- Email: [email protected]
Long Term Toxicity of Interstitial Brachytherapy for Soft Tissue Sarcomas
I. J. Radiation Oncology d Biology d Physics
S620
Volume 78, Number 3, Supplement, 2010
In two pts we considered an hypofractioned schedule (2.2Gy/fraction: total dose: 77Gy/35 applications) using VMAT by Varian Accelerator. Median (range) follow-up is 44 months (4-66). Therapy was well tolerated (1 case of G2 gastrointestinal toxicity) without neurological side effects, even in 2 pts submitted to hypofractioned radiation treatment. All 16 pts had a radiological tumor response (increased necrosis in 100% of pts, tumor shrinkage in 10/16 pts, i.e. 62%), along with symptomatic improvement. After a good radiological response, one pt progressed 14 months after the end of RT and is now on medical treatment with clinical benefit. 19 pts were excluded from definitive X-IMRT: 6 underwent surgery + adjuvant RT and are alive and disease-free; 2 skull-base + 1 sacral chordoma were sent for definitive H-RT elsewhere and are alive and progression-free; 8 are lost to follow-up; 2 died for disease progression. Conclusions: Our series provides preliminary evidence that high-dose photon radiation therapy in extra-cranial chordoma, mainly in sacrum, is feasible. Further studies are needed to compare these results to of H-RT. Evaluation of treatment results needs a longer follow-up. Author Disclosure: C. Sangalli, None; P. Pittoni, None; S. Stacchiotti, None; M. Fiore, None; P. Casali, None; E. Pignoli, None; E. Palassini, None; P. Olmi, None.
2930
Variations in the Gross Target Volume and Clinical Target Volume Evaluated by RTOG Sarcoma Radiation Oncologists for Preoperative Radiotherapy of Primary Extremity Sarcoma
D. Wang1, W. Bosch2, D. kirsch3, R. Lozi2, I. Naqa2, D. Roberge4, S. Finkelstein5, I. Petersen6, N. Saito7, T. DeLaney8 1 Medical College of Wisconsin, Milwaukee, WI, 2Washington University, St Louis, MO, 3Duke University, Durham, NC, 4McGill University, Montre´al, QC, Canada, 5Moffitt Cancer Center, Tampa Bay, FL, 6Mayo Clinic, Rochester, MN, 7Roswell Park Cancer Institute, Buffalo, NY, 8Massachusetts General Hospital, Boston, MA
Purpose/Objective(s): to evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists. Materials/Methods: Extremity sarcoma radiation planning computed tomography (CT) scans along with corresponding diagnostic MRI from 2 patients (one from lower extremity sarcoma with fused CT-MRI and one from upper extremity sarcoma without fused CT-MRI) were distributed to 10 RTOG sarcoma radiation oncologists with instructions to define GTVs and CTVs as described in the protocol RTOG 0630. The CT data with contours were then returned for central analysis. Contours representing statistically-corrected 95% (V95) and 100% (V100) agreement were computed for each structure. Results: Minimal variations in the GTV in both lower extremity and upper extremity cases were seen among physicians; minimal variations were also noted in the lower extremity CTV, but more variability was seen for the upper extremity CTV. For GTV, the minimum, maximum, mean (SD) volumes (mL) were 673.58, 798.33, 751.72±34.58 for the lower extremity case and 383.28, 543.41, 447.25 ± 46.18 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882.14, 761.46, and 752.41 for the lower, and 587.16, 460.68, and 455.27 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases [kappa = 0.9 (p \ 0.0001) and kappa = 0.86 (p \ 0.0001)]. For CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145.27, 1911.49, 1604.78±210.95 for the lower extremity case and 637.27, 1245.92, 1005.57±180.45 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 2093.72, 1609.23, and 1593.26 for the lower, and 1533.12, 1020.24, and 964.83 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case [kappa = 0.85 (p \ 0.0001)], but only substantial in the upper extremity case [kappa = 0.77 (p \ 0.0001)]. Conclusions: Almost perfect agreement existed in the GTV of these two representative lower and upper extremity cases, regardless CT-MRI fusion status. Similarly, there was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI. This study is supported by ATC Grant U24 CA81647 from the NIH. Author Disclosure: D. Wang, None; W. Bosch, None; D. kirsch, None; R. Lozi, None; I. Naqa, None; D. Roberge, None; S. Finkelstein, None; I. Petersen, None; N. Saito, None; T. DeLaney, None.
2931
Long Term Toxicity of Interstitial Brachytherapy for Soft Tissue Sarcomas
S. Poddar, S. Laskar, A. Puri, N. Jambhekar, M. A. Muckaden, G. Bahl Tata Memorial Hospital, Mumbai, India Purpose/Objective(s): To evaluate the clinical outcome and long term adverse effects of interstitial brachytherapy (BRT) for adult patients with soft tissue sarcomas (STS). Materials/Methods: From July 1990 to June 2008, 198 patients (median age 42 years, range 18 to 90) with STS received BRT as part of loco-regional treatment at our institute. There were 128 males and 70 females, majority (n = 138, 69.6%) had primary lesions, spindle cell sarcoma (26%) was the most common histological type, and 52.5% had high-grade sarcomas. Treatment included wide local excision followed by BRT with or without external beam radiotherapy (EBRT). Eighty one patients (41%) received BRT alone. Results: The 10-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 77.1%, 62.6%, and 70.8%, respectively. Patients receiving a combination of BRT and EBRT had comparable LC to those receiving BRT alone (76.1% vs. 81.6%, p = 0.081). Furthermore, there was no significant difference in LC for patients receiving LDR versus HDR BRT (75.1% vs. 80.9%, p = 0.120). Post-brachytherapy, surgical wound healing complications was seen in 26 (13.1%) patients (delay/dehiscence: n = 15, wound infection: n = 11). The 5-yr cumulative incidence (CI) of RT related late toxicity was 28.5% (Subcutaneous fibrosis: 26.4%, limb edema 7.4%, joint stiffness/arthritis: 6.6%, osteoradionecrosis: 2.4%, fracture: 2.4%). There was a trend towards reduction in late toxicity with the use of BRT alone (5yr CI: 19.5% vs. 32.4%, p = 0.081). Only one patient developed a second cancer (OGS). No patient had any vascular or nerve injury due to RT.
Proceedings of the 52nd Annual ASTRO Meeting Conclusions: Interstitial BRT with or without EBRT results in excellent outcome for patients with STS. Radical BRT alone, when used judiciously in select groups of patient, results in excellent local control and functional outcome with reduced treatment-related morbidity. Author Disclosure: S. Poddar, None; S. Laskar, None; A. Puri, None; N. Jambhekar, None; M.A. Muckaden, None; G. Bahl, None.
2932
The Initial Experience of Electronic Brachytherapy for the Treatment of Non-melanomatous Cutaneous Malignancies
A. Bhatnagar12, A. Loper1 1
Cancer Treatment Services Arizona, Casa Grande, AZ, 2University of Pittsburgh School of Medicine, Pittsburgh, PA
Purpose/Objective(s): To evaluate the acute adverse effects and early cosmetic outcomes of patients treated with electronic brachytherapy for the treatment of cutaneous malignancies. Materials/Methods: From July 2009 till March 2010, 34 patients with 40 cutaneous malignancies were treated with Xoft Axxent Electronic Brachytherapy system using surface applicators to a dose of 40.0 Gy in 8 fractions, 5 Gy per fraction, delivered twice weekly with minimum of 48 hour interval. The appropriately sized surface applicator, 10mm, 20mm, 35mm, or 50mm, was selected to allow for complete coverage of target lesion with acceptable margin. CT scan was performed to assess skin depth. The prescription depth was 3-7mm, 5mm for 83% of the lesions, 3mm for 15% of the fractions, and 7mm for the patient with T-cell lymphoma. All patients were treated outside of a linear accelerator vault in CT simulator room. Photographs were taken for all patients at initial consultation and follow-up visits. Acute safety outcomes and cosmetic results were analyzed. Cosmetic results were documented in the patient record using a standardized cosmesis scale. Results: There were 34 T1 lesions and 6 T2 lesions; 38 were primary cancers, and 2 were recurrences. 26 skin lesions were basal cell carcinoma, 12 were squamous cell carcinoma, 1 was Merkle cell carcinoma, and 1 was T-cell lymphoma. 17 lesions were located on the nose, 5 on the ear, 10 on the face, 4 on the scalp, and 4 on the extremities. Median follow-up was 3.2 months (range, 1-7.3). Average treatment time was 6.8 minutes per fraction. 91% developed radiation dermatitis grade 1 or 2 during treatment and resolved by the 1 month, 3 month or 6 month visit. There were no severe (Grade 3 or higher) acute toxicities. 1 patient developed moist desquamation during treatment which resolved at 1-month follow-up. One patient developed hypopigmentation at 3 months, and 3 patients developed hypopigmentation at 6 months. Cosmetic assessments of the treated areas done at various intervals from the last fraction are grouped for reporting: 25 were assessed at 1 month, 17 at 3 months, 8 at 6 months, and 1 at 7 months. The cosmetic results showed 88.0%, 94.1% 71.4%, 100.0% excellent at 1, 3, 6 and 7 months respectively and 12%, 5.9%, and 28.6% showed good results at 1, 3, and 6 months respectively. There was no evidence of tumor recurrence for all lesions. Conclusions: The early outcomes of electronic brachytherapy for the treatment of non-melanomatous cutaneous malignancies appear to show acceptable acute toxicities and favorable early cosmesis. The early results seem comparable to High Dose Rate Brachytherapy. The hypofractionated approach provides patient convenience approach with effective early outcomes. Longterm follow-up is being collected to further assess efficacy and cosmesis. Author Disclosure: A. Bhatnagar, Principal Investigator of Multi-Center Prospective Clinical Study Funded by Xoft, G. Other; A. Loper, None.
2933
Does the Risk of Late Radiation-Associated Malignancy Offset the Survival Benefit of Post-lumpectomy/ Mastectomy Radiation for Young Women? A Quantitative Study Based on SEER-data
L. Xie1,2, D. V. Fried1, J. E. Bailey1, R. Chen1, N. DeMore3, E. L. Jones1, J. S. Halle1, L. B. Marks1 1 Departments of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Department of Radiation Oncology, Fudan University Cancer Center, Shanghai, China, 3Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC
Purpose/Objective(s): Radiation therapy (RT) improves overall survival (OS) in the post-lumpectomy/mastectomy settings. The benefits reported at 10-20 years reflect the combined effects of a reduction in breast cancer-specific mortality and RT-induced mortality manifest in this ‘‘short’’ time interval. However, the longer-term risk for RT-associated second malignant neoplasms (RT-SMN) is likely not reflected in this data, particularly for younger women. We herein compare the risk of late RT-associated malignancy to the survival benefits afforded from post-operative RT. Materials/Methods: Data from randomized trials (e.g. Overgaard, Ragaz, EBCTCG meta-analysis) were used to estimate the 15-year RT-related improvement in OS. SEER data were used to estimate the age-dependence of RT-SMN. We quantitatively compared the magnitude of OS benefits at 15 years to RT-SMN risks beyond 15 years. Data was fit to a model describing the age-dependent nature of this comparison. Results: The estimated RT-related OS benefit for women age \50 is z10% at 15 years. The absolute risk of RT-SMN estimated from SEER was z0.5% within 0-10 years post-RT, with minimal age dependence. The mortality associated with these ‘‘early’’ RT-SMN is likely reflected in the 15-year OS data. The risks of RT-SMN in the 10-15, 15-20 and $20 year intervals were agedependent: z4.1, 3.8 and 3.1%, respectively for those age 20-29 at time of RT; z1.4, 3.4 and 2.0% for age 30-34, z1-2% in all intervals for age $35 (rates declining z linearly with age). If one conservatively assumes that the risks in all intervals are independent, the cumulative risk of death (among survivors at 15 years) from a RT-SMN at .15 years would be z 11.0, 6.8 and 4% for women irradiated at ages 20-29, 30-34 and $35 (SMN occurring at 10-15 years are assumed to cause death at .15 years). The improvement in OS (at 15 years) MINUS the risk of an RT-SMN that may cause mortality ($15 years) may be estimated as = 10 - (15-year survival rate with RT) [-0.7 (age at time of RT/10) + 6]. Conclusions: In women\30, the magnitude of the risk of RT-SMN $ 15 years post-RT is comparable to the 15-year OS benefit. In women $30, the magnitude of the risk of RT-SMN is less than the 15-year OS benefit afforded by RT. These risks are conservative (i.e. overstated) as many RT-SMN will not lead to mortality. Further, RT affords a higher survival rate in the initial 15-years and the risk of SMN is manifest only in those cured of breast cancer. One needs to project the years of life lost to an RT-SMN well into the future before it offsets the additional life-years gained. Therefore, this risk of RT-SMN should generally not dissuade the use of radiation. Author Disclosure: L. Xie, None; D.V. Fried, None; J.E. Bailey, None; R. Chen, None; N. DeMore, None; E.L. Jones, None; J.S. Halle, None; L.B. Marks, None.
S621
S620
Volume 78, Number 3, Supplement, 2010
In two pts we considered an hypofractioned schedule (2.2Gy/fraction: total dose: 77Gy/35 applications) using VMAT by Varian Accelerator. Median (range) follow-up is 44 months (4-66). Therapy was well tolerated (1 case of G2 gastrointestinal toxicity) without neurological side effects, even in 2 pts submitted to hypofractioned radiation treatment. All 16 pts had a radiological tumor response (increased necrosis in 100% of pts, tumor shrinkage in 10/16 pts, i.e. 62%), along with symptomatic improvement. After a good radiological response, one pt progressed 14 months after the end of RT and is now on medical treatment with clinical benefit. 19 pts were excluded from definitive X-IMRT: 6 underwent surgery + adjuvant RT and are alive and disease-free; 2 skull-base + 1 sacral chordoma were sent for definitive H-RT elsewhere and are alive and progression-free; 8 are lost to follow-up; 2 died for disease progression. Conclusions: Our series provides preliminary evidence that high-dose photon radiation therapy in extra-cranial chordoma, mainly in sacrum, is feasible. Further studies are needed to compare these results to of H-RT. Evaluation of treatment results needs a longer follow-up. Author Disclosure: C. Sangalli, None; P. Pittoni, None; S. Stacchiotti, None; M. Fiore, None; P. Casali, None; E. Pignoli, None; E. Palassini, None; P. Olmi, None.
2930
Variations in the Gross Target Volume and Clinical Target Volume Evaluated by RTOG Sarcoma Radiation Oncologists for Preoperative Radiotherapy of Primary Extremity Sarcoma
D. Wang1, W. Bosch2, D. kirsch3, R. Lozi2, I. Naqa2, D. Roberge4, S. Finkelstein5, I. Petersen6, N. Saito7, T. DeLaney8 1 Medical College of Wisconsin, Milwaukee, WI, 2Washington University, St Louis, MO, 3Duke University, Durham, NC, 4McGill University, Montre´al, QC, Canada, 5Moffitt Cancer Center, Tampa Bay, FL, 6Mayo Clinic, Rochester, MN, 7Roswell Park Cancer Institute, Buffalo, NY, 8Massachusetts General Hospital, Boston, MA
Purpose/Objective(s): to evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists. Materials/Methods: Extremity sarcoma radiation planning computed tomography (CT) scans along with corresponding diagnostic MRI from 2 patients (one from lower extremity sarcoma with fused CT-MRI and one from upper extremity sarcoma without fused CT-MRI) were distributed to 10 RTOG sarcoma radiation oncologists with instructions to define GTVs and CTVs as described in the protocol RTOG 0630. The CT data with contours were then returned for central analysis. Contours representing statistically-corrected 95% (V95) and 100% (V100) agreement were computed for each structure. Results: Minimal variations in the GTV in both lower extremity and upper extremity cases were seen among physicians; minimal variations were also noted in the lower extremity CTV, but more variability was seen for the upper extremity CTV. For GTV, the minimum, maximum, mean (SD) volumes (mL) were 673.58, 798.33, 751.72±34.58 for the lower extremity case and 383.28, 543.41, 447.25 ± 46.18 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882.14, 761.46, and 752.41 for the lower, and 587.16, 460.68, and 455.27 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases [kappa = 0.9 (p \ 0.0001) and kappa = 0.86 (p \ 0.0001)]. For CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145.27, 1911.49, 1604.78±210.95 for the lower extremity case and 637.27, 1245.92, 1005.57±180.45 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 2093.72, 1609.23, and 1593.26 for the lower, and 1533.12, 1020.24, and 964.83 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case [kappa = 0.85 (p \ 0.0001)], but only substantial in the upper extremity case [kappa = 0.77 (p \ 0.0001)]. Conclusions: Almost perfect agreement existed in the GTV of these two representative lower and upper extremity cases, regardless CT-MRI fusion status. Similarly, there was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI. This study is supported by ATC Grant U24 CA81647 from the NIH. Author Disclosure: D. Wang, None; W. Bosch, None; D. kirsch, None; R. Lozi, None; I. Naqa, None; D. Roberge, None; S. Finkelstein, None; I. Petersen, None; N. Saito, None; T. DeLaney, None.
2931
Long Term Toxicity of Interstitial Brachytherapy for Soft Tissue Sarcomas
S. Poddar, S. Laskar, A. Puri, N. Jambhekar, M. A. Muckaden, G. Bahl Tata Memorial Hospital, Mumbai, India Purpose/Objective(s): To evaluate the clinical outcome and long term adverse effects of interstitial brachytherapy (BRT) for adult patients with soft tissue sarcomas (STS). Materials/Methods: From July 1990 to June 2008, 198 patients (median age 42 years, range 18 to 90) with STS received BRT as part of loco-regional treatment at our institute. There were 128 males and 70 females, majority (n = 138, 69.6%) had primary lesions, spindle cell sarcoma (26%) was the most common histological type, and 52.5% had high-grade sarcomas. Treatment included wide local excision followed by BRT with or without external beam radiotherapy (EBRT). Eighty one patients (41%) received BRT alone. Results: The 10-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 77.1%, 62.6%, and 70.8%, respectively. Patients receiving a combination of BRT and EBRT had comparable LC to those receiving BRT alone (76.1% vs. 81.6%, p = 0.081). Furthermore, there was no significant difference in LC for patients receiving LDR versus HDR BRT (75.1% vs. 80.9%, p = 0.120). Post-brachytherapy, surgical wound healing complications was seen in 26 (13.1%) patients (delay/dehiscence: n = 15, wound infection: n = 11). The 5-yr cumulative incidence (CI) of RT related late toxicity was 28.5% (Subcutaneous fibrosis: 26.4%, limb edema 7.4%, joint stiffness/arthritis: 6.6%, osteoradionecrosis: 2.4%, fracture: 2.4%). There was a trend towards reduction in late toxicity with the use of BRT alone (5yr CI: 19.5% vs. 32.4%, p = 0.081). Only one patient developed a second cancer (OGS). No patient had any vascular or nerve injury due to RT.
Proceedings of the 52nd Annual ASTRO Meeting Conclusions: Interstitial BRT with or without EBRT results in excellent outcome for patients with STS. Radical BRT alone, when used judiciously in select groups of patient, results in excellent local control and functional outcome with reduced treatment-related morbidity. Author Disclosure: S. Poddar, None; S. Laskar, None; A. Puri, None; N. Jambhekar, None; M.A. Muckaden, None; G. Bahl, None.
2932
The Initial Experience of Electronic Brachytherapy for the Treatment of Non-melanomatous Cutaneous Malignancies
A. Bhatnagar12, A. Loper1 1
Cancer Treatment Services Arizona, Casa Grande, AZ, 2University of Pittsburgh School of Medicine, Pittsburgh, PA
Purpose/Objective(s): To evaluate the acute adverse effects and early cosmetic outcomes of patients treated with electronic brachytherapy for the treatment of cutaneous malignancies. Materials/Methods: From July 2009 till March 2010, 34 patients with 40 cutaneous malignancies were treated with Xoft Axxent Electronic Brachytherapy system using surface applicators to a dose of 40.0 Gy in 8 fractions, 5 Gy per fraction, delivered twice weekly with minimum of 48 hour interval. The appropriately sized surface applicator, 10mm, 20mm, 35mm, or 50mm, was selected to allow for complete coverage of target lesion with acceptable margin. CT scan was performed to assess skin depth. The prescription depth was 3-7mm, 5mm for 83% of the lesions, 3mm for 15% of the fractions, and 7mm for the patient with T-cell lymphoma. All patients were treated outside of a linear accelerator vault in CT simulator room. Photographs were taken for all patients at initial consultation and follow-up visits. Acute safety outcomes and cosmetic results were analyzed. Cosmetic results were documented in the patient record using a standardized cosmesis scale. Results: There were 34 T1 lesions and 6 T2 lesions; 38 were primary cancers, and 2 were recurrences. 26 skin lesions were basal cell carcinoma, 12 were squamous cell carcinoma, 1 was Merkle cell carcinoma, and 1 was T-cell lymphoma. 17 lesions were located on the nose, 5 on the ear, 10 on the face, 4 on the scalp, and 4 on the extremities. Median follow-up was 3.2 months (range, 1-7.3). Average treatment time was 6.8 minutes per fraction. 91% developed radiation dermatitis grade 1 or 2 during treatment and resolved by the 1 month, 3 month or 6 month visit. There were no severe (Grade 3 or higher) acute toxicities. 1 patient developed moist desquamation during treatment which resolved at 1-month follow-up. One patient developed hypopigmentation at 3 months, and 3 patients developed hypopigmentation at 6 months. Cosmetic assessments of the treated areas done at various intervals from the last fraction are grouped for reporting: 25 were assessed at 1 month, 17 at 3 months, 8 at 6 months, and 1 at 7 months. The cosmetic results showed 88.0%, 94.1% 71.4%, 100.0% excellent at 1, 3, 6 and 7 months respectively and 12%, 5.9%, and 28.6% showed good results at 1, 3, and 6 months respectively. There was no evidence of tumor recurrence for all lesions. Conclusions: The early outcomes of electronic brachytherapy for the treatment of non-melanomatous cutaneous malignancies appear to show acceptable acute toxicities and favorable early cosmesis. The early results seem comparable to High Dose Rate Brachytherapy. The hypofractionated approach provides patient convenience approach with effective early outcomes. Longterm follow-up is being collected to further assess efficacy and cosmesis. Author Disclosure: A. Bhatnagar, Principal Investigator of Multi-Center Prospective Clinical Study Funded by Xoft, G. Other; A. Loper, None.
2933
Does the Risk of Late Radiation-Associated Malignancy Offset the Survival Benefit of Post-lumpectomy/ Mastectomy Radiation for Young Women? A Quantitative Study Based on SEER-data
L. Xie1,2, D. V. Fried1, J. E. Bailey1, R. Chen1, N. DeMore3, E. L. Jones1, J. S. Halle1, L. B. Marks1 1 Departments of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Department of Radiation Oncology, Fudan University Cancer Center, Shanghai, China, 3Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC
Purpose/Objective(s): Radiation therapy (RT) improves overall survival (OS) in the post-lumpectomy/mastectomy settings. The benefits reported at 10-20 years reflect the combined effects of a reduction in breast cancer-specific mortality and RT-induced mortality manifest in this ‘‘short’’ time interval. However, the longer-term risk for RT-associated second malignant neoplasms (RT-SMN) is likely not reflected in this data, particularly for younger women. We herein compare the risk of late RT-associated malignancy to the survival benefits afforded from post-operative RT. Materials/Methods: Data from randomized trials (e.g. Overgaard, Ragaz, EBCTCG meta-analysis) were used to estimate the 15-year RT-related improvement in OS. SEER data were used to estimate the age-dependence of RT-SMN. We quantitatively compared the magnitude of OS benefits at 15 years to RT-SMN risks beyond 15 years. Data was fit to a model describing the age-dependent nature of this comparison. Results: The estimated RT-related OS benefit for women age \50 is z10% at 15 years. The absolute risk of RT-SMN estimated from SEER was z0.5% within 0-10 years post-RT, with minimal age dependence. The mortality associated with these ‘‘early’’ RT-SMN is likely reflected in the 15-year OS data. The risks of RT-SMN in the 10-15, 15-20 and $20 year intervals were agedependent: z4.1, 3.8 and 3.1%, respectively for those age 20-29 at time of RT; z1.4, 3.4 and 2.0% for age 30-34, z1-2% in all intervals for age $35 (rates declining z linearly with age). If one conservatively assumes that the risks in all intervals are independent, the cumulative risk of death (among survivors at 15 years) from a RT-SMN at .15 years would be z 11.0, 6.8 and 4% for women irradiated at ages 20-29, 30-34 and $35 (SMN occurring at 10-15 years are assumed to cause death at .15 years). The improvement in OS (at 15 years) MINUS the risk of an RT-SMN that may cause mortality ($15 years) may be estimated as = 10 - (15-year survival rate with RT) [-0.7 (age at time of RT/10) + 6]. Conclusions: In women\30, the magnitude of the risk of RT-SMN $ 15 years post-RT is comparable to the 15-year OS benefit. In women $30, the magnitude of the risk of RT-SMN is less than the 15-year OS benefit afforded by RT. These risks are conservative (i.e. overstated) as many RT-SMN will not lead to mortality. Further, RT affords a higher survival rate in the initial 15-years and the risk of SMN is manifest only in those cured of breast cancer. One needs to project the years of life lost to an RT-SMN well into the future before it offsets the additional life-years gained. Therefore, this risk of RT-SMN should generally not dissuade the use of radiation. Author Disclosure: L. Xie, None; D.V. Fried, None; J.E. Bailey, None; R. Chen, None; N. DeMore, None; E.L. Jones, None; J.S. Halle, None; L.B. Marks, None.
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