Hypofractionation in locally advanced NSCLC: outcome, toxicity and predictive factors
Davide Franceschini,
Italy
PO-1281
Abstract
Hypofractionation in locally advanced NSCLC: outcome, toxicity and predictive factors
Authors: Davide Franceschini1, Antonio Marzo2,3, Lorenzo Lo Faro4,3, Beatrice Marini4,3, Luciana Di Cristina4,5, Ciro Franzese4,5, Carmela Galdieri4, Maria Massaro6, Ruggero Spoto4, Luca Dominici4, Marta Scorsetti6,3
1IRCCS Humanitas Research Hospital, Radiotherapy and Radiosurgery, Rozzano, Milan, Italy; 2IRCCS Humanitas Research Hospital, Radiotherapy and Radiosurgery, Rozzano-Milan, Italy; 3Humanitas University, Biomedical Sciences, Pieve Emanuele – Milan, Italy; 4IRCCS Humanitas Research Hospital, Radiotherapy and Radiosurgery, Rozzano – Milan, Italy; 5Humanitas University, Biomedical Sciences , Pieve Emanuele – Milan, Italy; 6IRCCS Humanitas Research Hospital, Radiotherapy and Radiosurgery, Rozzano – Milan, Italy
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Purpose or Objective
The aim of this study was to evaluate clinical outcome, toxicity and predictive factors of recurrence and mortality in a cohort of patients treated with hypofractionated sequential chemo-radiotherapy (CT-RT) or exclusive radiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC).
Material and Methods
The study included patients affected by LA-NSCLC (stage II-IVA) treated with sequential CT-RT or exclusive RT. RT was delivered in 20 fractions for a total dose of 50-60 Gy with Volumetric Modulated Arc Therapy (VMAT). We excluded patients receiving adjuvant immunotherapy after CT-RT. Acute and late toxicities were recorded according to CTCAE v5.0. The Kaplan Meier analysis was applied to assess local control (LC), progression-free survival (PFS) and overall survival (OS). Univariate analysis was used to correlate outcomes to prognostic factors of recurrence and mortality.
Results
Between 2011 and 2019, 210 patients were treated with hypofractionated RT, 113 patients (53,8%) with sequential CT-RT and 97 patients (46.2%) with exclusive RT. Patients and treatment characteristics are shown in table 1. After a median follow up of 16.5 months (range 1.9 – 94.1 months), 74 patients (35.2%) had a local progression and 133 patients (63.3%) had a distant progression. One, two and 5-year LC rate were 73.6% (95% CI 66.2% - 79.6%), 55.3% (95% CI 46.5% – 63.2%) and 47.9% (95% CI 38,1 – 57%), respectively. At the time of analysis 167 patients (79.5%) died. One, two and 5-year OS rate were 64.7% (95% CI 57.8% - 70.7%), 36% (95% CI 29.5% - 42.6%) and 20% (95% CI 14.2% - 25.8%), respectively. PTV volume, as a continuous variable, correlated with OS (p=0.056), PFS (p=0.001) and LC (p=0.005). Exclusive RT was correlated with a worse OS (with a borderline statistically significance, p=0.07). We recorded a better outcome in terms of LC and OS of the sequential regimen after 2 and 5 years compared to the exclusive one: 62% vs 46.6% at 2 years and 54% vs 40% at 5 years for LC, and 41% vs 30% at 2 years and 27% vs 11.6% at 5 years for OS. Acute toxicity was recorded in 82% of patients, while late side effects occurred in 26% of cases. The most common acute toxicities were grade 1 and 2 and included asthenia (21,8%), dyspnea (11,9%), dysphagia (41,4%), cough (32,3%). Two patients had G3 pneumonitis and one patient had G5 pneumonitis. Late esophageal toxicity and dyspnea occurred in 6 and 16 patients, respectively. There were 9 cases of G4 pneumonitis and one patient with G5 pneumonitis. Toxicities are listed in table 2.
Conclusion
Hypofractionated sequential CT-RT or exclusive RT offer a good local control, a safe toxicity profile and a promising survival rate in LA-NSCLC patients unfit for concurrent CT-RT scheme. The target volume correlated with OS, PFS and LC and exclusive RT was associated with a worse OS compared to the sequential scheme. Larger prospective trials are necessary to evaluate toxicity and survival.