Long-Term Results of a Phase II Study of Accelerated Hyperfractionated Thoracic Radiotherapy with Dose Escalation to 54 Gy for Limited-Stage Small-Cell Lung Cancer

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The combination of accelerated hyperfractionated thoracic radiotherapy (AHF-TRT) of 45 Gy and concurrent chemotherapy is the standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, the optimal dose and fractionation remain controversial. We herein report the results of a phase II study investigating the utility of dose escalation to 54 Gy on AHF-RT for LS-SCLC. We enrolled patients ≤80 years old with treatment-naïve confirmed LS-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. The radiation dose was 54 Gy delivered in 36 fractions in 18 treatment days over 3.6 weeks. The chemotherapy regimens were PE (cisplatin and etoposide)- or CE (carboplatin and etoposide)-based. AHF-TRT was given in 2 phases: patients initially received 36 Gy to the gross tumor plus uninvolved mediastinal nodes, followed by a boost to the gross tumor of 18 Gy. All patients were treated with three-dimensional conformal radiation therapy with multiple fields to reduce the elevated dose volume to the surrounding tissues, such as the lungs and esophagus, as much as possible. All patients were evaluated for the overall survival (OS), progression-free survival (PFS), and non-hematological toxicity. Between 2013 and 2016, a total of 13 patients were enrolled in the present study. All the patients were assessable for the response and toxicity. The median age was 67 (range, 54-78) years old, and 9 patients were male, while 4 were female. Twelve patients had a ECOG performance status of 0. The numbers of patients with Stage IIA, IIB, IIIA, and IIIB disease were one, one, eight, and three, respectively. The median follow-up for all patients was 79 (range, 13-107) months, and that for surviving patients was 90 (range, 79-107) months. The patterns of failure were locoregional-only recurrence in 0% (0 patients), both locoregional and distant in 15.4% (2 patients), and distant-only in 30.8% (4 patients). Recurrence from the elective nodal irradiation area was seen in 0% (0 patients). The 1-, 3-, 5-, and 7-year OS rates were 100%, 76.9%, 53.9%, and 44.9%, respectively, and the median OS was 83.0 months. The 1-, 3-, 5-, and 7-year PFS rates were 76.9%, 53.9%, 53.9%, and 44.9%, respectively, and the median PFS was 83.0 months. No patient experienced a grade ≥3 non-hematological adverse effect, such as esophagitis or pneumonitis, during treatment or follow-up. Grade 2 pneumonitis was observed in 2 patients (15.4%), Grade 2 esophagitis was observed in 12 patients (92.3%), and Grade 2 esophageal pain was observed in 2 patients (15.4%). In this study, AHF-TRT of 54 Gy with concurrent PE- or CE-based regimens resulted in a good OS and PFS without increasing severe toxicity. Although this regimen needs to be evaluated in more patients to fully confirm its efficacy, these outcomes suggest that dose escalation to 54 Gy may be a promising radical treatment for LS-SCLC.