Comparison Of Simultaneous Integrated Boost Intensity-modulated Radiation Therapy And Conventional Accelerated Hyper-fractionated Radiotherapy For Limited Disease Small-Cell Lung Cancer

OBJECTIVE:This study was designed to compare toxicities, disease control and survival outcomes for limited disease small-cell lung cancer (LD-SCLC) treated with simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) versus conventional accelerated hyper-fractionated radiotherapy.METHODS:Two cycles chemotherapy before thoracic radiotherapy (TRT) with EP regimen (etoposide 100mg/m2 day 1-5, and cisplatin 25mg/m day 1-3,21 days per cycle) were delivered. Then adjuvant chemotherapy were administered after completion of thoracic radiotherapy. Chemotherapy was administered every 3 weeks. A total of 4-6 cycles were administered. Doses were adjusted based on blood counts and toxicity levels. The gross tumor volume (GTV) was consisted of primary tumor as defined on imaging scans, or anatomical locations of the tumor should be included if achieved complete remission after chemotherapy. When enlarged lymph nodes (the lymph nodes greater than 1.0 cm in short axis measurement on CT, or demonstrated positive on the FDG-PET/CT scan) resolved after induction chemotherapy, the previously involved lymph node regions were still included in the radiation target by reviewing the pre-chemotherapy CT scan. Elective treatment of clinically uninvolved lymphatic regions was not carried out. In the SIB-IMRT group (group A) clinical target volume (CTV) was defined by expanding the GTV with 5 mm for the microscopic extension. To define the planning target volume (PTV), the CTV was then expanded by 5 mm set-up margin. In the conventional accelerated hyper-fractionated radiotherapy group (group B) the PTV was defined by the expanding GTV with a 1.0 cm margin. In the group A radiation doses were GTV 1.9Gy/time, CTV 1.7Gy/time, PTV 1.5Gy/time,2 times a day, total 30 times. In the group B the prescribed dose was 45Gy in 30 fractions at 1.5Gy per fraction to the PTV. All fractional doses were given twice daily with at least 6 h between fractions and 5 times each week. After completion of chemotherapy and TRT, prophylactic cranial irradiation (PCI,2.5Gy/fraction, once per day, and a total of 10 fractions) were delivered to patients who were with or close to complete response to the treatment. OS, PFS and LRFS were estimated using the Kaplan-Meier method. Differences between the two groups in patient characteristics, radiotherapy plan evaluation, toxicity or treatment response were assessed using the t test for numerical data and the Fisher exact test or Chi-square test for categorical data. A value of P< 0.05 was considered significant. Statistical calculations were performed using SPSS(?) v.17.0 (SPSS Inc, Chicago, IL).RESULTS:75 SCLC patients confirmed by pathology or cytology with stage I-III in Shandong Cancer Hospital & Institute were enrolled in the study.2 patients were ineligible, leaving 73 assessable patients. All of the 73 patients finished the planned induction chemotherapy, radiotherapy, and adjuvant chemotherapy.38 patients received conventional accelerated hyper-fractionated radiotherapy and 35 SIB-IMRT. The median age was 54 years (range,35 to 72) for the patients receiving SIB-IMRT, and 57 years (range,45 to 70) for the patients receiving conventional accelerated hyper-fractionated radiotherapy. There were no statistically significant differences in patient characteristics between the groups. Although the SIB-IMRT plans showing a trend to increasing the volume received irradiation, no significant differences were observed in the comparisons between the parameters of the total lung, ipsilateral lung and contralateral lung in present study (all P> 0.05). Compared to the conventional accelerated hyper-fractionated radiotherapy plans, the SIB-IMRT plans also do not show statistically significant (all P> 0.05) in dose sparing of the other evaluating OARs (Dmax to the spinal cord; V30, V40 and Dmean to the heart; V45 and mean esophagus dose). The hematologic toxicity were significantly more common in patients who received SIB-IMRT (P< 0.001). There were no significant differences between the groups in the incidence of other toxicities. Grade 3 esophagitis occurred in 17 percent of patients receiving SIB-IMRT and 13 percent of those receiving conventional accelerated hyper-fractionated radiotherapy. The patients with grade 3 esophagitis required intravenous nutrition. The median follow-up was 24.4 months, with a range of 6-61.3 months. There were no statistically significant differences in these outcomes between group A and group B Despite this, there was a trend toward improved local control and overall survival for the group A, with an estimated 2-year OS at 68.5% versus 54.6% for the group A versus group B, respectively.CONCLUSIONS:SIB-IMRT was well-tolerated in patients with LD-SCLC and the current study evaluated one program of SIB-IMRT for LD-SCLC that yielded an outcome better than conventional accelerated hyper-fractionated radiotherapy (45Gy with 1.5Gy twice daily in 3 weeks).