Comparison of Outcome and Toxicities of Concurrent Chemo-radiation Versus Sequential Chemo-radiation in Inoperable Locally Advanced Non-small Cell Lung Cancer

Concurrent chemoradiotherapy (CCRT) is the standard of care for inoperable locally advanced non-small cell lung cancer (LA-NSCLC), but its associated toxicities pose a significant challenge, particularly in resource-limited settings, and sequential chemoradiotherapy (SCRT) may offer a more feasible alternative, though with potentially inferior efficacy. This quasi-experimental study, conducted from January 2022 to June 2023, aimed to compare the treatment outcomes and toxicity profiles of CCRT versus SCRT in a real-world Bangladeshi cohort by enrolling 66 patients with LA-NSCLC (Stage IIIA-IIIC) allocated to Arm A (CCRT; n=33), receiving weekly paclitaxel (45 mg/m²) and carboplatin (AUC 2) with concurrent radiotherapy (50 Gy/25 fractions), or Arm B (SCRT; n=33), receiving three cycles of induction paclitaxel (175 mg/m²) and carboplatin (AUC 6) followed by the same radiotherapy regimen, with treatment response assessed using RECIST 1.1 and toxicities graded per CTCAE v5.0. The study population was predominantly male (77.3%), with a mean age of 55.9 years, and had a high prevalence of squamous cell carcinoma (57.6%), and at the 12-week follow-up, the CCRT arm demonstrated a higher complete response rate compared to the SCRT arm (51.5% vs. 33.3%, p=0.535) and a higher overall response rate (84.8% vs. 72.7%, p>0.05), though these differences were not statistically significant, but CCRT was associated with a higher incidence of acute toxicities, notably Grade 2-3 esophagitis (30.3% vs. 15.2%) and Grade 2-3 leucopenia (21.3% vs. 12.1%), while all other hematological and non-hematological toxicities were comparable between the arms and not statistically significant. In conclusion, while CCRT showed a clinically meaningful improvement in treatment response rates, it was associated with increased, though manageable, acute toxicities, and the lack of statistical significance in efficacy, combined with the higher toxicity burden, suggests that SCRT remains a viable and potentially more tolerable treatment option for selected patients in resource-constrained environments where supportive care capabilities are limited.