- Email: [email protected]
Bone density changes following radiation for extremity sarcomas
Proceedings of the 44th Annual ASTRO Meeting
3, chordoma 1, osteosarcoma 1, metastatic renal cell carcinoma 1) and two had paravertebral sarcomas (malignant peripheral nerve sheath tumor 1, leiomyosarcoma 1). Intraoperative dural doses of 7.5-15 Gy were given over 6.43-40.1 minutes in conjunction with external beam radiotherapy doses of 16.2-70.2 Gy (median 55 Gy). Surface dose rate ranged from 18.7-45.83 cGy/min with the 192Ir plaques, 45.19 cGy/min with the 90Y liquid plaque, and 39.27-187.5 (average 98.32) cGy/min with the 90Y foil plaques. Measured surface dose profiles of the 90Y plaques showed acceptable central dose homogeneity with some fall-off along the foil edge. Along the length of the plaque, the characteristic 50% and 95% isodose lines were 0.8 mm and 3.9 mm, respectively, within the foil edge. Along the arc width of the plaque, the 50% and 95% lines were 1.7 mm and 5.0 mm, respectively, within the foil edge. With the 90Y plaques, personnel radiation exposure was negligible. No acute complications of the plaques have been seen; no late complications, specifically neuropathies, have been seen. At median follow-up time of 14.5 months (range 1-25 months), seven of eight patients remain locally controlled. Long-term treatment efficacy assessment awaits further follow-up. Conclusions: Among these customized dural plaques, the 90Y foil applicator is the optimal design and is the focus for future development efforts. To date, no acute or late morbidity of dural brachytherapy has been observed. It has been incorporated into a protocol for treatment of patients with spinal and paravertebral tumors which incorporates IMRT and/or proton radiotherapy, surgical resection, and dural brachytherapy.
236
Bone Density Changes Following Radiation for Extremity Sarcomas 1
J. Chen , S. McCance2, R. O’Keefe2, L. Miller-Watelet3, J.P. Williams1, P. Okunieff1, L.S. Constine1 1 Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, 2Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 3Department of Biostatistics, University of Rochester Medical Center, Rochester, NY Purpose/Objective: Bone irradiation (RT) incidental to treating extremity sarcoma is generally presumed to “weaken” the bone by decreasing density and increasing the risk for pathologic fracture. Our primary goal was to determine the relative effects on bone density of both RT and diminished mechanical loading secondary to tumor/therapy-induced functional extremity impairment. Secondary goals included determining the association with bone density and: (1) RT dose, (2) time interval from RT, (3) age at RT. Materials/Methods: Nineteen patients treated with surgical excision and RT for soft tissue extremity sarcomas had bone density measured in 4 sites using dual energy X-ray absorptiometry: the irradiated (A) and contralateral (B) bone, an uninvolved bone (C) in the treated extremity and its contralateral counterpart (D). Average age was 48 years (range 20-75). Involved extremities included 9 femora, 3 humeri, 4 radii, and 3 tibiae with an average RT dose of 57 Gy, (range 50.4-63). Bone density was measured at an average of 3.3 years (range 1.1-9.9) from RT. Each patient was analyzed for: (#1) difference between the irradiated and contralateral bone [A-B]; (#2) difference between the ipsilateral uninvolved and contralateral bone [C-D]; (#3) the difference between #1 and #2 to correct for weight-bearing effects [(A-B)-(C-D)]; and (#4) normalization for anatomic site density variation plus weight bearing [(A-B)/B–(C-D)/D]. Results: Overall, the mean bone density for all irradiated sites was increased 0.08⫾0.22 g/cm2 (variance) compared to the contralateral unirradiated side when corrected for weight bearing effects (#3). A relative increase in the irradiated bone density of 9 ⫾22% (p ⫽ 0.08) was also seen when the differences were divided by individual control densities to normalize variation in density of different anatomic sites (#4). A bimodal effect was seen when relating RT dose to bone density. Patients receiving low (⬍54 Gy) and high dose (⬎60 Gy) RT had a greater average increase in normalized density than those receiving intermediate dose RT (54-60 Gy). No linear trend was noted when comparing bone density and age although the normalized density in the oldest age group (⬎60 years) was higher than the middle or younger age groups. A relationship between time interval from RT and bone density was observed with those patients less than one year from RT having a higher density (average 19%) with a more random distribution at longer intervals. Conclusions: The net result of RT on bone density, when corrected for weight bearing or mechanical effects, is an increase. Patients at the upper and lower RT dose ranges had higher density measurements which may be explained by a dose dependent inhibition of resorption and remodeling, with differential effects on osteoblasts and osteoclasts. Patients less than one year from RT tended to have higher density than those more than one year from RT, which may reflect an early inhibition of bone resorption with a slow recovery over time. Older patients tended to have higher densities after RT, which may be due to a weaker recovery of bone remodeling after radiation. The increased density after RT may result from preferential inhibition of osteoclastic function as well as an ischemic vascular process. Therefore, the risk of fracture associated with radiation is not due to a decrease in bone density but from perturbations of bone remodeling resulting in a decreased ability to remodel and repair microfractures that occur in everyday trauma to bones. Further clinical and basic studies are in process to confirm our unexpected findings.
237
Intensity Modulated Radiotherapy for Soft Tissue Sarcoma of Thigh
L. Hong, K. Alektiar*, M. Hunt, S. Leibel* Departments of Medical Physics and Radiation Oncology*, Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective: Fracture of the femur is one of the late complications of adjuvant radiotherapy for patients with soft tissue sarcomas of the thigh receiving external beam irradiation after limb-sparing surgery. When the target volume approximates the femur, it is often inevitable that the whole circumference of the femur will receive full prescription dose with conventional radiation techniques. We report the feasibility of intensity modulated radiation therapy (IMRT) techniques to achieve adequate target coverage and bone sparing. Materials/Methods: Treatment planning was performed using both 3D conformal and IMRT techniques for 10 patients with soft tissue sarcoma of thigh. For all patients, the GTV and the femur were contoured. The PTV was defined as the GTV with
139
3, chordoma 1, osteosarcoma 1, metastatic renal cell carcinoma 1) and two had paravertebral sarcomas (malignant peripheral nerve sheath tumor 1, leiomyosarcoma 1). Intraoperative dural doses of 7.5-15 Gy were given over 6.43-40.1 minutes in conjunction with external beam radiotherapy doses of 16.2-70.2 Gy (median 55 Gy). Surface dose rate ranged from 18.7-45.83 cGy/min with the 192Ir plaques, 45.19 cGy/min with the 90Y liquid plaque, and 39.27-187.5 (average 98.32) cGy/min with the 90Y foil plaques. Measured surface dose profiles of the 90Y plaques showed acceptable central dose homogeneity with some fall-off along the foil edge. Along the length of the plaque, the characteristic 50% and 95% isodose lines were 0.8 mm and 3.9 mm, respectively, within the foil edge. Along the arc width of the plaque, the 50% and 95% lines were 1.7 mm and 5.0 mm, respectively, within the foil edge. With the 90Y plaques, personnel radiation exposure was negligible. No acute complications of the plaques have been seen; no late complications, specifically neuropathies, have been seen. At median follow-up time of 14.5 months (range 1-25 months), seven of eight patients remain locally controlled. Long-term treatment efficacy assessment awaits further follow-up. Conclusions: Among these customized dural plaques, the 90Y foil applicator is the optimal design and is the focus for future development efforts. To date, no acute or late morbidity of dural brachytherapy has been observed. It has been incorporated into a protocol for treatment of patients with spinal and paravertebral tumors which incorporates IMRT and/or proton radiotherapy, surgical resection, and dural brachytherapy.
236
Bone Density Changes Following Radiation for Extremity Sarcomas 1
J. Chen , S. McCance2, R. O’Keefe2, L. Miller-Watelet3, J.P. Williams1, P. Okunieff1, L.S. Constine1 1 Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, 2Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 3Department of Biostatistics, University of Rochester Medical Center, Rochester, NY Purpose/Objective: Bone irradiation (RT) incidental to treating extremity sarcoma is generally presumed to “weaken” the bone by decreasing density and increasing the risk for pathologic fracture. Our primary goal was to determine the relative effects on bone density of both RT and diminished mechanical loading secondary to tumor/therapy-induced functional extremity impairment. Secondary goals included determining the association with bone density and: (1) RT dose, (2) time interval from RT, (3) age at RT. Materials/Methods: Nineteen patients treated with surgical excision and RT for soft tissue extremity sarcomas had bone density measured in 4 sites using dual energy X-ray absorptiometry: the irradiated (A) and contralateral (B) bone, an uninvolved bone (C) in the treated extremity and its contralateral counterpart (D). Average age was 48 years (range 20-75). Involved extremities included 9 femora, 3 humeri, 4 radii, and 3 tibiae with an average RT dose of 57 Gy, (range 50.4-63). Bone density was measured at an average of 3.3 years (range 1.1-9.9) from RT. Each patient was analyzed for: (#1) difference between the irradiated and contralateral bone [A-B]; (#2) difference between the ipsilateral uninvolved and contralateral bone [C-D]; (#3) the difference between #1 and #2 to correct for weight-bearing effects [(A-B)-(C-D)]; and (#4) normalization for anatomic site density variation plus weight bearing [(A-B)/B–(C-D)/D]. Results: Overall, the mean bone density for all irradiated sites was increased 0.08⫾0.22 g/cm2 (variance) compared to the contralateral unirradiated side when corrected for weight bearing effects (#3). A relative increase in the irradiated bone density of 9 ⫾22% (p ⫽ 0.08) was also seen when the differences were divided by individual control densities to normalize variation in density of different anatomic sites (#4). A bimodal effect was seen when relating RT dose to bone density. Patients receiving low (⬍54 Gy) and high dose (⬎60 Gy) RT had a greater average increase in normalized density than those receiving intermediate dose RT (54-60 Gy). No linear trend was noted when comparing bone density and age although the normalized density in the oldest age group (⬎60 years) was higher than the middle or younger age groups. A relationship between time interval from RT and bone density was observed with those patients less than one year from RT having a higher density (average 19%) with a more random distribution at longer intervals. Conclusions: The net result of RT on bone density, when corrected for weight bearing or mechanical effects, is an increase. Patients at the upper and lower RT dose ranges had higher density measurements which may be explained by a dose dependent inhibition of resorption and remodeling, with differential effects on osteoblasts and osteoclasts. Patients less than one year from RT tended to have higher density than those more than one year from RT, which may reflect an early inhibition of bone resorption with a slow recovery over time. Older patients tended to have higher densities after RT, which may be due to a weaker recovery of bone remodeling after radiation. The increased density after RT may result from preferential inhibition of osteoclastic function as well as an ischemic vascular process. Therefore, the risk of fracture associated with radiation is not due to a decrease in bone density but from perturbations of bone remodeling resulting in a decreased ability to remodel and repair microfractures that occur in everyday trauma to bones. Further clinical and basic studies are in process to confirm our unexpected findings.
237
Intensity Modulated Radiotherapy for Soft Tissue Sarcoma of Thigh
L. Hong, K. Alektiar*, M. Hunt, S. Leibel* Departments of Medical Physics and Radiation Oncology*, Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective: Fracture of the femur is one of the late complications of adjuvant radiotherapy for patients with soft tissue sarcomas of the thigh receiving external beam irradiation after limb-sparing surgery. When the target volume approximates the femur, it is often inevitable that the whole circumference of the femur will receive full prescription dose with conventional radiation techniques. We report the feasibility of intensity modulated radiation therapy (IMRT) techniques to achieve adequate target coverage and bone sparing. Materials/Methods: Treatment planning was performed using both 3D conformal and IMRT techniques for 10 patients with soft tissue sarcoma of thigh. For all patients, the GTV and the femur were contoured. The PTV was defined as the GTV with
139