Minutes of
FNCA FY2023 Workshop on Radiation Oncology Project
October 25-28, 2023
Chiba & Saitama, Japan
(1) Following the agreement at the 23rd Forum for Nuclear Cooperation in Asia (FNCA) Coordinators Meeting, the FNCA FY2023 Workshop on Radiation Oncology was held from 25th to 28th October 2023, in Chiba and Saitama, Japan. The meeting was co-organized by the National Institutes for Quantum Science and Technology (QST), the Saitama Medical University (SMU) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). Representatives from 11 FNCA member countries, namely Bangladesh, China, Indonesia, Japan, Kazakhstan, Korea, Malaysia, Mongolia, Philippines, Thailand and Vietnam participated in the workshop.
Opening Ceremony
(2) Dr. WAKATSUKI Masaru, Director of Department of Radiology and Radiation Oncology, QST Hospital, Quantum Life and Medical Science Directorate, QST moderated the session.
Mr. OBATA Ryoji, Deputy Director, International Nuclear and Fusion Energy Affairs Division, Research and Development Bureau, MEXT welcomed the participants with his address.
Dr. KOYASU Shigeo, President of QST gave participants a welcome address.
Dr. TAMADA Masao, FNCA Coordinator of Japan delivered an opening remark.
Mr. WADA Tomoaki, FNCA Advisor of Japan delivered an opening remark.
Prof. KATO Shingo, the Project Leader of Radiation Oncology Project gave his remark.
(3) Dr ISHIKAWA Hitoshi, Vice President of QST Hospital delivered a special lecture on Current Status of Particle Therapy in Japan.
(4) Introduction of individual participants followed.
(5) The agenda was adopted and chairpersons and rapporteurs were selected.
Session 1: Prospective Observational Study of 3D-Image Guided Brachytherapy for Locally Advanced Cervical Cancer (CERVIX-V)
(6) Dr. MURATA Kazutoshi, Chief Physician, Radiation Oncology Section, Department of Diagnostic Radiology and Radiation Oncology, QST Hospital, Quantum Life and Medical Science Directorate, QST presented the protocol of Cervix-V. This was followed by country presentations on clinical data.
(7) Newly registered cases were 15.
The number of target cases enrolled is 100 cases. From May 2017 to October 2023, 104 patients were enrolled in Cervix-V. Out of these, 96 patients were eligible. Case enrollment from member countries are: Bangladesh (2), China (12), Indonesia (9), Japan (13), Kazakhstan (8), Korea (0), Mongolia (4), Malaysia (11), the Philippines (8), Thailand (32) and Vietnam (5).
As per the preliminary analysis of Cervix-V, 82 patients with median follow-up of 27.7 months were analyzed. All patients were treated with 3D-IGBT. Among them, 31 patients were treated with the interstitial technique. Compared to the reference doses, 93% of cases satisfied those doses.
Regarding toxicities, grade 3 acute hematological toxicity was observed in 21 (25%) patients, and grade 3 acute non-hematological toxicity was observed in 2 (2%) patients. No grade 4 or severe acute toxicity was observed. No grade 3 or severe late toxicity was observed to date.
With a median follow-up time of 27.7 months, the 2-year, locoregional control (LC), progression-free survival (PFS), and overall survival (OS) were 92%, 73%, and 88%, respectively. Locoregional recurrence occurred in 15 cases; 8 were in regional lymph node recurrence, and 7 cases were local recurrence.
(8) An open discussion on CERVIX-V followed.
-A discussion regarding Local failure has been done and comments has been made by Prof. KATO Shingo and Dr. Kamal UDDIN, Associate Professor (CC), Department of Radiation Oncology, National Institute of Ear, Nose & Throat (ENT), Bangladesh that local failure can be stratified as failure at primary site and failure at Pelvic nodal Station. Prof. OHNO Tatsuya, Professor and Chairperson Department of Radiation Oncology, Gunma University Graduate School of Medicine made comment on the importance of Interstitial brachytherapy treating the large lesion.
- Prof. KATO Shingo announced that the target number of patients for Cervix V have been achieved hence enrollment will be closed. A follow-up of at least 2 years was recommended for the overall survival data. A close follow-up from member countries was encouraged.
Session 2: QA/QC for 3D-IGBT
(9) Dr. MIZUNO Hideyuki, Senior Principal Researcher, Radiation Quality Control Section, QST Hospital, Quantum Life and Medical Science Directorate, QST reported the results of on-site audits in 2022 and 2023.
The summary of the report is as follows.
- The dosimetry audit for IGBT was conducted for 3 centers from 2 countries.
- Measured dose for point A, bladder and rectum were agreed with TPS calculated value within a tolerance level for hospital A and B.
- Applicator offset value was measured for the centers and two centers showed out of tolerance difference between measured and stated value. The hospital staff re-measured the value after the on-site audit and confirmed the consistency with the audit results and fixed it.
- Measured source strength and TPS registered value agreed within a tolerance level for all centers.
- External dosimetry audit really improves the quality of radiation therapy of the member states.
(10) Dr. KIM Kum Bae, Chief Medical Physicist & Principal Researcher Radiation Oncology Department, Korea Institute of Radiological & Medical Sciences (KIRAMS) commented on the results.
(11) An open discussion followed.
Session 3: Phase II Study of Neoadjuvant Chemotherapy with Concurrent Chemoradiotherapy (CCRT) for Nasopharyngeal Carcinoma (NPC-III)
(12) Dr. MAKISHIMA Hirokazu, Professor (Assistant), Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba presented the summary of analyzed clinical data of NPC-III.
120 patients have been registered in this protocol. The number of patients by county is Bangladesh (1), China (9), Indonesia (12), Japan (0), Kazakhstan (0), Korea (0), Malaysia (31), Mongolia (0), Philippines (7) Thailand (0) and Vietnam (60).
The primary endpoint of this clinical trial is set to 3-year OS. Patient enrollment was completed in 2019. Total number of patients enrolled in NPC-III is 120. All enrolled cases have now reached primary endpoint evaluation period. Comparing NPC-III with NPC-I, it showed lower local control but comparable OS. Some data is missing for final analysis.
An open discussion on the clinical data of NPC-III followed.
- Prof. OHNO Tatsuya asked reasons about the higher local failure rate and lower progression free survival compared to NPC-I trial. One of the possible reasons is underestimation of local failure in NPC-I trial.
- Dr. OKONOGI Noriyuki Professor (Associate), Department of Radiation Oncology, Juntendo University Graduate School of Medicine asked to clarify regarding ‘human error’ as part of cause of interruption of radiotherapy over 14 days. Dr. MAKISHIMA Hirokazu explained that it was communication breakdown.
Session 4: Phase II Study of Hypofractionated Radiotherapy for Breast Cancer (Postmastectomy Radiation Therapy (PMRT) & (Whole Breast Irradiation (WBI) /BREAST-I)
(13) Dr. KONO Sawa, Assistant Professor, Department of Radiation Oncology, Tokyo Women’s Medical University presented the summary of analyzed clinical data of PMRT / BREAST-I. The summary is as follows.
From February 2013 to October 2019, 222 cases were registered. The number of patients registered from Bangladesh (84), China (13), Indonesia (0), Japan (15), Kazakhstan (20), Korea (0), Malaysia (0), Mongolia (26), Philippines (18), Thailand (0) and Vietnam (46). All but one completed the protocol treatment and was analyzed. The acute adverse effects of skin G1 (62%), G2 (10%), G3 (5%); subcutaneous tissue G1 (16%), G2 (2%); lung G1 (6%); heart G1 (9%). The Follow up period is 1 to 119 months with a median of 55 months. The late adverse effects of skin G1 (42%), G2 (1%); subcutaneous tissue G1 (16%), G2 (2%); breast G1 (5%); lung G1 (6%); heart G1 (2%). No grade 3 or over late toxicity has been observed. There were 7 loco-regional recurrence, 33 distant metastases, 23 breast cancer deaths and 9 intercurrent deaths. The five-year loco-regional control, progression free survival and overall survival rates are 97.1%, 81.7% and 89.7%, respectively.
(14) Next, Dr. KONO Sawa presented the summary of the analyzed clinical data of WBI / BREAST-I followed. The summary is as follows.
From February 2013 to October 2018, 227 cases were registered. The registered numbers were Bangladesh (31), China (6), Indonesia (16), Japan (134), Kazakhstan (14), Korea (9), Malaysia (0), Mongolia (3), Philippines (0), Thailand (14) and Vietnam (0). All patients with 228 tumors completed the protocol treatment and was analyzed. The acute adverse effects of skin G1 (80%), G2 (11%), G3 (2%); subcutaneous tissue G1 (11%); lung G1 (1%). The Follow up period is 6 to 125 months with a median of 69 months. The late adverse effects of skin G1 (21%), G2 (1%); subcutaneous tissue G1 (10%); breast G1 (9%); lung G1 (2%). The cosmetic outcome was excellent (148), good (74), fair (3) and poor (3) in patients with more than 3 years follow-up.
Two loco-regional recurrence, 6 distant metastases, 3 breast cancer deaths and 9 intercurrent death have been observed. No grade 3 or over late toxicity has been observed. The 5-year LC, PFS survival and OS are 99.6%, 95.6% and 96.1%, respectively.
An open discussion on the clinical data of BREAST-I followed.
Dr. KONO, Sawa, presented the proposed measurement instructions for upper arm edema for Breast-I patients.
Dr. Erdenetuya Yadamsuren, Radiation Oncologist of Department of Radiation Oncology, National Cancer Center of Mongolia (NCCM) congratulate the team as the study has been published in Clinical Oncology journal this year.
-Prof. KARASAWA Kumiko, Professor and Chair, Division of Radiation Oncology, Department of Radiology, School of Medicine, Tokyo Women’s Medical University encourage members to continue follow-up the patients.
Session 5: Palliative Radiotherapy (BONE-I and BRAIN-I)
-Research Study on Palliative Radiotherapy for Bone Metastasis
(15) Dr. MAKISHIMA Hirokazu reviewed the newly started research study on Palliative radiotherapy for Bone Metastasis (BONE-I).
He also presented the results of the first survey conducted prior to the workshop. The summary of the results is as follows.
- Shorter fractions were preferred in short life expectancy but not significant. Longer fractions were preferred in load-bearing bones and cases with mass effect. When fracture was imminent or existent 5 fractions was the most popular choice.
- Longer fractions were preferred in hospitalized cases.
- Hospital reimbursement didn't play a role in selecting fractions in most cases except when PS is good.
- Patients tend to prefer the more costly option when far from home.
For the second survey, he encouraged the member states to provide data on the current practice within their facilities.
(16) Discussion followed.
-Clinical Study on Palliative Radiotherapy for Brain Metastasis
(17) Dr Kullathorn Thephamongkhol, Associate Professor, Division of Radiation Oncology, Department of Radiology, Siriraj Hospital, Mahidol University introduced the protocol of BRAIN-I (Added Survival Benefit of Palliative Whole Brain Radiotherapy in Non-Small Cell Lung Cancer: An External Validation and model updating of a Prediction Model). The study design and schema for the prognostic multivariable modeling study were presented.
(18) Dr Kullathorn Thephamongkhol presented the proposed action plan for the study.
IRB submission would be until June 2024. Preliminary data collection until October 2024 and full data collection until October 2025. Data collection cohort of consecutive patients of brain metastasis in NSCLC with and without whole brain RT retrospectively from Jan 2020 to now. October 2025-October 2026 would be analysis of data.
Session 6: New Clinical Study and New Research Study
(19) As CERVIX-V and NPC-III come to an end, this project should consider the next clinical studies.
A clinical study of concurrent chemoradiotherapy using whole pelvic IMRT and 3D-IGBT for locally advanced cervical cancer (CERVIX-VI) was proposed by Prof. OHNO Tatsuya. The protocol of the study will be discussed in 2024.
An idea of a clinical study of preoperative short course radiotherapy for locally advanced rectal cancer was proposed by Dr. Rosdiana binti Abd Rahim, Clinical Oncologist, National Cancer Institute, Malaysia. The concept and its feasibility of the study will be discussed in 2024.
An idea of a clinical study of stereotactic body radiotherapy (SBRT) was proposed by Prof. KARASAWA Kumiko. The concept and target disease of the study will be discussed in 2024.
Session 7: Review of Project Activities and Future Plans
(20) Prof. KATO Shingo presented the review of the project activities for the last 3 years. The summaries are described in the "Final Report of the Project".
In brief,
Cervical Cancer
A prospective observational study on concurrent chemoradiotherapy (CCRT) with three-dimensional image-guided brachytherapy (3D-IGBT) “Cervix-V” is being conducted (2018-). This is the first international multicenter clinical study on CCRT + 3D-IGBT in Asia. As of October 2023, 104 patients were enrolled to Cervix-V in total, and 96 patients were eligible. Tentatively, FNCA Cervix-V has yielded favorable treatment outcomes with the 2-year local control and overall survival rates of 92% and 88%, respectively. Follow-up of patients for 2 more years is needed to evaluate the final results.
Nasopharyngeal Carcinoma
A phase II study “NPC-III” was conducted to evaluate the safety and efficacy of the combination of neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. A total of 120 patients were enrolled in the study. NPC-III produced favorable treatment outcome with the 3-year overall survival rate of 72% with acceptable toxicity rates. This study has been completed in 2023.
Breast Cancer
Two phase II clinical studies (Breast-I) are being conducted (2013-); 1) postoperative hypofractionated radiotherapy for early-stage breast cancer after breast conserving surgery (Breast Conserving Treatment; BCT), and 2) postoperative hypofractionated radiotherapy for advanced-stage breast cancer after total mastectomy (Post Mastectomy Radiation Therapy; PMRT). The results have showed favorable treatment outcomes; 5-year locoregional control rates were 98.9% and 96.3%, respectively, for patients treated with BCT and PMRT. The early results were published in the international medical journal in 2023 (Clinical Oncology 2023; 35: 463-471). We confirmed that the assessment of edema in the upper extremities should also be conducted. Follow-up of the patients for 2 more years is necessary to evaluate the final results.
Palliative Radiotherapy: Bone metastasis (Bone-I) and Brain metastasis (Brain-I).
Bone-I
A questionnaire-based survey, named Bone-I, has carried out in the FNCA member facilities to investigate the current practices of palliative radiotherapy for bone metastasis in Asian countries and to understand the factors associated with the practices (2023-).
Brain-I
Prediction models for brain metastasis are important to assist with clinical decision-making of treatment. Researchers of Thailand (FNCA active members) have developed a new prediction model for survival benefit of adding Whole brain radiotherapy (WBRT) for aforementioned groups of patients. To validate and update the prediction model and to compare the existing prediction models, a retrospective observational cohort study, named Brain-I, has started in the FNCA MSs (2023-).
That protocol was confirmed, and case enrollment will begin within the next year.
Hands on Training of 3D-IGBT
Training of medical personnel is very important to implement 3D-IGBT for cervical cancer. The project conducted hands on training of 3D-IGBT in Bangladesh (WS in 2018) followed in China (WS 2019) and Mongolia (WS in 2022).
Physical QA/QC for Radiotherapy
QA/QC of 3D-IGBT is essential for the reliable radiotherapy. FNCA medical physicist team has been conducting on-site audits on brachytherapy (3D-IGBT) in institutions of FNCA MSs since 2019. The audits include source intensity/source offset position check, end-to-end tests, and immediate dosimetry with ionization chambers. Audits have been successfully completed at institutions in Japan, Korea, China, Philippines, Indonesia, and Malaysia.
(21) Prof. KATO also proposed the future activities in the next 3 years (April 2024 - March 2027) as follows.
Based on the policy to enhance cancer therapy with radiation technology in the Asian region, established by the member countries, promote FNCA Radiation Oncology Project in the member countries under each project leader. Continue and intensify the efforts also through the cooperation with the relevant international organizations to develop and disseminate innovative technology related to radiation therapy.
The objectives of this project for the next three years are as follows.
- To establish optimal treatment protocols of radiotherapy and chemotherapy for predominant cancers in FNCA Member states (MSs).
- To improve the quality of radiotherapy in FNCA MSs.
- To improve treatment outcomes of predominant cancers in FNCA MSs.
To achieve these objectives, specific project activities were confirmed.
A. Clinical Trials:
1) Cervical Cancer
A prospective observational study of 3D-IGBT for locally advanced cervical cancer (Cervix-V).
2) Breast Cancer
2-1) A phase II clinical study of postoperative hypofractionated radiotherapy for early-stage breast cancer after breast conserving surgery (Breast-I, BCT).
2-2) A phase II clinical study of postoperative hypofractionated radiotherapy for locally advanced breast cancer after total mastectomy (Breast-I, PMRT).
3) Palliative Radiotherapy
3-1) Survey on the current practices of palliative radiotherapy for painful bone metastasis in Asian countries (BONE-I)
3-2) Added survival benefit of palliative whole brain radiotherapy in non-small cell lung cancer: An external validation and model updating of a prediction model (BRAIN-I)
4) New clinical trials
New clinical trial was proposed at the 2023 WS. The protocol of the study will be discussed and finalized in 2024, include:
4-1) A clinical study of concurrent chemoradiotherapy using whole pelvic IMRT and 3D-IGBT for locally advanced cervical cancer was proposed at the 2023 WS. The protocol of the study will be discussed in 2024.
4-2) An idea of a clinical study of neoadjuvant short course radiotherapy for locally advanced rectal cancer was proposed. The concept of the study will be discussed in 2024.
4-3) An idea of a clinical study of stereotactic body radiotherapy (SBRT) was proposed. The concept of the study will be discussed in 2024.
B. Physical QA/QC for Radiotherapy
- On-site audits of 3D-IGBT
C. Workshop
D. Hands-on training on 3D-IGBT
E. Open Lecture
F. Technical Visit
G. Collaboration of FNCA and IAEA
The following were also confirmed for the success of this project;
At least 2 delegates from each country should participate in the WS to meet the need for adequate representation of clinical trials of various tumor sites as well as representation of both radiation oncologist and medical physicist.
(22) Next workshop will be held in Thailand tentatively between 11-16 or 25-30 November 2024. In 2025, the workshop will be held in Kazakhstan.
Session 8: Drafting Workshop Minutes
(23) The WS participants reviewed workshop discussion.
The draft of the minutes was submitted by rapporteurs, discussed and amended. The draft of the minutes will be circulated after the workshop and finalized.
(24) Prof. KATO Shingo reviewed the workshop of the first two days and thanked all the participants.
Session 9: Technical Visit to QST
(25) Workshop participants divided into 2 groups visited a site of Ion Source Room of Heavy Ion Beam Therapy and a site of radiation emergency medicine respectively.
Session 10: Technical Visit to SMU International Medical Center
(26) On the third day of the workshop, participants visited Saitama Medical University (SMU) International Medical Center.
Dr. SAEKI Toshiaki, President of SMU International Medical Center welcomed the participants and introduced the hospital.
(27) Prof. KATO Shingo, Prof. NODA Shin-ei and Dr. ABE Takanori took the workshop participants on a tour of the Department of Radiation Oncology.
(28) Prof. NODA and Dr ABE gave a presentation on Cyber knife and MR-Linac.
Session 11: Open Lectures
(29) On the last day of the workshop, Open Lectures was held at Moroyama Campus of Saitama Medical University.
(30) Prof. KATO Shingo moderated the session and Dr TAKEUCHI Tsutomu. President of SMU opened the Open Lecture with his remark.
Prof. TAKAHASHI Takeo, Vice President of SMU welcomed the audience with his remark.
Mr. OBATA Ryoji, MEXT delivered a remark.
(31) Dr. TAMADA Masao gave a presentation about the FNCA. He introduced its overview and spoke about the on-going 8 projects’ activities and achievements.
(32) Prof. Miriam Joy Calaguas, Active Consultant, Department of Radiation Oncology, St. Luke's Medical Center delivered a lecture on Radiation Oncology in the Philippines -A Health Systems Analysis-.
(33) Dr. Kullathorn Thephamongkhol spoke on International Perspective for Medical Student: an Example using Cancer Data from Thailand.
(34) Dr. A F M Kamal Uddin, Associate Professor (CC), Department of Radiation Oncology, National Institute of Ear, Nose & Throat (ENT), delivered a lecture titled “Radiotherapy in Bangladesh: Past, Present and Future”.
(35) Prof. KATO Shingo gave a lecture on Radiation Oncology in Japan and International Cooperation among Asian Countries.
(36) Prof. KATO Shingo concluded the Open Lecture with his remark.
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