45 Gy Versus 54 Gy of Accelerated Hyperfractionated Radiation Therapy for Patients With Limited-Stage Small Cell Lung Cancer: A Retrospective Analysis of a 7-Year Experience

Purpose/Objective(s): The optimal dose of accelerated hyperfractionated radiation therapy (AHF-RT) for limited-stage small-cell lung cancer (LSCLC) remains unknown. We herein report the assessment of the possibility of escalating the doses of AHF-RT for L-SCLC. Materials/Methods: Between 2006 and 2012, 18 patients diagnosed with L-SCLC and treated with chemotherapy and thoracic radiation therapy (TRT) were enrolled in this study. The chemotherapy regimens were PE (cisplatin and etoposide)or CE (carboplatin and etoposide)based regimens. Nine patients treated between 2006 and 2010 were irradiated with 45 Gy in 30 fractions for three weeks with AHF. Nine patients treated between 2011 and 2012 were irradiated with 54 Gy in 36 fractions for three and a half weeks with AHF. AHF-RT was given in two phases: patients initially received 36 Gy to the gross tumor plus uninvolved mediastinal nodes, followed by a boost to the gross tumor of nine or 18 Gy. Complete responders received prophylactic cranial irradiation (PCI). All patients were treated with three-dimensional conformal radiation therapy with multiple fields to reduce the irradiated volume of the surrounding tissues, such as the esophagus, as much as possible. Variables related to survival and loco-regional control were estimated by the Kaplan-Meier method, and the Log Rank test was used to evaluate the significance of survival and tumor control, using a p value of 0.05 to indicate significance. The CTCAE v3.0 was used to grade toxicities. Results: The median follow-up of the 45 Gy and 54 Gy groups was 20.2 months (range: 6.3-61.2 months) and 18.5 months (range: 8.1-31.0 months), respectively. No significant differences between the two groups regarding the patients and tumor characteristics were noted. The median duration of TRTwas 22 days, ranging from 19-27, in the 45 Gy group, and 28 days, ranging from 22-30, in the 54 Gy group. PCI was administered to four patients (44%) in 45 Gy group, and to eight patients (89%) in the 54 Gy (p Z 0.0790). A comparison between the 45 Gy and 54 Gy groups at two years showed that the overall survival rate was 77.8% vs 33.3%, (p Z 0.2120); the disease free-survival (DFS) was 66.7% vs 0% (p Z 0.0036); the local-regional control was 83.3% vs 30.0% (p Z 0.0812) and the distant metastasis-free survival (DMFS) was 66.7 vs 11.1% (p Z 0.0340). No Grade 3+ non-hematological adverse effects, such as acute esophagitis, pneumonitis or lung fibrosis were encountered. Conclusions: TRT with AHF of 54 Gy with concurrent PE or CE regimens significantly improved the DFS and DMFS control without increasing the toxicity, compared with 45 Gy. Although more patients with longer follow-up periods are needed to fully evaluate the usefulness and safety of this dose escalation of 9 Gy, these outcomes suggest that the dose escalation to 54 Gy on AHF-RT for L-SCLC could be a promising modality to improve the treatment results, with a low incidence of severe toxicity. Author Disclosure: Y. Takeuchi: None. K. Matsuura: None. T. Katsuta: None. T. Okabe: None. M. Kagemoto: None.