(1) Following the agreement of the 8th Forum for Nuclear Cooperation in Asia (FNCA) Coordinators Meeting in February 2007, and the 7th FNCA Meeting in November 2007, the FNCA FY2007 Workshop on Radiation Oncology was held from January 22 to 25, 2008, in Manila, Philippines. The meeting was organized by St. Luke's Medical Center and the Philippine Nuclear Research Institute (PNRI) and co-organized by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, in cooperation with Nuclear Safety Research Association (NSRA) of Japan. Representatives from 9 FNCA Member States, namely Bangladesh, China, Indonesia, Japan, Republic of Korea, Malaysia, the Philippines, Thailand and Vietnam, participated in the workshop.
(2) Dr. R. De los Reyes, Jose R. Reyes Memorial Medical, the Philippines, acted as the chairperson. Following the National anthem of the Philippines, Ms. Victoria Fe O. Medina prayed to God for success of the meeting. The opening remarks were delivered by Dr. Miriam Joy. C. Calaguas, St. Luke's Medical Center, the Philippines, on behalf of host country. She recalled some of the history of FNCA Radiation Oncology project. Mr. Kenichi Miyazawa, Researcher, International Nuclear and Fusion Affairs Division, Research and Development Bureau, MEXT, Japan, gave his remarks expressing his appreciation to the hosts and stressing the importance of this project in the frame of sciences and technologies. Dr. Corazon Bernido, Deputy Director of PNRI, the Philippines gave her remarks and stressed the importance of FNCA and this project. Finally, Dr. Hirohiko Tsujii, Project Leader of Japan, from National Institute of Radiological Sciences, made his remarks and mentioned some of the achievement of the project including recent publications in international journals. He also addressed the importance of cooperation with the IAEA RCA project.
(3) Dr. Teresa Sy-Ortin, Past President, Philippine Radiation Oncology Society (PROS), gave a Special Lecture "Present status of radiation therapy in the Philippines". She explained the history and present status of radiation oncology in the Philippines. Dr. Hirohiko Tsujii, Japan, explained the objectives of the meeting and the outline of the program.
(4) The agenda was adopted, and chairpersons and rapporteurs were elected. (See Attachment 1) All the participants including the new participants, Dr. Faridul Alam, Bangladesh, Dr. Xu Xiaoting, China, Dr. Dyah Erawati, Indonesia, and Dr. Ngo Thanh Tung, Vietnam, were introduced. Dr. Syed Md Akram Hussain, Bangladesh, was introduced later. Bangladesh attended the radiation oncology workshop for the first time as a protocol participant.
Session 1: Phase II Study of Chemoradiotherapy for Uterine Cervix Cancer (CERVIX-III)
(5) Between April 2003 and March 2006, a total of 120 patients (China; 18, Indonesia; 5, Japan; 32, Korea; 10, Malaysia; 14, Philippines; 12, Thailand; 19, and Vietnam; 10) with locally advanced cervical cancer were registered in the study and were treated with concurrent chemoradiotherapy (CCRT) with weekly cisplatin at a dose of 40mg/m2. The 2-year follow-up data of the patients were reported from each country. (Annex 3)
Session 2: Phase II Study of Chemoradiotherapy for Uterine Cervix Cancer (CERVIX-III), Evaluation of the Treatment Results
(6) Detailed analyses of the treatment results of CERVIX-III were reported by Dr. Kato, Japan, of the data center. Total 120 patients were treated.
(7) The 2-year local control and overall survival rates for all patients were 87% and 80%, respectively. On the univariate analyses, FIGO stage and biological effective dose (BED) were significant prognostic factors for local control, while tumor size, histological subtype, dose rate of brachytherapy did not show any significance. The 2-year actuarial rate of grade 3-4 late toxicity was 2%. These treatment outcomes were comparable with those of several large studies of CCRT in the US and Canada. The results have suggested that CCRT using Cervix-III protocol is feasible and effective for patients with locally advanced cervical cancer in Asian countries. However, we agreed that further follow-up is necessary to evaluate long-term toxicities and efficacies.
(8) We also agreed that Dr. Kato, Japan, submit the preliminary reports of the CEREVIX-III to the international journal of radiation oncology and that we continue to follow-up patients at least 3 years in order to report 5-year survival rate.
Session 3: Phase II Study of Concurrent Cisplatin Chemotherapy and Extended-Field Radiotherapy for Locally Advanced Cervical Cancer (Cervix-IV)
(9) Each country presented its clinical data. (Annex 4)
(10) Dr. Kato, Japan, reported a review of clinical trials, GOG 125 and RTOG0116. The GOG 125 combining infusional 5-FU and Cisplatin with EFRT in 86 patients with positive PALN metastases. The dose to treat PALN was 45 Gy (1.5 Gy/FX, upper borders L1 - L2). The investigator reported that the most frequent grade 3 to 4 toxicities to be gastrointestinal 18.6 % and hematological 15.1%. The 3-year rates of local control and survival were 69% and 39%, respectively. The RTOG0116 reported 26 patients Stage I - IVA, PALN and common iliac LN metastases, with pathologically positive 56%, CT/MRI positive 42%, PALN RT 45 Gy, 1.8 Gy/FX. To involved parametrium and lymph nodes 54-60 Gy (with boost) was given. Acute toxicities were high: 54% grade 3 hematological, 8% grade 4. Late toxicities grade 3 - 4 were 40%.
(11) Dr. Kulllathorn Thephamongkhol, Thailand, reported a review of the role of prophylactic PALN RT, to evaluate the benefit and risk. The RTOG 79-20 presented very high toxicity (grade 5: 1/30 patients). The RTOG 79 - 20 reported 10 years' results of 44% vs. 55%, with more benefit for patients received EFRT. Based on these presented data, the role of prophylactic PALN RT was discussed together with the benefit of PET for detection of PALN.
Session 4: Phase II Study of Chemoradiotherapy for NPC (TxN2-3) (NPC-I)
(12) Each country presented its clinical data. (Annex 5)
(13) Dr. Tatsuya Ohno, Japan, presented accumulated data of the Phase II Study, NPC-I. 61 patients were enrolled in the NPC-I study. 1 patient was ineligible due to patient age. Acute side effects were lower than those reported in other studies. The clearance rate was reported as 84%. One more year of patients' enrollment was decided. Vietnam presented additional 51 patients and will be registered later after reception of official registration form.
Session 5: Phase 2 Study of Chemoradiotherapy for NPC (T3-4N0-1) (NPC-II)
(14) This session opened for data report from each country and summary report. There were data reports from 3 countries, Indonesia, Malaysia and Thailand (Annex 6). China, Japan, and Korea have no patients yet. The data from Vietnam (Ho Chi Minh City) has been registered to the data center but not presented here.
(15) Summary data were presented by Dr. Ohno, Japan. Up to now, the data center has 40 patients but 1 patient was excluded from analysis. Most patients have undifferentiated cell type. Interruption of treatment in 5 patients (13%) was due to non-hematological toxicity, hematological toxicity, bleeding, machine broken down and concomitant disease for each patient. Totally, 82% of the patients received chemotherapy at least 6 cycles. The total dose of cisplatin lower than Chan's study and this explained better compliance than Chan's study. When compared with other major studies, our study has less toxicity than INT0099, Singapore's, Hong Kong's and Chan's study. The discussion from participants widely about the reason why toxicity of NPC II is less than the toxicity of NPC I even the chemotherapy in concurrent part is exactly the same. The hypothesis would be the misinterpretation between grade 2 and grade 3 toxicity or possibility to grading toxicity differently among countries. The preliminary analysis shows evaluable 36 patients with complete remission in 31 patients or 86%. Up to now 33 patients were alive in the median follow up time of 16 months. The question from Dr. Kullathorn, Thailand, regarding high rate of distant metastases about 16% in one year when compared with other trials about 20+ % in 3 year has been raised.
Session 6: Technical Visits to St. Luke's Medical Center and Open Lecture
(16) The participants conducted a Technical Visit to St. Luke's Medical Center and observed the Radiation Oncology Department.
(17) Open lecture was held at St. Luke's Medical Center as a part of the workshop. There were around 150 participants including medical doctors, medical physicists, researchers, technical staff, and medical students. One of the five lectures was on "Target Delineation in 3-D Conformal Radiotherapy - IAEA/RCA Report" by Dr. Nakano, Japan. This was very well received by the audience who requested for copies of the lecture. The other lecture was on Radiotherapy and Chemoradiotherapy for Cervical and Nasopharyngeal Cancer - FNCA Report by Dr Ohno, Japan. Detailed open lecture program is listed in the program (Attachment 1).
Session 7: Technical Visits to Philippine General Hospital
(18) The participants conducted a Technical Visit to Philippine General Hospital and observed the radiation oncology department and the Cancer Institute.
Session 8: QA/QC of Radiation Dosimetry
(19) Presentations for the above were made by Ms. Lilian V. Rodriguez, Philippines and Dr Tang Tieng Swee, Malaysia. Dr Hideyuki Mizuno, Japan presented a report on the field work and the schedule of the next field work on QA/QC in teletherapy work. A presentation on QA/QC for Guideline on Intracavitary brachytherapy was also presented by Dr Yuzuru Nakamura, Japan.
(20) The presentations were followed by questions and comments from the floor, as follows:
1. Limitations of equipments in various treatment institutions hinder the proposal of a comprehensive QA/QC protocol in radiation therapy.
2. Matters related to custom duty when sending test kits to various countries on postal audit using glass dosimeter from Japan were discussed thoroughly. Several suggestions were given to solve this problem.
3. Matters related to scarcity of medical physicist in Bangladesh - lack of post, training program, etc. were discussed. Several suggestions were given on how best to solve these problems.
Session 9: Future plan, Other activities
(21) Dr. Tsujii described the achievements of the projects. Collaboration with IAEA/RCA was discussed. Dr. Nakano, Project Lead Country Coordinator of RCA radiotherapy project, proposed to invite FNCA member to RCA training courses as lecturer, and offer RCA teaching materials to FNCA participants. Comments from IAEA are also valuable for FNCA clinical trial and attendance of IAEA staff as an observer to FNCA meetings is recommended. Participation of RCA members other than current FNCA members to clinical trials was discussed.
(22) In each country, the same investigator responsible for the studies should be recommended to attend FNCA meeting continuously during the project. e-mail help line for assisting the clinical trial was proposed, but this is already a part of current project.
(23) Continuation of the current protocols and implementation of QA/QC for external beam in non-completed country were suggested as the future plan.
(24) The meeting suggested Indonesia as the venue for the next workshop subject to an agreement of the Government of Indonesia. The tentative schedule is January 19-23, 2009, and Bandung or Surabaya was suggested as tentative venues.
(25) Dr. Hideo Tatsuzaki, Japan, reported a questionnaire on the status of cancer treatment and the future plan with limited questions was decided.
Session 10: Evaluation of the FNCA Project
(26) Each country presented the scientific and socioeconomic impact of the project. Overall evaluation was discussed and agreed (see annex).
Session 11: Drafting the Workshop Minutes
(27) The draft minutes presented by rapporteurs were discussed, amended and adopted.
(28) Participants expressed appreciation to local host, PNRI, St. Luke's Medical Center, local organizing committee, especially Dr. Miriam Joy Calaguas and Dr. Rey de los Reyes, and Dr. Hirohiko Tsujii for his dynamic leadership, and NSRA. The participants especially expressed their gratitude for the continuing support from MEXT of Japan for this project. Closing Remarks were given by Dr. Hirohiko Tsujii, Japan, who expressed his appreciation to the host institute and participants as well as his expectations for the future of the project.
List of Annexes
Annex 1 Agenda
Annex 2 Participants list
Annex 3 Country presentations on CERVIX-III
Annex 4 Country presentations on Cervix-IV
Annex 5 Country presentations on NPC-I
Annex 6 Country presentations on NPC-II