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Survival following surgery with or without adjuvant chemotherapy for stage I-IIIA non-small cell lung cancer: an east asian population-based study.

ABSTRACT: BACKGROUND: Asian ethnicity is associated with a distinct molecular etiology, treatment response, and survival outcome among patients with non-small cell lung cancer (NSCLC). This study examines the survival impact of platinum-based adjuvant chemotherapy for Asian patients with stage I-IIIA NSCLC. METHODS: This study recruited patients aged ?18 years with histologically proven stage IA-IIIA NSCLC registered in the Taiwan Cancer Registry database in January 2004 to December 2007. Platinum-containing adjuvant chemotherapy had to be started within 90 days of the primary surgery. Kaplan-Meier survival curves, log-rank tests, and the Cox proportional hazards regression model were used to assess the influence of various risk factors on survival time. RESULTS: This study included 2,231 patients with stage IA-IIIA NSCLC who underwent primary surgery with a clear surgical margin. The percentages of all causes of death were significantly lower for the chemotherapy group for both stage II and stage IIIA patients. Multivariate analysis identified platinum-based adjuvant chemotherapy as an independent prognostic factor for the overall survival outcome of stage II (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.39-0.94; p = .024) and IIIA (HR, 0.71; 95% CI, 0.52-0.96; p = .029) patients. Among these patients, those who received adjuvant chemotherapy had a superior overall survival outcome for both genders, for the subgroup of patients aged ?70 years, and for those with adenocarcinoma. CONCLUSION: Platinum-based adjuvant chemotherapy should be considered in the treatment plan for Asian patients with resected stage II and stage IIIA NSCLC.

SUBMITTER: Lin ZZ

PROVIDER: S-EPMC3481895 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Survival following surgery with or without adjuvant chemotherapy for stage I-IIIA non-small cell lung cancer: an east asian population-based study.

Lin Zhong-Zhe ZZ Shau Wen-Yi WY Shao Yu-Yun YY Yang Yen-Yun YY Kuo Raymond Nien-Chen RN Yang James Chih-Hsin JC Lai Mei-Shu MS

The oncologist 20120723 10

<h4>Background</h4>Asian ethnicity is associated with a distinct molecular etiology, treatment response, and survival outcome among patients with non-small cell lung cancer (NSCLC). This study examines the survival impact of platinum-based adjuvant chemotherapy for Asian patients with stage I-IIIA NSCLC.<h4>Methods</h4>This study recruited patients aged ≥18 years with histologically proven stage IA-IIIA NSCLC registered in the Taiwan Cancer Registry database in January 2004 to December 2007. Pla ...[more]

PMID: 22826374

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Project description:ImportanceAdjuvant chemotherapy offers a survival benefit to a number of staging scenarios in non-small-cell lung cancer. Variable recovery from lung cancer surgery may delay a patient's ability to tolerate adjuvant chemotherapy, yet the urgency of chemotherapy initiation is unclear.ObjectiveTo assess differences in survival according to the time interval between non-small-cell lung cancer resection and the initiation of postoperative chemotherapy to determine the association between adjuvant treatment timing and efficacy.Design, setting, and participantsThis retrospective observational study examined treatment-naive patients with completely resected non-small-cell lung cancer who received postoperative multiagent chemotherapy between 18 and 127 days after resection between January 2004 and December 2012. The study population was limited to patients with lymph node metastases, tumors 4 cm or larger, or local extension. Patients were identified from the National Cancer Database, a hospital-based tumor registry that captures more than 70% of incident lung cancer cases in the United States. The association between time to initiation of adjuvant chemotherapy and survival was evaluated using Cox models with restricted cubic splines.ExposuresAdjuvant chemotherapy administered at different time points after surgery.Main outcomes and measuresEffectiveness of adjuvant chemotherapy according to time to initiation after surgery.ResultsA total of 12 473 patients (median [interquartile range] age, 64 [57-70] years) were identified: 3073 patients (25%) with stage I disease; 5981 patients (48%), stage II; and 3419 patients (27%), stage III. A Cox model with restricted cubic splines identified the lowest mortality risk when chemotherapy was started 50 days postoperatively (95% CI, 39-56 days). Initiation of chemotherapy after this interval (57-127 days; ie, the later cohort) did not increase mortality (hazard ratio [HR], 1.037; 95% CI, 0.972-1.105; P = .27). Furthermore, in a Cox model of 3976 propensity-matched pairs, patients who received chemotherapy during the later interval had a lower mortality risk than those treated with surgery only (HR, 0.664; 95% CI, 0.623-0.707; P < .001).Conclusions and relevanceIn the National Cancer Database, adjuvant chemotherapy remained efficacious when started 7 to 18 weeks after non-small-cell lung cancer resection. Patients who recover slowly from non-small-cell lung cancer surgery may still benefit from delayed adjuvant chemotherapy started up to 4 months after surgery.

Project description:ObjectiveConcern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic radiation for resectable N2+ stage IIIA non-small cell lung cancer.MethodsTwo prospective trials were recently conducted by NRG Oncology in patients with resectable N2+ stage IIIA non-small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m2) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab + chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here.ResultsOne hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9).ConclusionsLobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.

Project description:BackgroundThe survival impact of multi-agent (MAC) compared with single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study was to compare survival outcomes of MAC and SAC in this population utilizing the National Cancer Database (NCDB).Patients and methodsPatients aged ≥70 years with pathological stage III CC diagnosed in 2004-2015 were identified in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify associations between MAC vs. SAC and overall survival (OS).ResultsAmong 41 707 elderly patients (≥70 years old) with stage III CC, about half (n = 20 257; 48.5%) received AC; the majority (n = 12 923, 63.8%) received MAC. The median age was 79 (range 70-90). The majority were female (n = 11 201, 55.3%), Caucasians (88%) and had moderately differentiated tumor grade (n = 12 619, 62.3%), tumor size >4 cm (11 785, 58.2%), and negative surgical margins (18 496, 91.3%). Low-risk stage III CC constituted 50.6% (n = 10 264) of the study population. High-risk stage III CC was associated with worse OS compared with low-risk disease (HR 0.35, 0.34-0.36, P < .001). Multi-agent chemotherapy was associated with a better 5-year OS compared with SAC (P < .001). High-risk stage III patients who received MAC vs. SAC had an OS of 4.2 vs. 3.4 years, respectively (P < .001). Low-risk stage III patients who received MAC vs. SAC had a median OS of 8.5 vs. 7 years (P < .001). In univariate and multivariable analyses, male sex, positive surgical margin, insurance and facility types, age, year of diagnosis, tumor size, and Charlson-Deyo score of >2 were associated with worse OS (P < .05).ConclusionsAny adjuvant chemotherapy has a trend of survival benefits. Multi-agent chemotherapy seems to have an enhanced benefit in the 70-75 age group. Multi-agent chemotherapy seemed to have similar efficacy as SAC in those aged >76 years.

Project description:BackgroundPatients with stage II-III colorectal cancer (CRC) treated with adjuvant chemotherapy, gain a 25% survival benefit. In the context of personalized medicine, there is a need to identify patients with CRC who may benefit from adjuvant chemotherapy. Molecular profiling could guide treatment decisions in these patients. Thymidylate synthase (TYMS) gene polymorphisms, KRAS and BRAF could be included in the molecular profile under consideration.AimTo investigate the association of TYMS gene polymorphisms, KRAS and BRAF mutations with survival of CRC patients treated with chemotherapy.MethodsA retrospective study studied formalin-fixed paraffin-embedded tissues (FFPEs) of consecutive patients treated with adjuvant chemotherapy during January/2005-January/2007. FFPEs were analysed with PCR for the detection of TYMS polymorphisms, mutated KRAS (mKRAS) and BRAF (mBRAF). Patients were classified into three groups (high, medium and low risk) according to 5'UTR TYMS polymorphisms Similarly, based on 3'UTR polymorphism ins/loss of heterozygosity (LOH) patients were allocated into two groups (high and low risk of relapse, respectively). Cox regression models examined the associated 5-year survival outcomes.ResultsOne hundred and thirty patients with early stage CRC (stage I-II: 55 patients; stage III 75 patients; colon: 70 patients; rectal: 60 patients) were treated with surgery and chemotherapy. The 5-year disease free survival and overall survival rate was 61.6% and 73.9% respectively. 5'UTR polymorphisms of intermediate TYMS polymorphisms (2RG/3RG, 2RG/LOH, 3RC/LOH) were associated with lower risk for relapse [hazard ratio (HR) 0.320, P = 0.02 and HR 0.343, P = 0.013 respectively] and death (HR 0.368, P = 0.031 and HR 0.394, P = 0.029 respectively). The 3'UTR polymorphism ins/LOH was independently associated with increased risk for disease recurrence (P = 0.001) and death (P = 0.005). mBRAF (3.8% of patients) was associated with increased risk of death (HR 4.500, P = 0.022) whereas mKRAS (39% of patients) not.ConclusionProspective validating studies are required to confirm whether 2RG/3RG, 2RG/LOH, 3RC/LOH, absence of ins/LOH and wild type BRAF may indicate patients at lower risk of relapse following adjuvant chemotherapy.

Project description:ImportanceTumor size larger than 4 cm is accepted as an indication for adjuvant chemotherapy in patients with node-negative non-small cell lung cancer (NSCLC). Treatment guidelines suggest that high-risk features are also associated with the efficacy of adjuvant chemotherapy among patients with early-stage NSCLC, yet this association is understudied.ObjectiveTo assess the association between adjuvant chemotherapy and survival in the presence and absence of high-risk pathologic features in patients with node-negative early-stage NSCLC.Design, setting, and participantsThis retrospective cohort study using data from the National Cancer Database included 50 814 treatment-naive patients with a completely resected node-negative NSCLC diagnosed between January 1, 2010, and December 31, 2015. The study was limited to patients who survived at least 6 weeks after surgery (ie, estimated median time to initiate adjuvant chemotherapy after surgery) to mitigate immortal time bias. Statistical analysis was performed from December 1, 2018, to February 29, 2020.ExposuresAdjuvant chemotherapy use vs observation, stratified according to the presence or absence of high-risk pathologic features (visceral pleural invasion, lymphovascular invasion, and high-grade histologic findings), sublobar surgery, and tumor size.Main outcomes and measuresThe association of high-risk pathologic features with survival after adjuvant chemotherapy vs observation was evaluated using Cox proportional hazards regression models.ResultsOverall, 50 814 eligible patients with NSCLC (27 365 women [53.9%]; mean [SD] age, 67.4 [9.5] years]) were identified, including 4220 (8.3%) who received adjuvant chemotherapy and 46 594 (91.7%) who did not receive adjuvant chemotherapy. Among patients with tumors 3 cm or smaller, chemotherapy was not associated with improved survival (hazard ratio [HR], 1.10; 95% CI, 0.96-1.26; P = .17). For patients with tumors larger than 3 cm to 4 cm, adjuvant chemotherapy was associated with a survival benefit among patients who underwent sublobar surgery (HR, 0.72; 95% CI, 0.56-0.93; P = .004). For tumors larger than 4 cm to 5 cm, a survival benefit was associated with adjuvant chemotherapy only in patients with at least 1 high-risk pathologic feature (HR, 0.67; 95% CI, 0.56-0.80; P = .02). For tumors larger than 5 cm, adjuvant chemotherapy was associated with a survival benefit irrespective of the presence of high-risk pathologic features (HR, 0.75; 95% CI, 0.61-0.91; P = .004).Conclusions and relevanceIn this cohort study, tumor size alone was not associated with improved efficacy of adjuvant chemotherapy in patients with early-stage (node-negative) NSCLC. High-risk clinicopathologic features and tumor size should be considered simultaneously when evaluating patients with early-stage NSCLC for adjuvant chemotherapy.

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Survival following surgery with or without adjuvant chemotherapy for stage I-IIIA non-small cell lung cancer: an east asian population-based study.

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Survival following surgery with or without adjuvant chemotherapy for stage I-IIIA non-small cell lung cancer: an east asian population-based study.

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