Pathological response in resectable non-small cell lung cancer: a systematic literature review and meta-analysis.

BACKGROUND: Surrogate endpoints for overall survival in patients with resectable non-small cell lung cancer receiving neoadjuvant therapy are needed to provide earlier treatment outcome indicators and accelerate drug approval. This study's main objectives were to investigate the association among pathological complete response, major pathological response, event-free survival and overall survival and to determine whether treatment effects on pathological complete response and event-free survival correlate with treatment effects on overall survival. METHODS: A comprehensive systematic literature review was conducted to identify neoadjuvant studies in resectable non-small cell lung cancer. Analysis at the patient level using frequentist and Bayesian random effects (hazard ratio [HR] for overall survival or event-free survival by pathological complete response or major pathological response status, yes vs no) and at the trial level using weighted least squares regressions (hazard ratio for overall survival or event-free survival vs pathological complete response, by treatment arm) were performed. RESULTS: In both meta-analyses, pathological complete response yielded favorable overall survival compared with no pathological complete response (frequentist, 20 studies and 6530 patients: HR = 0.49, 95% confidence interval = 0.42 to 0.57; Bayesian, 19 studies and 5988 patients: HR = 0.48, 95% probability interval = 0.43 to 0.55) and similarly for major pathological response (frequentist, 12 studies and 1193 patients: HR = 0.36, 95% confidence interval = 0.29 to 0.44; Bayesian, 11 studies and 1018 patients: HR = 0.33, 95% probability interval = 0.26 to 0.42). Across subgroups, estimates consistently showed better overall survival or event-free survival in pathological complete response or major pathological response compared with no pathological complete response or no major pathological response. Trial-level analyses showed a moderate to strong correlation between event-free survival and overall survival hazard ratios (R2 = 0.7159) but did not show a correlation between treatment effects on pathological complete response and overall survival or event-free survival. CONCLUSION: There was a strong and consistent association between pathological response and survival and a moderate to strong correlation between event-free survival and overall survival following neoadjuvant therapy for patients with resectable non-small cell lung cancer.

Real-world treatment patterns and survival outcomes for patients with stage III non-small cell lung cancer in Spain: a nationwide cohort study.

Background: The burden of non-small cell lung cancer (NSCLC) remains high in Spain, with lung cancer accounting for 20% of cancer-related deaths annually. Programs such as the Spanish Thoracic Tumour Registry (TTR) and the global I-O Optimise initiative have been developed to observe patients in clinical practice with the aim of improving outcomes. This analysis examined treatment patterns and survival in patients with stage III NSCLC from the TTR. These patients represent a heterogenous group with complex treatment pathways. Methods: The TTR is an ongoing, observational, prospective, and retrospective cohort multicentre study (NCT02941458) that follows patients with thoracic cancer in Spain. Adults aged ≥18 years with stage IIIA/IIIB NSCLC enrolled in the TTR between 01 Jan 2010 and 31 Oct 2019 were included in this analysis. Initial treatment received was described by cancer stage and histology (squamous and non-squamous NSCLC). Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated over a 5-year period. Results: A total of 1,838 patients were included in the cohort, including 1,082 with stage IIIA (58.9%) and 756 with stage IIIB (41.1%). Median follow-up was 18.3 months. The median age of patients was 66 years, and most had non-squamous NSCLC (54.0%), were male (81.2%), and were active or former smokers (93.4%). Overall, 26.3% of patients received surgical resection (37.0% for stage IIIA and 11.1% for stage IIIB). The most frequent initial treatment received was concurrent chemoradiotherapy for stage IIIA (30.2%) and stage IIIB (37.0%) patients. Median OS was lower in patients with stage IIIB than stage IIIA (28 vs. 37 months) disease and was lower for patients with squamous than non-squamous histology (19 vs. 26 months). Median PFS and OS varied when patients were stratified by initial treatment. Conclusions: This TTR analysis describes the clinical reality surrounding the initial management and survival outcomes for stage III NSCLC in Spain and presents survival outcomes comparable with other real-world evidence. It provides insights into the diverse approaches used before the availability of immunotherapies and targeted treatments in the non-metastatic NSCLC setting.

Real-world relationship of early end points to survival end points in patients with resectable non-small-cell lung cancer.

Aim: Pathologic response has been shown to be a promising surrogate for survival in non-small-cell lung cancer. We examined the real-world relationship between these end  points in patients with resectable stage IB-IIIA non-small-cell lung cancer receiving neoadjuvant chemotherapy/chemoradiotherapy (CT/CRT). Methods: Electronic health records/medical charts were analyzed. Overall and event-free survival (OS/EFS) were assessed by Kaplan-Meier stratified by pathologic response. Associations between the end  points were assessed by Cox analyses. Results: A total of 425 patients were selected for the study; 147 and 278 received CT and CRT, respectively. Pathologic complete response (pCR) was associated with longer OS (adjusted HR = 0.50; 95% CI: 0.29-0.85) and EFS (adjusted HR = 0.44; 95% CI: 0.28-0.68) versus no pCR, and EFS was associated with OS (HR = 0.51, 95% CI: 0.38, 0.69). Conclusion: In patients receiving neoadjuvant CT/CRT, pCR and EFS were associated with improved survival in this real-world dataset.

Real-world treatment patterns in resectable (stages I-III) non-small-cell lung cancer: a systematic literature review.

Aim: The aim of this systematic literature review was to describe treatment patterns in nonmetastatic non-small-cell lung cancer. Methods: A search was conducted in MEDLINE and EMBASE. Eligible studies were multicentered (>50 patients) and conducted after 2000 in North America, Europe and Asia. Results: Twenty studies met the eligibility criteria. Based on US and Canadian studies in the resectable population, the proportion of patients who received neoadjuvant chemotherapy/chemoradiotherapy and adjuvant chemotherapy/chemoradiotherapy increased with increasing stage (i.e., from <3% in stage I to about 40% in stage III and from 15% in stage I to 30% in stage III, respectively). Within the resectable population, the breakdown between bimodal and trimodal therapy was variable, suggesting that clinical practice is not uniform. Conclusion: Overall, studies were heterogeneous, precluding data extrapolation across regions. Despite heterogeneity and limited evidence, this review suggested an increase in neoadjuvant and adjuvant chemotherapy with increasing stage, generally in line with treatment guidelines.

This literature review aimed to describe the treatment patterns in nonmetastatic non-small-cell lung cancer. This review was performed according to the highest methodological standards and searched published and unpublished records of stages I­III non-small-cell lung cancer treatment in North America, Europe and Asia. A limited number of studies were identified showing that in North America treatment with neoadjuvant and adjuvant chemotherapy (with or without radiotherapy) increased with stage. Identified studies in all regions showed that the treatment received, such as bimodal with surgery and chemotherapy compared with trimodal with surgery, chemotherapy and radiotherapy, was quite variable and that practice was not uniform. Overall, the studies were heterogeneous and data could not be extrapolated to practice across all regions. However, the studies suggested an increase in neoadjuvant and adjuvant usage with increasing stage, which is generally in line with treatment guidelines.

Regional postprandial differences in pH within the stomach and gastroesophageal junction.

Our objective was to determine regional differences in intragastric pH after different types of meals. Ten normal subjects underwent 27-hr esophagogastric pH monitoring using a four-probe pH catheter. Meals were a spicy lunch, a high-fat dinner, and a typical bland breakfast. The fatty dinner had the highest postprandial buffering effect, elevating proximal and mid/distal gastric pH to 4.9 +/- 0.4 and 4.0 +/- 0.4, respectively, significantly (P < 0.05) higher compared to 4.2 +/- 0.3 and 3.0 +/- 0.4 for the spicy lunch and 3.0 +/- 0.3 and 2.5 +/- 0.8 for the breakfast. The buffering effect of the high-volume fatty meal to pH > 4 was also longer (150 min) compared to that of the spicy lunch (45 min) and the bland breakfast, which did not increase gastric pH to > 4 at any time. Proximal gastric acid pockets were seen between 15 and 90 min postprandially. These were located 3.4 +/- 0.8 cm below the proximal LES border, extending for a length of 2.3 +/- 0.8 cm, with a drop in mean pH from 4.7 +/- 0.4 to 1.5 +/- 0.9. Acid pockets were seen equally after the spicy lunch and fatty dinner but less frequently after the bland breakfast. We conclude that a high-volume fatty meal has the highest buffering effect on gastric pH compared to a spicy lunch or a bland breakfast. Buffering effects of meals are significantly higher in the proximal than in the mid/distal stomach. Despite the intragastric buffering effect of meals, focal areas of acidity were observed in the region of the cardia-gastroesophageal junction during the postprandial period.