1. Introduction Osteosarcoma is the most common primary bone tumor diagnosed in childhood and adolescence, with peak incidence from ages 12-16; overall survival at 5 years for localized disease has been approximately 70%. Since the 1970’s, medical treatment has consisted generally of multidrug chemotherapy regimens with high-dose methotrexate, doxorubicin and cisplatin. While osteosarcoma has been found to be associated with inherited disorders such as hereditary retinoblastoma, Li- Fraumeni and Rothman-Thomson syndrome, it is not known to have any association with Down syndrome. There has been only one report of a case of osteosarcoma in a child with Down syndrome, and he died from sepsis 18 days following treatment with high-dose methotrexate. Although chemotherapy regimens with high-dose methotrexate have been the mainstay of medical therapy for osteosarcoma in pediatric patients, literature of acute lymphoblastic leukemia in Down syndrome patients has shown that these individuals have heightened sensitivity to the toxicities of methotrexate. Since that time, there have been no published treatment plans for osteosarcoma specific to patients with Down syndrome. In this case, we describe the diagnosis and novel chemotherapy regimen for osteosarcoma in a pediatric patient with Down syndrome. Treatment of Osteosarcoma Without Methotrexate in a Pediatric Patient with Down Syndrome Audrey Nath, MD, PhD (PGY-2), Aaron Sugalski, DO The University of Texas Health Science Center at San Antonio, Department of Pediatrics Treatment Plan Given that this patient with Down syndrome likely would not be able to tolerate treatment with high-dose methotrexate, an alternative treatment plan was created without methotrexate. A combination of carboplatin, ifosfamide and doxorubicin was chosen based on the results from the St. Jude’s Children’s Research Hospital OS99 trial. These patients had an estimated 5-year survival rate of 78%, and 61% of the patients exhibited greater than 90% tumor necrosis following chemotherapy. Dosages of each chemotherapeutic agent were approximated based on the dosages used in both the OS99 trial as well as in the Children’s Oncology Group AOST0331 protocol for osteosarcoma in poor responders post-induction. Two days following the first treatment of ifosfamide and carboplain, the patient had worsening left lower extremity pain. MRI was repeated and showed progression of the lesion. At this point, the tumor was resected with an above- the-knee amputation of the left lower extremity. Case Presentation 13-year-old Hispanic male with Down syndrome presented with a two month history of limping. X-rays showed a non- displaced fracture of the left proximal tibia. His left lower extremity was placed in a cast for three weeks, after which time he was noted to have pronounced swelling of the left proximal tibia. Plain films were concerning for malignancy due to a noted periosteal reaction without fracture. MRI showed an aggressive bony lesion, and biopsy was consistent with high-grade osteosarcoma. Bone scan and chest CT were negative, and staging was completed with diagnosis consistent with localized, high-grade osteosarcoma. Conclusions We have described the first known case of the successful treatment of osteosarcoma in a child with Down syndrome. Prior to this case, there has been only one report of a child with Down syndrome who developed osteosarcoma, and he died from sepsis following the standard therapy with high-dose methotrexate. In the current case study, our patient with Down syndrome received one dose of carboplatin, 480 mg/m2 of cisplatin, 450 mg/m2 of doxorubicin and 56 g/m2 of ifosfamide. The original regimen was adjusted secondary to chronic renal insufficiency to include cisplatin instead of carboplatin and fewer doses of ifosfamide. After completing this chemotherapy regimen and undergoing tumor resection, our patient was alive after one year, with no new tumors or metastases found on end-of-therapy imaging. He tolerated chemotherapy well without any incidents of sepsis. Given the lack of recurrence or progression of his high- grade osteosarcoma with the combination of cisplatin/carboplatin, ifosfamide and doxorubicin, this regimen may be of benefit to other pediatric patients with Down syndrome who require treatment of osteosarcoma and are unable to tolerate the toxicities of high-dose methotrexate. References Gorlick R, Janeway K, Lessnick S, et al. Children’s Oncology Group’s 2013 blueprint for research: bone tumors. Pediatr Blood Cancer 2013;60:1009-1015. Bacci G, Ferrari S, Mercuri M, et al. Neoadjuvant chemotherapy for extremity osteosarcoma. Acta Oncologia 1998;37(1):41-48. Wilimas J, Barrett G, Pratt C. Osteosarcoma in 2 very young children. Clin Pediatr 1977;16(6):548-51. Shah N, Al-Ahmari A, Al-Yamani A, et al. Outcome and toxicity of chemotherapy for acute lymphoblastic leukemia in children with Down syndrome. Pediatr Blood Cancer 2009;52:14-19. Daw N, Neel M, Rao B, et al. Frontline treatment of localized osteosarcoma without methotrexate. Cancer 2011;117:2770-8. National Cancer Institute at the National Institutes of Health. Clinical trials: combination chemotherapy, PEG-interferon alfa-2b, and surgery in treating patients with osteosarcoma. Sponsor: Children’s Oncology Group. Texas Pediatric Society Electronic Poster Contest Plain films of left knee showing aggressive lesion of the proximal left tibia. MRI of left tibia and fibula with IV contrast, showing aggressive bony lesion within the proximal tibial epiphysis, metaphysis and mid-diaphysis. Carboplatin (# doses) Cisplatin (mg/m 2 ) Doxorubicin (mg/m2) Ifosfamide (g/m2) OS998 37564 AOST0331 48045051 Current study148045062 Clinical Outcome Throughout our patient’s treatment course, he had two episodes of febrile neutropenia without any positive blood cultures or sepsis. He received standard Pneumocystis carinii prophylaxis with trimethoprim-sulfamethoxazole. Following one year of chemotherapy, there were no bony tumors or metastases found on x-rays, bone scan or chest CT.