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2006 年 7 月 12 日第 4 回 OPTA 粒子線 がんセミナー 1 Department of Oral and Maxillofacial Surgery II Osaka University, Graduate School of Dentistry, Osaka, Japan 2 Department.

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Presentation on theme: "2006 年 7 月 12 日第 4 回 OPTA 粒子線 がんセミナー 1 Department of Oral and Maxillofacial Surgery II Osaka University, Graduate School of Dentistry, Osaka, Japan 2 Department."— Presentation transcript:

1 2006 年 7 月 12 日第 4 回 OPTA 粒子線 がんセミナー 1 Department of Oral and Maxillofacial Surgery II Osaka University, Graduate School of Dentistry, Osaka, Japan 2 Department of Oral and Maxillofacial Surgery, Higashi-Osaka General Hospital, Osaka, Japan 3 Department of Oral and Maxillofacial Surgery, Rinku General Center, Izumisano, Osaka, Japan 4 Radiation Oncology Research Laboratory, Research Reactor Institut, Kyoto University, Osaka, Japan 5 Division of Electrical, Electronic and Information Engineering, Graduate School of Engineering, Osaka University, Japan I. Kato 1, Y. Fujita 2, M. Ohmae 3, Y. Sakrai 4, M. Suzuki 4, I. Murata 5, H. Horiike 5, T. Sumi 1, S. Iwai 1, M. Nakazawa 1, Y. Yura 1 and K. Ono 4 BNCT in Patients with Recurrent Head and Neck Cancers Who Have No Other Treatment Options 16th ICNCT 6.14 -19.2014 Helsinki

2 To estimate safety and effectiveness of BNCT for patients with advanced / recurrent head and neck cancer (HNC) for which there were no other treatment options. Purposes 16th ICNCT 6.14 -19.2014 Helsinki

3 Period: December, 2001-2007, 2010-2012 26 squamous cell carcinomas, 7 salivary gland carcinomas ( 3 mucoepidermoid carcinomas, 4 adenoid cystic carcinoma ), 4 sarcomas Starting point of survival periods: the day of first BNCT Estimation day: March 2014 1. but one had developed recurrent HNC for which there were no other treatment options after the standard therapy. 2. had the approval of the ethical committees, medical committee of KUR and that of Osaka University, Graduate School of Dentistry. 3. have good accumulation in tumor by FBPA-PET study 4. had not developed distant metastasis at the time. 5. had got “informed consent” by printed forms before the treatment. 37Patients 16th ICNCT 6.14 -19.2014 Helsinki

4 Results 1.Survival Periods after BNCT: 1-105 months Mean Survival Times ： 26.3 months 2. ： Regression rates CR: 19 cases (51%) PR: 15 cases （ 40%) (10cases out of 15:Regression rate: >90%) PD: 3 cases (8%) NE:1 例 （ 1 ％） 3.4-year overall survival rate ： 42 ％ (Kaplan-Meiyer) 7-year overall survival rate ： 36 ％ (Kaplan-Meiyer) 9-year overall survival rate ： 31 ％ (Kaplan-Meiyer) 1.18 out of 37 cases (49 ％ ) developed LN metastasis. 2.10 out of 37 cases (27%) developed distant metastasis. Response rate:91 ％ 37 Advanced Cases 16th ICNCT 6.14 -19.2014 Helsinki

5 Without BNCT: n=15 Overall Survival Rate after BNCT （ Kaplan Meier ） Months after BNCT With BNCT: n=37 4y-Survival Rate:42% 7y-Sutvivsl Rate:36% 9y-Survial Rate:31% 生存率 (%) （ 2001-2010-2014-2012) 16th ICNCT 6.14 -19.2014 Helsinki

6 1.The 2-year DFS rate of salvage operation for recurrent head and neck cancer (RHNC) including oral cancer was 44%. (Goodwin, W.J., et al. Laryngoscope 2000) 2.The 2-year DFS rate of chemo-radiation therapy was 10-26%, and the 5- year DFS rate was 0-14.6%. (Schwartz, G.J., et al. Head Neck 2000) 3.The 5-year DFS rate of chemotherapy alone was less than 5%. (Wong, S.J., et al. J Clin Oncol 2006) Conclusion 1 1.The 2-year and 7-year overall survival (OS) rate of BNCT was 42% and 36%, respectively. 2.The 2-year and 7-year disease-free survival (DFS) rate of BNCT was 36% and 31%, respectively. References In recurrent head and neck cancer, OS and DFS of patients who received BNCT might be better than those of patients who received operation. 16th ICNCT 6.14 -19.2014 Helsinki

7 Adverse Event Remarkabble Improvement of QOL 1. Remarkable reduction of tumors. 2. Remarkable improvement of OS and DFS. 3. Improvement of performance status. 4. Relief of pain. 5. Decrease of bleeding and exudates from the tumor. 6. Disappearance of ulceration and covered with skin 7. Preservation of normal tissues and functions Brain necrosis ： 1, Osteonecrosis ： 6, Mucositis:3, Alopesia Conclusion 2 16th ICNCT 6.14 -19.2014 Helsinki

8 Case 1 : 67y Female: Parotid gl. carcinoma mucoepidermoid Ca. mucoepidermoid Ca. Reduction: 94% BNCT(3) ： 22M Before BNCT T/N ＝ 3.5 47M after Regrowth→BNCT4, 5th CR Died of pneumonia 84 Ｍ Tumor volume ＝ 675 cm 3 History of 45Gy-RT 16th ICNCT 6.14 -19.2014 Helsinki

9 Case 1 :MR findings Before BNCT 15M after BNCT Tumor was pushing Lt-pharygeal wall Tumor reduction reversed pharyngeal dislocation 16th ICNCT 6.14 -19.2014 Helsinki

10 Regression rate: 94% 1.17:2003 ： 3rd 4.26.20025.22.2003 T/N ratio ＝ 3.5 12.18.2001:1st1.22.2002:2nd Case 1 : 67y F:Mucoepidermoid Ca. of Parotis 2.22.2002 16th ICNCT 6.14 -19.2014 Helsinki

11 Selective intra-artery chemotherapy After selective intra-artery infusion Tumor was feeded by Internal Carotid Artery （ arrow ） 1/19-2/1 ： Cannulation from occipital artery ⇒ (CDDP:50mg/body+STS)×3Kur （ stopped ） Case 22 ： 56y Male Maxillary Sinus(SCC) History of 52Gy-RT 16th ICNCT 6.14 -19.2014 Helsinki

12 Before BNCT rT4N0M0 CR 6M after BNCT CD3-LAK ： 2 times 84M Disease free survival 3/12 9/27 3/27/07 BNCT (T/N ＝ 5.7) Case22 ： 56y Male Maxillary Ca.(SCC) Transplanted Cornea History of RT ： 52Gy 16th ICNCT 6.14 -19.2014 Helsinki

13 1M 5.5-month after BNCT 4.24.12 12.04.12 4.24.12 5.24 12.05 Case33: 40Y ： R-ACC, op. Infraorbital, rec. T/N ratio= 2.5 T/B ratio= 2.0 History of 50Gy-RT 23M Disease free survival 16th ICNCT 6.14 -19.2014 Helsinki

14 Mean 10 B conccentration ： 25.7ppm Skin ： 6.9Gy-Eq 、 Normal mucosa<18 Gy-Eq Maximum GTV-dose ( 1.6cm depth) ： 26 Gy-Eq Minumum GTV-dose (3cm deepest) ： 24Gy-Eq Irradiation time ： 55 min. BNCT: 6/14/2012 Case33: 40Y ： R-ACC, op. Infraorbital, rec. T/B ratio= 2.0 T/N ratio= 2.5 16th ICNCT 6.14 -19.2014 Helsinki

15 Case29: 60Y ： op.OGK, LN metastasis 7.31.2012 11.15.2011 1.31.2012 Before BNCT (12.15.11) 11.08.2011 12.01.2011 11.15.2011 1M7M 10.23.2012 10M after BNCT T/N ratio= 2.8 T/B ratio= 2.6 27M Disease free survival History of 63.3Gy-RT 16th ICNCT 6.14 -19.2014 Helsinki

16 Mean 10 B concentration ： 20ppm Skin ： 4.9Gy-Eq 、 Normal mucosa:12 Gy-E Maximum GTV-dose (2.2cm depth) ： 28.3 Gy- Eq Minumum GTV-dose (4cm deepest):25.0 Gy- Eq Irradiation time ： 87 min. 12/15/2011 Case29: 60Y ： op.OGK, LN metastasis T/N ratio= 2.8 T/B ratio= 2.6 16th ICNCT 6.14 -19.2014 Helsinki

17 1.23:BNCT 前 照射既往 RT ： 54Gy 5.07 ： BNCT-3M 後 8.08 ： 6M after BNCT T/N ratio= 3.6 T/B ratio= 4.0 1.22:Before BNCT Case34: 65Y ： L-WK,SCC, rec., LN meta History of 54Gy-RT 5.10cm×4.34cm 13M DFS 16th ICNCT 6.14 -19.2014 Helsinki

18 Mean 10 B conccentration ： 23ppm Skin ： 6.8Gy-Eq Maximum GTV-dose(1.5cm depth) ： 44Gy-Eq Minumum GTV-dose (5cm deepest): 28Gy-Eq Normal mucosa < 12.0Gy-Eq Irradiation time ： 56 min. 2/07/2013 T/N ratio= 3.6 T/B ratio= 4.0 Case34: 65Y ： L-WK,SCC, rec., LN meta 16th ICNCT 6.14 -19.2014 Helsinki

19 Case40 : 56Y ： Z.K, LN metastasis 11.08.2011 1M7M History of Interstitial:60Gy 4.09.2014 5.14.2014 4.04.2014 3.31.20144.22.2014 Before BNCT 1M after BNCT T/N ratio= 3.8 T/B ratio= 4.2 5.26.2014 5.23.2014 16th ICNCT 6.14 -19.2014 Helsinki

20 Mean 10 B concentration ： 22ppm Skin ： 7.9Gy-Eq 、 Normal mucosa:12 Gy-E Maximum GTV-dose (1.8cm depth) ： 46.0 Gy- Eq Minumum GTV-dose (5cm deepest):27.0 Gy- Eq Irradiation time ： 70 min. T/N ratio= 3.8 T/B ratio= 4.2 Case40 : 56Y ： Z.K, LN metastasis 5/01/2014 16th ICNCT 6.14 -19.2014 Helsinki

21 Case14: 59Y male ： Angiosarcoma 【 Diagnosis 】 Angiosarcoma at the left maxilla a painless, rounded, ulcerated submucosal mass at the left maxilla. ※ Intra-oral appearance of the tumor after the IL-2 treatment 16th ICNCT 6.14 -19.2014 Helsinki

22 The standard therapy of angiosarcoma has not established yet! 2005, ４ /20 ： Admission ４ /26 ： Canulation of the lt-superficial lateral artery 4/22-5/5 ： IL-2 therapy local injection (L.I) 、 I.A ： 700,000U/fr. X 14days 4/27-5/10 ： IL-2 therapy local injection 、 I.A ： 700,000U/fr, X 14days IL-2 therapy-effects :NC (rapid growth was stopped) 5/31 ： Operation: Lt-Subtotal maxillectomy 6/7 ： BNCT (1) 6/8 ： CD3-LAK immunotherapy 6/15-6/22 ： IL-2 local injection 、 I.A ： 400,000U/fr. X 8days (side effects) 7/13 ： BNCT(2) 7/14 ： CD3-LAK immunotherapy 8/25 ： CD3-LAK immunotherapy Case14: 59Y male ： Angiosarcoma 16th ICNCT 6.14 -19.2014 Helsinki

23 BPA ： 500mg iv Mean １０ B conc. ： 28.5ppm Atomic power ： 5000 ｋ W Irradiation time ： 45 min. MaximumGTV-dose(1.5cm): 27.6Gy-Eq Minimum GTV-dose(5.7cm): 11.8Gy-Eq Maximum mucous-dose ： 15.3Gy-Eq Maximum Skin-dose ： 6.92Gy-Eq Maximum thermal neutron fluence ： 7.88e+11 (n/cm2) T/N ratio= 2.8 T/B ratio= 2.5 Case14: 59Y male ： Angiosarcoma ② nd 7.13.2005 16th ICNCT 6.14 -19.2014 Helsinki

24 7.19.2005 7/13 ： The 2 nd BNCT 11.29.2005 3.2.2006 6/7 ： The 1st BNCT PET-CT:8.11.2006 6.21.2005 105M DFS Case14: 59Y ： Angiosarcoma 16th ICNCT 6.14 -19.2014 Helsinki

25 T/N ratio= 2.3 T/B ratio= 2.2 Before BNCT 9M after BNCT Case31 63Y ： Chondroblasitic OS at Lt-TMJ No history of RT 26M DFS 16th ICNCT 6.14 -19.2014 Helsinki

26 Mean 10 B conccentration ： 32ppm Skin ： 8.1Gy-Eq Maximum GTV-dose(1.9cm depth) ： 52Gy-Eq Minumum GTV-dose (5cm deepest): 28Gy-Eq Normal mucosa : 4.9Gy-Eq Irradiation time ： 60 min. 1/26/2012 T/N ratio= 2.3 T/B ratio= 2.2 Case31 63Y ： Chondroblasitic OS at Lt-TMJ 16th ICNCT 6.14 -19.2014 Helsinki

27 Co-researchers 1. K. Ono, Y. Sakurai, A. Maruhashi, M. Suzuki, S. Masunaga, T. Kinashi, N. Kondo, H. Tanaka Research Reactor Institut, Kyoto University 2. H. Kumada Tsukuba University, Tokai Research and Development Center 3. M. Ohmae, Y. Takaoka Department of Oral and Maxillofacial Surgery, Izimisano Municipal Hospital, Rinku General Hospital 4. M. Kirihata, T. Asano Graduate School of Environment and Life Science, Osaka prefectural University 5. Y. Imahori, R. Fujii Department of Neurosurgery, Kyoto Prefectural University, Kyoto, and CEO of Cancer Intelligence Care Systems, Inc. 6. H. Horiike, I. Murata, Division of Electrical, Electronic and Information Engineering, Graduate School of Engineering, Osaka University 7. N. Yamamoto, Y. Fujita, T. Sumi, S. Iwai, M. Nakazawa, Y. Yura Department of Oral and Maxillofacial Surgery II Osaka University, Graduate School of Dentistry 16th ICNCT 6.14 -19.2014 Helsinki

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