CARBON ION THERAPY FOR SACRAL CHORDOMAS CTOS 14th Annual Meeting November 13-15, 2008 London UK CARBON ION THERAPY FOR SACRAL CHORDOMAS Thank you chairman. Ladies and gentlemen It’s my great pleasure to give a talk to you here in london In my presentation, I would like to talk about our experience in carbon therapy for sacral chordomas Tadashi KAMADA, MD Research Center for Charged Particle Therapy National Institute of Radiological Sciences Chiba, JAPAN

Bragg peak This slide shows a brief summary of carbon ion beam. carbon beam has a definite range and the bragg peak. In addition to this physical selectivity. At the bragg peak, carbon beam ionization is enormous, and showing several radiobiological advantages such as cell cycle independent effect or less repairable damages. Carbon beam has a definite range and the Bragg peak.In addition to this physical selectivity, ionization is enormous at the Bragg peak, and showing biological advantages such as cell cycle independent effect. Therefore, carbon beam could be a potentially curable armament for radio-resistant tumors such as chordoma.

Carbon ion therapy for chodoma : Background & Material Surgery is the mainstay of treatment for chordomas. However, complete excision is frequently difficult in S2 or higher lesions without severe functional loss. On the other hand, chordoma shows minimal response to radiation or chemotherapy. Between 1996 and 2007, 95 patients with sacral chordoma were included in the phase I/II (Kamada, JCO 2002) and phase II (Kamada, JCO 2008) study of carbon ion therapy for bone and soft tissue sarcomas.

Patients Characteristics No. of Pts : 95 sacral chordma Gender : 68 males / 27 females Age : 30 - 85(median65) Presentation : 84 primary / 11 post op rec Tumor Diameter : 3～17 cm （Median：9 cm） Tumor Volume : 47～1497 cc （Median：370 cc） (From Jun 1996 to Feb 2007)

Sacral Chordoma : Level of Invasion Post op rec 11 This slide shows tumor characteristics in 95 sacral chordoma More than 80 % were S2 or higher level lesions

Carbon ion Dose Distribution in Sacral Chordoma 代表的なものに変更 96% 90% 50% 30% 10% Bowels were spared ! This slide shows the dose distributions in sacral chordoma.s As you can see in this slide, margins at the skin and bowel were reduced accordingly. In the right hand side, to spare the rectum, we employed the patch technique. With 3 ports; right-left, left-right, posterior-anterior With 3 ports; right-left, left-right anterior-posterior(patch) Carbon ion therapy - all 16 Fractions over 4week Total dose: 52.8-64GyE : 2, 70.4GyE : 86, 73.6GyE : 7 (3.3-4.6GyE/fr.) Number of port : Two ports : 2 , Three ports : 91, Patch : 2

Overall Survival and Local Control after Carbon Ion Therapy in Sacral Chordoma 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Probability 12 24 36 48 60 72 84 96 108 120 Months 5 year LC: 88 % 5 year OS: 86% Sacral Chordoma 95 patients Median survival time 42 mo (13-112) Median time to local failure 35 mo(13-60) Until Feb, 2007, the 95-chordoma patients were treated and showing 88% five-year local control rate and 86 % five-year survival rate.

Radiation Morbidity Acute grade No. 0 1 2 3 4 5 Skin 95 0 81 11 3 0 0 GI tract 95 93 2 0 0 0 0 　　　 Late grade Skin 95 0 86 5 2* 2* 0 GI tract 95 94 1 0 0 0 0 Radiation morbidities are summarized in this slide. High grade skin complication was experienced at the very beginning of study and we reduce the dose and skin margins and increase the ports number. The incidence of skin complication was dramatically decreased. *receiving TD of 73.6GyE However, 15 patients required persistent medication for peripheral neuropathy in this series.

DVHs of 44 Sciatic Nerve According to the Sciatic Symptoms in 22 patients with Sacral Chordoma (ml) (GyE) 5 10 15 20 25 30 40 50 60 70 80 Severe Moderate None-slight DVH (n=44) 70GyE and 10cm Volume Among the observed late reactions, we analyzed the sciatic nerve symptoms persisting after treatment. We carried out the Dose Volume Histogram analysis of 44 sciatic nerves in 22 patients with sacral chordoma receiving total dose of 70.4 to 73.6 GyE followed more than 2 years. This slide shows the DVHS of each sciatic nerve and severity of symptoms. @We found that length of more than 10cm, and a total dose of 70GYE could be critical points for sciatic nerve outcome. Now, we give 67.4GyE for sacral chordoma. This slide shows DVHs of 44 sciatic nerves in 22 patients with sacral chordoma receiving total dose of 70.4 to 73.6 GyE followed more than 2 years. We found that length of more than 10cm, and a total dose of 70GyE could be a critical point for sciatic nerve outcome. Now, we give 67.4GyE for sacral chordoma. 9

Carbon Ion Radiotherapy for Sacral Chordoma (S2, 65 yo, Male) Before treatment These is a 65 yo male with S2 level chordoma. . Sixty six months after 70.4GyE, he has no neurological deficit and spending normal life. 66 months after, no neurological deficit, and spending normal life 60 m after 70.4 GyE

Sacral Chordoma (S1) 57yo Female C- Ion RT 70.4GyE/16Fr/4wks CTV:991cc Dose distribution Before treatment 54 months after Alive no evidence of re-growth of tumor and ambulant. Working as a housewife with slight urinary incontinence

Local Control and Survival Rate in Chordoma No. Site treatment Local Survival of Pts. 5-year 5year 10year (new pts /y) MGH 1) 21 S surgery 77% - 50% 1972-1992 (1.1) Sweden 2) 39 S+Sp surgery 44 84% 64 1963-1998 (1.1) MGH. 3) 27 S surgery 72 82 62 1982-2002 　　 (2.7 ) + Proton LBL 4) 14 S surgery 55 85 22 1977-1989 (1.2 ) + He-ion Mayo 5) 52 S surgery 56 74 52 1980-2001 (2.5 ) NIRS 95 S C-ion 88 86 - 1996-2007.2 (9 ) S:sacrum Sp:mobile spine (disease free) The reported 5-year local control rates of surgical treatment were 44 to 77 %, while the 5-year local control rate of our series was 88 %. Follow up period is rather short, however, carbon ion may appear to represent a promising alternative to surgery because of rather advanced lesions were treated in our series. 1) J Bone Joint Surg. 1998 2) Cancer.2000 3)IJROBP.2006 4) IJROBP.1993 5) J Bone Joint Surg. 2005

Summary Five years overall survival rate (86%) and Local control rate (88%) in patients with sacral chordoma treated by carbon ion therapy are similar to or even better than those in reported data on patients treated by surgical resection. Four patients treated with a total dose of 73.6 GyE experienced Grade 3/4 skin complications. No other treatment-related surgical interventions including colostomy or urinary diversion were carried out.

In Conclusion Carbon ion therapy is suggested to be an effective and safe treatment for sacral chordomas and could be a promising alternative to surgery.

Carbon ion therapy--New horizon in cancer treatment Thank you for your attention Carbon ion therapy--New horizon in cancer treatment

C-ion Rx RCC：55yo Male IJROBP. 2008 80.0GyE / 16 F Before 6 years after C-ion Rx 80.0GyE / 16 F No pain No bleeding No wound No anesthesia RCC：55yo Male However, today I would like to start with this slide. This is a CT image of 55 years old male with left kidney cancer. He refused surgical intervention and referred for carbon therapy. Kidney cancer is rather radio-resistant, so we gave 80 GyE in 16 fractions over 4 weeks. Slide shows a CT 6 years after treatment, complete tumor regression was observed. It looks like cut by a sharp KNIFE, but no wound, no blood loss, no pains ,and no anesthesia. Before IJROBP. 2008