta, Kenneth J; Kim, Scott Y; Roberts, J Scott; Rae, James M; Van Poznak, Catherine H; Hayes, Daniel F; Chugh, Rashmi; Kunju, Lakshmi P; Talpaz, Moshe; Schott, Anne F; Chinnaiyan, Arul M

    2013-12-01

    Breast cancer is the most prevalent cancer in women, and over two-thirds of cases express estrogen receptor-α (ER-α, encoded by ESR1). Through a prospective clinical sequencing program for advanced cancers, we enrolled 11 patients with ER-positive metastatic breast cancer. Whole-exome and transcriptome analysis showed that six cases harbored mutations of ESR1 affecting its ligand-binding domain (LBD), all of whom had been treated with anti-estrogens and estrogen deprivation therapies. A survey of The Cancer Genome Atlas (TCGA) identified four endometrial cancers with similar mutations of ESR1. The five new LBD-localized ESR1 mutations identified here (encoding p.Leu536Gln, p.Tyr537Ser, p.Tyr537Cys, p.Tyr537Asn and p.Asp538Gly) were shown to result in constitutive activity and continued responsiveness to anti-estrogen therapies in vitro. Taken together, these studies suggest that activating mutations in ESR1 are a key mechanism in acquired endocrine resistance in breast cancer therapy.

  10. Exon-level transcriptome profiling in murine breast cancer reveals splicing changes specific to tumors with different metastatic abilities.

    Directory of Open Access Journals (Sweden)

    Amandine Bemmo

    2010-08-01

    Full Text Available Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases.To identify alternative splicing events (ASEs that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07 and highly metastatic (4T1 mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4% exons and in 1725 out of 189,460 (1% intronic regions, which affect 2623 out of 16,654 (16% genes. These changes correspond to putative alternative isoforms-several of which are novel-that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1. These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers.Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of metastasis-specific isoforms may contribute to the

  11. [Standards, Options and Recommendations (SOR) for endocrine therapy in patients with non metastatic breast cancer. FNCLCC].

    Science.gov (United States)

    Mauriac, L; Blanc-Vincent, M P; Luporsi, E; Cutuli, B; Fourquet, A; Garbay, J R; Giard, S; Spyratos, F; Zafrani, B; Dilhuydy, J M

    2000-06-01

    The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for endocrine therapy in patients with non metastatic breast cancer. Data have been identified by literature search using Medline, Embase, Cancerlit and Cochrane databases - until july 1999 - and the personal reference lists of the expert group. Once the guidelines were defined, the document was submitted for review to 125 independent reviewers. The main recommendations for the endocrine therapy of patients with non metastatic breast cancer are: 1) Endocrine therapy modalities depend on menopausal status or age of women: ovarian suppression for premenopausal women, antiestrogen drug therapy for postmenopausal women (standard). 2) Tamoxifen (20 mg/d - 5 years) is beneficial to women with positive estrogen receptor tumor (standard, level of evidence A). There is no indication of tamoxifen treatment for women with negative estrogen receptor tumor (standard, level of evidence A). 3) For postmenopausal women with positive estrogen receptor tumor, tamoxifen is the standard adjuvant treatment (level of evidence A). For postmenopausal women with negative estrogen receptor, adjuvant chemotherapy has to be considered (option, level of evidence A). No adjuvant treatment has to be considered for women with poor health condition (option). 4) For premenopausal women with estrogen receptor

  12. Actin cytoskeleton regulation of epithelial mesenchymal transition in metastatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Jay Shankar

    Full Text Available Epithelial-mesenchymal transition (EMT is associated with loss of the cell-cell adhesion molecule E-cadherin and disruption of cell-cell junctions as well as with acquisition of migratory properties including reorganization of the actin cytoskeleton and activation of the RhoA GTPase. Here we show that depolymerization of the actin cytoskeleton of various metastatic cancer cell lines with Cytochalasin D (Cyt D reduces cell size and F-actin levels and induces E-cadherin expression at both the protein and mRNA level. Induction of E-cadherin was dose dependent and paralleled loss of the mesenchymal markers N-cadherin and vimentin. E-cadherin levels increased 2 hours after addition of Cyt D in cells showing an E-cadherin mRNA response but only after 10-12 hours in HT-1080 fibrosarcoma and MDA-MB-231 cells in which E-cadherin mRNA level were only minimally affected by Cyt D. Cyt D treatment induced the nuclear-cytoplasmic translocation of EMT-associated SNAI 1 and SMAD1/2/3 transcription factors. In non-metastatic MCF-7 breast cancer cells, that express E-cadherin and represent a cancer cell model for EMT, actin depolymerization with Cyt D induced elevated E-cadherin while actin stabilization with Jasplakinolide reduced E-cadherin levels. Elevated E-cadherin levels due to Cyt D were associated with reduced activation of Rho A. Expression of dominant-negative Rho A mutant increased and dominant-active Rho A mutant decreased E-cadherin levels and also prevented Cyt D induction of E-cadherin. Reduced Rho A activation downstream of actin remodelling therefore induces E-cadherin and reverses EMT in cancer cells. Cyt D treatment inhibited migration and, at higher concentrations, induced cytotoxicity of both HT-1080 fibrosarcoma cells and normal Hs27 fibroblasts, but only induced mesenchymal-epithelial transition in HT-1080 cancer cells. Our studies suggest that actin remodelling is an upstream regulator of EMT in metastatic cancer cells.

  13. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

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    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  14. Prognostic factors in patients with metastatic (stage D2) prostate cancer: experience from the Scandinavian Prostatic Cancer Group Study-2.

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    Jørgensen, T; Kanagasingam, Y; Kaalhus, O; Tveter, K J; Bryne, M; Skjørten, F; Berner, A; Danielsen, H E

    1997-07-01

    Nuclear texture reflects the overall structures of the chromatin organization. We recently reported the principles and prognostic importance of image analysis of nuclei from metastatic prostate cancer. Immunohistochemical up regulation of the adhesion molecule sialyl Lewis(x) is also reported to be a prognostic parameter. Presently we analyzed statistically the prognostic impact of these 2 new parameters compared to well-known clinical parameters in metastatic prostate cancer. Prognostic factors, such as sedimentation rate, alkaline and acid phosphatases, hemoglobin, testosterone, performance status, pain due to metastasis, T category, histological grade and patient age, were included in a multivariate Cox proportional hazards regression analysis based on 262 patients from the Scandinavian Prostatic Cancer Group Study-2. Extent of bone lesions, deoxyribonucleic acid ploidy, texture analysis and sialyl Lewis(x) molecules based on subsets of these 262 patients were also analyzed in the same multivariate model. This test identified chromatin texture as the most important factor (p < 0.001), followed by reaction of the oligosaccharide sialyl Lewis(x) (p < 0.01). Among the routine clinical and laboratory data, sedimentation rate, alkaline phosphatase and hemoglobin (p < 0.05) showed prognostic importance. Performance status, pain due to metastasis and extent of bone lesions showed prognostic value in the univariate analysis (p < 0.05). These data indicate that computerized nuclear texture analysis as well as up regulation of sialyl Lewis(x) molecules may be new important prognostic factors in metastatic prostate cancer. Furthermore the prognostic importance of sedimentation rate, alkaline phosphatase and hemoglobin was confirmed.

  15. The Subclonal Architecture of Metastatic Breast Cancer: Results from a Prospective Community-Based Rapid Autopsy Program “CASCADE”

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    Flensburg, Christoffer; Alsop, Kathryn; Mansour, Mariam; Francis, Prudence A.; Thorne, Heather A.; Silva, Maria Joao; Kanu, Nnennaya; Dietzen, Michelle; Bowtell, David D.; Speed, Terence P.; Swanton, Charles; Loi, Sherene

    2016-01-01

    Background Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. However, evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Methods and Findings Three patients with oestrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program (CASCADE). Cases represented a range of management problems in breast cancer, including late relapse after early stage disease, de novo metastatic disease, discordant disease response, and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism (SNP) arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing. Between cases, there were significant differences in mutational burden, driver mutations, mutational processes, and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross-seeding was found in each case, and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We

  16. The Subclonal Architecture of Metastatic Breast Cancer: Results from a Prospective Community-Based Rapid Autopsy Program "CASCADE".

    Science.gov (United States)

    Savas, Peter; Teo, Zhi Ling; Lefevre, Christophe; Flensburg, Christoffer; Caramia, Franco; Alsop, Kathryn; Mansour, Mariam; Francis, Prudence A; Thorne, Heather A; Silva, Maria Joao; Kanu, Nnennaya; Dietzen, Michelle; Rowan, Andrew; Kschischo, Maik; Fox, Stephen; Bowtell, David D; Dawson, Sarah-Jane; Speed, Terence P; Swanton, Charles; Loi, Sherene

    2016-12-01

    Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. However, evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Three patients with oestrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program (CASCADE). Cases represented a range of management problems in breast cancer, including late relapse after early stage disease, de novo metastatic disease, discordant disease response, and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism (SNP) arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing. Between cases, there were significant differences in mutational burden, driver mutations, mutational processes, and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross-seeding was found in each case, and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We also observed the role of

  17. Leptin signals via TGFB1 to promote metastatic potential and stemness in breast cancer.

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    Ameet K Mishra

    Full Text Available Epidemiological studies have shown obesity to be linked with poorer outcomes in breast cancer patients. The molecular mechanisms responsible for the increased risk of invasive/metastatic disease with obesity are complex, but may include elevated levels of adipokines such as leptin. Using physiological levels of leptin found in obesity in a novel chronic in vitro treatment model (≤200 ng/ml for 14 days, we confirmed the occurrence of leptin-mediated changes in growth, apoptosis and metastatic behavior, and gene expression changes representing epithelial-to-mesenchymal transition (EMT and a cancer stem cell (CSC like phenotype in breast epithelial and cancer cell lines (MCF10A, MCF10AT1, MCF7 and MDA-MB-231. Further, we have discovered that these effects were accompanied by increased expression of TGFB1, and could be significantly reduced by co-treatment with neutralizing antibody against TGFB1, indicating that the induction of these characteristics was mediated via TGFB1. Occurring in both MCF7 and MCF10AT1 cells, it suggests these actions of leptin to be independent of estrogen receptor status. By linking leptin signalling to the established TGFB1 pathway of metastasis / EMT, this study gives a direct mechanism by which leptin can contribute to the poorer outcomes of obese cancer patients. Inhibitors of TGFB1 are in currently in phase III clinical trials in other malignancies, thus identifying the connection between leptin and TGFB1 will open new therapeutic opportunities for improving outcomes for obese breast cancer patients.

  18. Development of fragment-specific osteopontin antibodies and ELISA for quantification in human metastatic breast cancer

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    Miesfeldt Susan

    2008-01-01

    Full Text Available Abstract Background Osteopontin (OPN is associated with human cancers, and circulating blood OPN may have diagnostic or prognostic value in clinical oncology. Methods To evaluate OPN as a cancer biomarker, we generated and characterized five novel mouse monoclonal antibodies against the human full-length OPN (fl-OPN. Epitopes recognized by four antibodies (2C5, 2F10, 2H9, and 2E11 map to N-terminal OPN (aa1-166; one (1F11 maps to C-terminal OPN (aa167-314. These antibodies recognize recombinant and native OPN by ELISA and immunoblot, cross reacting with human and mouse OPN. Two of these novel antibodies (2F10 and 1F11 were used to develop a quantitative enzyme linked immunosorbent assay (ELISA for fl-OPN. Results In comparison with commercially available ELISAs, our assay had high accuracy in measuring fl-OPN standards, and high sensitivity. Specifically, our ELISA has a linear dose response between 0.078 ng/ml-10 ng/ml, with a sensitivity of 13.9 pg/ml. We utilized this assay to quantify fl-OPN in the plasma of healthy volunteers in comparison with patients with metastatic breast cancer. The average circulating plasma fl-OPN in healthy volunteers was 1.2 ng/ml, compared to 4.76 ng/ml in patients with metastatic breast cancer (p = 0.0042. Although the increase in fl-OPN in cancer patients is consistent with previous studies, the measured quantity varied greatly between all existing fl-OPN ELISAs. Conclusion Because OPN is a complex molecule with diversity from alternative splicing, post-translational modification, extracellular proteolytic modification, and participation in protein complexes, we suggest that further understanding of specific isoform recognition of multiple OPN species is essential for future studies of OPN biomarker utility.

  19. Effect of yoga on sleep quality and neuroendocrine immune response in metastatic breast cancer patients

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    Raghavendra Mohan Rao

    2017-01-01

    Full Text Available Background: Studies have shown that distress and accompanying neuroendocrine stress responses as important predictor of survival in advanced breast cancer patients. Some psychotherapeutic intervention studies have shown have modulation of neuroendocrine-immune responses in advanced breast cancer patients. In this study, we evaluate the effects of yoga on perceived stress, sleep, diurnal cortisol, and natural killer (NK cell counts in patients with metastatic cancer. Methods: In this study, 91 patients with metastatic breast cancer who satisfied selection criteria and consented to participate were recruited and randomized to receive “integrated yoga based stress reduction program” (n = 45 or standard “education and supportive therapy sessions” (n = 46 over a 3 month period. Psychometric assessments for sleep quality were done before and after intervention. Blood draws for NK cell counts were collected before and after the intervention. Saliva samples were collected for three consecutive days before and after intervention. Data were analyzed using the analysis of covariance on postmeasures using respective baseline measure as a covariate. Results: There was a significant decrease in scales of symptom distress (P < 0.001, sleep parameters (P = 0.02, and improvement in quality of sleep (P = 0.001 and Insomnia Rating Scale sleep score (P = 0.001 following intervention. There was a decrease in morning waking cortisol in yoga group (P = 0.003 alone following intervention. There was a significant improvement in NK cell percent (P = 0.03 following intervention in yoga group compared to control group. Conclusion: The results suggest modulation of neuroendocrine responses and improvement in sleep in patients with advanced breast cancer following yoga intervention.

  20. Influence of the location and number of metastases in the survival of metastatic prostatic cancer patients.

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    Guijarro, A; Hernández, V; de la Morena, J M; Jiménez-Valladolid, I; Pérez-Fernández, E; de la Peña, E; Llorente, C

    2017-05-01

    The prognosis of patients diagnosed with metastatic prostate cancer seems to be modulated by factors such as the number and site of metastases. Our objective is to evaluate survival outcomes according to the number and site of metastases in our series of metastatic patients over the last 15 years. A retrospective analysis was performed on patients diagnosed between 1998 and 2014. We analyzed overall survival and progression-free survival, depending on the number and location of metastases on patients with newly diagnosed metastatic prostate cancer. Other potential prognostic factors were also evaluated: age, clinical stage, PSA at diagnosis, Gleason, PSA nadir, time till PSA nadir and first-line or second-line treatment after progression. We analyzed a series of 162 patients. The mean age was 72.7yr (SD: 8.5). The estimated median overall survival was 3.9 yr (95% CI 2.6-5.2). The overall survival in patients with only lymph node metastases was 7 yr (95% CI 4.1-9.7), 3.9 (95%CI 2.3-5.5) in patients with only bone metastases, 2.5 yr (95% CI 2-2.3) in lymph nodes and bone metastases, and 2.2 yr (95% CI 1.4-3) in patients with visceral metastases (Pnumber of metastases showed no association with survival. The site of metastases has a clear impact on both overall survival and progression-free survival. Patients with only lymph node involvement had a better prognosis. The number of metastases showed no significant impact on survival in our series. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer.

    Science.gov (United States)

    Yaeger, Rona; Cowell, Elizabeth; Chou, Joanne F; Gewirtz, Alexandra N; Borsu, Laetitia; Vakiani, Efsevia; Solit, David B; Rosen, Neal; Capanu, Marinela; Ladanyi, Marc; Kemeny, Nancy

    2015-04-15

    RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site-specific metastasis. Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site-specific pattern of metastatic spread. The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site-specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. © 2014 American Cancer Society.

  2. A survey of treatments used in patients with metastatic melanoma: analysis of 189 patients referred to the National Cancer Institute.

    Science.gov (United States)

    Touloukian, C E; Rosenberg, S A

    1999-01-01

    Few effective treatments exist for patients with metastatic melanoma. The United States Food and Drug Administration has approved the use of interferon alfa-2b after the resection of locoregional disease, and dacarbazine or interleukin-2 for the treatment of patients with metastatic melanoma beyond the locoregional area, although many additional agents and combinations of agents are currently in use. Between January 1997 and June 1998, the Surgery Branch of the National Cancer Institute conducted a prospective analysis of 226 consecutive patients with metastatic melanoma referred for protocol evaluation. The previous systemic treatments these patients received both before and after the development of metastatic disease were tabulated, along with the association of these treatments with formal institutional protocols. Only the identity of the agents and not the dose or the schedule of treatments was considered in this analysis. Complete information could be obtained from 189 of the 226 patients. Of the 189 patients evaluated for this study, 135 (71%) received some form of systemic therapy before referral to the National Cancer Institute. Before the development of metastatic disease, 80 patients were administered 25 different systemic treatments, including 23 different agents. After the development of metastatic disease, 53 patients were administered 57 different systemic and regional treatments, including 37 different agents. After the resection of all metastatic sites, 23 patients were administered nine different systemic adjuvant treatments. Overall, 78 different systemic treatments were administered to these patients. The majority of treatments in each group were not associated with formal institutional protocols. This study has demonstrated that a large number of agents and different combinations of agents are currently being administered to patients before and after the development of metastatic melanoma, and frequently not within the context of an approved

  3. Expression of mucin 1 possessing a 3'-sulfated core1 in recurrent and metastatic breast cancer.

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    Ideo, Hiroko; Hinoda, Yuji; Sakai, Kohei; Hoshi, Ikue; Yamamoto, Shigeru; Oka, Masaaki; Maeda, Kazunari; Maeda, Noriko; Hazama, Shoichi; Amano, Junko; Yamashita, Katsuko

    2015-10-01

    Breast cancer is the most frequent cancer threatening the lives of women between the ages of 30 and 64. The cancer antigen 15-3 assay (CA15-3) has been widely used for the detection of breast cancer recurrence; however, its sensitivity and specificity are inadequate. We previously found that the breast cancer cell line YMBS secretes mucin 1 possessing 3'-sulfated core1 (3Score1-MUC1) into the medium. Therefore, we here evaluated whether 3Score1-MUC1 is secreted into the blood streams of breast cancer patients, and whether it can serve as an improved breast cancer marker. We developed a lectin-sandwich immunoassay, called Gal4/MUC1, using a 3'-sulfated core1-specific galectin-4 and a MUC1 monoclonal antibody. Using the Gal4/MUC1 assay method, we found that 3Score1-MUC1 was profoundly expressed in the blood streams of patients with recurrent and/or metastatic breast cancer. The positive ratio of the Gal4/MUC1 assay was higher than that of the CA15-3 assay in both primary (n = 240) and relapsed (n = 43) patients, especially in the latter of which the positive ratio of Gal4/MUC1 was 86%. whereas that of CA15-3 was 47%. Furthermore, serum Gal4/MUC1 levels could more sensitively reflect the recurrence of primary breast cancer patients after surgery. Therefore, the Gal4/MUC1 assay should be an excellent alternative to the CA15-3 tumor marker for tracking the recurrence and metastasis of breast cancer. © 2015 UICC.

  4. Impedimetric detection of mutant p53 biomarker-driven metastatic breast cancers under hyposmotic pressure.

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    Menglu Shi

    Full Text Available In cancer cells, the oncogenic mutant p53 (mtp53 protein is present at high levels and gain-of-function (GOF activities with more expression of mtp53 proteins contribute to tumor growth and metastasis. Robust analytical approaches that probe the degree of metastasis of cancer cells in connection with the mtp53 activity will be extremely useful not only for establishing a better cancer prognosis but also understanding the fundamental mechanism of mtp53 oncogenic action. Here we assessed the influence of mtp53 in breast cancers to the mechanical property of breast cancer cells. Recently, ovarian and kidney cancer cell lines have been shown to have higher cellular elasticity as compared to normal cells assessed by monitoring the degree of deformation under hyposmotic pressure. To make fast detection in large scale, the impedance measurement was applied to monitor the swelling ratio of cells with time. The results showed that knockdown of mtp53 leads to decrease in cell swelling. In addition, by means of two types of impedimetric detection systems we consistently detected enhancement of impedance signal in mtp53-expressing breast cancer cells. Based on this observation we hypothesize that highly expressed mtp53 in metastatic mutant breast cancers can promote tumor progression by making cells more deformable and easier to spread out through extracellular matrix. The identification via the electric measurement can be accomplished within 10 minutes. All results in this report suggest that electric probing for the extent of the mtp53 expression of breast cancer cells may serve as a meaningful fingerprint for the cancer diagnostics, and this outcome will also have an important clinical implication for the development of mtp53-based targeting for tumor detection and treatment.

  5. REPTILE HEMATOLOGY

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    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

  6. A case of metastatic carcinoma of anal fistula caused by implantation from rectal cancer.

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    Takahashi, Rina; Ichikawa, Ryosuke; Ito, Singo; Mizukoshi, Kosuke; Ishiyama, Shun; Sgimoto, Kiichi; Kojima, Yutaka; Goto, Michitoshi; Tomiki, Yuichi; Yao, Takashi; Sakamoto, Kazuhiro

    2015-12-01

    This case involved an 80-year-old man who was seen for melena. Further testing revealed a tubular adenocarcinoma 50 mm in size in the rectum. In addition, an anal fistula was noted behind the anus along with induration. A biopsy of tissue from the external (secondary) opening of the fistula also revealed adenocarcinoma. Nodules suspected of being metastases were noted in both lung fields. The patient was diagnosed with rectal cancer, a cancer arising from an anal fistula, and a metastatic pulmonary tumor, and neoadjuvant chemotherapy was begun. A laparoscopic abdominoperineal resection was performed 34 days after 6 cycles of mFOLFOX-6 therapy. Based on pathology, the rectal cancer was diagnosed as moderately differentiated adenocarcinoma, and this adenocarcinoma had lymph node metastasis (yp T3N2aM1b). There was no communication between the rectal lesion and the anal fistula, and a moderately differentiated tubular adenocarcinoma resembling the rectal lesion was noted in the anal fistula. Immunohistochemical staining indicated that both the rectal lesion and anal fistula were cytokeratin 7 (CK7) (-) and cytokeratin 20 (CK20) (+), and the patient's condition was diagnosed as implantation of rectal cancer in an anal fistula.In instances where an anal fistula develops in colon cancer, cancer implantation in that fistula must also be taken into account, and further testing should be performed prior to surgery.

  7. Effects of aspirin on small-cell lung cancer mortality and metastatic presentation.

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    Maddison, Paul

    2017-04-01

    Although meta-analysis data have shown that taking regular aspirin may reduce lung cancer mortality, individual trial data results are conflicting, and the data on the effects of aspirin on different histological subtypes of lung tumours, in particular small-cell lung cancer, are sparse. We conducted a prospective observational study of 313 patients with a new diagnosis of small-cell lung cancer and recorded use of aspirin before and after tumour diagnosis. Seventy-one (23%) patients were taking regular daily aspirin for more than 2 years at the time of tumour diagnosis. We found that regular use of aspirin had no effect on survival nor metastatic presentation compared to data from small-cell lung cancer patients not taking aspirin. The lack of survival benefit in patients with small-cell lung cancer taking long-term aspirin may be due to the low expression of cyclooxygenase-2 in small-cell lung cancer tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Novel Therapeutic Strategies for Metastatic Prostate Cancer in the Post-Docetaxel Setting

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    Sartor, Oliver; Michels, Ross M.; Massard, Christophe

    2011-01-01

    Prostate cancer is the most common noncutaneous cancer and the second leading cause of death from cancer in men in most western countries. Advanced prostate cancer is typically sensitive to androgen-deprivation therapy, but invariably progresses to the castration-resistant state. Most current prostate cancer treatments are based on cytotoxicity directed against tumor cells via androgen-deprivation therapy or chemotherapy. Chemotherapy with docetaxel represents the standard first-line treatment in patients with castration-resistant prostate cancer (CRPC). Following progression after treatment with docetaxel, cabazitaxel (XRP6258)–prednisone treatment leads to a significantly longer overall survival (OS) time than with mitoxantrone–prednisone. Several other novel agents are currently being evaluated, including sipuleucel-T, abiraterone acetate, and MDV3100, as well as the radionuclide alpharadin. The cell-based immunotherapy sipuleucel-T produces longer OS times in chemotherapy-naïve patients, whereas the androgen biosynthesis inhibitor abiraterone acetate results in longer OS times following docetaxel. It is envisioned that these agents will change the standard of care for patients with metastatic CRPC. This review focuses on the clinical development of cabazitaxel and abiraterone acetate. PMID:22048000

  9. Docetaxel monotherapy in heavily pretreated metastatic breast cancer: a multicenter, community-based feasibility trial.

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    Schmidinger, M; Budinsky, A C; Wenzel, C; Locker, G J; Pluschnig, U; Brodowicz, T; Kubista, E; Maca, S; Zabernigg, A; Ilsinger, P; Seewann, L; Hojas, S; Blach, M; Zielinski, C C; Steger, G G

    2001-01-01

    To evaluate the efficacy and safety of docetaxel in heavily pretreated and anthracycline-resistant patients with metastatic breast cancer in an outpatient setting. Between February 1996 and June 1998, 98 consecutive patients who had progressed during or relapsed following prior anthracycline-containing chemotherapy were enrolled into the trial. Docetaxel was administered at a dose of 100 mg/m2 by intravenous infusion every 3 weeks. The administration of colony-stimulating factors was at the discretion of the attending physician. Premedication with dexamethasone was mandatory for all patients. Of the 98 patients, 93 were evaluable for toxicity and response. Patients had received two palliative regimens (median, range 1-5) prior to docetaxel treatment. The most frequent toxicity observed was leukopenia grade III and IV (WHO grading system) which occurred in 47% of patients (grade IV only in 14%). Except for alopecia grade III (64% of patients), nonhematologic side effects grade III-IV were rare (1-7% of patients) and included nausea, stomatitis, diarrhea, peripheral neuropathy, fluid retention and pulmonary toxicities. There were no treatment-related deaths. Objective responses occurred in 40% of patients (CR 6%, PR 34%), and stable disease in 38% of patients. The median duration of response was 5.3 months (range 0.7-18.1 months) while the median survival was 15 months (range 2 36 months). Docetaxel is a highly active agent in patients with anthracycline-resistant metastatic breast cancer, even in heavily pretreated patients, with moderate toxicity.

  10. First-line capecitabine monotherapy for slowly progressing metastatic breast cancer: do we need aggressive treatment?

    Science.gov (United States)

    Debled, Marc; Madranges, Nicolas; Trainaud, Alexandra; Floquet, Anne; Donamaria, Catherine; Brouste, Véronique; Durand, Michel; Mauriac, Louis

    2009-01-01

    Primary treatment goals in less aggressive metastatic breast cancer (MBC) are prolonged survival, good quality of life and control of the disease and its symptoms. High activity, oral administration and no alopecia make capecitabine monotherapy attractive in slowly evolving disease. We retrospectively analysed 226 patients who had received single-agent capecitabine as 1st-line chemotherapy at our institution. The median interval between breast cancer diagnosis and MBC was 52 months (range 0-479); 76% had received endocrine therapy for MBC, 58% had visceral involvement and 30% had 3 or more metastatic sites. The median starting dose was 1,000 mg/m(2) twice daily. Disease was improved in 56% of the patients (median duration: 13.2 months) and stabilised in 20%. Median time to treatment failure was 8.8 months (95% CI: 7.1-10.5); median overall survival from initiating capecitabine was 23.6 months (95% CI: 19.7-27.4). Prior adjuvant chemotherapy, endocrine therapy for MBC, visceral disease, hormone receptor status and initial capecitabine dose did not influence time to treatment failure. Among 161 patients <75 years, 90% received further chemotherapy. Based on these findings, 1st-line capecitabine should be considered in slowly progressing disease, offering an active, well-tolerated oral treatment with minimal toxicity and no alopecia. More toxic treatments may be reserved for more aggressive disease. Copyright 2009 S. Karger AG, Basel.

  11. Functional TP53 mutations have no impact on response to cytotoxic agents in metastatic colon cancer.

    Science.gov (United States)

    Netter, Jeanne; Lehmann-Che, Jacqueline; Lambert, Jerome; Tallet, Anne; Lourenco, Nelson; Soliman, Hany; Bertheau, Philippe; Pariente, Benjamin; Chirica, Mircea; Pocard, Marc; Allez, Matthieu; De The, Hugues; Gornet, Jean-Marc

    2015-02-01

    Survival of metastatic colon cancer (mCC) patients has considerably improved with optimization of new drugs regimen. Inactivation of TP53 pathway by TP53 mutations is observed in nearly half of colorectal tumors. The impact of such mutations has been poorly studied in the metastatic setting. The files of 254 mCC treated in a single institution at Saint-Louis hospital between January 1999 and April 2011 were retrospectively reviewed. Tissue samples for analysis of TP53 mutations were available for 68 patients, performed using FASAY. The prognostic value of TP53 status was evaluated by comparing progression free survival (PFS) and overall survival (OS) in the group of TP53-mutated and wild type patients. PFS was 6.9 months and OS 21.7 months in the whole population. There was no statistical difference in TP53-mutated and wild type groups in term of PFS (HR=1.04; IC 95%=0.6-1.79) and OS (HR=0.99; IC 95%=0.53-1.55) whatever the chemotherapy regimen (oxaliplatin- or irinotecan-based). Only BRAF V600 mutation was demonstrated to be a poor prognostic factor for PFS and OS, and CEA level for OS. Routine determination of TP53 mutations, even with a highly sensitive method, cannot be recommended to predict chemotherapy response in mCC. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  12. Nutritional assessment in overweight and obese patients with metastatic cancer: does it make sense?

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    Gioulbasanis, I; Martin, L; Baracos, V E; Thézénas, S; Koinis, F; Senesse, P

    2015-01-01

    Obesity is causally related with tumor development, and thus, many cancer patients are overweight or obese at diagnosis. Whether these patients need regular nutritional assessment is not known. In the present study, we evaluated the utility of Mini Nutritional Assessment (MNA), a nutritional screening/assessment questionnaire, in overweight or obese patients with metastatic tumors. Overweight or obese patients referred for initiation of systemic therapy in three cancer centers were eligible. Basic demographics and clinical data were recorded. MNA was completed at baseline and patients were divided into three groups: A (well nourished), B (at risk), and C (malnourished). Survival data were subsequently collected. The prevalence of malnutrition and prognostic significance were evaluated. In total, 1469 patients with metastatic primaries were identified. Of them, 594 (41.9%) were overweight or obese and included in the analysis. According to MNA, almost 50% were at risk and around 12% were already malnourished at presentation. A significant difference in overall survival was found between groups [group A 17.8 (15.5-20.1) months, group B 8.2 (7.3-9.3) months, and group C 6.4 (3.2-9.6) months, P nutritional risk and this is moreover related with adverse prognosis. An MNA score could be used for the identification of this risk. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Consensus on precision medicine for metastatic cancers: a report from the MAP conference.

    Science.gov (United States)

    Swanton, C; Soria, J-C; Bardelli, A; Biankin, A; Caldas, C; Chandarlapaty, S; de Koning, L; Dive, C; Feunteun, J; Leung, S-Y; Marais, R; Mardis, E R; McGranahan, N; Middleton, G; Quezada, S A; Rodón, J; Rosenfeld, N; Sotiriou, C; André, F

    2016-08-01

    Recent advances in biotechnologies have led to the development of multiplex genomic and proteomic analyses for clinical use. Nevertheless, guidelines are currently lacking to determine which molecular assays should be implemented in metastatic cancers. The first MAP conference was dedicated to exploring the use of genomics to better select therapies in the treatment of metastatic cancers. Sixteen consensus items were covered. There was a consensus that new technologies like next-generation sequencing of tumors and ddPCR on circulating free DNA have convincing analytical validity. Further work needs to be undertaken to establish the clinical utility of liquid biopsies and the added clinical value of expanding from individual gene tests into large gene panels. Experts agreed that standardized bioinformatics methods for biological interpretation of genomic data are needed and that precision medicine trials should be stratified based on the level of evidence available for the genomic alterations identified. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer.

    Science.gov (United States)

    Kim, Esther S; Scott, Lesley J

    2017-06-01

    Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates. Neutropenia was the most commonly reported any-grade and grade ≥ 3 adverse event. It was infrequently associated with febrile neutropenia (palbociclib dose delay, interruption or reduction, without the routine use of growth factors, and without affecting efficacy. In conclusion, oral palbociclib combination therapy is a valuable emerging option for use in patients with HR-positive, HER2-negative advanced or metastatic breast cancer.

  15. Spirituality and quality of life in low-income men with metastatic prostate cancer.

    Science.gov (United States)

    Zavala, Mary Wassel; Maliski, Sally L; Kwan, Lorna; Fink, Arlene; Litwin, Mark S

    2009-07-01

    To determine how spirituality is associated with health-related quality of life (HRQOL) in an ethnically diverse cohort of low-income men with metastatic prostate cancer. Eighty-six participants in a state-funded program that provides free prostate cancer treatment to uninsured, low-income men completed written surveys and telephone interviews containing validated measures of spirituality, and general and disease-specific HRQOL. Assessments were made following diagnosis of metastatic disease. We used multivariate analyses to assess the effect of spirituality and its two subscales, faith and meaning/peace, on HRQOL. African American and Latino men, and men with less than a high-school education had the highest spirituality scores. Spirituality was significantly associated with general and disease-specific HRQOL. We also found a significant interaction between faith and meaning/peace in the physical and pain domains. Greater spirituality was associated with better HRQOL and psychosocial function. Meaning/peace closely tracks with HRQOL. Higher faith scores, in the absence of high meaning/peace scores, are negatively associated with HRQOL. (c) 2008 John Wiley & Sons, Ltd.

  16. Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab.

    Science.gov (United States)

    Yeo, B; Kotsori, K; Mohammed, K; Walsh, G; Smith, I E

    2015-12-01

    Trastuzumab has changed the natural history of metastatic HER2 positive breast cancer. Some patients remain well and in remission for many years. There is currently no established duration after which trastuzumab in the advanced setting can be safely discontinued. This study aims to evaluate long-term efficacy and cardiac safety of trastuzumab when used as first-line treatment for patients with metastatic HER2 positive breast cancer. We retrospectively identified 215 patients with HER2 positive, locally advanced or metastatic breast cancer who commenced first line trastuzumab-containing therapy for metastatic disease between 2001 and 2010 at The Royal Marsden Hospital. The median progression free survival for all patients was 12 months (95%CI: 10.3-14.6 months); 103 (48%) patients remained in remission beyond one year, 59 (27%) beyond two years and 25 (12%) beyond five years. The median overall survival was 2.6 years (95% confidence interval (CI): 2.2-3.3). The objective response rate (ORR) was 65% with 17 (8%) complete responses and 120 (57%) partial responses. Trastuzumab was well tolerated. Twenty eight (13%) patients recorded any grade of left ventricular dysfunction. There was no significant difference in cardiac toxicity between those patients on less than or more than one year of trastuzumab. Trastuzumab is associated with long-term remissions in a significant proportion of patients with metastatic HER2 positive disease when used in the first-line advanced setting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. A Phase I Study of Oral Lenalidomide in Patients with Refractory Metastatic Cancer

    Science.gov (United States)

    Dahut, William L.; Aragon-Ching, Jeanny B.; Woo, Sukyung; Tohnya, Tanyifor M.; Gulley, James L.; Arlen, Philip M.; Wright, John J.; Figg, William D.

    2009-01-01

    Objectives of this study were to determine the maximum tolerated dose and to characterize the side-effect profile and pharmacokinetics of lenalidomide in patients with advanced refractory solid tumors. Patients were treated on a modified Fibronacci dose-escalation scheme with an oral daily dose of lenalidomide. A total of 45 patients with 8 different tumor types were accrued. Doses administered included 5, 10, and 20 mg continuous daily doses, every 28 days (n=15); later modified to intermittent doses of 15, 20, 25, 30, 35, and 40 mg, 21 days-on and 7 days off schedule, due to observed side effects. Lenalidomide exhibited a linear pharmacokinetics over a wide range doses with the mean half-life of 3.9 hours. The renal function affected lenalidomide clearance, resulting in 50% reduction in patients with mild renal impairment compared wiht patients with normal function (CL/F = 257 mL/min). Stable disease was documented in 12 of 44 evaluable patients, of whom 9 patients had prostate cancer. Most frequent grade 1 and 2 toxicities included fatigue, nausea, pruritus/rash, neutropenia, and neuropathy. Grade 3/4 events were predominantly hematologic. Lenalidomide was well tolerated up to 35 mg/day intermittent dosing schedule at doses higher than previously indicated for hematologic malignancies. PMID:19451403

  18. Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Borch, Troels Holz; Ellebaek, Eva

    2017-01-01

    Background aims  We investigated whether the addition of an autologous dendritic cell–based cancer vaccine (DCvac) induces an immune response in patients with metastatic castration-resistant prostate cancer treated with docetaxel.  Methods  Forty-three patients were randomized 1:1 to receive up...... twice through treatment cycles 1–4 and once through treatment cycles 5–10. Immune cell composition and antigen-specific responses were analyzed using flow cytometry, ELISpot and delayed type hypersensitivity (DTH) tests. Toxicity was graded according to Common Terminology Criteria for Adverse Events...... to local reactions. Decline in myeloid-derived suppressor cells at the third treatment cycle was found to be an independent predictor of DSS.  Conclusions  The addition of DCvac was safe. Immune responses were detected in approximately half of the patients investigated....

  19. Irofulven, a novel inhibitor of DNA synthesis, in metastatic renal cell cancer.

    Science.gov (United States)

    Amato, Robert J; Perez, Cherie; Pagliaro, Lance

    2002-11-01

    Irofulven (6-Hydroxymethylacylfulvene, MGI-114) is the first of a new class of anticancer compounds the acylfulvenes which are derived from the natural product, illudin S. Irofulven is a potent anticancer agent with activity against a broad range of human tumors in vitro and in vivo. Irofulven covalently binds to DNA, inhibits DNA synthesis and induces apoptosis. Clinical activity has been observed in phase I studies. Because disease stabilizations were observed in kidney cancer patients in the phase I trials, we performed a phase II trial of irofulven in this patient population. Twenty patients were accrued. Irofulven (11 milligrams per meter squared per day) was administered as a 5 minute intravenous infusion for 5 consecutive days, and response was evaluated every 8 weeks. There were no objective responses. The most common toxicities were nausea, emesis, and thrombocytopenia. Irofulven, at the dose and schedule administered in this trial, showed no effect in metastatic renal cell cancer.

  20. Neurological Toxicity in Metastatic Colorectal Cancer Patients Treated with Modified FOLFOX6 plus Bevacizumab

    Directory of Open Access Journals (Sweden)

    Satoshi Otsu

    2014-01-01

    Full Text Available This study was conducted to investigate the toxicity and efficacy of modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer with particular regard to oxaliplatin-induced neuropathy. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE (version 3.0. The evaluation was especially focused on grade 2 oxaliplatin-induced neuropathy. The estimated median treatment time to occurrence of grade 2 sensory neuropathy was 7.3 months. The estimated median cumulative dose to occurrence of grade 2 sensory neuropathy was 931 mg/m 2 . This study clarified the treatment time from first dose as well as the cumulative dose of oxaliplatin leading to grade 2 neuropathy. It may be important to institute some clinical countermeasures when grade 2 neuropathy occurs so as to reduce the chance of progression to irreversible grade 3 neuropathy.