2006 年 7 月 12 日第 4 回 OPTA粒子線がんセミナー

11Department of Oral and Maxillofacial Surgery II Department of Oral and Maxillofacial Surgery II Osaka UniversityOsaka University, Graduate School of Dentistry, , Graduate School of Dentistry, Osaka, Japan Osaka, Japan 22Department of Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Surgery, Higashi-Osaka General HospitalHigashi-Osaka General Hospital, Osaka, Japan, Osaka, Japan33 Department of Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Surgery, Rinku General CenterRinku General Center, Izumisano, Osaka, Japan, Izumisano, Osaka, Japan44 Radiation Oncology Research Laboratory, Research Reactor Institut, Radiation Oncology Research Laboratory, Research Reactor Institut, Kyoto UniversityKyoto University, Osaka, , Osaka, JapanJapan 55 Division of Electrical, Electronic and Information Engineering, Graduate School of Engineering,Division of Electrical, Electronic and Information Engineering, Graduate School of Engineering,Osaka UniversityOsaka University, Japan, Japan

I. KatoI. Kato11, Y. Fujita, Y. Fujita22, M. Ohmae, M. Ohmae33, Y. Sakrai, Y. Sakrai44, M. Suzuki, M. Suzuki44, I. , I. MurataMurata55, H. Horiike, H. Horiike55, T. Sumi, T. Sumi11, S. Iwai, S. Iwai11, M. Nakazawa, M. Nakazawa11, Y. , Y. YuraYura11 and K. Ono and K. Ono44

BNCT in Patients with Recurrent BNCT in Patients with Recurrent Head and Neck Cancers Who Have Head and Neck Cancers Who Have

No Other Treatment OptionsNo Other Treatment Options

16th ICNCT 6.14 -19.2014 Helsinki

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

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Period: December, 2001-2007 , 2010-2012 26 squamous cell carcinomas, 7 salivary gland

carcinomas( 3 mucoepidermoid carcinomas, 4 adenoid cystic

carcinoma ), 4 sarcomasStarting point of survival periods: the day of first BNCTEstimation day: March 20141. 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 study4. had not developed distant metastasis at the time.5. had got “informed consent” by printed forms before the

treatment.

37Patients

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Results

1. Survival Periods after BNCT: 1-105 months　　　 Mean Survival Times ：　 26.3 months2. ： 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

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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)

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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 11. 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.

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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 skin7. Preservation of normal tissues and functions

Brain necrosis ： 1, Osteonecrosis ： 6, Mucositis:3, Alopesia

Conclusion 2

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Case 1Case 1: 67y Female: Parotid gl. carcinoma: 67y Female: Parotid gl. carcinoma mucoepidermoid Ca.mucoepidermoid Ca.Reduction: 94%

BNCT(3) ： 22MBefore BNCT

T/N ＝ 3.5

47M after Regrowth→BNCT4, 5thCR Died of pneumonia 84 Ｍ

Tumor volume ＝ 675 cm3

History of 45Gy-RT

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Case 1Case 1:MR findings: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

Regression rate: 94%

1.17:2003 ： 3rd4.26.2002 5.22.2003

T/N ratio ＝3.5

12.18.2001:1st 1.22.2002:2nd

Case 1Case 1: 67y : 67y F:Mucoepidermoid Ca. of ParotisF:Mucoepidermoid Ca. of Parotis

2.22.2002

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Selective intra-artery chemotherapy

After selective intra-artery infusion

Tumor was feededby Internal Carotid Artery （ arrow ）

1/19-2/1 ： Cannulation from occipital artery ⇒(CDDP:50mg/body+STS)×3Kur （ stopped ）

Case 22Case 22 ：： 56y Male56y Male Maxillary Sinus(SCC)Maxillary Sinus(SCC)History of 52Gy-RT

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Before BNCT

rT4N0M0

CR

6M after BNCT

CD3-LAK ： 2 times84M Disease free survival

3/12

9/27 3/27/07 BNCT (T/N ＝ 5.7)

Case22Case22 ：： 56y Male56y Male Maxillary Ca.(SCC)Maxillary Ca.(SCC)

Transplanted Cornea

History of RT ： 52Gy

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1M

5.5-month after BNCT

4.24.12 12.04.12 12.04.12

4.24.12

5.24

12.05

Case33: 40YCase33: 40Y ：： R-ACC, op.R-ACC, op.Infraorbital, rec. Infraorbital, rec.

T/N ratio= 2.5T/B ratio= 2.0

History of 50Gy-RT

23M Disease free survival

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Mean 10B 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: 40YCase33: 40Y ：： R-ACC, op.R-ACC, op.Infraorbital, rec. Infraorbital, rec.

T/B ratio= 2.0T/N ratio= 2.5

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Case29: 60YCase29: 60Y ：： op.OGK, LN metastasisop.OGK, LN metastasis

7.31.20127.31.2012

11.15.201111.15.2011

1.31.20121.31.2012

Before BNCT (12.15.11)

11.08.201111.08.2011 12.01.201112.01.2011 11.15.201111.15.2011

1M 7M

10.23.201210.23.2012

10M after BNCT

T/N ratio= 2.8T/B ratio= 2.6

27M Disease free survival

History of 63.3Gy-RT

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Mean 10B 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: 60YCase29: 60Y ：： op.OGK, LN metastasisop.OGK, LN metastasis

T/N ratio= 2.8T/B ratio= 2.6

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1.23:BNCT 前

照射既往 RT ： 54Gy

5.07 ： BNCT-3M 後 8.08 ： 6M after BNCT

T/N ratio= 3.6T/B ratio= 4.0

1.22:Before BNCT

Case34: 65YCase34: 65Y ：： L-WK,SCC, rec.L-WK,SCC, rec., LN meta , LN meta History of 54Gy-RT 5.10cm×4.34cm

13M DFS

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Mean 10B 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= 3.6T/B ratio= 4.0

Case34: 65YCase34: 65Y ：： L-WK,SCC, rec.L-WK,SCC, rec., LN meta , LN meta

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Case40 : 56YCase40 : 56Y ：： Z.K, LN metastasisZ.K, LN metastasis11.08.201111.08.2011

1M 7M

History of Interstitial:60Gy4.09 .20144.09 .2014

5.14.20145.14.2014

4.04.20144.04.20143.31.20143.31.2014 4.22.20144.22.2014

Before BNCT

1M after BNCT

T/N ratio= 3.8T/B ratio= 4.2

5.26.20145.26.20145.23.20145.23.2014

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Mean 10B 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= 3.8T/B ratio= 4.2

Case40 : 56YCase40 : 56Y ：： Z.K, LN metastasisZ.K, LN metastasis

5/01/2014

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Case14: 59Y Case14: 59Y malemale ：：AngiosarcomaAngiosarcoma

【 Diagnosis 】 Angiosarcoma at the left maxillaa painless, rounded, ulcerated submucosal mass at the left maxilla.

※ Intra-oral appearance of the tumor after the IL-2 treatment

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The standard therapy of angiosarcoma has not established yet!

<Course of Treatments >2005, ４ /20 ： Admission４ /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 maxillectomy6/7 ： BNCT (1)6/8 ： CD3-LAK immunotherapy6/15-6/22 ： IL-2 local injection 、 I.A ： 400,000U/fr. X 8days (side effects)7/13 ： BNCT(2) 7/14 ： CD3-LAK immunotherapy8/25 ： CD3-LAK immunotherapy

Case14: 59Y Case14: 59Y malemale ：：AngiosarcomaAngiosarcoma

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BPA ： 500mg ivMean １０ B conc. ： 28.5ppmAtomic power ： 5000 ｋ WIrradiation time ： 45 min.

MaximumGTV-dose(1.5cm): 27.6Gy-EqMinimum GTV-dose(5.7cm): 11.8Gy-EqMaximum mucous-dose ： 15.3Gy-Eq Maximum Skin-dose ： 6.92Gy-Eq

Maximum thermal neutron fluence 　： 7.88e+11 (n/cm2)

T/N ratio= 2.8T/B ratio= 2.5

Case14: 59Y Case14: 59Y malemale ：：AngiosarcomaAngiosarcoma

0

5

10

15

20

25

30

0 5 10 15

Depth (cm)

RBE,

CBE-

wei

ghte

d Abs

orbe

d Dos

e (G

y-Eq

)

TotalMucosaNormalGamma- raysFastThermal

②nd 7.13.2005

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7.19.20057.19.2005

7/13 ： The 2nd BNCT

11.29.200511.29.2005 3.2.20063.2.2006

6/7 ： The 1st BNCT PET-CT:8.11.2006PET-CT:8.11.20066.21.20056.21.2005

105M DFS

Case14: 59YCase14: 59Y ：： AngiosarcomaAngiosarcoma

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T/N ratio= 2.3T/B ratio= 2.2

Before BNCT

9M after BNCT

Case31 Case31 63Y63Y ：： Chondroblasitic OS at Lt-Chondroblasitic OS at Lt-TMJTMJNo history of RT

26M DFS

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Mean 10B 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= 2.3T/B ratio= 2.2

Case31 Case31 63Y63Y ：： Chondroblasitic OS at Lt-Chondroblasitic OS at Lt-TMJTMJ

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Co-researchers 　1. K. Ono, Y. Sakurai, A. Maruhashi, M. Suzuki, S. Masunaga, T. Kinashi, N. Kondo, H. TanakaResearch Reactor Institut, Kyoto University

2. H. KumadaTsukuba University, Tokai Research and Development Center

3. M. Ohmae, Y. TakaokaDepartment of Oral and Maxillofacial Surgery, Izimisano Municipal Hospital, Rinku General Hospital

4. M. Kirihata, T. AsanoGraduate School of Environment and Life Science, Osaka prefectural University

5. Y. Imahori, R. FujiiDepartment 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