Outcome and toxicity of chemoradiation using volumetric modulated arc therapy followed by 3D image-guided brachytherapy for cervical cancer: Vietnam National Cancer Hospital experience.

Background: Volumetric modulated arc therapy (VMAT) and 3D image-guided brachytherapy (3D-IGBT) have recently been introduced in Vietnam for the treatment of locally advanced cervical cancer. This study aims to assess the outcomes and toxicities of chemoradiation using VMAT followed by 3D-IGBT in Vietnamese cervical cancer patients. Materials and methods: A prospective interventional study on 72 patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IIIC2 disease who underwent concurrent chemoradiation using VMAT, followed by 3D-IGBT according to EMBRACE-II protocol. Primary endpoints were locoregional control; secondary endpoints were systemic control and toxicity. Results: Median body volume received 43 Gy was 1589.1 cm3 (range 1214.8-2574.8). Median high-risk clinical target volume (CTV-HR) was 18.8 cm3 (range 8.6-61.2) with a median dose to 90% (D90) of CTV-HR of 90.6 Gy (range 86.8-99.6). Mean doses to 2cc (D2cc) of bladder, rectum, and sigmoid were 75.8, 55.2, and 62.1 Gy, respectively. At median 19-month follow-up (range 12-25), locoregional control and systemic control were 95.8% and 81.9%, respectively. Systemic control was the lowest in N2 disease (54.5%). Grade ≥ 3 acute toxicities were less than 10%, except neutropenia (31.9%). Extended-field radiation increased significantly nausea, fatigue, and thrombocytopenia. No grade ≥ 3 proctitis or cystitis; 8.3% had grade 3 vaginal stenosis. Conclusions: VMAT-based chemoradiation therapy followed by 3D-IGBT achieved high locoregional control with manageable toxicities in locally advanced cervical cancer. Systemic control correlated with disease stage.

Accelerated hyperfractionated radiotherapy for cervical cancer: multi-institutional prospective study of forum for nuclear cooperation in Asia among eight Asian countries.

PURPOSE: To evaluate the toxicity and efficacy of accelerated hyperfractionated radiotherapy (RT) for locally advanced cervical cancer. METHODS AND MATERIALS: A multi-institutional prospective single-arm study was conducted among eight Asian countries. Between 1999 and 2002, 120 patients (64 with Stage IIB and 56 with Stage IIIB) with squamous cell carcinoma of the cervix were treated with accelerated hyperfractionated RT. External beam RT consisted of 30 Gy to the whole pelvis, 1.5 Gy/fraction twice daily, followed by 20 Gy of pelvic RT with central shielding at a dose of 2-Gy fractions daily. A small bowel displacement device was used with the patient in the prone position. In addition to central shielding RT, intracavitary brachytherapy was started. Acute and late morbidities were graded according to the Radiation Therapy Oncology Group and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: The median overall treatment time was 35 days. The median follow-up time for surviving patients was 4.7 years. The 5-year pelvic control and overall survival rate for all patients was 84% and 70%, respectively. The 5-year pelvic control and overall survival rate was 78% and 69% for tumors > or = 6 cm in diameter, respectively. No treatment-related death occurred. Grade 3-4 late toxicities of the small intestine, large intestine, and bladder were observed in 1, 1, and 2 patients, respectively. The 5-year actuarial rate of Grade 3-4 late toxicity at any site was 5%. CONCLUSION: The results of our study have shown that accelerated hyperfractionated RT achieved sufficient pelvic control and survival without increasing severe toxicity. This treatment could be feasible in those Asian countries where chemoradiotherapy is not available.

A regional cooperative clinical study of radiotherapy for cervical cancer in east and south-east Asian countries.

PURPOSE: Radiotherapy differed widely in east and south-east Asia because of technical, cultural, and socio-economic differences. With the purpose of standardizing radiotherapy for cervical cancer in the region, an international clinical study was conducted. MATERIALS AND METHODS: Eleven institutions in eight Asian countries participated in the study. Between 1996 and 1998, 210 patients with stage IIIB cervical cancer were enrolled. Patients were treated with a combination of external beam radiotherapy (total dose, 50Gy) and either high-dose-rate (HDR) or low-dose-rate (LDR) intracavitary brachytherapy (ICBT) according to the institutional practice. The planned point A dose was 20-28Gy/4 fractions for HDR-ICBT and 30-40Gy/1-2 fractions for LDR-ICBT. RESULTS: Hundred patients were treated with HDR-ICBT and 110 were treated with LDR-ICBT. The ICBT doses actually delivered to point A ranged widely: 12-32Gy in the HDR group and 26-52.7Gy in the LDR group. The 5-year follow-up rate among the countries differed greatly, from 29% to 100%. The 5-year major complication rates were 6% in the HDR group and 10% in the LDR group. The 5-year overall survival rates were 51.1% in the HDR group and 57.5% in the LDR group. CONCLUSIONS: Although there were several problems with treatment compliance and patients' follow-up, the study suggests that the protocols provided favorable outcomes with acceptable rates of late complications in the treatment of advanced cervical cancer in east and south-east Asia.

Multicentre dose audit for clinical trials of radiation therapy in Asia.

A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy.

Long-term follow-up results of a multi-institutional phase 2 study of concurrent chemoradiation therapy for locally advanced cervical cancer in east and southeast Asia.

PURPOSE: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. METHODS AND MATERIALS: Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m(2)) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. RESULTS: Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. CONCLUSIONS: The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.

Multi-institutional phase II clinical study of concurrent chemoradiotherapy for locally advanced cervical cancer in East and Southeast Asia.

PURPOSE: To evaluate the toxicity and efficacy of concurrent chemoradiotherapy using weekly cisplatin for patients with locally advanced cervical cancer in East and Southeast Asia, a multi-institutional Phase II clinical study was conducted among eight Asian countries. METHODS AND MATERIALS: Between April 2003 and March 2006, 120 patients (60 with bulky Stage IIB and 60 with Stage IIIB) with previously untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiotherapy consisted of pelvic external beam radiotherapy (total dose, 50 Gy) and either high-dose-rate or low-dose-rate intracavitary brachytherapy according to institutional practice. The planned Point A dose was 24-28 Gy in four fractions for high-dose-rate-intracavitary brachytherapy and 40-45 Gy in one to two fractions for low-dose-rate-intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m(2)) were administered during the radiotherapy course. RESULTS: All patients were eligible for the study. The median follow-up was 27.3 months. Of the 120 patients, 100 (83%) received four or five cycles of chemotherapy. Acute Grade 3 leukopenia was observed in 21% of the patients, and Grade 3 gastrointestinal toxicity was observed in 6%. No patient failed to complete the radiotherapy course because of toxicity. The 2-year local control and overall survival rate for all patients was 87.1% and 79.6%, respectively. The 2-year major late rectal and bladder complication rate was 2.5% and 0%, respectively. CONCLUSION: The results have suggested that concurrent chemoradiotherapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.