Report of
FNCA 2016 Workshop on Radiation Oncology

Outline of Workshop

The FNCA 2016 Workshop on Radiation Oncology was held from 8 to 11November2016 in Surabaya, Indonesia.
The workshop was co-organized by Dr. Soetomo General Hospital and National Nuclear Energy Agency (BATAN) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).
28 participants from 11 FNCA Member Countries, namely Bangladesh, China, Indonesia, Japan, Kazakhstan, Korea, Malaysia, Mongolia, the Philippines, Thailand and Vietnam participated in the workshop.
This project carries out some international joint clinical studies in order to establish treatment protocols for Uterine Cervix cancer, Nasopharyngeal cancer and Breast cancer, which affect large number of people in FNCA member countries, and finally to improve the technique of radiation oncology in the Asian region.

Opening Ceremony
Dr. DyahErawati, Head of Radiotherapy Department, Dr. Soetomo General Hospital moderated the session. She officially opened the workshop.
Mr. Tomoaki WADA, FNCA Coordinator of Japan gave the opening address.
Dr. HendigWinarno, FNCA Coordinator of Indonesia welcomed the participants with his remarks.
Prof. Shingo KATO, Professor /Department of Radiation Oncology, International Medical Center, Saitama Medical University gave his opening remarks as the new project leader.
Dr. Joni Wahyuadi, Vice director of medical services and nursing, Dr.Soetomo General Hospital gave a special lecture entitled "Overview management of tumor malignancy in Dr. Soetomo General Hospital as A Referral of Cancer Treatment for East Indonesia and National". His talk focused on the current situation of cancer treatment within Indonesia and the role of Dr. Soetomo General Hospital.

Phase II Study of Concurrent Chemotherapy and Extended-Field Radiotherapy for Locally Advanced Cervical Cancer (CERVIX-IV)
In this protocol, 105 patients were registered from all the countries at the point of this workshop. The 105cases were consisted of Bangladesh (31), China (8), Indonesia (9), Japan (20), Korea (7), Malaysia (5), Mongolia (8), Philippines (4) Thailand (4) and Viet Nam (8).

93casesout of the 105 cases were considered evaluable. Of the 93, 49patients had stage IIB disease and 44 had stage IIIB disease. All patients had positive pelvic lymph node (PLN) and negative paraaortic lymph node (PALN) assessed by CT (or US). Grade 3 leukopenia occurred in 19 (21 %) patients. Mean overall treatment time was 57 days. Mean dose to point A was 83.6 Gy. 75(81%) patients received. 75 (81 %) patients received > 4 cycles of chemotherapy. The 2-year follow-up is 88%. The 2-year and 5-year local control (LC) were 96% and 93%, respectively. The 2-year and 5-year progression free survival (PFS) were 75% and 66%, respectively. The 2-year and 5-year overall survival were 91% and 75%, respectively.

An open discussion on the clinical data of Cervix-IV followed. The result of Cervix-IV is better than Cervix-III, patients with distant metastases decreased. On the other hand, the follow-up patients need CT. Preliminary analysis showed no difference in overall survival (OS) between stage IIB and IIIB. Long follow-up (5-year) is needed to evaluate OS and late toxicity.

ANew Protocol forCervical Cancers (Retro CERVIX-V)
In last year's WS, 3D image-guided brachytherapy (3D-IGBT) Retrospective Study was proposed in order to consider 3D-IGBT method for cervical cancer in FNCA member country.This includes dose volume histogram parameters used for assessment of the doses to the target volume and OARs at brachytherapy, the dose of external beam radiotherapy to the whole pelvis, the planning aim doses of brachytherapy, and actual delivered doses to the target volume and OARs, etc. The goal of the study is to develop a consensus on 3D-IGBT for cervical cancer among FNCA member countries which will serve as the basis for CERVIX-V.
Japan presented the results of the survey on 3D-IGBT for cervical cancer, which was conducted among FNCA members as a part of the proposed retrospective study.The results were based on the treatment data from clinical practice.

Many aspects of routine practice of 3D-IGBT in each country were presented and discussed in order to estimate the feasibility of 3D-IGBT protocol of CERVIX-V (e.g., requirement of imaging, delineation of the high-risk clinical target volume [HR-CTV], dose and fractionation schedule of 3D-IGBT, technique to avoid unnecessary rectal and bladder dose, dose and technique of external beam radiotherapy with or without central shielding, and regimen of chemotherapy).

Japan introduced the concept of new protocol to use 3D-IGBT for the cervical cancer, named "CERVIX-V". The objective of this protocol is to evaluate the efficacy and toxicity of 3D-IGBT for cervical cancer. The primary endpoint is 2-year overall survival, and secondary endpoint is 2-year local control and toxicities. The historical control will be CERVIX-III.

Discussion on CERVIX-V followed. Several issues were discussed in order to explore the rationale and feasibility to be adopted as final protocol, for example eligibility criteria, imaging requirement before treatment and at the time of brachytherapy, treatment protocol including external beam radiotherapy, dose and fractionation schedule with 3D-IGBT, dose constraints of the rectum and bladder, regimen of chemotherapy and imaging required during follow-up in order to confirm tumor response and recurrence. The final protocol will be drafted and circulated among participants.

Quality Assurance and Quality Control (QA/QC) for 3D-IGBT
This activity aims to put in place reliable dosimetry in the institutes among the member countries for effective joint clinical studies. The audits in QA/QC of dosimetry measurement and radiation calibration have been conducted, which is for the reliable radiotherapy.
Along with the initiation of CERVIX-V, this QA/QC activity also focuses on the brachytherapy.
A summary of the questionnaire regarding brachytherapy was reported by Japan. This questionnaire was distributed on 26th July in 2016 and included 22 items related to brachytherapy treatment / modalities / staffing / QA and additional 3 items related to external beam radiotherapy. 11 facilities from 10 countries responded to this. There were some differences within the member countries regarding modality, tools and methodology, and on-site audit will be optimized based on these results. Both clinical and physical aspects of audit should be performed after the initiation of CERVIX-V protocol study.

In addition, a medical physicist from Dr. Soetomo General Hospital presented on the status of 3D-IGBT in his hospital and Indonesia. He introduced the department facility and number of patients in his hospital and Indonesia. He also briefly explained the procedure of 3D IGBT in his center. The QA/QC programme that covers daily and annual QA is elaborated. He recommended that FNCA could audit QA/QC in his centre in order to give more accurate and precise treatment.

Phase II Study of Concurrent Chemoradiotherapy (CCRT) for NPC (NPC-III)
A total of 65 patients were registered in this protocol at the time of this workshop. The 65 cases were consisted of Bangladesh (1), China (8), Indonesia (12), Japan (0), Kazakhstan (0), Korea (0), Malaysia (17), Mongolia (0), Philippines (7), Thailand (0) and Vietnam (20).
58 cases out of the 61 cases submitted before the workshop were analyzed and evaluated in this workshop.

Median age was 47 years old. Most patients had 2 -3 cycles of neoadjuvant chemotherapy for a compliance rate of 97%, while concurrent chemotherapy had 75% compliance rate for 4 cycles or more. Median overall treatment time of radiotherapy was 55 days (range 44 - 232 days). Radiotherapy treatment interruption of >14 days occurred in 30% of patients mainly due to machine breakdown and toxicities. In the induction phase, grade 3/4 hematological toxicities occurred in 12% of patients and non-hematological toxicities in 8%. During the concurrent phase, grade 3/4 hematological toxicities occurred in 24% of patients and non-hematological toxicities in 35%. Late toxicities of grade 3 occurred in 5 patients (8%), mainly salivary gland and mucous membrane toxicities.

Efficacy results: 2 year survival results: OS was 79%. Loco-regional control rate (LRC) was 83%. Distant metastasis free rate (DMF) was 85%. PFS was 76%. When compared with the results from NPC-I study, these results showed better rates in DMF and OS but worse rates in LRC, but all of which were not statistically significant. Failure was mainly in the distant metastasis sites (17%) but this figure is lower compared to NPC-I study (28%). The target enrolment is 120 patients but only 65 were accrued so far.

The current problems with enrolment in some countries were discussed. Factors include: different chemotherapy protocol, ethics review board getting more stringent, low NPC incidence, unavailability of LINAC, and competing trials. However, some of these factors were deemed solvable and enrolment is expected to be better next year. So it was decided to continue with enrolment for 1 more year and to review again then.

Phase II Study of Hypofractionated Radiotherapy for Breast Cancer (Postmastectomy Radiation Therapy (PMRT) / (BREAST-I)
In this session, a protocol PMRT/BREST-I was reviewed and the following numbers were reported: Bangladesh (74), China (11), Indonesia (2), Japan (1), Kazakhstan (14), Korea (0), Malaysia (0), Mongolia (19), Philippines (10), Thailand (0) and Vietnam (0). The total number of PMRT patients was (131).

Japan presented the summary of the PMRT clinical data of breast cancer cases (131).
Overall 131 patients in HF-PMRT arm were enrolled during 44 months.
All patients completed protocol treatment. The median age was 48 years old (range, 24-74). Seventy patients (55%) had right-sided breast cancer.
The T stage was T1 in 21 patients (16%), T2 in 84 (64%), T3 in 23 (18%), and T4 in 3 (2%), respectively. The N stage was N0 in 47 patients (36%), N1 in 66 (50%), N2 in 17 (13%), and N3 in 1 (1%), respectively.
The clinical stage was 2A in 50 patients (38%), 2B in 50 (38%), 3A in 27 (21%), 3B in 3 (2%), and 3C in 1 (1%), respectively.
The median treatment duration was 21 days (range, 19-49). Only 6 patients experienced treatment interruption.
Acute dermatitis of grade 2 or more have been observed in 6 patients (5%) and grade 2 acute subcutaneous toxicity has been observed in one patient (1%). Acute grade 1 heart toxicity has been observed in 15 patients (11%) and late grade 1 heart toxicity in 6 patients (5%).
Some patients among them had right-sided breast cancer. Three loco-regional recurrence, 7 distant metastases and 3 breast cancer deaths had been observed.
The result of this protocol will be presented in the ICARO2 (International Conference on Advances in Radiation Oncology) that will be held in Vienna in June 2017.

An open discussion on the clinical data followed.
Some data is missing or probably wrongly filled out in registration sheet. It is unreliable that some patients with right-sided breast cancer developed heart toxicity. All co-investigators need to re-check their data, especially about the late toxicity.
The criteria and methods to evaluate radiotherapy-related toxicity were discussed.
We agreed with the exclusion of 2 cases with phyllodes tumor due to positive resection margin and sarcomatous histology.

Phase II Study of Hypofractionated Radiotherapy for Breast Cancer (Whole Breast Irradiation(WBI)/ (BREAST-I)
In this session, a protocol WBI/BREST-I was reviewed and the following numbers were reported:Bangladesh (26), China (6), Indonesia (12), Japan (107), Kazakhstan (14), Korea (4), Malaysia (0), Mongolia (0), Philippines (0), Thailand (14) and Vietnam (0). Total number of WBI patients was (183).

Japan presented the summary of the WBI clinical data of breast cancer cases (183 patients and 184 breast lesions).
Overall 184 breast lesions in HF-WBI arm were enrolled during 44 months.
All the patients except one patient completed protocol treatment.
The median age was 50 years old (range, 24-79). Ninety-seven patients (53%) had right-sided breast cancer. The T stage was Tis in 21 patients (11%), T1 in 113 (61%), and T2 in 50 (27%), respectively. The N stage was N0 in 155 patients (84%) and N1 in 29 (16%), respectively.
The clinical stage was 0 in 21 patients (11%), 1A in 100 (54%), 1B in 2 (1%), 2A in 42 (23%), and 2B in 19 (10%), respectively.
125 patients received boost radiotherapy to tumor bed with 8.1 Gy in 122 patients and 10 Gy in 3.
The high risk factors were observed as follows: age less than 50 years old in 78 patients, involved lymph node in 29, lymphovascular invasion in 8, and positive resection margin in 11, respectively.
The median treatment duration was 26 days (range, 18-54). Only 2 patients experienced treatment interruption. Acute dermatitis of grade 2 or more have been observed in 30 patients (17%) and grade 2 acute subcutaneous toxicity in 6 patients (3%).
In regards with the late toxicity, grade 2 lung toxicity was observed in 2 patients, grade 2 skin toxicity in 1, grade 2 subcutaneous toxicity in 1, grade 1 heart toxicity in 5, and grade 2 heart toxicity in 2. One loco-regional recurrence, 2 distant metastases and 1 breast cancer death have been observed. The result of this protocol will be presented in the ICARO2 (International Conference on Advances in Radiation Oncology) that will be held in Vienna at June 2017.

An open discussion on the clinical data followed.
Some data is missing or probably wrongly filled out in registration sheet. It is unreliable that some patients with right-sided breast cancer developed heart toxicity. All co-investigators need to re-check their data, especially about the late toxicity.
The participants discussed why the high rates of heart toxicity were observed in some countries. There may be ethnic or regional differences in the incidence of cardiovascular disease. These will be considered in the analysis.
The criteria and methods to evaluate cosmesis were discussed. We discussed about including the patients who received radiotherapy with different fraction sizes. It was agreed to include all fraction sizes between 2.66 Gy and 2.7 Gy. Boost radiotherapy of 10-16 Gy in 5-8 fractions will be allowed because there is no standard boost dose-fraction schedule in hypofractionated breast radiotherapy.
To exclude cases with other protocol violations was agreed. This protocol was initially planned to enroll for 4 years. Additional cases of each country were estimated.
All co-investigators agreed with enrolling the additional cases until Jan 31, 2017.

Review of Project Activities and Future Plan (Including e year's Evaluation)
FNCA projects reviews and evaluate their activities every 3 years.
In this session, the participants reviewed 3 years' activities (JFY2014-2016) and discussed the future plan (JFY2017-2019).

Participants acknowledged that the clinical trials for cervical cancer, nasopharyngeal cancer, breast cancer were conducted as planned with good results and they have become the standard protocols in the FNCA member countries.
Besides clinical trials, a survey with glass dosimeters were conducted as a part of the activities of QA/QC for external therapy, which has improved the quality of radiation therapy in the member countries.
These achievements will be reported in "3 years' evaluation report".

It was agreed that the next workshop will be held in either the Philippines or Malaysia tentatively from 23-27 October or 30 October-3 November, 2017.

Technical Visit
In the morning of the 3rd day, the participants conducted a technical visit to Radiotherapy Division of Dr. Soetomo General Hospital.Linac, HDR treatment system, treatment planning system (2D, 3D and IMRT), and their new medical oncology department.

Open Seminar
TheOpen Seminar,as a part of the workshop, was held atDr. Soetomo General Hospitalin the afternoon of the 3rd day. There were 6lectures on the themes of 1) Overview and Introduction of FNCA, 2) FNCA Oncology Projects and its achievements in cervical cancer treatment, 3)Present Status of Radiation Oncology and Comprehensive Cancer Treatment in Indonesia,4) CT-based brachytherapy for cervical cancer, 5) IMRT and Clinical Quality Assurance and 6) Carbon Ion Therapy.

Closing Session
The workshop was officially closed by Dr. Yuichi MICHIKAWA and Prof. Shingo KATO with their remarks.

Minutes of
FNCA 2016 Workshop on Radiation Oncology Project

(1) Following the agreement at the 17th Forum for Nuclear Cooperation in Asia (FNCA) Coordinators Meeting, the FNCA FY2016 Workshop on Radiation Oncology was held from November 7th to 11th, 2016, in Surabaya, Indonesia. The meeting was co-organized by National Nuclear Energy Agency of Indonesia (BATAN), Dr. Soetomo General Hospital 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, the Philippines, Thailand and Vietnam participated in the workshop.

Opening Ceremony
(2) Dr. Dyah Erawati, Head of Radiotherapy Department, Dr. Soetomo General Hospital moderated the session. She officially opened the workshop.

Mr. Tomoaki WADA, FNCA Coordinator of Japan gave the opening address.

Dr. Hendig Winarno, FNCA Coordinator of Indonesia welcomed the participants with his remarks.

Prof. Shingo KATO, Professor /Department of Radiation Oncology, International Medical Center, Saitama Medical University gave his opening remarks as the new project leader.

(3) Dr. Joni Wahyuadi, Vice director of medical services and nursing, Dr.Soetomo General Hospital gave a special lecture entitled"Overview management of tumor malignancy in Dr. Soetomo General Hospital". His talk focused on the current situation of cancer treatment within Indonesia and the role of Dr. Soetomo General Hospital as A Referral of Cancer Treatment for East Indonesia and National".

(4) Introduction of individual participants followed.

(5) The agenda was adopted and chairpersons and rapporteurs were selected. (Annex 1)

Session 1: Phase II Study of Concurrent Chemotherapy and Extended-Field Radiotherapy for Locally Advanced Cervical Cancer (CERVIX-IV)
(6) Dr. Noriyuki Okonogi, Section Chief, Gynecologic Tumor, National Institute of Radiological Science (NIRS), Hospital, National Institutes for Quantum and Radiological Science and Technology, Japan (QST), presented the protocol of Cervix IV, a Phase II Study of Concurrent Chemotherapy and Extended-Field Radiotherapy for Locally Advanced Cervical Cancer.

An update on the clinical data of (CERVIX-IV) was presented by representatives of each participating country with the following number of patients: Bangladesh (31), China (8), Indonesia (9), Japan (20), Kazakhstan (1), Korea (7), Malaysia (5), Mongolia (8), Philippines (4), Thailand (4) and Vietnam (8). The total number of the patients was (105).

Dr. Okonogi then presented the summary of the follow-up data. As of today, a total of 105 cases were submitted for this study. Two (2) new cases were added this year(China 1 and Kazakhstan 1). Of the 105 cases that were eligible for this study, 12 cases were not evaluable.

Of the 93 evaluable cases: 49 patients had stage IIB disease and 44 had stage IIIB disease. All patients had positive pelvic lymph node (PLN) and negative paraaortic lymph node (PALN) assessed by CT (or US). Grade 3 leukopenia occurred in 19 patients (21%). Mean overall treatment time was 57 days. Mean dose to point A was 83.6 Gy. 75 (81 %) patients received > 4 cycles of chemotherapy. The 2-year follow-up is 88%. The 2-year and 5-year local control (LC) were 96% and 93%, respectively. The 2-year and 5-year progression free survival (PFS) were 75% and 66%, respectively. The 2-year and 5-year overall survival were 91% and 75%, respectively.

(7) An open discussion on the clinical data of Cervix-IV followed. The result of Cervix-IV is better than Cervix-III, patients with distant metastases decreased. On the other hand, the follow-up patients need CT. Preliminary analysis showed no difference in overall survival (OS) between stage IIB and IIIB. Long follow-up (5-year) is needed to evaluate OS and late toxicity.

Session 2: A New Protocol for Cervical Cancer (CERVIX-V)
(8) Dr. Noriyuki Okonogi presented the results of the survey on 3D image-guided brachytherapy (3D-IGBT) for cervical cancer. This survey was conducted among FNCA members in order to know the current status of 3D-IGBT in their hospitals. The results are based on the treatment data from clinical practice.

Many aspects of routine practice of 3D-IGBT in each country were presented and discussed in order to estimate the feasibility of 3D-IGBT protocol of CERVIX-V (e.g., requirement of imaging, delineation of the high-risk clinical target volume [HR-CTV], dose and fractionation schedule of 3D-IGBT, technique to avoid unnecessary rectal and bladder dose, dose and technique of external beam radiotherapy with or without central shielding, and regimen of chemotherapy).

(9) Prof. Masaru Wakatsuki, Professor, Department of Radiology, Jichi Medical University, introduced the concept of new protocol to use 3D-IGBT for the cervical cancer, named "CERVIX-V". The objective of this protocol is to evaluate the efficacy and toxicity of 3D-IGBT for cervical cancer. The primary endpoint is 2-year overall survival, and secondary endpoint is 2-year local control and toxicities. The historical control will be CERVIX-III.

(10) Discussion on CERVIX-V followed. Several issues were discussed in order to explore the rationale and feasibility to be adopted as final protocol, for example eligibility criteria, imaging requirement before treatment and at the time of brachytherapy, treatment protocol including external beam radiotherapy, dose and fractionation schedule with 3D-IGBT, dose constraints of the rectum and bladder, regimen of chemotherapy and imaging required during follow-up in order to confirm tumor response and recurrence. The final protocol will be drafted and circulated among participants.

Session 3: Quality Assurance and Quality Control (QA/QC) for 3D-IGBT
(11) A summary of the questionnaire regarding brachytherapy was reported by Dr. Hideyuki MIZUNO, Senior Researcher, Department of Radiation Measurement and Dose Assessment, NIRS, QST.The questionnaire was distributed on 26th July in 2016 and included 22 items related to brachytherapy treatment / modalities / staffing / QA and additional 3 items related to external beam radiotherapy. 11 facilities from 10 countries responded to this.
There were some differences within the member countries regarding modality, tools and methodology, and on-site audit will be optimized based on these results. Both clinical and physical aspects of audit should be performed after the initiation of CERVIX-V protocol study.

(12) Mr.Bambang Haris Suhartono, Medical Physicist of Radiotherapy Department, Dr. Soetomo General Hospital presented on the status of 3D-IGBT in his hospital and also Indonesia.

Mr. Bambang introduced the department facility and number of patients in his hospital and Indonesia. He briefly explained the procedure of 3D IGBT in his center. The QA/QC programme that covers daily and annual QA is elaborated. He recommended that FNCA could audit QA/QC in his centre in order to give more accurate and precise treatment.

Also, the total time for the treatment was shared among countries.

Session 4: Phase II Study of Concurrent Chemoradiotherapy (CCRT) for Nasopharyngeal Carcinoma (NPC-III)
(13) Dr. Hirokazu Makishima, Attending Physician, Urological Tumor Section, NIRS, QST introduced the protocol of NPC-III, a Phase II Study of CCRT for Nasopharyngeal Carcinoma (NPC). Recent clinical data was presented by representatives of each participating country.

An update on the clinical data of NPC-III was presented by representatives of each participating country with the following number of patients: Bangladesh (1), China (8), Indonesia (12), Japan (0), Kazakhstan (0), Korea (0), Malaysia (17), Mongolia (0), Philippines (7) Thailand (0) and Vietnam (20). The total number of the patients was (65). New cases: 7.

(14) Dr. Makishima then presented the summary of the follow-up data.

Total patients: 65.

Median age was 47 years old. Most patients had 2 -3 cycles of neoadjuvant chemotherapy for a compliance rate of 97%, while concurrent chemotherapy had 75% compliance rate for 4 cycles or more. Median overall treatment time of radiotherapy was 55 days (range 44 - 232 days). Radiotherapy treatment interruption of >14 days occurred in 30% of patients mainly due to machine breakdown and toxicities. In the induction phase, grade 3/4 hematological toxicities occurred in 12% of patients and non-hematological toxicities in 8%. During the concurrent phase, grade 3/4 hematological toxicities occurred in 24% of patients and non-hematological toxicities in 35%. Late toxicities of grade 3 occurred in 5 patients (8%), mainly salivary gland and mucous membrane toxicities.

Efficacy results: 2 year survival results: OS was 79%. Loco-regional control rate (LRC) was 83%. Distant metastasis free rate (DMF) was 85%. PFS was 76%. When compared with the results from NPC-I study, these results showed better rates in DMF and OS but worse rates in LRC, but all of which were not statistically significant. Failure was mainly in the distant metastasis sites (17%) but this figure is lower compared to NPC-I study (28%). The target enrolment is 120 patients but only 65 were accrued so far.

The current problems with enrolment in some countries were discussed. Factors include: different chemotherapy protocol, ethics review board getting more stringent, low NPC incidence, unavailability of LINAC, and competing trials. However, some of these factors were deemed solvable and enrolment is expected to be better next year. So it was decided to continue with enrolment for 1 more year and to review again then.

Session 5: Phase II Study of Hypofractionated Radiotherapy for Breast Cancer (Postmastectomy Radiation Therapy (PMRT)/BREAST-I)
(15) Prof. Kumiko KARASAWA, Professor and Chair, Department of Radiation Oncology, School of Medicine, Tokyo Women's Medical University introduced and reviewed the protocol of PMRT /BREAST-I.

The clinical data of Phase II Study of Postmastectomy Radiation Therapy (PMRT) was presented by representatives of each participating countries. The following numbers were reported: Bangladesh (74), China (11), Indonesia (2), Japan (1), Kazakhstan (14), Korea (0), Malaysia (0), Mongolia (19), Philippines (10), Thailand (0) and Vietnam (0). The total number of PMRT patients was (131).

(16) Prof. KARASAWA presented the summary of the PMRT clinical data of breast cancer cases (131).
Overall 131 patients in HF-PMRT arm were enrolled during 44 months. All patients completed protocol treatment. The median age was 48 years old (range, 24-74). Seventy patients (55%) had right-sided breast cancer. The T stage was T1 in 21 patients (16%), T2 in 84 (64%), T3 in 23 (18%), and T4 in 3 (2%), respectively. The N stage was N0 in 47 patients (36%), N1 in 66 (50%), N2 in 17 (13%), and N3 in 1 (1%), respectively. The clinical stage was 2A in 50 patients (38%), 2B in 50 (38%), 3A in 27 (21%), 3B in 3 (2%), and 3C in 1 (1%), respectively. The median treatment duration was 21 days (range, 19-49). Only 6 patients experienced treatment interruption. Acute dermatitis of grade 2 or more have been observed in 6 patients (5%) and grade 2 acute subcutaneous toxicity has been observed in one patient (1%). Acute grade 1 heart toxicity has been observed in 15 patients (11%) and late grade 1 heart toxicity in 6 patients (5%). Some patients among them had right-sided breast cancer. Three loco-regional recurrence, 7 distant metastases and 3 breast cancer deaths had been observed. The result of this protocol will be presented in the ICARO 2 (International Conference on Advances in Radiation Oncology) that will be held in Vienna in June 2017.

(17) An open discussion on the clinical data followed.
Some data is missing or probably wrongly filled out in registration sheet. It is unreliable that some patients with right-sided breast cancer developed heart toxicity. All co-investigators need to re-check their data, especially about the late toxicity. The criteria and methods to evaluate radiotherapy-related toxicity were discussed. We agreed with the exclusion of 2 cases with phyllodes tumor due to positive resection margin and sarcomatous histology.

Session 6: Phase II Study of Hypofractionated Radiotherapy for Breast Cancer(Whole Breast Irradiation (WBI)/BREAST-I)
(18) Prof. KARASAWA introduced and reviewed the protocol of WBI /BREAST-I.

The clinical data of Phase II Study of Whole Breast Irradiation (WBI) was presented by representatives of each participating countries. The following numbers were reported: Bangladesh (26), China (6), Indonesia (12), Japan (107), Kazakhstan (14), Korea (4), Malaysia (0), Mongolia (0), Philippines (0), Thailand (14) and Vietnam (0). Total number of WBI patients was (183).

(19) Prof. KARASAWA presented the summary of the WBI clinical data of breast cancer cases (183 patients and 184 breast lesions).
Prof. KARASAWA summarized the data of 183 patients and 184 breast lesions. Overall 184 breast lesions in HF-WBI arm were enrolled during 44 months. All the patients except one patient completed protocol treatment. The median age was 50 years old (range, 24-79). Ninety-seven patients (53%) had right-sided breast cancer. The T stage was Tis in 21 patients (11%), T1 in 113 (61%), and T2 in 50 (27%), respectively. The N stage was N0 in 155 patients (84%) and N1 in 29 (16%), respectively. The clinical stage was 0 in 21 patients (11%), 1A in 100 (54%), 1B in 2 (1%), 2A in 42 (23%), and 2B in 19 (10%), respectively. 125 patients received boost radiotherapy to tumor bed with 8.1 Gy in 122 patients and 10 Gy in 3. The high risk factors were observed as follows: age less than 50 years old in 78 patients, involved lymph node in 29, lymphovascular invasion in 8, and positive resection margin in 11, respectively. The median treatment duration was 26 days (range, 18-54). Only 2 patients experienced treatment interruption. Acute dermatitis of grade 2 or more have been observed in 30 patients (17%) and grade 2 acute subcutaneous toxicity in 6 patients (3%). In regards with the late toxicity, grade 2 lung toxicity was observed in 2 patients, grade 2 skin toxicity in 1, grade 2 subcutaneous toxicity in 1, grade 1 heart toxicity in 5, and grade 2 heart toxicity in 2. One loco-regional recurrence, 2 distant metastases and 1 breast cancer death have been observed. The result of this protocol will be presented in the ICARO2 (International Conference on Advances in Radiation Oncology) that will be held in Vienna in June 2017.

(20) An open discussion on the clinical data followed.
Some data is missing or probably wrongly filled out in registration sheet. It is unreliable that some patients with right-sided breast cancer developed heart toxicity. All co-investigators need to re-check their data, especially about the late toxicity. The participants discussed why the high rates of heart toxicity were observed in some countries. There may be ethnic or regional differences in the incidence of cardiovascular disease. These will be considered in the analysis. The criteria and methods to evaluate cosmesis were discussed. We discussed about including the patients who received radiotherapy with different fraction sizes. It was agreed to include all fraction sizes between 2.66 Gy and 2.7 Gy. Boost radiotherapy of 10-16 Gy in 5-8 fractions will be allowed because there is no standard boost dose-fraction schedule in hypofractionated breast radiotherapy. To exclude cases with other protocol violations was agreed. This protocol was initially planned to enroll for 4 years. Prof. Karasawa surveyed the estimated additional cases of each country. All co-investigators agreed with enrolling the additional cases until Jan 31, 2017.

Session 7: Review of Project Activities and Future Plan (including 3 years' Evaluation)
(21) Following the FNCA regulation, this project reviewed its last 3 years' activities and achievements (between JFY 2014 and 2016) and designed the future plan (between JFY 2017 and 2019).

(22) The following outputs and outcomes were achieved from the activities of Radiation Oncology Project.

(23) The participants also discussed the future plans of the project (between JFY 2017 and 2019). The following activities were planned:

A. Clinical Trials
1) Cervical Cancer
2) Nasopharyngeal Carcinoma
3) Breast Cancer
B. QA/QC Activities
C. Workshop
D. Open Lecture
E. Technical Visit
F. Collaboration of FNCA and IAEA/RCA

(24) The next workshop is tentatively scheduled to be held in the Philippines or Malaysia from October 23rd to 27th or October 30th to November 3rd 2017.

Session 8: Technical Visit at Radiotherapy Division of Dr. Soetomo General Hospital
(25) The participants conducted a Technical Visit to Radiotherapy Division of Dr. Soetomo General Hospital. Linac, HDR treatment system, treatment planning system (2D, 3D and IMRT), and their new medical oncology department.

Session 9: Open Seminar
(26) The Open Seminar was held at Dr. Soetomo General Hospital as part of the workshop. Dr. Joni Wahyuadi, Vice-Director of the hospital gave his remarks. Six interesting and innovative topics were presented by distinguished speakers. Dr. Nana Supriana and Dr. Dyah Erawati moderated the session.

(27) Mr. Tomoaki WADA gave a lecture on the FNCA. He introduced its overview and spoke about the on-going 10 projects' activities and achievements.

(28) Prof. Masaru WAKATSUKI introduced the FNCA Oncology Project and its achievements in cervical cancer treatment.

(29) Prof. Dr. Soehartati G., Sp. Rad(K) Onk. Rad, President of Indonesia Radiation Oncology Society (IROS) and Chairman of National Committee of Cancer Prevention and Treatment, gave a lecture on Present Status of Radiation Oncology and Comprehensive Cancer Treatment in Indonesia.

(30) Prof Tatsuya OHNO, Professor / Medical Director, Heavy Ion Medical Center, Gunma University, gave a lecture on CT-based brachytherapy for cervical cancer.

(31) Dr. Jaemelyn Marie O. Fernandez spoke on Intensity Modulated Radiotherapy (IMRT) and Clinical Quality Assurance (QA).

(32) The last lecture was delivered by Prof. Takashi NAKANO,Professor,
Gunma University Graduate School of Medicine. He gave a lecture on Carbon Ion therapy.

(33) Prof. Shingo KATO concluded the Open Seminar with his closing remarks.

Session 10: Protocol Drafting for CERVIX-V
(34) Protocol for CERVIX-V was drafted, moderated by Dr. Noriyuki OKONOGI. Dose prescription and treatment schedule was confirmed by member countries. Protocol draft was agreed to be sent to each facility by January 2017 and protocol is expected to be cleared by IRB (NIRS) by April 2017 and aim to commence recruitment within the year.

Session 11: Workshop Minutes Drafting
(35) The draft of the minutes was submitted by rapporteurs, discussed and then amended. The draft of the minutes was unanimously adopted by the workshop participants.

Session 12: Proposals and Suggestions from member countries
(36) Dr. A.F.M Kamal Uddin from Bangladesh, proposed an idea of on-site training for cervical cancer brachytherapy and promotion of FNCA treatment protocols. The demand for on-site training within member countries appeared to be strong. This proposal was agreed to be discussed within Japanese and all other member country authorities for funding and procedures.

Session 13: Closing Ceremony
(37) Dr. Yuiichi Michikawa, MEXT and Prof. Shingo KATO gave their closing remarks. The workshop was officially closed.

Program of
FNCA 2016 Workshop on Radiation Oncology Project

Day 1Tue, 8thNovember 2016
Place: Swiss-BelinnTunjungan Surabaya

Day 2Wed, 9thNovember 2016
Place: Swiss-BelinnTunjungan Surabaya

Day 3Thu, 10thNovember 2016
Place: Dr. Soetomo Hospital

Day 4Fri, 11thNovember 2016
Place :Swiss-BelinnTunjungan Surabaya

List of Participants
FNCA 2016 Workshop on Radiation Oncology Project

Bangladesh

China

Indonesia

Japan

Kazakhstan

Korea

Malaysia

Mongolia

The Philippines

Thailand

Viet Nam