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TU_43_3741 - Significant Risk of Secondary Malignancy In Ewing Sarcoma and Osteosarcoma Survivors

Tuesday, October 23
2:45 PM - 4:15 PM
Location: Innovation Hub, Exhibit Hall 3

Significant Risk of Secondary Malignancy In Ewing Sarcoma and Osteosarcoma Survivors
Y. L. E. Chen1,2, R. Miao3, S. I. Goldberg1, A. Jacobson3, H. Wang1, G. M. Cote4, E. Choy4, F. J. Hornicek5, and T. F. DeLaney1; 1Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 2Harvard Medical School, Boston, MA, 3Massachusetts General Hospital, Boston, MA, 4Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, 5Department of Orthopaedic Surgery, University of California Los Angeles, Los Angeles, CA

Purpose/Objective(s): Secondary malignancy (SM) is a major late effect of Ewing sarcoma (ES) and osteosarcoma (OS) treatment. We examined a large single institutional cohort to evaluate the rate of SM and potential risk factor.

Materials/Methods: We retrospectively reviewed 1071 patients with ES and OS from a database of 13,500 sarcoma cases treated at our institution between 1985-2015. Cumulative incidence of SM was estimated using Fine and Gray’s competing risk model and contribution of clinical and treatment factors were assessed on univariate and multivariate analysis.

Results: The cohort was distributed as follows: ES (314) and OS (757), with median age at initial diagnosis of 23 years (1-92 yrs), median tumor size 8 cm (0.5 to 47 cm). 382 patients were treated with RT to a median dose of 55.8 Gy (10 to 104 Gy; latter from reirradiation). 77.9% of patients received chemotherapy (VAC+/-IE and MAP based chemotherapy for majority of ES and OS, respectively). At median follow up of 55.3 months (13.5-380 months), 34 patients developed 36 SM, including 14 solid tumors (4 undifferentiated pleomorphic sarcomas, 2 breast cancers, 2 melanomas, 1 MPNST, 1 osteosarcoma, 1 rhabdomyosarcoma, 1 meningioma, 1 GBM, 1 desmoid tumor, 1 papillary carcinoma, and 20 leukemia/MDS at a rate of 1.8% at 5 years, 2.7% at 10 years, and 4.6%. SM rate for ES was 3.4% at 5 years, 4% at 10 years, and 10% at 20 years. SM rate for osteosarcoma at 5 years was 1.2%, at 10 years 2.1%, and at 20 years 3%. Median Interval between initial tumor and SM was 52.8 months (13.4 – 298.8mo), mean 95.5 months. Mean time to SM was 70.2 months in 17 OS patients vs. 119.2 months for 17 ES patients (p=0.114). SM rate for all patients who received RT was 3.3% at 5 years, 5.1% at 10 years and 6.9% at 20 years. SM rate for those not receiving any RT was 1% at 5 years, 1.4% at 10 years, and 2% at 20 years. There does not appear to be a RT dose response for SM. For patients receiving chemotherapy, SM risk was 2.3% at 5 years, 3.4% at 10 years, and 6.1% at 20 years. Overall Survival after SM was 35.2% at 5 years with median 48.1 months. On multivariate analysis, ES, RT and later diagnosis year was associated with increased risk of SM (0.0001). Later diagnosis year is associated with more pelvic and spine cases (p=0.0001), more head and neck sites (p=0.001), and increasing use of both chemotherapy and radiation therapy at our institution.

Conclusion: Rate of SM (solid and heme) is higher for ES than OS, with both increasing over the two decades after therapy. Patients should be counseled accordingly. Continued long-term follow up of ES and OS survivors is important part of survivorship.
Table 1: Factors associated with SM HR P-value
Treatment type: Chemo+RT 5.52 0.0001
RT 4.49 0.0001
Chemo 1 0.2910
Histology: ES vs. OS 3.02 0.0016
Sites: Head & Neck 2.13 0.0737
Pelvis&Spine 1.86 0.0819
Trunk 1.63 0.4213
Low Extremity 0.49 0.0512
Upper Extremity 0.27 0.1915
Diagnosis Year 1.05 per year 0.0090

Author Disclosure: Y.E. Chen: Employee; Beth Israel Deaconess Medical Center. R. Miao: None. S.I. Goldberg: None. A. Jacobson: None. G.M. Cote: None. T.F. DeLaney: None.

Yen-Lin Chen, MD

Massachusetts General Hospital

Beth Israel Deaconess Medical Center: Dermatologist: Employee; Massachusetts General Hospital: Assistant Radiation Oncologist: Employee


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