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

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          Abstract

          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.

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          Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis.

          Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V(20)) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P 0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V(20), and lower-lobe tumor location. Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Prediction of radiation pneumonitis by dose - volume histogram parameters in lung cancer--a systematic review.

            To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy. Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data were abstracted from the various reports to calculate operating characteristics and odds ratios for the different DVH metrics. A total of 12 published studies and two abstracts were identified. Eleven studies assessed V(dose), seven assessed MLD, and eight assessed NTCP. Nine studies exclusively analyzed the association between various DVH metrics and RP risk. Five studies also analyzed other patient, tumor, and treatment variables in conjunction with standard DVH metrics. A direct comparison between studies and the generation of summary statistics (i.e. meta-analysis) could not be achieved due to significant predictive and outcome variable heterogeneity. Most studies did show an association between DVH parameters and RP risk. However, overall accuracy, sensitivity, specificity, and positive predictive value were generally poor to fair for all three classes of DVH metrics. An association between DVH parameters and RP risk has been demonstrated in the literature. However, the ideal DVH metric with excellent operating characteristics, either alone or in a model with other predictive variables, for RP risk prediction has not yet been identified. Several recommendations for reporting and conduct of future research into the association between DVH metrics and RP risk are provided.
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              Impact of comorbidity on chemotherapy use and outcomes in solid tumors: a systematic review.

              The treatment of cancer in patients with comorbidities can be challenging as these individuals are underrepresented in clinical trials. We conducted a systematic review to determine the impact of comorbidity on chemotherapy use, delivery, tolerability, and survival among patients with solid tumors to summarize current data and provide recommendations for future research. METHODS All English-language articles from 1990 to 2009 that explored the association between comorbidity and chemotherapy were identified from MEDLINE and EMBASE. Abstracts were reviewed for eligibility, and data on study design and results were extracted. Thirty-four articles met the inclusion criteria. Study populations and design were heterogeneous, and the quality of reporting was generally poor. Most studies were retrospective (76%), were based on a cancer registry linked with administrative data (47%), and assessed the overall effect of comorbidity using an index score (76%). Sixteen studies (47%) investigated chemotherapy use, and 29 (85%) addressed survival. The majority reported decreased chemotherapy use (75%) and inferior survival (69%) for patients with comorbidities compared to those without. In 11 of 14 studies, inferior survival was independent of treatment. Of the few studies that addressed chemotherapy tolerability, seven of 10 reported an increased rate of severe toxicity, and three of five reported increased treatment delays for patients with comorbidity. CONCLUSION Chemotherapy use and outcomes among cancer patients with comorbidities are generally inferior, but the existing evidence is limited and of insufficient quality to determine the relationship between decreased use and inferior survival. Further studies that are prospective and site and stage specific are warranted.
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                Author and article information

                Journal
                Cancer Med
                Cancer Med
                cam4
                Cancer Medicine
                Blackwell Publishing Ltd
                2045-7634
                2045-7634
                December 2013
                16 October 2013
                : 2
                : 6
                : 916-924
                Affiliations
                [1 ]Austin-Ludwig Oncology Unit, Olivia Newton-John Cancer and Wellness Centre, Austin Health Melbourne, Australia
                [2 ]Ludwig Institute for Cancer Research, Olivia Newton-John Cancer & Wellness Centre, Austin Health Melbourne, Australia
                [3 ]Department of Medicine, Austin Health Melbourne, Australia
                [4 ]University of Melbourne Melbourne, Australia
                [5 ]Department of Radiation Oncology, Olivia Newton-John Cancer & Wellness Centre, Austin Health Melbourne, Australia
                [6 ]Informatics and Biocomputing Platform, Ontario Institute for Cancer Research Toronto, Canada
                [7 ]Department of Radiation Oncology (Maastro), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center Maastricht, the Netherlands
                Author notes
                Mun Sem Liew and Thomas John, Level 4, Olivia Newton-John Cancer & Wellness Centre, Austin Health. 145 Studley Rd, Heidelberg 3084, Victoria, Australia. Tel: +613 9496 3702; Fax: +613 9457 6698; E-mail: semliew@ 123456hotmail.com and tom.john@ 123456ludwig.edu.au

                Funding Information M. S. L. is supported by Australian National Health and Medical Research Council (NHMRC) postgraduate scholarship. P. C. B. is supported by the Institute for Cancer Research funding provided by the Government of Ontario. T. J. is a Victorian Cancer Agency Fellow.

                M. S. L. and J. S. contributed equally as first authors.

                Article
                10.1002/cam4.142
                3892396
                24403265
                802a7d6c-7e78-4983-9970-4eeb3ddc3159
                © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 27 June 2013
                : 25 August 2013
                : 02 September 2013
                Categories
                Clinical Cancer Research

                Oncology & Radiotherapy
                carboplatin/paclitaxel,cisplatin/etoposide,concurrent chemoradiotherapy,locally advanced,stage iii,non–small cell lung cancer

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