scholarly journals Pooled Analysis of the Prognostic and Predictive Effects of TP53 Comutation Status Combined With KRAS or EGFR Mutation in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy

2017 ◽  
Vol 35 (18) ◽  
pp. 2018-2027 ◽  
Author(s):  
Frances A. Shepherd ◽  
Benjamin Lacas ◽  
Gwénaël Le Teuff ◽  
Pierre Hainaut ◽  
Pasi A. Jänne ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Prognostic Effect ◽  
Disease Free

Purpose Our previous work evaluated individual prognostic and predictive roles of TP53, KRAS, and EGFR in non–small-cell lung cancer (NSCLC). In this analysis, we explore the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations in randomized trials of adjuvant chemotherapy versus observation. Patients and Methods Mutation analyses (wild-type [WT] and mutant) for TP53, KRAS, and EGFR were determined in blinded fashion in multiple laboratories. Primary and secondary end points of pooled analysis were overall survival and disease-free survival. We evaluated the role of TP53/KRAS comutation in all patients and in the adenocarcinoma subgroup as well as the TP53/EGFR comutation in adenocarcinoma only through a multivariable Cox proportional hazards model stratified by trial. Results Of 3,533 patients with NSCLC, 1,181 (557 deaths) and 404 (170 deaths) were used for TP53/KRAS and TP53/EGFR analyses. For TP53/KRAS mutation status, no prognostic effect was observed ( P = .61), whereas a borderline predictive effect ( P = .04) was observed with a deleterious effect of chemotherapy with TP53/KRAS comutations versus WT/WT (hazard ratio, 2.49 [95% CI, 1.10 to 5.64]; P = .03). TP53/EGFR comutation in adenocarcinoma was neither prognostic ( P = .83), nor significantly predictive ( P = .86). Similar results were observed for both groups for disease-free survival. Conclusion We could identify no prognostic effect of the KRAS or EGFR driver and TP53 tumor suppressor comutation. Our observation of a potential negative predictive effect of TP53/KRAS comutation requires validation.

Preoperative Chemotherapy Plus Surgery Versus Surgery Plus Adjuvant Chemotherapy Versus Surgery Alone in Early-Stage Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (19) ◽  
pp. 3138-3145 ◽  
Author(s):  
Enriqueta Felip ◽  
Rafael Rosell ◽  
José Antonio Maestre ◽  
José Manuel Rodríguez-Paniagua ◽  
Teresa Morán ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Preoperative Chemotherapy ◽  
Early Stage ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Disease Free

Purpose To address whether preoperative chemotherapy plus surgery or surgery plus adjuvant chemotherapy prolongs disease-free survival compared with surgery alone among patients with resectable non–small-cell lung cancer. Patients and Methods In this phase III trial, 624 patients with stage IA (tumor size > 2 cm), IB, II, or T3N1 were randomly assigned to surgery alone (212 patients), three cycles of preoperative paclitaxel-carboplatin followed by surgery (201 patients), or surgery followed by three cycles of adjuvant paclitaxel-carboplatin (211 patients). The primary end point was disease-free survival. Results In the preoperative arm, 97% of patients started the planned chemotherapy, and radiologic response rate was 53.3%. In the adjuvant arm, 66.2% started the planned chemotherapy. Ninety-four percent of patients underwent surgery; surgical procedures and postoperative mortality were similar across the three arms. Patients in the preoperative arm had a nonsignificant trend toward longer disease-free survival than those assigned to surgery alone (5-year disease-free survival 38.3% v 34.1%; hazard ratio [HR] for progression or death, 0.92; P = .176). Five-year disease-free survival rates were 36.6% in the adjuvant arm versus 34.1% in the surgery arm (HR 0.96; P = .74). Conclusion In early-stage patients, no statistically significant differences in disease-free survival were found with the addition of preoperative or adjuvant chemotherapy to surgery. In this trial, in which the treatment decision was made before surgery, more patients were able to receive preoperative than adjuvant treatment.

scholarly journals Determination of prognostic factors of surgically treated pathological Stage IIIA non-small cell lung cancer

2020 ◽  
Vol 28 (3) ◽  
pp. 496-504
Author(s):  
Muhammet Sayan
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Disease Free

Background: This study aims to identify the prognostic factors in Stage IIIA non-small cell lung cancer and to investigate whether there was a significant difference in terms of overall survival and disease-free survival among the subgroups belonging to this disease stage. Methods: Between January 2010 and December 2018, a total of 144 patients (125 males, 19 females; median age 60 years; range, 41 to 80 years) who were operated for non-small cell lung cancer in our clinic and whose pathological stage was reported as IIIA were retrospectively analyzed. Data including demographic and clinical characteristics of the patients, histopathological diagnosis, the standardized uptake value of the mass on positron emission tomography-computed tomography, tumor diameter, type of surgery, lymph node metastasis status, visceral pleural invasion, and overall and disease-free survival rates were recorded. Results: The median survival was 39 (range, 27.8 to 46.1) months and the five-year overall survival rate was 28%. The mean tumor diameter was 4.3±2.7 cm. The median disease-free survival was 37 (range, 28.1 to 48.6) months and the five-year disease-free survival rate was 26.9%. In the multivariate analysis, overall survival and disease-free survival in T2N2M0 subgroup were significantly worse than the other subgroups. The other poor prognostic factors of survival were the standardized uptake value of the tumor, pneumonectomy, and histopathological subtypes other than squamous cell carcinoma and adenocarcinoma. Parietal pleural invasion was significantly associated with worse disease-free survival rates. Conclusion: Our results showed that there may be significant survival differences between subgroups created by tumor histopathology, lymph node invasion and the type of surgery in a heterogeneous lung cancer stage.

scholarly journals Association of Mps one binder kinase activator 1 ( MOB1) expression with poor disease‐free survival in individuals with non‐small cell lung cancer

2020 ◽  
Vol 11 (10) ◽  
pp. 2830-2839
Author(s):  
Nobuhisa Ando ◽  
Kentaro Tanaka ◽  
Kohei Otsubo ◽  
Gouji Toyokawa ◽  
Yuki Ikematsu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Disease Free

scholarly journals Tumor Mutation Burden as a Biomarker in Resected Non–Small-Cell Lung Cancer

2018 ◽  
Vol 36 (30) ◽  
pp. 2995-3006 ◽  
Author(s):  
Siddhartha Devarakonda ◽  
Federico Rotolo ◽  
Ming-Sound Tsao ◽  
Irena Lanc ◽  
Elisabeth Brambilla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
Resected Nsclc ◽  
Mutation Burden ◽  
Disease Free

Purpose The survival benefit with adjuvant chemotherapy for patients with resected stage II-III non–small-cell lung cancer (NSCLC) is modest. Efforts to develop prognostic or predictive biomarkers in these patients have not yielded clinically useful tests. We report findings from the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-II study, in which we analyzed next-generation sequencing and long-term outcomes data from > 900 patients with early-stage NSCLC treated prospectively in adjuvant landmark clinical trials. We used a targeted gene panel to assess the prognostic and predictive effect of mutations in individual genes, DNA repair pathways, and tumor mutation burden (TMB). Methods A total of 908 unmatched, formalin-fixed, paraffin-embedded, resected lung cancer tumor specimens were sequenced using a targeted panel of 1,538 genes. Stringent filtering criteria were applied to exclude germline variants and artifacts related to formalin fixation. Disease-free survival, overall survival, and lung cancer—specific survival (LCSS) were assessed in Cox models stratified by trial and adjusted for treatment, age, sex, performance score, histology, type of surgery, and stage. Results Nonsynonymous mutations were identified in 1,515 genes in 908 tumor samples. High nonsynonymous TMB (> 8 mutations/Mb) was prognostic for favorable outcomes (ie, overall survival, disease-free survival, and LCSS) in patients with resected NSCLC. LCSS benefit with adjuvant chemotherapy was more pronounced in patients with low nonsynonymous TMBs (≤ 4 mutations/Mb). Presence of mutations in DNA repair pathways, tumor-infiltrating lymphocytes, TP53 alteration subtype, and intratumor heterogeneity was neither prognostic nor predictive. Statistically significant effect of mutations in individual genes was difficult to determine due to high false-discovery rates. Conclusion High nonsynonymous TMB was associated with a better prognosis in patients with resected NSCLC. In addition, the benefit of adjuvant chemotherapy on LCSS was more pronounced in patients with low nonsynonymous TMBs. Studies are warranted to confirm these findings.

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