WorldWideScience

Sample records for early stage non-small

  1. Socioeconomic position and surgery for early-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Kærgaard Starr, Laila; Osler, Merete; Steding-Jessen, Marianne

    2013-01-01

    AIM: To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer...... in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer....... was associated with greater odds for no surgery in stage I and stage II patients as was living alone for stage I patients. Comorbidity, a short diagnostic interval and small diagnostic volume were all associated with higher odds for not undergoing surgery; but these factors did not appear to explain...

  2. SSX2-4 expression in early-stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E

    2014-01-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...... was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

  3. Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chien-Hung Huang

    2014-01-01

    Full Text Available Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

  4. Carbon Ion Therapy for Early-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yusuke Demizu

    2014-01-01

    Full Text Available Carbon ion therapy is a type of radiotherapies that can deliver high-dose radiation to a tumor while minimizing the dose delivered to the organs at risk; this profile differs from that of photon radiotherapy. Moreover, carbon ions are classified as high-linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. Recently, high-precision radiotherapy modalities such as stereotactic body radiotherapy (SBRT, proton therapy, and carbon ion therapy have been used for patients with early-stage non-small-cell lung cancer, and the results are promising, as, for carbon ion therapy, local control and overall survival rates at 5 years are 80–90% and 40–50%, respectively. Carbon ion therapy may be theoretically superior to SBRT and proton therapy, but the literature that is currently available does not show a statistically significant difference among these treatments. Carbon ion therapy demonstrates a better dose distribution than both SBRT and proton therapy in most cases of early-stage lung cancer. Therefore, carbon ion therapy may be safer for treating patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. Furthermore, carbon ion therapy may also be suitable for dose escalation and hypofractionation.

  5. Stereotactic radiotherapy for early stage non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ricardi, Umberto; Badellino, Serena; Filippi, Andrea Riccardo [Dept. of Oncology, Radiation Oncology, University of Torino, Torino (Italy)

    2015-06-15

    Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice.

  6. Methylation markers of early-stage non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Kaie Lokk

    Full Text Available BACKGROUND: Despite of intense research in early cancer detection, there is a lack of biomarkers for the reliable detection of malignant tumors, including non-small cell lung cancer (NSCLC. DNA methylation changes are common and relatively stable in various types of cancers, and may be used as diagnostic or prognostic biomarkers. METHODS: We performed DNA methylation profiling of samples from 48 patients with stage I NSCLC and 18 matching cancer-free lung samples using microarrays that cover the promoter regions of more than 14,500 genes. We correlated DNA methylation changes with gene expression levels and performed survival analysis. RESULTS: We observed hypermethylation of 496 CpGs in 379 genes and hypomethylation of 373 CpGs in 335 genes in NSCLC. Compared to adenocarcinoma samples, squamous cell carcinoma samples had 263 CpGs in 223 hypermethylated genes and 513 CpGs in 436 hypomethylated genes. 378 of 869 (43.5% CpG sites discriminating the NSCLC and control samples showed an inverse correlation between CpG site methylation and gene expression levels. As a result of a survival analysis, we found 10 CpGs in 10 genes, in which the methylation level differs in different survival groups. CONCLUSIONS: We have identified a set of genes with altered methylation in NSCLC and found that a minority of them showed an inverse correlation with gene expression levels. We also found a set of genes that associated with the survival of the patients. These newly-identified marker candidates for the molecular screening of NSCLC will need further analysis in order to determine their clinical utility.

  7. [Treatment of non-small cell lung carcinoma in early stages].

    Science.gov (United States)

    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA.

  8. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan Starup; Schytte, Tine; Jensen, Henrik R

    2013-01-01

    Abstract Introduction. Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single...... and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients....

  9. Telomere length of tumor tissues and survival in patients with early stage non-small cell lung cancer.

    Science.gov (United States)

    Jeon, Hyo-Sung; Choi, Yi Young; Choi, Jin Eun; Lee, Won Kee; Lee, Eungbae; Yoo, Seung Soo; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2014-04-01

    Telomere shortening leads to genomic instability that drives oncogenesis through the activation of telomerase and the generation of other mutations necessary for tumor progression. This study was conducted to determine the impact of telomere shortening on the survival of patients with early stage non-small cell lung cancer (NSCLC). Relative telomere length in tumor tissues was measured by quantitative polymerase chain reaction in 164 patients with surgically resected NSCLC. The association between telomere length and overall survival (OS) and disease-free survival (DFS) was analyzed. When the patients were categorized into quartiles based on telomere length, those patients with the 1st quartile (shortest) of telomere length had a significantly worse OS and DFS compared to patients with the 2nd to the 4th quartiles of telomere length (adjusted hazard ratio for OS = 2.67, 95% confidence interval = 1.50-4.75, P = 0.001; and adjusted hazard ratio for DFS = 1.92, 95% confidence interval = 1.17-3.14, P = 0.01). An association between telomere length and survival outcome was more pronounced in squamous cell carcinomas than adenocarcinomas (P-value of test for homogeneity for OS and DFS = 0.05 and 0.02, respectively). Telomere length of tumor tissues is an independent prognostic factor in patients with surgically resected early stage NSCLC.

  10. CLINICAL SIGNIFICANCE OF THE LYMPH NODE MICRO-METASTASIS IN PATEINTS WITH EARLY STAGE NON-SMALL-CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ The postoperative 5-year survival rate is about 50-85% in the patient with the stage I non-small-cell lung cancer (NSCLC). It is remains unclear how we should give these patients adjuvant radiotherapy and chemotherapy after operation. We performed a postspective study to assess the prognostic and treatment guiding significance of lymph nodes micrometastasis (LMM) in patients with completely resected NSCLC at stage I.

  11. Comparative effectiveness of 5 treatment strategies for early-stage non-small cell lung cancer in the elderly.

    Science.gov (United States)

    Shirvani, Shervin M; Jiang, Jing; Chang, Joe Y; Welsh, James W; Gomez, Daniel R; Swisher, Stephen; Buchholz, Thomas A; Smith, Benjamin D

    2012-12-01

    The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Treatment strategy and covariates were determined in 10,923 patients aged ≥ 66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations. Evaluation of these therapies in randomized trials

  12. Absence of toxicity with hypofractionated 3-dimensional radiation therapy for inoperable, early stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Vuong Te

    2006-11-01

    Full Text Available Abstract Purpose Hypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC treated with hypofractionation. Materials and methods Stage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients. Results Thirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade ≤ 2 acute pneumonitis and 3 had mild (grade 1 acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively. Conclusion 3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy.

  13. FGFR1, 2 and 3 protein overexpression and molecular aberrations of FGFR3 in early stage non-small cell lung cancer

    NARCIS (Netherlands)

    Theelen, Willemijn Sme; Mittempergher, Lorenza; Willems, Stefan M; Bosma, Astrid J; Peters, Dennis Dgc; van der Noort, Vincent; Japenga, Eva J; Peeters, Ton; Koole, Koos; Šuštić, Tonći; Blaauwgeers, J L; van Noesel, Carel J; Bernards, René; van den Heuvel, Michel M

    2016-01-01

    This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non-small cell lung cancer (NSCLC). Additionally, a screen to define the frequency of FGFR3-TACC3 translocation and FGFR3 amplification was performed. Archived tissues from

  14. Robotic stereotactic body radiation therapy for elderly medically inoperable early-stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Karam SD

    2013-08-01

    Full Text Available Sana D Karam,1 Zachary D Horne,1 Robert L Hong,1,2 Nimrah Baig,1 Gregory J Gagnon,4 Don McRae,2 David Duhamel,3 Nadim M Nasr1,21Department of Radiation Oncology, Georgetown University Hospital, Washington, DC, USA; 2Department of Radiation Oncology, Virginia Hospital Center, Arlington, VA, USA; 3Department of Pulmonary/Critical Care Medicine, Virginia Hospital Center, Arlington, VA, USA; 4Department of Radiation Oncology, Frederick Memorial Hospital, Frederick, MD, USAIntroduction: Stereotactic body radiation therapy (SBRT is being increasingly applied in the treatment of non-small cell lung cancer (NSCLC because of its high local efficacy. This study aims to examine survival outcomes in elderly patients with inoperable stage I NSCLC treated with SBRT.Methods: A total of 31 patients with single lesions treated with fractionated SBRT from 2008 to 2011 were retrospectively analyzed. A median prescribed dose of 48 Gy was delivered to the prescription isodose line, over a median of four treatments. The median biologically effective dose (BED was 105.6 (range 37.50–180, and the median age was 73 (65–90 years. No patient received concurrent chemotherapy.Results: With a median follow up of 13 months (range, 4–40 months, the actuarial median overall survival (OS and progression-free survival (PFS were 32 months, and 19 months, respectively. The actuarial median local control (LC time was not reached. The survival outcomes at median follow up of 13 months were 80%, 68%, and 70% for LC, PFS, and OS, respectively. Univariate analysis revealed a BED of >100 Gy was associated with improved LC rates (P = 0.02, while squamous cell histology predicted for worse LC outcome at median follow up time of 13 months (P = 0.04. Increased tumor volume was a worse prognostic indicator of both LC and OS outcomes (P < 0.05. Finally, female gender was a better prognostic factor for OS than male gender (P = 0.006. There were no prognostic indicators of PFS that reached

  15. Integrin expression profiling identifies integrin alpha5 and beta1 as prognostic factors in early stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    van Suylen Robert-Jan

    2010-06-01

    Full Text Available Abstract Background Selection of early stage non-small cell lung cancer patients with a high risk of recurrence is warranted in order to select patients who will benefit from adjuvant treatment strategies. We evaluated the prognostic value of integrin expression profiles in a retrospective study on frozen primary tumors of 68 patients with early stage non-small cell lung cancer. Methods A retrospective study was performed on frozen primary tumors of 68 early stage non-small cell lung cancer patients with a follow up of at least 10 years. From all tumor tissues, RNA was isolated and reverse transcribed into cDNA. qPCR was used to generate mRNA expression profiles including integrins alpha1, 2, 3, 4, 5, 6, 7, 11, and V as well as integrins beta1, 3, 4, 5, 6, and 8. Results The expression levels of integrins alpha5, beta1 and beta3 predicted overall survival and disease free survival in early stage NSCLC patients. There was no association between integrin expression and lymph node metastases. Comparison between the histological subtypes revealed a distinct integrin signature for squamous cell carcinoma while the profiles of adenocarcinoma and large cell carcinoma were largely the same. Conclusion Integrin expression in NSCLC is important for the development and behavior of the tumor and influences the survival of the patient. Determining the integrin expression profile might serve as a tool in predicting the prognosis of individual patients.

  16. Advances in Lymph Node Metastasis and the Modes of Lymph Node 
Dissection in Early Stage Non-small Cell Lung Caner

    Directory of Open Access Journals (Sweden)

    Ningning DING

    2016-06-01

    Full Text Available Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. Anatomical lobectomy with systematic mediastinal lymph node dissection have been the standard surgical treatment for NSCLC. However, it is controversial in the extent of lymph node dissection for early stage NSCLC. Accurate nodes stage and the extent of mediatinal nodes dissection affect the peri-operative complications and the prognosis of NSCLC greatly. In the past decade, more and more surgeons demostrated that lobe-specific or selective mediastinal lymph node dissection is suitable for clinical stage I NSCLC, especially the stage Ia lesions, and may become the standard lymph node dissection mode in the future.

  17. [Advances in Lymph Node Metastasis and the Modes of Lymph Node 
Dissection in Early Stage Non-small Cell Lung Caner].

    Science.gov (United States)

    Ding, Ningning; Mao, Yousheng

    2016-06-20

    Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC) accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. Anatomical lobectomy with systematic mediastinal lymph node dissection have been the standard surgical treatment for NSCLC. However, it is controversial in the extent of lymph node dissection for early stage NSCLC. Accurate nodes stage and the extent of mediatinal nodes dissection affect the peri-operative complications and the prognosis of NSCLC greatly. In the past decade, more and more surgeons demostrated that lobe-specific or selective mediastinal lymph node dissection is suitable for clinical stage I NSCLC, especially the stage Ia lesions, and may become the standard lymph node dissection mode in the future.

  18. Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non-small cell lung cancer.

    Science.gov (United States)

    Medairos, Robert A; Clark, James; Holoubek, Simon; Kubasiak, John C; Pithadia, Ravi; Hamid, Fatima; Chmielewski, Gary W; Warren, William H; Basu, Sanjib; Borgia, Jeffrey A; Liptay, Michael J; Seder, Christopher W

    2016-07-01

    There are little clinical data assessing the antineoplastic effect of metformin in patients with non-small cell lung cancer. We hypothesized that in diabetic patients undergoing pulmonary resection for early-stage non-small cell lung cancer, metformin exposure is associated with improved survival. An institutional database was used to identify patients with stage I or II non-small cell lung cancer who underwent pulmonary resection between 2004 and 2013. Patients were divided into 3 cohorts: type II diabetic patients with metformin exposure (cohort A, n = 81), type II diabetic patients without metformin exposure (cohort B, n = 57), and nondiabetic individuals (cohort C, n = 77). Univariate, multivariate, and propensity-matched analyses were performed to assess progression-free and overall survivals between groups. A total of 215 patients with stage I and II non-small cell lung cancer treated with surgical resection were identified for analysis with a median follow-up of 19.5 months. Patients in cohort A had lower T- and N-stage tumors than those in cohorts B or C. However, on multivariate analysis adjusting for age, gender, and T and N stage, progression-free survival was greater for cohort A than cohort B (hazard ratio [HR], 0.410; 95% confidence interval, 0.199-0.874; P = .022) or cohort C (HR, 0.415; 95% confidence interval, 0.201-0.887; P = .017). Likewise, when propensity-matched analyses were performed, cohort A demonstrated a trend toward improved progression-free survival compared with cohort B (P = .057; HR, 0.44; c-statistic = 0.832) and improved progression-free survival compared with cohort C (P = .02; HR, 0.41; c-statistic = 0.843). No differences were observed in overall survival. Metformin exposure in diabetic patients with early-stage non-small cell lung cancer may be associated with improved progression-free survival, but no effect was seen on overall survival. Further studies are warranted to evaluate if there is a therapeutic

  19. An Immune Response Enriched 72-Gene Prognostic Profile for Early-Stage Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Roepman, P.; Jassem, J; Smit, E.F.; Muley, T.; Niklinski, J.; Vel, van de T.; Witteveen, A.T.; Rzyman, W.; Floore, A.; Burgers, S.; Giaccone, G.; Meister, M.; Dienemann, H.; Skrzypski, M.; Kozlowski, M.; Mooi, W.J.; Zandwijk, van N.

    2009-01-01

    0.01; n = 69). Genes in our prognostic signature were strongly enriched for genes associated with immune response. Conclusions: Our 72-gene signature is closely associated with recurrence-free and overall survival in early-stage NSCLC patients and may become a tool for patient selection for adjuvant

  20. Myeloid clusters are associated with a pro-metastatic environment and poor prognosis in smoking-related early stage non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Wang Zhang

    Full Text Available BACKGROUND: This study aimed to understand the role of myeloid cell clusters in uninvolved regional lymph nodes from early stage non-small cell lung cancer patients. METHODS: Uninvolved regional lymph node sections from 67 patients with stage I-III resected non-small cell lung cancer were immunostained to detect myeloid clusters, STAT3 activity and occult metastasis. Anthracosis intensity, myeloid cluster infiltration associated with anthracosis and pSTAT3 level were scored and correlated with patient survival. Multivariate Cox regression analysis was performed with prognostic variables. Human macrophages were used for in vitro nicotine treatment. RESULTS: CD68+ myeloid clusters associated with anthracosis and with an immunosuppressive and metastasis-promoting phenotype and elevated overall STAT3 activity were observed in uninvolved lymph nodes. In patients with a smoking history, myeloid cluster score significantly correlated with anthracosis intensity and pSTAT3 level (P<0.01. Nicotine activated STAT3 in macrophages in long-term culture. CD68+ myeloid clusters correlated and colocalized with occult metastasis. Myeloid cluster score was an independent prognostic factor (P = 0.049 and was associated with survival by Kaplan-Maier estimate in patients with a history of smoking (P = 0.055. The combination of myeloid cluster score with either lymph node stage or pSTAT3 level defined two populations with a significant difference in survival (P = 0.024 and P = 0.004, respectively. CONCLUSIONS: Myeloid clusters facilitate a pro-metastatic microenvironment in uninvolved regional lymph nodes and associate with occult metastasis in early stage non-small cell lung cancer. Myeloid cluster score is an independent prognostic factor for survival in patients with a history of smoking, and may present a novel method to inform therapy choices in the adjuvant setting. Further validation studies are warranted.

  1. Genetic variants of the Wnt signaling pathway as predictors of recurrence and survival in early-stage non-small cell lung cancer patients.

    Science.gov (United States)

    Coscio, Angela; Chang, David W; Roth, Jack A; Ye, Yuanqing; Gu, Jian; Yang, Ping; Wu, Xifeng

    2014-06-01

    Early-stage non-small cell lung cancer (NSCLC) is potentially curative. Nevertheless, many patients will show disease recurrence after curative treatment. The Wnt signaling pathway is a developmental and stem cell pathway that plays an important role in tumorigenesis and may affect cancer progression. We hypothesize that genetic variants of the Wnt pathway may influence clinical outcome in early-stage NSCLC patients. We genotyped 441 functional and tagging single nucleotide polymorphisms (SNPs) from 54 genes of the Wnt pathway in 535 early-stage NSCLC patients treated with curative intent therapy including surgery and chemotherapy. For validation, 4 top SNPs were genotyped in 301 early-stage NSCLC patients from the Mayo Clinic. Cox proportional hazard model and combined SNP analyses were performed to identify significant SNPs correlated with recurrence-free and overall survival. Results from discovery group showed a total of 40 SNPs in 20 genes correlated with disease recurrence (P recurrence-free and overall survival. Joint SNP analyses identified predictive markers for recurrence stratified by treatment. Our findings suggest inherited genetic variation in the Wnt signaling pathway may contribute to variable clinical outcomes for patients with early-stage NSCLC. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Strategies of Individual Surgical Treatment for Early Stage Non-small Cell Lung Cancer and the Guidance of Intraoperative Frozen Pathology

    Directory of Open Access Journals (Sweden)

    Bin HU

    2016-06-01

    Full Text Available Early stage non-small cell lung cancer patients, especially those who presented small GGO on image, are increasing in Asia population. Retrospective clinical data indicated that the efficacy of sub-lobectomy for these patients may be non-inferior to that of lobectomy. Meanwhile, sub-lobectomy could preserve more pulmonary function for the patients. Researches have demonstrated that careful evaluation for the image manifestation is essential before sub-lobectomy and those who diagnosed as adenocarcinoma in situ or minimally invasive adenocarcinoma may be more appropriate for this procedure. Precise diagnosis of Intraoperative frozen section is an effective method toward personalization of surgical care for early-stage non-smallcell lung cancer.

  3. Stereotactic Body Radiotherapy for Early-stage Non-small-cell Lung Cancer in Patients 80 Years and Older: A Multi-center Analysis.

    Science.gov (United States)

    Cassidy, Richard J; Patel, Pretesh R; Zhang, Xinyan; Press, Robert H; Switchenko, Jeffrey M; Pillai, Rathi N; Owonikoko, Taofeek K; Ramalingam, Suresh S; Fernandez, Felix G; Force, Seth D; Curran, Walter J; Higgins, Kristin A

    2017-09-01

    Stereotactic body radiotherapy (SBRT) is the standard of care for medically inoperable early-stage non-small-cell lung cancer. Despite the limited number of octogenarians and nonagenarians on trials of SBRT, its use is increasingly being offered in these patients, given the aging cancer population, medical fragility, or patient preference. Our purpose was to investigate the efficacy, safety, and survival of patients ≥ 80 years old treated with definitive lung SBRT. Patients who underwent SBRT were reviewed from 2009 to 2015 at 4 academic centers. Patients diagnosed at ≥ 80 years old were included. Kaplan-Meier and multivariate logistic regression and Cox proportional hazard regression analyses were performed. Recursive partitioning analysis was done to determine a subgroup of patients most likely to benefit from therapy. A total of 58 patients were included, with a median age of 84.9 years (range, 80.1-95.2 years), a median follow-up time of 19.9 months (range, 6.9-64.9 months), a median fraction size of 10.0 Gy (range, 7.0-20.0 Gy), and a median number of fractions of 5.0 (range, 3.0-8.0 fractions). On multivariate analysis, higher Karnofsky performance status (KPS) was associated with higher local recurrence-free survival (hazard ratio [HR], 0.92; P patients with KPS ≥ 75 had improved 3-year cancer-specific and overall survival (99.4% and 91.9%, respectively) compared with patients with KPS lung SBRT for early-stage non-small-cell lung cancer was efficacious and safe in patients ≥ 80 years old. Patients with a KPS of ≥ 75 derived the most benefit from therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    Science.gov (United States)

    Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

    2012-02-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

  5. Recurrence Patterns and Second Primary Lung Cancers After Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: Implications for Surveillance.

    Science.gov (United States)

    Spratt, Daniel E; Wu, Abraham J; Adeseye, Victoria; Din, Shaun U; Shaikh, Fauzia; Woo, Kaitlin M; Zhang, Zhigang; Foster, Amanda; Rosenzweig, Kenneth E; Gewanter, Richard; Huang, James; Rimner, Andreas

    2016-05-01

    Patients treated with stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) are subject to locoregional and distant recurrence, as well as the formation of second primary lung cancers (SPLCs). The optimal surveillance regimen for patients treated with SBRT for early-stage NSCLC remains unclear; we therefore investigated the posttreatment recurrence patterns and development of SPLCs. Three hundred sixty-six patients with pathologically proven inoperable early-stage NSCLC treated with SBRT between 2006 and 2013 were assessed. Patients underwent a computed tomographic (CT) scan of the chest every 3 months during years 1 and 2, every 6 months during years 3 and 4, and annually thereafter. Competing risk analysis was used for all time-to-event analyses. With a median follow-up of 23 months, the 2-year cumulative incidence of local, nodal, and distant treatment failures were 12.2%, 16.1%, and 15.5%, respectively. In patients with disease progression after SBRT (n = 108), 84% (n = 91) of cases occurred within the first 2 years. Five percent (n = 19) of patients experienced SPLCs. The median time to development of an SPLC was 16.5 months (range, 6.5-71.1 months), with 33% (n = 6) of these patients experiencing SPLCs after 2 years. None of the never smokers, but 4% of former tobacco smokers and 15% of current tobacco smokers, experienced an SPLC (P = .005). Close monitoring with routine CT scans within the first 2 years after SBRT is effective in detecting early disease progression. In contrast, the risk for the development of an SPLC remains elevated beyond 2 years, particularly in former and current smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. [Intraoperative methylene blue and (99m)Tc-sulfur colloid isotope tracing for sentinel node mapping in early-stage non-small cell lung cancer].

    Science.gov (United States)

    Hong, Bin; Shen, Xueyuan; Chen, Jiangyong

    2014-06-01

    To compare the accuracy of intaoperative methylene blue alone and in combination with (99m)Tc-sulfur colloid isotopic tracing for detection of sentinel lymph nodes (SLNs) in early-stage non-small cell lung cancer (NSCLC). Sixty-one patients with operable NSCLC who did not receive previous radiotherapy or chemotherapy were enrolled. Methylene blue and (99m)Tc-sulfur colloid were injected into the subserosal layer adjacent to the tumor, and SLNs were defined as those with blue staining or those containing 3 times more radioactivity than the surrounding tissue detected with a gamma probe. The SLN were removed with systematic lymph node dissection. All the removed lymph nodes were examined histopathologically with HE staining and immunohistochemistry. Methylene blue alone showed a low detection rate (60.0%) and sensitivity (58.33%) for SLNs compared with the combination of methylene blue and isotope tracing (96.15% and 92.86%, respectively). The combination of methylene blue and (99m)Tc-sulfur colloid isotopic tracing allows accurate detection of the SLNs in early-stage NSCLC.

  7. Lack of a Dose-Effect Relationship for Pulmonary Function Changes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guckenberger, Matthias, E-mail: Guckenberger_M@klinik.uni-wuerzburg.de [Department of Radiation Oncology, University Hospital Wuerzburg, Wuerzburg (Germany); Klement, Rainer J. [Department of Radiation Oncology, University Hospital Wuerzburg, Wuerzburg (Germany); Kestin, Larry L. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Hope, Andrew J. [Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada); Belderbos, Jose [The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Werner-Wasik, Maria [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Yan, Di [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Sonke, Jan-Jakob [The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Bissonnette, Jean-Pierre [Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada); Xiao, Ying [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Grills, Inga S. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States)

    2013-03-15

    Purpose: To evaluate the influence of tumor size, prescription dose, and dose to the lungs on posttreatment pulmonary function test (PFT) changes after stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). Methods and Materials: The analysis is based on 191 patients treated at 5 international institutions: inclusion criteria were availability of pre- and post-SBRT PFTs and dose-volume histograms of the lung and planning target volume (PTV); patients treated with more than 1 SBRT course were excluded. Correlation between early (1-6 months, median 3 months) and late (7-24 months, median 12 months) PFT changes and tumor size, planning target volume (PTV) dose, and lung doses was assessed using linear regression analysis, receiver operating characteristics analysis, and Lyman's normal tissue complication probability model. The PTV doses were converted to biologically effective doses and lung doses to 2 Gy equivalent doses before correlation analyses. Results: Up to 6 months after SBRT, forced expiratory volume in 1 second and carbon monoxide diffusion capacity changed by −1.4% (95% confidence interval [CI], −3.4% to 0) and −7.6% (95% CI, −10.2% to −3.4%) compared with pretreatment values, respectively. A modest decrease in PFTs was observed 7-24 months after SBRT, with changes of −8.1% (95% CI, −13.3% to −5.3%) and −12.4% (95% CI, −15.5% to −6.9%), respectively. Using linear regression analysis, receiver operating characteristic analysis, and normal tissue complication probability modeling, all evaluated parameters of tumor size, PTV dose, mean lung dose, and absolute and relative volumes of the lung exposed to minimum doses of 5-70 Gy were not correlated with early and late PFT changes. Subgroup analysis based on pre-SBRT PFTs (greater or equal and less than median) did not identify any dose-effect relationship. Conclusions: This study failed to demonstrate a significant dose-effect relationship for

  8. Recurrence and Survival After Segmentectomy in Patients With Prior Lung Resection for Early-Stage Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Brown, Lisa M; Louie, Brian E; Jackson, Nicole; Farivar, Alexander S; Aye, Ralph W; Vallières, Eric

    2016-10-01

    Lobectomy is the standard of care for patients with early-stage non-small cell lung cancer (NSCLC). However, the treatment of choice for patients with prior lung resection and a second primary NSCLC has not been established. We compared rates and patterns of recurrence and survival in patients with and without prior lung resection treated by segmentectomy and determined predictors of recurrence. This was a retrospective cohort study of 90 patients who underwent 91 consecutive segmentectomies for early-stage NSCLC between April 2004 and December 2014. Logistic regression was used to determine predictors of recurrence, and Kaplan-Meier curves were used to determine survival. Of the 91 segmentectomies, 21 (23%) had a prior lung cancer resection and 70 (77%) were primary resections. There were 18 recurrences (20%): 9 of 21 (43%) in those with prior lung resection and 9 of 70 (13%) in those without. The 90-day mortality was 0%. The recurrence-free survival and 5-year survival were 61% and 55% in those with prior lung resection (p = 0.09) and 84% and 65% in those without (p = 0.4). Close parenchymal margin and number of lymph nodes examined were significant modifiable predictors of recurrence. Segmentectomy is a reasonable option for patients with early-stage NSCLC who have had a prior lung resection. It results in similar survival but trends toward lower recurrence-free survival compared with patients undergoing primary resection. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer.

    Science.gov (United States)

    Chang, Joe Y; Zhang, Wencheng; Komaki, Ritsuko; Choi, Noah C; Chan, Shen; Gomez, Daniel; O'Reilly, Michael; Jeter, Melenda; Gillin, Michael; Zhu, Xiaorong; Zhang, Xiaodong; Mohan, Radhe; Swisher, Stephen; Hahn, Stephen; Cox, James D

    2017-02-01

    The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.5Gy/fraction of proton therapy. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time was 83.1months (95% CI: 69.2-97.1months). For all 35 patients, the 1, 3, and 5-year overall survival rates were 85.7%, 42.9%, and 28.1%, respectively. The 5-year local recurrence-free, regional recurrence-free, and distant metastasis-free survival rates were 85.0%, 89.2%, and 54.4%, respectively. Different T stages had no effect on local and regional recurrence (p=0.499, p=1.00). However, with the increase in T stages, the distant metastasis rate increased significantly (p=0.006). The most common adverse effects were dermatitis (grade 2, 51.4%; grade 3, 2.9%) and radiation pneumonitis (grade 2, 11.4%; grade 3, 2.9%). Other grade 2 toxicities included esophagitis (2.9%), rib fracture (2.9%), heart toxicities (5.7%), and chest wall pain (2.9%). According to our long-term follow-up data, proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. Systemic therapy should be considered to reduce the rate of distant metastasis in cases of T2 and T3 lesions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes

    Directory of Open Access Journals (Sweden)

    Wang T

    2016-03-01

    Full Text Available Tao Wang,1 Yang Liu,1 Bin Zhou,1 Zhi Wang,1 Naichao Liang,1 Yundong Zhang,1 Zhouhuan Dong,2 Jie Li2 1Department of Thoracic Surgery, 2Department of Pathology, People’s Liberation Army General Hospital, Beijing, People’s Republic of China Purpose: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC. Preliminary findings suggested that EGFR–TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC.Patients and methods: We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA–IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis.Results: A total of 67 patients with NSCLC were reviewed, and approximately half (38/67 of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2–4 weeks’ assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028 and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011 were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3% and dry skin (34.4%, which were tolerable.Conclusion: Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings. Keywords: non-small-cell lung cancer

  11. Volumetric Modulated Arc Radiotherapy for Early Stage Non-Small-Cell Lung Carcinoma: Is It Better Than the Conventional Static Beam Intensity Modulated Radiotherapy?

    Directory of Open Access Journals (Sweden)

    Vincent Wing Cheung Wu

    2014-01-01

    Full Text Available This study compared the performance of volumetric modulated arc therapy (VMAT techniques: single arc volumetric modulated arc therapy (SA-VMAT and double arc volumetric modulated arc therapy (DA-VMAT with the static beam conventional intensity modulated radiotherapy (C-IMRT for non-small-cell lung carcinoma (NSCLC. Twelve stage I and II NSCLC patients were recruited and their planning CT with contoured planning target volume (PTV and organs at risk (OARs was used for planning. Using the same dose constraints and planning objectives, the C-IMRT, SA-VMAT, and DA-VMAT plans were optimized. C-IMRT consisted of 7 static beams, while SA-VMAT and DA-VMAT plans consisted of one and two full gantry rotations, respectively. No significant difference was found among the three techniques in target homogeneity and conformity. Mean lung dose in C-IMRT plan was significantly lower than that in DA-VMAT plan P=0.04. The ability of OAR sparing was similar among the three techniques, with no significant difference in V20, V10, or V5 of normal lungs, spinal cord, and heart. Less MUs were required in SA-VMAT and DA-VMAT. Besides, SA-VMAT required the shortest beam on time among the three techniques. In treatment of early stage NSCLC, no significant dosimetric superiority was shown by the VMAT techniques over C-IMRT and DA-VMAT over SA-VMAT.

  12. Comprehensive dosimetric planning comparison for early-stage, non-small cell lung cancer with SABR: fixed-beam IMRT versus VMAT versus TomoTherapy.

    Science.gov (United States)

    Xhaferllari, Ilma; El-Sherif, Omar; Gaede, Stewart

    2016-09-08

    Volumetric-modulated arc therapy (VMAT) is emerging as a leading technology in treating early-stage, non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR). However, two other modalities capable of deliver-ing intensity-modulated radiation therapy (IMRT) include fixed-beam and helical TomoTherapy (HT). This study aims to provide an extensive dosimetric compari-son among these various IMRT techniques for treating early-stage NSCLC with SABR. Ten early-stage NSCLC patients were retrospectively optimized using three fixed-beam techniques via nine to eleven beams (high and low modulation step-and-shoot (SS), and sliding window (SW)), two VMAT techniques via two partial arcs (SmartArc (SA) and RapidArc (RA)), and three HT techniques via three different fan beam widths (1 cm, 2.5 cm, and 5 cm) for 80 plans total. Fixed-beam and VMAT plans were generated using flattening filter-free beams. SS and SA, HT treatment plans, and SW and RA were optimized using Pinnacle v9.1, Tomoplan v.3.1.1, and Eclipse (Acuros XB v11.3 algorithm), respectively. Dose-volume histogram statistics, dose conformality, and treatment delivery efficiency were analyzed. VMAT treatment plans achieved significantly lower values for contralat-eral lung V5Gy (p ≤ 0.05) compared to the HT plans, and significantly lower mean lung dose (p VMAT techniques, a significant reduction in the total monitor units (p = 0.05) was found in the SA plans, while a significant decrease was observed in the dose falloff parameter, D2cm, (p = 0.05), for the RA treatments. The maximum cord dose was significantly reduced (p = 0.017) in grouped RA&SA plans com-pared to SS. Estimated treatment time was significantly higher for HT and fixed-beam plans compared to RA&SA (p VMAT is dosimetrically advantageous in treating early-stage NSCLC with SABR compared to fixed-beam, while providing significantly shorter treatment times.

  13. Clinical Analysis of stereotactic body radiation therapy using extracranial gamma knife for patients with mainly bulky inoperable early stage non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Tang Hanjun

    2011-07-01

    Full Text Available Abstract Purpose To evaluate the clinical efficacy and toxicity of stereotactic body radiation therapy (SBRT using extracranial gamma knife in patients with mainly bulky inoperable early stage non-small cell lung carcinoma (NSCLC. Materials and methods A total of 43 medically inoperable patients with mainly bulky Stage I/II NSCLC received SBRT using gamma knife were reviewed. The fraction dose and the total dose were determined by the radiation oncologist according to patients' general status, tumor location, tumor size and the relationship between tumor and nearby organ at risk (OAR. The total dose of 34~47.5 Gy was prescribed in 4~12 fractions, 3.5~10 Gy per fraction, one fraction per day or every other day. The therapeutic efficacy and toxicity were evaluated. Results The median follow-up was 22 months (range, 3-102 months. The local tumor response rate was 95.35%, with CR 18.60% (8/43 and PR 76.74% (33/43, respectively. The local control rates at 1, 2, 3, 5 years were 77.54%, 53.02%, 39.77%, and 15.46%, respectively, while the 1- and 2-year local control rates were 75% and 60% for tumor ≤3 cm; 84% and 71% for tumor sized 3~5 cm; 55% and 14.6% for tumor sized 5~7 cm; and 45%, 21% in those with tumor size of >7 cm. The overall survival rate at 1, 2, 3, 5 years were 92.04%, 78.04%, 62.76%, 42.61%, respectively. The toxicity of stereotactic radiation therapy was grade 1-2. Clinical stages were significantly important factor in local control of lung tumors (P = 0.000. Both clinical stages (P = 0.015 and chemotherapy (P = 0.042 were significantly important factors in overall survival of lung tumors. Conclusion SBRT is an effective and safe therapy for medically inoperable patients with early stage NSCLC. Clinical stage was the significant prognostic factors for both local tumor control and overall survival. The toxicity is mild. The overall local control for bulky tumors is poor. Tumor size is a poor prognostic factor, and the patients for

  14. No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

    Energy Technology Data Exchange (ETDEWEB)

    Stanic, Sinisa, E-mail: sinisa.stanic@carle.com [Carle Cancer Center and University of Illinois College of Medicine, Urbana, Illinois (United States); Paulus, Rebecca [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Timmerman, Robert D. [University of Texas Southwestern, Dallas, Texas (United States); Michalski, Jeff M. [Washington University, St. Louis, Missouri (United States); Barriger, Robert B. [Indiana University, Indianapolis, Indiana (United States); Bezjak, Andrea [Princess Margaret Cancer Center, Toronto, Ontario (Canada); Videtic, Gregory M.M. [Cleveland Clinic Foundation, Cleveland, Ohio (United States); Bradley, Jeffrey [Washington University, St. Louis, Missouri (United States)

    2014-04-01

    Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.

  15. A Panel of Genetic Polymorphism for the Prediction of Prognosis in Patients with Early Stage Non-Small Cell Lung Cancer after Surgical Resection.

    Directory of Open Access Journals (Sweden)

    Shin Yup Lee

    Full Text Available This study was conducted to investigate whether a panel of eight genetic polymorphisms can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC after surgical resection.We selected eight single nucleotide polymorphisms (SNPs which have been associated with the prognosis of lung cancer patients after surgery in our previous studies. A total of 814 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the eight SNPs with overall survival (OS and disease-free survival (DFS was analyzed.The eight SNPs (CD3EAP rs967591, TNFRSF10B rs1047266, AKT1 rs3803300, C3 rs2287845, HOMER2 rs1256428, GNB2L1 rs3756585, ADAMTSL3 rs11259927, and CD3D rs3181259 were significantly associated with OS and/or DFS. Combining those eight SNPs, we designed a prognostic index to predict the prognosis of patients. According to relative risk of death, a score value was assigned to each genotype of the SNPs. A worse prognosis corresponded to a higher score value, and the sum of score values of eight SNPs defined the prognostic index of a patient. When we categorized the patients into two groups based on the prognostic index, high risk group was significantly associated with worse OS and DFS compared to low risk group (aHR for OS = 2.21, 95% CI = 1.69-2.88, P = 8.0 x 10-9, and aHR for DFS = 1.58, 95% CI = 1.29-1.94, P = 1.0 x 10-5.Prognostic index using eight genetic polymorphisms may be useful for the prognostication of patients with surgically resected NSCLC.

  16. Mid-radiotherapy PET/CT for prognostication and detection of early progression in patients with stage III non-small cell lung cancer.

    Science.gov (United States)

    Gensheimer, Michael F; Hong, Julian C; Chang-Halpenny, Christine; Zhu, Hui; Eclov, Neville C W; To, Jacqueline; Murphy, James D; Wakelee, Heather A; Neal, Joel W; Le, Quynh-Thu; Hara, Wendy Y; Quon, Andrew; Maxim, Peter G; Graves, Edward E; Olson, Michael R; Diehn, Maximilian; Loo, Billy W

    2017-08-19

    Pre- and mid-radiotherapy FDG-PET metrics have been proposed as biomarkers of recurrence and survival in patients treated for stage III non-small cell lung cancer. We evaluated these metrics in patients treated with definitive radiation therapy (RT). We also evaluated outcomes after progression on mid-radiotherapy PET/CT. Seventy-seven patients treated with RT with or without chemotherapy were included in this retrospective study. Primary tumor and involved nodes were delineated. PET metrics included metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax. For mid-radiotherapy PET, both absolute value of these metrics and percentage decrease were analyzed. The influence of PET metrics on time to death, local recurrence, and regional/distant recurrence was assessed using Cox regression. 91% of patients had concurrent chemotherapy. Median follow-up was 14months. None of the PET metrics were associated with overall survival. Several were positively associated with local recurrence: pre-radiotherapy MTV, and mid-radiotherapy MTV and TLG (p=0.03-0.05). Ratio of mid- to pre-treatment SUVmax was associated with regional/distant recurrence (p=0.02). 5/77 mid-radiotherapy scans showed early out-of-field progression. All of these patients died. Several PET metrics were associated with risk of recurrence. Progression on mid-radiotherapy PET/CT was a poor prognostic factor. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Surgical Management of Early-Stage Non-small Cell Lung Carcinoma and the Present and Future Roles of Adjuvant Therapy: A Review for the Radiation Oncologist

    Energy Technology Data Exchange (ETDEWEB)

    Medford-Davis, Laura [Department of Emergency Medicine, Ben Taub General Hospital, Houston, TX (United States); DeCamp, Malcom [Division of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Flickinger, John [Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Belani, Chandra P. [Department of Medical Oncology, Penn State Hershey Cancer Institute, Hershey, Pennsylvania (United States); Varlotto, John, E-mail: jvarlotto@hmc.psu.edu [Division of Radiation Oncology, Penn State Hershey Cancer Institute, Hershey, Pennsylvania (United States)

    2012-12-01

    We review the evidence for optimal surgical management and adjuvant therapy for patients with stages I and II non-small cell lung cancer (NSCLC) along with factors associated with increased risks of recurrence. Based on the current evidence, we recommend optimal use of mediastinal lymph node dissection, adjuvant chemotherapy, and post-operative radiation therapy, and make suggestions for areas to explore in future prospective randomized clinical trials.

  18. Telomere length and recurrence risk after curative resection in patients with early-stage non-small-cell lung cancer: a prospective cohort study.

    Science.gov (United States)

    Kim, Eric S; Ye, Yuanqing; Vaporciyan, Ara A; Xing, Jinliang; Huang, Maosheng; Gu, Jian; Roth, Jack A; Lippman, Scott M; Wu, Xifeng

    2015-02-01

    We hypothesized that telomere length in peripheral blood would have significant predictive value for risk of recurrence after curative resection in non-small-cell lung cancer (NSCLC). This prospective study included 473 patients with histologically confirmed early stage NSCLC who underwent curative therapy at MD Anderson Cancer Center between 1995 and 2008. Relative telomere length (RTL) of peripheral leukocytes was measured by real-time polymerase chain reaction. The risk of recurrence was estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) using a multivariable Cox proportional hazard regression model. Median duration of follow-up was 61 months, and 151 patients (32%) had developed recurrence at time of analysis. Patients who developed recurrence had significantly longer mean RTL compared with those without recurrence (1.13 versus 1.07, p = 0.046). A subgroup analysis indicates that women had longer RTL compared with men (1.12 versus 1.06, p = 0.025), and the patients with adenocarcinoma demonstrated longer RTL compared with those with other histologic types (1.11 versus 1.05, p = 0.042). To determine whether longer RTL in women and adenocarcinoma subgroup would predict risk of recurrence, multivariate Cox analysis adjusting for age, sex, stage, pack year and treatment regimens was performed. Longer telomeres were significantly associated with higher risk of developing recurrence in women (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.02-4.96, p = 0.044) and adenocarcinoma subgroups (HR, 2.19; 95% CI, 1.05-4.55, p = 0.036). The increased risk of recurrence due to long RTL was more apparent in women with adenocarcinoma (HR, 2.67; 95% CI, 1.19-6.03, p = 0.018). This is the first prospective study to suggest that long RTL is associated with recurrence in early stage NSCLC after curative resection. Women and adenocarcinoma seem to be special subgroups in which telomere biology may play an important role.

  19. The Impact of Tumor Size on Outcomes After Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allibhai, Zishan [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada); Taremi, Mojgan [Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket (Canada); Bezjak, Andrea; Brade, Anthony; Hope, Andrew J.; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada); Cho, B.C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada)

    2013-12-01

    Purpose: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm

  20. Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma.

    Science.gov (United States)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E; Ditzel, Henrik J

    2013-10-08

    The unique expression pattern and immunogenic properties of cancer/testis antigens make them ideal targets for immunotherapy of cancer. The MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC. Tumor biopsies from normal lung tissue and from a large cohort (n = 169) of NSCLC patients were examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical analysis. The expression of these antigens was further matched to clinical and pathological features using univariate cox regression analysis. GAGE and NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1 and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7% (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not significantly associated with a specific histotype (adenocarcinoma vs. squamous cell carcinoma), but high-level GAGE expression (>50%) was more frequent in squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of GAGE and NY-ESO-1 and survival endpoints revealed no significant associations. Our study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis antigens are candidate targets for immunotherapy of NSCLC and further suggest that multi-antigen vaccines may be beneficial.

  1. Support Vector Machine-Based Prediction of Local Tumor Control After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klement, Rainer J., E-mail: rainer_klement@gmx.de [Department of Radiation Oncology, University of Würzburg (Germany); Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital, Schweinfurt (Germany); Allgäuer, Michael [Department of Radiotherapy, Barmherzige Brüder Regensburg, Regensburg (Germany); Appold, Steffen [Department of Radiation Oncology, Technische Universität Dresden (Germany); Dieckmann, Karin [Department of Radiotherapy, Medical University of Vienna (Austria); Ernst, Iris [Department of Radiotherapy, University Hospital Münster (Germany); Ganswindt, Ute [Department of Radiation Oncology, Ludwigs-Maximilians-University Munich, München (Germany); Holy, Richard [Department of Radiation Oncology, RWTH Aachen University, Aachen (Germany); Nestle, Ursula [Department of Radiation Oncology, University Hospital Freiburg, Freiburg i Br (Germany); Nevinny-Stickel, Meinhard [Department of Therapeutic Radiology and Oncology, Innsbruck Medical University (Austria); Semrau, Sabine [Department of Radiation Oncology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (Germany); Sterzing, Florian [Department of Radiation Oncology, University Hospital Heidelberg (Germany); Wittig, Andrea [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg (Germany); Andratschke, Nicolaus [Department of Radiation Oncology, Technische Universität München (Germany); Guckenberger, Matthias [Department of Radiation Oncology, University of Würzburg (Germany)

    2014-03-01

    Background: Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control. Methods and Materials: We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection. Results: Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED{sub ISO}) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED{sub ISO} and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED{sub ISO}, age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively. Conclusions: These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP

  2. Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E

    2013-01-01

    NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC....

  3. A Gene Signature Combining the Tissue Expression of Three Angiogenic Factors is a Prognostic Marker in Early-stage Non-small Cell Lung Cancer

    National Research Council Canada - National Science Library

    Sanmartín, Elena; Sirera, Rafael; Usó, Marta; Blasco, Ana; Gallach, Sandra; Figueroa, Santiago; Martínez, Nieves; Hernando, Cristina; Honguero, Antonio; Martorell, Miguel; Guijarro, Ricardo; Rosell, Rafael; Jantus-Lewintre, Eloisa; Camps, Carlos

    .... The aim of this study was to analyze relative expression levels of angiogenic markers in resectable non-small cell lung cancer patients in order to asses a prognostic signature that could improve...

  4. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-06-28

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  5. Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Pøhl, Mette; Olsen, Karen Ege; Holst, Rene

    2016-01-01

    BACKGROUND: Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell...... proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7......) and keratin 34βE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients. RESULTS: Based on keratin 34βE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34βE12+/K7...

  6. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small ... clinical trials before, during, or after starting their cancer treatment. Some clinical trials only include patients who have ...

  7. Lymph node micrometastases are associated with disease recurrence and poor survival for early-stage non-small cell lung cancer patients: a meta-analysis.

    Science.gov (United States)

    Deng, Xu Feng; Jiang, Li; Liu, Quan Xing; Zhou, Dong; Hou, Bing; Cui, Kefan; Min, Jia Xin; Dai, Ji Gang

    2016-02-16

    We performed a meta-analysis to clarify whether the molecular detection of tumor cells or micrometastases in the lymph node (LN) indicates a high risk of disease recurrence and poor survival in negative pathologic lymph node status non-small cell lung cancer (NSCLC). A literature search was performed using relevant keywords. We searched relevant studies from PubMed, Embase, and the Cochrane Library. Direct and indirect meta-estimates were generated using Review Manager software with fixed effects for the study. Study-to-study heterogeneity was summarized using I (2) statistics and predictive intervals (PIs). Our analysis of eight eligible studies revealed that patients with lymph node micrometastases (LNMM) were associated with poor overall survival (OS) (HR, 1.98; 95 % CI, 1.50 to 2.62; p recurrence and poor survival in patients with negative pathologic node negative NSCLC. Thus, these patients need to be carefully followed up after the initial pulmonary resection.

  8. Expression Levels of Some Antioxidant and Epidermal Growth Factor Receptor Genes in Patients with Early-Stage Non-Small Cell Lung Cancer

    Science.gov (United States)

    De Palma, Giuseppe; Mozzoni, Paola; Acampa, Olga; Internullo, Eveline; Carbognani, Paolo; Rusca, Michele; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Apostoli, Pietro; Mutti, Antonio

    2010-01-01

    This study was aimed at: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others. PMID:20700416

  9. Expression levels of some antioxidant and epidermal growth factor receptor genes in patients with early-stage non-small cell lung cancer.

    Science.gov (United States)

    De Palma, Giuseppe; Mozzoni, Paola; Acampa, Olga; Internullo, Eveline; Carbognani, Paolo; Rusca, Michele; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Apostoli, Pietro; Mutti, Antonio

    2010-01-01

    THIS STUDY WAS AIMED AT: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others.

  10. Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Early Stage Non-small Cell Lung Cancer%早期非小细胞肺癌立体定向放射治疗后的放射性肺炎

    Institute of Scientific and Technical Information of China (English)

    陈露; 赵娅琴; 许峰

    2014-01-01

    With the development of radiation technology, stereotactic body radiation therapy (SBRT) has been widely used in early stage non-small cell lung cancer (NSCLC). It is not only the standard therapy for medically inoperable early-stage NSCLC, but also one of the therapies for operable early-stage NSCLC. Radiation pneumonitis (RP) is one of the most common adverse effects atfer SBRT, it may reduce the patients’ quality of life, even cause treatment failure. hTerefore, in order to improve the patients’ quality of life and enhance local control rate of tumor, it is important to reduce the risk of RP. hTe unique fractionation schemes and the dose distribution of SBRT make it not only different from conventional fraction radiation therapy in treatment outcomes, but also in the incidence of radiation pneumonitis. hTis article reviews the applying of SBRT for early stage NSCLC, the incidence of radiation pneumonitis, radiological appearance atfer SBRT and predictive factors.%随着放疗技术的进步,立体定向放射治疗(stereotactic body radiation therapy, SBRT)在早期非小细胞肺癌(non-small cell lung cancer, NSCLC)中得到了广泛应用,其不仅是不可手术的早期NSCLC的标准治疗方法,也是可手术的早期NSCLC的治疗方法之一。放射性肺炎(radiation pneumonitis, RP)是SBRT治疗后最常见的并发症。SBRT独特的分割计划和剂量分布使其不仅在治疗效果上和常规分割放疗不同,而且治疗后引起的RP和常规分割放疗引起的RP也有所不同。RP的发生可降低患者的生活质量,甚至导致治疗失败。因此,降低RP的风险对提高患者的生活质量和肿瘤的控制率有重要意义。本文就SBRT在早期NSCLC治疗中应用、治疗后RP的发生率、影像学表现以及预测因素方面作一综述。

  11. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer - An updated retrospective study on local failure and survival rates

    Energy Technology Data Exchange (ETDEWEB)

    Jeppesen, Stefan S. [Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark)], e-mail: Stefan.Jeppesen@rsyd.dk; Schytte, Tine; Hansen, Olfred [Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark); Inst. of Clinical Research, Univ. of Southern Denmark, Odense (Denmark); Jensen, Henrik R. [Lab. of Radiation Physics, Odense Univ. Hospital, Odense (Denmark); Brink, Carsten [Lab. of Radiation Physics, Odense Univ. Hospital, Odense (Denmark); Inst. of Clinical Research, Univ. of Southern Denmark, Odense (Denmark)

    2013-10-15

    Introduction: Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single-institutional report is to describe survival outcome for medically inoperable patients with early stage NSCLC treated with SBRT compared with high dose conventional RT. Material and methods: From August 2005 to June 2012, 100 medically inoperable patients were treated with SBRT at Odense Univ. Hospital. The thoracic RT consisted of 3 fractions (F) of 15-22 Gy delivered in nine days. For comparison a group of 32 medically inoperable patients treated with conventional RT with 80 Gy/35-40 F (5 F/week) in the period of July 1998 to August 2011 were analyzed. All tumors had histological or cytological proven NSCLC T1-2N0M0. Results: The median overall survival was 36.1 months versus 24.4 months for SBRT and conventional RT, respectively (p = 0.015). Local failure-free survival rates at one year were in SBRT group 93 % versus 89 % in the conventional RT group and at five years 69 % versus 66 %, SBRT and conventional RT respectively (p = 0.99). On multivariate analysis, female gender and performance status of 0-1 and SBRT predicted improved prognosis. Conclusion: In a cohort of patients with NSCLC there was a significant difference in overall survival favoring SBRT. Performance status of 0-1, female gender and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients.

  12. 早期非小细胞肺癌立体定向消融放疗现状%Current Status of Stereotactic Ablative Radiotherapy (SABR) for Early-stage Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    石安辉; 朱广迎

    2016-01-01

    目前比较立体定向消融放疗(stereotactic ablative radiotherapy, SABR)与手术治疗早期非小细胞肺癌(non-small cell lung cancer, NSCLC)的随机研究证据尚不多,高水平的循证医学证据更是缺乏。尽管STARS和ROSEL两项随机研究结果荟萃分析显示SABR较手术耐受性更好,生存不劣于手术,但是目前仍仅推荐拒绝手术或不可手术的早期NSCLC首选SABR,期待着正在进行的随机研究VALOR(Veterans Affairs Lung Cancer Surgery or Stereotactic Ra-diotherapy in the US)和SABRTooth(SABRTooth study in the United Kingdom)的结果。许多回顾性的研究和病例对照研究显示了SABR治疗的安全性和有效性(局部控制率达90%以上,5年生存率达70%),但是由于肿瘤分期定义、如何决定可否手术及手术患者采用手术方式(开胸或胸腔镜辅助)等不同,很难比较SABR和手术的优劣,尽管大部分结论是两种方法疗效相似,但难以成为循证医学证据,因此争论热点是哪一种方法更安全、创伤更小。本文将就以上争论热点进行述评。%High level evidence from randomized studies comparing stereotactic ablative radiotherapy (SABR) to surgery is lacking. Although the results of pooled analysis of two randomized trials for STARS and ROSEL showed that SABR is better tolerated and might lead to better overall survival than surgery for operable clinical stage I non-small cell lung cancer (NSCLC), SABR, however, is only recommended as a preferred treatment option for early stage NSCLC patients who cannot or will not undergo surgery. We, therefore, are waiting for the results of the ongoing randomized studies [Veterans af-fairs lung cancer surgery or stereotactic radiotherapy in the US (VALOR) and the SABRTooth study in the United Kingdom (SABRTooths)]. Many retrospective and case control studies showed that SABR is safe and effective (local control rate higher than 90%, 5 years survival rate

  13. Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer.

    Directory of Open Access Journals (Sweden)

    Wangyu Zhu

    Full Text Available BACKGROUND: Altered expression of miRNA expression contributes to human carcinogenesis. This study was designed to detect aberrant miRNA expressions as a potential biomarker for early detection and prognosis prediction of non-small cell lung cancer (NSCLC. METHODS: miRNA array was used to profile differentially expressed miRNAs and Taqman-based quantitative RT-PCR assays were used to analyze levels of miR-29c, miR-93, and miR-429 expression in NSCLC tissue samples, corresponding normal tissue samples, and serum samples from 70 NSCLC patients as well as in serum samples from 48 healthy controls. RESULTS: Levels of miR-29c and miR-93 expression were upregulated in NSCLC tissues, while serum levels of miR-29c were also upregulated, but levels of serum miR-429 were decreased in NSCLC. Moreover, the levels of miR-429 expression in NSCLC tissues were associated with those in serum samples. Receiver operating characteristic (ROC curve analysis showed that at the optimal cut-off point, the areas under the ROC curve for serum levels of miR-29c and miR-429 were 0.723 and 0.727, respectively, levels which are higher than that of carcinoma embryonic antigen (0.534 in diagnosis of stage I NSCLC. In addition, serum levels of miR-429 were associated with poor overall survival of NSCLC patients. Both univariate and multivariate analyses showed that serum miR-429 level was an independent prognostic predictor for NSCLC. CONCLUSIONS: The results of the current study suggest that detection of serum miR-29c and miR-429 expression should be further evaluated as a novel, non-invasive biomarker for early stage NSCLC.

  14. A comparative study of the target volume definition in radiotherapy with «Slow CT Scan» vs. 4D PET/CT Scan in early stages non-small cell lung cancer.

    Science.gov (United States)

    Molla, M; Anducas, N; Simó, M; Seoane, A; Ramos, M; Cuberas-Borros, G; Beltran, M; Castell, J; Giralt, J

    To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow»-CT (CTs) in the radiotherapy planning process. A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  15. The potential role of respiratory motion management and image guidance in the reduction of severe toxicities following stereotactic ablative radiation therapy for patients with centrally located early stage non-small cell lung cancer or lung metastases

    Directory of Open Access Journals (Sweden)

    Alexander eChi

    2014-06-01

    Full Text Available Image guidance allows delivery of very high doses of radiation over a few fractions, known as stereotactic ablative radiotherapy (SABR. This treatment is associated with excellent outcome for early stage non-small cell lung cancer and metastases to the lungs. In the delivery of SABR, central location constantly poses a challenge due to the difficulty of adequately sparing critical thoracic structures that are immediately adjacent to the tumor if an ablative dose of radiation is to be delivered to the tumor target. As of current, various respiratory motion management and image guidance strategies can be used to ensure accurate tumor target localization prior and/ or during daily treatment, which allows for maximal and safe reduction of set up margins. The incorporation of both may lead to the most optimal normal tissue sparing and the most accurate SABR delivery. Here, the clinical outcome, treatment related toxicities, and the pertinent respiratory motion management/image guidance strategies reported in the current literature on SABR for central lung tumors are reviewed.

  16. High-Dose Hypofractionated Proton Beam Radiation Therapy Is Safe and Effective for Central and Peripheral Early-Stage Non-Small Cell Lung Cancer: Results of a 12-Year Experience at Loma Linda University Medical Center

    Energy Technology Data Exchange (ETDEWEB)

    Bush, David A., E-mail: dbush@llu.edu [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Cheek, Gregory [Department of Pulmonary Medicine, Loma Linda University Medical Center, Loma Linda, California (United States); Zaheer, Salman; Wallen, Jason [Department of Thoracic Surgery, Loma Linda University Medical Center, Loma Linda, California (United States); Mirshahidi, Hamid [Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Katerelos, Ari; Grove, Roger; Slater, Jerry D. [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States)

    2013-08-01

    Purpose: We update our previous reports on the use of hypofractionated proton beam radiation therapy for early-stage lung cancer patients. Methods and Materials: Eligible subjects had biopsy-proven non-small cell carcinoma of the lung and were medically inoperable or refused surgery. Clinical workup required staging of T1 or T2, N0, M0. Subjects received hypofractionated proton beam therapy to the primary tumor only. The dose delivered was sequentially escalated from 51 to 60 Gy, then to 70 Gy in 10 fractions over 2 weeks. Endpoints included toxicity, pulmonary function, overall survival (OS), disease-specific survival (DSS), and local control (LC). Results: One hundred eleven subjects were analyzed for treatment outcomes. The patient population had the following average characteristics; age 73.2 years, tumor size 3.6 cm, and 1.33 L forced expiratory volume in 1 second. The entire group showed improved OS with increasing dose level (51, 60, and 70 Gy) with a 4-year OS of 18%, 32%, and 51%, respectively (P=.006). Peripheral T1 tumors exhibited LC of 96%, DSS of 88%, and OS of 60% at 4 years. Patients with T2 tumors showed a trend toward improved LC and survival with the 70-Gy dose level. On multivariate analysis, larger tumor size was strongly associated with increased local recurrence and decreased survival. Central versus peripheral location did not correlate with any outcome measures. Clinical radiation pneumonitis was not found to be a significant complication, and no patient required steroid therapy after treatment for radiation pneumonitis. Pulmonary function was well maintained 1 year after treatment. Conclusions: High-dose hypofractionated proton therapy achieves excellent outcomes for lung carcinomas that are peripherally or centrally located. The 70-Gy regimen has been adopted as standard therapy for T1 tumors at our institution. Larger T2 tumors show a trend toward improved outcomes with higher doses, suggesting that better results could be seen with

  17. A Phase I Trial of an Immune Checkpoint Inhibitor Plus Stereotactic Ablative Radiotherapy in Patients with Inoperable Stage I Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-10-01

    with Inoperable Stage I Non-Small Cell Lung Cancer PRINCIPAL INVESTIGATOR: Karen Kelly, MD CONTRACTING ORGANIZATION: University of California...Checkpoint Inhibitor Plus Stereotactic Ablative Radiotherapy in Patients with Inoperable Stage I Non-Small Cell Lung Cancer 5b. GRANT NUMBER W81XWH-15...checkpoint inhibitor MPDL3280A (atezolizumab) in early stage inoperable non-small cell lung cancer. The trial is comprised of a traditional 3 + 3 phase I

  18. Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients.

    Science.gov (United States)

    Scrima, Marianna; Zito Marino, Federica; Oliveira, Duarte Mendes; Marinaro, Cinzia; La Mantia, Elvira; Rocco, Gaetano; De Marco, Carmela; Malanga, Donatella; De Rosa, Nicla; Rizzuto, Antonia; Botti, Gerardo; Franco, Renato; Zoppoli, Pietro; Viglietto, Giuseppe

    2017-01-01

    Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease.

  19. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Paracelsus Medizinische Privatuniversitaet, Institute for Research and Development of Advanced Radiation Technologies (radART), Salzburg (Austria); Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Porsch, Peter; Studnicka, Michael [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Pneumologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria)

    2014-09-23

    While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for < 2.5 cm, 79.2 Gy for 2.5-4.5 cm, 84.6 Gy for 4.5-6 cm, 90 Gy for > 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [German] Die Standardbehandlung fuer nichtkleinzellige Bronchialkarzinome (NSCLC) im Stadium I/II ist die Operation, wobei Radiotherapie fuer Patienten, die nicht operabel sind oder die Operation ablehnen, als Alternative

  20. Computed tomography-based anatomic assessment overestimates local tumor recurrence in patients with mass-like consolidation after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

    Science.gov (United States)

    Dunlap, Neal E; Yang, Wensha; McIntosh, Alyson; Sheng, Ke; Benedict, Stanley H; Read, Paul W; Larner, James M

    2012-12-01

    To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade ≥ 2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying

  1. Computed Tomography-Based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients With Mass-like Consolidation After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dunlap, Neal E. [Department of Radiation Oncology, University of Louisville, Louisville, KY (United States); Yang Wensha [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); McIntosh, Alyson [Department of Radiation Oncology, John and Dorothy Morgan Cancer Center, Lehigh Valley Hospital, Allentown, PA (United States); Sheng, Ke [Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA (United States); Benedict, Stanley H.; Read, Paul W. [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Larner, James M., E-mail: jml2p@virginia.edu [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States)

    2012-12-01

    Purpose: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Methods and Materials: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Results: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade {>=}2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Conclusion: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will

  2. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    Science.gov (United States)

    2016-10-13

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  3. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-01-23

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  4. Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer.

    Science.gov (United States)

    Jin, Ying; Zhao, Li; Peng, Fang

    2013-05-01

    Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. Stage I non-small cell lung cancer patients who underwent complete surgical resection of the primary tumor at Zhejiang Hospital were analyzed in this study. Serum albumin levels were measured before surgery and once again after surgery in 101 histologically diagnosed non-small cell lung cancer patients. Correlations between the pre- and post-operative serum albumin levels and various clinical demographics and recurrence-free survival rates were analyzed. Patients with pre-operative hypoalbuminemia (recurrence. Serum albumin levels appear to be a significant independent prognostic factor for tumor recurrence in patients with stage I non-small cell lung cancer who have undergone complete resection. Patient pre-treatment and post-treatment serum albumin levels provide an easy and early means of discrimination between patients with a higher risk for recurrence and patients with a low risk of recurrence.

  5. 77 FR 24717 - Scientific Information Request on Local Therapies for the Treatment of Stage I Non-Small Cell...

    Science.gov (United States)

    2012-04-25

    ... Therapies for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to... for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to Advanced... effectiveness review of the evidence for local therapies for the treatment of stage I non-small cell lung...

  6. Treatment Burden of Medicare Beneficiaries With Stage I Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Presley, Carolyn J; Soulos, Pamela R; Tinetti, Mary; Montori, Victor M; Yu, James B; Gross, Cary P

    2016-12-20

    To quantify the burden and complexity associated with treatment of Medicare beneficiaries with stage I non-small-cell lung cancer (NSCLC). Using the SEER-Medicare database, we conducted a retrospective cohort study of Medicare beneficiaries who were diagnosed with stage I NSCLC from 2007 to 2011 and who were treated with surgery, stereotactic body radiation therapy, or external beam radiation therapy. Main outcome measures were the number of days a patient was in contact with the health care system (encounter days), the number of physicians involved in a patient's care, and the number of medications prescribed. Logistic regression modeled the association between patient characteristics, treatment type, and high treatment burden (defined as ≥ 66 encounter days). On average, 7,955 patients spent 1 in 3 days interacting with the health care system during the initial 60 days of treatment. Patients experienced a median of 44 encounter days with high variability (interquartile range [IQR], 29 to 66) in the 12 months after treatment initiation. The median number of physicians involved was 20 (IQR, 14 to 28), and the median number of medications prescribed was 12 (IQR, 8 to 17). Patients who were treated with surgery had high treatment burden (predicted probability, 21.6%; 95% CI, 20.2 to 23.1) compared with patients who were treated with stereotactic body radiation therapy (predicted probability, 16.1%; 95% CI, 12.9 to 19.3), whereas patients who were treated with external beam radiation therapy had the highest burden (predicted probability, 46.8%; 95% CI, 43.3 to 50.2). The treatment burden imposed on patients with early-stage NSCLC was substantial in terms of the number of encounters, physicians involved, and medications prescribed. Because treatment burden varied markedly across patients and treatment types, future work should identify opportunities to understand and ameliorate this burden.

  7. Stereotactic Ablative Radiation Therapy for Centrally Located Early Stage or Isolated Parenchymal Recurrences of Non-Small Cell Lung Cancer: How to Fly in a “No Fly Zone”

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Qiao-Qiao; Xu, Qing-Yong; Allen, Pamela K.; Rebueno, Neal; Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Balter, Peter [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza; Swisher, Stephen G.; Roth, Jack A. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-04-01

    Purpose: We extended our previous experience with stereotactic ablative radiation therapy (SABR; 50 Gy in 4 fractions) for centrally located non-small cell lung cancer (NSCLC); explored the use of 70 Gy in 10 fractions for cases in which dose-volume constraints could not be met with the previous regimen; and suggested modified dose-volume constraints. Methods and Materials: Four-dimensional computed tomography (4DCT)-based volumetric image-guided SABR was used for 100 patients with biopsy-proven, central T1-T2N0M0 (n=81) or isolated parenchymal recurrence of NSCLC (n=19). All disease was staged with positron emission tomography/CT; all tumors were within 2 cm of the bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus, or vertebral body. Endpoints were toxicity, overall survival (OS), local and regional control, and distant metastasis. Results: At a median follow-up time of 30.6 months, median OS time was 55.6 months, and the 3-year OS rate was 70.5%. Three-year cumulative actuarial local, regional, and distant control rates were 96.5%, 87.9%, and 77.2%, respectively. The most common toxicities were chest-wall pain (18% grade 1, 13% grade 2) and radiation pneumonitis (11% grade 2 and 1% grade 3). No patient experienced grade 4 or 5 toxicity. Among the 82 patients receiving 50 Gy in 4 fractions, multivariate analyses showed mean total lung dose >6 Gy, V{sub 20} >12%, or ipsilateral lung V{sub 30} >15% to independently predict radiation pneumonitis; and 3 of 9 patients with brachial plexus D{sub max} >35 Gy experienced brachial neuropathy versus none of 73 patients with brachial D{sub max} <35 Gy (P=.001). Other toxicities were analyzed and new dose-volume constraints are proposed. Conclusions: SABR for centrally located lesions produces clinical outcomes similar to those for peripheral lesions when normal tissue constraints are respected.

  8. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-10-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  9. Recurrence Risk Factors Analysis for Stage I Non-small Cell Lung Cancer.

    Science.gov (United States)

    Wu, Ching-Feng; Fu, Jui-Ying; Yeh, Chi-Ju; Liu, Yun-Hen; Hsieh, Ming-Ju; Wu, Yi-Cheng; Wu, Ching-Yang; Tsai, Ying-Huang; Chou, Wen-Chi

    2015-08-01

    Lung cancer is the leading cause of cancer-related death worldwide. Even early-stage patients might encounter disease recurrence with relative high risk. Effective postoperative therapy is based on an accurate assessment of treatment failure after surgery. The aim of this study is to construct a disease-free survival (DFS) prediction model and stratify patients into different risk score groups.A total of 356 pathological stage I patients (7th American Joint Committee on Cancer) who underwent lung resection from January 2005 through June 2011 were retrospectively reviewed. Of these patients, 63 patients were eliminated for this study. A total of 293 p-stage I patients were included for further univariate and multivariate analysis. Clinical, surgical, and pathological factors associated with high risk of recurrence were analyzed, including age, gender, smoking status, additional primary malignancy (APM), operation method, histology, visceral pleural invasion, angiolymphatic invasion, tumor necrosis, and tumor size.Of the 293 p-stage I non-small cell lung cancer (NSCLC) patients examined, 143 were female and 150 were male, with a mean age of 62.8-years old (range: 25-83-years old). The 5-year DFS and overall survival rates after surgery were 58.9% and 75.3%, respectively. On multivariate analysis, current smoker (hazards ratio [HR]: 1.63), APM (HR: 1.86), tumor size (HR: 1.54, 2.03), nonanatomic resections (HR: 1.81), adenocarcinoma histology (HR: 2.07), visceral pleural invasion (HR: 1.54), and angiolymphatic invasion (HR: 1.53) were found to be associated with a higher risk of tumor recurrence. The final model showed a fair discrimination ability (C-statistic = 0.68). According to the difference risk group, we found patients with intermediate or higher risk group had a higher distal relapse tendency as compared with low risk group (P = 0.016, odds ratio: 3.31, 95% confidence interval: 1.21-9.03).Greater than 30% of disease recurrences occurred after surgery

  10. Multidetector Computed Tomography Findings in the Revised Tumor, Nodal and Metastasis Staging of Non-Small Cell Carcinoma of the Lung: APictorial Essay

    Directory of Open Access Journals (Sweden)

    N. S. Mahmood

    2010-06-01

    Full Text Available Non-small cell carcinoma of the lung is one of the leading causes of cancer deaths. Early diagnosis and accurate staging is hence crucial. Through this pictorial essay, we aim to create awareness regarding the revised staging system for this lung tumor and CT findings of different stages of non-small cell carcinoma of the lung."nMDCT with its multiplanar imaging capability plays an important role not only in making the diagnosis but also in accurate staging which determines the prognosi

  11. Controversies in the management of stage IIIA non-small-cell lung cancer.

    Science.gov (United States)

    Santos, Edgardo S; Castrellon, Aurelio; Blaya, Marcelo; Raez, Luis E

    2008-12-01

    New developments in the management of non-small-cell lung cancer, as well as recent proposals for changing the current lung cancer staging system, are posing a challenge in the therapeutic decision making regarding this disease. For the last two decades, the management of stage IIIA (N2) disease has been controversial and the target for clinical trials has been to determine the best therapeutic approach that may result in better survival outcomes without increasing toxicity. For many years, combined modality treatment (systemic chemotherapy plus radiation therapy) became the standard of care in this setting. However, the poor outcomes seen with combined modality for N2 has obligated us to explore other possibilities. In this sense, recent clinical trials in the neoadjuvant setting using chemotherapy alone or combined modality are providing fruitful results and shifting the paradigm on this stage. A recent, large randomized multicenter trial argues against what has slowly become a current practice in some centers - the use of preoperative modality for N2 disease. Another controversy that we will discuss here is the acceptance of adjuvant therapy for resected stage IB-IIIA non-small-cell lung cancer. It was not long ago that adjuvant radiation therapy was still the standard of care for patients who have pathological nodal disease. We will present the current data on these debatable issues and how to implement this new knowledge into clinical practice.

  12. The influence of TP53 mutations on the prognosis of patients with early stage non-small cell lung cancer may depend on the intratumor heterogeneity of the mutations.

    Science.gov (United States)

    Lee, Shin Yup; Jeon, Hyo-Sung; Hwangbo, Yup; Jeong, Ji Yun; Park, Ji Young; Lee, Eun Jin; Jin, Guang; Shin, Kyung Min; Yoo, Seung Soo; Lee, Jaehee; Lee, Eung Bae; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2015-02-01

    A large number of studies have evaluated the impact of TP53 mutations on the prognosis of patients with non-small cell lung cancer (NSCLC); however, the results of these studies are still controversial. Recently, considerable intratumor heterogeneity for genetic alterations has been demonstrated in various human cancers, including lung cancer. In the present study, we evaluated TP53 mutations in NSCLCs by direct sequencing and observed remarkable variation in the values of relative intensity (RI, the height of the peak of mutated allele/the height of the peak of non-mutated allele) of the mutations. We also examined whether the RI values were associated with intratumor heterogeneity of TP53 mutations. In addition, we evaluated the relationship between TP53 mutations and survival outcome. The patients with a TP53 mutation did not have significantly worse survival compared to those without the mutation. However, when tumors with a TP53 mutation were categorized into two groups, those with a low and those with a high RI, the latter group had significantly worse survival compared to those with wild-type TP53 (adjusted hazard ratio = 2.58, 95% confidence interval = 1.21-5.48, P = 0.01), whereas the former group did not. These results suggest that intratumor genetic heterogeneity may be an important factor in determining the role of TP53 mutations on the prognosis of NSCLC patients.

  13. Upregulation of APE/ref-1 in recurrence stage I, non small cell lung cancer.

    Science.gov (United States)

    Kang, Min-Woong; Kang, Shin Kwang; Choi, Songyi; Lee, Choong Sik; Jeon, Byeong Hwa; Lim, Seung Pyung

    2012-02-01

    Lung cancer, the leading cause of cancer-related death, still lacks reliable biomarkers. Apurinic/apyrimidinic endonuclease 1/Ref-1 is a multifunctional protein involved in the base excision repair of DNA damaged by oxidative stress or alkylating compounds, as well as in the regulation of multiple transcription factors. To validate apurinic/apyrimidinic endonuclease 1/Ref-1 as a biomarker for prediction of lung cancer recurrence, we studied 42 patients who received curative resection and mediastinal lymph node dissection for stage I non-small-cell lung cancer. They were divided into 2 groups based on recurrence, and compared by immunohistochemistry staining of paraffin-embedded tissues and Western blot analysis. Immunohistochemical staining showed a significant difference between the cytoplasm and nucleus in patients who had a recurrence compared to those with nonrecurrent adenocarcinoma. In Western blot analysis, the recurrent adenocarcinoma group showed increased expression of apurinic/apyrimidinic endonuclease 1/Ref-1 in cytoplasm, nucleus, and in total. This indicates that apurinic/apyrimidinic endonuclease 1/Ref-1 is unregulated in recurrent stage I adenocarcinoma. For clinical application as a prognostic marker for non-small-cell lung cancer, further investigation into the role of apurinic/apyrimidinic endonuclease 1/Ref-1 in carcinogenesis is needed in an expanded prospective study.

  14. Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Høyer, Morten; Roed, Henrik; Hansen, Anders Traberg

    2006-01-01

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

  15. Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-06-17

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  16. Relationship between tumor size and disease stage in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yang Fu

    2010-09-01

    Full Text Available Abstract Background Whether tumor size and stage distribution are correlated remains controversial. The objective is to assess the relationship between tumor size and disease stage distribution in non-small cell lung cancer (NSCLC. Methods We conducted a retrospective analysis of 917 cases of NSCLC that were resected in the Cancer Hospital of Fudan University and Shanghai Sixth Hospital between January 2000 and February 2009. Tumor sizes were grouped into five categories: ≤20 mm, 21 to 30 mm, 31 to 50 mm, 51 to 70 mm and ≥71 mm. Results Age and tumor size affected stage distribution: patients 60 years or older had a higher percentage of N0M0 disease than patients younger than 60 years (61.67% vs. 44.85%, p Conclusions There is a statistically significant relationship between tumor size and distribution of disease stage of primary NSCLC tumors: the smaller the tumor, the more likely the disease is N0M0 status.

  17. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Kumarakulasinghe, Nesaretnam Barr; van Zanwijk, Nico; Soo, Ross A

    2015-04-01

    Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.

  18. Novel treatment options in stage I non-small-cell lung cancer.

    Science.gov (United States)

    Tarasevych, Svitlana; Lauwers, Patrick; Vandaele, Frederik; van Meerbeeck, Jan P

    2014-09-01

    In the last 5 years, the current management of stage I non-small-cell lung cancer has been challenged due to novel surgical approaches and advances in radiation technology. The outcome after a sublobar resection is promising, especially for tumors less than 2 cm. Other treatment opportunities are available for high risk patients with comorbidity and impaired pulmonary function. Stereotactic ablative body radiotherapy is a good alternative treatment to surgery, especially in elderly and comorbid patients. However, randomized evidence comparing sublobar resection and stereotactic radiotherapy is presently lacking. The most recent development in radiotherapy is hadron therapy with a presumed reduced toxicity because of its peculiar physical and biological effects. Promising thermal and microwave ablative techniques are in development and have specific niche indications.

  19. Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hofman, Michael S. [St Thomas' Hospital, PET Imaging Centre, London (United Kingdom)]|[Southern Health, Nuclear Medicine, Melbourne (Australia); Smeeton, Nigel C. [King' s College London, Division of Health and Social Care Research, London (United Kingdom); Rankin, Sheila C.; Nunan, Tom; O' Doherty, Michael J. [St Thomas' Hospital, PET Imaging Centre, London (United Kingdom)

    2009-02-15

    Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. A series of {sup 18}F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa ({kappa}) was used to compare ratings from two categories and weighted kappa ({kappa}{sub w}) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement ({kappa} = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver {kappa}{sub w} = 0.79, 0.91; interobserver {kappa}{sub w} = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease ({kappa} = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial ({kappa}{sub w} = 0.71-0.88), but lower for hilar nodes (10; {kappa}{sub w} = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; {kappa}{sub w} = 0.48-0.55). Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC. (orig.)

  20. A Pilot Study of Circulating Tumor Cells in Stage IV Non-Small Cell Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Max Haid

    2016-08-01

    Full Text Available Purpose: Measurement of the number of circulating tumor cells (CTCs in the bloodstream has been shown to have prognostic significance in treating breast carcinoma. This pilot study was formulated to determine if stage IV non-small cell lung carcinomas similarly shed malignant cells into the circulation and if their presence has prognostic significance. Methods: Patients with stage IV non-small cell lung carcinomas were tested once for CTCs in 7.5 ml of their blood prior to receiving any treatments. A proprietary blood collection kit produced by Veridex LLC (Raritan, NJ, which manufactures the instrument that performs the immunomagnetic CELLSEARCH® CTC assay, was used. Tumor measurements were determined in three dimensions by the same radiologist using computerized axial tomography. The three-dimensional sum was used to represent tumor size. Survival from the date of the pretreatment CTC assay was monitored and recorded. Data were analyzed statistically using NCSS8 statistical software (NCSS LLC, Kaysville, UT. Results: Of 19 evaluable patients, 10 had no detectable CTCs. There was no relation between intrapulmonary primary tumor size and the number of CTCs, nor between tumor size and survival. Survival was not affected by gender or age at entry into the trial. The mean survival of those with no detectable CTCs was 536 ± 91.1 days versus 239 ± 96.0 days for those with 1 or more detectable CTCs, a statistically significant advantage (P=0.034 favoring those without CTCs. Conclusions: Patients with a CTC score of 0 survived significantly longer than those with a CTC score of ≥ 1. Survival was not correlated with gender, age or primary tumor size. Recovery of CTCs potentially provides a noninvasive source of tumor cells for genomic profiling, which may enable development of a custom treatment plan for the individual patient. Further investigations are warranted and needed.

  1. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)] [and others

    1999-06-01

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m{sup 2}) on day 1 and oral Etoposide (50 mg/m{sup 2}/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post

  2. Survival after Pneumonectomy for Stage III Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Sibu P. Saha

    2014-01-01

    Full Text Available Objectives: Stage III non-small cell lung cancer (NSCLC has a poor prognosis. Reports suggest that five-year survival after current treatment is between 14 to 24 percent. The purpose of this retrospective study was to investigate the morbidity and mortality of patients diagnosed with stage III NSCLC and treated with pneumonectomy at the University of Kentucky Medical Center in Lexington, KY. Methods: We reviewed the medical record and tumor registry follow-up data on 100 consecutive patients who underwent pneumonectomy for lung cancer at the University of Kentucky. Results: We identified thirty-six patients in stage III who underwent pneumonectomy. Ten patients had surgery only, eight patients received adjuvant chemotherapy, and eighteen patients received neoadjuvant therapy. There was one surgical death in this series. Mean follow-up was 2.9 years. One-, three-, and five-year survival was 66%, 38%, and 38%, respectively. Five-year survival for the group with adjuvant therapy was 60%. Conclusion: Most lung cancer patients present with advanced disease and the prognosis remains poor. Our experience indicates resection offers an above average chance of long-term survival when supplemented with neoadjuvant and/or adjuvant therapy.

  3. Survival Analysis of 1,742 Patients with Stage IV Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hong PENG

    2011-04-01

    Full Text Available Background and objective At present non-small cell lung cancer (NSCLC is still the leading cause of death induced by cancer. The aim of this study is to investigate the prognostic factors of advanced NSCLC. Methods Total 1,742 cases of stage IV NSCLC data from Jan 4, 2000 to Dec 25, 2008 in Shanghai Chest Hospital were collected, confirmed by pathological examinations. Analysis was made to observe the impact of treatment on prognosis in gender, age, smoking history, pathology, classification, clinical TNM stage. Survival rate, survival difference were evaluated by Kaplan-Meire method and Logrank test respectively. The prognosis were analyzed by Cox multivariate regression. Results The median survival time of 1,742 patients was 10.0 months (9.5 months-10.5 months. One, two, three, four, and five-year survival rates were 44%, 22%, 13%, 9%, 6% respectively. The median survivals of single or multiple metastasis were 11 months vs 7 months (P < 0.001. Survival time were different in metastasic organs, with the median survival time as follows: lung for about 12 months (11.0 months-12.9 months, bone for 9 months (8.3 months-9.6 months, brain for 8 months (6.8 months-9.1 months, liver, adrenal gland, distannt lymph node metastasis for 5 months (3.8 months-6.1 months, and subcutaneous for 3 months (1.7 months-4.3 months. The median survival times of adenocarcinoma (n=1,086, 62% and squamous cell carcinoma cases (n=305, 17.5% were 12 months vs 8 months (P < 0.001. The median survival time of chemotherapy and best supportive care were 11 months vs 6 months (P < 0.001; the median survival times of with and without radiotherapy were 11 months vs 9 months (P=0.017. Conclusion Gender, age, gross type, pathological type, clinical T stage, N stage, numbers of metastatic organ, smoking history, treatment of advanced non-small cell lung cancer were independent prognostic factors.

  4. Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, In Hye; Song, Si Yeol; Cho, Byung Chul; Kwak, Jung Won; Jung, Nuri Hyun; Kim, Su Ssan; Choi, Eun Kyung [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jung, Jin Hong [Dept. of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul (Korea, Republic of); Je, Hyoung Uk [Dept. of Radiation Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Choi, Won Sik [Dept. of Radiation Oncology, Gangneung Asan Hospital, Uiversity of Ulsan College of Medicine, Gangneung (Korea, Republic of)

    2015-06-15

    To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication.

  5. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R [Brigham and Women’s Hospital, Boston, MA (United States)

    2015-06-15

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after the same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye

  6. Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Høyer, Morten; Roed, Henrik; Hansen, Anders Traberg

    2006-01-01

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT...... with a       central dose of 15 Gy x 3 within 5-8 days. Results: Eight patients (20%)       obtained a complete response, 15 (38%) had a partial response, and 12       (30%) had no change or could not be evaluated. Only 3 patients had a local       recurrence, and the local control rate 2 years after SBRT was 85...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

  7. Micrometastasis in non-small-cell lung cancer: Detection and staging

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohajeri

    2012-01-01

    Full Text Available Background: The clinical relevance of bone marrow micrometastasis (BMM in non-small-cell lung cancer is undetermined, and the value of such analyses in advanced stage patients has not been clearly assessed previously. This study was conducted to estimate the accuracy of both polymerase chain reaction (PCR and immunohistochemistry (IHC in micrometastases detection and determine the best site for bone marrow biopsy in order to find micrometastasis. Methods: This prospective cross-sectional study was performed in the Department of Thoracic Surgery, Alzahra University Hospital from September 2008 to June 2009. To evaluate the bone marrow, a 3-cm rib segment and an aspirated specimen from the iliac bone prior to tumor resection were taken. PCR and IHC were performed for each specimen to find micrometastasis. Results: Of 41 patients, 14 (34% were positive for BMM by PCR compared with two positive IHC (4.8%. All BMMs were diagnosed in rib segments, and iliac specimens were all free from metastatic lesion. Our data showed no significant association between variables such as age, sex, histology, tumor location, side of tumor, involved lobe, smoking, or weight loss and presence of BMM. Conclusion: PCR could use as a promising method for BMM detection. BMM in a sanctuary site (rib is not associated with advanced stages of lung cancer. In addition, when predictor variables such as age, sex, histology, tumor location, smoking, or weight loss are analyzed, no correlation can be found between micrometastasis prevalence and any of those variables.

  8. POST-OPERATIVE STAGING AND SURVIVAL BASED ON THE REVISED TNM STAGING SYSTEM FOR NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the factors affecting post-operative staging and survival in non-small cell lung cancer (NSCLC) patients based on the revised TNM staging system adopted by the UICC in 1977. Methods: Data were collected from 1757 consecutively operated NSCLC patients, including those receiving complete tumor excision, tumor debulking and exploratory thoractomy from April 1969 through Dec. 1993. the end point of follow-up was Nov. 30, 1998. Cumulative survival and its influencing factors were analyzed by Kaplan-Meier and Cox model of SPSS software. Results: In this series, 30 patients (1.7%) were lost from follow-up. The 5-year cumulative survival was 88.0% for patients in stage I A, and 53.9% in stage IB, 33.5% in stage II, 14.7% in stage IIIA, 5.5% in stage IIIB and 7.0% in stage IV. The overall 5-year survival rate was 28.2%. The 5-year survivals were 39.8%, 14.4% and 4.2% in patients treated with completely tumor resection, tumor debulking and explorative thoractomy, respectively. The 10-year survival rate was 31.4%, 9.5% and 0, respectively. Factors affecting long-term cumulative survival, in the order of decreasing significance, were the type of operation, lymph node status, staging, size and pathological type of the primary tumor. Conclusion: the revised staging system for NSCLC is superior to that used since 1986 as far as the end results of treatment in patients in different stage and the staging specificity are concerned. The T3N1M0 classification and the definition of M1 need to be further studied.

  9. Time-varying pattern of postoperative recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC): results of a single-center study of 994 Chinese patients.

    Science.gov (United States)

    Zhu, Jian-fei; Feng, Xing-yu; Zhang, Xue-wen; Wen, Ying-sheng; Lin, Peng; Rong, Tie-hua; Cai, Ling; Zhang, Lan-jun

    2014-01-01

    The aim of this study was to analyze the time-varying pattern of recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC) after surgery using the hazard function and identify patients who might benefit from adjuvant chemotherapy. This retrospective study enrolled 994 patients with early-stage NSCLC who underwent radical surgical resection between January 1999 and October 2009. Survival curves were generated using the Kaplan-Meier method, and the annual recurrence hazard was estimated using the hazard function. The median recurrence-free survival (RFS) was 8.8 years. The life table survival analysis showed that the 1-year, 3-year, 5-year and 10-year recurrence rates were 82.0%, 67.0%, 59.0% and 48.0%, respectively. Approximately 256 (25.7%) patients experienced relapse [locoregional: 32 (3.2%) and distant: 224 (22.5%)], and 162 patients died from cancer. The annual recurrence hazard curve for the entire population showed that the first major recurrence surge reached a maximum 1.6 years after surgery. The curve subsequently declined until reaching a nadir at 7.2 years. A second peak occurred at 8.8 years. An analysis of clinical-pathological factors demonstrated that this double-peaked pattern was present in several subgroups. The presence of a double-peaked pattern indicates that there is a predictable temporal distribution of the recurrence hazard of early-stage NSCLC. The annual recurrence hazard may be an effective method of selecting patients at high risk of recurrence, who may benefit from adjuvant therapy.

  10. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-08-18

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  11. Outcomes of patients with unresected stage III and stage IV non-small cell lung cancer: A single institution experience

    Directory of Open Access Journals (Sweden)

    Manpreet Singh Tiwana

    2013-01-01

    Full Text Available Introduction: To report on the demographic profile and survival outcomes of North Indian population affected with stage III and stage IV non-small cell lung cancer (NSCLC. Materials and Methods: From November 2008 to January 2012, 138 consecutively diagnosed NSCLC patients were included in this study. The patient, tumor and treatment related factors were analyzed. Median overall survival (OS, Kaplan-Meier survival plots, t-test, Cox proportional hazards models were generated by multivariate analysis [MVA] and analyzed on SPSS software (version 19.0; SPSS, Inc., Chicago, IL. Results: Median OS of stage III patients was 9.26 ± 1.85 months and 2-year survival rate of 13% while stage IV patients had median OS of 5 ± 1.5 months with a 2-year survival rate of 8%. Cox regression modeling for MVA demonstrated higher biologically equivalent dose (BED ( P = 0.01 in stage III while in stage IV non-squamous histology ( P = 0.01, administration of chemotherapy ( P = 0.02, partial responders to chemotherapy ( P = 0.001, higher BED ( P = 0.02, and those with skeletal metastasis alone ( P = 0.17 showed a better OS. Conclusion: Our data showed that a higher BED is associated with favorable outcomes, indicating a role of dose escalated radiation therapy to the primary lesion in both stage III and essentially in stage IV NSCLC. Additionally, optimal use of chemotherapy relates to better survival. The developing, resource restrained nations need to follow an economically feasible multimodality approach.

  12. Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer

    Science.gov (United States)

    Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

    2017-01-01

    Background The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Methods Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. Results The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. Conclusions The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

  13. Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer.

    Science.gov (United States)

    Tsukioka, Takuma; Nishiyama, Noritoshi; Izumi, Nobuhiro; Mizuguchi, Shinjiro; Komatsu, Hiroaki; Okada, Satoshi; Toda, Michihito; Hara, Kantaro; Ito, Ryuichi; Shibata, Toshihiko

    2017-04-01

    Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patient's physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease.

  14. Pretreatment [{sup 18}F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Vimoj J.; MacRae, Robert [Division of Radiation Oncology, University of Ottawa, Ottawa, Ontario (Canada); Ottawa Hospital Research Institute, Ottawa, Ontario (Canada); Sirisegaram, Abby [Ottawa Hospital Research Institute, Ottawa, Ontario (Canada); Pantarotto, Jason R., E-mail: jpantarotto@toh.on.ca [Division of Radiation Oncology, University of Ottawa, Ottawa, Ontario (Canada); Ottawa Hospital Research Institute, Ottawa, Ontario (Canada)

    2014-02-01

    Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUV{sub max}) of the primary tumor for [{sup 18}F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUV{sub max} were 8.1 and 7, respectively. Progression-free survival at 2 years with SUV{sub max} <7 was better than that of the patients with tumor SUV{sub max} ≥7 (67% vs 51%; P=.0096). Tumors with SUV{sub max} ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUV{sub max} ≥7 was an independent prognostic factor for distant metastasis-free survival. Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUV{sub max} ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

  15. Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2017-06-12

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  16. Application of sub-pulmonary lobectomy under thoracoscope and mediation lymph node sampling in treat-ment of non-small cell lung cancer at early stage%胸腔镜下亚肺叶切除及纵隔淋巴结采样治疗早期非小细胞肺癌临床疗效探讨

    Institute of Scientific and Technical Information of China (English)

    王杰

    2016-01-01

    目的:探讨胸腔镜下亚肺叶切除以及纵隔淋巴结采样在早期非小细胞肺癌患者中的临床治疗效果。方法选取2013年4月至2014年4月我院收治的80例早期非小细胞肺癌患者资料进行分析,根据不同治疗方案将患者分为对照组和实验组,对照组采用开胸肺叶切除手术治疗,实验组采用胸腔镜下亚肺叶切除以及纵隔淋巴结采样治疗,比较两组疗效。结果实验组手术时间、术中出血量、术后疼痛评分、术后胸腔引流管时间、住院时间等指标显著少于对照组( P<0.05);实验组并发症发生率为7.5%,显著低于对照组(并发症发生率为22.5%)(P<0.05);实验组经过病理诊断6例浸润性鳞癌,20例浸润性腺癌,8例微浸润性腺癌,6例浸润前病变。2例确诊纵隔淋巴结转移,给予放疗和化疗治疗。结论早期非小细胞肺癌患者采用胸腔镜下亚肺叶切除以及纵隔淋巴结采样治疗效果理想,值得推广使用。%Objective To investigate the clinical effect of sub-pulmonary lobectomy under thoracoscope and mediation lymph node sampling in treatment of non-small cell lung cancer at early stage. Methods 72 NSCLC pa-tients at early stage from April 2013 to April 2014 in our hospital were randomly divided into the control group and the experimental group. The control group was given thorazine lobotomy treatment, and the experimental group was given sub-pulmonary lobectomy under thoracoscope and mediation lymph node sampling. The clinical effect of the two groups were compared. Results The operation time, blood loss, postoperative pain scores, postoperative chest tube time, and duration of hospital stay were significantly better in the experimental group than in the control group ( P<0. 05). The complication rate was 7. 5% in the experimental group, which was significantly lower than that in the control group (2. 5%, P<0. 05). There were 6 cases of invasive squamous cell carcinoma, 20 cases

  17. Definition of stereotactic body radiotherapy. Principles and practice for the treatment of stage I non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guckenberger, M.; Sauer, O. [University of Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Andratschke, N. [University of Rostock, Department of Radiotherapy and Radiation Oncology, Rostock (Germany); Alheit, H. [Distler Radiation Oncology, Bautzen/Pirna (Germany); Holy, R. [RWTH Aachen University, Department of Radiation Oncology, Aachen (Germany); Moustakis, C. [University of Muenster, Department of Radiation Oncology, Muenster (Germany); Nestle, U. [University of Freiburg, Department of Radiation Oncology, Freiburg (Germany)

    2014-01-15

    This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft fuer Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy. (orig.) [German] Die Arbeitsgruppe ''Stereotaktische Radiotherapie'' der Deutschen Gesellschaft fuer Radioonkologie (DEGRO) erarbeitete eine Definition der Koerperstereotaxie (SBRT), die sich an vorhandene internationale Definitionen anlehnt: Die SBRT ist eine Form der perkutanen Strahlentherapie, die mit hoher Praezision eine hohe Bestrahlungsdosis in einer oder wenigen Bestrahlungsfraktionen in einem extrakraniellen Zielvolumen appliziert. Zur Praxis der SBRT beim nichtkleinzelligen Bronchialkarzinom (NSCLC) im fruehen Stadium werden detaillierte Empfehlungen gegeben, die den gesamten Ablauf der Behandlung von der Indikationsstellung, Staging, Behandlungsplanung und Applikation sowie Nachsorge umfassen. Die Koerperstereotaxie wurde als Methode der Wahl im Vergleich zu Best Supportive Care, zur konventionell fraktionierten Strahlentherapie sowie zur Radiofrequenzablation identifiziert. Die Ergebnisse nach SBRT und sublobaerer Resektion

  18. Standard treatment option in stage III non-small-cell lung cancer: case against trimodal therapy and consolidation drug therapy.

    Science.gov (United States)

    Jeremić, Branislav

    2015-03-01

    Prospective randomized trials and meta-analyses established concurrent radiochemotherapy (RT-CHT) as standard treatment approach in patients with inoperable, locally advanced (stage IIIA and B) non-small-cell lung cancer (NSCLC). In patients with either clinically (c) or pathologically (p) staged disease (stage IIIA), including those with pN2 disease, trimodal therapy was also frequently practiced in the past and is currently still advocated by large cooperative groups and organizations. Similarly, consolidation CHT provided after concurrent RT-CHT was suggested to be feasible and effective in inoperable stage III NSCLC. Contrasting these practices and suggestions, there is no evidence that trimodal therapy in stage IIIA (clinically or pathologically staged) or consolidation CHT in inoperable stage III NSCLC plays any role in its treatment. In both cases, evidence clearly demonstrates that concurrent RT-CHT is of similar efficacy and less toxic, and it should be considered a standard treatment option for all patients with stage III NSCLC.

  19. Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer.

    Science.gov (United States)

    Mozzoni, Paola; Banda, Iris; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Acampa, Olga; Balestra, Valeria; Ampollini, Luca; Casalini, Angelo; Carbognani, Paolo; Mutti, Antonio

    2013-12-01

    Lung cancer is a major cause of death in Western countries. Current screening methods are invasive and still lead to a high percentage of false positives. There is, therefore, a need to find biomarkers that increase the probability of detecting lung cancer early. MicroRNAs (miRNAs) are stable molecules in blood plasma and exhaled breath condensate (EBC). We quantified miRNA-21 and miRNA-486 expression from plasma and EBC samples from patients with a diagnosis of non-small-cell lung cancer (NSCLC) and controls. miRNA-21 was significantly higher in plasma and in EBC of the NSCLC patients and miRNA-486 was significantly lower. This difference indicates a significantly improved diagnostic value, and suggests that these miRNAs could be clinically used as a first-line screening test in high-risk subjects.

  20. MicroRNA-486 as a Biomarker for Early Diagnosis and Recurrence of Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Li, Wanshuai; Wang, Yong; Zhang, Qi; Tang, Lili; Liu, Xiaoping; Dai, Yunhua; Xiao, Liang; Huang, Shuguang; Chen, Lu; Guo, Zhongmin; Lu, Jim; Yuan, Kai

    2015-01-01

    Non-small cell lung cancer (NSCLC) is a leading cause of cancer death worldwide. Early diagnosis is essential for improvements of prognosis and survival of the patients. Currently, there is no effective biomarker available in clinical settings for early detection of lung cancer. Altered expressions in many cancer types including NSCLC and stable existence in plasma make microRNAs (miRNAs) a group of potentially useful biomarkers for clinical assessments of patients with NSCLC. To evaluate the potential values of miRNAs as blood-based biomarkers for early diagnosis and prognosis in NSCLC patients. Peripheral blood samples from healthy volunteers and early-staged NSCLC patients before and after surgery were collected, and plasma was separated. Expression of ten miRNAs in the plasma and tumor sections of the patients was detected by quantitative real-time polymerase chain reaction. MiRNA (miR)-486 and miR-150 were found to significantly distinguish lung cancer patients from healthy volunteers. Area under curve of miR-486 and miR-150 were 0.926 (sensitivity, 0.909; specificity, 0.818) and 0.752 (sensitivity, 0.818; specificity, 0.818), respectively. In response to therapy, patients with down-regulated miR-486 expression showed prolonged recurrence-free survival than those with un-reduced miR-486 expression (median, unreached vs. 19 months; hazard ratio, 0.1053; 95% confidence interval, 0.01045 to 1.060; P=0.056). The results suggest that miR-486 and miR-150 could be potential blood-based biomarkers for early diagnosis of NSCLC. Monitoring change of miR-486 expression in plasma might be an effective and non-invasive method for recurrence prediction of early-staged NSCLC patients.

  1. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection.

    Science.gov (United States)

    Bayarri-Lara, Clara; Ortega, Francisco G; Cueto Ladrón de Guevara, Antonio; Puche, Jose L; Ruiz Zafra, Javier; de Miguel-Pérez, Diego; Ramos, Abel Sánchez-Palencia; Giraldo-Ospina, Carlos Fernando; Navajas Gómez, Juan A; Delgado-Rodriguez, Miguel; Lorente, Jose A; Serrano, María Jose

    2016-01-01

    Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC) stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs) is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC. 56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR) expression. 51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1%) (p = 0.035). The mean number of CTCs was 3.16 per 10 ml (range 0-84) preoperatively and 0.66 (range 0-3) in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018) and a shorter disease free survival (DFS) (p = .008). In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50-21.946, p = 0.010) and N status (HR = 0.296, 95% CI: 0.091-0.961, p = 0.043) were independent prognostic factors for DFS. CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence.

  2. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection.

    Directory of Open Access Journals (Sweden)

    Clara Bayarri-Lara

    Full Text Available Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC.56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR expression.51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1% (p = 0.035. The mean number of CTCs was 3.16 per 10 ml (range 0-84 preoperatively and 0.66 (range 0-3 in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018 and a shorter disease free survival (DFS (p = .008. In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50-21.946, p = 0.010 and N status (HR = 0.296, 95% CI: 0.091-0.961, p = 0.043 were independent prognostic factors for DFS.CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence.

  3. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection

    Science.gov (United States)

    Cueto Ladrón de Guevara, Antonio; Puche, Jose L.; Ruiz Zafra, Javier; de Miguel-Pérez, Diego; Ramos, Abel Sánchez-Palencia; Giraldo-Ospina, Carlos Fernando; Navajas Gómez, Juan A.; Delgado-Rodriguez, Miguel; Lorente, Jose A.; Serrano, María Jose

    2016-01-01

    Background Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC) stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs) is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC. Patients and Methods 56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR) expression. Results 51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1%) (p = 0.035). The mean number of CTCs was 3.16 per 10 ml (range 0–84) preoperatively and 0.66 (range 0–3) in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018) and a shorter disease free survival (DFS) (p = .008). In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50–21.946, p = 0.010) and N status (HR = 0.296, 95% CI: 0.091–0.961, p = 0.043) were independent prognostic factors for DFS. Conclusion CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence. PMID:26913536

  4. Accelerated hyperfractionated radiation, concurrent paclitaxel/cisplatin chemotherapy and surgery for stage III non-small cell lung cancer.

    Science.gov (United States)

    Adelstein, David J; Rice, Thomas W; Rybicki, Lisa A; Greskovich, John F; Ciezki, Jay P; Carroll, Marjorie A; DeCamp, Malcolm M

    2002-05-01

    The low surgical cure rate in patients with stage III non-small cell lung cancer has prompted an exploration of multimodality treatment strategies. Mature results are presented from a phase II trial of accelerated hyperfractionated radiation therapy, concurrent paclitaxel/cisplatin chemotherapy and surgery for these patients. Between 1994 and 1997, 45 patients with surgically demonstrated stage III non-small cell lung cancer underwent induction treatment with a 96 h continuous cisplatin infusion (20 mg/m(2) per day) and a 24 h infusion of paclitaxel (175 mg/m(2)) given concurrently with accelerated hyperfractionated radiation therapy (1.5 Gy twice daily) to a total dose of 30 Gy. Induction was completed in ten treatment (12 total) days. Surgical resection was scheduled 4 weeks later with a second identical course of chemoradiotherapy given 4-6 weeks post-operatively, to a total radiation dose of 60-63 Gy. Thirty-five patients had stage III(A) disease and ten had stage III(B) disease (eight with N(3) tumors). Induction toxicity included nausea in 89%, dysphagia in 89%, and neutropenia tolerable despite significant myelosuppression. Locoregional control is excellent and survival is better than historical expectations. Patients downstaged to mediastinal node negativity have a prognosis similar to those with de novo stage I(B) and II disease. Distant metastases are the major cause of treatment failure.

  5. Preoperative nodal staging of non-small cell lung cancer using 99mTc-sestamibi spect/ct imaging

    Directory of Open Access Journals (Sweden)

    Juliana Muniz Miziara

    2011-01-01

    Full Text Available OBJECTIVES: The proper nodal staging of non-small cell lung cancer is important for choosing the best treatment modality. Although computed tomography remains the first-line imaging test for the primary staging of lung cancer, its limitations for mediastinum nodal staging are well known. The aim of this study is to evaluate the accuracy of hybrid single-photon emission computed tomography and computed tomography using 99mTc-sestamibi in the nodal staging of patients with non-small cell lung cancer and to identify potential candidates for surgical treatment. METHODS: Prospective data were collected for 41 patients from December 2006 to February 2009. The patients underwent chest computed tomography and single-photon emission computed tomography/computed tomography examinations with 99mTc-sestamibi within a 30-day time period before surgery. Single-photon emission computed tomography/computed tomography was considered positive when there was focal uptake of sestamibi in the mediastinum, and computed tomography scan when there was lymph nodes larger than 10 mm in short axis. The results of single-photon emission computed tomography and computed tomography were correlated with pathology findings after surgery. RESULTS: Single-photon emission computed tomography/computed tomography correctly identified six out of 19 cases involving hilar lymph nodes and one out of seven cases involving nodal metastases in the mediastinum. The sensitivity, specificity, positive predictive value, and negative predictive value for 99mTc-sestamibi single-photon emission computed tomography/computed tomography in the hilum assessment were 31.6%, 95.5%, 85.7%, and 61.8%, respectively. The same values for the mediastinum were 14.3%, 97.1%, 50%, and 84.6%, respectively. For the hilar and mediastinal lymph nodes, chest tomography showed sensitivity values of 47.4% and 57.1%, specificity values of 95.5% and 91.2%, positive predictive values of 90% and 57.1% and negative

  6. EGFR mutation positive stage IV non-small-cell lung cancer : Treatment beyond progression

    Directory of Open Access Journals (Sweden)

    Katrijn eVan Assche

    2014-12-01

    Full Text Available Non-small-cell lung cancer (NSCLC is the leading cause of death from cancer for both men en women. Chemotherapy is the mainstay of treatment in advanced disease, but is only marginally effective. In about 30% of patients with advanced NSCLC in East Asia and in 10-15% in Western countries, EGFR mutations are found. In this population, first-line treatment with the tyrosine kinase inhibitors (TKI erlotinib, gefitinib or afatinib is recommended. The treatment beyond progression is less well-defined. In this paper we present 3 patients, EGFR mutation positive, with local progression after an initial treatment with TKI. These patients were treated with local radiotherapy. TKI was temporarily stopped and restarted after radiotherapy. We give an overview of the literature and discuss the different treatment options in case of progression after TKI: TKI continuation with or without chemotherapy, TKI continuation with local therapy, alternative dosing or switch to next-generation TKI or combination therapy. There are different options for treatment beyond progression in EGFR mutation positive metastatic NSCLC, but the optimal strategy is still to be defined. Further research on this topic is ongoing.

  7. Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer

    Science.gov (United States)

    Hinde, S; McKenna, C; Whyte, S; Peake, M D; Callister, M E J; Rogers, T; Sculpher, M

    2015-01-01

    Background: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. Methods: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the ‘worried-well' population and the route of diagnosis that might occur as a result of the campaigns. Results: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of £13 660 and £18 173 per QALY gained, respectively. The scenarios found that increases in the ‘worried-well' population may impact the cost-effectiveness conclusions. Conclusions: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population. PMID:26010412

  8. A Prospective Randomized Study of Adjuvant Chemotherapy in Completely Resected Stage Ⅲ-N2 Non Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage Ⅲ-N2 non-small-cell lung cancer. Methods: From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who were diagnosed as stage Ⅲ-N2 non-small cell lung cancer after operation, were randomly devided into chemotherapy group and control group. The former received four cycles of chemotherapy with NVB (25 mg/m2,D1, D5)/paclitaxel (175 mg/m2, DI) and Carboplatin (AUC=5, D1). Results: In chemotherapy group, 75.8% (68/79) of patients had finished the 4 cycles of chemotherapy and no one died of toxic effects of chemotherapy.Twenty-five percent of the patients had grade 3-4 neutropenia and 2% had febrile neutropenia. The median survival for the entire 150 patients was 879 d, with 1-year survival rate of 81%, 2-year survival rate of 59% and 3-year survival rate of 43%. There was no significant difference in median survival between chemotherapy and control group (897 d vs 821 d, P=0.0527), but there was significant difference in the 1-year and 2-year overall survival (94.71%, 76.28% vs 512 d, P=0.122), but there was significant difference in the 2-year survival rate between two groups with brain metastases (66.7% vs 37.6% P<0.05). The median survival after brain metastasis appeared was 190 days. Conclusion: Postoperative adjuvant chemotherapy does not significantly improve median survival among patients with completely resected stage Ⅱ-N2 non-small-cell lung cancer, but significantly improves the 1-year and 2-year overall survival. It neither decreases the incidence of brain metastasis but put off the time of brain metastasis.

  9. Circulating MicroRNAs as Non-Invasive Biomarkers for Early Detection of Non-Small-Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Magdalena B Wozniak

    Full Text Available Detection of lung cancer at an early stage by sensitive screening tests could be an important strategy to improving prognosis. Our objective was to identify a panel of circulating microRNAs in plasma that will contribute to early detection of lung cancer.Plasma samples from 100 early stage (I to IIIA non-small-cell lung cancer (NSCLC patients and 100 non-cancer controls were screened for 754 circulating microRNAs via qRT-PCR, using TaqMan MicroRNA Arrays. Logistic regression with a lasso penalty was used to select a panel of microRNAs that discriminate between cases and controls. Internal validation of model discrimination was conducted by calculating the bootstrap optimism-corrected AUC for the selected model.We identified a panel of 24 microRNAs with optimum classification performance. The combination of these 24 microRNAs alone could discriminate lung cancer cases from non-cancer controls with an AUC of 0.92 (95% CI: 0.87-0.95. This classification improved to an AUC of 0.94 (95% CI: 0.90-0.97 following addition of sex, age and smoking status to the model. Internal validation of the model suggests that the discriminatory power of the panel will be high when applied to independent samples with a corrected AUC of 0.78 for the 24-miRNA panel alone.Our 24-microRNA predictor improves lung cancer prediction beyond that of known risk factors.

  10. Value of 18F-FDG PET in Clinical Staging of Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Suwen Liu; Jinming Yu; Ligang Xing

    2005-01-01

    OBJECTIVE To evaluate the feasibility of 18F-deoxyglucose positron emission tomography (18F-FDG PET) in the staging of non-small cell lung cancer(NSCLC).METHODS 105 patients with NSCLC had been examined by 18F-FDG PET before radiotherapy. The results of the 18F-FDG PET examination were compared with those of CT:RESULTS The staging was changed in 38 patients because of 18F-FDG PET findings, with PET resulting in upstaging in 31 patients and downstaging in seven patients. Because of distant metastasis detected by PET, 21 patients received palliative treatment. Six of the seven downstaged patients underwent radical surgery, among which the PET findings were concordant with the pathological findings in five patients. Distant metastasis detected by PET elevated the pre-PET stage: at stage 110.0% (2/20), stage Ⅱ 14.3% (3/21 ) and stage Ⅲ 25.0% (16/64), respectively.CONCLUSION 18F-FDG PET, by changing clinical staging in 36.2% (38/105)of NSCLC patients, has an impact on treatment strategy in NSCLC patients.

  11. Risk factors for both recurrence and survival in patients with pathological stage I non-small-cell lung cancer.

    Science.gov (United States)

    Kozu, Yoshiki; Maniwa, Tomohiro; Takahashi, Shoji; Isaka, Mitsuhiro; Ohde, Yasuhisa; Nakajima, Takashi

    2013-07-01

    Even after curative resection, a significant fraction of patients with stage I non-small-cell lung cancer (NSCLC) die primarily because of systemic relapse. The purpose of the present study was to investigate the risk factors for both recurrence and poor survival in patients with pathological (p-) stage I NSCLC. We retrospectively reviewed 467 consecutive patients from a single institution with completely resected p-stage I NSCLC. Patients with multiple lung tumours or malignancies from other organs and those who had undergone preoperative therapies were excluded. The correlation between clinicopathological factors and surgical outcomes, including disease-free survival (DFS) and overall survival (OS), was analysed. The clinicopathological factors examined were age, gender, smoking history, serum carcinoembryonic antigen (CEA) levels, serum cytokeratin 19 fragment levels, surgical procedure, tumour histology, p-stage, angiolymphatic invasion and differentiation grade. The 5-year DFS and OS rates of the total study population were 91.4 and 92.8%, respectively. Multivariate analysis results indicated that high serum CEA levels (>5.0 ng/ml) and p-stage IB were independent factors for recurrence, whereas older age (>70 years), high serum CEA levels and p-stage IB were independent factors for poor survival. The risks of recurrence and death in patients with both high serum CEA levels and p-stage IB was 10.3 and 5.2 times higher than those observed in patients with both normal serum CEA levels and p-stage IA, respectively. High serum CEA levels and p-stage IB were independent factors for both recurrence and poor survival in p-stage I NSCLC patients.

  12. The Role of Postoperative Radiotherapy on Stage N2 Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Fangfang DU

    2009-11-01

    Full Text Available Background and objective The clinical value of postoperative radiotherapy (PORT in stage N2 nonsmall-cell lung cancer (NSCLC is controversy. The aim of this study is to analyze the efficacy of PORT in subgroup of stage N2 NSCLC, which can help clinicians to choose proper patients for PORT. Methods Clinical data of 359 patients with stage N2 NSCLC treated with radical surgery between Mar. 2000 and Jul. 2005 were retrospectively reviewed. Two hundred and seven patients received adjuvant chemotherapy and one hundred and four patients received adjuvant radiotherapy. First, the group of patients were analyzed to evaluate the factors affecting the overall survival. The all patients were divided based on tumor size and the number of lymph node metastasis station (single station or multiple station so as to evaluate the role of PORT. The endpoint was overall survival (OS and local recurrence-free survival (LRFS. Kaplan-Meier method was used to calculate the OS, LRFS and Log-rank was used to compare the difference in OS and LRFS between different groups. Results The median duration of follow-up was 2.3 years. 224 patients died. The median survival was 1.5 years and 1, 3, 5-year survival were 78%, 38% and 26%. Univariate analysis showed tumor size, the number of lymph node metastasis station and PORT were correlated with OS. Among patients, 5-year survival rates in PORT and non-PORT were 29% and 24% (P=0.047 respectively. In subgroups, PORT was related with high survival in patients with multiple station N2 compared to non-PORT: 36% vs 20% (P=0.013 and 33% vs 15% (P=0.002 in patients in patients with tumor size > 3 cm. Also, it was related with low local recurrence compared to non-PORT: 65% vs 48% (P=0.006 and 62% vs 48% (P=0.033. Conclusion PORT can improve overall survival for N2 NSCLC, especially the patients with the factors as follows: tumor size > 3 cm and multiple station N2 can benefit from PORT more or less.

  13. Increasing the accuracy of 18F-FDG PET/CT interpretation of "mildly positive" mediastinal nodes in the staging of non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Moloney, F

    2014-05-01

    The aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC).

  14. M2型丙酮酸激酶同工酶在人体早期非小细胞肺癌中的表达及临床意义%The expression of PKM2 in early stage human non-small cell lung cancer and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    袁素娟; 乔田奎; 陈伟; 庄喜兵

    2015-01-01

    目的:研究 M2型丙酮酸激酶同工酶(PKM2)在人体早期非小细胞肺癌(NSCLC)、癌旁正常肺组织及肺炎组织中的表达及临床意义。方法收集外科手术切除并经病理确诊的非小细胞肺癌及癌旁正常组织标本以及纤维支气管镜肺活检病理检查确诊为肺炎的肺组织标本各99例,采用免疫组织化学法检测其 PKM2的表达水平,并分析其表达与临床病理的关系。结果PKM2在 NSCLC 组织、癌旁正常肺组织和肺炎组织中的阳性率分别为69.70%、0%和9.09%。鳞状细胞癌明显高于腺癌(P <0.01)、腺鳞癌(P <0.05)和其他少见病理类型(P <0.01)。肿瘤直径>3 cm 的 PKM2表达率为76.92%,肿瘤直径≤3 cm 的阳性表达率为42.86%,两组比较差异有统计学意义(P <0.01)。有淋巴结转移患者的 PKM2表达率为87.18%,无淋巴结转移者为58.33%,两组比较差异有统计学意义(P <0.01)。Ⅰ期和Ⅱ期患者的 PKM2阳性表达率分别为58.62%和85.36%,两组比较差异有统计学意义(P <0.01)。结论PKM2在早期 NSCLC 中的表达率升高,对临床早期诊断 NSCLC 有一定的价值。%Objective To explore the expression of M2 isoform of pyruvate kinase(PKM2)in early non-small cell lung cancer(NSCLC),normal lung tissue adjacent to carcinoma and pneumonia and related clinical significance.Methods Immunohistochemistry was used to detect the expression of PKM2 in NSCLC and normal lung tissue adjacent to carcinoma in 99 cases taken by surgical operation and pneu-monia in 99 cases taken by fiberoptic bronchoscopy lung biopsy,and analyzed the relationship between PKM2 and the clinical characteristics.Results The positive rate of PKM2 expression was 69.70%,0%and 9.09% respectively in NSCLC,normal lung tissue adjacent to carcinoma and pneumonia.The positive rate of PKM2 was the biggest in squamous carcinoma group

  15. Establishment of a biomarker model for predicting bone metastasis in resected stage III non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zhou Zhen

    2012-04-01

    Full Text Available Abstract Background This study was designed to establish a biomarker risk model for predicting bone metastasis in stage III non-small cell lung cancer (NSCLC. Methods The model consists of 105 cases of stage III NSCLC, who were treated and followed up. The patients were divided into bone metastasis group (n = 45 and non-bone metastasis group (other visceral metastasis and those without recurrence (n = 60. Tissue microarrays were constructed for immunohistochemical study of 10 molecular markers associated with bone metastasis, based on which a model was established via logistic regression analysis for predicting the risk of bone metastases. The model was prospectively validated in another 40 patients with stage III NSCLC. Results The molecular model for predicting bone metastasis was logit (P = − 2.538 + 2.808 CXCR4 +1.629 BSP +0.846 OPN-2.939 BMP4. ROC test showed that when P ≥ 0.408, the sensitivity was up to 71% and specificity of 70%. Model validation in the 40 cases in clinical trial (NCT 01124253 demonstrated that the prediction sensitivity of the model was 85.7%, specificity 66.7%, Kappa: 0.618, with a high degree of consistency. Conclusion The molecular model combining CXCR4, BSP, OPN and BMP4 could help predict the risk of bone metastasis in stage IIIa and IIIb resected NSCLC.

  16. Gene-expression signature predicts postoperative recurrence in stage I non-small cell lung cancer patients.

    Science.gov (United States)

    Lu, Yan; Wang, Liang; Liu, Pengyuan; Yang, Ping; You, Ming

    2012-01-01

    About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. The purpose of this study is to develop and validate a novel gene-expression signature that can predict tumor recurrence of stage I NSCLC patients. Cox proportional hazards regression analysis was performed to identify recurrence-related genes and a partial Cox regression model was used to generate a gene signature of recurrence in the training dataset -142 stage I lung adenocarcinomas without adjunctive therapy from the Director's Challenge Consortium. Four independent validation datasets, including GSE5843, GSE8894, and two other datasets provided by Mayo Clinic and Washington University, were used to assess the prediction accuracy by calculating the correlation between risk score estimated from gene expression and real recurrence-free survival time and AUC of time-dependent ROC analysis. Pathway-based survival analyses were also performed. 104 probesets correlated with recurrence in the training dataset. They are enriched in cell adhesion, apoptosis and regulation of cell proliferation. A 51-gene expression signature was identified to distinguish patients likely to develop tumor recurrence (Dxy = -0.83, P85%. Multiple pathways including leukocyte transendothelial migration and cell adhesion were highly correlated with recurrence-free survival. The gene signature is highly predictive of recurrence in stage I NSCLC patients, which has important prognostic and therapeutic implications for the future management of these patients.

  17. Prognostic significance of telomeric repeat length alterations in pathological stage I-IIIA non-small cell lung cancer.

    Science.gov (United States)

    Hirashima, T; Komiya, T; Nitta, T; Takada, Y; Kobayashi, M; Masuda, N; Matui, K; Takada, M; Kikui, M; Yasumitu, T; Ohno, A; Nakagawa, K; Fukuoka, M; Kawase, I

    2000-01-01

    This study was performed to evaluate the prognostic significance of alteration in telomere length in pathological stage (p-stage) I-IIIA non-small cell lung cancer (NSCLC). Paired cancer and normal lung tissues were obtained from 72 patients with histologically confirmed p-stage I-IIIA NSCLC. Terminal restriction fragment (TRF) length, which indicates telomere length, was measured by Southern blot analysis. Tumor telomerase activity was also assayed by non-radioactive PCR-ELISA in 55 patients. TRF length (mean +/- SD) in normal tissue was 6.2 +/- 1.1 Kb. Therefore, upper and lower limits of normal range in TRF length was set at 8.4 (mean + 2SD) Kb and 4.0 (mean-2SD) Kb, respectively. A tumor showing TRF length over normal range was defined as positive for the alteration. In 72 patients, 25 (34.7%) with alteration in TRF length had significantly shorter survival durations than those of the others. Telomerase activity did not correlate with survival duration. In multivariate analysis, alteration in TRF length (P = 0.0033) was second to p-stage (P = 0.0004) in importance among the various parameters.

  18. Gene-expression signature predicts postoperative recurrence in stage I non-small cell lung cancer patients.

    Directory of Open Access Journals (Sweden)

    Yan Lu

    Full Text Available About 30% stage I non-small cell lung cancer (NSCLC patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. The purpose of this study is to develop and validate a novel gene-expression signature that can predict tumor recurrence of stage I NSCLC patients. Cox proportional hazards regression analysis was performed to identify recurrence-related genes and a partial Cox regression model was used to generate a gene signature of recurrence in the training dataset -142 stage I lung adenocarcinomas without adjunctive therapy from the Director's Challenge Consortium. Four independent validation datasets, including GSE5843, GSE8894, and two other datasets provided by Mayo Clinic and Washington University, were used to assess the prediction accuracy by calculating the correlation between risk score estimated from gene expression and real recurrence-free survival time and AUC of time-dependent ROC analysis. Pathway-based survival analyses were also performed. 104 probesets correlated with recurrence in the training dataset. They are enriched in cell adhesion, apoptosis and regulation of cell proliferation. A 51-gene expression signature was identified to distinguish patients likely to develop tumor recurrence (Dxy = -0.83, P85%. Multiple pathways including leukocyte transendothelial migration and cell adhesion were highly correlated with recurrence-free survival. The gene signature is highly predictive of recurrence in stage I NSCLC patients, which has important prognostic and therapeutic implications for the future management of these patients.

  19. A Case of Stage IV Non-Small Cell Lung Cancer Treated with Korean Medicine Therapy Alone

    Directory of Open Access Journals (Sweden)

    Dong-hyun Lee

    2013-11-01

    Full Text Available This report presents a case that shows a significant anticancer effect of Korean medicine therapy (KMT. A 79-year-old man, who was diagnosed as stagenon-small cell lung cancer (NSCLC in December 2012, was treated with KMT including intravenous pharmacopunctures and oral herbal medicine from February 22, 2013, until September 2013 without any surgical intervention, chemotherapy or radiotherapy. The intravenous pharmacopunctures were the wild ginseng pharmacopuncture, Cordyceps sinensis pharmacopuncture and Trichosanthes kirilowii pharmacopuncture. The oral herbal medicine used was soramdan, made of cultivated wild ginseng. The effectiveness of this therapy was evaluated with computed tomography and the Eastern Cooperative Oncology Group (ECOG performance scale. The size of the tumor mass was markedly decreased and the ECOG performance scale was also improved. These results suggest that KMT alone can be an effective method to treat NSCLC.

  20. Use of PET/CT for staging and radiation therapy planning in patients with non-small cell lung cancer.

    Science.gov (United States)

    Mac Manus, M P

    2010-10-01

    Positron emission tomography (PET) and more recently PET/computed tomography (CT) scanning represent major advances in the imaging of lung cancer and have an especially high impact on the management of patients who are candidates for potentially curative or "radical" radiotherapy (RT). This article reviews the current status of PET and PET/CT for staging patients before RT and considers the use of PET and PET/CT images for target volume definition. The relevant literature on the use of PET for staging lung cancer is reviewed and placed in the context of patients who are candidates for RT. Research that specifically considers the use of PET for RT planning is considered critically and some promising areas for future research are discussed. The available literature is almost exclusively devoted to non small cell lung cancer (NSCLC) with few relevant studies of small cell lung cancer (SCLC). The primary PET radiopharmaceutical shown to have value for staging and RT planning is 18F-fluorodeoxyglucose (FDG). In prospective studies where PET imaging was used to stage radical RT candidates, 25-30% of patients were excluded from radical therapy because of PET detected advanced disease. In all studies where "PET-assisted" and conventional target or treatment volumes were compared, there were major differences between PET and conventional volumes. Because PET-assisted staging is proven to be significantly more accurate than conventional staging and because all studies show major differences between PET-assisted and conventional treatment volumes in NSCLC, routine use of PET/CT for RT planning is recommended.

  1. Preoperative staging of non-small cell lung cancer: prospective comparison of PET/MR and PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Min [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Goo, Jin Mo; Park, Chang Min [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Cancer Research Institute, Seoul (Korea, Republic of); Yoon, Soon Ho [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Paeng, Jin Chul; Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Young Tae [Seoul National University College of Medicine, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of); Park, Young Sik [Seoul National University Hospital, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of)

    2016-11-15

    To prospectively compare the accuracies of PET/MR and PET/CT in the preoperative staging of non-small cell lung cancer (NSCLC). Institutional review board approval and patients' informed consents were obtained. 45 patients with proven or radiologically suspected lung cancer which appeared to be resectable on CT were enrolled. PET/MR was performed for the preoperative staging of NSCLC followed by PET/CT without contrast enhancement on the same day. Dedicated MR images including diffusion weighted images were obtained. Readers assessed PET/MR and PET/CT with contrast-enhanced CT. Accuracies of PET/MR and PET/CT for NSCLC staging were compared. Primary tumour stages (n = 40) were correctly diagnosed in 32 patients (80.0 %) on PET/MR and in 32 patients (80.0 %) on PET/CT (P = 1.0). Node stages (n = 42) were correctly determined in 24 patients (57.1 %) on PET/MR and in 22 patients (52.4 %) on PET/CT (P = 0.683). Metastatic lesions in the brain, bone, liver, and pleura were detected in 6 patients (13.3 %). PET/MR missed one patient with pleural metastasis while PET/CT missed one patient with solitary brain metastasis and two patients with pleural metastases (P = 0.480). This study demonstrated that PET/MR in combination with contrast-enhanced CT was comparable to PET/CT in the preoperative staging of NSCLC while reducing radiation exposure. (orig.)

  2. FDG PET for staging of advanced non-small cell lung cancer prior to neoadjuvant radio-chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Eschmann, S.M.; Harer-Mouline, C.; Dohmen, B.M.; Bares, R. [Department of Nuclear Medicine, University Hospital Tuebingen (Germany); Friedel, G. [Schillerhoehe-Hospital for Lung Diseases, Gerlingen (Germany); Paulsen, F.; Budach, W. [Department of Radiotherapy, University Hospital Tuebingen (Germany)

    2002-06-01

    The aim of this study was to evaluate positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) for the staging of non-small cell lung cancer (NSCLC) before combined neoadjuvant, i.e. preoperative, radio-chemotherapy (RCT). From November 1998 until September 2001, 101 patients with NSCLC were investigated prospectively. The inclusion criterion was a histologically proven NSCLC of stage IIIA or B according to conventional staging including biopsy. The results of PET were compared with those obtained by mediastinoscopy, computed tomography (CT), bone scan and abdominal ultrasonography. Validation of discrepant findings was achieved by biopsy or repeated CT. PET proved to be highly accurate for the detection of lymph node metastases (sensitivity 96%, specificity 73%, positive predictive value 88%, negative predictive value 89%, accuracy 88%) as well as distant metastases (in 25/101 patients, all previously unknown). PET findings changed further treatment in 29/101 patients (29%). Twenty-five were excluded from RCT due to the presence of previously unknown distant metastases. One patient was free of metastases and therefore was operated on without pre-treatment. Two patients did not receive any further treatment because a malignant tumour could be excluded after PET. In the final patient PET demonstrated a tumour pattern not typical for NSCLC which could be attributed to a seminoma after repeated biopsy. FDG PET is the most accurate non-invasive diagnostic procedure for the staging of advanced NSCLC. Therefore use of FDG PET is highly recommended in order to select patients for neoadjuvant or other stage-dependent treatment modalities. (orig.)

  3. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer.

    Science.gov (United States)

    Altorki, Nasser; Lane, Maureen E; Bauer, Thomas; Lee, Paul C; Guarino, Michael J; Pass, Harvey; Felip, Enriqueta; Peylan-Ramu, Nili; Gurpide, Alfonso; Grannis, Frederic W; Mitchell, John D; Tachdjian, Sabrina; Swann, R Suzanne; Huff, Anne; Roychowdhury, Debasish F; Reeves, Anthony; Ottesen, Lone H; Yankelevitz, David F

    2010-07-01

    Patients with early-stage, resectable, non-small-cell lung cancer (NSCLC) are at risk for recurrent disease, and 5-year survival rates do not exceed 75%. Angiogenesis inhibitors have shown clinical activity in patients with late-stage NSCLC, raising the possibility that targeting the vascular endothelial growth factor pathway in earlier-stage disease may be beneficial. This proof-of-concept study examined safety and efficacy of short-term, preoperative pazopanib monotherapy in patients with operable stage I/II NSCLC. Patients scheduled for resection received oral pazopanib 800 mg/d for 2 to 6 weeks preoperatively. Tumor response was measured by high-resolution computed tomography, permitting estimation of change in tumor volume and diameter. Gene-expression profiling was performed on 77 pre- and post-treatment lung samples from 34 patients. Of 35 patients enrolled, 33 (94%) had clinical stage I NSCLC and two (6%) had clinical stage II NSCLC. Median treatment duration was 16 days (range, 3 to 29 days). Thirty patients (86%) achieved tumor-volume reduction after pazopanib treatment. Two patients achieved tumor-volume reduction > or = 50%, and three patients had partial response according to Response Evaluation Criteria in Solid Tumors. Pazopanib was generally well tolerated. The most common adverse events included grade 2 hypertension, diarrhea, and fatigue. One patient developed pulmonary embolism 11 days after surgery. Several pazopanib target genes and other angiogenic factors were dysregulated post-treatment. Short-duration pazopanib was generally well tolerated and demonstrated single-agent activity in patients with early-stage NSCLC. Several target genes were dysregulated after pazopanib treatment, validating target-specific response and indicating a persistent pazopanib effect on lung cancer tissue. Further clinical evaluation of pazopanib in NSCLC is planned.

  4. Pneumonectomy for non-small cell lung cancer: predictors of early mortality and morbidity.

    Science.gov (United States)

    Stolz, A J; Harustiak, T; Simonek, J; Schützner, J; Lischke, R

    2014-01-01

    The aim of this study was to determine independent risk factors affecting postoperative morbidity and mortality after pneumonectomy for non-small cell lung cancer (NSCLC). A review of 329 patients having pneumonectomy for NSCLC between January 1, 1998 and July 31,2012 was undertaken. Factors affecting morbidity and mortality were analyzed by univariate and multivariate analyses. The overall 30-day mortality rate was 5.1%. Smoking habits, chronic obstructive pulmonary disease (COPD) status, neoadjuvant therapy and obesity had no statistical influence on the short-term outcome. Coronary artery disease and respiratory failure were identified as risk factors for increased 30-day mortality (p < 0.01). Right pneumonectomy and presence of respiratory failure with mechanical ventilation increased the incidence of bronchopleural fistula (p < 0.01). Pneumonectomy for NSCLC carries an acceptable operative morbidity and mortality. Coronary artery disease, right pneumonectomy and respiratory failure adversely affect morbidity and mortality after this procedure.

  5. Chronic obstructive pulmonary disease in stage I non-small cell lung cancer that underwent anatomic resection: the role of a recurrence promoter.

    Science.gov (United States)

    Kuo, Chih-Hsi; Wu, Ching-Yang; Lee, Kang-Yun; Lin, Shu-Min; Chung, Fu-Tsai; Lo, Yu-Lun; Liu, Chien-Ying; Hsiung, Te-Chih; Yang, Cheng-Ta; Wu, Yi-Cheng

    2014-08-01

    Despite the use of anatomic resection, the post-surgical recurrence rate remains high in early-stage non-small cell lung cancer (NSCLC). Chronic inflammation plays a role in the mechanism that promotes tumor initiation. This study aimed to investigate the association between recurrence outcome and chronic inflammation-related co-morbidities in early-stage resected NSCLC. A review of medical records for recurrence outcome and co-morbidities, in terms of chronic obstructive pulmonary disease (COPD), DM, asthma and cardiovascular diseases, was performed with 181 patients with stage I NSCLC that underwent anatomic resection. Subjects with T descriptors as T2a disease (49.5 vs. 28.0%, p recurrence. Univariate analysis for recurrence-free survival showed T descriptor as T2a (21.5 months vs. NR, p recurrence-free survival in the Cox regression model. Patients with COPD were at higher risk of brain recurrence (OR: 7.88; 95% CI, 1.50-41.3, p recurrence in bone and liver (OR: 4.13; 95% CI, 1.08-15.8, p = 0.05). Subjects with COPD and T2a disease had a higher risk of recurrence. The role of COPD as a recurrence promoter merits further prospective investigation.

  6. Methylation of breast cancer susceptibility gene 1 (BRCA1) predicts recurrence in patients with curatively resected stage I non-small cell lung cancer.

    Science.gov (United States)

    Harada, Hiroaki; Miyamoto, Kazuaki; Yamashita, Yoshinori; Nakano, Kikuo; Taniyama, Kiyomi; Miyata, Yoshihiro; Ohdan, Hideki; Okada, Morihito

    2013-02-15

    Even after early detection and curative resection of early stage non-small cell lung cancer (NSCLC), a significant fraction of patients develop recurrent disease. Molecular biomarkers that can predict the risk of recurrence thus need to be identified to improve clinical outcomes. Using the methylation-specific polymerase chain reaction assay, promoter methylation of the breast cancer susceptibility gene 1 (BRCA1) was assessed in cancer tissues from 70 patients with curatively resected stage I NSCLC. The clinical relevance of BRCA1 methylation status was evaluated in terms of outcome of the disease. Methylation of the BRCA1 promoter was detected in 13 of 70 patients (18.6%). Multiple logistic regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence (P = .0197) and that patients with BRCA1 methylation demonstrated significantly poorer recurrence-free survival compared to those without (P = .0139). Cox's proportional hazard regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence-free survival (P = .0155). Methylated BRCA1 can be a potential biomarker that predicts the prognosis after curative resection of stage I NSCLC. Considering that BRCA1 plays a role in chemotherapy-induced apoptosis, it is plausible that identification of methylated BRCA1 could provide information that is clinically relevant to tailored adjuvant therapy. Copyright © 2013 American Cancer Society.

  7. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Jeremy P. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Murphy, James D. [Department of Radiation Medicine and Applied Science, University of California– San Diego, Moores Cancer Center, La Jolla, California (United States); Hanlon, Alexandra L. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania (United States); Le, Quynh-Thu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W., E-mail: BWLoo@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: diehn@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States)

    2014-03-15

    Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.

  8. Multimodality approach to mediastinal staging in non-small cell lung cancer. Faults and benefits of PET-CT: a randomised trial

    DEFF Research Database (Denmark)

    Fischer, Barbara M; Mortensen, Jann; Hansen, Hanne

    2011-01-01

    Correct mediastinal staging is a cornerstone in the treatment of patients with non-small cell lung cancer. A large range of methods is available for this purpose, making the process of adequate staging complex. The objective of this study was to describe faults and benefits of positron emission t...

  9. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer : a pooled analysis of two randomised trials

    NARCIS (Netherlands)

    Chang, Joe Y.; Senan, Suresh; Paul, Marinus A.; Mehran, Reza J.; Louie, Alexander V.; Balter, Peter; Groen, Harry; McRae, Stephen E.; Widder, Joachim; Feng, Lei; van den Borne, Ben E. E. M.; Munsell, Mark F.; Hurkmans, Coen; Berry, Donald A.; van Werkhoven, Erik; Kresl, John J.; Dingemans, Anne-Marie; Dawood, Omar; Haasbeek, Cornelis J. A.; Carpenter, Larry S.; De Jaeger, Katrien; Komaki, Ritsuko; Slotman, Ben J.; Smit, Egbert F.; Roth, Jack A.

    2015-01-01

    Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 tria

  10. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer : a pooled analysis of two randomised trials

    NARCIS (Netherlands)

    Chang, Joe Y.; Senan, Suresh; Paul, Marinus A.; Mehran, Reza J.; Louie, Alexander V.; Balter, Peter; Groen, Harry; McRae, Stephen E.; Widder, Joachim; Feng, Lei; van den Borne, Ben E. E. M.; Munsell, Mark F.; Hurkmans, Coen; Berry, Donald A.; van Werkhoven, Erik; Kresl, John J.; Dingemans, Anne-Marie; Dawood, Omar; Haasbeek, Cornelis J. A.; Carpenter, Larry S.; De Jaeger, Katrien; Komaki, Ritsuko; Slotman, Ben J.; Smit, Egbert F.; Roth, Jack A.

    Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3

  11. Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schirrmeister, Holger [Department of Nuclear Medicine, University of Kiel, Kiel (Germany); Arslandemir, Coskun; Hetzel, Martin [Department of Internal Medicine II, University of Ulm, Robert-Koch-Strasse 8, 89081, Ulm (Germany); Glatting, Gerhard; Buck, Andreas [Department of Nuclear Medicine, University of Ulm, Ulm (Germany); Mayer-Steinacker, Regine; Bommer, Martin [Department of Hematology and Oncology, University of Ulm, Ulm (Germany); Dreinhoefer, Karsten [Department of Orthopedics, University of Ulm, Ulm (Germany)

    2004-07-01

    The leading European and American professional societies recommend that bone scans (BS) should be performed in the staging of lung cancer only in those patients with bone pain. This prospective study investigated the sensitivity of conventional skeletal scintigraphy in detecting osseous metastases in patients with lung cancer and addressed the potential consequences of failure to use this method in the work-up of asymptomatic patients. Subsequent to initial diagnosis of non-small cell lung cancer, 100 patients were examined and questioned regarding skeletal complaints. Two specialists in internal medicine decided whether they would recommend a bone scan on the basis of the clinical evaluation. Skeletal scintigraphy was then performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI) of the vertebral column, positron emission tomography (PET) of skeletal bone and the subsequent clinical course served as the gold standard for the identification of osseous metastases. Bone scintigraphy showed an 87% sensitivity in the detection of bone metastases. Failure to perform skeletal scintigraphy in asymptomatic patients reduced the sensitivity of the method, depending on the interpretation of the symptoms, to 19-39%. Without the findings of skeletal scintigraphy and the gold standard methods, 14-22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. On this basis it is concluded that bone scans should not be omitted in asymptomatic patients. (orig.)

  12. Clinical Application of Adjuvant Treatment after Operation in Patients with Stage IIIa Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yajie GAO

    2010-04-01

    Full Text Available Background and objective The efficacy of complete resection of the cancer for patients with stage IIIa non-small cell lung cancer (NSCLC is limited. Synthetic therapy is taken the lead in advocating at present. However, the value of post-operative radiotherapy is not still clear. The aim of this study is to evaluate the survival time and side effects of postoperative chemotherapy or chemoradiotherapy in the treatment of stage IIIa NSCLC. Methods Between December 2003 and June 2007, 52 cases that have completed followed-up data with stage IIIa of NSCLC received in the First Affiliated Hospital of Dalian Medical University. Twenty-three patients received postoperative chemoradiotherapy (group A and 29 patients received postoperative chemotherapy combined with radiotherapy (group B. Group A adopted platinum-based combination chemotherapy for 4-6 cycles. The chemotherapeutics included gemcitabine, vinorelbine and docetaxel. Group B used chemotherapy for 2-4 cycles and then received 3-dimensional conformal radiotherapy (3D-CRT. The prescribe dose of target volume was 50 Gy. The chemotherapy was same as for group A and needed 4 cycles in all. The impact of postoperative adjuvant treatment on survival and toxicity was observed in patients with stage IIIa NSCLC and the reason of disease progression was analyzed. Results The median survival was 32.5 months in group A and 31.9 months in group B (P=0.371. Progression-free survival extended about 6 months (P=0.044. The survival rate was 87% at 1 year, 0.1% at 2 year, 33% at 3 year for group A compared with 93%, 69%, 45% for group B. The major side effects were hematological and gastrointestinal toxicities, including nausea, vomiting and neutropenia. There was no significant difference in these toxicities between the two groups (P>0.05. Radioactiv esophageal infection occurred in 17.2% of the patients. Acute and late radioactive lung infection occurred in 13.8% and 27.6% of the patients. All these toxicities

  13. Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

    Energy Technology Data Exchange (ETDEWEB)

    Varlotto, John M., E-mail: john.varlotto@umassmemorial.org [Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts (United States); Yao, Aaron N. [Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia (United States); DeCamp, Malcolm M. [Division of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Chicago, Illinois (United States); Northwestern University School of Medicine, Chicago, Illinois (United States); Ramakrishna, Satvik [Northwestern University School of Medicine, Chicago, Illinois (United States); Recht, Abe [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Flickinger, John [Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Andrei, Adin [Northwestern University, Chicago, Illinois (United States); Reed, Michael F. [Pennsylvania State University College of Medicine, Hershey, Pennsylvania (United States); Heart and Vascular Institute, Pennsylvania State University-Hershey, Hershey, Pennsylvania (United States); Toth, Jennifer W. [Pennsylvania State University College of Medicine, Hershey, Pennsylvania (United States); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Pennsylvania State University-Hershey, Hershey, Pennsylvania (United States); Fizgerald, Thomas J. [Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts (United States); Higgins, Kristin [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Zheng, Xiao [Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia (United States); Shelkey, Julie [Department of Anesthesiology, Columbia University, New York, New York (United States); and others

    2015-03-15

    Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective

  14. A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically-resected stage I-IIIA non-small cell lung cancers

    Science.gov (United States)

    Drilon, Alexander; Sugita, Hirofumi; Sima, Camelia S.; Zauderer, Marjorie; Rudin, Charles M.; Kris, Mark G.; Rusch, Valerie W.; Azzoli, Christopher G.

    2014-01-01

    Introduction While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene (TSG) promoter methylation in early-stage non-small cell lung cancers (NSCLCs), few studies have investigated this question prospectively. Methods Primary tumor tissue from patients with resected pathologic stage I-IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse-transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual TSGs (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. Results 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (66%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p=0.03). The total number of genes with methylated promoters did not correlate with RFS (p=0.89) or OS (p=0.55). Conclusions Contrary to data established by previous retrospective series, TSG promoter methylation (CDKN2A, CDH13, RASSF1,APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs. PMID:25122424

  15. Macrophage Inhibitory Cytokine-1 (MIC-1 as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuning LIU

    2016-04-01

    Full Text Available Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1, member of transforming growth factor-β (TGF-β superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC. Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001 and benign pulmonary disease patients (P<0.001. A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001, female (P=0.03 and T2 (P=0.022. A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%. Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

  16. Clinical outcome and predictors of survival and pneumonitis after stereotactic ablative radiotherapy for stage I non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Chang Joe Y

    2012-09-01

    Full Text Available Abstract Background Stereotactic ablative radiotherapy (SABR can achieve excellent local control rates in early-stage non-small cell lung cancer (NSCLC and has emerged as a standard treatment option for patients who cannot undergo surgery or those with isolated recurrences. However, factors that may predict toxicity or survival are largely unknown. We sought here to identify predictors of survival and pneumonitis after SABR for NSCLC in a relatively large single-institution series. Methods Subjects were 130 patients with stage I NSCLC treated with four-dimensional computed tomography (4D CT –planned, on-board volumetric image–guided SABR to 50 Gy in 4 fractions. Disease was staged by positron emission tomography/computed tomography (PET/CT and scans were obtained again at the second follow-up after SABR. Results At a median follow-up time of 26 months, the 2-year local control rate was 98.5%. The median overall survival (OS time was 60 months, and OS rates were 93.0% at 1 year, 78.2% at 2 years, and 65.3% at 3 years. No patient experienced grade 4–5 toxicity; 15 had radiation pneumonitis (12 [9.3%] grade 2 and 3 [2.3%] grade 3. Performance status, standardized uptake value (SUVmax on staging PET/CT, tumor histology, and disease operability were associated with OS on univariate analysis, but only staging SUVmax was independently predictive on multivariate analysis (P = 0.034. Dosimetric factors were associated with radiation pneumonitis on univariate analysis, but only mean ipsilateral lung dose ≥9.14 Gy was significant on multivariate analysis (P = 0.005. Conclusions OS and radiation pneumonitis after SABR for stage I NSCLC can be predicted by staging PET SUVmax and ipsilateral mean lung dose, respectively.

  17. Dosimetric Feasibility of Dose Escalation Using SBRT Boost for Stage III Non-Small Cell Lung Cancer

    Science.gov (United States)

    Hepel, Jaroslaw T.; Peter, Justin; Hiatt, Jessica R.; Patel, Salil; Osibanjo, Oluwademilade; Safran, Howard; Curran, Bruce; DiPetrillo, Thomas

    2012-01-01

    Purpose: Standard chemoradiation therapy for stage III non-small cell lung cancer (NSCLCa) results in suboptimal outcomes with a high rate of local failure and poor overall survival. We hypothesize that dose escalation using stereotactic body radiotherapy (SBRT) boost could improve upon these results. We present here a study evaluating the dosimetric feasibility of such an approach. Methods: Anonymized CT data sets from five randomly selected patients with stage III NSCLCa undergoing definitive chemoradiation therapy in our department with disease volumes appropriate for SBRT boost were selected. Three-dimensional conformal radiation therapy (3D-CRT) plans to 50.4 Gy in 28 fractions were generated follow by SBRT plans to two dose levels, 16 Gy in two fractions and 28 Gy in two fractions. SBRT plans and total composite (3D-CRT and SBRT) were optimized and evaluated for target coverage and dose to critical structures; lung, esophagus, cord, and heart. Results: All five plans met predetermined target coverage and normal tissue dose constraints. PTV V95 was equal to or greater than 95% in all cases. The cumulative lung V20 and V5 of the combined 3D-CRT and SBRT plans were less than or equal to 30 and 55%, respectively. The 5 cc esophageal dose was less than 12 Gy for all low and high dose SBRT plans. The cumulative dose to the esophagus was also acceptable with less than 10% of the esophagus receiving doses in excess of 50 Gy. The cumulative spinal cord dose was less than 33 Gy and heart V25 was less than 5%. Conclusion: The combination of chemoradiation to 50.4 Gy followed by SBRT boost to gross disease at the primary tumor and involved regional lymph nodes is feasible with respect to normal tissue dose constraints in this dosimetric pilot study. A phase I/II trial to evaluate the clinical safety and efficacy of this approach is being undertaken. PMID:23057009

  18. Dosimetric and technical aspects of intraoperative I-125 brachytherapy for stage I non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Mark [Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 (United States); Colonias, Athanasios [Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 (United States); Parda, David [Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 (United States); Trombetta, Mark [Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 (United States); Gayou, Olivier [Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 (United States); Reitz, Bodo [Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 (United States); Miften, Moyed [Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 (United States)

    2007-03-07

    Initial treatment outcome data from our institution for stage I non-small cell lung cancer (NSCLC) patients have shown that sublobar resection in combination with iodine-125 (I-125) brachytherapy is associated with recurrence rates of 2.0%, compared to 18.6% with sublobar resection alone. In this work, the technical and dosimetric aspects required to execute this procedure from the radiation oncology perspective as well as an analysis of the dose distributions of patients treated with this technique are presented. In this treatment technique, I-125 seeds in vicryl suture are embedded into vicryl mesh and surgically inserted providing a 2.0 cm margin on each side of the resection staple line. A nomogram is developed to determine the suture spacing in the vicryl mesh, as a function of seed activity in order to deliver 120 Gy at a distance of 0.5 cm above and below the seed array. Post-operative dosimetry consists of a CT-based planning and dose volume analysis. Dose distributions, dose volume histograms and mean dose data for lung are analysed in a group of patients. Dosimetric results show significant lung sparing with only a small volume of lung irradiated for all patients with mean lung dose values ranging from 1.5 Gy to 5.4 Gy. Lung brachytherapy with I-125 at the time of sublobar resection is a highly conformal option of dose delivery for stage I NSCLC patients with compromised physiologic reserve. Patient-related toxicity clinically measured by loss of pulmonary function and radiation-induced pneumonitis have not been linked to this procedure.

  19. Dosimetric and technical aspects of intraoperative I-125 brachytherapy for stage I non-small cell lung cancer

    Science.gov (United States)

    Johnson, Mark; Colonias, Athanasios; Parda, David; Trombetta, Mark; Gayou, Olivier; Reitz, Bodo; Miften, Moyed

    2007-03-01

    Initial treatment outcome data from our institution for stage I non-small cell lung cancer (NSCLC) patients have shown that sublobar resection in combination with iodine-125 (I-125) brachytherapy is associated with recurrence rates of 2.0%, compared to 18.6% with sublobar resection alone. In this work, the technical and dosimetric aspects required to execute this procedure from the radiation oncology perspective as well as an analysis of the dose distributions of patients treated with this technique are presented. In this treatment technique, I-125 seeds in vicryl suture are embedded into vicryl mesh and surgically inserted providing a 2.0 cm margin on each side of the resection staple line. A nomogram is developed to determine the suture spacing in the vicryl mesh, as a function of seed activity in order to deliver 120 Gy at a distance of 0.5 cm above and below the seed array. Post-operative dosimetry consists of a CT-based planning and dose volume analysis. Dose distributions, dose volume histograms and mean dose data for lung are analysed in a group of patients. Dosimetric results show significant lung sparing with only a small volume of lung irradiated for all patients with mean lung dose values ranging from 1.5 Gy to 5.4 Gy. Lung brachytherapy with I-125 at the time of sublobar resection is a highly conformal option of dose delivery for stage I NSCLC patients with compromised physiologic reserve. Patient-related toxicity clinically measured by loss of pulmonary function and radiation-induced pneumonitis have not been linked to this procedure.

  20. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Osti, Mattia Falchetto [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy); Agolli, Linda, E-mail: lindaagolli@yahoo.it [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy); Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy)

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  1. Is there a role for surgery in stage Ⅲ A-N2 non-small cell lung cancer?

    Institute of Scientific and Technical Information of China (English)

    Paul E. VAN SCHIL; Michèle DE WAELE; Jeroen M. HENDRIKS; Patrick R. LAUWERS

    2008-01-01

    The role of surgery in stage Ⅲ A-N2 non-small cell lung cancer (NSCLC) remains controversial.Most important prognostic factors are mediastinal downstaging and complete surgical resection. Different restaging techniques exist to evaluate response after induction therapy and these are subdivided into non-invasive, invasive and alternative or minimally invasive techniques. In contrast to imaging or functional studies, remediastinoscopy provides pathological evidence of response after induction therapy. Although technically more challenging than a first procedure,remediastinoscopy can select patients for subsequent thoracotomy and provides prognostic information. An alternative approach consists of the use of minimally invasive staging procedures as endobronchial or endoscopic esophageal ultrasound to obtain an initial proof of mediastinal nodal involvement. Mediastinoscopy is subsequently performed after induction therapy to evaluate response. In this way, a technically more difficult remediastinoscopy can be avoided. Stage ⅢA-N2 NSCLC represents a heterogenous spectrum of locally advanced disease and different subsets exist. When N2 disease is discovered during thoracotomy after negative, careful preoperative staging a resection should be performed if this can be complete. Postoperative radiotherapy will decrease local recurrence rate but not overall survival. Adjuvant chemotherapy increases survival and is presently recommended in these cases. Most patients with pathologically proven N2 disease detected during preoperative work-up will be treated by induction therapy followed by surgery or radiotherapy.In two large, recently completed, phase Ill trials there was no difference in overall survival between the surgical and radiotherapy arm, but in one trial there was a difference in progression-free survival in favor of the surgical arm. In the surgery ann the rate of local recurrences was also lower in beth trials. Surgical resection may be recommended in those

  2. Prognostic factors for post-recurrence survival in patients with completely resected Stage I non-small-cell lung cancer.

    Science.gov (United States)

    Song, In Hag; Yeom, Sung Won; Heo, Seohee; Choi, Won Suk; Yang, Hee Chul; Jheon, Sanghoon; Kim, Kwhanmien; Cho, Sukki

    2014-02-01

    The clinical course from recurrence to cancer-related death after curative resection has not been clearly elucidated in non-small-cell lung cancer (NSCLC). This study examined the clinical outcomes after postoperative recurrence in patients with completely resected Stage I NSCLC. This study included patients who had recurrence after complete resection for pathological Stage I NSCLC between 2003 and 2009. Clinical data evaluated in this study included the diagnostic process of recurrence, recurrence pattern, treatment process and prognosis. A number of clinicopathological factors were analysed for post-recurrence survival by univariate and multivariate analyses. Seventy-two patients experienced recurrence during a median follow-up period of 37.5 months. Thirteen patients (18%) presented symptoms at the initial recurrence. Tumour markers, computed tomography (CT) and positron emission tomography/CT were chosen as the initial diagnostic tools and detected recurrences in 1 (1%), 51 (71%) and 7 (10%) patients, respectively. The mean recurrence-free interval (RFI) was 15.4 months (≤12 months in 34, >12 months in 38 patients). The patterns of recurrence were presented as loco-regional recurrence in 36 (50%) and distant metastasis in 36 patients (50%). Types of the initial treatment included operations in 28 (39%), chemotherapy and/or radiotherapy in 38 (53%) and radiofrequency ablation in 2 patients (3%). Four patients (6%) rejected treatment. Forty-three patients (62%) presented a good response to the initial treatment. Thirty-seven patients (51%) died, and the cause of death in all of these patients was cancer-related. The median survival duration after recurrence was 43.6 (1-136) months. Univariate analysis identified no recurrence of symptoms, a good response to treatment and a longer RFI as good prognostic factors, while a good response to treatment and a longer RFI were independent prognostic factors in multivariate analysis. Most postoperative recurrences were

  3. The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer.

    Science.gov (United States)

    Ishikawa, Rie; Amano, Yosuke; Kawakami, Masanori; Sunohara, Mitsuhiro; Watanabe, Kousuke; Kage, Hidenori; Ohishi, Nobuya; Yatomi, Yutaka; Nakajima, Jun; Fukayama, Masashi; Nagase, Takahide; Takai, Daiya

    2016-02-01

    Stage IA non-small-cell lung cancer cases have been recognized as having a low risk of relapse; however, occasionally, relapse may occur. To predict clinical outcome in Stage IA non-small-cell lung cancer patients, we searched for chimeric transcripts that can be used as biomarkers and identified a novel chimeric transcript, RUNX1-GLRX5, comprising RUNX1, a transcription factor, and GLRX5. This chimera was detected in approximately half of the investigated Stage IA non-small-cell lung cancer patients (44/104 cases, 42.3%). Although there was no significant difference in the overall survival rate between RUNX1-GLRX5-positive and -negative cases (P = 0.088), a significantly lower relapse rate was observed in the RUNX1-GLRX5-positive cases (P = 0.039), indicating that this chimera can be used as a biomarker for good prognosis in Stage IA patients. Detection of the RUNX1-GLRX5 chimeric transcript may therefore be useful for the determination of a postoperative treatment plan for Stage IA non-small-cell lung cancer patients.

  4. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer.

    Science.gov (United States)

    Azzoli, Christopher G; Baker, Sherman; Temin, Sarah; Pao, William; Aliff, Timothy; Brahmer, Julie; Johnson, David H; Laskin, Janessa L; Masters, Gregory; Milton, Daniel; Nordquist, Luke; Pfister, David G; Piantadosi, Steven; Schiller, Joan H; Smith, Reily; Smith, Thomas J; Strawn, John R; Trent, David; Giaccone, Giuseppe

    2009-12-20

    The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non-small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy.

  5. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ding Xiao

    2012-07-01

    Full Text Available Abstract Background Brain metastases (BM is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2 NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. Methods Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. Results Fifty-three (24.4 % patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001 and the ratio of metastatic to examined nodes or lymph node ratio (LNR ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000 were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. Conclusions In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

  6. COMPARISON OF COMPUTED-TOMOGRAPHY AND CO-57 BLEOMYCIN SCINTIGRAPHY IN STAGING THE MEDIASTINAL LYMPH-NODES OF PATIENTS WITH NON-SMALL-CELL LUNG-CANCER

    NARCIS (Netherlands)

    VANDERLAAN, JG; VANDENBRINK, A; PIERS, DA; BEEKHUIS, H; KENGEN, RA

    1990-01-01

    The value of computed tomography (CT) and of Co-57-bleomycin scintigraphy (Co-57-BLM) in staging the mediastinal lymph nodes was compared in 28 patients suffering from non-small-cell lung cancer. The results were assessed against the pathological findings obtained during thoracotomy or

  7. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer

    NARCIS (Netherlands)

    J.P. van Meerbeeck (Jan); G.W.P.M. Kramer (Gijs); P.E.Y. van Schil (Paul); C. Legrand; E.F. Smit (Egbert); F.M.N.H. Schramel (Franz); V.C.G. Tjan-Heijnen (Vivianne); B. Biesma (Bonne); C. Debruyne (Channa); N. van Zandwijk (Nico); T.A.W. Splinter (Ted); G. Giaccone (Giuseppe)

    2007-01-01

    textabstractBackground: Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non - small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be su

  8. Impact of Introducing Stereotactic Lung Radiotherapy for Elderly Patients With Stage I Non-Small-Cell Lung Cancer : A Population-Based Time-Trend Analysis

    NARCIS (Netherlands)

    Palma, David; Visser, Otto; Lagerwaard, Frank J.; Belderbos, Jose; Slotman, Ben J.; Senan, Suresh

    2010-01-01

    Purpose Stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) is associated with high local control rates. The impact of introducing SBRT in patients 75 years of age or older was studied using a population-based cancer registry. Methods The Amsterdam Cancer Registry wa

  9. Residual F-18-FDG-PET Uptake 12 Weeks After Stereotactic Ablative Radiotherapy for Stage I Non-Small-Cell Lung Cancer Predicts Local Control

    NARCIS (Netherlands)

    Bollineni, Vikram Rao; Widder, Joachim; Pruim, Jan; Langendijk, Johannes A.; Wiegman, Erwin M.

    2012-01-01

    Purpose: To investigate the prognostic value of [F-18]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake at 12 weeks after stereotactic ablative radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC). Methods and Materials: From November 2006 to February 2010, 132 medically

  10. Influence of Body Mass Index on the Prognostic Value of Tumor ¹⁸F-FDG Uptake in Stage I Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Hyun, Seung Hyup; Lee, Kyung-Han; Choi, Joon Young; Kim, Byung-Tae; Kim, Jhingook; Zo, Jae Ill; Kim, Hojoong; Kwon, O Jung; Ahn, Hee Kyung

    2015-01-01

    The impact of host energy balance status on outcome of lung cancer has not been fully explored. It is also unknown if there is a potential modifying effect of body mass index (BMI) on tumor cell behavior in patients with early-stage non-small cell lung cancer (NSCLC). We therefore investigated the interactive effects of tumor [18F]-fluorodeoxyglucose (FDG) avidity and BMI. We investigated 1,197 patients with stage I NSCLC who underwent preoperative FDG positron emission tomography followed by curative resection. The primary outcome measure was disease-free survival (DFS). A multivariable Cox proportional hazards model was used to assess the potential independent effects of the prognostic variables. A stratified Cox regression analysis was also performed to assess the potential modifying effects of BMI on the relationship between tumor FDG uptake and patient survival. There were 145 tumor recurrences and 19 deaths during a median follow-up of 30 months. Tumor-related variables, including tumor size, maximum standardized uptake value (SUVmax), histologic cell type, differentiation, lymphovascular invasion, and visceral pleural invasion, did not differ significantly according to BMI status. In multivariable Cox regression analysis, overweight or obesity [hazard ratio (HR), 0.59; 95% CI, 0.43-0.81; P = 0.001] and tumor SUVmax (HR, 1.72; 95% CI, 1.43-2.07; P obese patients (HR, 2.61; 95% CI, 1.58-4.31; P obese patients. These results suggest that the host-tumor interaction between host energy balance status and tumor glucose metabolism plays an important role in the outcome of early-stage NSCLC.

  11. Cell proliferation and apoptosis in stage III inoperable non-small cell lung carcinoma treated by radiotherapy

    NARCIS (Netherlands)

    Langendijk, H; Thunnissen, E; Arends, JW; de Jong, J; ten Velde, G; Lamers, R; Guinee, D; Holden, J; Wouters, M

    2000-01-01

    Purpose: The purpose of this study was to assess the prognostic value of the expression of p53 and bcl-2, the apoptotic index and the expression of topoisomerase II alpha in patients with inoperable non-small cell lung cancer (NSCLC) treated with high dose radiotherapy. Patients and methods: A numbe

  12. 扣除杂交法筛选与非小细胞性肺癌转移相关的基因%Identification of Metastasis-associated Genes in Early Stage Non-small Cell Lung Cancer by Subtractive Hybridization

    Institute of Scientific and Technical Information of China (English)

    王文兵; B(..O)ING Sebastian; 周小琴; 季平; 董英; 姚勤; M(..U)LLER-TIDOW Carsten

    2002-01-01

    Nons-mall cell lung cancer (NSCLC) is a leading cause of death and asubstantial fraction of patients with surgically resected disease ultimately dies due to distant metastasis. To identify gene expression differences in early stage adenocarcinoma that either did or did not metastasize within a 5year period, we employed a subtractive hybridization strategy of pooled RNA from primary adenocarcinomas (stage I) of the lung. Individual clones (n=225) of the subtracted Cdna library were sequenced. Further analyses of Mrna expression levels in a cohort of 70 NSCLC patients (stage I to IIIA) showed that the metastasis association of the identified genes was stage and histology specific. Cox regression analyses identified two genes (EIF4A1, MALA1) to be independent prognostic parameters for patients' survival in stage I and II disease. These findings could help to identify early-stage NSCLC patients at high risk for the development of distant metastasis.%非小细胞性肺癌病人的术后死亡率很高, 其原因是该病易发生转移. 收集了肺癌早期患者的样品, 并根据患者资料分成转移型(n=4)和非转移型(n=5), 采用扣除杂交法筛选与非小细胞性肺癌转移相关的基因. 扣除后的cDNA文库中得到了225个有效克隆. 对这些克隆进行了测序, 在基因文库中比较了核苷酸同源性, 初步确定了这些克隆对应的基因, 并根据基因可能涉及的功能加以分类. 通过实时(real time) RT-PCR鉴定, 发现10种基因在用于扣除试验的转移病人样品中的平均表达量比非转移病人高. 进一步对 70位患非小细胞性肺癌病人(I至IIIA期)的样品进行了检测. 根据统计分析, 在I和II期病人中, 2种基因MALA1和EIF4A1在发生转移的病人样品中的表达与在非转移的病人中有显著差异性. 这些结果将有助于分析非小细胞性肺癌病变发生转移的可能性.

  13. Influence of Body Mass Index on the Prognostic Value of Tumor ¹⁸F-FDG Uptake in Stage I Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Seung Hyup Hyun

    Full Text Available The impact of host energy balance status on outcome of lung cancer has not been fully explored. It is also unknown if there is a potential modifying effect of body mass index (BMI on tumor cell behavior in patients with early-stage non-small cell lung cancer (NSCLC. We therefore investigated the interactive effects of tumor [18F]-fluorodeoxyglucose (FDG avidity and BMI.We investigated 1,197 patients with stage I NSCLC who underwent preoperative FDG positron emission tomography followed by curative resection. The primary outcome measure was disease-free survival (DFS. A multivariable Cox proportional hazards model was used to assess the potential independent effects of the prognostic variables. A stratified Cox regression analysis was also performed to assess the potential modifying effects of BMI on the relationship between tumor FDG uptake and patient survival.There were 145 tumor recurrences and 19 deaths during a median follow-up of 30 months. Tumor-related variables, including tumor size, maximum standardized uptake value (SUVmax, histologic cell type, differentiation, lymphovascular invasion, and visceral pleural invasion, did not differ significantly according to BMI status. In multivariable Cox regression analysis, overweight or obesity [hazard ratio (HR, 0.59; 95% CI, 0.43-0.81; P = 0.001] and tumor SUVmax (HR, 1.72; 95% CI, 1.43-2.07; P < 0.001 were significantly associated with DFS. There was a significant modifying effect of BMI (P for interaction < 0.001 in multivariable analysis. High tumor SUVmax was more strongly associated with worse DFS in normal weight patients (HR, 4.72; 95% CI, 2.77-8.06; P < 0.001 than in overweight or obese patients (HR, 2.61; 95% CI, 1.58-4.31; P < 0.001.Tumor FDG avidity is an independent predictor of DFS in patients with early-stage NSCLC and this prognostic value was strengthened in normal weight patients than in overweight or obese patients. These results suggest that the host-tumor interaction between

  14. Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer

    Science.gov (United States)

    Grossi, Francesco; Dal Bello, Maria Giovanna; Salvi, Sandra; Puzone, Roberto; Pfeffer, Ulrich; Fontana, Vincenzo; Alama, Angela; Rijavec, Erika; Barletta, Giulia; Genova, Carlo; Sini, Claudio; Ratto, Giovanni Battista; Taviani, Mario; Truini, Mauro; Merlo, Domenico Franco

    2015-01-01

    Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients. PMID:26663950

  15. Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Grossi

    2015-01-01

    Full Text Available Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1, breast cancer 1 (BRCA1, ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2, subunit p53R2, thymidylate synthase (TS, and class III beta-tubulin (TUBB3. Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS. Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients.

  16. New positron emission tomography derived parameters as predictive factors for recurrence in resected stage I non-small cell lung cancer.

    Science.gov (United States)

    Melloni, G; Gajate, A M S; Sestini, S; Gallivanone, F; Bandiera, A; Landoni, C; Muriana, P; Gianolli, L; Zannini, P

    2013-11-01

    The recurrence rate for stage I non-small cell lung cancer is high, with 20-40% of patients that relapse after surgery. The aim of this study was to evaluate new F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) derived parameters, such as standardized uptake value index (SUVindex), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as predictive factors for recurrence in resected stage I non-small cell lung cancer. We retrospectively reviewed 99 resected stage I non-small cell lung cancer patients that were grouped by SUVindex, TLG and MTV above or below their median value. Disease free survival was evaluated as primary end point. The 5-year overall survival and the 5-year disease free survival rates were 62% and 73%, respectively. The median SUVindex, MTL and TLG were 2.73, 2.95 and 9.61, respectively. Patients with low SUVindex, MTV and TLG were more likely to have smaller tumors (p ≤ 0.001). Univariate analysis demonstrated that SUVindex (p = 0.027), MTV (p = 0.014) and TLG (p = 0.006) were significantly related to recurrence showing a better predictive performance than SUVmax (p = 0.031). The 5-year disease free survival rates in patients with low and high SUVindex, MTV and TLG were 84% and 59%, 86% and 62% and 88% and 60%, respectively. The multivariate analysis showed that only TLG was an independent prognostic factor (p = 0.014) with a hazard ratio of 4.782. Of the three PET-derived parameters evaluated, TLG seems to be the most accurate in stratifying surgically treated stage I non-small cell lung cancer patients according to their risk of recurrence. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Predictive Impact for Postoperative Recurrence of Preoperative Serum Krebs von den Lungen-6 Concentration in Pathologic Stage IA Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Shoji, Fumihiro; Yamazaki, Koji; Kouso, Hidenori; Mori, Ryo; Takeo, Sadanori

    2016-05-01

    Although stage IA non-small cell lung cancer has an optimistic survival rate, up to 10% of these patients relapse after surgical procedures and die. We retrospectively analyzed clinicopathologic features of patients with stage IA non-small cell lung cancer to identify recurrence predictors and to investigate effects of preoperative serum Krebs von den Lungen-6 (PS-KL-6) concentrations. We selected 204 consecutive patients with stage IA non-small cell lung cancer treated from December 2003 to December 2009 for this study and tested their PS-KL-6 concentrations in univariate and multivariate Cox regression analyses of recurrence-free survival (RFS). High PS-KL-6 concentration (PS-KL6(High)) was significantly associated with sex (p = 0.0006), smoking status (p = 0.0438), histology (p = 0.0049), and postoperative recurrence (p = 0.0058). Both intratumoral blood vessel invasion (p = 0.0345) and PS-KL6(High) (p = 0.0021) were identified as independent predictors of shorter RFS. Relative risk of patients with PS-KL6(High) was 3.478 compared with patients with low PS-KL-6 concentration (PS-KL6(Low); 95% confidence interval: 1.576 to 8.013). Among patients with tumors larger than 2 cm (T1b), the PS-KL6(High) group had significantly shorter RFS than the PS-KL6(Low) group (p = 0.0040). PS-KL-6 concentration is a simple and novel predictor of recurrence in patients with stage IA non-small cell lung cancer and might help to identify patients who will need more careful follow-up among T1bN0M0 series. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. CyberKnife radiosurgery for inoperable stage IA non-small cell lung cancer: 18F-fluorodeoxyglucose positron emission tomography/computed tomography serial tumor response assessment

    Directory of Open Access Journals (Sweden)

    Chang Thomas

    2010-02-01

    Full Text Available Abstract Objective To report serial 18F-fluorodeoxyglucose (18F-FDG positron emission tomography (PET/computed tomography (CT tumor response following CyberKnife radiosurgery for stage IA non-small cell lung cancer (NSCLC. Methods Patients with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved study. Targeting was based on 3-5 gold fiducial markers implanted in or near tumors. Gross tumor volumes (GTVs were contoured using lung windows; margins were expanded by 5 mm to establish the planning treatment volumes (PTVs. Doses ranged from 42-60 Gy in 3 equal fractions. 18F-FDG PET/CT was performed prior to and at 3-6-month, 9-15 months and 18-24 months following treatment. The tumor maximum standardized uptake value (SUVmax was recorded for each time point. Results Twenty patients with an average maximum tumor diameter of 2.2 cm were treated over a 3-year period. A mean dose of 51 Gy was delivered to the PTV in 3 to 11 days (mean, 7 days. The 30-Gy isodose contour extended an average of 2 cm from the GTV. At a median follow-up of 43 months, the 2-year Kaplan-Meier overall survival estimate was 90% and the local control estimate was 95%. Mean tumor SUVmax before treatment was 6.2 (range, 2.0 to 10.7. During early follow-up the mean tumor SUVmax remained at 2.3 (range, 1.0 to 5.7, despite transient elevations in individual tumor SUVmax levels attributed to peritumoral radiation-induced pneumonitis visible on CT imaging. At 18-24 months the mean tumor SUVmax for controlled tumors was 2.0, with a narrow range of values (range, 1.5 to 2.8. A single local failure was confirmed at 24 months in a patient with an elevated tumor SUVmax of 8.4. Conclusion Local control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional. Early transient increases in tumor SUVmax are likely related to radiation-induced pneumonitis. Tumor SUVmaxvalues return to background levels at 18-24 months, enhancing 18F-FDG PET

  19. DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update

    Directory of Open Access Journals (Sweden)

    Laird-Offringa Ite A

    2008-10-01

    Full Text Available Abstract Lung cancer is the number one cancer killer in the United States. This disease is clinically divided into two sub-types, small cell lung cancer, (10–15% of lung cancer cases, and non-small cell lung cancer (NSCLC; 85–90% of cases. Early detection of NSCLC, which is the more common and less aggressive of the two sub-types, has the highest potential for saving lives. As yet, no routine screening method that enables early detection exists, and this is a key factor in the high mortality rate of this disease. Imaging and cytology-based screening strategies have been employed for early detection, and while some are sensitive, none have been demonstrated to reduce lung cancer mortality. However, mortality might be reduced by developing specific molecular markers that can complement imaging techniques. DNA methylation has emerged as a highly promising biomarker and is being actively studied in multiple cancers. The analysis of DNA methylation-based biomarkers is rapidly advancing, and a large number of potential biomarkers have been identified. Here we present a detailed review of the literature, focusing on DNA methylation-based markers developed using primary NSCLC tissue. Viable markers for clinical diagnosis must be detectable in 'remote media' such as blood, sputum, bronchoalveolar lavage, or even exhaled breath condensate. We discuss progress on their detection in such media and the sensitivity and specificity of the molecular marker panels identified to date. Lastly, we look to future advancements that will be made possible with the interrogation of the epigenome.

  20. Predictors of early recurrence for node-negative t1 to t2b non-small cell lung cancer.

    Science.gov (United States)

    Kiankhooy, Armin; Taylor, Matthew D; LaPar, Damien J; Isbell, James M; Lau, Christine L; Kozower, Benjamin D; Jones, David R

    2014-10-01

    Recurrence develops in nearly one-third of patients who undergo complete resection for non-small cell lung cancer (NSCLC). We sought to identify predictors of early recurrence (lung cancer database. Exclusion criteria included carcinoid, adenocarcinoma in situ, and minimally invasive adenocarcinoma histologies, and any induction therapy. Patient demographics, clinical, and pathologic variables were analyzed. Recurrence was confirmed histologically in 86 patients (85%) or radiographically in 16 (15%). Univariable and multivariable logistic regression (C statistic = 0.7) and Cox proportional hazards analyses were performed (p Recurrence was present in 102 patients (19%) and was locoregional in 33 (32%), distant in 40 (39%), and multisite in 29 (29%). T size, tumor histology, tumor grade, smoking status, maximum standardized uptake value, and albumin were not associated with recurrence. Multivariable predictors of recurrence were lymphovascular invasion (odds ratio, 2.48), sublobar resection (odds ratio, 2.37), and age (odds ratio, 0.96). Recurrence was independently associated with lung cancer-specific death (relative risk, 11.78; 95% confidence interval, 5.46 to 25.36; p recurrence rate in R0 resected node-negative T1 to T2b NSCLC. The identification of unique predictors of recurrence is an important step toward defining a patient population that may benefit from adjuvant therapy. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Prediction of response by FDG PET early during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Su Zi; Oh, So Won; Kim, Jin Soo; Kim, Ki Hwan; Kim, Yu Kyeong [SMG-Seoul National University Boramae Medical Center, Seoul (Korea, Republic of)

    2014-12-15

    To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT.One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non-responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %DeltaSUVmax > or = 50% had PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with %DeltaSUVmean > or = 50% had PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT (p = 0.026). The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.

  2. 联合亚甲蓝和99mTc-硫胶体核素示踪法在早期非小细胞肺癌前哨淋巴结定位中的应用%Intraoperative methylene blue and 99mTc-sulfur colloid isotope tracing for sentinel node mapping in early-stage non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    洪斌; 沈学远; 陈江勇

    2014-01-01

    Objective To compare the accuracy of intaoperative methylene blue alone and in combination with 9 mTc-sulfur colloid isotopic tracing for detection of sentinel lymph nodes (SLNs) in early-stage non-small cell lung cancer (NSCLC). Methods Sixty-one patients with operable NSCLC who did not receive previous radiotherapy or chemotherapy were enrolled. Methylene blue and 9 mTc-sulfur colloid were injected into the subserosal layer adjacent to the tumor, and SLNs were defined as those with blue staining or those containing 3 times more radioactivity than the surrounding tissue detected with a gamma probe. The SLN were removed with systematic lymph node dissection. All the removed lymph nodes were examined histopathologically with HE staining and immunohistochemistry. Results Methylene blue alone showed a low detection rate (60.0%) and sensitivity (58.33%) for SLNs compared with the combination of methylene blue and isotope tracing (96.15%and 92.86%, respectively). Conclusion The combination of methylene blue and 9 mTc-sulfur colloid isotopic tracing allows accurate detection of the SLNs in early-stage NSCLC.%目的:通过评估亚甲蓝单独和联合99mTc-硫胶体核素示踪法在早期非小细胞肺癌(NSCLC)前哨淋巴结(SLN)定位的可行性,探讨SLN概念在NSCLC中的适用性。方法选择我院2008年3月~2011年5月收治的早期NSCLC 61例为研究对象,术中行SLN示踪剂注射并切除,其中注射亚甲蓝35例,亚甲蓝联合99mTc-硫胶体26例,并行肺叶切除+肺门及纵隔淋巴结清扫术,术后所有淋巴结均石蜡切片,行HE染色和抗细胞角蛋白抗体免疫组化检查。结果单独使用亚甲蓝组的SLN检出率60.0%,准确性76.19%,灵敏度58.33%,阴性预测值和假阴性率分别为90.0%和8.33%;亚甲蓝联合99mTc-硫胶体组在检出率96.15%,准确性96.0%,灵敏度92.86%,阴性预测值和假阴性率分别为91.67%和7.14%。结论(1)SLN的状态能够反映NSCLC肺

  3. Modeling Local Control After Hypofractionated Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Report From the Elekta Collaborative Lung Research Group

    Energy Technology Data Exchange (ETDEWEB)

    Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Werner-Wasik, Maria [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Grills, Inga S. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Belderbos, Jose [Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam (Netherlands); Hope, Andrew [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Yan Di; Kestin, Larry L. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Guckenberger, Matthias [Department of Radiation Oncology, University of Wuerzburg, Wuerzburg (Germany); Sonke, Jan-Jakob [Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam (Netherlands); Bissonnette, Jean-Pierre [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Xiao, Ying [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2012-11-01

    Purpose: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size. Methods and Materials: We formulated our TCP model as follows: TCP = e{sup [BED10-c Asterisk-Operator L-TCD50]/k} Division-Sign (1 + e{sup [BED10-c Asterisk-Operator L-TCD50]/k}), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates. Results: Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008). Conclusion: We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted.

  4. Radical cyberknife radiosurgery with tumor tracking: an effective treatment for inoperable small peripheral stage I non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Esposito Giuseppe

    2009-01-01

    Full Text Available Abstract Objective Curative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC, but radical radiosurgery may be effective. Methods Inoperable patients with small peripheral clinical stage I NSCLC were enrolled in this study. Three-to-five fiducial markers were implanted in or near tumors under CT guidance. Gross tumor volumes (GTVs were contoured using lung windows. The GTV margin was expanded by 5 mm to establish the planning treatment volume (PTV. A dose of 42–60 Gy was delivered to the PTV in 3 equal fractions in less than 2 weeks using the CyberKnife radiosurgery system. The 30-Gy isodose contour extended at least 1 cm from the GTV. Physical examination, CT imaging and pulmonary function testing were completed at 6 months intervals for three years following treatment. Results Twenty patients with an average maximum tumor diameter of 2.2 cm (range, 1.1 – 3.5 cm and a mean FEV1 of 1.08 liters (range, 0.53 – 1.71 L were treated. Pneumothorax requiring tube thoracostomy occurred following CT-guided fiducial placement in 25% of the patients. All patients completed treatment with few acute side effects and no procedure-related mortality. Transient chest wall discomfort developed in 8 of the 12 patients with lesions within 5 mm of the pleura. The mean percentage of the total lung volume receiving a minimum of 15 Gy was 7.3% (range, 2.4% to 11.3%. One patient who received concurrent gefitinib developed short-lived, grade III radiation pneumonitis. The mean percent predicted DLCO decreased by 9% and 11% at 6 and 12 months, respectively. There were no local failures, regional lymph node recurrences or distant metastases. With a median follow-up of 25 months for the surviving patients, Kaplan-Meier overall survival estimate at 2 years was 87%, with deaths due to COPD progression. Conclusion Radical CyberKnife radiosurgery is a well-tolerated treatment option for inoperable patients with small

  5. Classification and Risk-factor Analysis of Postoperative Cardio-pulmonary 
Complications after Lobectomy in Patients with Stage I Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yutian LAI

    2016-05-01

    Full Text Available Background and objective There are incresing lung cancer patients detected and diagnosed at the intermediate stage when the pre-malignant or early lesions are amenable to resection and cure, owing to the progress of medical technology, the renewal of detection methods, the popularity of medical screening and the improvement of social health consciousness. The aim of this study is to investigate the risk factors of the occurrence of postoperative cardio-pulmonary complications in stage I non-small cell lung cancer (NSCLC patients, based on routine laboratory tests, basic characteristics, and intraoperative variables in hospital. Methods The 421 patients after lobectomy in patients with stage I NSCLC at the West China Hospital of Sichuan University from January 2012 to December 2013 were included into the study and stratified into complication group and non-complication group, according to whether to occur postoperative cardio-pulmonary complications after lobectomy in 30 days. Results Of them, 64 (15.2% patients were finally identified and selected into the complication group, compared with 357 (84.8% in non-complication group: pneumonia (8.8%, 37/421 was the primary complication, and other main complications included atelectasis (5.9%, 25/421, pleural effusion (≥middle (5.0%, 21/421, persistent air leak (3.6%, 15/421; The operation time (P=0.007, amount of blood loss (P=0.034, preoperative chronic obstructive pulmonary disease (COPD (P=0.027, white blood cell (WBC count (P<0.001, neutrophil-lymphocyte ratio (NLR (P<0.001 were significantly different between the two groups. According to the binary logistics regression analysis, preoperative COPD (OR=0.031, 95%CI: 0.012-0.078, P<0.001 and WBC count (OR=1.451, 95%CI: 1.212-1.736, P<0.001 were independent risk factors for postoperative cardio-pulmonary complications. Conclusion Among an array of clinical variables in hospital, operation time, preoperative white blood cell count, preoperative COPD

  6. Preoperative nodal staging of non-small cell lung cancer using {sup 99m}Tc-sestamibi SPECT/CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Miziara, Juliana Muniz; Rocha, Euclides Timoteo da; Miziara, Jose Elias Abrao; Garcia, Gustavo Fabene; Simoes, Maria Izilda Previato; Lopes, Marco Antonio; Kerr, Ligia Maria [Hospital de Cancer de Barretos, Barretos, SP (Brazil); Buchpiguel, Carlos Alberto, E-mail: julimiziara@ig.com.br [Faculdade de Medicina da Universidade da Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, SP (Brazil)

    2011-07-01

    Objectives: The proper nodal staging of non-small cell lung cancer is important for choosing the best treatment modality. Although computed tomography remains the first-line imaging test for the primary staging of lung cancer, its limitations for mediastinum nodal staging are well known. The aim of this study is to evaluate the accuracy of hybrid single-photon emission computed tomography and computed tomography using {sup 99m}Tc-sestamibi in the nodal staging of patients with non-small cell lung cancer and to identify potential candidates for surgical treatment. Methods: Prospective data were collected for 41 patients from December 2006 to February 2009. The patients underwent chest computed tomography and single-photon emission computed tomography/computed tomography examinations with {sup 99m}Tc-sestamibi within a 30-day time period before surgery. Single-photon emission computed tomography/computed tomography was considered positive when there was focal uptake of sestamibi in the mediastinum, and computed tomography scan when there was lymph nodes larger than 10 mm in short axis. The results of single-photon emission computed tomography and computed tomography were correlated with pathology findings after surgery. Results: Single-photon emission computed tomography/computed tomography correctly identified six out of 19 cases involving hilar lymph nodes and one out of seven cases involving nodal metastases in the mediastinum. The sensitivity, specificity, positive predictive value, and negative predictive value for {sup 99m}Tc-sestamibi single-photon emission computed tomography/computed tomography in the hilum assessment were 31.6%, 95.5%, 85.7%, and 61.8%, respectively. The same values for the mediastinum were 14.3%, 97.1%, 50%, and 84.6%, respectively. For the hilar and mediastinal lymph nodes, chest tomography showed sensitivity values of 47.4% and 57.1%, specificity values of 95.5% and 91.2%, positive predictive values of 90% and 57.1% and negative

  7. Radiation induced chemotherapy sensitization in trimodality therapy of stage 3 non small cell lung cancer. A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Takita, H. [Millard Fillmore Hospital, Buffalo (United States); Shin, K. H. [CCS Oncology Center, Kenmore, NY, (United States)

    2000-12-01

    The overall cure rate of locally advanced non-small cell lung carcinoma (NSCLC) remains poor. Although there have been encouraging reports of preoperative use of chemotherapy, more recent trend is the trimodal approach of radiation, chemo, and surgical-therapies. With the trimodal therapy, increased tumor response and resectability are reported, however, there are increased treatment related side effects. It was observed that a relatively small dose of radiation given prior to induction chemotherapy greatly enhanced the tumor response to the chemotherapy without increased toxicity. A total of 18 patients (8 3. A and 10 3.B) were initially given 20 Gy of radiation therapy in 10 fractions and then received 2 courses of Taxol combination chemotherapy. The overall response rate was 83% (15/18) and 13 out of 18 patients underwent surgery. There was one postoperative death (not therapy related). It is speculated that the small dose of radiation therapy may have sensitized the tumor to subsequent chemotherapy, and it was suggested a new hypothesis of radiation therapy induced chemotherapy sensitization.

  8. Accuracy of 18F-FDG PET/CT for lymph node staging in non-small-cell lung cancers

    Institute of Scientific and Technical Information of China (English)

    LIU Bao-jun; DONG Jing-cheng; XU Chang-qing; ZUO Chuan-tao; LE Jing-jing; GUAN Yi-hui; ZHAO Jun; WU Jin-feng; DUAN Xiao-hong; CAO Yu-xue

    2009-01-01

    Background This retrospective study evaluated the diagnostic accuracy of 2-(F18)-fluoro-2-deoxy-D-glucose-positron emission tomography(18F-FDG-PET)/COmputed tomography(PET/CT)in the preoperative diagnosis of metastatic mediastinal and hilar lymph node in patients with non-small-cell lung cancer(NSCLC).Methods A total of 39 patients received preoperative 18F-FDG PET/CT and the postoperative biopsy.We compared preoperative PET/CT scan results with corresponding intraoperative histopathalogic findings in 39 NSCLC patients.The sensitivity,specificity,accuracy,positive and negative predictive value of 18F-FDG PET/CT were assessed.Results Histopathologic examination confirmed metastasis in 57 out of the 208 excised lymph nodes;23 of the 57 nodes were mediastinal and hilar lymph nodes.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of PET/CT in the preoperative diagnosis of mediastinal lymph node metastasis in NSCLC patients were 65%,96.8%,92%,78.5%and 90%,respectively.Conclusions PET/CT scan showed good accuracy in the preoperative diagnosis of mediastinal and hilar lymph node metastasis in the patients with NSCLC.We recommend that PET/CT scanning be used as a first-line evaluation tool for tumor diagnosis,therapy evaluation and follow-up.

  9. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Higginson, Daniel S., E-mail: daniel.higginson@gmail.com [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Socinski, Mark A. [Department of Medicine, Division of Hematology and Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States)

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  10. Dosimetric comparison of flattened and unflattened beams for stereotactic ablative radiotherapy of stage I non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hrbacek, Jan, E-mail: jan.hrbacek@psi.ch [Klinik für Radio-Onkologie, UniversitätsSpital Zürich, 8091 Zürich, Switzerland and Center for Proton Therapy, Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Lang, Stephanie; Graydon, Shaun N.; Klöck, Stephan; Riesterer, Oliver [Klinik für Radio-Onkologie, UniversitätsSpital Zürich, 8091 Zürich (Switzerland)

    2014-03-15

    Purpose: To compare contribution and accuracy of delivery for two flattening filter free (FFF) beams of the nominal energy 6 and 10 MV and a 6 MV flattened beam for early stage lung cancer. Methods: For each of 11 patients with stage I nonsmall cell lung cancer three volumetric modulated arc therapy plans were prepared utilizing a 6 MV flattened photon beam (X6FF) and two nonflattened beams of nominal energy 6 and 10 MV (X6FFF, X10FFF). Optimization constraints were set to produce dose distributions that meet the criteria of the RTOG-0915 protocol. The radiation schedule used for plan comparison in all patients was 50 Gy in five fractions. Dosimetric parameters of planning target volume (PTV) and organs-at-risk and delivery times were assessed and compared. All plans were subject to verification using Delta{sup 4} unit (Scandidos, Sweden) and absolutely calibrated gafchromic films in a thorax phantom. Results: All plans had a qualitatively comparable outcome. Obtained dose distributions were conformal (CI < 1.17) and exhibited a steep dose fall-off outside the PTV. The ratio of monitor units for FFF versus FF plans in the authors' study ranged from 0.95 to 1.21 and from 0.93 to 1.25 for X6FFF/X6FF and X10FFF/X6FF comparisons, respectively. The ratio systematically increased with increasing size of the PTV (up to +25% for 150 cm{sup 3} PTV). Yet the integral dose to healthy tissue did not follow this trend. Comparison of cumulative dose volume histograms for a patient's body showed that X6FFF plans exhibit improved conformity and reduced the volume of tissue that received more than 50% of the prescription dose. Parameters related to dose gradient showed statistically significant improvement. CI{sub 50%}, CI{sub 60%}, CI{sub 80%}, and CI{sub 100%} were on average reduced by 4.6% (p < 0.001), 4.6% (p = 0.002), 3.1% (p = 0.002), and 1.2% (p = 0.039), respectively. Gradient measure was on average reduced by 4.2% (p < 0.001). Due to dose reduction in the

  11. The relationship between stage 1 and 2 non-small cell lung cancer and lung function in men and women

    Directory of Open Access Journals (Sweden)

    Man SF Paul

    2006-02-01

    Full Text Available Abstract Background Reduced forced expiratory volume in one second (FEV1 has been linked to non small cell lung cancer (NSCLC. However, it is unclear whether all or only certain histological subtypes of NSCLC are associated with reduced FEV1. Moreover, there is little information on whether gender modifies this relationship. Using a large tissue registry, we sought to determine the relationship between FEV1 and subtypes of NSCLC and determine whether this relationship is modified by gender. Methods We used data from patients who underwent tumor resection for NSCLC at a teaching hospital in Vancouver and had various pre-operative clinical measurements including FEV1. We divided the cohort into quartiles of predicted FEV1 and using both logistic and linear regression modeling techniques determined whether FEV1 was related to the occurrence of adeno or squamous cell carcinoma in men and women. Results There were 610 patients in the study (36% females. On average, women were more likely to have adenocarcinoma than were men (72% of all cases of NSCLC in women versus 40% in men; p 1 and the risk of any histological subtypes of NSCLC. In men, however, there was an inverse relationship between the risk of adenocarcinoma and FEV1 such that the lowest quartile of FEV1 was 47% less likely to have adenocarcinoma compared with the highest FEV1 quartile (adjusted odds ratio, 0.52; 0.28 to 0.98; p for trend, 0.028. The reverse was observed for squamous cell carcinoma. Conclusion In individuals undergoing lung resection for NSCLC, the risk of adenocarcinoma and squamous cell carcinoma of the lung varies as a function of FEV1, independent of smoking intensity in men but not in women. Clinical Implications These data indicate that women are much more susceptible to adenocarcinoma than are men especially when they have normal or near normal lung function. It may thus be useful to conduct periodic surveillance chest radiographs in asymptomatic female smokers (or ex

  12. The association of race with timeliness of care and survival among Veterans Affairs health care system patients with late-stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zullig LL

    2013-07-01

    Full Text Available Leah L Zullig,1,2 William R Carpenter,2 Dawn T Provenzale,1,3 Morris Weinberger,1,2 Bryce B Reeve,2 Christina D Williams,1 George L Jackson1,4 1Center of Excellence for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Durham, NC, USA; 2Department of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 3Division of Gastroenterology, Duke University, Durham, NC, USA; 4Division of General Internal Medicine, Duke University, Durham, NC, USA Background: Non-small cell lung cancer is the leading cause of cancer-related mortality in the United States. Patients with late-stage disease (stage 3/4 have five-year survival rates of 2%–15%. Care quality may be measured as time to receiving recommended care and, ultimately, survival. This study examined the association between race and receipt of timely non-small cell lung cancer care and survival among Veterans Affairs health care system patients. Methods: Data were from the External Peer Review Program, a nationwide Veterans Affairs quality-monitoring program. We included Caucasian or African American patients with pathologically confirmed late-stage non-small cell lung cancer in 2006 and 2007. We examined three quality measures: time from diagnosis to (1 treatment initiation, (2 palliative care or hospice referral, and (3 death. Unadjusted analyses used log-rank and Wilcoxon tests. Adjusted analyses used Cox proportional hazard models. Results: After controlling for patient and disease characteristics using Cox regression, there were no racial differences in time to initiation of treatment (72 days for African American versus 65 days for Caucasian patients, hazard ratio 1.04, P = 0.80 or palliative care or hospice referral (129 days versus 116 days, hazard ratio 1.10, P = 0.34. However, the adjusted model found longer survival for African American patients than for Caucasian patients (133 days versus 117 days, hazard ratio 0

  13. Reirradiation of recurrent node-positive non-small cell lung cancer after previous stereotactic radiotherapy for stage I disease. A multi-institutional treatment recommendation

    Energy Technology Data Exchange (ETDEWEB)

    Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Ruysscher, Dirk de [MAASTRO Clinic, Department of Radiation Oncology, Maastricht (Netherlands); Gaspar, Laurie E. [University of Colorado School of Medicine, Department of Radiation Oncology, Aurora, CO (United States); Guckenberger, Matthias [University Hospital Zurich, Department of Radiation Oncology, Zurich (Switzerland); Mehta, Minesh P. [Miami Cancer Institute, Department of Radiation Oncology, Miami, FL (United States); Cheung, Patrick; Sahgal, Arjun [Sunnybrook Health Sciences Centre and University of Toronto, Department of Radiation Oncology, Toronto (Canada)

    2017-07-15

    Practice guidelines have been developed for early-stage and locally advanced non-small cell lung cancer (NSCLC). However, many common clinical scenarios still require individualized decision making. This is true for locoregional relapse after initial stereotactic radiotherapy (stereotactic body radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an increasingly utilized curative treatment option for stage I NSCLC. A consortium of expert radiation oncologists was established with the aim of providing treatment recommendations. In this scenario, a case was distributed to six radiation oncologists who provided their institutions' treatment recommendations. In this case, a patient developed local and mediastinal relapse after SABR (45 Gy, 3 fractions), comparable to the tumor burden in de novo stage IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion was developed. Three institutions recommended evaluation for surgery. If the patient was not a surgical candidate, and/or refused surgery, definitive chemoradiation was recommended, including retreating the primary to full dose. European participants were more in favor of a non-surgical approach. None of the participants were reluctant to prescribe reirradiation, but two institutions prescribed doses lower than 60 Gy. Platinum-based doublets together with intensity-modulated radiotherapy were preferred. The institutional recommendations reflect the questions and uncertainties discussed in current stage III guidelines. All institutions agreed that previous SABR is not a contraindication for salvage chemoradiation. In the absence of high-quality prospective trials for recurrent NSCLC, all treatment options recommended in current guidelines for stage III disease can be considered in clinical scenarios such as this. (orig.) [German] Fuer fruehe und lokal fortgeschrittene Stadien des nicht-kleinzelligen Bronchialkarzinoms (NSCLC) wurden Behandlungsleitlinien publiziert

  14. Validation of the Eighth Edition of the TNM Staging System for Lung Cancer in 2043 Surgically Treated Patients With Non-small-cell Lung Cancer.

    Science.gov (United States)

    Chen, Kezhong; Chen, Haiqing; Yang, Fan; Sui, Xizhao; Li, Xiao; Wang, Jun

    2017-04-12

    The International Association for the Study of Lung Cancer has proposed a revision of the Tumor, Node, Metastasis (TNM) classification for lung cancer. The purpose of this study is to evaluate the prognostic value of the eighth edition of the TNM staging system in surgically treated patients with non-small-cell lung cancer. Data from 2043 consecutive patients with non-small-cell lung cancer who underwent surgical treatment in our single center between January 2006 and September 2015 were collected and analyzed retrospectively. Cox proportional hazard models were used to assess the prognostic significance of the T and N descriptors. The reversed overall survival curves of stage IIA and stage IIB in the seventh edition were corrected in the eighth edition. Better prognostic value in predicting overall survival, including a higher log rank test of trend χ(2) statistic (433.6 vs. 414.2), a smaller Akaike Information Criterion value (4759.6 vs. 4768.2), a higher Harrell C-index (0.776 vs. 0.769), and a lower integrated Brier score (0.092 vs. 0.093), was observed for the eighth edition relative to the seventh edition. Recurrence-free survival analysis of subsets of patients stratified by T and N descriptors showed a stepwise deterioration. Significant differences were found between patients of subdivided stage IA (IAI vs. IA2; P = .003 and IA2 vs. IA3; P = .004). The eighth edition of the TNM staging system for lung cancer has prognostic value superior to that of the seventh edition. It was able to predict recurrence-free survival well. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Accelerated split-course (Type B) thoracic radiation therapy plus vinorelbine/carboplatin combination chemotherapy in Stage III inoperable non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iaffaioli, R.V.; Tortoriello, A.; Facchini, G.; Maccauro, M.; Dimitri, P. [Cagliari Univ. (Italy). Ist. Medicina Interna; Caponigro, F. [Istituto Medico Legale, Milan (Italy); Ravo, V.; Muto, P. [Naples Univ. (Italy). Ist. Scienze Radiologiche; Crovella, F. [Ospedale Oliveto, Citra (Italy). Div. Chirurgia Generale

    1996-10-01

    43 patients with stage III NSCLC (non-small cell lung cancer) entered a phase II study aimed at evaluating the toxicity and the activity of a combined modality programme including an accelerated split-course schedule (type B) of thoracic radiation therapy and a combination chemotherapy with vinorelbine and carboplatin. An objective response was achieved in 18/42 evaluable patients (5 complete and 13 partial responses), for an overall response rate of 43% (95% confidence interval, 28-58%). Four complete responses had a duration which exceeded 16 months. Treatment was well tolerated; grade III myelotoxicity occurred in only 14% of patients and treatment was delayed in only 2 cases because of grade 3 oesophagitis. Both tolerability and efficacy data suggest that this regimen holds promise for the treatment of patients with stage III NSCLC. (author).

  16. Experience of segmentectomy from 36 Chinese patients with non-small cell lung cancer at stage

    Institute of Scientific and Technical Information of China (English)

    QIAN Li-qiang; ZHAO Xiao-jing; LUO Qing-quan; HUANG Jia

    2013-01-01

    Background Although video-assisted radical operation for lung cancer has been widely accepted for treatment of nonsmall cell lung cancer (NSCLC),the debate over video-assisted thoracic surgery (VATS) segmentectomy still remains.This study analyzed the clinical outcomes using VATS segmentectomy for stage Ⅰ NSCLC patients to explore the safety and efficacy of VATS segmentectomy for la NSCLC.Methods Retrospective review was conducted of patients who underwent VATS segmentectomy for clinical stage Ⅰ NSCLC at Shanghai Chest Hospital between November 2009 and May 2012.VATS segmentectomy was performed on 36 patients.Analyses of the patient group were performed on patient demographics and clinical characteristics,intraoperative parameters,complications,and postoperative survival.Results Thirty-five of thirty-six patients underwent VATS segmentectomy with only one conversion to open thoracic surgery.There was one peri-operative mortality from the segmentectomy group and all other patients are alive with a median follow up of 327 days.The mean volume of chest tube drainage after operation for segmentectomy was 1021.4 ml.Among other parameters,the mean blood loss was 162.5 ml (50.0-1600.0 ml),the mean operation time 124.8 minutes (75.0-271.0 minutes),chest tube duration 4.1 days (2-8 days),and the mean length of hospital stay 6.2 days (4-11 days).There was one (2.8%) locoregional recurrence after segmentectomy.Two patients successfully underwent bilateral segmentectomies and are still disease free.Conclusion For patients with stage Ⅰ NSCLC,VATS segmentectomy offers a safe and equally effective option and can be applied to complicated operations such as bilateral segmentectomy.

  17. Application of the new 8th TNM staging system for non-small cell lung cancer: treated with curative concurrent chemoradiotherapy.

    Science.gov (United States)

    Choi, Hoon Sik; Jeong, Bae Kwon; Jeong, Hojin; Lee, Yun Hee; Ha, In Bong; Song, Jin Ho; Kang, Ki Mun

    2017-07-21

    The eighth tumor, node, metastasis (TNM) staging system (8-TNM) for non-small cell lung cancer (NSCLC) was newly released in 2015. This system had limitation because most patients included in the analysis were treated with surgery. Therefore, it might be difficult to reflect prognosis of patients treated with curative concurrent chemoradiotherapy (CCRT). Purpose of this study was to investigate clinical impact of the newly published 8-TNM compared to the current seventh TNM staging system (7-TNM) for locally advanced NSCLC patients treated with CCRT. New 8-TNM was applied to 64 patients with locally advanced NSCLC who were treated with CCRT from 2010 to 2015. Changes in T category and stage group by 8-TNM were recorded and patterns of change were evaluated. Survival was analyzed according to T category, N category, and stage group in each staging system, respectively. Among the total of 64 patients, 38 (59.4%) patients showed change in T category while 22 (34.4%) patients showed change in stage group using 8-TNM compared to 7-TNM. Survival curves were significantly separated in the 8-TNM stage group (p = 0.001) than those in the 7-TNM (p > 0.05). Especially, survival of newly introduced stage IIIC by 8-TNM was significantly lower than that of others. On the other hand, there was no significant survival difference between T categories in each staging system. Subdivision of stage III into IIIA, IIIB, and IIIC by 8-TNM for patients treated with CCRT better reflected prognosis than 7-TNM. However, subdivision of T category according to tumor size in 8-TNM might be less significant.

  18. Phase 0 Trial of Itraconazole for Early-Stage Non-Small Cell Lung Cancer

    Science.gov (United States)

    2015-10-01

    Surgery, Pulmonary Medicine, Hematology -Oncology; Texas Tech School of Pharmacy; Hamon Center for Therapeutic Oncology Research; and the Biomarker...include a brief description of opportunities for training and professional development. Training activities may include, for example, courses or one-on-one 10

  19. Thoracic staging of non-small-cell lung cancer using integrated {sup 18}F-FDG PET/MR imaging: diagnostic value of different MR sequences

    Energy Technology Data Exchange (ETDEWEB)

    Schaarschmidt, Benedikt [University of Dusseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); University of Duisburg-Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Medical Faculty, Essen (Germany); Buchbender, Christian; Rubbert, Christian; Hild, Florian; Antoch, Gerald; Heusch, Philipp [University of Dusseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Gomez, Benedikt; Ruhlmann, Verena [University of Duisburg-Essen, Department of Nuclear Medicine, Medical Faculty, Essen (Germany); Koehler, Jens [University of Duisburg-Essen, Department of Medical Oncology, Medical Faculty, Essen (Germany); Grueneisen, Johannes; Wetter, Axel [University of Duisburg-Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Medical Faculty, Essen (Germany); Reis, Henning [University of Duisburg-Essen, Institute of Pathology, Medical Faculty, Essen (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for MR Imaging, Essen (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany)

    2015-07-15

    To compare the accuracy of different MR sequences in simultaneous PET/MR imaging for T staging in non-small-cell lung cancer in relation to histopathology. The study included 28 patients who underwent dedicated thoracic PET/MR imaging before tumour resection. Local tumour staging was performed separately by three readers with each of the following MR sequences together with PET: transverse T2 BLADE, transverse non-enhanced and contrast-enhanced T1 FLASH, T1 3D Dixon VIBE in transverse and coronal orientation, coronal T2 HASTE, and coronal TrueFISP. The staging results were compared with histopathology after resection as the reference standard. Differences in the accuracy of T staging among the MR sequences were evaluated using McNemar's test. Due to multiple testing, Bonferroni correction was applied to prevent accumulation of α errors; p < 0.0024 was considered statistically significant. Compared with histopathology, T-staging accuracy was 69 % with T2 BLADE, 68 % with T2 HASTE, 59 % with contrast-enhanced T1 FLASH, 57 % with TrueFISP, 50 % with non-enhanced T1 FLASH, and 45 % and 48 % with T1 3D Dixon VIBE in transverse and coronal orientation, respectively. Staging accuracy with T2 BLADE was significantly higher than with non-enhanced T1 FLASH and with T1 3D Dixon VIBE in transverse and coronal orientations (p < 0.0024). T2 HASTE had a significantly higher T-staging accuracy than transverse T1 3D-Dixon-VIBE (p < 0.0024). Transverse T2 BLADE images provide the highest accuracy for local tumour staging and should therefore be included in dedicated thoracic PET/MR protocols. As T1 3D Dixon VIBE images acquired for attenuation correction performed significantly worse, this sequence cannot be considered sufficiently accurate for local tumour staging in the thorax. (orig.)

  20. Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection†.

    Science.gov (United States)

    Guerrera, Francesco; Errico, Luca; Evangelista, Andrea; Filosso, Pier Luigi; Ruffini, Enrico; Lisi, Elena; Bora, Giulia; Asteggiano, Elena; Olivetti, Stefania; Lausi, Paolo; Ardissone, Francesco; Oliaro, Alberto

    2015-06-01

    Despite impressive results in diagnosis and treatment of non-small-cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within 5 years after surgical treatment. Identification of prognostic factors to select patients with a poor prognosis and development of tailored treatment strategies are then advisable. The aim of our study was to design a model able to define prognosis in patients with Stage I NSCLC, submitted to surgery with curative intent. A retrospective analysis of two surgical registries was performed. Predictors of survival were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: age, gender, smoking habit, morbidity, previous malignancy, Eastern Cooperative Oncology Group performance status, clinical N stage, maximum standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic lymphadenectomy, vascular invasion, pathological T stage, histology and histological grading. The final model included predictors with P fair discrimination ability (C-statistic = 0.69): the calibration of the model indicated a good agreement between observed and predicted survival. We designed an effective prognostic model based on clinical, pathological and surgical covariates. Our preliminary results need to be refined and validated in a larger patient population, in order to provide an easy-to-use prognostic tool for Stage I NSCLC patients. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  1. [Analyses of risk factors for postoperative recurrence after curative resection of stage III A-N2 non-small cell lung cancer].

    Science.gov (United States)

    Qiang, Guangliang; Guo, Yongqing; Xiao, Fei; Yu, Qiduo; Liang, Chaoyang; Song, Zhiyi; Tian, Yanchu; Shi, Bin; Liu, Deruo

    2014-11-11

    To explore the patterns of mediastinal lymph node metastases and prognostic factors of recurrence in patients undergoing curative resection of stage IIIA-N2 non-small cell lung cancer (NSCLC). A total of 92 patients underwent curative operation and pathologically diagnosed as stage IIIA-N2 NSCLC were retrospectively reviewed. The clinicopathological data were compared between the recurrence and non-recurrence groups. And the potential prognostic factors were included for multivariate analysis using Cox proportional hazard model. The 3 and 5-year recurrence rates were 61.0% and 70.2% respectively. For univariate analysis, the prognostic factors were number of metastatic lymph nodes, positive lymph node ratio, number of metastatic mediastinal lymph nodes (MLN), positive MLN ratio, number of MLN metastasis > 3, multiple station metastasis, trans-regional metastasis and multi-zonal metastasis. A multivariate analysis using Cox regression identified 2 independent factors of prognosis: trans-regional MLN metastasis (P = 0.035) and number of MLN metastasis >3 (P = 0.045). The recurrence risk of patients with trans-regional MLN metastasis was 2.0 times higher than those with regional MLN metastasis while the recurrence risk of patients with number of MLN metastasis >3 was 2.2 times higher than those with number of MLN metastasis of 1-3. Recurrence risk of stage IIIA-N2 non-small cell lung cancer (NSCLC) after curative resection may be estimated by location and number of MLN metastasis. And the subgroup with trans-regional MLN metastasis and number of MLN metastasis >3 carries the highest risk of recurrence.

  2. Correlation of early PET findings with tumor response to molecular targeted agents in patients with advanced driver-mutated non-small cell lung cancer.

    Science.gov (United States)

    Koizumi, Tomonobu; Fukushima, Toshirou; Gomi, Daisuke; Kobayashi, Takashi; Sekiguchi, Nodoka; Mamiya, Keiko; Tateishi, Kazunari; Katou, Akane; Oguchi, Kazuhiro

    2017-09-01

    Recent advances in positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) have facilitated not only the diagnosis and staging of lung cancer, but also the prediction of treatment outcome. The present study was designed to assess the usefulness of early FDG-PET examination for predicting subsequent tumor size reduction in response to molecular targeted agents in metastatic non-small cell lung cancer (NSCLC) with sensitive gene anomalies. I. In 29 targeted lesions of 10 NSCLC patients, changes in FDG uptake before and on day 7 after the initiation of molecular targeted therapy (gefitinib, n = 7; crizotinib, n = 3) were compared with subsequent radiographic tumor size reduction by RECIST. FDG uptake was evaluated as the maximum standardized uptake value (SUVmax) of each targeted lesion. SUVmax decreased in all lesions after therapy (mean SUVmax 8.3 ± 3.4 before to 3.7 ± 1.8 after therapy, p < 0.05). The % decrease in SUVmax of each lesion was significantly correlated with the % tumor size reduction (r = 0.44). In addition, the reduction rate of SUVmax in metastatic bone lesions after initiation of molecular targeted therapy was significantly lower than that in targeted organs (27.1 ± 27.5 vs. 51.2 ± 21.3%, respectively, p < 0.05). Early reduction in FDG-PET uptake after initiation of molecular targeted agents was able to predict subsequent tumor reduction in patients harboring EGFR-mutated or ALK-positive NSCLC. In addition, nontargeted bone metastasis may have different glucose metabolism after TKI treatment compared with other involved organs.

  3. Multidisciplinary management of non small cell lung cancer (NSCLC in stage III: clinical case description. Recommendations and state of the art

    Directory of Open Access Journals (Sweden)

    Simona Carnio

    2013-03-01

    Full Text Available Lung cancer is the leading cause of cancer death in industrialized countries with progressive increase of its mortality rate. Non Small Cell Lung Cancer (NSCLC is approximately 80-85% of all lung cancers, being adenocarcinoma and squamous cell carcinoma the most common histologies. The majority of the patients with stage III clinical stage, presents a mediastinal lymph node involvement described with computed tomography (TC and/or positron emission tomography (PET. The current approach to patients with NSCLC is multidisciplinary, especially for those staged as potentially operable, both for staging and for a correct definition of best treatment strategy. Updated international and national Guidelines and recommendations can provide valuable support to the clinician.The case described concerns the accidental detection of a tumour in the lung in a 58-year-old man with arterial hypertension controlled with ACE inhibitors. The treatments agreed after a multidisciplinary approach are cisplatin and docetaxel, the surgical resection, and the radiotherapy. After three months the patient has neither metastasis nor relapse.

  4. The role of consolidation therapy for stage III non-small cell lung cancer with persistent N2 disease after induction chemotherapy.

    Science.gov (United States)

    Amini, Arya; Correa, Arlene M; Komaki, Ritsuko; Chang, Joe Y; Tsao, Anne S; Roth, Jack A; Swisher, Stephen G; Rice, David C; Vaporciyan, Ara A; Lin, Steven H

    2012-09-01

    Persistent pathologic mediastinal nodal involvement after induction chemotherapy and surgical resection is a negative prognostic factor for stage III-N2 non-small cell lung cancer patients. This population has high rates of local-regional failure and distant failure, yet the effectiveness of additional therapies is not clear. We assessed the role of consolidative therapies (postoperative radiation therapy and chemotherapy) for such patients. In all, 179 patients with stage III-N2 non-small cell lung cancer at MD Anderson Cancer Center were treated with induction chemotherapy followed by surgery from 1998 through 2008; 61 patients in this cohort had persistent, pathologically confirmed, mediastinal nodal disease, and were treated with postoperative radiation therapy. Local-regional failure was defined as recurrence at the surgical site or lymph nodes (levels 1 to 14, including supraclavicular), or both. Overall survival was calculated using the Kaplan-Meier method, and survival outcomes were assessed by log rank tests. Univariate and multivariate Cox proportional hazards models were used to identify factors influencing local-regional failure, distant failure, and overall survival. All patients received postoperative radiation therapy after surgery, but approximately 25% of the patients also received additional chemotherapy: 9 (15%) with concurrent chemotherapy, 4 (7%) received adjuvant sequential chemotherapy, and 2 (3%) received both. Multivariate analysis indicated that additional postoperative chemotherapy significantly reduced distant failure (hazard ratio 0.183, 95% confidence interval: 0.052 to 0.649, p=0.009) and improved overall survival (hazard ratio 0.233, 95% confidence interval: 0.089 to 0.612, p=0.003). However, additional postoperative chemotherapy had no affect on local-regional failure. Aggressive consolidative therapies may improve outcomes for patients with persistent N2 disease after induction chemotherapy and surgery. Copyright © 2012 The

  5. Reduced expression of cyclin D2 is associated with poor recurrence-free survival independent of cyclin D1 in stage III non-small cell lung cancer.

    Science.gov (United States)

    Ko, Eunkyung; Kim, Yujin; Park, Seong-Eun; Cho, Eun Yoon; Han, Jungho; Shim, Young Mog; Park, Joobae; Kim, Duk-Hwan

    2012-08-01

    Compared to well-known function of cyclin D1 in lung cancer, the role of cyclin D2 is not clear. This study was aimed at understanding the clinicopathological significance of cyclin D2 in primary non-small cell lung cancer (NSCLC). We retrospectively analyzed expression statuses of cyclin D1, cyclin D2, p16, p21, p27, Ki-67, and phospho-pRb (Ser-807/811) using immunohistochemistry in 626 NSCLCs. Cyclin D2 was expressed in normal lung tissue, and its expression was reduced in 170 (27%) of 626 NSCLCs with a median duration of follow-up of 64 months. Mean phospho-pRb (Ser-807/811) levels were not associated with expression levels of cyclin D2 (P=0.15). The relationship between recurrence and the reduced expression of cyclin D2 was not homogenous by stage (Breslow-Day test for homogeneity, P=0.04). Reduced expression of cyclin D2 was not associated with patient's prognosis in 370 stage I, 112 stage II, and 18 stage IV NSCLCs. However, for 126 stage III NSCLCs, reduced expression of cyclin D2 was adversely associated with recurrence-free survival (RFS) (hazard ratio [HR]=3.71, 95% CI=1.54-13.17; P=0.01), independent of histology and expression of cyclin D1. The reduced expression of cyclin D2 was not associated with the overexpression of cyclin D1 (P=0.65). The present study suggests that reduced expression of cyclin D2 in stage III NSCLC may be associated with poor RFS. And, cyclin D2 may have a distinct role from cyclin D1 in NSCLC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Bioelectrical impedance phase angle in clinical practice: implications for prognosis in stage IIIB and IV non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Grutsch James F

    2009-01-01

    Full Text Available Abstract Background A frequent manifestation of advanced lung cancer is malnutrition, timely identification and treatment of which can lead to improved patient outcomes. Bioelectrical impedance analysis (BIA is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated the prognostic role of BIA-derived phase angle in advanced non-small cell lung cancer (NSCLC. Methods A case series of 165 stages IIIB and IV NSCLC patients treated at our center. The Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle, independent of stage at diagnosis and prior treatment history. Results 93 were males and 72 females. 61 had stage IIIB disease at diagnosis while 104 had stage IV. The median phase angle was 5.3 degrees (range = 2.9 – 8. Patients with phase angle 5.3 had 12.4 months (95% CI: 10.5 to 18.7; n = 84; (p = 0.02. After adjusting for age, stage at diagnosis and prior treatment history we found that every one degree increase in phase angle was associated with a relative risk of 0.79 (95% CI: 0.64 to 0.97, P = 0.02. Conclusion We found BIA-derived phase angle to be an independent prognostic indicator in patients with stage IIIB and IV NSCLC. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with advanced NSCLC.

  7. Effect of Neoadjuvant Chemotherapy on Improvement of Surgical Resectibility and Survival of Patients with Stage ⅢA Non Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    LIJian; YULichao; 等

    2002-01-01

    Ojbective To assess the effect of neoadjuvant chemotherapy on surgical resectibility and survival in patients with stage ⅢA non small cell lung cancer(NSCLC).Methods 42 patients with stage ⅢA NSCLC were randomized to receive either two cycles chemotherapy followed by surgery(neoadjuvant chemotherapy group)or surgery alone(surgery alone group).All patients received four cycles chemotherapy after surgery.Results The overall response to chemotherapy was 42.9%(38.1% partial response and 4.8% complete response).Toxicity of chemotherapy was minor and consisted mainly of gastroenterological side effects and myelosuppression.Patients treated with neoadjuvant chemotherapy had estimated surgical resection rate of 95.2%(n=20)and a complete resection rate in 52.4%(n=11) compared to 66.7%(n=14)and 28.6%(n=6)respectively,for patients with surgery alone(P<0.05).None of the patients died from the operation.The median survival was 24.6 months in the neoadjuvant chemotherapy group as compared to only 10.8 months in the surgery alone group(P<0.05).The 2-year survival rate was 57.1% in the chemotherapy group as compared to 28.6% in the surgery alone group(P<0.05).Conclusion Neoadjuvant chemotherapy improves the surgical resectibility and increases the median survival and 2-year survival rate of patients with stage ⅢA NSCLC.

  8. Improved specificity of {sup 18}F-FDG PET/CT for lymph node staging of non-small cell lung cancer considering calcified lymph node as benign

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Seong Young; Seo, Young Soon; Min, Jung Joon; Song, Ho Chun; Na, Kook Joo; Choi, Chan; Kim, Young Chul; Kim, Yun Hyun; Bom, Hee Seung [Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2007-02-15

    We evaluated the diagnostic value of {sup 18}F-FDG PET/CT (PET/CT) in lymph node staging of non-small cell lung cancer (NSCLC) considering calcification and histologic types as well as FDG uptake. Fifty-three patients (38 men, 15 women; mean age, 62 years) with NSCLC underwent surgical resection (tumor resection and lymph node dissection) after PET/CT. After surgery, we compared PET/CT results with the biopsy results, and analyzed lymph node metastases, based on histologic types. PET diagnosis of lymph node metastasis was determined by maximum SUV (maxSUV) > 3.0, and PET/CT diagnosis was determined by maxSUV > 3.0 without lymph node calcification. By PET diagnosis, the sensitivity, specificity, and accuracy of overall lymph node staging were 45% (13 of 29), 91% (228 of 252), and 86% (241 of 281). Specificity was 91% in both squamous cell carcinoma and adenocarcinoma, while sensitivity was 71% in squamous cell carcinoma and 36% in adenocarcinoma. When we excluded calcified lymph node with maxSUV > 3.0 from metastasis by PET/CT diagnosis, specificity improved to 98% in squamous cell carcinoma and 97% in adenocarcinoma. The degree of improvement was not dependent on histologic types. PET/CT improved specificity of lymph node staging by reducing false positive lymph node regardless of histologic types of NSCLC.

  9. Effects of multidisciplinary team care on the survival of patients with different stages of non-small cell lung cancer: a national cohort study.

    Directory of Open Access Journals (Sweden)

    Chien-Chou Pan

    Full Text Available In Taiwan, cancer is the top cause of death, and the mortality rate of lung cancer is the highest of all cancers. Some studies have demonstrated that multidisciplinary team (MDT care can improve survival rates of non-small cell lung cancer (NSCLC patients. However, no study has discussed the effect of MDT care on different stages of NSCLC. The target population for this study consisted of patients with NSCLC newly diagnosed in the 2005-2010 Cancer Registry. The data was linked with the 2002-2011 National Health Insurance Research Database and the 2005-2011 Cause of Death Statistics Database. The multivariate Cox proportional hazards model was used to explore whether the involvement of MDT care had an effect on survival. This study applied the propensity score as a control variable to reduce selection bias between patients with and without involvement of MDT care. The adjusted hazard ratio (HR of death of MDT participants with stage III & IV NSCLC was significantly lower than that of MDT non-participants (adjusted HR = 0.87, 95% confidence interval = 0.84-0.90. This study revealed that MDT care are significantly associated with higher survival rate of patients with stage III and IV NSCLC, and thus MDT care should be used in the treatment of these patients.

  10. Predictive Parameters of CyberKnife Fiducial-less (XSight Lung) Applicability for Treatment of Early Non-Small Cell Lung Cancer: A Single-Center Experience

    Energy Technology Data Exchange (ETDEWEB)

    Bahig, Houda; Campeau, Marie-Pierre; Vu, Toni; Doucet, Robert; Béliveau Nadeau, Dominic [Radiation Oncology Department, Centre Hospitalier de l' Université de Montréal, Montréal, Quebec (Canada); Fortin, Bernard [Radiation Oncology Department, Maisonneuve-Rosemont Hospital, Montréal, Quebec (Canada); Roberge, David; Lambert, Louise; Carrier, Jean-François [Radiation Oncology Department, Centre Hospitalier de l' Université de Montréal, Montréal, Quebec (Canada); Filion, Edith, E-mail: edith.filion.chum@ssss.gouv.qc.ca [Radiation Oncology Department, Centre Hospitalier de l' Université de Montréal, Montréal, Quebec (Canada)

    2013-11-01

    Purpose: To determine which parameters allow for CyberKnife fiducial-less tumor tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. Methods and Materials: A total of 133 lung SBRT patients were preselected for direct soft-tissue tracking based on manufacturer recommendations (peripherally located tumors ≥1.5 cm with a dense appearance) and staff experience. Patients underwent a tumor visualization test to verify adequate detection by the tracking system (orthogonal radiographs). An analysis of potential predictors of successful tumor tracking was conducted looking at: tumor stage, size, histology, tumor projection on the vertebral column or mediastinum, distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass index. Results: Tumor visualization was satisfactory for 88 patients (66%) and unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm{sup 3} vs 6.5 cm{sup 3} in success and failure group, respectively) (P<.0001), and higher tumor density (0.86 g/cm{sup 3} vs 0.79 g/cm{sup 3}) were predictive of adequate detection. There was a 63% decrease in failure risk with every 1-cm increase in maximum tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to-soft tissue ratio, distance to diaphragm, patient's body mass index, and tumor projection on vertebral column and mediastinum were not found to be predictive of success. Conclusions: Tumor size, volume, and density were the most predictive factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have ≥80% chance of being adequately visualized and therefore should all be considered for direct tumor tracking.

  11. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    Energy Technology Data Exchange (ETDEWEB)

    Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  12. Expressions of CLDN1 and insulin-like growth factor 2 are associated with poor prognosis in stage N2 non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhen-fa; PEI Bao-xiang; WANG An-lei; ZHANG Lian-min; SUN Bing-sheng; JIANG Ri-cheng; WANG Chang-li

    2013-01-01

    Background Patients with single station mediastinal lymph node (N2) non-small call lung ccancer (NSCLC) have a better prognosis than those with multilevel N2.The molecular factors which are involved in disease progression remain largely unknown.The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.Methods Gene expression analysis was performed using Agilent 4x44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients.Real-time reverse transcription (RT)-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed.Immunohistochemical staining for these validated genes was performed on formalin-fixed,paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.Results We identified a 14 gene expression signature by comparative analysis of gene expression.Expression of these genes strongly differed between single station and multilevel N2 NSCLC.Four genes (ADAM28,MUC4,CLDN1,and IGF2) correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients.Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.Conclusions Our results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC.Further,CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.

  13. Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2011-02-01

    Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

  14. Concurrent chemoradiotherapy with low-dose weekly docetaxel followed by consolidation chemotherapy with docetaxel and cisplatin in the treatment of stage III non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Tianlin XIAO

    2008-02-01

    Full Text Available Background and objective Concurrent chemoradiotherapy is regarded as the standard care for locally advanced non-small cell lung cancer at present. This paper is designed to evaluate the efficacy and toxicity of low-dose weekly docetaxel (DTX with concurrent chemoradiotherapy followed by consolidation chemotherapy with DTX and cisplatin for unresectable stage III non-small cell lung cancer(NSCLC. Methods 44 previously untreated patients with stage III NSCLC were randomized into low-dose weekly DTX group and control group concomitant with radiotherapy. Both groups were treated by the standard fractionation schedule with three-dimensional conformal radiotherapy. An involved-field irradiation technique was performed. Gross tumor and metastatic lymph nodes were irradiated to a total dose of 66 Gy~70 Gy. Patients in the former group received chemotherapy with DTX 20mg. m-2.w-1,and the other group patients received DTX 60 mg/m2 on day 1 and DDP 30 mg/m2 on day 1~3 every 21 days. All patients received consolidation chemotherapy with DP regime after chemoradiotherapy for no more than 4 cycles. Results The overall response rates of patients in the low-dose weekly DTX group and control group were 81.8% with 27.3% CR(complete response and 86.4% with 27.3% CR respectively (Chisquare=0.120, P=0.942. After a median follow-up of 20months, the median survival time was 20 months and 17 months respectively. The 1-, 2- year survival rates of patients in low-dose weekly DTX group and control group were 69.8%, 48.1% versus 66.5%, 40.2% respectively;there was no difference between two groups. Grade 3 or 4 neutropenia and esophagitis occurred in 26.3%, 14.3% and 15.8%, 28.6% respectively (Chiquare=0.765,P =0.382(Chiquare=1.108,P =0.292.Grade 3 and 4 pulmonary toxicity was unusual.Conclusion Concurrent chemoradiotherapy with low-dose weekly docetaxel followed by consolidation chemotherapy with docetaxel and cisplatin is highly active with manageable toxicity in patients

  15. Differences between pulmonologists, thoracic surgeons and radiation oncologists in deciding on the treatment of stage I non-small cell lung cancer: A binary choice experiment.

    Science.gov (United States)

    Hopmans, Wendy; Zwaan, Laura; Senan, Suresh; van der Wulp, Ineke; Damman, Olga C; Hartemink, Koen J; Smit, Egbert F; Timmermans, Danielle R M

    2015-06-01

    Surgery is the standard of care in stage I non-small cell lung cancer (NSCLC), but stereotactic ablative radiotherapy (SABR) is increasingly used to treat patients at high-risk for surgical complications. We studied which patient- and clinician-related characteristics influenced treatment recommendations. A binary choice experiment with hypothetical cases was conducted. Cases varied on five patient-related characteristics: patient age, Chronic Obstructive Pulmonary Disease Global Initiative for Chronic Obstructive Lung Disease (COPD GOLD) score, Charlson co-morbidity index, World Health Organization performance status (WHO-PS) and patient treatment preference (surgery/SABR). Clinician characteristics were recorded. Responses were analyzed using generalized linear mixed models. 126 clinicians completed the survey. All patient-related characteristics, the clinician speciality, and whether clinicians considered outcomes of surgery comparable to SABR, significantly influenced treatment recommendations. Pulmonologists were most influenced by WHO-PS and comorbidity, whereas comorbidity and age had greatest influence on radiation oncologists and surgeons. Clinicians were less influenced by stated patient preference and COPD GOLD score. Limited consistency was observed in treatment recommendations. This study suggests that more efforts are needed to develop uniform approaches for making treatment recommendations, and also to incorporate patient preferences when making treatment decisions for stage I NSCLC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies.

    Science.gov (United States)

    Choy, Hak; Gerber, David E; Bradley, Jeffrey D; Iyengar, Puneeth; Monberg, Matthew; Treat, Joseph; Govindan, Ramaswamy; Koustensis, Andrew; Barker, Scott; Obasaju, Coleman

    2015-03-01

    Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0-16% and 0-23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed-cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.

  17. Survival prognostic value of morphological and metabolic variables in patients with stage I and II non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Domachevsky, L. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Beilinson Hospital, Petah Tikva (Israel); Groshar, D.; Bernstine, H. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Galili, R. [Lady Davis-Carmel Medical Center, Department of Cardiothoracic Surgery, Haifa (Israel); Saute, M. [Rabin Medical Center, Department of Cardiothoracic Surgery, Petah Tiqva (Israel)

    2015-11-15

    The prognosis of patients with non-small cell lung cancer (NSCLC) is important, as patients with resectable disease and poor prognostic variables might benefit from neoadjuvant therapy. The goal of this study is to evaluate SUVmax, SUVmax ratio, CT volume (CTvol), metabolic tumour volume (MTV) and total lesion glycolisis (TLG) as survival prognostic markers. In addition, we defined two variables; MTV x SUVmax (MTVmax) and CTvol x SUVmax (CTvolmax) and assessed whether they can be used as prognostic markers. Patients with stage I-II NSCLC who underwent 18 F FDG PET/CT and surgery were evaluated. Cox proportional-hazard model was used to determine the association between variables and survival. Similar analysis was performed in cases with no lymph node (LN) involvement. One hundred and eighty-one patients were included (at the end of the study, 140 patients were alive). SUVmax with a cut-off value of 8.2 was significant survival prognostic factor regardless of LN involvement (P = 0.012). In cases with no LN involvement, SUVmax and CTvol (≥7.1 ml) were significant survival prognostic factors with P = 0.004 and 0.03, respectively. SUVmax may be a useful prognostic variable in stage I-II NSCLC while morphologic tumour volume might be useful in cases with no lymph node involvement. (orig.)

  18. Predictive value of 18F-FDG PET and CT morphologic features for recurrence in pathological stage IA non-small cell lung cancer.

    Science.gov (United States)

    Ko, Kai-Hsiung; Hsu, Hsian-He; Huang, Tsai-Wang; Gao, Hong-Wei; Cheng, Cheng-Yi; Hsu, Yi-Chih; Chang, Wei-Chou; Chu, Chi-Ming; Chen, Jia-Hong; Lee, Shih-Chun

    2015-01-01

    Patients with pathological stage IA non-small cell lung cancer (NSCLC) may relapse despite complete surgical resection without lymphovascular invasion. A method of selecting a high-risk group for adjuvant therapy is necessary. The aim of this study was to assess the predictive value of F-fluorodeoxyglucose (FDG) uptake and the morphologic features of computed tomography (CT) for recurrence in pathological stage IA NSCLC.One hundred forty-five patients with pathological stage IA NSCLC who underwent pretreatment with FDG positron emission tomography and CT evaluations were retrospectively enrolled. The associations among tumor recurrence and patient characteristics, maximal standard uptake value (SUVmax) of primary tumors, and CT imaging features were investigated using univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors.Tumor recurrence developed in 21 (14.5%) of the 145 patients, and the 5-year recurrence-free survival rate was 77%. The univariate analysis demonstrated that SUVmax, the grade of histological differentiation, tumor size, and the presence of bronchovascular bundle thickening were significant predictive factors (P recurrence in the multivariate analysis. The use of this predictive model yielded a greater area under the ROC curve (0.877), which suggests good discrimination.The combined evaluation of FDG uptake and CT morphologic features may be helpful in the prediction of recurrence in patients with pathological stage IA NSCLC and in the stratification of a high-risk group for postoperative adjuvant therapy or prospective clinical trials.

  19. Outcome Study of Cobalt Based Stereotactic Body Radiation Therapy for Patients with Inoperable Stage III Non-small Cell Lung Cancer.

    Science.gov (United States)

    Wang, Yingjie; Lan, Fengming; Kang, Xiaoli; Shao, Yinjian; Li, Hongqi; Li, Ping; Wu, Weizhang; Wang, Jidong; Chang, Dongshu; Wang, Yong; Xia, Tingyi

    2015-10-01

    Aim of this paper is to retrospectively evaluate the efficacy and toxicity of specialized Body Cobalt based system (BCBS) treatment in the senior patients group (.65 years) with Stage III non-small cell lung carcinoma (NSCLC). A total of 49 patients (41 males and 8 females) with Stage III NSCLC according to UICC TNM classification (6(th) edition) were treated using OUR-QGD™ BCBS which was designed and manufactured in China. Post treatment evaluation with follow-up information was collected from April 2001 to December 2006 in our department. Median age of enrolled patients was 71 years old (65-85). Among those patients, 36 patients were pathologically identified with squamous cell carcinoma, and the other 13 patients were confirmed as adenocarcinoma. All patients were immobilized by vacuum based immobilization mold and then performed slow CT scan without any respiration gating devices. The daily radiation prescription dose was defined at 50% isodose line covering primary lesions and metastatic lymph nodes with doses from 2.5 to 6 Gy in 5 fractions per week according to the tumor stage and internally approved treatment protocols by the Institutional Review Board (IRB). Median daily dose and total delivery dose of 50% isodose line were 4 Gy and 41 Gy, respectively. In this study group, total of 3 patients received neoadjuvant cisplatin-based chemotherapy. Tumor response evaluated 12 weeks after radiation has demonstrated 13 complete responses (26.5%), 21 partial responses (42.9%). The overall survival (OS) rate of 1-year, 2-year and 3-year was 63.3%, 40.8% and 20.4%, respectively. The median and mean survival time was 22 and 24 months. All 49 patients tolerated the treatment well and have completed the planned therapy regiment. Body Cobalt based system treatment of those over 65 years old patients with Stage III NSCLC had reasonable and superior curative effect as well as local control, and at the same time without severe radiation side effects.

  20. Analysis of Expression of Vascular Endothelial Growth Factor A and Hypoxia Inducible Factor-1alpha in Patients Operated on Stage I Non-Small-Cell Lung Cancer

    Science.gov (United States)

    Honguero Martínez, Antonio Francisco; Arnau Obrer, Antonio; Figueroa Almánzar, Santiago; León Atance, Pablo; Guijarro Jorge, Ricardo

    2014-01-01

    Objectives. Recent studies show that expression of hypoxia inducible factor-1alpha (HIF-1α) favours expression of vascular endothelial growth factor A (VEGF-A), and these biomarkers are linked to cellular proliferation, angiogenesis, and metastasis in different cancers. We analyze expression of HIF-1α and VEGF-A to clinicopathologic features and survival of patients operated on stage I non-small-cell lung cancer. Methodology. Prospective study of 52 patients operated on with stage I. Expression of VEGF-A and HIF-1α was performed through real-time quantitative polymerase chain reaction (qRT-PCR). Results. Mean age was 64.7 and 86.5% of patients were male. Stage IA represented 23.1% and stage IB 76.9%. Histology classification was 42.3% adenocarcinoma, 34.6% squamous cell carcinoma, and 23.1% others. Median survival was 81.0 months and 5-year survival 67.2%. There was correlation between HIF-1α and VEGF-A (P = 0.016). Patients with overexpression of HIF-1α had a tendency to better survival with marginal statistical significance (P = 0.062). Patients with overexpression of VEGF-A had worse survival, but not statistically significant (P = 0.133). Conclusion. The present study revealed that VEGF-A showed correlation with HIF-1α. HIF-1α had a tendency to protective effect with a P value close to statistical significance. VEGF-A showed a contrary effect but without statistical significance. PMID:26316946

  1. Differential expression of Yes-associated protein is correlated with expression of cell cycle markers and pathologic TNM staging in non-small-cell lung carcinoma.

    Science.gov (United States)

    Kim, Jin Man; Kang, Dong Wook; Long, Liang Zhe; Huang, Song-Mei; Yeo, Min-Kyung; Yi, Eunhee S; Kim, Kyung-Hee

    2011-03-01

    Yes-associated protein, a downstream effector of the Hippo signaling pathway, has been linked to progression of non-small-cell lung carcinoma. The aim of this study was to investigate expression of Yes-associated protein in lung adenocarcinoma and squamous cell carcinoma. Associations of Yes-associated protein expression with clinicopathologic parameters, expression of cell cycle-specific markers, and epidermal growth factor receptor gene amplification were also analyzed. In a univariate analysis of the 66 adenocarcinomas, high nuclear expression of Yes-associated protein was significantly correlated with expression of cyclin A and mitogen-activated protein kinase. Multivariate analysis, including age and sex, showed that cyclin A expression was independently correlated with nuclear expression of Yes-associated protein in adenocarcinomas. Furthermore, high nuclear expression of Yes-associated protein was also a significant predictor of epidermal growth factor receptor gene amplification for adenocarcinoma. For the 102 squamous cell carcinomas, univariate analysis revealed that high cytoplasmic expression of Yes-associated protein was correlated with the low pathologic TNM staging (stage I) and histologic grading. Multivariate analysis, including age and sex, showed that cytoplasmic expression of Yes-associated protein was an independent predictor of low pathologic TNM staging. These results indicate that nuclear overexpression of Yes-associated protein contributes to pulmonary adenocarcinoma growth and that high cytoplasmic expression of Yes-associated protein is an independent predictor of low pathologic TNM staging and histologic grading. The differential effects of Yes-associated protein expression patterns in adenocarcinomas and squamous cell carcinomas suggest that Yes-associated protein may play important roles in different pathways in distinct tumor subtypes. These observations may, therefore, lead to new perspectives on therapeutic targeting of these tumor

  2. Analysis of Expression of Vascular Endothelial Growth Factor A and Hypoxia Inducible Factor-1alpha in Patients Operated on Stage I Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Antonio Francisco Honguero Martínez

    2014-01-01

    Full Text Available Objectives. Recent studies show that expression of hypoxia inducible factor-1alpha (HIF-1α favours expression of vascular endothelial growth factor A (VEGF-A, and these biomarkers are linked to cellular proliferation, angiogenesis, and metastasis in different cancers. We analyze expression of HIF-1α and VEGF-A to clinicopathologic features and survival of patients operated on stage I non-small-cell lung cancer. Methodology. Prospective study of 52 patients operated on with stage I. Expression of VEGF-A and HIF-1α was performed through real-time quantitative polymerase chain reaction (qRT-PCR. Results. Mean age was 64.7 and 86.5% of patients were male. Stage IA represented 23.1% and stage IB 76.9%. Histology classification was 42.3% adenocarcinoma, 34.6% squamous cell carcinoma, and 23.1% others. Median survival was 81.0 months and 5-year survival 67.2%. There was correlation between HIF-1α and VEGF-A (P=0.016. Patients with overexpression of HIF-1α had a tendency to better survival with marginal statistical significance (P=0.062. Patients with overexpression of VEGF-A had worse survival, but not statistically significant (P=0.133. Conclusion. The present study revealed that VEGF-A showed correlation with HIF-1α. HIF-1α had a tendency to protective effect with a P value close to statistical significance. VEGF-A showed a contrary effect but without statistical significance.

  3. Morphogenesis of early stage melanoma

    Science.gov (United States)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  4. Research on Postoperative Radiotherapy for Non-small Cell Lung Cancer of Stage IIIA (N2 according to the Failure Patterns after Pulmonary Resection

    Directory of Open Access Journals (Sweden)

    Peiyan QIN

    2009-10-01

    Full Text Available Background and objective Postoperative radiotherapy (PORT after complete resection of non-small cell lung cancer (NSCLC has been introduced in order to reduce locoregional recurrence, but it remains controversy whether PORT can improve survival. Therefore, we want to investigate the effect of PORT and the relationship between failure patterns and primarily location of stage IIIA (N2 in NSCLC. Methods This retrospective analysis included 233 patients who underwent resection of NSCLC, first recurrence involving a local-regional site. It illustrated the factors affecting local recurrence and the sites of failure on the basis of lobe of primary tumor. Results Multivariable analysis demonstrated the number of positive lymph nodes (P=0.003, T stage (P<0.001, histological type (P=0.038, modus operandi (P=0.013 and the number of mediastinal lymph node stations involved (P=0.018 were the independent factors. For all patients, the most common site of failure was the bronchial stump/staple line, which was present more often in those who had a wedge resection than in those who had a more radical procedure (P<0.001. The local-region frequency of squamous was higher than adenocarcinoma carcinoma (P=0.025. The recurrence frequency of mediastinal lymph node among T1 and T2-3 were 36.4%, 62.0% (P=0.009 respectively. The localregion recurrence among primarily tumor location were different. Conclusion The number of positive lymph nodes, T stage, histological type, modus operations and the number of mediastinal lymph node stations involved were the independent factors in IIIA (N2 NSCLC.

  5. Diagnostic impact of integrated 18F-FDG PET/MRI in cerebral staging of patients with non-small cell lung cancer.

    Science.gov (United States)

    Deuschl, Cornelius; Nensa, Felix; Grueneisen, Johannes; Poeppel, Thorsten D; Sawicki, Lino M; Heusch, Philipp; Gramsch, Carolin; Mönninghoff, Christoph; Quick, Harald H; Forsting, Michael; Umutlu, Lale; Schlamann, Marc

    2017-08-01

    Background Integrated positron emission tomography/magnetic resonance imaging (PET/MRI) systems are increasingly being available and used for staging examinations. Brain metastases (BM) are frequent in patients with non-small cell lung cancer (NSCLC) and decisive for treatment strategy. Purpose To assess the diagnostic value of integrated 18F-2-fluoro-2-deoxy-D glucose (18F-FDG) PET/MRI in initial staging in patients with NSCLC for BM in comparison to MRI alone. Material and Methods Eighty-three patients were prospectively enrolled for an integrated 18F-FDG PET/MRI examination. The 3 T MRI protocol included a fluid-attenuated inversion-recovery sequence (FLAIR) and a contrast-enhanced three-dimensional magnetization prepared rapid acquisition GRE sequence (MPRAGE). Two neuroradiologists evaluated the datasets in consensus regarding: (i) present lesions; (ii) size of lesions; and (iii) number of lesions detected in MRI alone, compared to the PET component when reading the 18F-FDG PET/MRI. Results Based on MRI alone, BM were detected in 15 out of the 83 patients, comprising a total of 39 metastases. Based on PET alone, six patients out of the 83 patients were rated positive for metastatic disease, revealing a total of 15 metastases. PET detected no additional BM. The size of the BM correlated positively with sensitivity of detection in PET. Conclusion The sensitivity of PET in detection of BM depends on their size. 18F-FDG PET/MRI does not lead to an improvement in diagnostic accuracy in cerebral staging of NSCLC patients, as MRI alone remains the gold standard.

  6. The Preoperative Controlling Nutritional Status Score Predicts Survival After Curative Surgery in Patients with Pathological Stage I Non-small Cell Lung Cancer.

    Science.gov (United States)

    Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

    2017-02-01

    The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; pcancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

    Science.gov (United States)

    Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

    2016-08-01

    To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

  8. [Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?].

    Science.gov (United States)

    Gómez, Ana M; Jarabo, José Ramón; Fernandez, Cristina; Calatayud, Joaquín; Fernández, Elena; Torres, Antonio J; Balibrea, José L; Hernando, Florentino

    2014-04-01

    Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

  9. Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xiangpeng [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Schipper, Matthew [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Kidwell, Kelley [Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Lin, Jules; Reddy, Rishindra [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Ren, Yanping [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Chang, Andrew [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Lv, Fanzhen [Department of Thoracic Surgery, Huadong Hospital, Fudan University, Shanghai (China); Orringer, Mark [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Spring Kong, Feng-Ming, E-mail: Fkong@gru.edu [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States)

    2014-11-01

    Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

  10. Survival Benefit of Surgery after Chemoradiotherapy for Stage III (N0-2) Non-Small-Cell Lung Cancer Is Dependent on Pathologic Nodal Response.

    Science.gov (United States)

    Ziel, Ellis; Hermann, Gregory; Sen, Neilayan; Bonomi, Philip; Liptay, Michael J; Fidler, Mary Jo; Batus, Marta; Warren, William H; Chmielewski, Gary; Sher, David J

    2015-10-01

    The benefit of surgery (trimodality therapy [TMT]) after chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer (NSCLC) is controversial, but nodal pathologic complete response (N-PCR) is accepted as a strong predictor of overall survival (OS). We compared the outcomes of patients treated with TMT versus CRT, focusing on the importance of N-PCR. Patients with stage III NSCLC treated with CRT or TMT from December 2004 through December 2012 were included; patients with N3 disease were excluded. Pathologic nodal response dichotomized surgical patients into N-PCR versus residual nodal disease (RND) groups. Actuarial OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) were compared between patients treated with CRT and TMT and between CRT and N-PCR/RND. The cohort was composed of 138 patients (52% CRT and 48% TMT). The median OS was significantly higher after TMT than after CRT (81 versus 31.8 mo, p = 0.0068). This benefit was restricted to N-PCR (n = 50, 83.2 versus 31.8 mo, p = 0.0004), as RND (n = 19) experienced poor OS (16.1 mo). On multivariable analyses, N-PCR had superior OS (hazard ratio [HR], 0.38; p = 0.0012), PFS (HR, 0.42; p = 0.0005), and DMFS (HR, 0.42; p = 0.0007) compared with CRT. Conversely, there were trends for worse OS and PFS for RND versus CRT, although only inferior DMFS was significant (HR, 1.83; p = 0.04). Surgical patients with complete nodal clearance experienced superior survival, but those with RND fared no better than CRT alone. Mediastinal response may play an important role in the decision to proceed with surgical resection after CRT for stage III NSCLC.

  11. Which Is the Optimal Biologically Effective Dose of Stereotactic Body Radiotherapy for Stage I Non-Small-Cell Lung Cancer? A Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jian; Yang Fujun [Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, Tianjin (China); Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Shandong' s Key Laboratory of Radiation Oncology, Jinan (China); Li Baosheng, E-mail: baoshli@yahoo.com [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Shandong' s Key Laboratory of Radiation Oncology, Jinan (China); Li Hongsheng [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Shandong' s Key Laboratory of Radiation Oncology, Jinan (China); Liu Jing [School of Public Health, Shandong University, Jinan (China); Huang Wei; Wang Dongqing; Yi Yan; Wang Juan [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Shandong' s Key Laboratory of Radiation Oncology, Jinan (China)

    2011-11-15

    Purpose: To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2010. According to the quartile of included studies, BED was divided into four dose groups: low (<83.2 Gy), medium (83.2-106 Gy), medium to high (106-146 Gy), high (>146 Gy). To obtain pooled estimates of overall survival (OS), cancer-specific survival (CSS), and local control rate (LCR), data were combined in a random effect model. Pooled estimates were corrected for the percentage of small tumors (<3 cm). Results: Thirty-four observational studies with a total of 2,587 patients were included in the meta-analysis. Corrected pooled estimates of 2- or 3-year OS in the medium BED (76.1%, 63.5%) or the medium to high BED (68.3%, 63.2%) groups were higher than in the low (62.3%, 51.9%) or high groups (55.9%, 49.5%), respectively (p {<=} 0.004). Corrected 3-year CSS in the medium (79.5%), medium to high (80.6%), and high groups (90.0%) were higher than in the low group (70.1%, p = 0.016, 0.018, 0.001, respectively). Conclusion: The OS for the medium or medium to high BED groups were higher than those for the low or high BED group for SBRT in Stage I NSCLC. The medium or medium to high BED (range, 83.2-146 Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.

  12. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment.

    Science.gov (United States)

    van der Meij, Barbara S; Langius, Jacqueline A E; Smit, Egbert F; Spreeuwenberg, Marieke D; von Blomberg, B Mary E; Heijboer, Annemieke C; Paul, Marinus A; van Leeuwen, Paul A M

    2010-10-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.

  13. Pathomorphological prognostic factors as the basis of optimization for multimodality treatment of IIIA stage of non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Sukhoversha O.A.

    2007-01-01

    Full Text Available The aim of the study was the investigation the influence of pathomorphological prognosis factors on the results for multimodality treatment of IIIA stage of non-small cell lung cancer, as well as their use for therapeutic strategy optimization. The investigation has been carried out on 262 operated patients who being held the surgical treatment and platinum-based chemotherapy (CT. The control group consisted of 157 patients (77 – with adjuvant CT, the clinical group consisted of 105 patients, who being held the CT before and after the operation. Conducted correlation analysis (to the survival rate of operated patients defined as a negative prognosis factors the presence of adenogenic histotype and low level of tumor differ-entiation. The positive factor for tumor respectability and patients’ survival is the high level of treatment pathomorphism (TPM, which is the proof of advisability of achievement the best effect from induction CT. Chemoresistance of the NSCLC is the feature for neoplasms with the high level of differentiation and it correlates with overexpression Her-2/neu2+/3+.

  14. Clinical efficacy of concurrent carboplatin, etoposide, and definitive radiotherapy for stage III non-small-cell lung cancer. Consideration as to therapeutic outcomes and morbidity

    Energy Technology Data Exchange (ETDEWEB)

    Kodaira, Takeshi; Yamakawa, Kouji; Taniguchi, Hiroyuki [Tosei General Hospital, Seto, Aichi (Japan); Matsubara, Kazuhito; Ishigaki, Takeo

    1998-08-01

    To improve the therapeutic outcome for inoperable non-small-cell lung cancer, we applied definitive thoracic radiotherapy combined with concurrent administration of carboplatin and etoposide. We retrospectively analyzed 55 eligible patients with Stage III disease. The one-year rate of overall survival (OAS) and distant metastasis-free survival (DMFS) of the total group were 46.1% and 36.1%, respectively. Twenty-nine patients developed thoracic failures (52.7%) and 23 (41.8%) distant failures. Using univariate and multivariate analyses, radiation dose, performance status and LDH were revealed as significant prognostic factors of OAS, and LDH had a strong adverse effect on DMFS. Leucopenia of Grade 3 or higher was noted in 75.9%, anemia in 55.6%, thrombocytopenia in 59.3%, esophagitis in 20.4%, and lung injury in 10.9%. Sufficient gain was not obtained by out strategy, and higher morbidity, especially of lung, was noted than was expected. It was suspected that simultaneous use of oral etoposide might increase radiation pneumonitis, so one should take special care of unexpected toxicity in concurrent chemoradiotherapy. Both the hyperfractionated technique of radiotherapy and the time-dose modification of anti-tumor drugs should be considered in further steps. (author)

  15. Intratumoral Metabolic Heterogeneity for Prediction of Disease Progression After Concurrent Chemoradiotherapy in Patients with Inoperable Stage III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Saeryung; Song, Hochun; Byun, Byung Hyun and others

    2014-03-15

    We evaluated the value of variable {sup 18}F-FDG PET/CT parameters for the prediction of disease progression after concurrent chemoradiotherapy (CCRT) in patients with inoperable stage III non-small-cell lung cancer (NSCLC). One hundred sixteen pretreatment FDG PET/CT scans of inoperable stage III NSCLC were retrospectively reviewed (stage IIIA: 51; stage IIIB: 65). The volume of interest was automatically drawn for each primary lung tumor, and PET parameters were assessed as follows: maximum standardized uptake value (SUV{sub max}), metabolic tumor volume (MTV) using the boundaries presenting SUV intensity exceeding 3.0, and the area under the curve of the cumulative SUV-volume histograms (AUC-CSH), which is known to reflect the tumor heterogeneity. Progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared with each PET and clinical parameters by univariate and multivariate survival analysis.In the ROC analysis, the optimal cutoff values of SUV{sub max}, MTV (cm{sup 3}), and AUC-CSH for prediction of PFS were determined as 21.5, 27.7, and 4,800, respectively. In univariate analysis, PFS was statistically significantly reduced in those with AUC-CSH<4,800 (p =0.004). In multivariate analysis, AUC-CSH and SUV{sub max} were statistically significant independent prognostic factors (HR 3.35, 95 % CI 1.79.6.28, p <0.001; HR 0.25, 95% CI 0.09.0.70, p =0.008, respectively). Multivariate analysis showed that AUC-CSH was the most significant independent prognostic factor for LRFS and DMFS (HR 3.27, 95 % CI 1.54.6.94, p =0.002; HR 2.79, 95 % CI 1.42.5.50, p =0.003). Intratumoral metabolic heterogeneity of primary lung tumor in {sup 18}F-FDG PET/CT can predict disease progression after CCRT in inoperable stage III NSCLC.

  16. Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data.

    Science.gov (United States)

    Reboul, François L

    2004-02-01

    Over the past 20 years, combined treatment with radiotherapy and second-generation chemotherapy drugs was extensively studied in patients with locally advanced NSCLC and became the standard over radiotherapy alone in patients with good performance status. Radiosensitizing properties of cisplatin have been identified in the laboratory. Close temporal administration of cisplatin and radiation is mandatory for enhanced antitumor efficacy, but results in significant toxicity to normal tissues. Early clinical studies demonstrated that the concurrent administration of cisplatin during STD-RT was feasible, with acceptable esophageal toxicity, and had the potential of significantly improving locoregional control. Carboplatin administered concurrently with accelerated HFX-RT was responsible for a higher rate of esophageal toxicity. Further improvement in survival also requires an effective treatment of micro-metastatic disease through full-dose delivery of cytotoxic drugs and the addition of at least one more active drug in conjunction with cisplatin and radiotherapy to further improve locoregional control of the disease. In most clinical studies, etoposide was the second drug of choice because of its own radiosensitizing properties and possible synergy with cisplatin. In numerous phase II studies, concurrent radiotherapy and PE resulted in reproducible results in terms of local control (30%-40%), median survival (15-18 months), survival at 2 years (35%-40%), and survival at 5 years (25%-30%). In phase III studies, these results were shown to be superior to radiotherapy alone and to induction chemotherapy followed by STD-RT. The question of the potential benefit of HFX-RT combined with PE has been addressed in phase II and III studies. At this time, there is no firm evidence that concurrent chemotherapy with HFX-RT is superior to concurrent chemotherapy with STD-RT in terms of local control and survival. Only a significant benefit in terms of local control or survival would

  17. Curative Treatment of Stage I Non-Small-Cell Lung Cancer in Patients With Severe COPD: Stereotactic Radiotherapy Outcomes and Systematic Review

    Energy Technology Data Exchange (ETDEWEB)

    Palma, David, E-mail: david.palma@uwo.ca [VU University Medical Center, Amsterdam (Netherlands); Division of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Lagerwaard, Frank [VU University Medical Center, Amsterdam (Netherlands); Rodrigues, George [Division of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Haasbeek, Cornelis; Senan, Suresh [VU University Medical Center, Amsterdam (Netherlands)

    2012-03-01

    Objectives: Patients with severe chronic obstructive pulmonary disease (COPD) have a high risk of lung cancer and of postsurgical complications. We studied outcomes after stereotactic body radiotherapy (SBRT) in patients with severe COPD, as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and performed a systematic review of the literature on outcomes after SBRT or surgery in these patients. Methods: A single-institution cohort of 176 patients with COPD GOLD III-IV and Stage I non-small-cell lung cancer (NSCLC) treated with SBRT was evaluated. A systematic review identified studies reporting outcomes after SBRT or surgery for Stage I NSCLC in patients with GOLD III-IV or a predicted postoperative forced expiratory volume in 1 second (FEV1) of {<=}40%. Results: In the single-institution cohort, median follow-up was 21 months and median overall survival (OS) was 32 months. Actuarial 3-year local control was 89%, and 1- and 3-year OS were 79% and 47%, respectively. COPD severity correlated with OS (p = 0.01). The systematic review identified four other studies (two surgical, two SBRT, n = 196 patients). SBRT studies were published more recently and included older patients than surgical studies. Mean 30-day mortality was 0% post-SBRT and 10% after surgery. Local or locoregional control was high ({>=}89%) after both treatments. Post-SBRT, actuarial OS was 79-95% at 1 year and 43-70% at 3 years. Postsurgical actuarial OS was 45-86% at 1 year and 31-66% at 3 years. Conclusions: SBRT and surgery differ in risk of 30-day mortality in patients with severe COPD. Despite the negative selection of SBRT patients, survival at 1 and 3 years is comparable between the two treatments.

  18. PET/CT vs. non-contrast CT alone for surveillance 1-year post lobectomy for stage I non-small-cell lung cancer.

    Science.gov (United States)

    Dane, Bari; Grechushkin, Vadim; Plank, April; Moore, William; Bilfinger, Thomas

    2013-01-01

    (18)F-FDG PET/CT was compared with non-contrast chest CT in monitoring for recurrence 1-year after lobectomy of stage 1 non-small-cell lung cancer (NSCLC). For surveillance after treatment with curative intent, current (April 2012) National Comprehensive Cancer network guidelines recommend chest CT with or without contrast every 6-12 months for 2 years, then non-contrast chest CT annually. PET/CT is not currently indicated for routine follow-up. One hundred patients receiving surveillance PET/CT 1-year after lobectomy for the treatment of stage 1a or 1b NSCLC were included in the study. Exclusion criteria included the presence or interval diagnosis of a second malignancy, or surgical treatment more radical than single lobectomy. The non-contrast CT obtained from the 1-year PET/CT was interpreted by an experienced chest radiologist blinded to the PET/CT for evidence of recurrence using the following findings: pulmonary nodule, pleural effusion, pleural mass, adenopathy, and extrathoracic mass. The ecision about recurrence was made solely from the non-contrast CT without PET/CT findings. This was compared with the determination made with PET/CT. The reference standard for determination of recurrence was the multi-disciplinary tumor board who had access to all imaging and clinical data. Recurrence at 1 year was documented in 16 of 90 patients. All 16 recurrences were documented with PET/CT and 9 were found with non-contrast CT. Five of the 7 recurrences missed with non-contrast CT were extrathoracic metastases. Sensitivity of CT and PET/CT for recurrence was 56.3% and 100%, respectively (p = 0.015). Specificity of CT and PET/CT for recurrence was 95.9% and 93.2%, respectively (p = 0.62).

  19. Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers.

    Science.gov (United States)

    Yoshino, Mitsuru; Suzuki, Makoto; Tian, Lei; Moriya, Yasumitsu; Hoshino, Hidehisa; Okamoto, Tatsuro; Yoshida, Shigetoshi; Shibuya, Kiyoshi; Yoshino, Ichiro

    2009-11-01

    Hypermethylation of promoter CpG islands is a major inactivation mechanism of tumor suppressor genes, some of which are thought to be related to the prognosis of patients with non-small cell lung cancer (NSCLC). Therefore, hypermethylation of the specific genes may be expected to serve as a prognostic biomarker for NSCLC. In this study, the methylation status of 14 genes was analyzed in 44 stage IA NSCLC cases using methylation-specific PCR. Hypermethylation was detected in PTGER2 (70% of cases), DRM/Gremlin (66%), sFRP-2 (57%), IL-12Rbeta2 (48%), Reprimo (41%), APC (39%), CXCL12 (39%), HPP1 (30%), SPARC (30%), sFRP-5 (30%), p16 (25%), RUNX3 (20%), sFRP-1 (20%) and Wif-1 (16%). Patients with p16, sFRP-5, Wif-1 or CXCL12 methylation had a significantly shorter duration of relapse-free survival than their counterparts with an unmethylated gene (p16, P=0.011; sFRP-5, P=0.030, Wif-1, P=0.036; CXCL12, P=0.026). Also, those with methylated HPP1, p16 or Wif-1 had a significantly shorter duration of overall survival (HPP1, P=0.031; p16, P=0.026; Wif-1, P=0.008). Multivariate analysis revealed that p16 methylation in relapse-free survival and Wif-1 methylation in overall survival were the strongest independent prognostic factors (p16, P=0.036; Wif-1, P=0.035). In conclusion, the hypermethylation of the p16 and Wif-1 genes has potential as biomarkers that may be used to predict the prognosis of stage IA NSCLC.

  20. The prognostic impact of supraclavicular lymph node in N3-IIIB stage non-small cell lung cancer patients treated with definitive concurrent chemo-radiotherapy.

    Science.gov (United States)

    Oh, Dongryul; Ahn, Yong Chan; Park, Hee Chul; Lim, Do Hoon; Noh, Jae Myoung; Cho, Won Kyung; Pyo, Hongryull

    2017-05-30

    This study aimed to investigate the prognostic impact of supraclavicular lymph node (SCN) metastasis in patients who were treated with definitive chemoradiotherapy for N3-IIIB stage non-small cell lung cancer (NSCLC). The 2- and 5-year overall survival (OS) rates were 57.3% and 35.7% in patients without SCN metastasis and 56.4% and 26.7% in patients with SCN metastasis, respectively. The median OS was 34 months in both groups. There was no significant difference in OS between the two groups (p = 0.679). The 2- and 5-year progression-free survival (PFS) rates were 24.1% and 12.6% in patients without SCN metastasis and 18.0% and 16.0% in patients with SCN metastasis, respectively. Patients without SCN metastasis had slightly longer median PFS (10 months vs. 8 months), but the difference was not statistically significant (p = 0.223). In multivariate analysis, SCN metastasis was not a significant factor for OS (p = 0.391) and PFS (p = 0.149). This retrospective analysis included 204 consecutive patients who were treated with chemoradiotherapy for N3-IIIB stage NSCLC between May 2003 and December 2012. A median RT dose of 66 Gy was administered over 6.5 weeks. Of these, 119 patients (58.3%) had SCN metastasis and 85 (41.7%) had another type of N3 disease: mediastinal N3 nodes in 84 patients (98.8%) and contralateral hilar node in one (1.2%). The patients were divided into two groups according to SCN metastasis. SCN metastasis does not compromise treatment outcomes compared to other mediastinal metastasis in the setting of definitive chemoradiotherapy.

  1. PET-CT in presurgical lymph node staging in non-small cell lung cancer: the importance of false-negative and false-positive findings.

    Science.gov (United States)

    García de Castro, A Bustos; Domínguez, J Ferreirós; Bolton, R Delgado; Pérez, C Fernández; Martínez, B Cabeza; García-Esquinas, M García; Carreras Delgado, J L

    To assess the importance of false-negative and false-positive findings in computed tomography (CT) and (18)F-FDG positron emission tomography (PET) in mediastinal lymph node staging in patients undergoing surgery for non-small cell lung cancer (NSCLC). This retrospective study included 113 consecutive patients and 120 resected NSCLCs; 22 patients received neoadjuvant treatment. We compared the findings on preoperative (18)F-FDG PET-CT studies with the postoperative pathology findings. Lymph node size and primary tumor size were measured with CT, and lymph nodes and primary tumors were evaluated qualitatively and semiquantitatively (using standardized uptake values (SUVmax)) with PET. Metastatic lymph nodes were found in 26 (21.7%) of the 120 tumors and in 41 (7.7%) of the 528 lymph node stations analyzed. (18)F-FDG PET-CT yielded 53.8% sensitivity, 76.6% specificity, 38.9% positive predictive value, 85.7% negative predictive value, and 71.7% diagnostic accuracy. The false-negative rate was 14.2%. Multivariable analysis found that the factors associated with false-negative findings were a moderate degree of differentiation in the primary tumor (p = 0.005) and an SUVmax of the primary tumor >4 (p = 0.027). The false-positive rate was 61.1%, and the multivariable analysis found that lymph node size >1cm was associated with false-positive findings (p < 0.001). In mediastinal lymph node staging in patients with NSCLC, (18)F-FDG PET-CT improves the specificity and negative predictive value and helps clinicians to select the patients that will benefit from surgery. Given the high rate of false positives, histological confirmation of positive cases is recommendable. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Fibroblast Growth Factor 2-A Predictor of Outcome for Patients Irradiated for Stage II-III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk, E-mail: Rades.Dirk@gmx.net [Department of Radiation Oncology, University of Lubeck, Lubeck (Germany); Setter, Cornelia [Department of Radiation Oncology, University of Lubeck, Lubeck (Germany); Dahl, Olav [Section of Oncology, Institute of Medicine, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Schild, Steven E. [Department of Radiation Oncology, Mayo Clinic Scottsdale, Scottsdale, Arizona (United States); Noack, Frank [Institute of Pathology, University of Lubeck, Lubeck (Germany)

    2012-01-01

    Purpose: The prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients with non-small-cell lung cancer (NSCLC) is unclear. The present study investigated the effect of tumor cell expression of FGF-2 on the outcome of 60 patients irradiated for Stage II-III NSCLC. Methods and Materials: The effect of FGF-2 expression and 13 additional factors on locoregional control (LRC), metastasis-free survival (MFS), and overall survival (OS) were retrospectively evaluated. These additional factors included age, gender, Karnofsky performance status, histologic type, histologic grade, T and N category, American Joint Committee on Cancer stage, surgery, chemotherapy, pack-years, smoking during radiotherapy, and hemoglobin during radiotherapy. Locoregional failure was identified by endoscopy or computed tomography. Univariate analyses were performed with the Kaplan-Meier method and the Wilcoxon test and multivariate analyses with the Cox proportional hazard model. Results: On univariate analysis, improved LRC was associated with surgery (p = .017), greater hemoglobin levels (p = .036), and FGF-2 negativity (p <.001). On multivariate analysis of LRC, surgery (relative risk [RR], 2.44; p = .037), and FGF-2 expression (RR, 5.06; p <.001) maintained significance. On univariate analysis, improved MFS was associated with squamous cell carcinoma (p = .020), greater hemoglobin levels (p = .007), and FGF-2 negativity (p = .001). On multivariate analysis of MFS, the hemoglobin levels (RR, 2.65; p = .019) and FGF-2 expression (RR, 3.05; p = .004) were significant. On univariate analysis, improved OS was associated with a lower N category (p = .048), greater hemoglobin levels (p <.001), and FGF-2 negativity (p <.001). On multivariate analysis of OS, greater hemoglobin levels (RR, 4.62; p = .002) and FGF-2 expression (RR, 3.25; p = .002) maintained significance. Conclusions: Tumor cell expression of FGF-2 appeared to be an independent negative predictor

  3. Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel or cisplatin/etoposide in stage III non-small cell lung cancer.

    Science.gov (United States)

    Liew, Mun Sem; Sia, Joseph; Starmans, Maud H W; Tafreshi, Ali; Harris, Sam; Feigen, Malcolm; White, Shane; Zimet, Allan; Lambin, Philippe; Boutros, Paul C; Mitchell, Paul; John, Thomas

    2013-12-01

    Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each with concurrent radiotherapy, remain largely undefined. Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60 Gy chest radiotherapy between 2000 and 2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student's t and chi-squared tests. Seventy-five (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs. 63 years; P = 0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs. 14%, P = 0.024) and thrombocytopenia (10% vs. 0%, P = 0.039). Radiation pneumonitis was more common with PC (66% vs. 38%, P = 0.033). Five treatment-related deaths occurred (PC: 3 vs. PE: 2, P = 1.000). With a median follow-up of 51.6 months, there were no significant differences in relapse-free survival (median PC 12.0 vs. PE 11.5 months, P = 0.700) or overall survival (median PC 20.7 vs. PE 13.7 months; P = 0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities.

  4. The postoperative neutrophil-to-lymphocyte ratio and changes in this ratio predict survival after the complete resection of stage I non-small cell lung cancer

    Science.gov (United States)

    Jin, Feng; Han, Anqin; Shi, Fang; Kong, Li; Yu, Jinming

    2016-01-01

    Purpose Although numerous studies have demonstrated associations between the preoperative neutrophil-to-lymphocyte ratio (NLR) and long-term outcomes in patients with non-small cell lung cancer (NSCLC), the prognostic significance of postoperative NLR and change in NLR (ΔNLR) is unknown for patients who underwent complete resection of stage I NSCLC. The aim of this retrospective study was to evaluate the prognostic significance of postoperative NLR and ΔNLR in 123 patients with stage I NSCLC. Patients and methods This retrospective study included preoperative and postoperative data of 123 patients who underwent surgical resection for stage I NSCLC. The relationship between disease-free survival (DFS), overall survival (OS), and clinicopathological factors, including NLR, lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio, and their changes, was analyzed using both univariate Kaplan–Meier and multivariate Cox regression methods. Results The 5-year DFS and OS rates in our cohort were 60.16% and 67.48%, respectively. Univariate analysis revealed that age (P=0.045), smoking status (P=0.033), preoperative NLR (P=0.032), postoperative NLR (P<0.001), ΔNLR (P=0.004), and change in LMR (ΔLMR) (P=0.025) were significant predictors of DFS and that age (P=0.039), smoking status (P=0.042), postoperative NLR (P<0.001), ΔNLR (P=0.004), and ΔLMR (P=0.011) were independent predictors of OS. Multivariate analysis confirmed that postoperative NLR (hazard ratio [HR] =2.435, P=0.001) and ΔNLR (HR =2.103, P=0.012) were independent predictors of DFS and that postoperative NLR (HR =2.747, P=0.001) and ΔNLR (HR =2.052, P=0.018) were significant prognostic factors of OS. Conclusion Our study reported for the first time that postoperative NLR and ΔNLR – but not preoperative NLR – were independent prognostic factors of DFS and OS in patients with stage I NSCLC who underwent complete resection. This easily available biomarker might be helpful in individual risk

  5. A pilot study (SWOG S0429 of weekly cetuximab and chest radiotherapy for poor-risk stage III non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yuhchyau eChen

    2013-08-01

    Full Text Available Purpose: Stage III non-small cell lung cancer (NSCLC patients with poor performance status (PS or co-morbidities are often not candidates for standard chemoradiotherapy (chemoRT due to poor tolerance to treatments. A pilot study for poor-risk stage III NSCLC patients was conducted combining cetuximab, a chimeric monoclonal antibody targeting epidermal growth factor receptor (EGFR, with chest radiation (RT. Methods: Stage III NSCLC patients with Zubrod PS 2, or Zubrod PS 0-1 with poor pulmonary function and co-morbidities prohibiting chemoRT were eligible. A loading dose of cetuximab (400 mg/m2 was delivered week one, followed by weekly cetuximab (250 mg/m2/RT to 64.5 Gy in 1.8 Gy daily fractions, and maintenance weekly cetuximab (250 mg/m2 for two years or until disease progression. H-score for EGFR protein expression was conducted in available tumors.Results: Twenty-four patients were enrolled. Twenty two were assessed for outcome and toxicity. Median survival was 14 months and median progression-free survival was 8 months. The response rate was 47% and disease control rate was 74%. Toxicity assessment revealed 22.7% overall ≥ Grade 3 non-hematologic toxicities. Grade 3 esophagitis was observed in one patient (5%. The skin reactions were mostly Grade 1 or 2 except two of 22 (9% had Grade 3 acne and 1/22 (5% had Grade 3 radiation skin burn. Grade 3-4 hypomagnesemia was seen in 4 (18% patients. One patient (5% had elevated cardiac troponin and pulmonary emboli. H-score did not reveal prognostic significance. An initially planned second cohort of the study did not commence due to slow accrual, which would have added weekly docetaxel to cetuximab/RT after completion of the first cohort of patients. Conclusions: Concurrent weekly cetuximab/chest RT followed by maintenance cetuximab for poor-risk stage III NSCLC was well tolerated. Further studies with larger sample sizes will be useful to establish the optimal therapeutic ratio of this regimen.

  6. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Annemarie T. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Xanthopoulos, Eric [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Evans, Tracey; Stevenson, James; Langer, Corey [Department of Medical Oncology, University of Pennsylvania, Philadelphia, PA (United States); Kucharczuk, John C. [Department of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA (United States); Lin, Lilie; Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

    2012-05-01

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III

  7. A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus

    Directory of Open Access Journals (Sweden)

    Bang Sun-Hwi

    2012-06-01

    Full Text Available Background and Objectives: Non-small-cell lung cancer (NSCLC represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus (HAP has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. Methods: The study involved six patients treated at the East- West Cancer Center (EWCC from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS and progression-free survival (PFS. Results: Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD, and the other three showed progressive disease (PD. The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. Conclusion: HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

  8. Impact of Prophylactic Cranial Irradiation Timing on Brain Relapse Rates in Patients With Stage IIIB Non-Small-Cell Lung Carcinoma Treated With Two Different Chemoradiotherapy Regimens

    Energy Technology Data Exchange (ETDEWEB)

    Topkan, Erkan, E-mail: docdretopkan@gmail.com [Baskent University Adana Medical Faculty, Department of Radiation Oncology, Kisla Saglik Yerleskesi, Adana (Turkey); Parlak, Cem; Kotek, Ayse; Yuksel, Oznur [Baskent University Adana Medical Faculty, Department of Radiation Oncology, Kisla Saglik Yerleskesi, Adana (Turkey); Cengiz, Mustafa [Hacettepe University Medical Faculty, Oncology Hospital, Department of Radiation Oncology, Sihhiye, Ankara (Turkey); Ozsahin, Mahmut [University of Lausanne, University Hospital, Department of Radiation Oncology, Lausanne (Switzerland); Pehlivan, Berrin [Akdeniz University Medical Faculty, Department of Radiation Oncology, Antalya (Turkey)

    2012-07-15

    Purpose: To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy. Results: At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001). Conclusion: These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.

  9. Early diagnosis of early stage lung cancer

    Directory of Open Access Journals (Sweden)

    Andrej Debeljak

    2005-11-01

    Full Text Available Background: For the detection of premalignant changes of bronchial mucosa and early stages of lung cancer frequent chest X-ray, spiral low dose computed tomography, fluorescence bronchoscopy, sputum cytology (also with automated systems with genetic and molecular changes in the sputum cells and bronchial mucosa were used. These screening methods of the high-risk groups for lung cancer achieved: earlier diagnosis of lung cancer in lower stage, higher operability, longer 5-year survival, but without mortality reduction.Conclusions: In the clinical practice we can examine higher risk groups for lung cancer in randomised control trials with multimodality approach: frequent chest low-dose fast spiral computed tomography, sputum cytology with genetic and molecular examinations and fluorescence bronchoscopy. Smoking cessation remains the best means to achieve mortality reduction from lung cancer.

  10. Is there any maximum standardized uptake value variation among positron emission tomography scanners for mediastinal staging in non-small cell lung cancer?

    Science.gov (United States)

    Iskender, Ilker; Kadioglu, Salih Zeki; Kosar, Altug; Atasalihi, Ali; Kir, Altan

    2011-06-01

    The maximum standardized uptake value (SUV(max)) varies among positron emission tomography-integrated computed tomography (PET/CT) centers in the staging of non-small cell lung cancer. We evaluated the ratio of the optimum SUV(max) cut-off for the lymph nodes to the median SUV(max) of the primary tumor (ratioSUV(max)) to determine SUV(max) variations between PET/CT scanners. The previously described PET predictive ratio (PPR) was also evaluated. PET/CT and mediastinoscopy and/or thoracotomy were performed on 337 consecutive patients between September 2005 and March 2009. Thirty-six patients were excluded from the study. The pathological results were correlated with the PET/CT findings. Histopathological examination was performed on 1136 N2 lymph nodes using 10 different PET/CT centers. The majority of patients (group A: 240) used the same PET/CT scanner at four different centers. Others patients were categorized as group B. The ratioSUV(max) for groups A and B was 0.18 and 0.22, respectively. The same ratio for centers 1, 2, 3 and 4 was 0.2, 0.21, 0.21, and 0.23, respectively. The optimal cut-off value of the PPR to predict mediastinal lymph node pathology for malignancy was 0.49 (likelihood ratio +2.02; sensitivity 70%, specificity 65%). We conclude that the ratioSUV(max) was similar for different scanners. Thus, SUV(max) is a valuable cut-off for comparing-centers.

  11. Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597.

    Science.gov (United States)

    Karp, Daniel D; Lee, Sandra J; Keller, Steven M; Wright, Gail Shaw; Aisner, Seena; Belinsky, Steven Alan; Johnson, David H; Johnston, Michael R; Goodman, Gary; Clamon, Gerald; Okawara, Gordon; Marks, Randolph; Frechette, Eric; McCaskill-Stevens, Worta; Lippman, Scott M; Ruckdeschel, John; Khuri, Fadlo R

    2013-11-20

    Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 μg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.

  12. Patterns of abnormal FDG uptake by various histological types of non-small cell lung cancer at initial staging by PET

    Energy Technology Data Exchange (ETDEWEB)

    Wong, C.O.; Nunez, R.; Bohdiewicz, P.; Fink-Bennett, D.; Balon, H.; Dickinson, C.; Dworkin, H.J. [Dept. of Nuclear Medicine, William Beaumont Hospital, Royal Oak, MI (United States); Welsh, R.J.; Chmielewski, G.W.; Pursel, S.E. [Dept. of Thoracic Surgery, William Beaumont Hospital, Royal Oak, MI (United States); Ravikrishnan, K.P. [Dept. of Pulmonary Medicine, William Beaumont Hospital, Royal Oak, MI (United States); Hill, J.C. [Information Service, William Beaumont Hospital, Royal Oak, MI (United States)

    2001-11-01

    The aim of this study was to identify useful patterns of abnormal fluorine-18 fluorodeoxyglucose (FDG) uptake by different types of non-small cell (NSC) lung cancer and to assess their clinical implications. One hundred and three sequential patients with newly diagnosed, pathology-proven NSC lung cancer were included. FDG positron emission tomography (PET) images were acquired using a dedicated PET scanner. There were 35 squamous cell carcinomas (SQC), 17 large cell cancers (LGC), 38 adenocarcinomas (ADC), 1 bronchioloalveolar carcinoma (BAC) and 12 non-classified NSC cancers. PET images were categorized into detectable patterns of necrotic center in the primary tumor, satellite lesions (T4), hilar lymph nodes (N1), and N2, N3, and M1 lesions by visual interpretation of PET images for SQC, LGC, and ADC (n=90; BAC and non-classified NSC cancers were excluded). The PET lesions were correlated with surgical pathology and with CT findings in inoperable cases. Necrosis was more commonly present in the primary tumors of LGC (53%) and SQC (43%) than in those of ADC (26%) (P<0.0001 and <0.01, respectively). The frequencies of nodal uptake in ADC, SQC and LGC were similar (71%, 60%, and 59%, respectively). However, M1 lesions were present significantly more often in LGC (41%) and ADC (34%) than in SQC (3%) (both P<0.0001). Significantly more surgically inoperable cases were found by PET (T4, N3, M1) in ADC (50%) and LGC (41%) than in SQC (26%) (P<0.001 and <0.02, respectively). Our results suggest a wide variation of PET findings for different types of NSC lung cancer. Identification of these patterns is useful in clinical PET interpretation, in that knowledge of the most probable association between the PET patterns and the histological types will facilitate initial staging and planning of management. (orig.)

  13. Residual {sup 18}F-FDG-PET Uptake 12 Weeks After Stereotactic Ablative Radiotherapy for Stage I Non-Small-Cell Lung Cancer Predicts Local Control

    Energy Technology Data Exchange (ETDEWEB)

    Bollineni, Vikram Rao, E-mail: v.r.bollineni@umcg.nl [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Widder, Joachim [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Pruim, Jan [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A.; Wiegman, Erwin M. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

    2012-07-15

    Purpose: To investigate the prognostic value of [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake at 12 weeks after stereotactic ablative radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC). Methods and Materials: From November 2006 to February 2010, 132 medically inoperable patients with proven Stage I NSCLC or FDG-PET-positive primary lung tumors were analyzed retrospectively. SABR consisted of 60 Gy delivered in 3 to 8 fractions. Maximum standardized uptake value (SUV{sub max}) of the treated lesion was assessed 12 weeks after SABR, using FDG-PET. Patients were subsequently followed at regular intervals using computed tomography (CT) scans. Association between post-SABR SUV{sub max} and local control (LC), mediastinal failure, distant failure, overall survival (OS), and disease-specific survival (DSS) was examined. Results: Median follow-up time was 17 months (range, 3-40 months). Median lesion size was 25 mm (range, 9-70 mm). There were 6 local failures: 15 mediastinal failures, 15 distant failures, 13 disease-related deaths, and 16 deaths from intercurrent diseases. Glucose corrected post-SABR median SUV{sub max} was 3.0 (range, 0.55-14.50). Using SUV{sub max} 5.0 as a cutoff, the 2-year LC was 80% versus 97.7% for high versus low SUV{sub max}, yielding an adjusted subhazard ratio (SHR) for high post-SABR SUV{sub max} of 7.3 (95% confidence interval [CI], 1.4-38.5; p = 0.019). Two-year DSS rates were 74% versus 91%, respectively, for high and low SUV{sub max} values (SHR, 2.2; 95% CI, 0.8-6.3; p = 0.113). Two-year OS was 62% versus 81% (hazard ratio [HR], 1.6; 95% CI, 0.7-3.7; p = 0.268). Conclusions: Residual FDG uptake (SUV{sub max} {>=}5.0) 12 weeks after SABR signifies increased risk of local failure. A single FDG-PET scan at 12 weeks could be used to tailor further follow-up according to the risk of failure, especially in patients potentially eligible for salvage surgery.

  14. Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsy-proven stage IIIA N2 non-small cell lung cancer. an EORTC phase II study (EORTC 08958).

    NARCIS (Netherlands)

    O'Brien, ME; Splinter, T; Smit, E.F.; Biesma, B.; Krzakowski, M; Tjan-Heijnen, VC; Bochove, A Van; Stigt, J; Smid-Geirnaerdt, MJ; Debruyne, C.; Legrand, C; Giaccone, G.

    2003-01-01

    The aim of this study was to document the activity and toxicity of paclitaxel (Taxol)/carboplatin when used as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) prior to definitive local treatment within a large, ongoing comparative study (EORTC 08941). 52 elig

  15. Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for Stage IIIA and Stage IIIB non-small cell lung cancer: results of a Phase I-II study by the GOTHA group

    Energy Technology Data Exchange (ETDEWEB)

    Alberto, P.; Mermillod, B. [Hopital Cantonal Geneve, Geneva (Switzerland); Mirimanoff, R.O.; Leyvraz, S.; Nagy-Mignotte, H.; Bolla, M.; Wellmann, D.; Moro, D.; Brambilla, E. [Hopital Cantonal Universitaire, Lausanne (Switzerland)

    1995-08-01

    The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy. (author).

  16. 18F-FDG PET-CT: predicting recurrence in patients following percutaneous cryoablation treatment for stage I primary non-small-cell lung cancer.

    Science.gov (United States)

    LoGiurato, Brendan; Matthews, Robert; Safaie, Elham; Moore, William; Bilfinger, Thomas; Relan, Nand; Franceschi, Dinko

    2015-09-01

    The aim of this study was to understand the imaging features of fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET-computed tomography (CT) in postcryoablation lung cancer patients that could help predict recurrence. We identified 28 patients with 30 lesions treated by means of percutaneous cryoablation for stage I non-small-cell lung cancer. Two experienced nuclear radiologists blindly reviewed baseline images and follow-up (18)F-FDG PET-CT scans for a minimum of 24 months, with discrepancy in interpretation resolved by consensus. Nineteen lesions had undergone baseline PET-CT studies, whereas 11 lesions had undergone only baseline CT studies. Follow-up PET-CT studies were analyzed for up to 24 months, whereas the recurrence-free survival analysis was performed for 36 months. The average maximum standardized uptake value (SUV(max)) at baseline (n = 19) was 5.2 ± 3.9 and the average CT area at baseline was 2.2 ± 1.6 cm(2). Only the CT area was significantly different between recurring and nonrecurring lesions at baseline (P = 0.0028). The Kaplan-Meier survival analysis showed that dichotomizing lesions around 2 cm on CT did not result in a statistically significant survival difference (hazard ratio = 1.42, 95% confidence interval: 0.63-2.21). The average SUV(max) at first follow-up was 1.9 ± 1.8 for 27 lesions, whereas the average SUV(max) of recurrent lesions was 2.2 ± 2.2 and that of nonrecurrent lesions was 1.5 ± 0.3 (P = 0.17). Six lesions had SUV(max) more than or equal to 2.5 within 24 months, all of which recurred in the ablation zone. (18)F-FDG PET-CT is a valuable tool for determining treatment response and for distinguishing benign from malignant lesions after cryoablation. The CT area was most predictive of future recurrence at baseline, whereas SUV(max) more than or equal to 2.5 was most predictive of future recurrence at first follow-up.

  17. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Scagliotti, G.V.; Parikh, P.; Pawel, J. von

    2008-01-01

    Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study ...... neutropenia (P = .002); and alopecia (P

  18. Ablative dose proton beam therapy for stage I and recurrent non-small cell lung carcinomas. Ablative dose PBT for NSCLC

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Uk; Cho, Kwan Ho; Kim, Joo Young; Kim, Dae Yong; Kim, Tae Hyun; Suh, Yang-Gun; Kim, Yeon-Joo [Research Institute and Hospital, National Cancer Center, Proton Therapy Center, Goyang (Korea, Republic of); Moon, Sung Ho [Research Institute and Hospital, National Cancer Center, Proton Therapy Center, Goyang (Korea, Republic of); Research Institute and Hospital, National Cancer Center, Center for Lung Cancer, Goyang (Korea, Republic of); Research Institute and Hospital, National Cancer Center, Proton Therapy Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769 (Korea, Republic of); Pyo, Hong Ryull [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiation Oncology, Seoul (Korea, Republic of)

    2016-09-15

    To evaluate the efficacy and safety of ablative dose hypofractionated proton beam therapy (PBT) for patients with stage I and recurrent non-small cell lung carcinoma (NSCLC). A total of 55 patients with stage I (n = 42) and recurrent (n = 13) NSCLC underwent hypofractionated PBT and were retrospectively reviewed. A total dose of 50-72 CGE (cobalt gray equivalent) in 5-12 fractions was delivered. The median follow-up duration was 29 months (range 4-95 months). There were 24 deaths (43.6%) during the follow-up period: 11 died of disease progression and 13 from other causes. Kaplan-Meier overall survival rate (OS) at 3 years was 54.9% and the median OS was 48.6 months (range 4-95 months). Local progression was observed in 7 patients and the median time to local progression was 9.3 months (range 5-14 months). Cumulative actuarial local control rate (LCR), lymph node metastasis-free survival, and distant metastasis-free survival rates at 3 years were 85.4, 78.4, and 76.5%, respectively. Larger tumor diameter was significantly associated with poorer LCR (3-year: 94% for ≤3 cm vs. 65% for >3 cm, p = 0.006) on univariate analysis and also an independent prognostic factor for LCR (HR 6.9, 95% CI = 1.3-37.8, p = 0.026) on multivariate analysis. No grade 3 or 4 treatment-related toxicities developed. One grade 5 treatment-related adverse event occurred in a patient with symptomatic idiopathic pulmonary fibrosis. Ablative dose hypofractionated PBT was safe and promising for stage I and recurrent NSCLC. (orig.) [German] Beurteilung von Wirksamkeit und Sicherheit hypofraktionierter Protonentherapie (PBT) mit ablativen Dosen fuer nichtkleinzellige Lungenkarzinome (NSCLC) im Stadium I und rekurrierende NSCLC. Retrospektiv wurden insgesamt 55 NSCLC-Patienten (Stadium I: n = 42; rekurrierender Tumor: n = 13), analysiert. Sie waren mit einer Gesamtdosis von 50-72 CGE (''cobalt gray equivalent'') in 5-12 Fraktionen behandelt worden. Der Median der Follow

  19. Patterns of recurrence and survival after surgery or stereotactic radiotherapy for early stage NSCLC

    NARCIS (Netherlands)

    van den Berg, Liseth L.; Klinkenberg, Theo J.; Groen, Harry J. M.; Widder, Joachim

    Introduction: Surgery is the standard treatment for early stage non-small-cell lung cancer (NSCLC). For medically inoperable patients, stereotactic ablative radiotherapy (SABR) has emerged as widely used standard treatment. The aim of this study was to analyze survival and patterns of tumor

  20. Patterns of recurrence and survival after surgery or stereotactic radiotherapy for early stage NSCLC

    NARCIS (Netherlands)

    van den Berg, Liseth L.; Klinkenberg, Theo J.; Groen, Harry J. M.; Widder, Joachim

    2015-01-01

    Introduction: Surgery is the standard treatment for early stage non-small-cell lung cancer (NSCLC). For medically inoperable patients, stereotactic ablative radiotherapy (SABR) has emerged as widely used standard treatment. The aim of this study was to analyze survival and patterns of tumor recurren

  1. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

    OpenAIRE

    Wilson, Gareth A.; Constantin, Tudor; Quesne, John Le; Moore, David A.; Kirkizlar, Eser; Fraioli, Francesco; Bakir, Maise Al; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M.; Forster, Martin D.; Hafez, Dina; Ganguly, Apratim; Kareht, Stephanie

    2017-01-01

    The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution th...

  2. Multimodality treatment of stagenon-small cell lung cancer%Ⅲ期非小细胞肺癌的综合治疗

    Institute of Scientific and Technical Information of China (English)

    刘江泽; 黄原义; 魏嵬; 熊远奎; 廖欣彬; 李英

    2013-01-01

    Objective: :To investigate the effect of bronchial artery chemoembolization combined with radiotherapy, chemotherapy for stagenon-small cell lung cancer (NSCLC). Methods: 143 cases of NSCLC were divided into two groups. In group of chemotherapy and radiotherapy, 71 cases had chemotherapy and radiation therapy synchronously. The intervention group of 72 cases with bronchial artery infusion chemotherapy and embolization had interventional radiotherapy on the second day for 2 cycles. Total dose of radiotherapy was 60~70 G in 6~7 weeks. 3 to 4 weeks after, all patients used NP program, with a total of 2 to 4 cycles of chemotherapy. Results: Two groups completed treatment plan. The intervention group had CR 37. 5%, PR 45.8%, efficiency 83. 3 %. The control group had CR 23. 9 % , PR 39. 4 % , efficiency 63.3%. In the intervention group, median survival time was 22. 6 months, and it was 14. 5 months in the control group. In the intervention group, 1,2,3 year survival rate was 78. 6% , 44.3%, 23.5%, respectively. And, in control group, it was 63. 2%, 33.4%, 14.5%, respectively. The intervention group was significantly higher than that in the control group, there was significant difference ( P <0. 05). No serious complications occurred. Conclusion:Percutaneous bronchial artery chemoembolization combined with radiotherapy, chemotherapy in treatment of stageⅢ NSCLC can prolong median survival time, improve the survival rate of patients, have good clinical efficacy.%目的:探讨支气管动脉化疗栓塞结合同步放疗、静脉化疗治疗Ⅲ期非小细胞肺癌(NSCLC)的疗效.方法:143例Ⅲ期NSCLC患者分为2组,对照组71例,化疗与放射治疗同步进行;介入组72例,采用支气管动脉化疗栓塞,第2天行放疗,介入治疗2个周期.放疗总剂量60~70 Gy,6~7周完成.所有患者3~4周后采用长春瑞滨、顺铂(NP)方案,共化疗2~4个周期.结果:2组全部完成治疗计划.介入组完全缓解(CR)占37.5

  3. Early radiographic response to epidermal growth factor receptor-tyrosine kinase inhibitor in non-small cell lung cancer patients with epidermal growth factor receptor mutations: A prospective study

    Directory of Open Access Journals (Sweden)

    John WC Chang

    2015-06-01

    Full Text Available Background: The time schedules for response evaluation of epidermal growth factor receptor-tyrosine kinase Inhibitor (EGFR-TKI in non-small cell lung cancer (NSCLC patients are still ill-defined. Methods: Stage IIIB/IV patients with histologically proven NSCLC were enrolled in this study if the tumor cells bore EGFR mutations other than T790M. Eligible patients were treated with either 250 mg of gefitinib or 150 mg of erlotinib once daily. The early response rate [computed tomography (CT scan on Day 14], definitive response rate determined on Day 56, progression-free survival (PFS, overall survival (OS, and toxicity profile were assessed prospectively. Results: Thirty-nine patients were enrolled in this study. A total of 29 patients (29/39, 74.4% achieved partial response (PR. Twenty-one patients (21/39, 53.8% had early radiological response on Day 14. The early radiological response rate in patients with PR was 72.4% (21/29. Only eight patients without a PR on early CT still ended with PR. Among the 29 patients with PR, the PFS (8.1 months and OS (18.3 months of the 21 patients with early CT response were shorter than those of the 8 patients without early CT response (11.9 and 24.0 months for PFS and OS, respectively. But the survival differences were statistically non-significant. Conclusions: A very high percentage (72.4%, 21/29 of NSCLC patients with EGFR mutations with PR demonstrates early radiological response to EGFR-TKIs, which would advocate early radiological examination for EGFR-TKI therapy in NSCLC patients.

  4. 30 Gy or 34 Gy? Comparing 2 Single-Fraction SBRT Dose Schedules for Stage I Medically Inoperable Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Videtic, Gregory M.M., E-mail: videtig@ccf.org; Stephans, Kevin L.; Woody, Neil M.; Reddy, Chandana A.; Zhuang, Tingliang; Magnelli, Anthony; Djemil, Toufik

    2014-09-01

    Purpose: To review outcomes of 2 single-fraction lung stereotactic body radiation therapy (SBRT) schedules used for medically inoperable early stage lung cancer. Methods and Materials: Patients in our institution have been treated on and off protocols using single-fraction SBRT (30 Gy and 34 Gy, respectively). All patients had node-negative lung cancer measuring ≤5 cm and lying ≥2 cm beyond the trachea-bronchial tree and were treated on a Novalis/BrainLAB system with the ExactTrac positioning system for daily image guidance. Results: For the interval from 2009 to 2012, 80 patients with 82 lesions were treated with single-fraction lung SBRT. Fifty-five patients (69%) and 25 patients (31%) received 30 Gy and 34 Gy, respectively. In a comparison of 30 Gy and 34 Gy cohorts, patient and tumor characteristics were balanced and median follow-up in months was 18.7 and 17.8, respectively. The average heterogeneity-corrected mean doses to the target were 33.75 Gy and 37.94 Gy for the 30-Gy and 34-Gy prescriptions, respectively. Comparing 30-Gy and 34-Gy cohorts, 92.7% and 84.0% of patients, respectively, experienced no toxicity (P was not significant), and had neither grade 3 nor higher toxicities. For the 30-Gy and 34-Gy patients, rates of 1-year local failure, overall survival, and lung cancer-specific mortality were 2.0% versus 13.8%, 75.0% versus 64.0%, and 2. 1% versus 16.0%, respectively (P values for differences were not significant). Conclusions: This is the largest single-fraction lung SBRT series yet reported. and it confirms the safety, efficacy, and minimal toxicity of this schedule for inoperable early stage lung cancer.

  5. Impact of the new international association for the study of lung cancer staging system in non-small cell lung cancer: With comparison to the union for international cancer control 6th tumor, node, metastasis edition

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Jae; Lee, So Won; Shim, Sung Shine; Ryu, Yon Ju; Kim, Yoo Kyung [Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

    2014-04-15

    To investigate the impact of the proposed International Association for the Study of Lung Cancer (IASLC) tumor, node, metastasis (TNM) system on staging and outcome of non small cell lung cancer (NSCLC). With a total of 501 NSCLC patients with staging according to Union for International Cancer Control (UICC), 6th TNM (TNM-6) were reclassified according to the IASLC proposed TNM staging (TNM-7). The impact of TNM-7 in comparison with TNM-6 was evaluated at three levels: change in substage, staging, and outcome. The outcome measure was to compare the stage-specific overall survival of NSCLC between the two groups of patients. A total of 214 (42.7%) patients had changed TNM staging, and 101 (20.2%) patients had changed stage groupings in TNM-7 compared to TNM-6. Among 100 patients showing changed stage grouping, 72 (14.4%) showed upstage and 29 (5.8%) demonstrated downstage. The TNM-7 system resulted in better separation of survival curves among stage-specific NSCLC than TNM-6 system, especially in separation of stage IIA vs. IIB (p 0.023) and stage IIIB vs. IV (p < 0.001). TNM-7 for lung cancer appears to be superior in defining stage-specific survival groups than TNM-6, especially between stage IIA vs. stage IIB and stage IIIB vs. stage IV.

  6. Stromal CD8+ T-cell Density—A Promising Supplement to TNM Staging in Non-Small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Donnem, Tom; Hald, Sigurd M; Paulsen, Erna-Elise

    2015-01-01

    PURPOSE: Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates, which appears to be superior to the tumor-node-metastasis (TNM) classification in colorectal cancer. In non-small cell lung cancer (NSCLC), no immunoscore has been established, but in situ tumor...... from Bodo (n = 169), Oslo (n = 295), and Denmark (n = 178). Tissue microarrays and clinical routine CD8 staining were used for all cohorts. RESULTS: Stromal CD8(+) TIL density was an independent prognostic factor in the total material (n = 797) regardless of the endpoint: disease-free survival (P

  7. Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

    Science.gov (United States)

    2015-09-01

    Recurrent Large Cell Lung Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Squamous Cell Lung Carcinoma; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Squamous Cell Lung Carcinoma

  8. Effect of OK-432 combined UFT in patients with stage III non-small cell lung cancer treated by radiotherapy. A randomized prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Jingu, Kenichi [Fukuoka Univ. (Japan). School of Medicine; Ohmagari, Junichi; Masuda, Kouji [and others

    1997-06-01

    Distant metastasis and local recurrence are the causes of poor treatment results of unresectable non-small cell lung cancer patients. Inhibition of repair from radiation damage in tumors and distant metastases may improve the survival rate. Some authors of this paper previously reported that tegafur combined with OK-432 significantly improved the survival rate in these patients. We conducted a prospective randomized trial using UFT (mixed preparation of tegafur and uracil) with or without OK-432, after radiotherapy in these patients, to assess the effect of OK-432 on survival rate, the duration of continued response by previous treatment, and the effect on leucopenia due to UFT. However, unexpected results were obtained. OK-432 did not prolong response duration, did not improve the survival rate, and did not inhibit the leucopenia due to UFT. (author)

  9. Pulmonary CYP2A13 levels are associated with early occurrence of lung cancer-Its implication in mutagenesis of non-small cell lung carcinoma.

    Science.gov (United States)

    Chiang, Huai-Chih; Lee, Huei; Chao, How-Ran; Chiou, Yu-Hu; Tsou, Tsui-Chun

    2013-10-01

    CYP2A13, a human pulmonary specific cytochrome P450 enzyme, plays an important role in susceptibility to tobacco-specific nitrosamines (TSNAs)-induced lung cancer in humans. The pattern of CYP2A13 distribution in respiratory tract affects the susceptibility of the lung to carcinogens. CYP2A13 is expressed in the epithelium of trachea and bronchi; however its pattern of expression in human lung cancer remains largely unknown. This study aimed to determine the CYP2A13 expression in specimens from human non-small cell lung carcinomas (NSCLCs), i.e., adenocarcinoma and squamous carcinoma, by immunohistochemical (IHC) analysis and to identify the potential linkage between tumor CYP2A13 levels and some clinicopathological characteristics of NSCLC patients in Taiwan. The tumor CYP2A13 IHC staining signal was strong in 76% of the 112 study subjects. Study subjects (especially non-smoking or lung adenocarcinoma patients) with higher tumor CYP2A13 levels were younger. Multiple logistic regression analysis revealed that in younger subjects (age ≤ 66) and heavy smokers (pack-years ≥ 40), the odds ratio (OR) for positive tumor CYP2A13 staining was significantly higher than that for negative tumor CYP2A13 staining. Moreover, the association of EGFR gene mutations and positive tumor CYP2A13 staining was also revealed. In conclusion, these findings suggest the potential involvement of pulmonary CYP2A13 in the early occurrence of NSCLC as well as in the development of EGFR gene mutations.

  10. Dislocation generation during early stage sintering.

    Science.gov (United States)

    Sheehan, J. E.; Lenel, F. V.; Ansell, G. S.

    1973-01-01

    Discussion of the effects of capillarity-induced stresses on dislocations during early stage sintering. A special version of Hirth's (1963) theoretical calculation procedures modified to describe dislocation nucleation on planes meeting the sintering body's neck surface obliquely is shown to predict plastic flow at stress levels know to exist between micron size metal particles in the early stages of sintering.

  11. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

  12. The early predictive value of a decrease of metabolic tumor volume in repeated {sup 18}F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Wei, E-mail: weihuang@mcw.com [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Liu, Bo; Fan, Min [Department of Internal Medicine Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Zhou, Tao [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Fu, Zheng [PET/CT center, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Zhang, Zicheng; Li, Hongsheng [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Li, Baosheng, E-mail: alvinbird@163.com [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China)

    2015-03-15

    Highlights: •The patients underwent the second FDG PET during the early stage of concurrent chemoradiotherapy (CCRT). •To our knowledge, this could be the first study showing that the repeated FDG PET during the early stage of CCRT has added value by being a prognostic factor for recurrence of the locally advanced NSCLC patients. •This is a result of continuous research. •The decrease of MTV was the only significant risk factor for recurrence. -- Abstract: Purpose: The aim of this study is to investigate the value of [{sup 18}F] fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F FDG PET/CT) to predict recurrence of patients with locally advanced non-small cell lung cancer (NSCLC) during the early stage of concurrent chemoradiotherapy (CCRT). Methods: A total of 53 stage III NSCLC patients without diabetics or undergoing surgery were enrolled in the prospective study. Those patients were evaluated by FDG PET before and following 40 Gy radiotherapy (RT) with a concurrent cisplatin-based heterogeneous chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUVmax/SUVmean) and metabolic tumor volume (MTV) of the primary tumor. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analyses. The cutoffs of PET/CT parameters which have been determined by the previous study were used to separate the groups with Kaplan–Meier curves. Results: Recurrence rates at 1- and 2-years were 18.9% (10/53) and 50.9% (27/53) for all patients, respectively. Cox regression analysis showed that the only prognostic factor for recurrence was a decrease of MTV. Using the cutoff of 29.7%, a decrease of MTV can separate the patients into 2 groups with Kaplan–Meier curve successfully. Conclusion: The prospective study has reinforced the early predictive value of MTV in repeated {sup 18}F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who

  13. Early Change in Metabolic Tumor Heterogeneity during Chemoradiotherapy and Its Prognostic Value for Patients with Locally Advanced Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Xinzhe Dong

    Full Text Available To observe the early change of metabolic tumor heterogeneity during chemoradiotherapy and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC.From January 2007 to March 2010, 58 patients with NSCLC were included who were received 18F-fluorodeoxyglucose (18F-FDG PET/CT before and following 40 Gy radiotherapy with the concurrent cisplatin-based chemotherapy (CCRT. Primary tumor FDG uptake heterogeneity was determined using global and local scale textural features extracted from standardized uptake value (SUV histogram analysis (coefficient of variation [COV], skewness, kurtosis, area under the curve of the cumulative SUV histogram [AUC-CSH] and normalized gray-level co-occurrence matrix (contrast, dissimilarity, entropy, homogeneity. SUVmax and metabolic tumor volume (MTV were also evaluated. Correlations were analyzed between parameters on baseline or during treatments with tumor response, progression-free survival (PFS, and overall survival (OS.Compared with non-responders, responders showed significantly greater pre-treatment COV, contrast and MTV (AUC = 0.781, 0.804, 0.686, respectively. Receiver-operating-characteristic curve analysis showed that early change of tumor textural analysis serves as a response predictor with higher sensitivity (73.2%~92.1% and specificity (80.0%~83.6% than baseline parameters. Change in AUC-CSH and dissimilarity during CCRT could also predict response with optimal cut-off values (33.0% and 28.7%, respectively. The patients with greater changes in contrast and AUC-CSH had significantly higher 5-year OS (P = 0.008, P = 0.034 and PFS (P = 0.007, P = 0.039. In multivariate analysis, only change in contrast was found as the independent prognostic factor of PFS (HR 0.476, P = 0.021 and OS (HR 0.519, P = 0.015.The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be valuable for predicting treatment response

  14. SBRT in operable early stage lung cancer patients.

    Science.gov (United States)

    Roesch, Johannes; Andratschke, Nicolaus; Guckenberger, Matthias

    2014-08-01

    Since decades the gold standard for treatment of early stage non-small cell lung cancer (NSCLC) is surgical lobectomy plus mediastinal lymph node dissection. Patients in worse health status are treated with sublobar resection or radiation treatment. With development of stereotactic-body-radiotherapy (SBRT), outcome of patients treated with radiation was substantially improved. Comparison of SBRT and surgical techniques is difficult due to the lack of randomized trials. However, all available evidence in form of case control studies of population based studies show equivalence between sublobar resection and SBRT indicating that SBRT-when performed by a trained and experienced team-should be offered to all high-risk surgical patients. For patients not willing to take the risk of lobectomy and therefore refusing surgery, SBRT is an excellent treatment option.

  15. The early predictive value of a decrease of metabolic tumor volume in repeated (18)F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy.

    Science.gov (United States)

    Huang, Wei; Liu, Bo; Fan, Min; Zhou, Tao; Fu, Zheng; Zhang, Zicheng; Li, Hongsheng; Li, Baosheng

    2015-03-01

    The aim of this study is to investigate the value of [(18)F] fluorodeoxyglucose positron emission tomography/computed tomography ((18)F FDG PET/CT) to predict recurrence of patients with locally advanced non-small cell lung cancer (NSCLC) during the early stage of concurrent chemoradiotherapy (CCRT). A total of 53 stage III NSCLC patients without diabetics or undergoing surgery were enrolled in the prospective study. Those patients were evaluated by FDG PET before and following 40Gy radiotherapy (RT) with a concurrent cisplatin-based heterogeneous chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUVmax/SUVmean) and metabolic tumor volume (MTV) of the primary tumor. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analyses. The cutoffs of PET/CT parameters which have been determined by the previous study were used to separate the groups with Kaplan-Meier curves. Recurrence rates at 1- and 2-years were 18.9% (10/53) and 50.9% (27/53) for all patients, respectively. Cox regression analysis showed that the only prognostic factor for recurrence was a decrease of MTV. Using the cutoff of 29.7%, a decrease of MTV can separate the patients into 2 groups with Kaplan-Meier curve successfully. The prospective study has reinforced the early predictive value of MTV in repeated (18)F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who underwent CCRT. A decrease of MTV in (18)F-FDG uptake by the primary tumor correlates with higher LRFS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Definitive radiotherapy with or without chemotherapy for clinical stage T4N0-1 non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeon Joo; Song, Si Yeol; Jeong, Seong Yun; Kim, Sang We; Lee, Jung Shin; Kim, Su Ssan; Choi, Eun Kyung [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Won Sik [Dept. of Radiation Oncology, Gangneung Asan Hospital, Gangneung (Korea, Republic of)

    2015-12-15

    To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was 50 mg/m2 weekly paclitaxel combined with 20 mg/m2 cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.

  17. Variations in target volume definition for postoperative radiotherapy in stage III non-small-cell lung cancer: analysis of an international contouring study.

    Science.gov (United States)

    Spoelstra, Femke O B; Senan, Suresh; Le Péchoux, Cecile; Ishikura, Satoshi; Casas, Francesc; Ball, David; Price, Allan; De Ruysscher, Dirk; van Sörnsen de Koste, John R

    2010-03-15

    Postoperative radiotherapy (PORT) in patients with completely resected non-small-cell lung cancer with mediastinal involvement is controversial because of the failure of earlier trials to demonstrate a survival benefit. Improved techniques may reduce toxicity, but the treatment fields used in routine practice have not been well studied. We studied routine target volumes used by international experts and evaluated the impact of a contouring protocol developed for a new prospective study, the Lung Adjuvant Radiotherapy Trial (Lung ART). Seventeen thoracic radiation oncologists were invited to contour their routine clinical target volumes (CTV) for 2 representative patients using a validated CD-ROM-based contouring program. Subsequently, the Lung ART study protocol was provided, and both cases were contoured again. Variations in target volumes and their dosimetric impact were analyzed. Routine CTVs were received for each case from 10 clinicians, whereas six provided both routine and protocol CTVs for each case. Routine CTVs varied up to threefold between clinicians, but use of the Lung ART protocol significantly decreased variations. Routine CTVs in a postlobectomy patient resulted in V(20) values ranging from 12.7% to 54.0%, and Lung ART protocol CTVs resulted in values of 20.6% to 29.2%. Similar results were seen for other toxicity parameters and in the postpneumectomy patient. With the exception of upper paratracheal nodes, protocol contouring improved coverage of the required nodal stations. Even among experts, significant interclinician variations are observed in PORT fields. Inasmuch as contouring variations can confound the interpretation of PORT results, mandatory quality assurance procedures have been incorporated into the current Lung ART study. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Development of symptomatic brain metastases after chemoradiotherapy for stage III non-small cell lung cancer: Does the type of chemotherapy regimen matter?

    NARCIS (Netherlands)

    Hendriks, L.E.; Brouns, A.J.; Amini, M.; Uyterlinde, W.; Wijsman, R.; Bussink, J.; Biesma, B.; Oei, S.B.; Stigt, J.A.; Bootsma, G.P.; Belderbos, J.S.; Ruysscher, D.K. De; Heuvel, M.M. Van den; Dingemans, A.C.

    2016-01-01

    OBJECTIVES: Symptomatic brain metastases (BM) occur frequently after chemoradiotherapy (CRT) for stage III NSCLC. Aim of the current study was to determine whether the specific chemotherapy used in a CRT regimen influences BM development. MATERIALS AND METHODS: Retrospective multicenter study

  19. Traditional versus up-front [F-18] fluorodeoxyglucose-positron emission tomography staging of non-small-cell lung cancer : A Dutch cooperative randomized study

    NARCIS (Netherlands)

    Herder, GJM; Kramer, H; Hoekstra, OS; Smit, EF; Pruim, J; van Tinteren, H; Comans, EF; Verboom, P; Uyl-De Groot, CA; Welling, A; Paul, MA; Boers, M; Postmus, PE; Teule, GJ; Groen, HJM

    2006-01-01

    Purpose We investigated whether application of positron emission tomography (PET) immediately after first presentation might simplify staging while maintaining accuracy, as compared with traditional strategy in routine clinical setting. Methods At first presentation, patients with a provisional diag

  20. Comparison of RECIST, EORTC criteria and PERCIST for evaluation of early response to chemotherapy in patients with non-small-cell lung cancer.

    Science.gov (United States)

    Shang, Jingjie; Ling, Xueying; Zhang, Linyue; Tang, Yongjin; Xiao, Zeyu; Cheng, Yong; Guo, Bin; Gong, Jian; Huang, Li; Xu, Hao

    2016-10-01

    To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the European Organization for Research and Treatment of Cancer (EORTC) criteria and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 using PET volume computer-assisted reading (PET VCAR) for response evaluation in patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy. A total of 35 patients with NSCLC were included in this prospective study. All patients received standard chemotherapy and underwent (18)F-FDG PET/CT scans before and after treatment. With the assistance of PET VCAR, the chemotherapeutic responses were evaluated according to the RECIST 1.1, EORTC criteria and PERCIST 1.0. Concordance among these protocols was assessed using Cohen's κ coefficient and Wilcoxon's signed-ranks test. Progression-free survival (PFS) was calculated using the Kaplan-Meier test. RECIST 1.1 and EORTC response classifications were discordant in 20 patients (57.1 %; κ = 0.194, P EORTC and PERCIST 1.0 classifications were discordant in only 4 patients (11.4 %), resulting in better concordance (κ = 0.804, P > 0.05). Patients with a partial remission according to RECIST 1.1 had significantly longer PFS (P EORTC criteria and PERCIST 1.0, patients with a partial metabolic response had a significantly longer PFS than those with stable metabolic disease and those with progressive metabolic disease (P = 0.020 and P EORTC; both P EORTC criteria and PERCIST 1.0 are more sensitive and accurate than RECIST 1.1 for the detection of an early therapeutic response to chemotherapy in patients with NSCLC. Although EORTC criteria and PERCIST 1.0 showed similar results, PERCIST 1.0 is preferred because detailed and unambiguous definitions are given. We also found that response evaluations with PERCIST 1.0 using a single lesion and multiple lesions gave similar response classifications.

  1. Comparison of RECIST, EORTC criteria and PERCIST for evaluation of early response to chemotherapy in patients with non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shang, Jingjie; Ling, Xueying; Zhang, Linyue; Tang, Yongjin; Xiao, Zeyu; Cheng, Yong; Guo, Bin; Gong, Jian; Huang, Li; Xu, Hao [The First Affiliated Hospital of Jinan University, Department of Nuclear Medicine and PET/CT-MRI Centre, Guangzhou (China)

    2016-10-15

    To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the European Organization for Research and Treatment of Cancer (EORTC) criteria and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 using PET volume computer-assisted reading (PET VCAR) for response evaluation in patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy. A total of 35 patients with NSCLC were included in this prospective study. All patients received standard chemotherapy and underwent {sup 18}F-FDG PET/CT scans before and after treatment. With the assistance of PET VCAR, the chemotherapeutic responses were evaluated according to the RECIST 1.1, EORTC criteria and PERCIST 1.0. Concordance among these protocols was assessed using Cohen's κ coefficient and Wilcoxon's signed-ranks test. Progression-free survival (PFS) was calculated using the Kaplan-Meier test. RECIST 1.1 and EORTC response classifications were discordant in 20 patients (57.1 %; κ = 0.194, P < 0.05), and RECIST 1.1 and PERCIST 1.0 classifications were discordant in 22 patients (62.9 %; κ = 0.139, P < 0.05). EORTC and PERCIST 1.0 classifications were discordant in only 4 patients (11.4 %), resulting in better concordance (κ = 0.804, P > 0.05). Patients with a partial remission according to RECIST 1.1 had significantly longer PFS (P < 0.001) than patients with progressive disease, but not significantly longer than patients with stable disease (P = 0.855). According to both the EORTC criteria and PERCIST 1.0, patients with a partial metabolic response had a significantly longer PFS than those with stable metabolic disease and those with progressive metabolic disease (P = 0.020 and P < 0.001, respectively, for EORTC; both P < 0.001 for PERCIST 1.0). EORTC criteria and PERCIST 1.0 are more sensitive and accurate than RECIST 1.1 for the detection of an early therapeutic response to chemotherapy in patients with NSCLC. Although EORTC criteria and

  2. Dynamic contrast-enhanced perfusion area detector CT for non-small cell lung cancer patients: Influence of mathematical models on early prediction capabilities for treatment response and recurrence after chemoradiotherapy.

    Science.gov (United States)

    Ohno, Yoshiharu; Koyama, Hisanobu; Fujisawa, Yasuko; Yoshikawa, Takeshi; Seki, Shinichiro; Sugihara, Naoki; Sugimura, Kazuro

    2016-01-01

    To determine the capability and influence of the mathematical method on dynamic contrast-enhanced (CE-) perfusion area detector CT (ADCT) for early prediction of treatment response as well as progression free and overall survival (PFS and OS) of non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy. Sixty-six consecutive stage III NSCLC patients underwent dynamic CE-perfusion ADCT examinations, chemoradiotherapy and follow-up examinations. Response Evaluation Criteria in Solid Tumors (RECIST) criteria were used to divide all patients into responders and non-responders. Differences in each of the indices for all targeted lesions between measurements obtained 2 weeks prior to the first and the third course of chemotherapy were determined for all patients. ROC analyses were employed to determine the capability of perfusion indices as markers for distinguishing RECIST responders from non-responders. To evaluate their capability for early prediction of therapeutic effect, OS of perfusion index-based responders and non-responders were compared by using the Kaplan-Meier method followed by log-rank test. Area under the curve (Az) for total perfusion by means of the dual-input maximum slope method was significantly larger than that of pulmonary arterial perfusion using the same method (p=0.007) and of perfusion with the single-input maximum slope method (p=0.007). Mean OS demonstrated significantly difference between responder- and non-responder groups for total perfusion (p=0.02). Mathematical models have significant influence on assessment for early prediction of treatment response, disease progression and overall survival using dynamic CE-perfusion ADCT for NSCLC patients treated with chemoradiotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Salvage surgery for local failures after stereotactic ablative radiotherapy for early stage non-small cell lung cancer

    NARCIS (Netherlands)

    N. Verstegen (Naomi); A.W.P.M. Maat (Alex); F.J. Lagerwaard (Frank); M.A. Paul (Marinus); M. Versteegh (Michel); J.J. Joosten (Joris); W. Lastdrager (Willem); E.F. Smit (Egbert); B.J. Slotman (Ben); J.J.M.E. Nuyttens (Joost); S. Senan (Suresh)

    2016-01-01

    markdownabstract__Introduction:__ The literature on surgical salvage, i.e. lung resections in patients who develop a local recurrence following stereotactic ablative radiotherapy (SABR), is limited. We describe our experience with salvage surgery in nine patients who developed a local recurrence

  4. Completeness of TNM staging of small-cell and non-small-cell lung cancer in the Danish cancer registry, 2004-2009.

    Science.gov (United States)

    Deleuran, Thomas; Søgaard, Mette; Frøslev, Trine; Rasmussen, Torben Riis; Jensen, Henrik Kirstein; Friis, Søren; Olsen, Morten

    2012-01-01

    We examined the completeness of TNM staging of small-cell (SCLC) and nonsmall- cell (NSCLC) lung cancer in the national Danish Cancer Registry (DCR) and whether staging varied by year of diagnosis, gender, age, degree of comorbidity, or presence of histopathological diagnosis. We identified all patients with SCLCs and NSCLCs registered in the DCR during 2004-2009 and examined the completeness of their TNM registrations. Completeness was defined as the number of recorded individuals with TNM divided by the total number of patients. Completeness was calculated for TNM, T, N, and M individually, overall, and by year of diagnosis, gender, age at diagnosis, and comorbidity. Data regarding comorbidity was obtained from the Danish National Patient Register (DNPR). We performed separate analyses for patients with a histopathologically verified diagnosis of NSCLC. Finally, we designed an algorithm to categorize tumors with missing TNM components as limited, extensive, or distant disease. Overall TNM staging completeness was 77.5% (95% confidence interval (CI): 76.1%-78.8%) for SCLC and 77.9% (95% CI: 77.3%-78.4%) for NSCLC. Completeness did not vary by gender and increased during the study period. The proportion of staged patients was lower among patients above 80 years of age or with medium to high levels of comorbidity. Overall TNM completeness for SCLC and NSCLC in the Danish Cancer Registry is high, but decreases with increasing levels of comorbidity and at ages greater than 80 years. Researchers should be aware of these potential sources of bias.

  5. Radiation Therapy for Early Stage Lung Cancer

    OpenAIRE

    Parashar, Bhupesh; Arora, Shruthi; Wernicke, A. Gabriella

    2013-01-01

    Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In a...

  6. Radiation Therapy for Early Stage Lung Cancer

    OpenAIRE

    Parashar, Bhupesh; Arora, Shruthi; Wernicke, A. Gabriella

    2013-01-01

    Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In a...

  7. 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose positron-emission tomography is cost-effective in the initial staging of non-small cell lung cancer patients in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Cerci, Juliano Julio, E-mail: cercijuliano@hotmail.com [PET-CT Center, Quanta - Diagnostico e Terapia, Curitiba, PR (Brazil); Instituto do Coracao (InCor) - Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo, SP (Brazil); Takagaki, Teresa Yae [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil); Trindade, Evelinda; Morgado, Roberta; Morabito, Fausto; Musolino, Rafael Silva; Meneghetti, Jose Claudio; Soares Junior, Jose [Instituto do Coracao (InCor) - Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo, SP (Brazil)

    2012-07-15

    Objective: To evaluate the accuracy and cost-effectiveness of metabolic staging (MS) with FDG-PET as compared with the conventional staging (CS) strategy in the preoperative staging of non-small cell lung cancer (NSCLC). Materials And Methods: A total of 95 patients with initial diagnosis of NSCLC were staged before undergoing treatment. The MS and CS results were compared with regard to treatment definition and incidence of futile thoracotomies with both strategies. Results: Metabolic staging with FDG-PET upstaged 48.4% and down staged 5.3% of the patients, and would lead to change in the treatment of 41% of cases. Thoracotomy was considered as futile in 47% of the patients with CS, and in 19% of the patients with MS. The cost of futile thoracotomies in eight patients with MS was R$ 79,720, while in 31 patients with CS it would be R$ 308,915. Just such saving in costs would be more than enough to cover the costs of all FDG-PETs (R$ 126,350) or FDG-PET/CTs (R$ 193,515) for the 95 patients. Conclusion: The metabolic staging with FDG-PET is more accurate than CS in patients with NSCLC. Both FDG-PET and FDG-PET/CT are cost-effective methods and their utilization is economically justifiable in the Brazilian public health system. (author)

  8. CyberKnife with tumor tracking: An effective alternative to wedge resection for high-risk surgical patients with stage I non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Sean eCollins

    2012-02-01

    Full Text Available Published data suggests that wedge resection for stage I NSCLC results in improved overall survival compared to stereotactic body radiation therapy (SBRT. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV. Treatment plans were designed using hundreds of pencil beams. Doses delivered to the PTV ranged from 42-60 Gy in 3 fractions. The 30-Gy isodose contour extended at least 1cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3-month follow-up intervals. Forty patients (median age 76 with a median maximum tumor diameter of 2.6 cm (range, 1.4-5.0 cm and a mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV1 of 57% (range, 21 - 111% were treated. A mean dose of 50 Gy was delivered to the PTV over 3 to 13 days (median, 7 days. The 30-Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12 -72 months follow-up, the 3-year Kaplan-Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91% and 75% , respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1 to 2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

  9. Predictors for locoregional recurrence for clinical stage III-N2 non-small cell lung cancer with nodal downstaging after induction chemotherapy and surgery.

    Science.gov (United States)

    Amini, Arya; Lou, Feiran; Correa, Arlene M; Baldassarre, Randall; Rimner, Andreas; Huang, James; Roth, Jack A; Swisher, Stephen G; Vaporciyan, Ara A; Lin, Steven H

    2013-06-01

    Pathologic downstaging following chemotherapy for stage III-N2 NSCLC is a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown. Between 1998 and 2008, 153 patients with clinically or pathologically staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery. All had pathologic N0-1 disease, and none received postoperative radiotherapy. LRR were defined as recurrence at the surgical site, lymph nodes (levels 1-14 including supraclavicular), or both. Median follow-up was 39.3 months. Pretreatment N2 status was confirmed pathologically (18.2 %) or by PET/CT (81.8 %). Overall, the 5-year LRR rate was 30.8 % (n = 38), with LRR being the first site of failure in 51 % (22/+99877943). Five-year overall survival for patients with LRR compared with those without was 21 versus 60.1 % (p recurrence (p = 0.021, HR 1.91, 95 % CI 1.1-3.3) but only trended for poorer survival (p = 0.123, HR 1.48, 95 % CI 0.9-2.44). LRR remains high in resected stage III-N2 NSCLC patients after induction chemotherapy and nodal downstaging, particularly in patients with persistent N1 disease.

  10. [18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Evelyn E.C. de; Elmpt, Wouter van; Leijenaar, Ralph T.H.; Lambin, Philippe [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht (Netherlands); Hoekstra, Otto S. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Groen, Harry J.M. [University of Groningen and University Medical Center Groningen, Department of Pulmonary Diseases, Groningen (Netherlands); Smit, Egbert F. [VU University Medical Center, Department of Pulmonary Diseases, Amsterdam (Netherlands); The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Thoracic Oncology, Amsterdam (Netherlands); Boellaard, Ronald [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Noort, Vincent van der [The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Troost, Esther G.C. [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht (Netherlands); Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus of Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, Dresden (Germany); Dingemans, Anne-Marie C. [Maastricht University Medical Centre, Department of Pulmonology, GROW-School for Oncology and Developmental Biology, Maastricht (Netherlands)

    2017-01-15

    Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival. A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG. A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively). The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment showed more tumor responders

  11. [18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches.

    Science.gov (United States)

    de Jong, Evelyn E C; van Elmpt, Wouter; Leijenaar, Ralph T H; Hoekstra, Otto S; Groen, Harry J M; Smit, Egbert F; Boellaard, Ronald; van der Noort, Vincent; Troost, Esther G C; Lambin, Philippe; Dingemans, Anne-Marie C

    2017-01-01

    Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival. A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG. A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively). The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment

  12. [Factors influencing survival and recurrence and potential significance of postoperative radiotherapy and adjuvant chemotherapy for stage ⅢA-N2 non-small cell lung cancer].

    Science.gov (United States)

    Han, W; Song, Y Z; He, M; Li, J; Zhang, R; Qiao, X Y

    2016-11-23

    Objective: To investigate the survival, recurrence patterns and risk factors in patients with stage ⅢA-N2 NSCLC treated with curative surgery and adjuvant chemotherapy and to explore the significance of postoperative radiation therapy. Methods: The clinical data of 290 patients with pathologically diagnosed stage ⅢA-N2 NSCLC after curative resection and adjuvant chemotherapy from January 2010 to December 2014 at our department were retrospectively analyzed. The survival and recurrence patterns were observed, and the factors affecting locoregional recurrence were analyzed. Results: The median survival time was 31.5 months. The 1-, 3-and 5-year survival rates were 88.3%, 46.0% and 33.2%, respectively. The median locoregional control time was 38.5 months. The 1-, 3-and 5-year locoregional control rates were 78.6%, 55.2% and 41.0%, respectively. The median distant metastasis-free survival was 26.8 months. The 1-, 3-and 5-year distant metastasis-free survival rates were 76.4%, 45.5% and 39.5%, respectively. The median progression-free survival was 19.1 months. The 1-, 3-and 5-year progression-free survival rates were 64.1%, 32.5% and 23.8%, respectively. Univariate analysis showed that clinical N status, histological type, pathological T stage, operation mode, the number of positive N2 lymph nodes and the number of positive N2 lymph node stations had a significant influence on overall survival; clinical N status, histological type, the number of positive N2 lymph nodes and the number of positive N2 lymph node stations had a significant influence on locoregional control. Multivariate analysis demonstrated that the number of N2 positive lymph nodes (P= 0.017) was an independent factor for overall survival of stage ⅢA-N2 patients; the number of N2 positive lymph nodes (P=0.009) and histological type (P=0.005) were independent factors for locoregional recurrence. For left-sided lung cancer, the lymph node station failure sites were mostly in 2R, 4R, 5, 6 and 7, and

  13. Thoracic staging with {sup 18}F-FDG PET/MR in non-small cell lung cancer - does it change therapeutic decisions in comparison to {sup 18}F-FDG PET/CT?

    Energy Technology Data Exchange (ETDEWEB)

    Schaarschmidt, Benedikt M. [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany); University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Grueneisen, Johannes; Umutlu, Lale [University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Metzenmacher, Martin [University Duisburg-Essen, Medical Faculty, Department of Medical Oncology, Essen (Germany); Gomez, Benedikt; Ruhlmann, Verena [University Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, Essen (Germany); Gauler, Thomas [University Duisburg-Essen, Medical Faculty, Radiation and Tumour Clinic, Essen (Germany); Roesel, Christian [University Duisburg-Essen, Ruhrlandklinik, Thoracic Surgery and Endoscopy, Essen (Germany); Heusch, Philipp; Antoch, Gerald; Buchbender, Christian [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany)

    2017-02-15

    To investigate whether differences in thoracic tumour staging between {sup 18}F-FDG PET/CT and PET/MR imaging lead to different therapeutic decisions in Non-Small Cell Lung Cancer (NSCLC). Seventy-seven NSCLC patients that underwent whole-body {sup 18}F-FDG PET/CT from the base of skull to the upper thighs and thoracic PET/MR were enrolled in this retrospective study. Thoracic PET/CT and PET/MR images were staged according to the 7th edition of the AJCC staging manual. Staging results of both modalities were discussed separately in a simulated interdisciplinary tumour board and therapeutic decisions based on both imaging modalities were recorded. Descriptive statistics were used to compare the results and reasons for changes in the therapeutic decision were investigated. Staging results differed in 35 % of patients (27 patients) between thoracic PET/CT and PET/MR. Differences were detected when assessing the T-stage in 18 % (n = 14), the N-stage in 23 % (n = 18), and the M-stage in 1 % (n = 1). However, patient therapy management was changed in only six patients (8 %). Despite the variability of thoracic {sup 18}F-FDG PET/CT and PET/MR in TNM-staging, both modalities lead to comparable therapeutic decisions in patients suffering from NSCLC. Hence, {sup 18}F-FDG PET/MR can be considered an possible alternative to {sup 18}F-FDG PET/CT for clinical NSCLC staging. (orig.)

  14. Risk factors for brain metastases in surgically staged IIIA non-small cell lung cancer patients treated with surgery, radiotherapy and chemotherapy

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2011-01-01

    Full Text Available Introduction/Aim. Lung cancer is a leading cause of mortality among patients with carcinomas. The aim of this study was to point out risk factors for brain metastases (BM appearance in patients with IIIA (N2 stage of nonsmall cell lung cancer (NSCLC treated with three-modal therapy. Methods. We analyzed data obtained from 107 patients with IIIA (N2 stage of NSCLC treated surgically with neoadjuvant therapy. The frequency of brain metastases was examined regarding age, sex, histological type and the size of tumor, nodal status, the sequence of radiotherapy and chemotherapy application and the type of chemotherapy. Results. Two and 3-year incidence rates of BM were 35% and 46%, respectively. Forty-six percent of the patients recurred in the brain as their first failure in the period of three years. Histologically, the patients with nonsquamous cell lung carcinoma had significantly higher frequency of metastases in the brain compared with the group of squamous cell lung carcinoma (46% : 30%; p = 0.021. Examining treatment-related parameters, treatment with taxane-platinum containing regimens was associated with a lower risk of brain metastases, than platinum-etoposide chemotherapy regimens (31% : 52%; p = 0.011. Preoperative radiotherapy, with or without postoperative treatment, showed lower rate of metastases in the brain compared with postoperative radiotherapy treatment only (33% : 48%; p = 0.035. Conclusion. Brain metastases are often site of recurrence in patients with NSCLC (IIIA-N2. Autonomous risk factors for brain metastases in this group of patients are non-squamous NSCLC, N1-N2 nodal status, postoperative radiotherapy without preoperative radiotherapy.

  15. Prognostic factors in patients with stagenon-small cell lung cancer%Ⅳ期非小细胞肺癌预后影响因素分析

    Institute of Scientific and Technical Information of China (English)

    马美丽; 沈洁; 姜丽岩

    2006-01-01

    Objective: To investigate the prognostic factors for stagenon-small cell lung cancer (NSCLC) with distant metastasis and establish a reliable model of clinical prognostic index.Methods: From January 1990 to April 2005,313 primary NSCLC patients with metastasis,who had been treated in Shanghai Chest Hospital,were reviewed.Survival time was estimated according to the Kaplan-Meier method.Cox proportional hazard regression model was used for multivariate analysis.Results: Among the 313 cases of non-small cell lung cancer (NSCLC) at stage Ⅳ,there were 218 and 95 patients with metastasis to single and different organs,respectively.The overall median survival time for all 313 cases of NSCLC patients was 10.8 (9.00,12.30)months and the overall 1-,2-,3-,4- and 5-year survival rate was 45%,18%,12%,4% and 0%.There were 63,174,127,36,18,11 and 5 patients with metastasis to brain (20.13%),bone (55.59%),lung (40.58%),liver (11.50%),adrenal gland (5.75%),subcutaneous (3.51%) and others,respectively.The survival time was shortest in subcutaneous metastasis (4.6 months),and liver 7.0 months,brain 8.0 months,adrenal gland 8.6 months,bone 10.6 months,lung 11.8 months.Kaplan-Meier estimation showed that patients anatomic typing,KPS,numbers of organ with metastasis,appetite,liver,adrenal gland and subcutaneous metastasis,body weight loss,smoking,index of smoking,chemotherapy,cycles of chemotherapy were the predictors of survival.Multivariate analysis showed survival statistically significant correlation with anatomic typing,KPS,appetite,liver and subcutaneous metastasis,body weight loss,cycles of chemotherapy.The relative risk (RR) was 1.51,1.97,1.55,1.67,2.56,and 2.56 respectively.Conclusion: Survival time decreases distinctly in patients who had distant metastasis to more than two different organs (P<0.01).Bone is the commonest organ for distant metastasis in lung cancer.The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis

  16. Our experiences with erlotinib in second and third line treatment patients with advanced stage IIIB/ IV non-small cell lung cancer.

    Science.gov (United States)

    Mehić, Bakir; Stanetić, Mirko; Tinjić, Ljuljeta; Smoljanović, Vlatka

    2008-11-01

    HeadHER1/EGFR is known to play a pivotal role in tumorigenesis and is overexpressed in up to 80% of NSCLCs. The study of an Expanded Access Clinical Program of Erlotinib in NSCLC is a phase IV open-label, non-randomized, multicenter trial in patients with advanced (inoperable stage IIIb/IV) NSCLC who were eligible for treatment with erlotinib but had no access to trial participation. Patients for the study from Bosnia and Herzegovina (B&H) were selected from two Clinical centres (Sarajevo and Banja Luka). The aim of study was to evaluated efficacy and tolerability of erlotinib monotherapy in this setting. All patients who received at least one dose of erlotinib and data were entered in the database as of the CRF cut-off date of 14th May 2008 were included in analysis of data (n = 19). This population is defined as the Intent to Treat (ITT) population and includes all patients who had at least one dose of erlotinib regardless of whether major protocol violations were incurred. The findings are consistent with the results of the randomized, placebo-controlled BR.21 study. Indicating that erlotinib is an effective option for patients with advanced NSCLC who are unsuitable for, or who have previously failed standard chemotherapy. In B&H group of patients DCR was almost 84%, and PFS was approximately 24,7 weeks (compared with 44% and 9,7 weeks for erlotinib reported in phase III). Almost three quarter of the patients received erlotinib as their second line of therapy. Overall, erlotinib was well tolerated; there were no patients who withdrew due to a treatment-related AE (mainly rash) and there were few dose reductions. 24% of patients experienced an SAE (most commonly gastrointestinal (GI) disorders).

  17. Meta-analysis study of lymph node staging by 18 F-FDG PET/CT scan in non-small cell lung cancer: Comparison of TB and non-TB endemic regions

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Chih-Ying, E-mail: jine871@yahoo.com.tw [Department of Radiation Therapy and Oncology, Taichung Hospital, Department of Health, Executive Yuan, Taiwan (China); Institute of Integrated Medicine, China Medical University, Taichung, Taiwan (China); Chen, Jin-Hua, E-mail: chenjh12@gmail.com [Biostatistics Center and Graduate Institute of Biostatistics, China Medical University, Taichung, Taiwan (China); Liang, Ji-An, E-mail: hope.jal@msa.hinet.net [Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan (China); Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); Yeh, Jun-Jun, E-mail: anvin.funlan@msa.hinet.net [Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan (China); Department of Research, PingTung Christian Hospital and Meiho University, Pingtung, Taiwan (China); Kao, Chia-Hung, E-mail: d10040@mail.cmuh.org.tw [Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan (China); Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan (China)

    2012-11-15

    Lymph node staging in non-small cell lung cancer (NSCLC) is challenging and important for deciding treatment policy. The role of PET/CT scans in lymph node staging of NSCLC remains controversial when comparing TB and non-TB endemic regions. This study systematically reviews the literature regarding the diagnostic performance of PET/CT in lymph node staging of patients with NSCLC, and determines its pooled sensitivity and specificity. Methods: The databases of PubMed, Medline, and Cochrane library were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed. Results: Seven of 86 studies were included. These studies had moderate to good methodological quality. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for patient-based analyses (five studies) were 66%, 92.7%, 5.86%, and 0.41%, respectively, and those for lesion-based analyses (six studies) were 59.4%, 96.5%, 9.37%, and 0.31%, respectively. Subanalysis of endemic regions of tuberculosis (TB) showed that these regions had lower sensitivity and similar specificity to non-TB endemic regions. Conclusion: PET/CT showed high specificity in the lymph node staging of NSCLC and lower sensitivity in TB endemic regions.

  18. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

    DEFF Research Database (Denmark)

    Abbosh, Christopher; Birkbak, Nicolai Juul; Wilson, Gareth A.

    2017-01-01

    of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation......The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA...... of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience...

  19. Locoregional control of non-small cell lung cancer in relation to automated early assessment of tumor regression on cone beam computed tomography

    DEFF Research Database (Denmark)

    Brink, Carsten; Bernchou, Uffe; Bertelsen, Anders

    2014-01-01

    PURPOSE: Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its poten...... therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy....... potential use in response adapted personalized radiation therapy is evaluated empirically. METHODS AND MATERIALS: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment...... was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2...

  20. [Treatment of early stage Hodgkin disease

    DEFF Research Database (Denmark)

    Specht, Lena; Carde, P.; Mauch, P.

    1993-01-01

    In early stage Hodgkin's disease the optimal choice of treatment is still an unresolved issue. Twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out world-wide. The preliminary results of a global meta-analysis of these trials...

  1. Radiotherapy versus combined modality in early stages

    DEFF Research Database (Denmark)

    Specht, L.; Carde, P.; Mauch, P.;

    1992-01-01

    In early stage Hodgkin's disease the optimal choice of treatment for the individual patient is still an unresolved issue. So far, twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out worldwide. The preliminary results of a glob...

  2. Photodynamic therapy for the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Friedberg, Joseph S; Glatstein, Eli; Stevenson, James P; Sterman, Daniel H; Hahn, Stephen M; Cengel, Keith A

    2012-02-01

    Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers ≤1 cm with no extracartilaginous invasion. For patients with advanced-stage non-small cell lung cancer, photodynamic therapy can be used to palliate obstructing endobronchial lesions, as a component of definitive multi-modality therapy, or to increase operability or reduce the extent of operation required. A review of the available medical literature detailing all published studies utilizing photodynamic therapy to treat at least 10 patients with non-small cell lung cancer is performed, and treatment recommendations and summaries for photodynamic therapy applications are described.

  3. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

    Science.gov (United States)

    Silvestri, Gerard A; Gonzalez, Anne V; Jantz, Michael A; Margolis, Mitchell L; Gould, Michael K; Tanoue, Lynn T; Harris, Loren J; Detterbeck, Frank C

    2013-05-01

    Correctly staging lung cancer is important because the treatment options and prognosis differ significantly by stage. Several noninvasive imaging studies and invasive tests are available. Understanding the accuracy, advantages, and disadvantages of the available methods for staging non-small cell lung cancer is critical to decision-making. Test accuracies for the available staging studies were updated from the second iteration of the American College of Chest Physicians Lung Cancer Guidelines. Systematic searches of the MEDLINE database were performed up to June 2012 with the inclusion of selected meta-analyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables. The sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were approximately 55% and 81%, respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For PET scanning, estimates of sensitivity and specificity for identifying mediastinal metastasis were approximately 77% and 86%, respectively. These findings demonstrate that PET scanning is more accurate than CT scanning, but tissue biopsy is still required to confirm PET scan findings. The needle techniques endobronchial ultrasound-needle aspiration, endoscopic ultrasound-needle aspiration, and combined endobronchial ultrasound/endoscopic ultrasound-needle aspiration have sensitivities of approximately 89%, 89%, and 91%, respectively. In direct comparison with surgical staging, needle techniques have emerged as the best first diagnostic tools to obtain tissue. Based on randomized controlled trials, PET or PET-CT scanning is recommended for staging and to detect unsuspected metastatic disease and avoid noncurative resections. Since the last iteration of the staging guidelines, PET scanning has assumed a more prominent role both in its use prior to surgery and when evaluating for metastatic disease. Minimally invasive

  4. Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials.

    Science.gov (United States)

    Ichinose, Y; Kato, H; Koike, T; Tsuchiya, R; Fujisawa, T; Shimizu, N; Watanabe, Y; Mitsudomi, T; Yoshimura, M

    2001-10-01

    the group of completely resected stage IIIA-N2 non-small cell lung cancer patients (NSCLC) is considered to be heterogeneous in various aspects including survival and the recurrent pattern. In the present study, we attempted to clarify the factors which separate these patients into high and low risk groups based on the survival and local recurrence. a questionnaire survey on the survival and local recurrence of non-small cell lung cancer patients with pathological stage IIIA-N2 disease who underwent a complete resection from January 1992 to December 1993 was performed by the Japan Clinical Oncology Group as of July 1999. The information on the survival of 406 patients and that of local recurrence in 332 of them was available. the 5-year survival of the 406 patients was 31.0%. In a univariate analysis, the age, clinical and pathological T status, number of N2 stations, pathological N1 disease, operative modality and postoperative radiotherapy were all found to be important prognostic factors. Clinical N2 disease marginally influenced the survival (P=0.07). In a multivariate analysis of these variables including clinical N2 disease, the survival was significantly worse in the case of multiple N2 stations (hazard ratio=1.741), the presence of pathological N1 disease (1.403), pathological T2 or 3 disease (1.399) and an age older than 65 (1.327). The rate of freedom from any local recurrence at the bronchial stump, or in the hilar, mediastinal or supraclavicular lymph nodes at 5 years was 64%. In a univariate analysis of the freedom from local recurrence, the clinical N status, pathological T status, pathological N1 disease and number of N2 stations were all found to be important prognostic factors. A multivariate analysis revealed the freedom from local recurrence to be adversely influenced by multiple N2 stations (hazard ratio=2.05), and the presence of either clinical N1 or 2 (1.733) disease. The 5-year survival and the rate of freedom from local recurrence at 5

  5. Sublobar resection is associated with improved outcomes over radiotherapy in the management of high-risk elderly patients with Stage I non-small cell lung cancer: a systematic review and meta-analysis

    Science.gov (United States)

    Zhang, Bai-Lin; Chen, Jie; Zeng, Xian-Liang; Deng, Lei; Meng, Mao-Bin

    2017-01-01

    Background and Aim A matched-pair comparison was performed to compare the efficacy and safety of sublobar resection versus radiotherapy for high-risk elderly patients with Stage I non-small cell lung cancer (NSCLC). Patients and Methods We searched the Cochrane Library, MEDLINE, CENTRAL, EMBASE and manual searches. The meta-analysis was performed to compare overall survival, pattern of failure, and toxicity among the homogeneous studies. Subdivided analyses were also performed. Results Sixteen studies containing 11540 patients were included in the meta-analysis. Among these studies, 9 were propensity-score matched (PSM) cohort studies, and 7 were cohort studies. Sublobar resection, compared with radiotherapy (either conventional fraction radiation therapy or stereotactic body radiation therapy), significantly improved the overall survival regardless in both PSM and non-PSM analyses (all p 0.05). Conclusions Sublobar resection was associated with improved outcomes in high-risk elderly patients with Stage I NSCLC, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials. PMID:28002808

  6. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    Science.gov (United States)

    2012-12-13

    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  7. Value of dual time point F-18 FDG-PET/CT imaging for the evaluation of prognosis and risk factors for recurrence in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Satoh, Yoko, E-mail: pecampecam@yahoo.co.jp [PET Center, Kofu Neurosurgical Hospital, ZIP Code 400-0805, Sakaori 1-16-18, Kofu city, Yamanashi Prefecture (Japan); Nambu, Atsushi, E-mail: nambu-a@gray.plala.or.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Onishi, Hiroshi, E-mail: honishi@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Sawada, Eiichi, E-mail: e_sawaday_61674@ybb.ne.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Tominaga, Licht, E-mail: lichtt@gmail.com [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Kuriyama, Kengo, E-mail: kuriyama@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Komiyama, Takafumi, E-mail: takafumi-ymu@umin.ac.jp [Department of Radiology, Kofu Municipal Hospital, ZIP Code 400-0832, Masutsubo-cho 366, Kofu City, Yamanashi Prefecture (Japan); Marino, Kan, E-mail: marino-akrf@ych.pref.yamanashi.jp [Department of Radiology, Yamanashi Prefectural Hospital, ZIP Code 400-8506, Fujimi 1-1-1, Kofu City, Yamanashi Prefecture (Japan); Aoki, Shinichi, E-mail: aokis@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); and others

    2012-11-15

    Purpose: To investigate prognostic and risk factors for recurrence after stereotactic body radiation therapy (SBRT) in patients with stage I non-small cell lung carcinoma (NSCLC), focusing on dual time point [18]F-fluorodeoxyglucose positron emission tomography (FDG PET). Materials and methods: We prospectively evaluated 57 patients with stage I NSCLC (45 T1N0M0 and 12 T2N0M0) who had undergone pretreatment FDG-PET/CT and were subsequently treated with SBRT. All patients received a whole-body PET/CT scan at 60 min and a whole-lung at 120 min after the injection. The maximum standardized uptake value (SUV) and retention index (RI) of the lesions were calculated. Local recurrence, regional lymph node metastasis, distant metastasis, and the recurrence pattern were evaluated. Cox proportional hazard regression analyses were performed to evaluate prognostic factors or risk factors of recurrence. Results: During the median follow-up period of 27 months, local recurrence, regional lymph node metastasis, and distant metastasis were seen in 17 (30%), 12 (21%), and 17 (30%) of the 57 patients, respectively. The 3-year overall survival rate was 63.4%. SUV{sub max} did not affect any recurrence, DFS, OS, or CSS. RI significantly predicted higher distant metastasis (HR 47.546, p = 0.026). In contrast, RI tended to predict lower local recurrence (HR 0.175, p = 0.246) and regional lymph node metastasis (HR 0.109, p = 0.115). Conclusions: SUV{sub max} at staging FDG-PET does not predict any recurrence, DFS, OS or CSS. In contrast, higher RI predicts higher distant metastasis and tended to predict lower local or regional lymph node metastasis.

  8. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.

    Science.gov (United States)

    Thatcher, Nick; Hirsch, Fred R; Luft, Alexander V; Szczesna, Aleksandra; Ciuleanu, Tudor E; Dediu, Mircea; Ramlau, Rodryg; Galiulin, Rinat K; Bálint, Beatrix; Losonczy, György; Kazarnowicz, Andrzej; Park, Keunchil; Schumann, Christian; Reck, Martin; Depenbrock, Henrik; Nanda, Shivani; Kruljac-Letunic, Anamarija; Kurek, Raffael; Paz-Ares, Luis; Socinski, Mark A

    2015-07-01

    Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m(2) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2) administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash--a class effect of EGFR antibodies--that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients

  9. A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Vinzenz Kroeber

    2014-07-01

    Full Text Available Introduction: Two standard single-agent chemotherapy treatments (docetaxel and pemetrexed were combined in this trial and administered as second-line treatment in patients with non-small cell lung cancer (NSCLC. The aim of this study was to evaluate the safety and feasibility of combining docetaxel with pemetrexed. Methods: Six patients were enrolled between August 2007 and March 2009 with stage IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1 of 200-300 mg/m2 followed by infusion of docetaxel on days 1, 8 and 15 at doses from 20 to 30 mg/m2. Primary study endpoints included efficacy and safety variables, also progression-free, overall and 1-year survival and time to progression. Results: The study was abandoned due to adverse effects defined in the protocol. The major toxicities were all of grade 3 and included fatigue, stomatitis/mucositis, diarrhea and in one case, an episode of febrile neutropenia. Two patients died during the study, but not as a direct result of the treatment. Conclusions: We recommend that docetaxel or pemetrexed monotherapies should continue to be considered the standard second-line chemotherapy treatment against NSCLC. The results of this study warrant no further investigation into this particular combination treatment due to the severe toxicity effects encountered.

  10. A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Kroeber, Vinzenz; Nagel, Sylke; Schuette, Wolfgang; Blankenburg, Thomas

    2014-05-01

    Two standard single-agent chemotherapy treatments (docetaxel and pemetrexed) were combined in this trial and administered as second-line treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and feasibility of combining docetaxel with pemetrexed. Six patients were enrolled between August 2007 and March 2009 with stage IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1 of 200-300 mg/m(2) followed by infusion of docetaxel on days 1, 8 and 15 at doses from 20 to 30 mg/m(2). Primary study endpoints included efficacy and safety variables, also progression-free, overall and 1-year survival and time to progression. The study was abandoned due to adverse effects defined in the protocol. The major toxicities were all of grade 3 and included fatigue, stomatitis/mucositis, diarrhea and in one case, an episode of febrile neutropenia. Two patients died during the study, but not as a direct result of the treatment. We recommend that docetaxel or pemetrexed monotherapies should continue to be considered the standard second-line chemotherapy treatment against NSCLC. The results of this study warrant no further investigation into this particular combination treatment due to the severe toxicity effects encountered.

  11. The diagnostic ability of {sup 18}F-FDG PET/CT for mediastinal lymph node staging using {sup 18}F-FDG uptake and volumetric CT histogram analysis in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Won [Catholic Kwandong University College of Medicine, Department of Nuclear Medicine, International St. Mary' s Hospital, Incheon (Korea, Republic of); Kim, Eun Young [Yonsei University College of Medicine, Division of Pulmonology, Department of Internal Medicine, Seoul (Korea, Republic of); Kim, Dae Joon [Yonsei University College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of); Lee, Jae-Hoon [Yonsei University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Yonsei University College of Medicine, Department of Nuclear Medicine, Gangnam Severance Hospital, Seoul (Korea, Republic of); Kang, Won Jun; Yun, Mijin [Yonsei University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Lee, Jong Doo [Catholic Kwandong University College of Medicine, Department of Radiology, International St. Mary' s Hospital, Incheon (Korea, Republic of)

    2016-12-15

    To evaluate the clinical implications of lymph node (LN) density on {sup 18}F-FDG PET/CT for mediastinal LN characterization in non-small cell lung cancer (NSCLC). One hundred and fifty-two patients with 271 mediastinal LNs who underwent PET/CT and endobronchial ultrasound-guided transbronchial needle aspiration for staging were enrolled. Maximum standardized uptake value (SUVmax), short axis diameter, LN-to-primary cancer ratio of SUVmax, and median Hounsfield unit (HU) based on CT histogram were correlated to histopathology. Of 271 nodes, 162 (59.8 %) were malignant. SUVmax, short axis diameter, and LPR of malignant LNs were higher than those of benign nodes. Among malignant LNs, 71.0 % had median HU between 25 and 45, while 78.9 % of benign LNs had values <25 HU or >45 HU. Using a cutoff value of 4.0, SUVmax showed the highest diagnostic ability for detecting malignant LNs with a specificity of 94.5 %, but showing a sensitivity of 70.4 %. Using additional density criteria (median HU 25-45) in LNs with 2.0< SUVmax ≤4.0, the sensitivity increased to 88.3 % with the specificity of 82.6 %. LN density is useful for the characterization of LNs with mild {sup 18}F-FDG uptake. The risk of mediastinal LN metastasis in NSCLC patients could be further stratified using both {sup 18}F-FDG uptake and LN density. (orig.)

  12. Radiographic patterns and survival of patients with early and late brain metastases in EGFR wild type and mutant non small cell lung cancer

    DEFF Research Database (Denmark)

    Yuan, Ren; Yamada, Andrew; Weber, Britta

    2016-01-01

    Brain metastasis (BM) in NSCLC is a negative prognostic indicator. In the era of EGFR mutations we evaluated the difference between early (≤6 months from diagnosis) versus late BM (>6 months), in EGFR wild type (WT) and mutant (MT) NSCLC patients with respect to radiographic patterns and overall...... BM, EGFR MT have an OS comparable to late BM. In contrast, early BM EGFR WT have a significantly reduced survival compared to late BM. The positive outcome in EGFR MT may be secondary to systemic control and EGFR TKI penetrance across the blood brain barrier....

  13. Patterns of Local-Regional Failure in Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer Cases: Implications for Postoperative Radiation Therapy Clinical Target Volume Design

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Wen [Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai (China); Fu, Xiao-Long, E-mail: xlfu1964@hotmail.com [Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai (China); Cai, Xu-Wei; Yang, Huan-Jun; Wu, Kai-Liang; Fan, Min [Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai (China); Xiang, Jia-Qing; Zhang, Ya-Wei; Chen, Hai-Quan [Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai (China)

    2014-04-01

    Purpose: To analyze patterns of local-regional failure (LRF) for completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) patients treated in our hospital and to propose a clinical target volume (CTV) for postoperative radiation therapy (PORT) in these patients. Methods and Materials: From 2005 to 2011, consecutive patients with pT1-3N2 NSCLC who underwent complete resection in our hospital but who did not receive PORT were identified. The patterns of first LRF were assessed and evaluated as to whether these areas would be encompassed by our proposed PORT CTV. Results: With a median follow-up of 24 months, 173 of 250 patients (69.2%) experienced disease recurrence. Of the 54 patients with LRF as the first event, 48 (89%) had recurrence within the proposed PORT CTV, and 6 (11%) had failures occurring both within and outside the proposed CTV (all of which occurred in patients with right-lung cancer). Ninety-three percent of failure sites (104 of 112) would have been contained within the proposed PORT CTV. For left-sided lung cancer, the most common lymph node station failure site was 4R, followed by 7, 4L, 6, 10L, and 5. For right-sided lung cancer, the most common site was station 2R, followed by 10R, 4R, and 7. Conclusions: LRF following complete surgery was an important and potentially preventable pattern of failure in stage IIIA(N2) patients. Ipsilateral superior mediastinal recurrences dominated for right-sided tumors, whereas left-sided tumors frequently involved the bilateral superior mediastinum. Most of the LRF sites would have been covered by the proposed PORT CTV. A prospective investigation of patterns of failure after PORT (following our proposed CTV delineation guideline) is presently underway and will be reported in a separate analysis.

  14. Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sekine, Ikuo, E-mail: isekine@ncc.go.jp [Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Sumi, Minako; Ito, Yoshinori [Division of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Horinouchi, Hidehito; Nokihara, Hiroshi; Yamamoto, Noboru; Kunitoh, Hideo; Ohe, Yuichiro; Kubota, Kaoru; Tamura, Tomohide [Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2012-02-01

    Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.

  15. Radiotherapy versus combined modality in early stages

    DEFF Research Database (Denmark)

    Specht, L; Carde, P; Mauch, P;

    1992-01-01

    In early stage Hodgkin's disease the optimal choice of treatment for the individual patient is still an unresolved issue. So far, twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out worldwide. The preliminary results of a global...... be kept at a minimum. Recently, trials have been carried out testing chemotherapy alone. The results of these trials are however conflicting. In order not to jeopardize the good results achieved with the standard treatments developed over the last three decades, newer treatment approaches should...... be carefully tested in large randomized trials before being implemented for general clinical use....

  16. Early Stage of Pulsed Discharge in Water

    Institute of Scientific and Technical Information of China (English)

    卢新培; 潘垣; 刘克富; 刘明海; 张寒虹

    2001-01-01

    The bubble radius at the early stage of discharge in water is investigated using high-speed photography. Some simulation results on the bubble radius are presented, which are in agreement with the experimental results, with a maximum difference of about 10%. The reasons why the peak pressure of the first shock wave is only related to the energy released in the bubble during the first half period are addressed. The energy released in the bubble after the first half period increases the bubble pulsation period, but it produces no more than 10% under the peak pressure of the second shock wave.

  17. Dupuytren contracture. Radiotherapy of early stages

    Energy Technology Data Exchange (ETDEWEB)

    Herbst, M.; Regler, G.

    1985-03-01

    Conventional radiotherapy is the treatment of choice for the early stages of theDupuytren contracture. The conventional semi-deep therapy is more favorable than the soft ray technique and the moulage technique. 62 patients have been treated at Erlangen; 33 out of them (46 irradiated hands) with a minimum observation time of 18 months have been evaluated. The pathologic process was stopped in 98% of the cases. 85% of the patients showed an improvement of troubles by regression of tubercules and cords, pains and sensation of pressure. A recurrence was obseved only in one patient at the edge of the irradiated volume.

  18. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin;

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.......This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  19. Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE).

    Science.gov (United States)

    Reck, Martin; Thomas, Michael; Kropf-Sanchen, Cornelia; Mezger, Jörg; Socinski, Mark A; Depenbrock, Henrik; Soldatenkova, Victoria; Brown, Jacqueline; Krause, Thomas; Thatcher, Nick

    2016-01-01

    In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors. Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone. GC + N patients with no progression continued on necitumumab monotherapy until disease progression or intolerable toxicity. The primary endpoint was OS; the secondary endpoints included progression-free survival (PFS), safety and health-related quality of life (EQ-5D, Lung Cancer Symptom Scale (LCSS)). The 96 German SQUIRE patients with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles; the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically associated with EGFR antibody treatment (including rash, hypomagnesemia) were more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores showed no notable differences between the treatment arms, except for appetite loss (delayed for GC + N). The survival benefit from adding necitumumab to first-line GC was more pronounced in the German SQUIRE subpopulation with EGFR-expressing tumors than in the overall (intention-to-treat) population; toxicity was manageable and consistent with the overall population. © 2016 S. Karger GmbH, Freiburg.

  20. Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial.

    Science.gov (United States)

    Douillard, Jean-Yves; Rosell, Rafael; De Lena, Mario; Riggi, Marcello; Hurteloup, Patrick; Mahe, Marc-Andre

    2008-11-01

    To study the impact of postoperative radiation therapy (PORT) on survival in the Adjuvant Navelbine International Trialist Association (ANITA) randomized study of adjuvant chemotherapy. ANITA is a randomized trial of adjuvant cisplatin and vinorelbine chemotherapy vs. observation in completely resected non-small-cell lung carcinoma (NSCLC) Stages IB to IIIA. Use of PORT was recommended for pN+ disease but was not randomized or mandatory. Each center decided whether to use PORT before initiation of the study. We describe here the survival of patients with and without PORT within each treatment group of ANITA. No statistical comparison of survival was performed because this was an unplanned subgroup analysis. Overall, 232 of 840 patients received PORT (33.3% in the observation arm and 21.6% in the chemotherapy arm). In univariate analysis, PORT had a deleterious effect on the overall population survival. Patients with pN1 disease had an improved survival from PORT in the observation arm (median survival [MS] 25.9 vs. 50.2 months), whereas PORT had a detrimental effect in the chemotherapy group (MS 93.6 months and 46.6 months). In contrast, survival was improved in patients with pN2 disease who received PORT, both in the chemotherapy (MS 23.8 vs. 47.4 months) and observation arm (median 12.7 vs. 22.7 months). This retrospective evaluation suggests a positive effect of PORT in pN2 disease and a negative effect on pN1 disease when patients received adjuvant chemotherapy. The results support further evaluation of PORT in prospectively randomized studies in completely resected pN2 NSCLC.

  1. Increasing the accuracy of {sup 18}F-FDG PET/CT interpretation of “mildly positive” mediastinal nodes in the staging of non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Moloney, F., E-mail: fiachramoloney@hotmail.com [Department of Radiology, Cork University Hospital, Cork - 00353214922000 (Ireland); Ryan, D., E-mail: ryansurgeon@gmail.com [Department of Radiology, Cork University Hospital, Cork - 00353214922000 (Ireland); McCarthy, L., E-mail: lauraghmccarthy1@hotmail.com [Department of Radiology, Cork University Hospital, Cork - 00353214922000 (Ireland); McCarthy, J., E-mail: julie.mccarthy@hse.ie [Department of Pathology, Cork University Hospital, Cork - 0214922000 (Ireland); Burke, L., E-mail: louise.burke@hse.ie [Department of Pathology, Cork University Hospital, Cork - 0214922000 (Ireland); Henry, M.T., E-mail: michael.henry@hse.ie [Department of Respiratory Medicine, Cork University Hospital, Cork - 00353214922000 (Ireland); Kennedy, M.P., E-mail: marcus.kennedy@hse.ie [Department of Respiratory Medicine, Cork University Hospital, Cork - 00353214922000 (Ireland); Hinchion, J., E-mail: John.Hinchion@hse.ie [Department of Cardiothoracic Surgery, Cork University Hospital, Cork - 00353214922000 (Ireland); McSweeney, S., E-mail: Sean.McSweeny@hse.ie [Department of Radiology, Cork University Hospital, Cork - 00353214922000 (Ireland); Maher, M.M., E-mail: m.maher@ucc.ie [Department of Radiology, Cork University Hospital, Cork - 00353214922000 (Ireland); O’Regan, K., E-mail: kevin.ORegan1@hse.ie [Department of Radiology, Cork University Hospital, Cork - 00353214922000 (Ireland)

    2014-05-15

    Introduction: The aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC). Methods: This was a retrospective, interdisciplinary, per-node analysis study. We included patients with NSCLC and mediastinal nodes with an SUV max in the range of 2.5–4.0 on PET-CT. We hypothesized that the greatest number of false positive cases would occur in this cohort of patients. Results: A total of 92 mediastinal lymph nodes were analyzed in 44 patients. Mediastinal disease (N2/N3) was histologically confirmed in 15 of 44 patients and in 34 of 92 lymph nodes; positive predictive value of 37% and false positive rate of 63%. Lymph node SUV max, tumor size, ratio of node SUV max to tumor SUV max (SUVn/SUVp), and ratio of node SUV max to node size (SUV n/SADn) were significantly higher in true positive cases. Using a threshold of 0.3 for SUV node/tumor and 3 for SUV node/size yielded sensitivities of 91% and 71% and specificities of 71% and 69% respectively for the detection of mediastinal disease. Using both ratios in combination resulted in a sensitivity of 65% and a specificity of 88%. Concurrent benign lung disease was observed significantly more frequently in false-positive cases. Conclusion: SUVn/SUVpt and SUVn/SADn may be complimentary to conventional visual interpretation and SUV max measurement in the assessment of mediastinal disease in patients with NSCLC.

  2. 厄洛替尼治疗终末期非小细胞肺癌的疗效观察%Efficacy of erlotinib in treatment of end-stage non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    曾越灿; 蔡炜嵩; 吴荣; 迟峰; 邢锐; 肖玉平; 辛彦; 王乃乾

    2014-01-01

    Objective To investigate the effect of erlotinib in treatment of end -stage (PS score ≥ 3 points) non-small cell lung cancer.Methods 47 cases of end-stage non-small cell lung cancer patients were randomly divided into two groups, treatment group of 25 patients who received erlotinib treatment , the control group with 22 cases are not accepted erlo-tinib therapy and other chemotherapy , only accept nutritional support , control pain, relieve symptoms treatment.The clinical efficacy of the two groups, adverse reactions, survival and prognostic factors were observed .Results The disease control rate was 72.0% (18 /25) in treatment group which is higher than 27.3% (6 /22) in the control group, the difference was statisti-cally significant ( P <0.01); in treatment group, the incidence of rash reaction was 84.0% (21 /25) , the incidence of di-arrhea was 40.0% (10 /25), anorexia incidence was 12.0% (3 /25), the control group had no adverse reactions .The medi-an survival in the treatment group was 92 d, control group was 61 d ( P <0.01).Cox analysis showed that gender , age, number of previous chemotherapy and type of chemotherapy had little effect on the efficacy , and pathological type, EGFR mu-tation status and smoking history is curative factors ( P <0.05).Conclusion Erlotinib prolongs survival of end-stage non-small cell lung cancer patients and improve disease control rate .%目的:探讨厄洛替尼治疗终末期(PS 评分≥3分)非小细胞肺癌的疗效。方法终末期非小细胞肺癌患者47例,随机分为2组,治疗组25例接受厄洛替尼治疗,对照组22例不接受厄洛替尼治疗和其他放化疗,只接受营养支持、控制疼痛、缓解症状等治疗。观察2组的临床疗效、不良反应、生存期及预后影响因素。结果治疗组疾病控制率为72.0%(18/25),高于对照组的27.3%(6/22),差异有统计学意义( P ﹤0.01);治疗组不良反应皮疹发生率84.0%(21/25

  3. Ratio of mediastinal lymph node SUV to primary tumor SUV in {sup 18}F-FDG PET/CT for nodal staging in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Hyuk; Choe, Jae Gol; Pahk, Kisoo; Choi, Sun Ju; Kwon, Hye Ryeong; Kim, Sun Geun [Dept. of Nuclear Medicine, Korea University Anam Hospital, Seoul (Korea, Republic of); Eo, Jae Seon; Seo, Hyo Jung [Dept. of Nuclear Medicine, Korea University Guro Hospital, Seoul (Korea, Republic of); Kim, Chul Han [Dept. of Nuclear Medicine, Korea University Ansan Hospital, Ansan (Korea, Republic of)

    2017-06-15

    Following determination of the maximum standardized uptake values (SUVmax) of the mediastinal lymph nodes (SUV-LN) and of the primary tumor (SUV-T) on 18F-FDG PET/CT in patients with non-small-cell lung cancer (NSCLC), the aim of the study was to determine the value of the SUV-LN/SUV-T ratio in lymph node staging in comparison with that of SUV-LN. We retrospectively reviewed a total of 289 mediastinal lymph node stations from 98 patients with NSCLC who were examined preoperatively for staging and subsequently underwent pathologic studies of the mediastinal lymph nodes. We determined SUV-LN and SUV-R for each lymph node station on 18F-FDG PET/CT and then classified each station into one of three groups based on SUV-T (low, medium and high SUV-T groups). Diagnostic performance was assessed based on receiver operating characteristic (ROC) curve analysis, and the optimal cut-off values that would best discriminate metastatic from benign lymph nodes were determined for each method. The average of SUV-R of malignant lymph nodes was significantly higher than that of benign lymph nodes (0.79 ± 0.45 vs. 0.36 ± 0.23, P < 0.0001). In the ROC curve analysis, the area under the curve (AUC) of SUV-R was significantly higher than that of SUV-LN in the low SUV-T group (0.885 vs. 0.810, P = 0.019). There were no significant differences between the AUCs of SUV-LN and of SUV-R in the medium and high SUV-T groups. The optimal cut-off value for SUV-R in the low SUV-T group was 0.71 (sensitivity 87.5 %, specificity 85.9 %). The SUV-R performed well in distinguishing between metastatic and benign lymph nodes. In particular, SUV-R was found to have a better diagnostic performance than SUV-LN in the low SUV-T group.

  4. Urinary biomarkers at early ADPKD disease stage.

    Directory of Open Access Journals (Sweden)

    Katja Petzold

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course.ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL, Kidney Injury Molecule-1 (KIM-1, and Uromodulin (UMOD were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16 was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results.In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2 the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found.UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable

  5. Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer

    Science.gov (United States)

    2016-08-25

    Extensive Stage Small Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  6. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  7. 放化疗联合治疗对Ⅳ期非小细胞肺癌的疗效对比研究%Efficacy of chemoradiotherapy in the treatment of stage non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    鹿凯; 尤庆山

    2013-01-01

    目的:探讨三维适形放射治疗(3-dementional conformal radiation therapy,3D-CRT)在Ⅳ期非小细胞肺癌中的临床应用,为晚期非小细胞肺癌患者,特别是老年、伴有内科疾病及一般状况差的病人提供安全、有效的治疗方法.方法:回顾性分析我院2007年12月-2010年12月258例初诊经组织学或细胞学证实的Ⅳ期非小细胞肺癌患者.根据治疗方式不同分三组:单纯放疗组、单纯化疗组、放化联合组进行对照.结果:单纯放疗组、单纯化疗组、放化联合组中位生存时间分别为9个月、11个月和13个月;0.5年生存率为75.8%、71.8%和85.1%;1年生存率为29.8%、40.5%和56.4%;2年生存率为9.1%、12.3%和14.5%;近期有效率分别为57.6%、42.0%、64.9%;进展率分别为48.5%、49.6%、40.4%;中位无进展时间分别为6个月、7个月、9个月.放疗与化疗结合并未增加化疗的毒副反应(P>0.05).结论:3D-CRT联合化疗应用于Ⅳ期非小细胞肺癌,较单纯化疗和单纯放疗提高了中位生存期和0.5年、1年、2年生存率,而并未增加毒副反应;对老龄、合并内科疾病、一般状况差的病人单纯精确放疗也取得了比较理想的效果.%Objective:To evaluate the clinical effect of patients with stagenon-small cell lung cancer (NSCLC)treated with three dimensional conformal radiation therapy(3D-CRT).Methods:From 2004 to 2007,258 patients with stage Ⅳ NSCLC confirmed pathologically treated with radiotherapy,chemotherapy and chemoradiotherapy were restrospectively analyed.Results:The median survival time was 9 months in group 1,11 months in group 2 and 13 months in group 3.The half-year,1 and 2 year survival rates were 75.8%,29.8% and 9.1% in group 1,71.8%,40.5% and 12.3% in group 2 and 85.1%,56.4% and 14.5% in group 3.The complete and partial response rate was 57.6% in group 1,42.0% in group 2 and 64.9% in group 3.The progression rate was 48.5

  8. Early and late recurrence after intentional limited resection for cT1aN0M0, non-small cell lung cancer: from a multi-institutional, retrospective analysis in Japan.

    Science.gov (United States)

    Matsumura, Yuki; Yano, Motoki; Yoshida, Junji; Koike, Terumoto; Kameyama, Kotaro; Shimamoto, Akira; Nishio, Wataru; Yoshimoto, Kentaro; Utsumi, Tomoki; Shiina, Takayuki; Watanabe, Atsushi; Yamato, Yasushi; Watanabe, Takehiro; Takahashi, Yusuke; Sonobe, Makoto; Kuroda, Hiroaki; Oda, Makoto; Inoue, Masayoshi; Tanahashi, Masayuki; Adachi, Hirofumi; Saito, Masao; Hayashi, Masataro; Otsuka, Hajime; Mizobuchi, Teruaki; Moriya, Yasumitsu; Takahashi, Mamoru; Nishikawa, Shigeto; Suzuki, Hiroyuki

    2016-09-01

    In 2015, we reported the outcomes of patients undergoing intentional limited resection (ILR) for non-small-cell lung cancer (NSCLC) from a retrospective, multi-institutional large database in Japan. Here, we analyse the clinicopathological characteristics of the patients extracted from this database with late recurrence and compare them with those with early recurrence. Of 1538 patients in the database with cT1aN0M0 NSCLC, 92 (6%) had recurrence. In this study, early recurrence was defined as recurrence within 5 years and late recurrence as recurrence beyond 5 years after surgery. We compared the clinicopathological characteristics and post-recurrence survival (PRS) between patients with early and late recurrence. Of the 92 patients with recurrence, 21 (23%) had late recurrence. Compared with the early recurrence group, there were significantly more adenocarcinomas and local recurrences in the late recurrence group (P = 0.04 for both). The 3- and 5-year PRS rates were 53 and 24%, respectively, and the median PRS period was 38 months. There were no significant differences in the PRS curves between patients with early and late recurrence (P = 0.12). Only 3 patients (0.2%) had recurrence more than 10 years after ILR. Of the 21 late-recurrence patients, 17 (81%) had tumours with a consolidation/tumour ratio (CTR) >0.25. Late recurrence occurred in 21 (23%) of 92 patients with recurrence after ILR for cT1aN0M0 NSCLC. Late recurrence was more likely to involve adenocarcinoma and local recurrence. It is thus considered reasonable to follow patients with a CTR >0.25 for 10 years after ILR. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  9. Prognostic analysis of curative surgery for stage ⅢA-N2 non-small cell lung cancer%ⅢA-N2期非小细胞肺癌外科治疗的预后分析

    Institute of Scientific and Technical Information of China (English)

    刘敬伟; 李简; 林刚; 商学谦

    2013-01-01

    Objective To investigate the survival and prognostic factors in patients undergoing potentially curative resection of stage ⅢA-N2 non-small cell lung cancer.Methods Clinical data of eightynine patients,who underwent curative operation from January 2003 to April 2007 in the Peking University First Hospital and were pathologically diagnosed as stage Ⅲ A-N2 NSCLC,were reviewed.The patients were followed up until death or the cut-off date.The overall 3-year and 5-year survival rates were calculated,and Cox proportional hazard model was used to determine the clinical and pathological risk factors and evaluate their influence on the survival.Results The three-year and five-year survival rates were 51.7% and 31.5%,respectively.The univariate Cox regression analysis revealed five significant factors associated with prognosis:the arm of age < 55,T3 stage,lymphovascular invasion (LVI),multiple positive N2 station and the number of positive N2 nodes > 3 were found to be at increased risk of tumor-related death,and those risk factors were confirmed especially in the age ≥55 group.Multivariate Cox regression analysis indicated three independent prognostic factors:T3 stage,LVI and multiple positive N2 station.Conclusions The results of this preliminary study show that T3 stage,lymphovascular invasion and N2 level (single or multiple station) are associated with the prognosis of stage Ⅲ A-N2 NSCLC patients after potentially curative resection,and the characteristics of age < 55 and the number of positive N2 nodes > 3 may imply worse prognosis.%目的 探讨ⅢA-N2期非小细胞肺癌(NSCLC)患者经外科治疗的预后及其影响因素.方法 收集北京大学第一医院胸外科2003年1月至2007年4月期间行肺癌根治术、术后病理证实为ⅢA-N2期NSCLC的89例患者的临床资料,随访术后生存状况,计算术后3年和5年生存率.采用Cox模型对预后影响因素进行单因素和多因素分析.结果 89例ⅢA-N2期NSCLC患者,

  10. Distribution of T helper 17 and regulatory T cells in the different TNM stages of non-small cell lung cancer and the relationship between the level of T helper 17 and regulatory T cells and the progress of non-small cell lung cancer%辅助性T细胞17和调节性T细胞在非小细胞型肺癌中的分布及其与肿瘤进展的关系

    Institute of Scientific and Technical Information of China (English)

    秦伟; 王志斌

    2016-01-01

    Objective To investigate the percentage of T helper 17(Th17)and regulatory T cells(Treg)in the different TNM stages of non-small cell lung cancer(NSCLC),and to research the relationship between the level of Th17 and Treg cells and the development of NSCLC.Methods Th17 and Treg cells in blood samples from 95 patients with NSCLC and 20 normal controls were evaluated with flow cytometry(FCM).Statistical analysis was performed using the software SPSS 17.0.Results Th17 and Treg cells in 95 patients with NSCLC were increased as compared with control group[(4.496±0.181)%,(3.187±0.053)%,P<0.01;(8.001±0.240)%,(4.607±0.040)%,P<0.01;1.781±0.051,1.446±0.031,P<0.01].Thl7 and Treg cells displayed a positive linear correlation(r=0.621,P<0.01).The percentage of Th17 and Treg cells had a positive correlation with the TNM stage[(4.138±0.065)%,(4.504±0.162)%,(4.575±0.022)%,(4.625±0.018)%,F=41.896,P<0.01;(7.625±0.031)%,(7.892±0.050)%,(8.161±0.063)%,(8.423±0.032)%,F=704.212,P<0.01].The percentage of Th17 and Treg cells in NSCLC with advanced stage was significantly higher than that in early stage(LSD,P<0.01;Bonferroni,P<0.01).Conclusion The percentage of Th 17 and Treg cells was in a positive linear correlation,and had a positive correlation with the TNM stage.%目的 观察辅助性T细胞17(Th17)和调节性T细胞(Treg)在不同分期非小细胞型肺癌(NSCLC)患者中的表达,探讨Th17细胞和Treg细胞与非小细胞肺癌进展的关系.方法 采用流式细胞仪分析的方法分别测定95例NSCLC患者及20例健康对照组外周血中Th17细胞和Treg细胞的比例分布,应用SPSS 17.0统计学软件分析.结果95例NSCLC患者外周血标本中Th17、Treg数量及Treg/Th17明显高于正常对照组[(4.496±0.181)%,(3.187土0.053)%,P<0.01;(8.001±0.240)%,(4.607土0.040)%,P<0.01;1.781±0.051,1.446±0.031,P<0.01],其差异有统计学意义;Th17细胞与Treg细胞呈正向直线关系(r=0.621,P<0

  11. Preoperative PET/CT in early-stage breast cancer

    DEFF Research Database (Denmark)

    Bernsdorf, M; Berthelsen, A K; Wielenga, V T;

    2012-01-01

    The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer.......The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer....

  12. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Hong

    2015-05-01

    Interpretation: Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC.

  13. Very early stages of massive stars

    Science.gov (United States)

    Vasyunina, Tatiana

    2010-12-01

    The goal of this thesis work is to investigate the initial conditions and the early phases of the formation of high-mass stars by means of dedicated observational studies. We consider two object classes: infrared dark clouds (IRDCs), and a subsequent stage characterized by the presence of young embedded (proto-)stellar clusters. First, we estimate masses and column densities for a completely new sample of southern IRDCs, utilizing our own millimeter continuum emission maps as well as Spitzer satellite data. The parameters we derive show that IRDCs from our sample have the potential to form not only low- and intermediate-mass stars, but can also be the birth places of massive stars. In particular, the comparison of our results with previously obtained data for low-mass starless cores shows a clear trend for IRDCs to have systematically higher column densities. The interpolated IRDC peak column densities exceed the threshold for the onset of massive star formation previously advocated by theoretical studies. We also critically evaluate the limitations of the applied emission and extinction methods. Second, we investigate the physical conditions and the chemical composition of the dense gas within the IRDCs of our sample by means of a multi-line molecular spectroscopy analysis. All the clouds have complex HCO+ line pro les, and we detect SiO emission in some clouds. These ndings mark the presence of infall and out ow motions in at least some parts of the IRDCs, and hence, ongoing star formation. In comparison with low-mass starless cores, the IRDCs have broader and more intense lines. Thus, they may be characterised by more turbulent conditions. Nevertheless, we nd a tendency for the IRDCs to have molecular abundances similar to the case of low-mass starless cores. This indicates similar chemical initial conditions for low- and high-mass star-forming regions. Finally, we study the stellar composition and environmental conditions in the young embedded cluster IRAS

  14. Non-small cell lung cancer in never smokers: a clinical entity to be identified

    Directory of Open Access Journals (Sweden)

    Ilka Lopes Santoro

    2011-01-01

    Full Text Available OBJECTIVES: It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among neversmokers with non-small cell lung cancer. METHODS: All consecutive non-small cell lung cancer patients diagnosed (n = 285 between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable, gender (female vs. male, smoking status (never- vs. ever-smoker, the Karnofsky Performance Status Scale (continuous variable, histological type (adenocarcinoma vs. non-adenocarcinoma, AJCC staging (early vs. advanced staging, and treatment (chemotherapy and/or radiotherapy vs. the best treatment support. RESULTS: Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32% and have adenocarcinoma (70% vs. 51%. Overall median survival was 15.7 months (95% CI: 13.2 to 18.2. The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. CONCLUSIONS: Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

  15. 非小细胞肺癌纵隔淋巴结分期:孰优,孰劣?--一项比较PET与CT诊断价值的Meta分析%Which Is Better for Mediastinal Staging in Patients with Non-small-cell Lung Cancer:PET or CT?

    Institute of Scientific and Technical Information of China (English)

    陈盛祖; 耿建华; 廖日强

    2005-01-01

    @@ 1文献类型 诊断 2证据水平 1a 3文献来源 Gould MK, Kuschner WG, Rydzak CE, et al.Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis [J ]. Ann Intern Med, 2003,139: 879-892.

  16. Pancreatic Perfusion CT in Early Stage of Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Yoshihisa Tsuji

    2012-01-01

    Full Text Available Early intensive care for severe acute pancreatitis is essential for improving SAP mortality rates. However, intensive therapies for SAP are often delayed because there is no ideal way to accurately evaluate severity in the early stages. Currently, perfusion CT has been shown useful to predict prognosis of SAP in the early stage. In this presented paper, we would like to review the clinical usefulness and limitations of perfusion CT for evaluation of local and systemic complications in early stage of SAP.

  17. GILT - A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Flentje, Michael [University Hospital Wuerzburg, Dept. of Radiotherapy, Wuerzburg (Germany); Huber, Rudolf M. [University Hospital Munich, Member of the German Center for Lung Research (DZL CPC-M), Munich (Germany); Engel-Riedel, Walburga [University Hospital Merheim, Dept. of Pneumonology, Cologne (Germany); Andreas, Stefan [Dept. of Pneumonology, Immenhausen (Germany); Kollmeier, Jens [Helios Emil-von-Behring Hospital, Berlin (Germany); Staar, Susanne [Municipal Hospital Bremen-Mitte, Bremen (Germany); Dickgreber, Nicolas [University Hospital Hannover, Hannover (Germany); Vaissiere, Nathalie; Almeida, Cecilia de [Institut de Recherche Pierre Fabre, Boulogne (France); Edlich, Birgit [Pierre Fabre Pharma GmbH, Freiburg (Germany); Fietkau, Rainer [University Hospital Erlangen, Erlangen (Germany)

    2016-04-15

    Concurrent chemoradiotherapy (CRT) is considered standard for inoperable stage III non-small cell lung cancer (NSCLC). Consolidation chemotherapy (CC) following CRT is intended to further improve outcomes, yet studies have shown discordant results. This phase III study assessed CRT followed by best supportive care (BSC) or consolidation with oral vinorelbine and cisplatin. Patients received two cycles of oral vinorelbine (50 mg/m{sup 2} days 1, 8 and 15) + cisplatin (20 mg/m{sup 2} days 1-4) q4w + radiotherapy (RT; 66 Gy). Patients with at least stable disease (SD) were randomised to either two cycles oral vinorelbine (60-80 mg/m{sup 2} days 1 and 8) + cisplatin (80 mg/m{sup 2} day 1) q3w + BSC or BSC alone. Primary endpoint was progression-free survival (PFS). A total of 279 patients were enrolled for CRT and 201 patients were randomised to CC or BSC. Both CRT and CC were well tolerated, with limited radiation-mediated grade 3/4 toxicities (CRT/CC/BSC: oesophagitis-related events 12.9 %/3.1 %/0 %; grade 3 pneumonitis 0 %/0 %/2 %) and chemotherapy-mediated grade 3/4 toxicities (CRT/CC: neutropenia 11.2 %/22.1 %; leukopenia 18.3 %/26.7 %; grade 3 nausea 5.0 %/2.3 %, grade 3 vomiting 3.2 %/3.5 %). Median PFS from randomisation was 6.4 (5.0-8.7) and 5.5 (3.8-7.4) months in the CC and BSC arms (hazard ratio, HR = 0.93 [0.69-1.26]; p = 0.63), respectively; median overall survival (OS) 20.8 (13.5-25.3) and 18.5 (13.6-24.7) months, respectively. Consolidation chemotherapy after concurrent CRT did not prolong PFS or OS. Concurrent RT with oral vinorelbine and cisplatin demonstrated a favourable safety profile and represents a suitable treatment regimen for inoperable stage III NSCLC. (orig.) [German] Simultane Radiochemotherapie (CRT) wird als Standardtherapie beim inoperablen Stadium III des nicht-kleinzelligen Lungenkarzinoms (NSCLC) angesehen. Konsolidierende Chemotherapie (CC) nach der CRT zielt darauf ab, das Therapieergebnis zu verbessern, allerdings zeigen Studien

  18. 18 F-FDG PET-CT during chemo-radiotherapy in patients with non-small cell lung cancer: the early metabolic response correlates with the delivered radiation dose

    Directory of Open Access Journals (Sweden)

    Massaccesi Mariangela

    2012-07-01

    Full Text Available Abstract Background To evaluate the metabolic changes on 18 F-fluoro-2-deoxyglucose positron emission tomography integrated with computed tomography (18 F-FDG PET-CT performed before, during and after concurrent chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC; to correlate the metabolic response with the delivered radiation dose and with the clinical outcome. Methods Twenty-five NSCLC patients candidates for concurrent chemo-radiotherapy underwent 18 F-FDG PET-CT before treatment (pre-RT PET-CT, during the third week (during-RT PET-CT of chemo-radiotherapy, and 4 weeks from the end of chemo-radiotherapy (post-RT PET-CT. The parameters evaluated were: the maximum standardized uptake value (SUVmax of the primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume (MTV. Results SUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively decreased earlier during the third week of chemo-radiotherapy, with a further reduction 4 weeks from the end of treatment (p Conclusions In patients with locally advanced NSCLC, 18 F-FDG PET-CT performed during and after treatment allows early metabolic modifications to be detected, and for this SUVmax is the more sensitive parameter. Further studies are needed to investigate the correlation between the metabolic modifications during therapy and the clinical outcome in order to optimize the therapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates with the cumulative dose of fractionated radiotherapy delivered at the moment of the scan, special attention should be paid to methodological aspects, such as the radiation dose reached at the time of PET.

  19. Primary Treatment Options for High-Risk/Medically Inoperable Early Stage NSCLC Patients.

    Science.gov (United States)

    Jones, Guy C; Kehrer, Jason D; Kahn, Jenna; Koneru, Bobby N; Narayan, Ram; Thomas, Tarita O; Camphausen, Kevin; Mehta, Minesh P; Kaushal, Aradhana

    2015-11-01

    Lung cancer is among the most common cancers worldwide and is the leading cause of cancer death in both men and women. For patients with early stage (American Joint Committee on Cancer T1-2, N0) non-small-cell lung cancer, the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, patients with lung cancer often have medical comorbities, which may preclude the option of surgical resection. In such cases, a number of minimally invasive to noninvasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages, including patient convenience, treatment in an outpatient setting, and acceptable toxicities, including reduced impact on lung function and a modest risk of postprocedure chest wall pain. We provide a comprehensive review of the literature, including reported outcomes, complications, and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy, and stereotactic body radiotherapy.

  20. Drug development for breast, colorectal, and non-small cell lung cancers from 1979 to 2014.

    Science.gov (United States)

    Nixon, Nancy A; Khan, Omar F; Imam, Hasiba; Tang, Patricia A; Monzon, Jose; Li, Haocheng; Sun, Gavin; Ezeife, Doreen; Parimi, Sunil; Dowden, Scot; Tam, Vincent C

    2017-08-17

    Understanding the drug development pathway is critical for streamlining the development of effective cancer treatments. The objective of the current study was to delineate the drug development timeline and attrition rate of different drug classes for common cancer disease sites. Drugs entering clinical trials for breast, colorectal, and non-small cell lung cancer were identified using a pharmaceutical business intelligence database. Data regarding drug characteristics, clinical trials, and approval dates were obtained from the database, clinical trial registries, PubMed, and regulatory Web sites. A total of 411 drugs met the inclusion criteria for breast cancer, 246 drugs met the inclusion criteria for colorectal cancer, and 315 drugs met the inclusion criteria for non-small cell lung cancer. Attrition rates were 83.9% for breast cancer, 87.0% for colorectal cancer, and 92.0% for non-small cell lung cancer drugs. In the case of non-small cell lung cancer, there was a trend toward higher attrition rates for targeted monoclonal antibodies compared with other agents. No tumor site-specific differences were noted with regard to cytotoxic chemotherapy, immunomodulatory, or small molecule kinase inhibitor drugs. Drugs classified as "others" in breast cancer had lower attrition rates, primarily due to the higher success of hormonal medications. Mean drug development times were 8.9 years for breast cancer, 6.7 years for colorectal cancer, and 6.6 years for non-small cell lung cancer. Overall oncologic drug attrition rates remain high, and drugs are more likely to fail in later-stage clinical trials. The refinement of early-phase trial design may permit the selection of drugs that are more likely to succeed in the phase 3 setting. Cancer 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care

    Science.gov (United States)

    2016-03-01

    Adenocarcinoma of the Lung; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Squamous Cell Lung Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  2. An actuarial approach to comparing early stage and late stage lung cancer mortality and survival.

    Science.gov (United States)

    Goldberg, Sara W; Mulshine, James L; Hagstrom, Dale; Pyenson, Bruce S

    2010-02-01

    Comparing the mortality characteristics of different cohorts is an essential process in the life insurance industry. Pseudodisease, lead-time bias, and length bias, which are critical to determining the value of cancer screening, have close analogues in life insurance company management, including the temporal impact of underwriting. Ratios of all-cause mortality rates for cancer cohorts relative to standard population mortality rates can provide insights into early stage and late stage mortality differences, differences by age, sex, race, and histology, and allow modeling of biases associated with early stage detection or screening protocols. The Surveillance, Epidemiology and End Results (SEER) data set has characteristics that allow efficient application of actuarial techniques. We show the mortality burden associated with treated early stage lung cancer and that identifying all lung cancers at early stage could reduce US lung cancer deaths by over 70,000 per year.

  3. Identification of Serum Peptidome Signatures of Non-Small Cell Lung Cancer

    OpenAIRE

    Agnieszka Klupczynska; Agata Swiatly; Joanna Hajduk; Jan Matysiak; Wojciech Dyszkiewicz; Krystian Pawlak; Zenon J. Kokot

    2016-01-01

    Due to high mortality rates of lung cancer, there is a need for identification of new, clinically useful markers, which improve detection of this tumor in early stage of disease. In the current study, serum peptide profiling was evaluated as a diagnostic tool for non-small cell lung cancer patients. The combination of the ZipTip technology with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for the analysis of peptide pattern of cancer patients (n ...

  4. Expression Levels of Some Antioxidant and Epidermal Growth Factor Receptor Genes in Patients with Early-Stage Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Giuseppe De Palma

    2010-01-01

    In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others.

  5. Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance.

    Science.gov (United States)

    Lou, Feiran; Huang, James; Sima, Camelia S; Dycoco, Joseph; Rusch, Valerie; Bach, Peter B

    2013-01-01

    At present, there is no consensus on the optimal strategy for follow-up care after curative resection for lung cancer. We sought to understand the patterns of recurrence and second primary lung cancer, and their mode of detection, after resection for early-stage non-small cell lung cancer in patients who were followed by routine surveillance computed tomography scan. We reviewed the outcomes of consecutive patients who underwent resection for early-stage non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center between 2004 and 2009. A total of 1294 consecutive patients with early-stage non-small cell lung cancer underwent resection. The median length of follow-up was 35 months. Recurrence was diagnosed in 257 patients (20%), and second primary lung cancer was diagnosed in 91 patients (7%). The majority of new primary cancers (85 [93%]) were identified by scheduled routine computed tomography scan, as were a smaller majority of recurrences (157 [61%]). During the first 4 years after surgery, the risk of recurrence ranged from 6% to 10% per person-year but decreased thereafter to 2%. Conversely, the risk of second primary lung cancer ranged from 3% to 6% per person-year and did not diminish over time. Additional testing after false-positive surveillance computed tomography scan results was performed for 329 patients (25%), but only 4 of these patients (0.3%) experienced complications as a result of subsequent invasive diagnostic procedures. Almost all second primary cancers and the majority of recurrences were detected by post-therapeutic surveillance computed tomography scan. The risk of recurrence for early-stage non-small cell lung cancer survivors persisted during the first 4 years after resection, and vigilance in surveillance should be maintained. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  6. Diagnosis and minimally invasive treatment of early stage breast carcinoma

    NARCIS (Netherlands)

    van Esser, S.

    1979-01-01

    In this thesis the diagnostic work up and minimally invasive surgical treatment of early stage breast carcinoma is studied. Although the surgical treatment of breast carcinoma has improved significantly over the past decades, there is still room for improvement. On the one hand the focus is on early

  7. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | FNLCR Staging

    Science.gov (United States)

    The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective. For some time, the national lab’s Nanotechno

  8. [Cognitive rehabilitation in early stage Alzheimer's disease].

    Science.gov (United States)

    Kasper, E; Thöne-Otto, A; Bürger, K; Schröder, S G; Hoffmann, W; Schneider, W; Teipel, S

    2016-07-01

    Dementia impairs the coping with routine daily tasks and social relationships due to an increasing degeneration of cognitive abilities. An appropriate treatment must adequately consider the effects of declined cognitive abilities on patients and their environment. Therefore, in recent times, integrative procedures for cognitive rehabilitation (CR) have become increasingly important for the therapy of patients with mild cognitive impairment (MCI) and mild dementia (MD). CR approaches provide compensatory possibilities for clearly defined routine challenges and the individual needs of those affected. This overview article in the form of a selective review elaborates factors for the effectiveness of CR on the basis of the currently available literature: 1) individuality - consideration of personal needs and targets, 2) compensation - mediation of skills and strategies to compensate for cognitive impairments, 3) interaction - inclusion of relatives and environmental conditions and 4) integration - integration of various therapeutic disciplines and methods. On the basis of this assessment with regards to the content, a critical analysis of the methods of short and long-term therapeutic effects on MCD and MD was carried out. Although the resulting factors were of high long-term relevance for the improvement of depression and quality of life, effects on cognition were more pronounced for MCI than for MD, which emphasizes the importance of beginning therapy as early as possible. The results show that future studies on effectiveness must employ endpoints relevant for routine daily life, and that the possibility of an implementation of therapeutic concepts in a healthcare system should be considered as an essential criterion.

  9. Safety and Palliative Efficacy of Single-Dose 8-Gy Reirradiation for Painful Local Failure in Patients With Stage IV Non-Small Cell Lung Cancer Previously Treated With Radical Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Topkan, Erkan, E-mail: docdretopkan@gmail.com [Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana (Turkey); Yildirim, Berna Akkus; Guler, Ozan Cem; Parlak, Cem [Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana (Turkey); Pehlivan, Berrin [Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, and American Hospital, University of Texas MD Anderson Radiation Treatment Center, Istanbul (Turkey); Selek, Ugur [Medstar Hospital, Department of Radiation Oncology, Antalya (Turkey)

    2015-03-15

    Purpose: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal. Patients and Methods: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors. Results: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS. Conclusions: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.

  10. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    Directory of Open Access Journals (Sweden)

    Abigail T. Berman

    2015-07-01

    Full Text Available Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT, through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC, as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

  11. Impact on disease development, genomic location and biological function of copy number alterations in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Yen-Tsung Huang

    Full Text Available Lung cancer, of which more than 80% is non-small cell, is the leading cause of cancer-related death in the United States. Copy number alterations (CNAs in lung cancer have been shown to be positionally clustered in certain genomic regions. However, it remains unclear whether genes with copy number changes are functionally clustered. Using a dense single nucleotide polymorphism array, we performed genome-wide copy number analyses of a large collection of non-small cell lung tumors (n = 301. We proposed a formal statistical test for CNAs between different groups (e.g., non-involved lung vs. tumors, early vs. late stage tumors. We also customized the gene set enrichment analysis (GSEA algorithm to investigate the overrepresentation of genes with CNAs in predefined biological pathways and gene sets (i.e., functional clustering. We found that CNAs events increase substantially from germline, early stage to late stage tumor. In addition to genomic position, CNAs tend to occur away from the gene locations, especially in germline, non-involved tissue and early stage tumors. Such tendency decreases from germline to early stage and then to late stage tumors, suggesting a relaxation of selection during tumor progression. Furthermore, genes with CNAs in non-small cell lung tumors were enriched in certain gene sets and biological pathways that play crucial roles in oncogenesis and cancer progression, demonstrating the functional aspect of CNAs in the context of biological pathways that were overlooked previously. We conclude that CNAs increase with disease progression and CNAs are both positionally and functionally clustered. The potential functional capabilities acquired via CNAs may be sufficient for normal cells to transform into malignant cells.

  12. Photodynamic Therapy of Non-Small Cell Lung Cancer. Narrative Review and Future Directions.

    Science.gov (United States)

    Shafirstein, Gal; Battoo, Athar; Harris, Kassem; Baumann, Heinz; Gollnick, Sandra O; Lindenmann, Joerg; Nwogu, Chukwumere E

    2016-02-01

    Photodynamic therapy (PDT) is an established treatment modality for non-small cell lung cancer. Phototoxicity, the primary adverse event, is expected to be minimized with the introduction of new photosensitizers that have shown promising results in phase I and II clinical studies. Early-stage and superficial endobronchial lesions less than 1 cm in thickness can be effectively treated with external light sources. Thicker lesions and peripheral lesions may be amenable to interstitial PDT, where the light is delivered intratumorally. The addition of PDT to standard-of-care surgery and chemotherapy can improve survival and outcomes in patients with pleural disease. Intraoperative PDT has shown promise in the treatment of non-small cell lung cancer with pleural spread. Recent preclinical and clinical data suggest that PDT can increase antitumor immunity. Crosslinking of signal transducer and activator of transcription-3 molecules is a reliable biomarker to quantify the photoreaction induced by PDT. Randomized studies are required to test the prognosis value of this biomarker, obtain approval for the new photosensitizers, and test the potential efficacy of interstitial and intraoperative PDT in the treatment of patients with non-small cell lung cancer.

  13. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  14. Functioning in early and late stages of schizophrenia

    Directory of Open Access Journals (Sweden)

    Leonardo Gazzi Costa

    2014-12-01

    Full Text Available INTRODUCTION: Schizophrenia is frequently associated with a debilitating course and prominent impairment in social and occupational functioning. Although the criteria for classification into stages have not been defined in the literature, illness duration and functioning seem to be good candidates.OBJECTIVE:To compare functioning of patients with schizophrenia at different stages of the disease (early vs. late and healthy sex- and age-matched controls.METHODS: This double-blinded, case-controlled study included 79 individuals: 23 patients with schizophrenia diagnosed up to 5 years earlier; 19 patients with schizophrenia diagnosed at least 20 years earlier; and healthy matched controls. Diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV Axis I Disorder. Functioning was assessed using the Functioning Assessment Short Test (FAST.RESULTS: Patients in the early stage had significantly higher scores than healthy controls in total FAST and in autonomy, occupational functioning, cognitive functioning and interpersonal relationships. Individuals in the late stage had significantly poorer functioning than controls in all domains. The comparison of functioning between the two groups of patients revealed no significant differences, except in occupational functioning, in which late stage patients had a poorer performance.CONCLUSION: Functioning impairment in schizophrenia tends to remain stable despite illness duration. Therefore, functioning should be effectively assessed at an early stage, as illness duration alone may not be the most reliable criterion to stage patients with schizophrenia.

  15. Oncological outcomes from trimodality therapy receiving definitive doses of neoadjuvant chemoradiation (≥60 Gy and factors influencing consideration for surgery in stage III non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Melissa A.L. Vyfhuis, MD PhD

    2017-07-01

    Conclusions: Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

  16. DNA Methylation and Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Youwei ZHANG

    2010-08-01

    Full Text Available Genomic DNA methylation is a major form of epigenetic modification. Hypermethylation could affect the binding of transcription factors to DNA and change the structure of chromatin resulting in silence of tumor suppressor genes, which plays an important role in cancer initiation and progression. In recent years, the study of DNA methylation in lung cancer, mostly in non-small cell lung cancer, has made great progress and become a new target for early detection, risk assessment, prognosis and cancer therapy.

  17. Early Stage Software Reliability Estimation with Stochastic Reward Nets

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jing; LIU Hong-wei; CUI Gang; YANG Xiao-zong

    2005-01-01

    This paper presents software reliability modeling issues at the early stage of a software development for fault tolerant software management system. Based on Stochastic Reward Nets, an effective model of hierarchical view for a fault tolerant software management system is put forward, and an approach that consists of system transient performance analysis is adopted. A quantitative approach for software reliability analysis is given. The results show its usefulness for the design and evaluation of the early-stage software reliability modeling when failure data is not available.

  18. Detection of Recurrence Patterns After Wedge Resection for Early Stage Lung Cancer: Rationale for Radiologic Follow-Up.

    Science.gov (United States)

    Billè, Andrea; Ahmad, Usman; Woo, Kaitlin M; Suzuki, Kei; Adusumilli, Prasad; Huang, James; Jones, David R; Rizk, Nabil Pierre

    2016-10-01

    Wedge resection for selected patients with early stage non-small cell lung cancer is considered to be a valid treatment option. The aim of this study was to evaluate the recurrence patterns after wedge resection, to analyze the survival of patients under routine follow-up, and to recommend a follow-up regimen. A retrospective analysis was done of 446 consecutive patients between May 2000 and December 2012 who underwent a wedge resection for clinical stage I non-small cell lung cancer. All patients were followed up with a computed tomography scan with or without contrast. The recurrence was recorded as local (involving the same lobe of wedge resection), regional (involving mediastinal or hilar lymph nodes or a different lobe), or distant (including distant metastasis and pleural disease). Median follow-up for survivors (n = 283) was 44.6 months. In all, 163 patients died; median overall survival was 82.6 months. Thirty-six patients were diagnosed with new primary non-small cell lung cancer, and 152 with recurrence (79 local, 45 regional, and 28 distant). There was no difference in the incidence of recurrence detection detected by computed tomography scans with versus without contrast (p = 0.18). The cumulative incidence of local recurrences at 1, 2, and 3 years was higher than the cumulative incidence for local, regional, and distant recurrences: 5.2%, 11.1%, and 14.9% versus 3.7%, 6.6%, and 9.5% versus 2.3%, 4.7%, and 6.4%, respectively. Primary tumor diameter was associated with local recurrence in univariate analysis. Wedge resection for early stage non-small cell lung cancer is associated with a significant risk for local and regional recurrence. Long-term follow-up using noncontrast computed tomography scans at consistent intervals is appropriate to monitor for these recurrences. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Radiation therapy planning for early-stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Maraldo, Maja V; Dabaja, Bouthaina S; Filippi, Andrea R

    2015-01-01

    PURPOSE: Early-stage Hodgkin lymphoma (HL) is a rare disease, and the location of lymphoma varies considerably between patients. Here, we evaluate the variability of radiation therapy (RT) plans among 5 International Lymphoma Radiation Oncology Group (ILROG) centers with regard to beam arrangements...

  20. Early Stages of the Evolution of Life: a Cybernetic Approach

    Science.gov (United States)

    Melkikh, Alexey V.; Seleznev, Vladimir D.

    2008-08-01

    Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

  1. Radiation Plus Chemotherapy in Early-Stage Hodgkin Lymphoma

    Science.gov (United States)

    Adding radiation therapy to chemotherapy may improve outcomes in patients with early-stage Hodgkin lymphoma, according to a paper published in the Cochrane Database of Systematic Reviews in February 2011, but the long-term effects of this regimen are not

  2. [Surgical treatment of breast neoplasms in early stages].

    Science.gov (United States)

    Cheshuk, Ie V; Drozdov, V M; Neĭman, A M; Zotov, O S; Zakhartseva, L M; Anikus'ko, M F; Zaĭchuk, V V; Sydorchuk, O I

    2002-01-01

    Analysis of literary data and own investigation results for the modern surgical methods of treatment of mammary gland cancer in early stages was performed. Indexes of patients survival after surgical removal of mammary gland (MG) and quadranthectomy did not differ. Preservation of MG constitutes great social and psycho-emotional significance for women-patients.

  3. Stathmin基因在Ⅱ期非小细胞肺癌中表达的意义%Expression of Stathmin in stage II non-small cell lung cancer and its significance

    Institute of Scientific and Technical Information of China (English)

    王小红; 周星明; 江洪; 张谷; 苏丹

    2014-01-01

    目的:探讨Ⅱ期非小细胞肺癌(NSCLC)中Stathmin mRNA和蛋白表达水平与患者预后的关系。方法单基因定量法检测已手术Ⅱ期NSCLC患者肿瘤组织中Stathmin mRNA表达;免疫组化法检测患者肿瘤组织中Stathmin蛋白表达水平。所有患者行长春瑞滨联合顺铂方案化疗,统计学分析其表达水平与患者临床病理学特征之间的关系,并随访患者的无瘤生存时间(DFS)和总体生存时间(OS),统计学分析StathminmRNA和蛋白表达水平与患者的DFS、OS的关系。结果 Stathmin mRNA表达水平与患者的T、N分期显著相关,与患者的年龄,病理类型均无显著相关性;Stathmin蛋白表达水平与患者的年龄、病理类型、T、N分期均无显著相关性;Stathmin mRNA和蛋白表达水平与患者的OS,DFS均无显著相关性。结论Ⅱ期NSCLC患者肿瘤组织中Stathmin表达水平不能作为预测患者预后的指标。%Objective To investigate the expression of Stathmin in stageⅡ non- smal celllung cancer (NSCLC) and its significance. Methods The expression of Stathmin mRNA and protein was detected by Quanti- Gene Assay and immunohisto-chemistry, respectively. Al patients received NP chemotherapy. The patients were fol owed- up;the disease- free survival (DFS) and overal survival (OS) were observed. The correlation of Stathmin expression level with the clinicopathological features of NSCLC and prognosis of patients were analyzed. Results Stathmin mRNA expression levels was significantly correlated with T stage and N stage. There was no significant correlation of Stathmin mRNA and protein expression levels with the OS and DFS of patients. Conclusion In patients with stage Ⅱ NSCLC, the expression levels of Stathmin mRNA and protein in cancer tissue cannot be used as a prognostic indicator.

  4. Management of Early-stage Hodgkin Lymphoma: A Practice Guideline.

    Science.gov (United States)

    Herst, J; Crump, M; Baldassarre, F G; MacEachern, J; Sussman, J; Hodgson, D; Cheung, M C

    2017-01-01

    In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma. We conducted a systematic review searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from 2003 to 2015, and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two authors independently reviewed and selected studies, and appraised the evidence quality. The document underwent internal and external review by content, methodology experts, a patient representative and clinicians in Ontario. We have issued recommendations for patients with classical Hodgkin lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with favourable and unfavourable prognosis; and for the use of positron emission tomography to direct treatment. We have provided our interpretation of the evidence and considerations for implementation. Examples of recommendations are: 'Patients with early-stage classical Hodgkin lymphoma should not be treated with radiotherapy alone'; 'chemotherapy plus radiotherapy or chemotherapy alone are recommended treatment options for patients with early-stage non-bulky Hodgkin lymphoma'; 'The Working Group does not recommend the use of a negative interim positron emission tomography scan alone to identify patients with early-stage Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in progression-free survival'. Through the use of GRADE, recommendations were geared towards patient important outcomes and their strength reflected the available evidence and its interpretation from the patients' point of view. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  5. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    Science.gov (United States)

    2017-09-14

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer

  6. Observation on Clinical Efficacy of Self-Made Lung Cancer Prescription Combined with Pemetrexed and Cisplatin in the Treatment of Intermediate and Advanced Stage Non-Small Cell Lung Cancer%自拟肺癌方联合培美曲塞及顺铂治疗中晚期非小细胞肺癌的疗效观察

    Institute of Scientific and Technical Information of China (English)

    于小伟; 徐川; 方美花; 仝欣; 李敏

    2015-01-01

    Objective :To observe the clinical efficacy of pemetrexed and cisplatin in combination with self-made lung cancer prescription in the treatment of intermediate and advanced stage non-small cell lung cancer .Methods : A total of 71 patients with intermediate or advanced stage non-small cell lung cancer diagnosed by imaging and pathological or cytological method from Oct .2010 to Oct .2013 were randomly divided into 2 groups .The 35 cases in control group received chemotherapy using pemetrexed combined with cisplatin ,and the 36 cases in treatment group received self-made lung cancer prescription orally in combination with the same chemotherapy of control group . Results : The total effective rates of improvement on clinical symptoms ,quality of life and immune index in the treatment group were superior to those in the control group(P 0 .05) .Conclusions : Integrated Chinese and Western medicine show certain efficacy in the treatment of intermediate and advanced stage non-small cell lung cancer ,and thus is worthy of clinical promotion .%目的:观察培美曲塞联合顺铂方案(PC 方案)化疗加自拟肺癌方口服治疗中晚期非小细胞肺癌的临床疗效。方法:将2010年10月—2013年10月经影像学及病理或细胞学确诊为中晚期非小细胞肺癌的患者71例随机分为两组,治疗组36例,对照组35例。对照组给予 PC 方案化疗,治疗组在对照组的基础上给予自拟肺癌方口服。结果:治疗组在临床症状改善、生存质量提高、免疫指标变化方面的总有效率均优于对照组(P<0.05),但肿瘤客观疗效有效率及临床受益率、体质量变化总有效率与对照组比较差异无统计学意义(P>0.05)。结论:中西医结合治疗中晚期非小细胞肺癌疗效肯定,有临床推广价值。

  7. CT perfusion at early stage of hepatic diffuse disease

    Institute of Scientific and Technical Information of China (English)

    Sheng Guan; Wei-Dong Zhao; Kang-Rong Zhou; Wei-Jun Peng; Jian Mao; Feng Tang

    2005-01-01

    AIM: To determine the validity of the non-invasive method of CT perfusion (CTP) in rat model of hepatic diffuse disease. METHODS: Twenty-eight Wistar rats were divided into two groups. Liver diffuse lesions were induced by dietthylnitrosamine in 14 rats of test group. Rats in control groupwere bred with pure water. From the 1st to 12th wk after the test group was intervened, both groups were studied every week with CTP. CTP parameters of liver parenchymain different periods and pathologic changes in two groups were compared and analyzed.RESULTS: The process of hepatic diffuse lesions in test groups was dassified into three stages or periods according to the pathologic alterations, namely hepattitis, hepatic fibrosis, and cirrhosis. During this period, hepatic artery flow (HAF)of control group declined slightly, mean transit time (MTT),blood flow (BF) and volume (BV) increased, but there wereno significant differences between different periods. Tntest group, HAF tended to increase gradually, MTT prolonged obviously, BV and BF decreased at the same time. The results of statistical analysis revealed that the difference in the HAF ratio of test group to control group was significant.The ratio of BV and BF in test group to control group in stageof hepatitis and hepatic cirrhosis, hepatic fibrosis and early stage of hepatic cirrhosis was significantly different, but there was no significant difference between hepatitis and hepatic fibrosis. The main pathological changes in stage of hepatitis were swelling of hepatic cells, while sinusoid capillarization and deposition of collagen aggravated gradually in the extravascular Disse's spaces in stage of fibrosis and early stage of cirrhosis.CONCLUSION: The technique could reflect some early changes of hepatic blood perfusion in rat with liver diffuse disease and is valuable for their early diagnosis.

  8. Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer

    Science.gov (United States)

    Sculier, J-P; Lafitte, J-J; Paesmans, M; Thiriaux, J; Alexopoulos, C G; Baumöhl, J; Schmerber, J; Koumakis, G; Florin, M C; Zacharias, C; Berghmans, T; Mommen, P; Ninane, V; Klastersky, J

    2000-01-01

    A phase III randomized trial was conducted in patients with metastatic NSCLC, to determine if, in association with mitomycin (6 mg m–2) and ifosfamide (3 g m–2), the combination of moderate dosages of cisplatin (60 mg m–2) and carboplatin (200 mg m–2) – CarboMIP regimen – improved survival in comparison with cisplatin (50 mg m–2) alone – MIP regimen. A total of 305 patients with no prior chemotherapy were randomized, including 297 patients assessable for survival (147 in the MIP arm and 150 in the CarboMIP arm) and 268 patients assessable for response to chemotherapy. All but eight (with malignant pleural effusion) had stage IV disease. There was a 27% (95% CI, 19–34) objective response (OR) rate to MIP (25% of the eligible patients) and a 33% (95% CI, 24–41) OR rate to CarboMIP (29% of the eligible patients). This difference was not statistically significant (P = 0.34). Duration of response was not significantly different between both arms. There was also no difference (P = 0.67) in survival: median survival times were 28 weeks (95% Cl, 24–32) for MIP and 32 weeks (95% Cl, 26–35) for CarboMIP, with respectively 1-year survival rates of 24% and 23% and 2-year survival rates of 5% and 2%. The main toxicities consisted in emesis, alopecia, leucopenia and thrombocytopenia, that were, except alopecia, significantly more severe in the CarboMIP arm. Our trial failed to demonstrate a significant improvement in response or survival when patients with metastatic NSCLC were treated, in addition to ifosfamide and mitomycin, by combination of moderate dosages of cisplatin and carboplatin instead of moderate dosage of cisplatin alone. The results support the use of a moderate dose (50 mg m–2) of cisplatin in combination with ifosfamide and mitomycin for the chemotherapy of this disease. © 2000 Cancer Research Campaign PMID:11027424

  9. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    Science.gov (United States)

    Hong, Yu; Long, Jiang; Li, Hai; Chen, Shuhong; Liu, Qiqi; Zhang, Bei; He, Xiaomin; Wang, Yan; Li, Hongyi; Li, Yimei; Zhang, Tao; Lu, Chenzhen; Yan, Hao; Zhang, Minli; Li, Qing; Cao, Bangwei; Bai, Zhigang; Wang, Jin; Zhang, Zhongtao; Zhu, Shengtao; Zheng, Jiasheng; Ou, Xiaojuan; Ma, Hong; Jia, Jidong; You, Hong; Wang, Shengqi; Huang, Jian

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis. Methods Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing protein antigens of the candidate TAAs. Analyses were done by using receiver operating characteristics (ROC) to calculate diagnostic accuracy. Findings Twenty-two candidate TAAs were assessed by protein microarray analysis in 914 participants with serum α-fetoprotein (AFP) available. Twelve candidate TAAs were statistically different in signal intensity between HCC and controls. Among them, CENPF, HSP60 and IMP-2 showed AUC (area under the curve) values of 0.826, 0.764 and 0.796 respectively for early HCC. The highest prevalence of autoantibody positivity was observed in HCC cases with BCLC tumor stage A, well-differentiated histology and Child-Pugh grade C. Specifically, 73.6% or 79.3% cases of early HCC with negative AFP were positive for autoantibody to CENPF or HSP60. Interpretation Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC. PMID:26137588

  10. Early morbidity after simultaneous and staged bilateral total knee arthroplasty

    DEFF Research Database (Denmark)

    Lindberg-Larsen, Martin; Jørgensen, Christoffer Calov; Husted, Henrik;

    2015-01-01

    PURPOSE: The aim of this nationwide study was to investigate the early morbidity after bilateral simultaneous and staged total knee arthroplasty (TKA) in order to clarify potential benefits of a well-established fast-track regime. METHODS: The Danish National Patient Registry was searched for all...... bilateral simultaneous and staged TKA procedures from 2010 to 2011. The staged procedures were defined as two separate procedures done within 0-6 months or within 7-18 months. RESULTS: A total of 157 patients had bilateral simultaneous TKA, 346 patients had bilateral staged TKA within 0-6 months and 292...... simultaneous TKA versus three deaths (0.9 and 1.0 %) in each of the bilateral staged groups within 90 days of surgery (n.s.). The total readmission rate within 30 days of surgery was lower after bilateral simultaneous TKA (7 %, CI 4.0-12.0) and bilateral staged TKA within 0-6 months (9 %, CI 6.4-12.4) compared...

  11. The early stages in the oxidation of Na

    Energy Technology Data Exchange (ETDEWEB)

    Shek, M.L. (25 Old Saddle Road, Ridge, New York 11961 (USA)); Hrbek, J. (Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (USA)); Sham, T.K. (Department of Chemistry, University of Western Ontario, Ontario, NA6 5B7, Canada (CA)); Xu, G. (Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (USA))

    1991-05-01

    We report soft x-ray photoemission results on the early stages of the oxidation of Na at {similar to}80 K. The first stage (up to {approx gt}0.5 L exposure) is characterized by a narrow O 2{ital p} level and a Na 2{ital p} surface core level shifted by {minus}0.55 eV with respect to the bulk core level. The Na 2{ital p} surface plasmon loss intensity shifts toward smaller energies, consistent with a decrease in surface conduction electron density. The second stage (starting from {similar to}1 L) is characterized by the emergence of di-oxygen'' valence levels and a Na 2{ital p} component shifted by {similar to}0.8 eV with respect to the bulk binding energy. The oxidation is strongly nonuniform, as suggested by the small oxygen doses needed for the onset of the second oxidation stage, and the continued presence of the bulk plasmon loss from metallic Na. The two new Na 2{ital p} binding energies are tentatively attributed to different final-state screening of metallic Na adjacent to dispersed oxygen atoms in the first stage, and of the Na atoms with mostly oxygen nearest neighbors in the second stage. Observations regarding large negative core level shifts upon large oxygen exposures are also summarized.

  12. Information processing theory in the early design stages

    DEFF Research Database (Denmark)

    Cash, Philip; Kreye, Melanie

    2014-01-01

    suggestions for improvements and support. One theory that may be particularly applicable to the early design stages is Information Processing Theory (IPT) as it is linked to the design process with regard to the key concepts considered. IPT states that designers search for information if they perceive......, the new knowledge is shared between the design team to reduce ambiguity with regards to its meaning and to build a shared understanding – reducing perceived uncertainty. Thus, we propose that Information-Processing Theory is suitable to describe designer activity in the early design stages......Developing appropriate theory is one of the main challenges facing engineering design (Cross, 2007). Theory helps to both explain design activity but also support greater research impact in the domain. It is useful for gaining a more comprehensive understanding of design activity and developing...

  13. Information processing theory in the early design stages

    DEFF Research Database (Denmark)

    Cash, Philip; Kreye, Melanie

    2014-01-01

    Developing appropriate theory is one of the main challenges facing engineering design (Cross, 2007). Theory helps to both explain design activity but also support greater research impact in the domain. It is useful for gaining a more comprehensive understanding of design activity and developing...... suggestions for improvements and support. One theory that may be particularly applicable to the early design stages is Information Processing Theory (IPT) as it is linked to the design process with regard to the key concepts considered. IPT states that designers search for information if they perceive...... uncertainty with regard to the knowledge necessary to solve a design challenge. They then process this information and compare if the new knowledge they have gained covers the previous knowledge gap. In engineering design, uncertainty plays a key role, particularly in the early design stages which has been...

  14. Adjuvant chemotherapy for early-stage cervical cancer.

    Science.gov (United States)

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  15. Effects of genistein on early-stage cutaneous wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunkyo [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Seung Min [Research Institute of Health Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Jung, In-Kyung [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lim, Yunsook [Department of Foods and Nutrition, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Jung-Hyun, E-mail: jjhkim@cau.ac.kr [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of)

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results

  16. Awareness of memory deficits in early stage Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Laurent Cleret de Langavant

    Full Text Available Patients with Huntington's disease (HD are often described as unaware of their motor symptoms, their behavioral disorders or their cognitive deficits, including memory. Nevertheless, because patients with Parkinson's disease (PD remain aware of their memory deficits despite striatal dysfunction, we hypothesize that early stage HD patients in whom degeneration predominates in the striatum can accurately judge their own memory disorders whereas more advanced patients cannot. In order to test our hypothesis, we compared subjective questionnaires of memory deficits (in HD patients and in their proxies and objective measures of memory dysfunction in patients. Forty-six patients with manifest HD attending the out-patient department of the French National Reference Center for HD and thirty-three proxies were enrolled. We found that HD patients at an early stage of the disease (Stage 1 were more accurate than their proxies at evaluating their own memory deficits, independently from their depression level. The proxies were more influenced by patients' functional decline rather than by patients' memory deficits. Patients with moderate disease (Stage 2 misestimated their memory deficits compared to their proxies, whose judgment was nonetheless influenced by the severity of both functional decline and depression. Contrasting subjective memory ratings from the patients and their objective memory performance, we demonstrate that although HD patients are often reported to be unaware of their neurological, cognitive and behavioral symptoms, it is not the case for memory deficits at an early stage. Loss of awareness of memory deficits in HD is associated with the severity of the disease in terms of CAG repeats, functional decline, motor dysfunction and cognitive impairment, including memory deficits and executive dysfunction.

  17. Early Contact Stage of Apoptosis: Its Morphological Features and Function

    Directory of Open Access Journals (Sweden)

    Etheri Mikadze

    2006-01-01

    Full Text Available Apoptosis has been a biological phenomenon of intense interest for 20 years, but the earlier morphological features of apoptosis have not been determined hitherto. Using the methods of semi- and ultrathin sections, the livers of intact embryos and young rats have been studied under the effect of cycloheximide to determine morphological features of an early stage of apoptosis. It is discovered that both in hepatoblasts and hepatocytes, apoptosis, besides the well-known stages, also includes an early contact stage, distinguishing features of which are agglutination of bound ribosomes (breaking of translation, elimination of the nucleolus, reduction of free polysomes (and in hepatocytes, reduction of cisterns of rough endoplasmic reticulum, formation of cytoplasmic excrescences, and cell shape changes. The early stage of apoptosis is characterized by close contact with neighboring cells. At a certain phase of the contact stage of apoptosis, the nucleolus reappears in the nucleus and the number of free polysomes in the cytoplasm increases, which suggests the renewal of synthesis of new RNA and proteins. Close contact of differentiating and mitotic hepatoblasts with apoptotic cells indicates a certain functional relationship between these cells that is realized not only by micropinocytosis, but through gap junctions as well. We assume that the apoptotic cell, besides proteolytic products, can contain newly synthesized, low-molecular substances, the relocation of which from apoptotic to neighboring cells may contribute to both functional activity and proliferation of adjacent hepatoblasts and, therefore, the function of apoptosis may not be limited only to the elimination of harmful, damaged, and unwanted cells.

  18. 营养支持对非小细胞肺癌患者术前新辅助化疗后肺功能的影响%Influence of lung function of pre-operation patients with stage ⅡB-ⅢA non-small cell lung cancer after neoadjuvant chemotherapy by nutrition support

    Institute of Scientific and Technical Information of China (English)

    刘金锋; 田惠玉; 孙会凤; 苗伏龙; 李志杰; 郭斌; 张会军

    2014-01-01

    Objective To study the influence of lung function of pre-operation patients with stage ⅡB-ⅢA non-small cell lung cancer after neoadjuvant chemotherapy by nutrition support.Methods Fifty pre-operation patients with stage ⅡB-ⅢA non-small cell lung cancer were randomly divided into two groups:the control group (25 cases):normal diet,containing paclitaxel + platinum-based chemotherapy;experimental group (25 cases):increased the nutritional support during the chemotherapy treatment on the basis of the control group;the lung function indexes were tested such as FEV1,MVV,DLCO before and after chemotherapy.Results The lung function indexes had no significant difference before chemotherapy between the control group and the experimental group (P > 0.05 );DLCO dropped significantly after the chemotherapy,the difference was statistically significant (P 0.05);化疗后 DLCO 较化疗前有显著下降,差异有统计学意义(P <0.05)。试验组化疗后 FEV1、MVV 较化疗前及对照组化疗后有提高,差异有统计学意义(P <0.05)。结论术前化疗对肺弥散功能产生一定不良影响,有一定的肺毒性,营养支持能在一定程度上改善ⅡB~ⅢA 期非小细胞肺癌患者术前新辅助化疗后肺通气功能,但对肺弥散功能无显著影响。

  19. Phyllotactic pattern formation in early stages of cactus ontogeny

    Directory of Open Access Journals (Sweden)

    Edyta M. Gola

    2011-01-01

    Full Text Available Representatives of the family Cactaceae are characterized by a wide range of phyllotaxis. To assess the origin of this diversity, early stages of phyllotactic pattern formation were examined in seedlings. The analysis of the sequence of areole initiation revealed intertribal differences. In seedlings from the Trichocereeae (Gymnocalycium, Rebutia and Notocacteae (Parodia tribes, two opposite cotyledonal areoles developed as the first elements of a pattern. Usually, next pair of areoles was initiated perpendicularly to cotyledonal areoles, starting the decussate pattern. This pattern was subsequently transformed into bijugate or into simple spiral phyllotaxis. In seedlings from the Cacteae tribe (Mammillaria and Thelocactus, cotyledonal areoles were never observed and the first areoles always appeared in the space between cotyledons. It was either areole pair (mainly in Mammillaria, starting a decussate pattern, or a single areole (mainly in Thelocactus quickly followed by areoles spirally arranged, usually in accordance with the main Fibonacci phyllotaxis. Differences in the initial stages of pattern formation do not fully explain the phyllotaxis diversity in mature cacti. Only two, the most common phyllotactic patterns occurred in the early development of studied seedlings, i.e. the main Fibonacci and the decussate pattern. Discrepancy in the range of phyllotactic spectra in seedlings and in mature plants suggests that phyllotaxis diversity emerges during further plant growth. Initial phyllotactic transformations, occurring already in the very early stages, indicate great plasticity of cactus growth and seem to support the hypothesis of the ontogenetic increase of phyllotaxis diversity due to transformations.

  20. [Stereotactic radiotherapy for non-small cell lung cancer: From concept to clinical reality. 2011 update].

    Science.gov (United States)

    Girard, N; Mornex, F

    2011-10-01

    Only 60% of patients with early-stage non-small cell lung cancer (NSCLC), a priori bearing a favorable prognosis, undergo radical resection because of the very frequent co-morbidities occurring in smokers, precluding surgery to be safely performed. Stereotactic radiotherapy consists of the use of multiple radiation microbeams, allowing high doses of radiation to be delivered to the tumour (ranging from 7.5 to 20 Gy per fraction) in a small number of fractions (one to eight on average). Several studies with long-term follow-up are now available, showing the effectiveness of stereotactic radiotherapy to control stage I/II non-small cell lung cancer in medically inoperable patients. Local control rates are consistently reported to be above 95% with a median survival of 34 to 45 months. Because of these excellent results, stereotactic radiation therapy is now being evaluated in operable patients in several randomized trials with a surgical arm. Ultimately, the efficacy of stereotactic radiotherapy in early-stage tumours leads to hypothesize that it may represent an opportunity for locally-advanced tumors. The specific toxicities of stereotactic radiotherapy mostly correspond to radiation-induced chest wall side effects, especially for peripheral tumours. The use of adapted fractionation schemes has made feasible the use of stereotactic radiotherapy to treat proximal tumours. Overall, from a technical concept to the availability of specific treatment devices and the publication of clinical results, stereotactic radiotherapy represents a model of implementation in thoracic oncology. Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  1. Primary treatment options for high risk/medically inoperable early stage NSCLC patients

    Science.gov (United States)

    Jones, Guy C.; Kehrer, Jason D.; Kahn, Jenna; Koneru, Bobby N.; Narayan, Ram; Thomas, Tarita O.; Camphausen, Kevin; Mehta, Minesh P; Kaushal, Aradhana

    2015-01-01

    Lung cancer is among the most common cancers worldwide, and the leading cause of cancer death in both men and women. For patients with early stage (AJCC T1-2, N0) non-small cell lung cancer the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, medical comorbities often present in patients with lung cancer, may preclude the option of surgical resection . In such cases, a number of minimal to non-invasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages including patient convenience, treatment in an outpatient setting, and acceptable toxicities including reduced impact on lung function and a modest risk of post-procedure chest wall pain. This manuscript seeks to provide a comprehensive review of the literature including reported outcomes, complications and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy and stereotactic body radiation therapy. PMID:26027433

  2. Requirement Defect Mitigation Technique: An Early Stage Implementation

    Directory of Open Access Journals (Sweden)

    Md. Rizwan Beg

    2012-09-01

    Full Text Available Requirement defect identification and mitigation at early stage of Software Development Life Cycle (SDLC is very cost effective than to later stages. The requirements analysis in requirement engineering process is critical and major foundation of requirement defect identification. A poor requirement analysis process may lead to software requirement specification (SRS full of defects akin to misplaced, ambiguous, incompatible, misinterpreted, and incomplete requirements. In this paper, requirement defects are being identified and properly mitigated as per its severity in the requirement phase to get rid of major rework by spending extra cost and effort at the later stages. Here, a Defect Mitigation Technique (DMT is proposed for mitigating the identified requirement defect and also the reliability of requirement is being assessed to deliver Reliable Requirement. The proposed algorithm is helping the DMT for its proper processing, defect mitigation and reliability assessment. The prime motive of this study is an effort to put off requirements stage defects from entering into later stages of SDLC.

  3. Stage-specific proteome signatures in early bovine embryo development.

    Science.gov (United States)

    Deutsch, Daniela R; Fröhlich, Thomas; Otte, Kathrin A; Beck, Andrea; Habermann, Felix A; Wolf, Eckhard; Arnold, Georg J

    2014-10-03

    Development of early embryonic stages before activation of the embryonic genome depends on sufficiently stored products of the maternal genome, adequate recruitment and degradation of mRNAs, as well as activation, deactivation, and relocation of proteins. By application of an isobaric tagging for relative and absolute quantification (iTRAQ)-based approach, the proteomes of bovine embryos at the zygote and 2-cell and 4-cell stage with MII oocytes as a reference were quantitatively analyzed. Of 1072 quantified proteins, 87 differed significantly in abundance between the four stages. The proteomes of 2-cell and 4-cell embryos differed most from the reference MII oocyte, and a considerable fraction of proteins continuously increased in abundance during the stages analyzed, despite a strongly attenuated rate of translation reported for this period. Bioinformatic analysis revealed particularly interesting proteins involved in the p53 pathway, lipid metabolism, and mitosis. Verification of iTRAQ results by targeted SRM (selected reaction monitoring) analysis revealed excellent agreement for all five proteins analyzed. By principal component analysis, SRM quantifications comprising a panel of only five proteins were shown to discriminate between all four developmental stages analyzed here. For future experiments, an expanded SRM protein panel will provide the potential to detect developmental disturbances with high sensitivity and enable first insights into the underlying molecular pathways.

  4. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... leaking from the lung into the chest. Enlarge Fine-needle aspiration biopsy of the lung. The patient lies on a ... nodes , or other areas. Enlarge Endoscopic ultrasound-guided fine-needle aspiration biopsy. An endoscope that has an ultrasound probe and ...

  5. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    Science.gov (United States)

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Early stages of bipolar disorder: characterization and strategies for early intervention

    Directory of Open Access Journals (Sweden)

    Adiel C. Rios

    2015-12-01

    Full Text Available Objective: To characterize the early stages of bipolar disorder (BD, defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a characterized prodromal and first-episode stages of BD or b detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.

  7. Neural changes underlying early stages of L2 vocabulary acquisition.

    Science.gov (United States)

    Pu, He; Holcomb, Phillip J; Midgley, Katherine J

    2016-11-01

    Research has shown neural changes following second language (L2) acquisition after weeks or months of instruction. But are such changes detectable even earlier than previously shown? The present study examines the electrophysiological changes underlying the earliest stages of second language vocabulary acquisition by recording event-related potentials (ERPs) within the first week of learning. Adult native English speakers with no previous Spanish experience completed less than four hours of Spanish vocabulary training, with pre- and post-training ERPs recorded to a backward translation task. Results indicate that beginning L2 learners show rapid neural changes following learning, manifested in changes to the N400 - an ERP component sensitive to lexicosemantic processing and degree of L2 proficiency. Specifically, learners in early stages of L2 acquisition show growth in N400 amplitude to L2 words following learning as well as a backward translation N400 priming effect that was absent pre-training. These results were shown within days of minimal L2 training, suggesting that the neural changes captured during adult second language acquisition are more rapid than previously shown. Such findings are consistent with models of early stages of bilingualism in adult learners of L2 (e.g. Kroll and Stewart's RHM) and reinforce the use of ERP measures to assess L2 learning.

  8. Oligometastatic non-small-cell lung cancer: current treatment strategies

    Directory of Open Access Journals (Sweden)

    Richard PJ

    2016-11-01

    Full Text Available Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment

  9. Chemotherapy in non-small cell lung cancer:opportunities for advancement

    Institute of Scientific and Technical Information of China (English)

    Mani Akhtari; Eric H Bernicker; Bin S Teh

    2016-01-01

    Locally advanced non-small cell lung cancer (NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is significant interest in finding more biologically active chemotherapy regimens that can contribute to reduce both failures. The phase III PROCLAIM trial, recently published in the Journal of Clinical Oncology entitled“PROCLAIM: randomized phase III trial of pemetrexed–cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer”, compared two different chemotherapy regimens given concurrently with radiotherapy in patients with stage III non-squamous lung cancer: pemetrexed plus cisplatin versus cisplatin plus etoposide. Both groups received con-solidation chemotherapy. After enrolling 598 of planned 600 patients, the study was stopped early due to futility as no difference was seen in the primary end-point of overall survival. Since PROCLAIM was designed as a superiority trial, these results suggest that pemetrexed regimens do not offer a clinical advantage over standard cisplatin plus etopo-side. There are some subpopulations who might still benefit from pemetrexed, especially if clinicians are concerned about myelosuppression-related adverse events. Future trials are needed to investigate novel biologic agents and irradiation techniques that can result in more durable local and distant disease control in locally advanced NSCLC.

  10. Early stages of irradiation induced dislocations in urania

    Science.gov (United States)

    Chartier, A.; Onofri, C.; Van Brutzel, L.; Sabathier, C.; Dorosh, O.; Jagielski, J.

    2016-10-01

    The early stages of nucleation and growth of dislocations by irradiation in urania is clarified based on the combination of experiments and atomistic calculations. It is established that irradiation induced dislocations follow a five stage process: (i) point defects are first created by irradiation, (ii) they aggregate into clusters, (iii) from which nucleate Frank loops, (iv) which transform into unfaulted loops via Shockley that in turn grow, and (v) finally reorganize into forest dislocations. Stages (i)-(iii) participate in the lattice expansion while the onset of lattice contraction starts with stage (iv), i.e., when unfaulted loops nucleate. Irradiation induced dislocations operate in the spontaneous recombination regime, to be opposed to the thermal diffusion regime. Body of arguments collaborates to this statement, the main one is the comparison between characteristic distances estimated from the dose rate (Vat/(K0×τ ) ) 1/3 and from the diffusion coefficient (D×τ ) 1/2 . Such a comparison identifies materials under irradiation as belonging either into the recombination regime or not.

  11. Early stage design and analysis of biorefinery networks

    DEFF Research Database (Denmark)

    Sin, Gürkan

    2013-01-01

    Recent work regarding biorefineries resulted in many competing concepts and technologies for conversion of renewable bio-based feedstock into many promising products including fuels, chemicals, materials, etc. The design of a biorefinery process requires, at its earlier stages, the selection...... biorefinery concept for a lignocellulosic biorefinery. More specifically we highlight the required information management (management of various sources of data), the superstructure which is needed to represent the design space, generic but simple models covering all the processing steps of biorefineries...... of the process configuration which exhibits the best performances, for a given set of economical, technical and environmental criteria. To this end, we formulate a computer-aided framework as an enabling technology for early stage design and analysis of biorefineries. The tool represents different raw materials...

  12. [Ophthalmologic manifestations in early and late stages of AIDS].

    Science.gov (United States)

    Schnaudigel, O E; Gümbel, H; Richter, R; Subklew, R; Garweg, T

    1994-10-01

    In a prospective study of 101 patients with HIV infection and a medium CD4 lymphocyte cell count of 350 x 10(6)/l and a retrospective study of the records of 79 AIDS patients, we compared the first ocular symptoms in HIV-infected patients to the CD4 count. In Walter-Reed stages 2-4 (n = 101) we found sicca syndrome in 9.2%, in 52% lens opacities in the cortex and only in less than 1% HIV-related angiopathy of the retina. In Walter Reed stages 5-6 (n = 79), 26% of the AIDS patients developed CMV retinitis, 33% HIV angiopathy of the retina and only 1% retinal toxoplasmosis. The average CD4 lymphocyte cell count was never better than 100 x 10(6). Lens opacities in HIV-infected patients could be an early ophthalmological symptom of HIV infection.

  13. Effects of genistein on early-stage cutaneous wound healing.

    Science.gov (United States)

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung; Lim, Yunsook; Kim, Jung-Hyun

    2011-07-08

    Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-κB and TNF-α expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results suggest that genistein supplementation reduces oxidative stress by increasing antioxidant capacity and modulating proinflammatory cytokine expression during the early stage of wound healing.

  14. The application of 18F-fluorodeoxyglucose PET-CT in staging and curative effect evaluation of accepted therapy cases of non-small cell lung cancer%18F-氟脱氧葡萄糖PET-CT在非小细胞肺癌临床分期及经治患者疗效评价中的应用

    Institute of Scientific and Technical Information of China (English)

    曹霞; 谢爱民; 莫逸; 彭翔

    2008-01-01

    目的 评价18F-氟脱氧葡萄糖(18F-FDG)PET-CT在非小细胞肺癌临床分期和经治患者中的应用价值.方法 (1)比较32例初诊患者CT与PET-CT在临床分期上的差别.(2)观察肿瘤大小与最大标准化摄取值(SUVmax)相关性.(3)比较30例经治患者CT、PET-CT发现残留、新发病灶数的差异.结果 (1)PET-CT上调及下调分期各7例,分期改变率43.8%(14/32).PET-CT改变NM分期例数的差别无统计学意义.(2)SUV-与肿瘤大小呈正相关(rs=0.426,P<0.05).(3)PET-CT较CT多发现残留病灶3个(Z=0.520,P0.05),新发病灶数19个(Z=-2.871,P<0.05).结论 18F-FDG PET-CT对确定1P4,细胞肺癌临床分期具有优势;有助于对经治患者新发病灶的榆出.%Objective To assess the use value of 18F-FDG PET-CT in non-small cell lung cancer.Metheds (1) The CT and PET-CT image of 32 cases non-small cell lung cancer cases were compared in staging.(2)The relativety between tumor size and SUVmax was observed.(3) Thirty cases with accepted therapy were compared to find the differences of remains and new outbreak lesions.Results (1) Seven cases were upstaged and 7 cases were downstaged.Changing rate in staging by PET-CT was 43.8% (14/32).The difference of altered stage lymph node and metastasis in number was not in statistical significance by 18F-FDG PET-CT.(2) Spearman grade correlation coefficient rs was 0.426.There were positive correlation between SUVmax and the tumor size (P<0.05).(3) PET-CT found 3 more remain lesions(Z=-0.520,P0.05) and 19 more new outbreak lesion (Z=-2.871,P<0.05) than that of CT.Conclusion 18F-FDG PET-CT had superiority in determining staging of non-small cell lung cancer,and was conducive in cheaking new outbreak lesions of accepted therapy cases.

  15. 三维适形低分割放疗治疗Ⅲ、Ⅳ期非小细胞肺癌疗效观察%Three-dimensional conformal hypofractionated high-dose radiotherapy treatment for Ⅲ, Ⅳ stage non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    党亚正; 李小龙; 陆婉玲; 卫伟; 赵宏亮; 陆宙; 杨婷

    2013-01-01

    Objective: To investigate the clinical efficacy of hypofractionated high - dose radiotherapy treatment for staging Ⅲ, Ⅳ non - small - cell lung cancer. Methods: To analyze 43 lung cancer patients received chest radiation therapy dose fractionation 2. 5Gy/d,5f/w, total dose 50Gy. TNM staging were HI 17 cases, IV 26 cases. Results: Followed up for 4 - 12 months, follow - up rate was 100% ; Radiation esophagitis incidence was 34. 9% . The second class above radioactive pneumonia rate was 11.6%. CR 25. 6% ,PR 51. 2% SD 14.0% PD 9. 3% ; 1 - year survival rate was 65. 1%. Conclusion: Recent curative effect of non - small cell lung cancer patients with stage Ⅲ, Ⅳ treated by three - dimensional conformal hypofractionated high — dose radiotherapy is good, side effects can be tolerated.%目的:探讨低分割放疗治疗Ⅲ、Ⅳ期非小细胞肺癌的临床疗效.方法:分析接受胸部放疗肺癌患者43例,分割剂量2.5Gy/天,5次/周,总剂量50Gy; TNM分期Ⅲ、Ⅳ期17、26例.结果:随访4-12个月,随访率100%.放射性食管炎发生率34.9%,2级以上放射性肺炎发生率11.6%.近期疗效:CR 25.6%、PR51.2%、SD 14.0%、PD 9.3%;1年生存率65.1%.结论:三维适形低分割放疗对Ⅲ、Ⅳ期非小细胞肺癌患者近期疗效确切,放疗毒副反应可以耐受.

  16. USANS investigation of early stages of metal foam formation

    CERN Document Server

    Bellmann, D; Banhart, J

    2002-01-01

    Metallic foams are on the verge of being used in industrial applications. However, the mechanism of foam creation, especially the early stages, are still unexplored. Ultra small-angle neutron scattering (USANS), performed with the double-crystal diffractometer (DCD) at the Geesthacht Neutron Facility (GeNF), is a promising method for obtaining a three-dimensional average of a pore size distribution in a wide size range from about 100 nm to about 20 mu m. Analysis of the neutron scattering curves yielded pore size distributions which conformed with the results obtained by microscopy. (orig.)

  17. Histopathological diagnosis of acral lentiginous melanoma in early stages.

    Science.gov (United States)

    Fernandez-Flores, Angel; Cassarino, David S

    2017-02-01

    Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma.

  18. In vivo research using early life stage models.

    Science.gov (United States)

    Seabra, Rita; Bhogal, Nirmala

    2010-01-01

    Scientists, for a variety of reasons, need to carry out in vivo research. Since experiments that require the use of adult animals pose various logistical, economical and ethical issues, the use of embryonic and larval forms of some organisms are potentially attractive alternatives. Early life stages are appealing because, in general, large numbers of individuals can be maintained in relatively simple housing, minimising costs, and their use involves fewer legal formalities. With this succinct review, we aim to provide an overview of different biological issues that have been successfully explored with the help of eggs, embryos and larvae from the frog, zebrafish and chicken.

  19. The studies of nodular graphite cast iron early stages austempering

    OpenAIRE

    A. Krzyńska; M. Kaczorowski

    2008-01-01

    The results of early stage of ductile cast iron austempering are presented. The aim of the investigations was to look closer into the structure – mechanical properties relationships of this very attractive cast material. The experiment was carried out with enriched with Cu EN-GJS-500-7 grade ductile iron. The specimens were first solution heat treated 1 hour in 910oC and then isothermally quenched for different time in molten tin at the temperature 275oC. The mechanical properties of as cast ...

  20. Nontrivial dynamics in the early stages of inflation

    CERN Document Server

    Calzetta, E A

    1995-01-01

    Abstract: Inflationary cosmologies, regarded as dynamical systems, have rather simple asymptotic behavior, insofar as the cosmic baldness principle holds. Nevertheless, in the early stages of an inflationary process, the dynamical behavior may be very complex. In this paper, we show how even a simple inflationary scenario, based on Linde's ``chaotic inflation'' proposal, manifests nontrivial dynamical effects such as the breakup of invariant tori, formation of cantori and Arnol'd's diffusion. The relevance of such effects is highlighted by the fact that even the occurrence or not of inflation in a given Universe is dependent upon them.

  1. Emerging Literature on Cognitive Intervention Techniques for Early Stage Dementia

    Directory of Open Access Journals (Sweden)

    John W Den Boer

    2016-10-01

    Full Text Available Dementia is a growing world-wide phenomenon, impacting more than six million people in the United States. Despite its high projected prevalence, it is a significantly under-represented phenomena, with (underestimate ranging from 15-25% of the general population. The effect of the aging of the population and significant increase in life expectancy has combined to catapult dementia into the range of one of most alarming healthcare problems. Diverse and emerging literature in the area of cognitive prevention/intervention for mild cognitive impairment (MCI/early stage dementia will be reviewed. Additionally, future research and clinical directions will be explored.

  2. Reproductive and early life stages pathology - Histopathology workshop report

    Science.gov (United States)

    Bruno, D.W.; Nowak, B.; Elliott, D.G.

    2006-01-01

    Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.

  3. A patient with medulloblastoma in its early developmental stage.

    Science.gov (United States)

    Shinojima, Naoki; Nakamura, Hideo; Tasaki, Masayoshi; Kameno, Kouki; Anai, Shigeo; Iyama, Ken-ichi; Ando, Yukio; Seto, Hiroshi; Kuratsu, Jun-Ichi

    2014-12-01

    Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups- WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)-since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap-that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

  4. On Branching Processes and the Early Stages of the Spread of an Epidemic

    Institute of Scientific and Technical Information of China (English)

    Ahmed E; Yassen M T

    1998-01-01

    Branching process (BP) is used to model the early stages of the spread of a sexually transmitted disease. The early stages of AIDS spread which is transmitted both homosexually and heterosexually are studied as a BP.

  5. The effects of blocking angiotensin receptors on early stages of diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Alaleh Gheissari

    2012-01-01

    Conclusion: Angiotensin receptor blockers may reduce VCAM-1 and microalbuminuria and may increase NO levels in early stages of DN. Thus administration of ARBs might be considered even in early stages of DN.

  6. The surgical management of early-stage cervical cancer.

    Science.gov (United States)

    Salicrú, Sabina R; de la Torre, Javier F V; Gil-Moreno, Antonio

    2013-08-01

    The main objective is to update the literature data in the last year which may support a surgical approach to early cervical cancer [ECC; Stage International Federation of Gynecology and Obstetrics (FIGO) IA-IB1-IIA1]. Radical hysterectomy remains the gold standard by most international guidelines because surgical treatment has hardly changed in recent decades, except for stage IA1. Trends in clinical research in the past 12-18 months involve minimal invasive surgery (with laparoscopic surgery or robotic-assisted surgery), fertility preservation (in the initial stages and in the absence of bad prognostic factors), nerve-sparing and sentinel node techniques. Some institutions have published studies in specific groups such as older, obese or pregnant women. There is a growing trend to practice less aggressive surgery in order to preserve fertility in young women and avoid an excess of treatment in some selected patients. Therefore, nerve-sparing techniques can help to improve the quality of life. More studies are needed to demonstrate oncologic results of the sentinel node technique. Laparoscopic and robotic-assisted surgery can substitute open surgical treatment.

  7. Conservative surgery and radiation for early-stage breast cancer.

    Science.gov (United States)

    Fowble, B L; Orel, S G; Jardines, L

    1993-07-01

    In selected patients with early-stage breast cancer, conservative surgery and radiation represent an alternative equal to mastectomy in terms of local recurrence, distant metastasis, survival, and long-term complications. Patients with early-stage breast cancer who are candidates for conservative surgery and radiation include those whose primary tumor is less than 4 to 5 cm in size without evidence of gross multicentricity or diffuse microcalcifications. Patients with an extensive intraductal component may be appropriate candidates provided that margins of resection are negative. Young age is not a contraindication to the conservative treatment. A preexisting history of collagen vascular disease or prior mantle irradiation for Hodgkin's or non-Hodgkin's lymphoma represents a contraindication to conservative surgery and radiation because of the potential for severe complications. An additional contraindication is the pregnant woman in whom delivery cannot be accomplished before the initiation of radiation. Mammography is essential in the pretreatment evaluation and posttreatment follow-up of the conservatively treated patient. The goal of the pretreatment mammogram is to assess the extent of disease in the ipsilateral breast as well as to evaluate the contralateral breast. In patients who present with microcalcifications, a postbiopsy mammogram before radiation is essential to document complete removal of all malignant-appearing microcalcifications. Mammography is an essential part of the follow-up program in order to detect a recurrence in the treated breast as well as a cancer in the contralateral breast cancer. The optimal interval for follow-up mammography has not been determined, although programs employing mammography on a yearly basis after treatment have been associated with the detection of early recurrences and excellent survival after salvage mastectomy for these recurrences.

  8. Early stage health technology assessment (HTA) of biomedical devices: the MATCH experience

    OpenAIRE

    Pecchia, Leandro; Craven, Michael P

    2013-01-01

    Early stage Health Technology Assessment (HTA) of biomedical devices requires different methods than those usually employed for pharmaceuticals. This paper reviews widely used methods for HTA, discusses their limits for early stage evaluation of biomedical devices and presents two methods for early stage HTA being developed in the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH) project: Analytic Hierarchy Process (AHP) to elicit user needs; and early stage economic ev...

  9. Early stage health technology assessment (HTA) of biomedical devices: the MATCH experience

    OpenAIRE

    Pecchia, Leandro; Craven, Michael P

    2013-01-01

    Early stage Health Technology Assessment (HTA) of biomedical devices requires different methods than those usually employed for pharmaceuticals. This paper reviews widely used methods for HTA, discusses their limits for early stage evaluation of biomedical devices and presents two methods for early stage HTA being developed in the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH) project: Analytic Hierarchy Process (AHP) to elicit user needs; and early stage economic e...

  10. Actualización en el tratamiento del cáncer pulmonar de células no pequeñas en etapa IIIA con afectación N2 Update on treatment of stage IIIA non-small cell lung cancer with N2 disease

    Directory of Open Access Journals (Sweden)

    Miguel Emilio García Rodríguez

    2012-09-01

    Full Text Available Los pacientes afectados de cáncer de células no pequeñas del pulmón en etapa IIIA, con afectación ganglionar N2, son comunes y considerados por muchos médicos como un subgrupo heterogéneo, y su tratamiento es controversial. Con el objetivo de realizar una revisión bibliográfica actualizada del tema en cuestión y definir cuáles son las opciones de tratamiento de estos enfermos en esta etapa, se realizó una búsqueda de resúmenes y artículos completos en diferentes bases de datos (Medline, Cochrane, Pubmed, Ebsco, Hinari, y se utilizó para ello el buscador End Note, con las siguientes palabras en inglés y su traducción en español: lung cáncer, stage IIIA, radiotherapy, chemotherapy, adyuvant treatment, surgery, limphoadenectomy. El manejo óptimo de pacientes en etapa IIIA N2 permanece como una de las áreas más polémicas en el cuidado del paciente con cáncer pulmonar de células no pequeñas, probablemente por las amplias variaciones patológicas en esta etapa, por lo que se acepta el tratamiento quirúrgico de primera intención en aquellos pacientes con una enfermedad N2 mínima y en el otro extremo se realiza tratamiento con quimiorradioterapia definitivo o prequirúrgico de inducción en casos seleccionados.The patients suffering stage IIIA non-small cell lung cancer with N2 ganglionic diseases are common and considered as an heterogeneous group by many physicians. Their treatment arouses controversies. For the purpose of making an updated literature review on this topic and defining the treatment options for these patients on this stage III, a number of full articles and of abstracts was searched on several database (Medline, Cochrane, Pubmed, Ebsco, Hinari. To this end, the End Note locator was used with the following English words and their respective Spanish translations: lung cancer, stage IIIa, radiotherapy, chemotherapy, adjuvant treatment, surgery, lymphoadenectomy. The optimal management of patients classified

  11. Treatment Option Overview (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small ... clinical trials before, during, or after starting their cancer treatment. Some clinical trials only include patients who have ...

  12. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  13. Adjuvant chemotherapy for completely resected non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Toyooka,Shinichi

    2009-10-01

    Full Text Available For many years, surgery alone was the standard treatment for patients with stage I-IIIA non-small-cell lung cancer (NSCLC. However, recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit. The first adjuvant chemotherapy for NSCLC was performed in the 1960s using a key drug known as cyclophosphamide. In the 1980s and early 1990s, a new anti-cancer drug, cisplatin, was developed. The first meta-analysis of this drug was conducted by the Non-small Cell Lung Cancer Collaborative Group in 1995. This analysis comparing surgery with surgery plus chemotherapy containing cisplatin produced a hazard ratio of 0.87 and suggested an absolute benefit of chemotherapy of 5% at 5 years;this difference was not statistically significant (p0.08. Several clinical trials of adjuvant chemotherapy were planned after the meta-analysis conducted in 1995, but the efficacy of adjuvant chemotherapy remained a matter of controversy. However, useful evidence was reported after 2003. The International Adjuvant Lung Cancer Collaborative Group Trial (IALT demonstrated a 4.1% improvement in survival for patients with stage I to III NSCLC. The JBR. 10 trial demonstrated a 15% improvement in 5-year survival for the adjuvant chemotherapy arm in stage IB or II (excluding T3N0 patients. The Adjuvant Navelbine International Trialist Association (ANITA trial reported that the overall survival at 5 years improved by 8.6% in the chemotherapy arm and that this survival rate was maintained at 7 years (8.4% in stage II and IIIA patients. A meta-analysis based on collected and pooled individual patient data from the 5 largest randomized trials was conducted by the Lung Adjuvant Cisplatin Evaluation (LACE. This analysis demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with stage II or III cancer. Alterna-tively, uracil-tegafur has been developed and tested in Japan. The Japan Lung Cancer Research Group (JLCRG on Postsurgical

  14. Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

    Science.gov (United States)

    García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

    2016-01-01

    Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Chemotherapy versus best supportive care in stage IV non-small cell lung cancer, non metastatic to the brain Quimioterapia versus melhor tratamento de suporte em câncer de pulmão estádio clínico IV não metastático para o sistema nervoso central

    Directory of Open Access Journals (Sweden)

    Agnaldo Anelli

    2001-04-01

    Full Text Available Stage IV non-small cell lung cancer is a fatal disease, with a median survival of 14 months. Systemic chemotherapy is the most common approach. However the impact in overall survival and quality of life still a controversy. OBJECTIVES: To determine differences in overall survival and quality of life among patients with stage IV non-small cell lung cancer non-metastatic to the brain treated with best supportive care versus systemic chemotherapy. PATIENTS: From February 1990 through December 1995, 78 eligible patients were admitted with the diagnosis of stage IV non-small cell lung cancer . Patients were divided in 2 groups: Group A (n=31 -- treated with best supportive care , and Group B (n=47 -- treated with systemic chemotherapy. RESULTS: The median survival time was 23 weeks (range 5 -- 153 weeks in Group A and 55 weeks (range 7.4 -- 213 weeks in Group B (p=0.0018. In both groups, the incidence of admission for IV antibiotics and need of blood transfusions were similar. Patients receiving systemic chemotherapy were also stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and those receiving other combination regimens (platinum derivatives associated with other drugs, n=22. Patients receiving mytomycin, vinblastin, and cisplatinum, n=25 had a higher incidence of febrile neutropenia and had their cycles delayed for longer periods of time than the other group. These patients also had a shorter median survival time (51 versus 66 weeks, p=0.005. CONCLUSION: In patients with stage IV non-small cell lung cancer, non-metastatic to the brain, chemotherapy significantly increases survival compared with best supportive care.O câncer de pulmão de células não pequenas em estádio IV é uma doença fatal, com uma sobrevida mediana de seis meses. Quimioterapia é a abordagem mais freqüente, apresentando um impacto na sobrevida controverso e questionável alteração na qualidade de vida. OBJETIVOS: Comparar o impacto na

  16. Early Stage Disease Diagnosis System Using Human Nail Image Processing

    Directory of Open Access Journals (Sweden)

    Trupti S. Indi

    2016-07-01

    Full Text Available Human’s hand nail is analyzed to identify many diseases at early stage of diagnosis. Study of person hand nail color helps in identification of particular disease in healthcare domain. The proposed system guides in such scenario to take decision in disease diagnosis. The input to the proposed system is person nail image. The system will process an image of nail and extract features of nail which is used for disease diagnosis. Human nail consist of various features, out of which proposed system uses nail color changes for disease diagnosis. Here, first training set data is prepared using Weka tool from nail images of patients of specific diseases. A feature extracted from input nail image is compared with the training data set to get result. In this experiment we found that using color feature of nail image average 65% results are correctly matched with training set data during three tests conducted.

  17. Scalpel or SABR for Treatment of Early-Stage Lung Cancer: Clinical Considerations for the Multidisciplinary Team

    Directory of Open Access Journals (Sweden)

    Joe Y. Chang

    2011-09-01

    Full Text Available Treatment options for early-stage (T1-2 N0 non-small cell lung cancer are often limited by the patient’s advanced age, poor performance status, and comorbidities. Despite these challenges, stereotactic ablative radiotherapy (SABR provides a highly effective and safe therapy for intrathoracic tumors and has become the standard of care for delivering definitive treatment in medically inoperable patients. High-quality treatment, which includes reliable immobilization, accurate tumor targeting, and precise verification of dose delivery, is essential both to achieve successful cure and to avoid debilitating toxicities. Generally, SABR is well tolerated in patients with peripherally located tumors, but even centrally or superiorly located lesions can be treated if there is adequate conformal avoidance of normal structures and/or modified fractionation to meet dose constraints. While several preliminary studies suggest that SABR is as efficacious as surgery in operable patients, results of randomized data will illuminate whether the indications for SABR can be expanded to include patients who are candidates for surgical resection. Herein, we review the rationale for using SABR and its application in treating different patient populations with early-stage lung cancer.

  18. Infrared coagulation versus rubber band ligation in early stage hemorrhoids

    Directory of Open Access Journals (Sweden)

    P.J. Gupta

    2003-10-01

    Full Text Available The ideal therapy for early stages of hemorrhoids is always debated. Some are more effective but are more painful, others are less painful but their efficacy is also lower. Thus, comfort or efficacy is a major concern. In the present randomized study, a comparison is made between infrared coagulation and rubber band ligation in terms of effectiveness and discomfort. One hundred patients with second degree bleeding piles were randomized prospectively to either rubber band ligation (N = 54 or infrared coagulation (N = 46. Parameters measured included postoperative discomfort and pain, time to return to work, relief in incidence of bleeding, and recurrence rate. The mean age was 38 years (range 19-68 years. The mean duration of disease was 17.5 months (range 12 to 34 months. The number of male patients was double that of females. Postoperative pain during the first week was more intense in the band ligation group (2-5 vs 0-3 on a visual analogue scale. Post-defecation pain was more intense with band ligation and so was rectal tenesmus (P = 0.0059. The patients in the infrared coagulation group resumed their duties earlier (2 vs 4 days, P = 0.03, but also had a higher recurrence or failure rate (P = 0.03. Thus, we conclude that band ligation, although more effective in controlling symptoms and obliterating hemorrhoids, is associated with more pain and discomfort to the patient. As infrared coagulation can be conveniently repeated in case of recurrence, it could be considered to be a suitable alternative office procedure for the treatment of early stage hemorrhoids.

  19. Locomotor function in the early stage of Parkinson's disease.

    Science.gov (United States)

    Carpinella, Ilaria; Crenna, Paolo; Calabrese, Elena; Rabuffetti, Marco; Mazzoleni, Paolo; Nemni, Raffaello; Ferrarin, Maurizio

    2007-12-01

    The cardinal motor symptoms of Parkinson's disease (PD) have been widely investigated with particular reference to abnormalities of steady-state walking. The great majority of studies, however are related to severe forms of PD patients (phases > = 3 of Hoehn and Yahr scale), where locomotor abnormalities are clearly manifested. Goal of the present study was to quantitatively describe locomotor symptoms in subjects with mild PD. Accordingly, a multitask protocol involving instrumental analysis of steady-state linear walking, initiation of gait, and turning while walking was applied to a group of patients with idiopathic PD in their early clinical stage (phases 1 and 2 of Hoehn and Yahr scale), as well as in age-matched elderly controls. Kinematic, kinetic, and myoelectric measures were obtained by optoelectronic motion analysis, force platform, and telemetric electromyography. Results in PD patients showed a tendency to bradykinetic gait, with reduction of walking speed and cadence. Impairments of gait initiation consisted in reduction of the backward shift of the center of pressure (CoP) and prolongation of the stepping phase. Alterations of the turning task were more consistent and included delayed reorientation of the head toward the new direction, altered head-upper trunk rotational strategy, and adoption of a greater number of steps to complete the turning. It is concluded that patients in the early stage of PD reveal mild alterations of steady-state linear walking and more significant anomalies in the transitional conditions, especially during changes in the travel direction. Quantitative analysis of nonstationary locomotor tasks might be a potentially useful starting point for further studies on the pathophysiology of PD.

  20. Paranasal Manifestations of Early Stage Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ceren Günel

    2015-04-01

    Full Text Available OBJECTIVE: Chronic lymphocytic leukemia (CLL is the most common adult leukemia. A few studies have been reported about the relationship between CLL and paranasal sinuses. We aimed to investigate the paranasal manifestations of CLL and to determine the expression of nuclear factor-ĸB (NF-kB and tumor necrosis factor (TNF-α in the nasal mucosa in patients with CLL. MATERIALS AND METHODS: This study was a clinical trial that involved 40 patients. Group CLL (n=20 consisted of patients with early-stage CLL who were followed-up at the hematology clinic and who did not receive any treatment. The control group (n=20 consisted of patients who had undergone concha surgery because of nasal obstruction. Paranasal sinus computer tomography scans of all patients were taken, they were scored on the basis of the Lund–Mackay system, and sinusitis findings were recorded. The biopsy material taken from the inferior concha head of all patients was immunohistochemically stained with primary antibodies against NF-kB and TNF-α. RESULTS: There were no statistically significant differences between the two groups with respect to NF-κB (p=0.716 and TNF-α staining scores (p=1.000. The Lund–Mackay scores were significantly higher in the CLL group than in the control group (p=0.004. Fourteen patients had sinusitis at different locations, while the most common diagnosis was maxillary sinusitis (n=8 in the CLL group. CONCLUSION: This study showed that patients with early-stage CLL tend to have rhinosinusitis. However, NF-kB and TNF-α may not have a role in the inflammatory process involving the paranasal sinuses in patients with CLL.

  1. QUALITY ASSURANCE OF 4D-CT SCAN TECHNIQUES IN MULTICENTER PHASE III TRIAL OF SURGERY VERSUS STEREOTACTIC RADIOTHERAPY (RADIOSURGERY OR SURGERY FOR OPERABLE EARLY STAGE (STAGE 1A) NON-SMALL-CELL LUNG CANCER [ROSEL] STUDY)

    NARCIS (Netherlands)

    Hurkmans, Coen W.; van Lieshout, Maarten; Schuring, Danny; van Heumen, Marielle J. T.; Cuijpers, Johan P.; Lagerwaard, Frank J.; Widder, Joachim; van der Heide, Uulke A.; Senan, Suresh

    2011-01-01

    Purpose: To determine the accuracy of four-dimensional computed tomography (4D-CT) scanning techniques in institutions participating in a Phase III trial of surgery vs. stereotactic radiotherapy (SBRT) for lung cancer. Methods and Materials: All 9 centers performed a 4D-CT scan of a motion phantom (

  2. Longitudinal trajectories of awareness in early-stage dementia.

    Science.gov (United States)

    Clare, Linda; Nelis, Sharon M; Martyr, Anthony; Whitaker, Christopher J; Marková, Ivana S; Roth, Ilona; Woods, Robert T; Morris, Robin G

    2012-01-01

    Although it is often assumed that awareness decreases as dementia severity increases, there is limited evidence regarding changes in awareness over time. We examined awareness in 101 individuals with early-stage dementia (PwD) and their carers; 66 were reassessed after 12 months and 51 were seen again at 20 months. Awareness was assessed in relation to memory, everyday activities, and socio-emotional functioning using discrepancies between PwD and carer ratings on parallel questionnaires. PwD completed neuropsychological tests and measures of mood and quality of life. Carers completed measures of mood and stress. At initial assessment, discrepancies were greatest for activities of daily living, moderate for memory, and least pronounced for socio-emotional functioning. Discrepancy scores did not change over time. PwD self-ratings indicated perceived poorer functioning in everyday activities over time, but no change for memory and socio-emotional functioning. Carer ratings indicated perceived decline in everyday activities and socio-emotional functioning, but no change for memory. PwD declined in neuropsychological functioning, but self-ratings of depression, anxiety, and quality of life remained stable over time. Carer mood and stress levels also remained stable. At least in the earlier stages of dementia, it should not be assumed that awareness will inevitably decrease as dementia progresses.

  3. Treatment of early-stage Hodgkin lymphoma.

    Science.gov (United States)

    Engert, Andreas; Raemaekers, John

    2016-07-01

    Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed.

  4. HYPERMETHYLATION OF p14ARF PROMOTER REGION AND EXPRESION OF p14ARF GENE PRODUCT IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    TIAN Kai-hua; SHEN Yi; LUO Yi-rne; WANG Ming-zhao; LIU Hong-xu; ZHAO Hui-ru; ZHANG Lin

    2006-01-01

    Objective: This study was designed to investigate promoter methylation status and protein expression of p14ARF gene in non-small cell lung cancer, and value the role of p14ARF promoter methylation in carcinogenesis of non-small cell lung cancer. Methods: Promoter methylation status and protein expression of p14ARF gene in 40 cases of non-small cell lung cancer were analyzed by methylation specific polymerase china reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR) and immunohistochemistry (IHC). Results: The positive rates of p14ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer were 17.5% (7/40) and 2.5% (1/40) respectively. There were statistically significant differences between them, P<0.05. The results of RE-PCR were consistent with that of MSP. The expression rate of p14ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer, p<0.01. Promoter methylation status and protein expression of p14ARF gene in non-small cell lung cancer showed significantly an inverse correlation (r=-0.56, P<0.01), and both of them did not relate statistically with the clinicopathologic characteristics of patients such as histological classification, clinical stage, differentiation grade and lymph node involvement. Conclusion: Promoter methylation is a crucial mechanism of inactivation of p14ARF gene. Promoter methylation of p14ARF gene might be involved in carcinogenesis of non-small cell lung cancer, and is an early event in development process of non-small cell lung cancer. It might be used as a new target in gene treatments in the future.

  5. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    Science.gov (United States)

    Kang, Guhyun; Hwang, Woo Cheol; Do, In-Gu; Wang, Kai; Kang, So Young; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kang, Won Ki; Jang, Jiryeon; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Min Ji; Kim, Seonwoo; Park, Cheol Keun; Kim, Kyoung-Mee

    2013-01-01

    Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  6. Radiation therapy for early stages of Morbus Ledderhose

    Energy Technology Data Exchange (ETDEWEB)

    Heyd, Reinhard [Dept. of Radiotherapy, Klinikum Offenbach (Germany); Dorn, Anne Pia; Mueller-Schimpfle, Marcus [Central Inst. of Radiology, Municipal Hospitals, Frankfurt/Main-Hoechst (Germany); Herkstroeter, Markus [Radiotherapeutic Practice at the Municipal Hospitals, Frankfurt/Main-Hoechst (Germany); Roedel, Claus; Fraunholz, Ingeborg [Dept. of Radiotherapy and Oncology, Univ. Hospital Frankfurt/Main (Germany)

    2010-01-15

    Purpose: To evaluate the efficacy of radiation therapy (RT) in the treatment of early stages of benign plantar fibromatosis (Morbus Ledderhose [ML]). Patients and Methods: From 2003 to 2008, 24 patients (33 sites) with a mean age of 52 years received RT for symptomatic ML. Prior to RT, 19 patients complained of pain and 15 had walking difficulties. 21 patients (28 sites) were irradiated with orthovolt-age X-rays and three (five sites) received electron-beam irradiation. The RT protocol consisted of five weekly fractions of 3.0 Gy (15 Gy), repeated after 6 weeks to a total dose of 30 Gy in 20 patients (28 sites). In four patients (five sites), two single fractions of 4.0 Gy were applied, repeated at intervals of 4 weeks to total doses of 24-32 Gy. Primary study endpoints were the prevention of disease progression and the avoidance of a surgical intervention. Secondary endpoints were pain relief, improvement of gait, and patients' subjective satisfaction measured with a linear analog scale (LAS). Results: After a median follow-up of 22.5 months, none of the patients experienced a progression of number and size of the lesions or the clinical symptoms. In eleven sites (33.3%) complete remission of cords or nodules occurred, in 18 (54.5%) a reduced number or size was noted, and four sites (12.1%) were unchanged. Pain relief was achieved in 13/19 patients (68.4%), and an improvement of gait abnormalities was noted in 11/15 patients (73.3%). The patients' subjective satisfaction measured by means of the LAS revealed a median improvement of 3.5 points in 22/24 patients (91.6%). Skin or soft tissues toxicities RTOG grade > 2 were not noted. Conclusion: RT is effective for treatment of the early stages of ML and may obviate the need for a surgical intervention. Long-term follow-up studies including a larger number of patients are required to define the role of RT in the management of this disorder. (orig.)

  7. Native language change during early stages of second language learning.

    Science.gov (United States)

    Bice, Kinsey; Kroll, Judith F

    2015-11-11

    Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The coactivation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as in the second language (L2). The present study questioned whether L1 changes can be detected at early stages of L2 learning and how they are modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared with noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. In addition, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that L2 affects L1 only when L2 speakers are highly proficient, L2 learning begins to impact L1 early in the development of the L2 skill.

  8. Usefulness of {sup 99m}Tc-depreotide scintigraphy for the diagnosis of bone metastases in non-small cell lung cancer stage 3-4; Apport de la scintigraphie au {sup 99m}Tc-depreotide pour le diagnostic de lesions osseuses secondaires dans le cancer bronchopulmonaire non a petites cellules stade 3-4

    Energy Technology Data Exchange (ETDEWEB)

    Costo, S.; Dunet, V.; Agostini, D.; Bouvard, G. [CHU Cote de Nacre, Service de Medecine Nucleaire et Isotopes, 14 - Caen (France); Halley, A. [Centre Havrais d' Imagerie Nucleaire, 76 - Montivilliers (France); Bergot, E.; Porret, E.; Zalcman, G. [CHU Cote de Nacre, Service de Pneumologie, 14 - Caen (France)

    2009-02-15

    Objective In non-small cell lung cancer (NSCLC), metastatic bone involvement is usually assessed using conventional {sup 99m}Tc-HMDP bone scintigraphy, which has a high sensitivity but a poor specificity. The purpose of this study was to assess the usefulness of the {sup 99m}Tc-D scintigraphy for the detection of malignant bone metastases in patients with NSCLC stage III or IV and to compare these results with {sup 99m}Tc-HMDP bone scan findings. Methods Nineteen patients (13 M and 6 F, mean age 59 years) with proven NSCLC, suspected to have stage III or IV were enrolled prospectively. All patients underwent whole body {sup 99m}Tc-HMDP and {sup 99m}Tc-D scintigraphy to detect bone metastases within a mean interval of 14 days. Each focal uptake of {sup 99m}Tc-D or {sup 99m}Tc-HMDP was considered benign or malignant, leading to positive or negative diagnosis for bone involvement. The final diagnosis of bone metastases was established by a lung specialist, on the basis of additional imaging modalities and of 12 months follow-up. Results Twelve bone lesions were identified by {sup 99m}Tc-D scintigraphy, 10 were classified as bone metastases and two were classified as inflammatory bone lesions. Four patients were metastatic. Fifty eight bone lesions were detected by {sup 99m}Tc-HMDP scintigraphy, 26 of whom were considered malignant, eight patients were thus considered metastatic. Thereby, the two nuclear medicine modalities were concordant for 13 patients, that is 68% of cases and were discordant for six patients, representing 32% of cases. Diagnostic sensitivity, specificity and accuracy of depreotide scintigraphy and {sup 99m}Tc-HMDP bone scintigraphy were 75% for both, 93.3 and 73.3%, and 89.5 and 73.3% respectively. Conclusion Our data suggest that depreotide scintigraphy with the same sensitivity, a better accuracy and specificity than those of {sup 99m}Tc-HMDP bone scan can detect metastatic bone lesions in patients with NSCLC suspected to have stage III or IV

  9. Recent Therapeutic Effect of Late Course 3 Dimensional Conformal Therapy Concomitant with Chemotherapy on StageNon-small-cell Lung Cancer%后程适形放射治疗联合化学疗法治疗Ⅲ期非小细胞肺癌近期疗效观察

    Institute of Scientific and Technical Information of China (English)

    赵彩霞; 任勇军; 文世民; 李光明; 潘荣强

    2011-01-01

    目的 探讨后程适形放射治疗(3 dimensional cornformal radiation therapy,3D-CRT)同步化学疗法治疗Ⅲ期非小细胞肺癌(non-small-cell lung cancer,NS4CLC)的近期疗效.方法 搜集2005年1月-2008年6月NSCLC患者共115例,其中53例行单纯后程3D-CRT(单放组),62例行后程3D-CRT联合同步化学疗法(联合组),所有患者均经病理证实为Ⅲ期NSCLC.两组放射治疗方案均采用常规分割治疗加后程3D-CRT,DT 62~72Gy.联合组化学疗法采用TP(紫杉醇+顺铂)方案.结果 单放组和联合组近期疗效(完全缓解+部分缓解)分别为75.47%、91.94%,差异有统计学意义(P<0.05).单放组和联合组的治疗不良反应主要有白细胞、血小板减少,放射性食管炎,放射性气管炎,恶心、呕吐等胃肠道反应.骨髓抑制和消化道反应,联合组稍高于单放组.经对症治疗后,所有患者均可耐受.结论 后程3D-CRT联合TP方案化学疗法较单纯后程适形放射治疗明显提高Ⅲ期NSCLC近期疗效.患者耐受性尚可.%Objective To observe the recent therapeutic effect of late course 3 dimensional conformal therapy concomitant with chemotherapy on locally advanced stagenon-small-cell lung cancer (NSCLC). Methods From January 2005 to June 2008, 115 patients with stage Ⅲ NSCLC were confirmed by pathology, in whom 53 only underwent late course conformal therapy (radiotherapy group), and another 62 underwent late course conformal therapy concomitant with chemotherapy (combined group). The radiotherapy schema of the two groups was routine division plus late course conformal therapy (with DT 62-72 Gy). The chemotherapy schema in the combined group was performed with TP (paclitaxel and DDP). Results The recent curative effect (complete remission plus partial remission) in radiotherapy group and combined group was 75. 47% and 91. 94%, respectively (P<0. 05). The frequent adverse reactions in the two groups included leucocytopenia, thrombocytopenia

  10. Efficiency of teaching patients with early-stage rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Evgenia Vladislavovna Orlova

    2014-01-01

    Full Text Available Education programs are an important part of the management of patients with rheumatoid arthritis (RA.Objective: to develop a unified model of an education program for RA patients and to evaluate its efficiency at the early stage of the disease.Material and methods. A group education program was worked out with the support of the All-Russian public organization of the disabled “The Russian rheumatology organization “Nadezhda” (Hope” and encompassed 4 daily classes lasting 90 min. All information was presented by a multidisciplinary team of specialists (rheumatologists, a cardiologist, a psychologist, a physiotherapist, and a physical trainer. The study included 55 patients with early RA (89.1% of women aged 18 to 62 years; the duration of the disease was 2 to 22 months; of them 25 were taught using the education program (a study group; 30 received drug therapy only (a control group. Following 3 and 6 months, the number of tender and swollen joints, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and pain were determined applying a 100-ml VAS, DAS28, HAQ, and RAPID3. Adherence to non-drug treatments was assessed employing a special patient questionnaire.Results. Three and six months after being taught, two patient groups showed increases in adherence to joint protection methods by 13 and 10 times (p<0.01, regular physical training by 4 and 3.25 times (p<0.01, uses of orthoses for the wrist joint by 2 times and 75% (p<0.01 and knee orthoses by 33.3 and 50.0% (p<0.01, and orthopedic insoles by 71.4 and 57.1% (p<0.01, respectively. Following 6 months, there were statistically significant differences between the two groups in most parameters (p<0.05, except for ESR, CRP, and DAS28 (p>0.05. Further more, a good response to treatment was significantly more common in these periods, as shown by the EULAR response criteria (DAS28: 56.3% versus 40% in the control group (p<0.05.Conclusion. The education program decreases the intensity

  11. 多层螺旋CT首过期灌注成像和肿瘤微血管密度在评价周围型肺癌TNM分期的临床价值%Clinical Value of 16 Slice Spiral CT Perfusion Enhancement Parameters and Histological Microvessel Density in TNM Staging of Peripheral Non-small Cell lung Cancer

    Institute of Scientific and Technical Information of China (English)

    邓东; 武莹莹; 黄仲奎; 龙莉玲; 张小波; 李春兰; 林创武; 曾冠珍; 冯启明

    2011-01-01

    (CTP) enhancement parameters and histological microvessel density (MVD) in TNM staging of peripheral non-small cell lung cancer.Materials and Methods Thirty two patients with pathology proved peripheral non small cell lung cancer underwent CT perfusion scan before operation.The enhance index of CT perfusion were calculated based on the time-density curves (TDC) of fist pass phase.All cases were classified into several groups:diameter ≤3 cm and diameter of 3 -7 cm group,pleural invasion and no pleural invasion group,mediastinum lymphatic involvement and without mediastinum lymphatic involvement group,TNM staging of Ⅰ - Ⅱ and Ⅲ - Ⅳ group.The correlations were analyzed between the enhance index of CT perfusion with MVD.Two sample t or t' test was used for the statistics.The ROC curve was used to estimate the efficiency of the enhance index of CT perfusion and MVD in TNM staging of lung cancer.Results ( 1 ) CTP enhance index( PH, M/A, PV) and MVD between small ( diameter of ≤ 3 cm) and big ( diameter of 3 - 7 cm) tumor had no significant difference ( P > 0.05 ).( 2 ) PV and MVD were higher in tumors invloved pleura than without pleural invasion group( P < 0.05 ).(3) Tumors with mediastinum lymphatic involvement had significantly higher value of The CTP enhance index (PV 、PH 、M/A)and MVD than those without medistinum lymphatic involvement ( P < 0.01 ).(4) Tumors of Ⅲ - Ⅳ staging had higher value of CTP enhance index (PH,M/A,PV) and MVD than those in Ⅰ - Ⅱstaging(P<0.05).(5) The CTP enhance index (PH, M/A, PV) of lung cancer correlated positively with the MVD respectively.The highest correlation coefficient was between PV and MVD( r =0.703,P <0.01 ).(6)With ROC curve analysis,MVD and PV had high value in estimate and predict TNM staging of peripheral non small cell lung cancer.If MVD of 71.5/0.74 mm2 was taken as the threshold in TNM staging, the sensitivity, specificity, accuracy was 86.7%, 76.5%, 81.13%.If PV of 1.16 ml · min-1 · ml-1 was taken

  12. Silicon: The key element in early stages of biocalcification.

    Science.gov (United States)

    Matsko, Nadejda B; Znidaršič, Nada; Letofsky-Papst, Ilse; Dittrich, Maria; Grogger, Werner; Strus, Jasna; Hofer, Ferdinand

    2011-04-01

    Biocalcification is a widespread process of forming hard tissues like bone and teeth in vertebrates. It is also a topic connecting life sciences and earth sciences: calcified skeletons and shells deposited as sediments represent the earth's fossil record and are of paramount interest for biogeochemists trying to get an insight into the past of our planet. This study reports on the role of silicon in the early biocalcification steps, where silicon and calcium were detected on the surface of cyanobacteria (initial stage of lacustrine calcite precipitation) and in crustacean cuticles. By using innovative methodological approaches of correlative microscopy (AFM in combination with analytical TEM: EFTEM, EELS) the chemical form of silicon in biocalcifying matrices and organic-inorganic particles is determined. Previously, silicon was reported to be localized in active growth areas in the young bone of vertebrates. We have found evidence that biocalcification in evolutionarily distant organisms involves very similar initial phases with silicon as a key element at the organic-inorganic interface.

  13. Cytonuclear incompatibility contributes to the early stages of speciation.

    Science.gov (United States)

    Barnard-Kubow, Karen B; So, Nina; Galloway, Laura F

    2016-12-01

    Genetic incompatibility is a hallmark of speciation. Cytonuclear incompatibilities are proposed to be among the first genetic barriers to arise during speciation. Accordingly, reproductive isolation (RI) within species should be heavily influenced by interactions between the organelle and nuclear genomes. However, there are few clear examples of cytonuclear incompatibility within a species. Here, we show substantial postzygotic RI in first-generation hybrids between differentiated populations of an herbaceous plant (up to 92% reduction in fitness). RI was primarily due to germination and survival, with moderate RI for pollen viability. RI for survival was asymmetric and caused by cytonuclear incompatibility, with the strength of incompatibility linearly related to chloroplast genetic distance. This cytonuclear incompatibility may be the result of a rapidly evolving plastid genome. Substantial asymmetric RI was also found for germination, but was not associated with cytonuclear incompatibility, indicating endosperm or maternal-zygote incompatibilities. These results demonstrate that cytonuclear incompatibility contributes to RI within species, suggesting that initial rates of speciation could be influenced by rates of organelle evolution. However, other genetic incompatibilities are equally important, indicating that even at early stages, speciation can be a complex process involving multiple genes and incompatibilities.

  14. Affective motives for smoking among early stage smokers.

    Science.gov (United States)

    Mathew, Amanda R; Wahlquist, Amy E; Garrett-Mayer, Elizabeth; Gray, Kevin M; Saladin, Michael E; Carpenter, Matthew J

    2014-10-01

    As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16-20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR - NR), such that higher dependence was associated with more prominent NR motives for smoking. Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Early stages of diamond BEN-HFCVD on iridium

    Energy Technology Data Exchange (ETDEWEB)

    Arnault, J.C.; Faerber, J. [Groupe Surfaces-Interfaces, Institut de Physique et Chimie de Strasbourg, IPCMS-GSI, UMR 7504, BP 43, 23, rue du Loess, 67034 Strasbourg Cedex 2 (France); Vonau, F. [Laboratoire de Physique et Spectroscopie Electronique, 4, rue des Freres Lumiere, 68093 Mulhouse Cedex (France); Arabski, J.; Schmerber, G. [Groupe des Materiaux Metalliques, IPCMS-GEMM, 91404 Orsay (France); Wyczisk, F.; Legagneux, P. [Thales R and T, Domaine de Corbeville, 91404 Orsay Cedex (France)

    2003-09-01

    This study attempts to better understand the BEN effects on diamond nucleation on iridium buffer layers investigated by in situ electron spectroscopies (XPS, AES). The surface morphology is further characterised by AFM and SEM FEG. Nano-Auger experiments provide information about the chemical nature of the crystals. During the early stages of BEN, nano-Auger observations revealed a significant carbon sp{sup 3} contribution within the bright crystals whereas the surrounding areas are mainly sp{sup 2}. This emphasizes the BEN effect on the diamond nucleation. Moreover, AES experiments reveal the formation of graphite. The equivalent thickness of the graphite layer is estimated from XPS data, it is close to a monolayer. The graphite formation is not a proper effect of BEN because it is also obtained under CVD environment according to our study. Anisotrope crystals arranged along left angle 110 right angle directions have been characterized by HR-SEM and AFM. (copyright 2003 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  16. The studies of nodular graphite cast iron early stages austempering

    Directory of Open Access Journals (Sweden)

    A. Krzyńska

    2008-12-01

    Full Text Available The results of early stage of ductile cast iron austempering are presented. The aim of the investigations was to look closer into the structure – mechanical properties relationships of this very attractive cast material. The experiment was carried out with enriched with Cu EN-GJS-500-7 grade ductile iron. The specimens were first solution heat treated 1 hour in 910oC and then isothermally quenched for different time in molten tin at the temperature 275oC. The mechanical properties of as cast and heat treated specimens were tested to evaluate tensile Rm and yield strength R p, 0.2 and elongation A5. Additionally hardness measurements were carried out using Brinell-Rockwell method. Structure of the specimens both as cast and after austempering was studied using conventional light microscopy. Moreover, scanning electron microscopy (SEM was applied for fracture surface observations. It was concluded that short time low temperature austempering lead to formation martensitic microstructure characterized by very high hardness with almost zero ductility. The lack of ductility make the material very sensitive to any structure defects which work as a stress concentrators which strongly influence the strength of heat treated ductile iron specimens.

  17. Cognitive Stimulation for Apathy in Probable Early-Stage Alzheimer's

    Directory of Open Access Journals (Sweden)

    Linda L. Buettner

    2011-01-01

    Full Text Available We studied changes in apathy among 77 community-dwelling older persons with mild memory loss in a randomized clinical trial comparing two nonpharmacological interventions over four weeks. The study used a pre-post design with randomization by site to avoid contamination and diffusion of effect. Interventions were offered twice weekly after baseline evaluations were completed. The treatment group received classroom style mentally stimulating activities (MSAs while the control group received a structured early-stage social support (SS group. The results showed that the MSA group had significantly lower levels of apathy (P<.001 and significantly lower symptoms of depression (P<.001. While both groups improved on quality of life, the MSA group was significantly better (P=.02 than the SS group. Executive function was not significantly different for the two groups at four weeks, but general cognition improved for the MSA group and declined slightly for the SS group which produced a significant posttest difference (P<.001. Recruitment and retention of SS group members was difficult in this project, especially in senior center locations, while this was not the case for the MSA group. The examination of the data at this four-week time point shows promising results that the MSA intervention may provide a much needed method of reducing apathy and depressive symptoms, while motivating participation and increasing quality of life.

  18. Metformin inhibits early stage diethylnitrosamine‑induced hepatocarcinogenesis in rats.

    Science.gov (United States)

    Jo, Woori; Yu, Eun-Sil; Chang, Minsun; Park, Hyun-Kyu; Choi, Hyun-Ji; Ryu, Jae-Eun; Jang, Sungwoong; Lee, Hyo-Ju; Jang, Ja-June; Son, Woo-Chan

    2016-01-01

    Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)‑induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma‑specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S‑transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK‑dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high‑risk patients, including chronic hepatitis and cirrhosis.

  19. Building performance simulation in the early design stage: An introduction to integrated dynamic models

    DEFF Research Database (Denmark)

    Negendahl, Kristoffer

    2015-01-01

    Designing with building performance simulation feedback in the early design stage has existed since the early days of computational modeling. However, as a consequence of a fragmented building industry building performance simulations (BPSs) in the early design stage are closely related to who is...

  20. The Radiosensitizing Effect of Gemcitabine or Navelbine on Stage Ⅲ~Ⅳ Non-small Cell Lung Cancer%吉西他滨/长春瑞滨对Ⅲ~Ⅳ期非小细胞肺癌的放射增敏作用

    Institute of Scientific and Technical Information of China (English)

    高春玲; 王笑良; 吴晓安; 叶性景; 程小峰; 陈建清

    2012-01-01

    Objective To evaluate the clinical effect and toxicity of concurrent gemcitabine( GEM ) or navelbine( NVB ) chemotherapy and radio-therapy for stage III ~ IV non-small cell lung cancer( NSCLC ). Methods 27 cases of stage III ~ IV NSCLC were treated with concomitant gemcitabine or navelbine and radiotherapy, there were 12 patients in GEM group and 15 cases in NVB group. The induction chemotherapy consisted of 2 cycles of paclitaxel and cisplatin, paclitaxel with a dose of 135 mg/ m2 dl and cispl-atin with a dose of 30 mg/m2 dl ~3 ,21 days was a cycle. 27 patients were received three-dimensional conformal radiation therapy combined with gemcitabine 30 mg/m2 or navelbine 20 mg/m2 once a week for four weeks. Results The complete remission rate( CRR ),partial remission rate( PRR ) and overall response rate( ORR ) were 3.7%( 1/27 ),55. 6%( 15/27 ) and59.3%( 16/27 ),respectively. The CRR,PRR and ORR of the NVB group and GEM group were 6. 7% ( 1/15) and 0, 60.0% ( 9/15 ) and 50.0%( 6/12 ) ,66. 7%( 10/15 ) and 50. 0%( 6/12 ),respectively. The toxicity of lung,esophagus and blood in 27 patients were well tolerated and all patients completed their treatment successfully. Conclusion The radiotherapy combined with gemcitabine or navelbine for stage III ~ IV non-small cell lung cancer showed better effect and tolerable toxicity. We would further follow up the long-term result of 27 cases.%目的 探讨放疗联合吉西他滨/长春瑞滨治疗晚期非小细胞肺癌的近期疗效及不良反应.方法 27例Ⅲ~Ⅳ期非小细胞肺癌(non-small cell lung cancer,NSCLC),分为2组,其中吉西他滨组12例和长春瑞滨组15例.放疗前均先给予2个周期"紫杉醇+顺铂"方案诱导化疗,紫杉醇135 mg/m2 静脉滴注第1天,顺铂30 mg/m2 静脉滴注第1~3天,21天为1个周期.放疗同期予吉西他滨300 mg/m2,第1、8、15、22天,或长春瑞滨20 mg/m2,第1、8、15、22天.放疗均采用三维适形方式.结果 完全缓解率(CRR)、部分缓解

  1. Targeted therapy for localized non-small-cell lung cancer: a review

    Directory of Open Access Journals (Sweden)

    Paleiron N

    2016-07-01

    Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with