Literature DB >> 22588152

A pooled exploratory analysis of the effect of tumor size and KRAS mutations on survival benefit from adjuvant platinum-based chemotherapy in node-negative non-small cell lung cancer.

Sinead Cuffe1, Abderrahmane Bourredjem, Stephen Graziano, Jean-Pierre Pignon, Caroline Domerg, Monia Ezzalfani, Lesley Seymour, Elizabeth Strevel, Ronald Burkes, Marzia Capelletti, Pasi A Jänne, Ming-Sound Tsao, Frances A Shepherd.   

Abstract

INTRODUCTION: The staging of node-negative non-small-cell lung cancer is modified in the 7th edition TNM classification. Here, we pool data from the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Cancer and Leukemia Group B-9633 trial to explore the prognostic and predictive effects of the new T-size descriptors and KRAS mutation status.
METHODS: Node-negative patients were reclassified as T2a (>3-≤5 cm), T2b (>5-≤7 cm), T3 (>7 cm) or T ≤ 3 cm (≤3 cm, but other T2 characteristics).
RESULTS: Of 538 eligible patients, 288 (53.5%) were T2a, 111 (21%) T2b, 62 (11.5%) T3, whereas 77 (14%) T≤3 cm were excluded to avoid confounding. KRAS mutations were detected in 104 of 390 patients (27%). T-size was prognostic for disease-free survival (p = 0.03), but borderline for overall survival (OS; p = 0.10), on multivariable analysis. Significant interaction between the prognostic value of KRAS and tumor size was observed for OS (p = 0.01), but not disease-free survival (p = 0.10). There was a nonsignificant trend (p = 0.24) for increased chemotherapy effect on OS with advancing T-size (hazard ratio [HR] T2a 0.90, [0.63-1.30]; T2b 0.69, [0.38-1.24]; and T3 0.57, [0.28-1.17]). The HR for chemotherapy effect on OS in T2a patients with KRAS wild-type tumors was 0.81 (p = 0.36), whereas a trend for detrimental effect was observed in those with mutant tumors (HR 2.11; p = 0.09; interaction p = 0.05). Similar trends were observed in T2b to T3 patients with wild-type (HR 0.86; p = 0.62), and KRAS mutant tumors (HR 1.16; p = 0.74; interaction p = 0.58).
CONCLUSION: Chemotherapy effect seems to increase with tumor size. However, this small study could not identify subgroups of patients who did or did not derive significant benefit from adjuvant chemotherapy based on T-size or KRAS status.

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Year:  2012        PMID: 22588152      PMCID: PMC3638870          DOI: 10.1097/JTO.0b013e31824fe9e6

Source DB:  PubMed          Journal:  J Thorac Oncol        ISSN: 1556-0864            Impact factor:   15.609


  27 in total

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2.  Significance of the presence of microscopic vascular invasion after complete resection of Stage I-II pT1-T2N0 non-small cell lung cancer and its relation with T-Size categories: did the 2009 7th edition of the TNM staging system miss something?

Authors:  Enrico Ruffini; Sofia Asioli; Pier Luigi Filosso; Lucio Buffoni; Maria Cristina Bruna; Claudio Mossetti; Paolo Solidoro; Alberto Oliaro
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3.  Should the 7th edition of the lung cancer stage classification system change treatment algorithms in non-small cell lung cancer?

Authors:  Daniel J Boffa; Frank C Detterbeck; Erica J Smith; Ramon Rami-Porta; John Crowley; Daniel Zelterman; Lynn Tanoue; Anthony W Kim; Peter Goldstraw
Journal:  J Thorac Oncol       Date:  2010-11       Impact factor: 15.609

4.  Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy.

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5.  Adjuvant cisplatin and vinorelbine for completely resected non-small cell lung cancer: subgroup analysis of the Lung Adjuvant Cisplatin Evaluation.

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6.  Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer.

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7.  Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data.

Authors:  R Arriagada; A Auperin; S Burdett; J P Higgins; D H Johnson; T Le Chevalier; C Le Pechoux; M K B Parmar; J P Pignon; R L Souhami; R J Stephens; L A Stewart; J F Tierney; H Tribodet; J van Meerbeeck
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8.  Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10.

Authors:  Charles A Butts; Keyue Ding; Lesley Seymour; Philip Twumasi-Ankrah; Barbara Graham; David Gandara; David H Johnson; Kenneth A Kesler; Mark Green; Mark Vincent; Yvon Cormier; Glenwood Goss; Brian Findlay; Michael Johnston; Ming-Sound Tsao; Frances A Shepherd
Journal:  J Clin Oncol       Date:  2009-11-23       Impact factor: 44.544

9.  Recommended changes for T and N descriptors proposed by the International Association for the Study of Lung Cancer - Lung Cancer Staging Project: a validation study from a single-centre experience.

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  11 in total

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2.  Outcomes by tumor histology and KRAS mutation status after lung stereotactic body radiation therapy for early-stage non-small-cell lung cancer.

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Journal:  Transl Lung Cancer Res       Date:  2013-08

4.  Adjuvant Chemotherapy After Lobectomy for T1-2N0 Non-Small Cell Lung Cancer: Are the Guidelines Supported?

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5.  Clinical outcomes and changes in lung function after segmentectomy versus lobectomy for lung cancer cases.

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Journal:  J Thorac Cardiovasc Surg       Date:  2014-03-20       Impact factor: 5.209

Review 6.  Surgery in 2013 and beyond.

Authors:  Rishendran Naidoo; Morgan N Windsor; Peter Goldstraw
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Review 7.  Challenges in Implementing Personalized Medicine for Lung Cancer within a National Healthcare System.

Authors:  David E Dawe; Peter M Ellis
Journal:  J Pers Med       Date:  2012-09-10

8.  Variation in KRAS driver substitution distributions between tumor types is determined by both mutation and natural selection.

Authors:  Sheli L Ostrow; Einav Simon; Elad Prinz; Tova Bick; Talia Shentzer; Sima S Nagawkar; Edmond Sabo; Ofer Ben-Izhak; Ruth Hershberg; Dov Hershkovitz
Journal:  Sci Rep       Date:  2016-02-23       Impact factor: 4.379

9.  Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness.

Authors:  Massimo Moro; Giulia Bertolini; Roberto Caserini; Cristina Borzi; Mattia Boeri; Alessandra Fabbri; Giorgia Leone; Patrizia Gasparini; Carlotta Galeone; Giuseppe Pelosi; Luca Roz; Gabriella Sozzi; Ugo Pastorino
Journal:  Sci Rep       Date:  2017-07-27       Impact factor: 4.379

Review 10.  The seventh tumour-node-metastasis staging system for lung cancer: Sequel or prequel?

Authors:  Jan P van Meerbeeck; Annelies Janssens
Journal:  EJC Suppl       Date:  2013-09
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