Personalized Radiation Therapy In Small Cell Lung Cancer

Objectives: The main purposes of this study are: 1) to study if treatment responses after 2-3 cycles of introduce chemotherapy have any impact on the optimal timing of radiation therapy, the indications and the target contouring of prophylactic supraclavicular area radiation, and the indications for thoracic irradiation and prophylactic cranial irradiation(PCI). 2) To assess the feasibility of reduction of radiation dose to the selective irradiation area during the thoracic irradiation.Materials and Methods: Study materials and methods including the following two sections: 1) Retrospective analysis was performed for those who received definitive radiation therapy. Patients were divided into chemo-response group and chemo-nonresponse group and early irradiation group(early-RT group) and late irradiation group(late-RT group). The differences in overall survival(OS) and progression free survival(PFS) between different treatment groups were analyzed; the 3-dimentional treatment planning computed- tomography(CT) scans were retrieved into treatment planning system, and the risk factors and patterns of supraclavicular lymph node metastasis(SCLM) were analyzed based on the CT scans; Medical records of patients who received simultaneous integrated dose reduction to the prophylactic area with intensity-modulated radiation therapy(SIR-IMRT, 60 Gy in 30 fractions to the gross tumor volume and 54 Gy in 30 fractions to the planning target volume) and those who received conventional IMRT(C-IMRT, 60 Gy in 30 fractions to the planning target volume) were analyzed to compare the local-regional recurrence, survival and toxicities. 2) Medical records for those who received operation due to various reasons for small cell lung cancer were analyzed to compare the differences in OS and PFS between different pathological stages and different treatments. The medical records for those who had brain metastasis follow-up were analyzed to assess the risk factors of brain metastasis.Results: 1) The median OS were 40.7 months and 24.9 months(P = 0.009), and the median PFS were 23.3 months and 13.3 months(P = 0.001) in chemo-response patients respectively, and the median OS were 20.8 months and 19.7 months(P = 0.484), the median PFS were 11.1 months and 14.3 months(P = 0.949) in thechemo-nonresponse patients. 2) Among supra-mediastinal lymph node positive patients, 65.3% developed SCLM, while in the 121 supra-mediastinal lymph node negative patients, only 6(5.0%) had SCLM(P = 0.000). In the patients with SCLM, 95.2% had lower para-recurrent laryngeal neural lymph node(station I) and para-internal jugular venous lymph node(station II) involvement. Only 4.8% of the patients developed lymph node metastasis in the other stations without station I and station III involvement. 3) In patients with pathological N+, the median OS were 66.7 months in those with thoracic RT and 34.6 months in those without thoracic RT(P = 0.016); and in those with pathological N0, they were 37.3 months and 96.8 months respectively(P = 0.561). The incidence of brain metastasis was 6.3% for stage I, 28.2% for stage II and 29.0% for stage III patients(P = 0.026). 4) The 3 year OS for the SIR-IMRT and C-IMRT groups were 51.0% and 45.0%(P = 0.119) and the 3 year local regional recurrence free survival were 71.2% and 39.2%(P = 0.119) respectively. The incidences of grade 3 and above lung and esophagus toxicities were both 4.8% and 11.9% in the two groups.Conclusions: Radiation therapy should be started early after introduction chemotherapy, especially for those who respond well to the chemotherapy. Prophylactic supraclavicular area irradiation should be considered for those with supra-mediastinal lymph node metastasis. If lymph node metastasis was observed after operation, thoracic RT and PCI should be considered. SIR-IMRT was feasible, without compromised treatment outcomes.