Carbon ion radiotherapy for bone and soft tissue sarcomas

Carbon ion radiotherapy for bone and soft tissue sarcomas. T. Kamada, R. Imai, H. Tsujii, H. Tsuji, I. Serizawa; National Institute of Radiological Sciences, Chiba, JapanBackground: Carbon ion radiotherapy showed promising clinical outcomes in 57 patients with bone and STS during the phase I study (Kamada, JCO 22 4466-4471, 2002). This phase II study was planned thereafter.Methods: From April 2000 to February 2007, 301 lesions of 282 patients with bone and STS not suited for surgical resection were enrolled in this phase II study. A total dose of 64.0 GyE in 16 fractions over 4 weeks was indicated for 15 lesions, that of 70.4 GyE for 276 and remaining 10 receiving 73.6 GyE. Mean age was 52 yrs, (range 12-85); site of origin was the pelvis in 74%, spine or para-spinous softtissue in 20%, extremities in 5%; bone primarywas in 78% and softtissue in 22%; pathologic subtype in bone sarcoma was chordoma in 42%, chondrosarcoma in 21%, osteosarcoma in 21%; pathologic subtype in STS was MFH in 23%, MPNST in 21%, synovial sarcoma in 13%. Results: The 3- and 5-year overall actuarial survival rates were 68% (95% Cl, 61%-75%) and 52% (95% Cl, 43%-61%), respectively, and the actuarial overall local control rates were 85% (95% Cl, 80%- 90%), and 81% (95% Cl, 74%-88%) at 3 years and 5 years of follow-up, respectively. Overall toxicity was acceptable, with 2% skin/soft tissue late G3/4 toxicity. Conclusions: Carbon ion radiotherapy shows a substantial local control in the patients with bone and soft tissue sarcomas not suited for surgical resection with acceptable morbidity

Carbon ion radiotherapy for bone and soft tissue sarcomas

ASCO 44th Annual Meetin

Carbon Ion Radiotherapy for Bone and Soft Tissue Sarcomas

Background: Carbon ion radiotherapy showed promising clinical outcomes in 57 patients with bone and STS during the phase I study (Kamada, JCO 22 4466-4471, 2002). This phase II study was planned thereafter. Methods: From April 2000 to February 2007, 301 lesions of 282 patients with bone and STS not suited for surgical resection were enrolled in this phase II study. A total dose of 64.0 GyE in 16 fractions over 4 weeks was indicated for 15 lesions, that of 70.4 GyE for 276 and remaining 10 receiving 73.6 GyE. Mean age was 52 yrs, (range 12-85); site of origin was the pelvis in 74%, spine or para-spinous soft tissue in 20%, extremities in 5%: bone primary was in 78% and soft tissue in 22%; pathologic subtype in bone sarcoma was chordoma in 42%, chondrosarcoma in 21%, osteosarcoma in 21%; pathologic subtype in STS was MFH in 23%, MPNST in 21%, synovial sarcoma in 13%. Results: The 3- and 5-year overall actuarial survival rates were 68% (95% Cl, 61%-75%) and 52% (95% C1, 43%-61%), respectively, and the actuarial overall local control rates were 85% (95% C1, 80%- 90%), and 81% (95\u27%C1, 74%-88%) at 3 years and 5 years of follow-up, respectively. Overall toxicity was acceptable, with 2% skin/soft tissue late G3/4 toxicity. Conclusions: Carbon ion radiotherapy shows a substantial local control in the patients with bone and soft tissue sarcomas not suited for surgical resection with acceptable morbidity.44th ASCO Annual Meetin

Carbon Ion Radiotherapy for Unresectable Primary Bone Sarcoma of the Spine

Purpose/Objective(s): Primary bone sarcomas of the spine (PBSS) are rare. Common primary sarcomas include chondrosarcomas, chordoma, osteosarcoma, malignant fibrous histiocytoma (MFH), and Ewing\u27s sarcoma. Surgery remains the mainstay of treatment, although the anatomy of spine and spinal cord often limits complete surgical resection with a wide margin. Chemotherapy and radiation therapy have variable effects on these tumors. Due to the high energy transfer (LET) and the Bragg peak, carbon ion radiotherapy have been expected to be more effective and safe in the treatment for PBSS than low-LET radiation like photons. We evaluated the effectiveness and safety of carbon ion radiotherapy in patients with PBSS. Materials/Methods: From 1996 to 2006, 26 (male/female: 14/12) patients with PBSS (excluded C1-2 and sacrum primary), not suited for resection, received carbon ion radiotherapy. Ages ranged from 19 to 82 (mean 48 years). Nineteen patients had primary disease and 7 recurrent or post operative gross disease. Six tumors were located at cervical, 10 at thoracic, and 10 at lumber spine. Histologic diagnoses were as follows: chondrosarcoma in 8, chordoma in 7, osteosarcoma in 6, MFH in 2, Ewing\u27s sarcoma in 2, and angiosarcoma in 1 patients . Carbon ion radiotherapy was delivered in 16 fractions over 4 weeks. Ten patients were entered onto a phase I/II dose escalation study of carbon ion radiotherapy and the remaining 16 patients a phase II study with fixed doses. Total doses: 52.8 GyE (3.3 GyE/Fr) in 1, 57.6 GyE (3.6 GyE/Fr) in 3, 64.0 GyE (4.0 GyE/Fr) in 13, and 70.4 GyE (4.4 GyE/Fr) in 9 patients. Clinical target volumes ranged between 35 and 1232 cm3 (median 342 cm3).Results: Median survival time was 24 (range: 2-116) months for all patients and all living patients were followed more than 1 year. At 3 and 5 years, actuarial overall survival rates were 52% and 52%. Three patients experienced local recurrence, with time from carbon ion radiotherapy to local recurrence ranging from 1 to 20 months. At 3 years, actuarial local control rate was 8.6%. One grade 3 acute skin reaction and one grade 4 late skin reaction were observed. Three patients required surgical intervention for compression fracture of the affected spine at 2, 3, and 7 years after carbon ion radiotherapy. Conclusions: PBSS are rare. Local control at 3 years in patients with PBSS treated by carbon ion radiotherapy are almost similar to those in reported data on patients treated by surgical resection with/without adjuvant radiotherapy. Despite the higher doses delivered to the tumors and the locally more advanced nature of the patients in this series, toxicities were acceptable level. Carbon ion radiotherapy is suggested to be an effective and safe treatment for PBSS, but further experience and longer follow up are needed.50th Annual Meetin

Carbon Ion Radiotherapy for Unresectable Primary Bone Sarcoma of the Spine

Purpose/Objective(s): Primary bone sarcomas of the spine (PBSS) are rare. Common primary sarcomas include chondrosarcomas, chordoma, osteosarcoma, malignant fibrous histiocytoma (MFH), and Ewing\u27s sarcoma. Surgery remains the mainstay of treatment, although the anatomy of spine and spinal cord often limits complete surgical resection with a wide margin. Chemotherapy and radiation therapy have variable effects on these tumors. Due to the high energy transfer (LET) and the Bragg peak, carbon ion radiotherapy have been expected to be more effective and safe in the treatment for PBSS than low-LET radiation like photons. We evaluated the effectiveness and safety of carbon ion radiotherapy in patients with PBSS.Materials/Methods: From 1996 to 2006, 26 (male/female: 14/12) patients with PBSS (excluded C1-2 and sacrum primary), not suited for resection, received carbon ion radiotherapy. Ages ranged from 19 to 82 (mean 48 years). Nineteen patients had primary disease and 7 recurrent or post operative gross disease. Six tumors were located at cervical, 10 at thoracic, and 10 at lumber spine. Histologic diagnoses were as follows: chondrosarcoma in 8, chordoma in 7, osteosarcoma in 6, MFH in 2, Ewing\u27s sarcoma in 2, and angiosarcoma in 1 patients . Carbon ion radiotherapy was delivered in 16 fractions over 4 weeks. Ten patients were entered onto a phase I/II dose escalation study of carbon ion radiotherapy and the remaining 16 patients a phase II study with fixed doses. Total doses: 52.8 GyE (3.3 GyE/Fr) in 1, 57.6 GyE (3.6 GyE/Fr) in 3, 64.0 GyE (4.0 GyE/Fr) in 13, and 70.4 GyE (4.4 GyE/Fr) in 9 patients. Clinical target volumes ranged between 35 and 1232 cm3 (median 342 cm3).Results: Median survival time was 24 (range: 2-116) months for all patients and all living patients were followed more than 1 year. At 3 and 5 years, actuarial overall survival rates were 52% and 52%. Three patients experienced local recurrence, with time from carbon ion radiotherapy to local recurrence ranging from 1 to 20 months. At 3 years, actuarial local control rate was 8.6%. One grade 3 acute skin reaction and one grade 4 late skin reaction were observed. Three patients required surgical intervention for compression fracture of the affected spine at 2, 3, and 7 years after carbon ion radiotherapy.Conclusions: PBSS are rare. Local control at 3 years in patients with PBSS treated by carbon ion radiotherapy are almost similar to those in reported data on patients treated by surgical resection with/without adjuvant radiotherapy. Despite the higher doses delivered to the tumors and the locally more advanced nature of the patients in this series, toxicities were acceptable level. Carbon ion radiotherapy is suggested to be an effective and safe treatment for PBSS, but further experience and longer follow up are needed

Carbon ion radiotherapy for sacral chordoma

Objectives: To evaluate the effectiveness and safety of carbon ion radiotherapy in patients with sacral chorodma and to compare the results of carbon ion radiotherapy with those of surgical series in literature.Methods: Between 1996 and 2007, 95 patients with sacral chordoma were included in the phase I/II and phase II study of carbon ion radiotherapy for unresectable bone and soft tissue sarcomas. There were sixty-eight males and 27 females. Median age was 66 years (30-85). Eighty-four patients were presented with primary disease and 11 patients with post operative recurrent tumor. Total dose of52.8 to 73.6 GyE was given in 16 fractions over 4 weeks (4 days a week).Results: All patients completed the planned carbon ion radiotherapy. Median survival time was 42 months (13-112). Overall survival rate at 5 years (86%) in patients with sacral chordoma treated by carbon ion radiotherapy is similar to those in reported data on patients treated by surgical resection with/without adjuvant radiotherapy. Local control rate at 5years (88%) in patients with sacral chordoma treated by carbon ion radiotherapy is better than those in reported data. Median time local failure was 35 months (13-60). Four patients treated with a total dose of 73.6 GyE experienced Grade 3/4 skin/soft tissue complications. No other treatment-related surgical interventions including colostomy or urinary diversion were carried out in this series. Fifteen patients required persistent medication for peripheral neuropathy.Conclusions: Carbon ion therapy is suggested to be an effective and safe treatment for sacral chordomas, but further experience and longer follow-up are still needed.14th Annual CTOS Meetin

Prostate Cancer

Purpose: Analysis of the results of hypofractionated conformal carbon ion radiotherapy (C-ion RT) for localized prostate cancer was performed, with regard to normal tissue morbidity, biochemical relapse-free rate (bNED), and patient survival. Methods and Materials: Five hundreds and forty-two prostate cancer patients who received C-ion RT established through two preceding dose-escalation studies were analyzed in regard to toxicity, survival, and bNED. Results: Concerning radiation morbidity, no grade 3 or higher toxicities were observed either in the rectum or genitourinary system (GU), and the incidences of grade 2 rectum and GU morbidity were only 2.3% and 4.8%, respectively. The incidence of late GU toxicity in patients treated with 16 fractions of C-ion RT was lower than that of 20 fractions. Overall bNED at 5 years was 88.9%, with only four local recurrences. bNED of 16 fractions of C-ion RT was comparable to that of 20 fractions. Gleason\u27s score, T-stage, and initial PSA were significant prognostic factors for bNED, and T-stage was also a significant prognostic factor for overall survival rate. The duration of hormonal therapy also had an impact on biochemical control in high-risk patients, but it appeared possible to apply C-ion RT with short-course hormonal therapy to intermediate-risk patients. Conclusion: C-ion RT with the established dose fractionation regimen yielded satisfactory bNED with very few local recurrences, and with minimal morbidity. C-ion RT of 16 fractions could offer even lower incidence of GU toxicity than that of 20 fractions.NIRS-ETOILE Joint Symposium 2009 on Carbon Ion Radiotherap