(1) Following the agreement of the 9th Forum for Nuclear Cooperation in Asia (FNCA) Coordinators Meeting in March 2008, and the 9th FNCA Meeting in November 2008, the FNCA FY2008 Workshop on Radiation Oncology was held from January 28 to 31, 2009, in Surabaya, Indonesia. The meeting was organized by the National Nuclear Energy Agency of Indonesia (BATAN) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, in cooperation with Nuclear Safety Research Association (NSRA) of Japan. Representatives from 8 FNCA Member States, namely Bangladesh, China, Indonesia, Japan, Malaysia, the Philippines, Thailand and Vietnam, participated in the workshop. A representative of Korea could not attend the meeting this time, nevertheless he sent his data.
(2) Dr. Hudi Hastowo, Chairman of BATAN, opened the Workshop officially with his opening remarks on behalf of host country. He recalled some of the history of FNCA Radiation Oncology project, and stressed the importance of this project in the frame of sciences and technologies. Dr. Hirohiko Tsujii, Project Leader of Japan, made his remarks and mentioned some of the achievements of the project including recent publications on QA/QC. He also explained the objectives of the meeting and the outline of the program.
(3) Dr. Nana Supriana gave a Special Lecture “Present Status of Radiation Oncology in Indonesia”. He explained the history and present status of radiation oncology in Indonesia.
(4) The agenda was adopted, and chairpersons and rapporteurs were elected. (See Annex 1) All the participants including a new participant, Dr. Parvin Akhter Banu, Bangladesh, was introduced.
Session 1: Phase II Study of Chemoradiotherapy for Locally Advanced Cervical Cancer (CERVIX-III)
(5) The recent clinical data of Phase II study of chemoradiotherapy (CRT) for locally advanced cervical cancer (CERVIX-III) was presented by representatives of each participating country (China reported on 18 patients, Indonesia 5, Japan 32, Korea 10, Malaysia 14, Philippines 12, Thailand 19, and Vietnam 10). The summary of the follow-up data was presented by Dr. Shingo Kato. Total of 120 patients with stage IIB (60pts) and stage IIIB (60pts) diseases were registered and analyzed. The incidence and severity of acute toxicity were within acceptable level and most late complications were mild or moderate on the bases of the 3-year follow-up rate of 93%. The 3-year rates of grade 3-4 late rectal and bladder complications were 4% and 0%, respectively. The 3 year over all survival and local control rates of the patients were 68.8% and 80.9%, respectively.
(6) CERVIX-III results were comparable or somewhat superior to those of the recognized international clinical reports. This demonstrated that the concurrent CRT was feasible and effective for patients with locally advanced cervical cancer in FNCA countries. The result highlighted that PALN and distant metastases be analyzed for further improvement of treatment strategy. The relationship between rectal and bladder doses and late toxicities will be evaluated. The follow-up was recommended to continue for at least 5 years.
Session 2: Phase II Study of Concurrent Chemotherapy and Extended-Field Radiotherapy for Locally Advanced Cervical Cancer (CERVIX-IV)
(7) Dr. Tatsuya Ohno presented published data on Extended Field Radiotherapy with Concurrent CRT. He reported on 8 studies published from 1998 to 2009 which showed that this method of treatment is associated with severe complications. He concluded that the Cis-Platin dose adopted in these trials may have an impact on the compliance of this treatment. He recommended reducing the bowel dose as much as possible. This was followed by the presentation of the experiences of the participating countries using the CERVIX-IV Protocol. China reported on 3 patients, Indonesia 4, Japan 3, Korea 7, Malaysia 1, Philippines 4, and Thailand 1. All countries except Japan and Korea expressed difficulty in patient recruitment because of the inclusion criteria of Abdominal CT Scan which they find quite expensive. Their experience also showed increased severe toxicity especially leucopenia, neutropenia, nausea and fatigue.
(8) Dr. Shingo Kato presented an analysis of the combined data submitted by the participating countries. Of the 25 patients recruited, 7 were considered not evaluable because of using a different chemotherapy dose, a (+) PALN before treatment and no treatment was given in 1 patient. Of the evaluable 18 patients, treatment deviations were also observed both in the administration of radiotherapy and chemotherapy. The preliminary analysis showed a higher incidence of dose limiting toxicity (Grade 3 and 4), both hematological and non-hematological toxicities and that there is difficulty in completing the protocol treatment due to these toxicities.
(9) An open discussion ensued on whether to discontinue CERVIX-IV and formulate a new protocol or to continue it with modification. The latter option was agreed upon and the modifications were made (Table 1).
|Table 1. Modification of CERVIX -IV protocol
|1. Modify PALN RT technique
4 field: recommended
|2. Reduce PALN RT volume
Upper level: L1/L2
Width of AP field: from 8 cm to 7 cm
|3. Modify the treatment schedule
Start PALN-RT 2-4 weeks after start of WP-RT
|4. CDDP dose (not modified)
Fixed to 40mg/m2
(10) Dr. Shingo Kato will provide each participating country with the original protocol with modifications and new registration sheets by email. Each country will again present their experiences at next year's FNCA Workshop.
Session 3: QA/QC of Radiation Dosimetry
(11) Report on intercomparison measurements using glass dosimeters done at 7 centers in 4 countries on 20 photon beams were presented by Dr. Hideyuki Mizuno. In all, 17 beams were within optimum level, 2 beams within the tolerance level, with 1 beam out of tolerance level. It was subsequently rectified and brought to within the tolerance level.
(11-b) “The Handbook in Brachytherapy Physics” was distributed to each country's participant for improvement of QA/QC.
(12) Regarding the schedule of the next field work, further work remains to be done in Thailand, Malaysia, Bangladesh, Vietnam (Hanoi). A problem of custom duty for the test equipment was mentioned. The proposed solution is to adopt the solution used by IAEA audit group; by declaring the test equipment as of no commercial value and a nominal value for custom duty purpose. The method seemed to work well and will be adopted for all future field works.
Session 4: Technical Visit to Radiotherapy Division, Dr. Soetomo General Hospital, Surabaya
(13) The participants conducted a Technical Visit to Dr. Soetomo General Hospital and observed the Radiation Oncology Department.
Session 5: Open Lecture
(14) Open lecture was held at the Diagnostic Center Building, Dr. Soetomo General Hospital, as a part of the workshop. Dr. Hirohiko Tsujii gave opening remarks and Dr. Usman Hadi, Vice Director of Dr. Soetomo General Hospital, gave Welcome Address. It was followed by the open lectures by 5 speakers. (Program attached in Annex 1). There were around 60 participants including radiation oncologists, medical physicists, radiotherapy technicians, nurses, medical doctors from other departments, and medical students.
Session 6: Phase II Study of Chemoradiotherapy for NPC (TxN2-3) (NPC-I)
(15) The session started with Dr. Takehiro Inoue's presentation on comparisons from different studies on treatment of NPC. One salient feature was highlighted to all participants about the grade III (40%) complications from the RTOG study. Then, reports from all participating countries were presented. (China 5 patients, Indonesia 5, Malaysia 25, Philippines 5, Thailand 5, and Vietnam 59) There were discussions on causes for interruption in treatment, on acute and late morbidities especially incidence of xerostomia, about re-irradiation of recurrent cases, residual neck nodal management and issues related to non-compliance of chemotherapy treatment.
(16) Dr. Tatsuya Ohno presented the summary of the FNCA NPC-I study results, showing comparisons with different studies. He highlighted that the FNCA study showed equivalent or slightly better results in many instances. The group discussed about the need to extend the study based on the results presented by Dr. Ohno. The group felt that it would be better for the study to continue and recruit more than 120 patients based on the review of other studies.
Session 7: Phase II Study of Chemoradiotherapy for NPC (T3-4N0-3) (NPC-II)
(17) Clinical data from this study were presented by China (1), Indonesia (8), Malaysia (6), Thailand (1) and Vietnam (36). Ninety five percent of patients completed 6 cycles of chemotherapy. Actual mean dose of cisplatin (165mg/m2) was slightly lower than Chan's study (174-187 mg/m2). Incidence of nausea, vomiting and leukopenia were also lower. Toxicities were manageable with only few patients developing grade IV toxicities. Clearance rate (CR) was 95%, which was a favorable response for T3-4 disease. With a median follow-up time of 24 months, the overall 1 and 2- year survival rates were 95% and 84%, respectively.
(18) Registration will be extended for another year. The total number of patients will be more than 70. Further follow-up is needed to confirm long-term efficacy and late toxicities.
Session 8: Future plans, Other activities
(19) The following was confirmed for the current protocols: The follow up for CERVIX -III will be continued for 2 more years; CERVIX -IV will be modified and continued; registration for NPC-I will be continued for 1 more year to recruit at least total of 120 patients; and registration for NPC-II will be continued for another year to recruit more than 70 patients.
(20) Possibility of the next protocols was discussed. For cervix cancer, CRT +adjuvant chemotherapy was suggested as one of them. A new trial including extended radiation fields needs to await results of the current study (CERVIX-IV). For NPC, a trial with or without adjuvant chemotherapy was also suggested. Further discussion will be continued at the next meeting.
(21) Dr. Tatsuya Ohno was nominated as the first author of NPC-I paper. The importance of the quality of the paper was stressed.
(22) Dr. Hideo Tatsuzaki presented work in progress for survey of status medical physicists in FNCA countries. A need for more description of educational qualifications and training was suggested.
(23) The meeting suggested Malaysia as the host for the next workshop subject to an agreement of the Government of Malaysia. The tentative schedule is January 18-22, 2010, and Kuching was suggested as tentative venues.
(24) Although the budget for the project was reduced FY2008, which only supported one participant from each country, the project has achieved significant outputs and is worthy to continue. It is important to convince the coordinator of each country and to get funding for additional participants. It is highly recommended that the Project Leader and/or persons involved in the registration of cases should come to the meeting. Continuity in participants' attendance is crucial to keep track of issues/data associated with the trials in order to maintain high quality of data input. Therefore, it was suggested that at least two participants from each country for each cervix and NPC trials attend the meetings.
(25) The importance to present the results in national and international meetings was emphasized.
Session 9: Drafting the Workshop Minutes
(26) At the beginning of session, Dr. Miriam J.C. Calaguas gave a special lecture on the experience of the American Society of Radiation Oncology (ASTRO) Educational Course. The educational contributions of FNCA open lectures was cited. Access to training opportunities organized by ASTRO, IAEA, JICA, etc. were discussed.
(27) The draft minutes presented by rapporteurs were discussed, amended and adopted.
(28) Participants expressed appreciation to the local organizing committee, especially to Dr. Nana Supriana and Dr. Dyah Erawati, for the excellent conduct of the Workshop and for their hospitality, to Dr. Hirohiko Tsujii for his dynamic leadership, and to 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 the participants as well as his expectations for the future of the project. Dr. Taswanda Taryo, Deputy chairman for Utilization of R&D Results and Socialization of Nuclear Science & Technology, BATAN, closed the workshop officially.
List of Annexes
Annex 1: Agenda
Annex 2: Participants list