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Single Institution Experience with Preoperative Hypofractionated Radiation and Concurrent Dose-intense Chemotherapy for Patients with High-risk Soft Tissue Sarcomas
I. J. Radiation Oncology d Biology d Physics
S120
1016
Volume 72, Number 1, Supplement, 2008
Single Institution Experience with Preoperative Hypofractionated Radiation and Concurrent Dose-intense Chemotherapy for Patients with High-risk Soft Tissue Sarcomas
A. Y. Hung, J. B. Hayden, A. Mansoor, J. Vetto, D. Sauser, C. W. Ryan Oregon Health & Science University, Portland, OR Purpose/Objective(s): A phase II study investigating a preoperative regimen of dose-intense chemotherapy with epirubicin and ifosfamide combined with hypofractionated radiation for high-risk soft tissue sarcomas. The primary objective of the study was the estimation of the rate of .95% pathologic necrosis after neoadjuvant therapy. Materials/Methods: 27 patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring .5 cm were treated with epirubicin at a dose of 30 mg/m2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 Gy of radiation was administered over 8 fractions concomitant with chemotherapy Cycle 2 (with the epirubicin omitted). If the patient still had positive margins after surgery, a boost of 12 Gy over 6 fractions was given before the patients resumed chemotherapy. Results: Median age was 45 years and median tumor size was 10 cm (5-30). 23 patients received all 6 cycles of chemotherapy. 26 patients received their radiation preoperatively and all but 1 underwent a limb-sparing procedure. 4 patients (15%) had a wound complication necessitating an additional procedure or closure and 4 more patients (15%) had persistent drainage or a seroma. The median length of stay after surgery was 3 days (range, 2-10). 7 patients (26%) had complete ($95%) pathologic necrosis in their surgical specimen. We did not observe a correlation between complete pathologic necrosis and any measures of clinical outcome. With a median follow-up of 26 months, the 2 yr overall survival is 86%. Freedom from local recurrence and distant metastasis rates are 78% and 65%, respectively. Conclusions: Our phase II protocol of a combined modality approach to neoadjuvant therapy with hypofractionated radiation appears to be well tolerated with comparable clinical outcomes to other reports utilizing chemotherapy and radiation adjuvantly for patients with large, high-grade sarcomas. Author Disclosure: A.Y. Hung, None; J.B. Hayden, None; A. Mansoor, None; J. Vetto, None; D. Sauser, None; C.W. Ryan, None.
1017
Bone Sarcomas in Atomic Bomb Survivors of Hiroshima and Nagasaki
D. Samartzis1, N. Nishi2, M. Hayashi2, Y. Shimizu2, J. Cologne2, H. Cullings2, K. Kodama2, E. F. Miles2, S. Funamoto2, A. Suyama2, et al. 1
Shriners Hospital for Children, Chicago, IL, 2Radiation Effects Research Foundation, Hiroshima, Japan
Purpose/Objective(s): Ionizing radiation-induced bone sarcomas have traditionally been associated with exposure to high levels of ionizing radiation. The role of exposure to lower levels of ionizing radiation in the development of such lesions remains speculative. Also, the appropriate dose-response model of radiation dose exposure to excess relative risk (ERR) in association with bone sarcomas is questionable. Materials/Methods: The data source of the longitudinal, population-based Life Span Study (N = 120,321) cohort of atomic bomb survivors of Hiroshima and Nagasaki was utilized to estimate the ERR per Gray (Gy) of ionizing radiation exposure in the development of bone sarcomas. Other factors regarding sarcoma demographics, age at time of exposure, time to diagnosis from exposure, survival, and additional clinical information were assessed. The follow-up period of the study was from January 1, 1958 to December 31, 2001. Bone marrow dose in Gy units was utilized. Results: Following review, 80,181 participants met the inclusion criteria with a total of 2,170,679 person-years at risk. Nineteen bone sarcomas were identified with an incidence rate of 0.9 per 100,000 person-years. There were 11 males (58%) and 8 females (42%). The mean age at the time of the bombings was 32.4 years. Six participants (32%) were younger than 16 years of age at the time of the bombings. The mean age of sarcoma diagnosis was 61.6 years. The mean time to sarcoma diagnosis since exposure was 29.3 years. The mean bone marrow dose was 0.433 Gy. The most common sarcoma was classified as a malignant neoplasm with no further specification (42%), followed by osteosarcomas (26%). The most common cancer sites were bones of the pelvis, sacrum, and coccyx as well as associated joints (47%). The mean survival time after diagnosis was 2.5 years. Two participants were noted to be alive at final followup. The overall 5-year survival rate unadjusted for treatment-type was 25% (males, 45%; females, 0). No association between radiation exposure to the time of diagnosis, morphology, or topography of the bone sarcoma could be discerned from this study. A linear model with a threshold at 0.85 Gy (95% CI 0.12-1.85) was found with an ERR of 1.1 at 1 Gy (8.7 at 2 Gy) (p = 0.002). Conclusions: In contrast to the reported literature, our study suggests that the development of radiation-induced bone sarcomas may be associated with exposure to much lower doses of ionizing radiation following a single whole body dose. A linear model with a threshold at 0.85 Gy was found to be the best predictive non-hormetic model with a statistically significant ERR of 1.1 at 1 Gy (ERR=8.7 at 2 Gy). Due to the small sample size, the affects of age at the time of exposure and radiation dose could not be properly discerned with regards to bone sarcoma development. A poor clinical prognosis was associated with bone sarcomas. Author Disclosure: D. Samartzis, None; N. Nishi, None; M. Hayashi, None; Y. Shimizu, None; J. Cologne, None; H. Cullings, None; K. Kodama, None; E.F. Miles, None; S. Funamoto, None; A. Suyama, None.
1018
Intraoperative Radiotherapy Plus External Beam Radiotherapy versus External Beam Radiotherapy Alone for Soft Tissue Sarcoma of the Extremity: A Case Control Study
T. P. Korytko1, C. Alvarez-Breckenridge2, J. L. Mayerson3, A. Neki4, P. E. Wakely5, G. S. Young6, E. Y. Kim1 1 Department of Radiation Medicine, James Cancer Hospital, Columbus, OH, 2The Ohio State University College of Medicine, Columbus, OH, 3Division of Orthopedic Oncology, The Ohio State University, Columbus, OH, 4Department of Medical Oncology, James Cancer Hospital, Columbus, OH, 5Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, 6Center for Biostatistics, The Ohio State University Medical Center, Columbus, OH
Purpose/Objectives: To compare wound complication (WC), radiotherapy (RT) delay, limb sparing, local control (LC), disease free survival (DFS), and overall survival (OS) in patients with extremity soft tissue sarcoma (STS) treated by intraoperative radiotherapy plus postoperative external beam radiotherapy (IORT) to postoperative external beam radiotherapy (EBRT) alone.
S120
1016
Volume 72, Number 1, Supplement, 2008
Single Institution Experience with Preoperative Hypofractionated Radiation and Concurrent Dose-intense Chemotherapy for Patients with High-risk Soft Tissue Sarcomas
A. Y. Hung, J. B. Hayden, A. Mansoor, J. Vetto, D. Sauser, C. W. Ryan Oregon Health & Science University, Portland, OR Purpose/Objective(s): A phase II study investigating a preoperative regimen of dose-intense chemotherapy with epirubicin and ifosfamide combined with hypofractionated radiation for high-risk soft tissue sarcomas. The primary objective of the study was the estimation of the rate of .95% pathologic necrosis after neoadjuvant therapy. Materials/Methods: 27 patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring .5 cm were treated with epirubicin at a dose of 30 mg/m2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 Gy of radiation was administered over 8 fractions concomitant with chemotherapy Cycle 2 (with the epirubicin omitted). If the patient still had positive margins after surgery, a boost of 12 Gy over 6 fractions was given before the patients resumed chemotherapy. Results: Median age was 45 years and median tumor size was 10 cm (5-30). 23 patients received all 6 cycles of chemotherapy. 26 patients received their radiation preoperatively and all but 1 underwent a limb-sparing procedure. 4 patients (15%) had a wound complication necessitating an additional procedure or closure and 4 more patients (15%) had persistent drainage or a seroma. The median length of stay after surgery was 3 days (range, 2-10). 7 patients (26%) had complete ($95%) pathologic necrosis in their surgical specimen. We did not observe a correlation between complete pathologic necrosis and any measures of clinical outcome. With a median follow-up of 26 months, the 2 yr overall survival is 86%. Freedom from local recurrence and distant metastasis rates are 78% and 65%, respectively. Conclusions: Our phase II protocol of a combined modality approach to neoadjuvant therapy with hypofractionated radiation appears to be well tolerated with comparable clinical outcomes to other reports utilizing chemotherapy and radiation adjuvantly for patients with large, high-grade sarcomas. Author Disclosure: A.Y. Hung, None; J.B. Hayden, None; A. Mansoor, None; J. Vetto, None; D. Sauser, None; C.W. Ryan, None.
1017
Bone Sarcomas in Atomic Bomb Survivors of Hiroshima and Nagasaki
D. Samartzis1, N. Nishi2, M. Hayashi2, Y. Shimizu2, J. Cologne2, H. Cullings2, K. Kodama2, E. F. Miles2, S. Funamoto2, A. Suyama2, et al. 1
Shriners Hospital for Children, Chicago, IL, 2Radiation Effects Research Foundation, Hiroshima, Japan
Purpose/Objective(s): Ionizing radiation-induced bone sarcomas have traditionally been associated with exposure to high levels of ionizing radiation. The role of exposure to lower levels of ionizing radiation in the development of such lesions remains speculative. Also, the appropriate dose-response model of radiation dose exposure to excess relative risk (ERR) in association with bone sarcomas is questionable. Materials/Methods: The data source of the longitudinal, population-based Life Span Study (N = 120,321) cohort of atomic bomb survivors of Hiroshima and Nagasaki was utilized to estimate the ERR per Gray (Gy) of ionizing radiation exposure in the development of bone sarcomas. Other factors regarding sarcoma demographics, age at time of exposure, time to diagnosis from exposure, survival, and additional clinical information were assessed. The follow-up period of the study was from January 1, 1958 to December 31, 2001. Bone marrow dose in Gy units was utilized. Results: Following review, 80,181 participants met the inclusion criteria with a total of 2,170,679 person-years at risk. Nineteen bone sarcomas were identified with an incidence rate of 0.9 per 100,000 person-years. There were 11 males (58%) and 8 females (42%). The mean age at the time of the bombings was 32.4 years. Six participants (32%) were younger than 16 years of age at the time of the bombings. The mean age of sarcoma diagnosis was 61.6 years. The mean time to sarcoma diagnosis since exposure was 29.3 years. The mean bone marrow dose was 0.433 Gy. The most common sarcoma was classified as a malignant neoplasm with no further specification (42%), followed by osteosarcomas (26%). The most common cancer sites were bones of the pelvis, sacrum, and coccyx as well as associated joints (47%). The mean survival time after diagnosis was 2.5 years. Two participants were noted to be alive at final followup. The overall 5-year survival rate unadjusted for treatment-type was 25% (males, 45%; females, 0). No association between radiation exposure to the time of diagnosis, morphology, or topography of the bone sarcoma could be discerned from this study. A linear model with a threshold at 0.85 Gy (95% CI 0.12-1.85) was found with an ERR of 1.1 at 1 Gy (8.7 at 2 Gy) (p = 0.002). Conclusions: In contrast to the reported literature, our study suggests that the development of radiation-induced bone sarcomas may be associated with exposure to much lower doses of ionizing radiation following a single whole body dose. A linear model with a threshold at 0.85 Gy was found to be the best predictive non-hormetic model with a statistically significant ERR of 1.1 at 1 Gy (ERR=8.7 at 2 Gy). Due to the small sample size, the affects of age at the time of exposure and radiation dose could not be properly discerned with regards to bone sarcoma development. A poor clinical prognosis was associated with bone sarcomas. Author Disclosure: D. Samartzis, None; N. Nishi, None; M. Hayashi, None; Y. Shimizu, None; J. Cologne, None; H. Cullings, None; K. Kodama, None; E.F. Miles, None; S. Funamoto, None; A. Suyama, None.
1018
Intraoperative Radiotherapy Plus External Beam Radiotherapy versus External Beam Radiotherapy Alone for Soft Tissue Sarcoma of the Extremity: A Case Control Study
T. P. Korytko1, C. Alvarez-Breckenridge2, J. L. Mayerson3, A. Neki4, P. E. Wakely5, G. S. Young6, E. Y. Kim1 1 Department of Radiation Medicine, James Cancer Hospital, Columbus, OH, 2The Ohio State University College of Medicine, Columbus, OH, 3Division of Orthopedic Oncology, The Ohio State University, Columbus, OH, 4Department of Medical Oncology, James Cancer Hospital, Columbus, OH, 5Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, 6Center for Biostatistics, The Ohio State University Medical Center, Columbus, OH
Purpose/Objectives: To compare wound complication (WC), radiotherapy (RT) delay, limb sparing, local control (LC), disease free survival (DFS), and overall survival (OS) in patients with extremity soft tissue sarcoma (STS) treated by intraoperative radiotherapy plus postoperative external beam radiotherapy (IORT) to postoperative external beam radiotherapy (EBRT) alone.