Steep dose-response relationship for stage I non-small cell lung cancer using hypo-fractionated high-dose irradiation by real-time tumor-tracking radiotherapy (RTRT)

Purpose: To investigate the clinical outcomes of patients with pathologically proven, peripherally located, stage I non-small cell lung cancer (NSCLC) who received stereotactic body radiotherapy (SBRT) using real-time tumor tracking radiotherapy (RTRT) during the developmental period. Materials and Methods: Forty-one patients were admitted (T1, 25; T2, 16) from February 2000 to June 2005. A 5 mm lanning target volume (PTV) margin was added to the clinical target volume determined with computed tomography at the end of expiratory phase. The gating window ranged from ± 2 to 3 mm. The dose fractionation schedule was 40 or 48 Gy in 4 fractions within 7 days. The dose was prescribed at the center of the PTV, giving more than an 80% dose at the PTV periphery. Results: For 28 patients treated with 48 Gy in 4 fractions, the overall actuarial survival (OAS) at 3 years was 82% for stage IA and 32% for stage IB. For patients treated with 40Gy/4Fr/1wk, OAS at 3 years was 50% for stage IA and 0% for stage IB. There was a significant difference in local control between 40 and 48 Gy in stage IB (p=0.0015) but not in stage IA (p=0.5811). No serious radiation morbidity was observed in either dose schedule. Conclusion: Forty-eight Gy in 4 fractions in one week was found to be a safe and effective treatment for peripherally located, stage IA NSCLC. A steep dose-response curve between 40 and 48 Gy using a daily dose of 12 Gy delivered in one week was identified for stage IB NSCLC in SBRT using RTRT

Prognostic factors in patients with advanced non-small cell lung cancer after long-term Anti-PD-1 therapy (HOT1902)

Objectives: Limited information is available on the appropriate treatment duration of immune checkpoint inhibitors (ICIs). We aimed to identify candidates who would benefit from ICI discontinuation after one year of treatment for metastatic non-small cell lung cancer (NSCLC). Materials and methods: This retrospective multi-institutional observational study examined medical records of all consecutive patients with advanced or recurrent NSCLC, who started ICI monotherapy at 15 institutions in Japan between December 2015 and December 2017. Patients who received initial ICI therapy for >1 year without progressive disease were defined as the long-term treatment (LT) group; others were defined as the non -longterm treatment (NLT) group. Primary outcomes included the prognostic factors in the LT group, whereas secondary outcomes included efficacy of ICI rechallenge, safety, and survival outcomes in the overall population. Results: In total, 676 patients were enrolled, and 114 (16.9 %) were assigned to the LT group. The median time interval from the start of initial ICI administration to data cutoff was 34.3 months (range, 24.1 & ndash;47.8); thus, all surviving patients were followed-up for at least 2 years from the start of initial ICI. Median progression-free survival (PFS) was longer in the LT than in the NLT group (33.6 months vs. 2.7 months; p < 0.001). On multivariate analysis, significantly better PFS was associated with smoking (hazard ratio [HR]=0.36, p = 0.04), and complete response (CR; HR=uncomputable, p < 0.001) in the LT group. Thirty-seven patients (5.5 %) received ICI rechallenge, including 10 in the LT group. Among patients receiving rechallenge treatment, the median PFS was 2.2 months, with no difference between the LT and NLT groups. Conclusions: In the LT group, smoking and achieving CR were significantly associated with better PFS. Since rechallenge treatment was not effective, careful consideration is required for discontinuing ICI. However, these prognostic factors are helpful in considering candidates for ICI discontinuation. Trial Registration: UMIN ID, UMIN00004140

First-line osimertinib in elderly patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer: a retrospective multicenter study (HOT2002)

Osimertinib is a standard of care therapy for previously untreated epidermal growth factor receptor mutation-positive non-small cell lung cancer. However, limited data exist regarding the efficacy and safety of osimertinib as a first-line therapy for elderly patients aged 75 years or older. To assess the potential clinical benefits of osimertinib in this population, this retrospective multi-institutional observational study included 132 patients with non-small cell lung cancer (age >= 75 years), who received osimertinib as first-line treatment. The proportion of patients with 1-year progression-free survival was 65.8% (95% confidence interval 57.1-73.5). The median progression-free survival was 19.4 (95% confidence interval 15.9-23.9) months. The median overall survival was not reached (95% confidence interval 24.6-not reached). The frequency of pneumonitis was 17.4%, with a grade 3 or higher rate of 9.1%. More than two-thirds of treatment discontinuations due to pneumonitis occurred within 3 months of starting osimertinib, and the prognosis of patients with pneumonitis was unsatisfactory. Osimertinib is one of the effective first-line therapeutic options for patients aged 75 years or older; however, special caution should be exercised due to the potential development of pneumonitis