Dataset Information

Association of Delayed Adjuvant Chemotherapy With Survival After Lung Cancer Surgery.

ABSTRACT:

Importance

Adjuvant 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.

Objective

To 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 participants

This 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.

Exposures

Adjuvant chemotherapy administered at different time points after surgery.

Main outcomes and measures

Effectiveness of adjuvant chemotherapy according to time to initiation after surgery.

Results

A 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 relevance

In 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.

SUBMITTER: Salazar MC

PROVIDER: S-EPMC5824207 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceAdjuvant chemotherapy improves outcomes of patients with breast cancer. However, the optimal timing of chemotherapy initiation is unknown. Delayed administration can decrease the benefit of cytotoxic systemic therapies.ObjectiveTo identify the determinants in delayed chemotherapy initiation and to determine the relationship between time to chemotherapy (TTC) and outcome according to breast cancer subtype. We hypothesized that prolonged TTC would be associated with adverse outcomes.Design, setting, and participantsIn an observational, population-based investigation using data from the California Cancer Registry, we studied a total of 24 843 patients with stage I to III invasive breast cancer diagnosed between January 1, 2005, and December 31, 2010, and treated with adjuvant chemotherapy. Data analysis was performed between August 2014 and August 2015.Main outcomes and measuresTime to chemotherapy was defined as the number of days between surgery and the first dose of chemotherapy, and delayed TTC was defined as 91 or more days from surgery to the first dose of adjuvant chemotherapy. We evaluated overall survival and breast cancer-specific survival. Logistic regression and Cox proportional hazard models were used.ResultsIn all, 24 843 patients were included. Median age at diagnosis was 53 years, and median was TTC was 46 days. Factors associated with delays in TTC included low socioeconomic status, breast reconstruction, nonprivate insurance, and Hispanic ethnicity or non-Hispanic black race. Compared with patients receiving chemotherapy within 31 days from surgery, there was no evidence of adverse outcomes among those with TTC of 31 to 60 or 60 to 90 days. Patients treated 91 or more days from surgery experienced worse overall survival (hazard ratio [HR], 1.34; 95% CI, 1.15-1.57) and worse breast cancer-specific survival (HR, 1.27; 95% CI, 1.05-1.53). In a subgroup analysis according to subtype, longer TTC caused patients with triple-negative breast cancer to have worse overall survival (HR, 1.53; 95% CI, 1.17-2.00) and worse breast cancer-specific survival (HR, 1.53; 95% CI 1.17-2.07).Conclusions and relevanceFor patients with breast cancer, adverse outcomes are associated with delaying initiation of adjuvant chemotherapy 91 or more days. Delayed TTC was particularly detrimental among patients with triple-negative breast cancer. The determinants of delays in chemotherapy initiation appeared to be sociodemographic, and clinicians should provide timelier care to all patients.

Project description:ImportanceThe current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy.ObjectiveTo construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer.Design, setting, and participantsIn this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study's inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016.Main outcomes and measuresConcordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival.ResultsOf the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival and disease-free survival, with P < .05. The survival prediction model demonstrated good calibration and discrimination, with relatively high bootstrap-corrected concordance indexes in the training and validation cohorts. In the validation cohort, the concordance index for overall survival was 0.693 (95% CI, 0.671-0.715) and for disease-free survival was 0.704 (95% CI, 0.681-0.728). Two nomograms and a calculating tool were built on the basis of specific input variables to estimate an individual's net survival gain attributable to adjuvant chemotherapy.Conclusions and relevanceThe survival prediction model can be used to make individualized predictions of the expected survival benefit from the addition of adjuvant chemotherapy for patients with stage II or stage III gastric cancer.

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.

Project description:BACKGROUND: Improved methods are needed for predicting prognosis and the benefit of delivering adjuvant chemotherapy (ACT) in patients with non-small-cell lung cancer (NSCLC). METHODS: A novel prognostic algorithm was identified using genomic profiles from 332 stage I-III adenocarcinomas and independently validated on a separate series of 264 patients with stage I-II tumors, compiled from five previous studies. The prognostic algorithm was used to interrogate genomic data from a series of patients treated with adjuvant chemotherapy. Those genes associated with outcome in the adjuvant treatment setting, independent to prognosis were used to train an algorithm able to classify a patient as either a responder or non-responder to ACT. The performance of this signature was independently validated on a separate series of genomic profiles from patients enrolled in a randomized controlled trial of cisplatin/vinorelbine vs. observation alone (JBR.10). RESULTS: NSCLC patients exhibiting the high-risk, poor-prognosis form of the 160-gene prognosis signature experienced a 2.80-times higher rate of 5-year disease specific death (log rank P?<?0.0001) compared to those with the low-risk, good prognosis profile, adjusted for covariates. The prognosis signature was found to especially accurate at identifying early stage patients at risk of disease specific death within 24?months of diagnosis when compared to traditional methods of outcome prediction.Separately, NSCLC patients with the 37-gene ACT-response signature (n?=?70, 64?%), benefited significantly from cisplatin/vinorelbine (adjusted HR: 0.23, P?=?0.0032). For those patients predicted to be responders, receiving this form of ACT conferred a 25?% improvement in the probability of 5-year-survival, compared to observation alone and adjusted for covariates. Conversely, in those patients predicted to be non-responders, ACT was observed to offer no significant survival benefit (adjusted HR: 0.55, P?=?0.32).The two gene signatures overlap by one gene only SPSB3, which interacts with the oncogene MET. In this study, higher levels of SPSB3 which were associated with favorable prognosis and benefit from ACT. CONCLUSIONS: These complimentary prognostic and predictive gene signatures may assist physicians in their management and treatment of patients with early stage lung cancer.