To investigate outcomes for elderly patients treated with chemotherapy (CT) alone versus chemoradiotherapy (CRT) in the modern era by using a large national database.
Elderly patients (age ≥ 70 ...years) with limited-stage small-cell lung cancer clinical stage I to III who received CT or CRT were identified in the National Cancer Data Base between 2003 and 2011. Hierarchical mixed-effects logistic regression with clustering by reporting facility was performed to identify factors associated with treatment selection. Overall survival (OS) of patients receiving CT versus CRT was compared by using the log-rank test, Cox proportional hazards regression, and propensity score matching.
A total of 8,637 patients were identified, among whom 3,775 (43.7%) received CT and 4,862 (56.3%) received CRT. The odds of receiving CRT decreased with increasing age, clinical stage III disease, female sex, and the presence of medical comorbidities (all P < .01). Use of CRT was associated with increased OS compared with CT on univariable and multivariable analysis (median OS, 15.6 v 9.3 months; 3-year OS, 22.0% v 6.3%; log-rank P < .001; Cox P < .001). Propensity score matching identified a matched cohort of 6,856 patients and confirmed a survival benefit associated with CRT (hazard ratio, 0.52; 95% CI, 0.50 to 0.55; P < .001). Subset analysis of CRT treatment sequence showed that patients alive 4 months after diagnosis derived a survival benefit with concurrent CRT over sequential CRT (median OS, 17.0 v 15.4 months; log-rank P = .01).
In elderly patients with limited-stage small-cell lung cancer, modern CRT appears to confer an additional OS advantage beyond that achieved with CT alone in a large population-based cohort. Our findings suggest that CRT should be the preferred strategy in elderly patients who are expected to tolerate the toxicities of the combined approach.
Bevacizumab and erlotinib have been shown to improve survival in stage IV non-small-cell lung cancer (NSCLC). This phase I/II trial was designed to incorporate these agents with induction and ...concurrent chemoradiotherapy in stage III NSCLC.
Patients received induction chemotherapy (carboplatin area under the curve AUC 6, paclitaxel 225 mg/m(2), and bevacizumab 15 mg/kg on days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly with bevacizumab 10 mg/kg every other week for four doses) and thoracic conformal radiation therapy (TCRT) to 74 Gy. In the phase I portion, cohort 1 received no erlotinib, whereas cohorts 2 and 3 received erlotinib at 100 and 150 mg, respectively, Tuesday through Friday, during TCRT. Consolidation therapy with erlotinib (150 mg daily) and bevacizumab (15 mg/kg every 3 weeks) was planned 3 to 6 weeks later for six cycles.
Forty-five eligible patients were enrolled. The objective response rates to induction and overall treatment were 39% (95% CI, 24% to 55%) and 60% (95% CI, 44% to 75%), respectively. The median progression-free and overall survival times were 10.2 months (95% CI, 8.4 to 18.3 months) and 18.4 months (95% CI, 13.4 to 31.7 months), respectively. The principal toxicity was esophagitis (29% grade 3 or 4 esophagitis, with one patient with grade 3 tracheoesophageal fistula), which was often prolonged. Consolidation therapy with bevacizumab and erlotinib was not feasible.
The use of bevacizumab and erlotinib as administered in this trial is not recommended given the lack of an efficacy signal and the substantial risk of esophageal toxicity.
Background
EBRT in resected, nonmetastatic anaplastic thyroid cancer (ATC) remains undefined. We evaluated patterns/outcomes with EBRT and chemotherapy in this setting.
Methods
This retrospective ...analysis included patients identified from the National Cancer Database with nonmetastatic ATC from 2004 to 2014 who underwent non‐palliative resection.
Results
Our analysis included 496 patients, including 375 who underwent adjuvant EBRT (among whom 198 received concurrent chemotherapy). The median age was 68 years. On MVA, EBRT was associated with sex (OR 0.5, 95% CI 0.3‐0.8, P = .002) and income (OR 2.2, 95% CI 1.4‐3.3, P < .001). EBRT was associated with longer OS on UVA (12.3 vs 9.1 months, P = .004) and MVA (HR 0.7 CI 0.6‐0.9, P = .004). Concurrent chemoradiation was associated with longer OS on UVA (14.0 vs 9.1 months, P = .003) and MVA (HR 0.6 CI 0.5‐0.8, P < .001).
Conclusion
Adjuvant EBRT is associated with longer OS in resected, nonmetastatic ATC, with additional improved survival with concurrent chemotherapy.
Distant metastases (DMs) are the primary driver of mortality for patients with early stage NSCLC receiving stereotactic body radiation therapy (SBRT), yet patient-level risk is difficult to predict. ...We developed and validated a model to predict individualized risk of DM in this population.
We used a multi-institutional database of 1280 patients with cT1-3N0M0 NSCLC treated with SBRT from 2006 to 2015 for model development and internal validation. A Fine and Gray (FG) regression model was built to predict 1-year DM risk and compared with a random survival forests model. The higher performing model was evaluated on an external data set of 130 patients from a separate institution. Discriminatory performance was evaluated using the time-dependent area under the curve (AUC). Calibration was assessed graphically and with Brier scores.
The FG model yielded an AUC of 0.71 (95% confidence interval CI: 0.57–0.86) compared with the AUC of random survival forest at 0.69 (95% CI: 0.63–0.85) in the internal test set and was selected for further testing. On external validation, the FG model yielded an AUC of 0.70 (95% CI: 0.57–0.83) with good calibration (Brier score: 0.08). The model identified a high-risk patient subgroup with greater 1-year DM rates in the internal test (20.0% 3 of 15 versus 2.9% 7 of 241, p = 0.001) and external validation (21.4% 3 of 15 versus 7.8% 9 of 116, p = 0.095). A model nomogram and online application was made available.
We developed and externally validated a practical model that predicts DM risk in patients with NSCLC receiving SBRT which may help select patients for systemic therapy.
The optimal fractionation schedule in unresected stage I non-small cell lung cancer (NSCLC) unsuitable for stereotactic body radiation therapy is unclear. Given the lack of comparative data regarding ...nonstereotactic body radiation therapy schemas, we compared overall survival (OS) with hypofractionated radiotherapy (HFRT) versus conventionally fractionated radiotherapy (CFRT) and examined the OS impact of different HFRT doses.
This retrospective analysis included 2159 patients from the National Cancer Database diagnosed with stage I (cT1-2aN0M0) NSCLC between 2008 and 2016. Patients underwent CFRT (70≤BED10 biologically effective dose <100 Gy10 in ≥30 fractions), low-dose HFRT (LD-HFRT; 70≤BED10 assuming α/β=10 <100 Gy10 in 11 to 24 fractions), or high-dose HFRT (HD-HFRT; 100≤BED10 ≤120 Gy10 in 6 to 10 fractions). Patients who received surgery, chemotherapy, or immunotherapy were excluded. We compared CFRT versus all HFRT, and separately CFRT versus LD-HFRT and CFRT versus HD-HFRT. OS was evaluated with the Kaplan-Meier estimator, log-rank test, and Cox regression.
A total of 63.2% of patients underwent CFRT, 23.5% LD-HFRT, and 13.3% HD-HFRT. OS was significantly longer with HFRT versus CFRT on univariable (28.2 mo 95% CI, 25.6-31.7 vs 26.4 mo 25.0-27.9; log-rank=0.0025) but not multivariable analysis (MVA; hazard ratio HR 0.90; P=0.062). MVA yielded no significant difference in OS between CFRT and LD-HFRT (HR 0.96, P=0.53). OS was significantly longer with HD-HFRT versus CFRT on MVA (HR, 0.75; P=0.003). However, on sensitivity analysis using different multivariable modeling techniques, this did not retain statistical significance (HR, 0.83; P=0.12).
For stage I NSCLC, HFRT does not show a robust OS benefit compared with CFRT but may be preferred given the convenience and lower costs.
A subset of patients with potentially resectable clinical stage IIIA NSCLC are managed with trimodality therapy. However, little data exist to guide the timing of surgery after neoadjuvant therapy. ...This study examined whether the time interval between neoadjuvant chemoradiation (NCRT) and surgical resection affects overall survival.
Patients with clinical stage IIIA disease (T1–3 N2) NSCLC who underwent NCRT were identified in the National Cancer Data Base (NCDB) between 2004 and 2012 and categorized on the basis of the interval between chemoradiation and surgery (0 to ≤3, >3 to ≤6, >6 to ≤9, and >9 to ≤12 weeks). Other clinical stages were excluded. The Kaplan-Meier method and log-rank tests were used to compare overall survival rates, and a bootstrapped Cox proportional hazards model was used to determine significant contributors to overall survival.
Of the 1623 patients identified, 7.9% underwent an operation 0 to 3 weeks or less after NCRT, 50.5% underwent an operation greater than 3 and less than or equal to 6 weeks after NCRT, 31.9% underwent an operation greater than 6 and less than or equal to 9 weeks after NCRT, and 9.6% underwent an operation greater than 9 and less than or equal to 12 weeks after NCRT. Multivariate survival analysis demonstrated no significant difference in survival in those who underwent an operation within 6 weeks of NCRT. However, significant drops in overall survival were observed in those who had an operation greater than 6 and less than or equal to 9 weeks after NCRT (hazard ratio = 1.33, 95% confidence interval: 1.01–1.76, p = 0.043) and greater than 9 and less than or equal to 12 weeks after NCRT (hazard ratio = 1.44, 95% confidence interval: 1.04–2.01, p = 0.030).
The findings from this retrospective study suggest that overall survival may be significantly lower in patients with clinical stage IIIA N2 NSCLC who undergo an operation later than 6 weeks after NCRT. These results discourage unnecessary delays in surgery.
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