te: Consider Clinical Trials as treatment options for eligible patients. Referral to a center with both pediatric oncology and orthopedic surgery is essential. CLINICAL EVALUATION This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, NEOADJUVANT TREATMENT ADJUVANT TREATMENT History and Physical CBC, differential, platelets, total protein, albumin, calcium, total bilirubin, phosphorus, magnesium, BUN, creatinine, alkaline Phosphatase, LDH, AST, sodium, potassium, chloride, CO 2, and coagulation battery. Plain films of primary MRI of primary Bone Scan CR CT chest Consider PET scan Biopsy (open vs. needle) Histology review by Bone Tumor Pathologist EKG/ECHO CVC Urine pregnancy test if clinically indicated Discuss fertility Audiogram Consult Physical Therapy/Occupational therapy and Childlife Metastasis? See page 3 Neoadjuvant chemotherapy 1 for 2 cycles Assess treatment response: Clinical exam of primary tumor Reimage - -ray of primary -CT chest - Bone Scan -MRI 1 Doxorubicin and dexrazoxane for cardioprotection plus cisplatin and high-dose methotrexate 2 After surgical clearance. Progressive disease of primary site? Is primary tumor resectable? See page 2 Surgery: (limb salvage vs. amputation) Consider definitive radiotherapy Approximately 4 additional cycles of adjuvant chemotherapy beginning 2 weeks 2 after surgery Continue adjuvant chemotherapy and consider high-dose Ifosfamide plus or minus Etoposide See page 4 for Surveillance
te: This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, Consider Clinical Trials as treatment options for eligible patients. Referral to a center with both pediatric oncology and orthopedic surgery is essential. ADJUVANT TREATMENT Progressive Progressive disease of disease of primary site primary site Pulmonary metastases? Consider local treatment options for primary disease Is primary tumor resectable? Surgery: (limb salvage vs. amputation) Consider definitive radiotherapy 1-2 cycles of chemotherapy Assess histology response of resected tumor Consider adding or changing to high dose ifosfamide plus or minus etoposide Is there disease Consider gemcitabine/docetaxel Consider phase I or II trials Consider palliative local therapies to primary and metastatic sites Consider local therapies 1 for pulmonary metastasis and other metastatic sites Complete post op chemotherapy See page 4 for Surveillance 1 Surgery is the primary modality of local therapy
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, te: PRIMARY TREATMENT ADJUVANT TREATMENT Metastasis Doxorubicin, cisplatin, high dose methotrexate for 2 cycles 1 Restage to assess for progression Is there disease High-dose ifosfamide plus or minus etoposide for 2 cycles Reassess for treatment response Is there disease Consider gemcitabine/docetaxel Consider phase I or II trials Consider palliative local therapies to primary and metastatic sites Local control of primary tumor Continue chemotherapy Consider local therapies 2 to metastatic sites Local control of primary tumor. Continue chemotherapy. Consider adding high-dose ffosfamide plus or minus etoposide Consider local therapies 2 to metastatic sites Is there disease See page 4 for Surveillance 1 Doxorubicin and dexrazoxane for cardioprotection plus cisplatin and high-dose methotrexate 2 Surgery is the primary modality of local therapy
te: This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, Pediatric Osteosarcoma Surveillance Total years for Surveillance Frequency of Surveillance by month History and Physical Monitor and discuss with patient late effects of primary treatment CBC, differential and platelets Total protein, albumin, calcium, phosphorous, magnesium, glucose, AST, creatinine, total bilirubin, alkaline phosphatase, LDH Plain films of primary Pelvic primaries: MRI Bone scan 1 CT chest 2 1 3 6 9 12 15 18 21 24 28 32 36 42 48 60 2 3 4 5 10 120 ECHO Audiogram 1 Consider PET CT in patients with metastatic disease, those who underwent surgery for resection of lung nodules, or at relapse. 2 May omit if concurrent with PET CT NOTE: Functional assessments post-limb salvage and cardiac surveillance should continue for life
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, te: SUGGESTED READINGS Akihiko T, Lewis VO, Stacher RL, et al. (2014). What are the factors that affect survival and relapse after local recurrence of osteosarcoma? Clin Orthop Relate Res; 472:3188-3195 Bielack SS, Kempf-Bielack B, Delling G, et al. (2002). Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol; 20:776-790. Children s Oncology Group Protocols: CCG7921 and COG AOST 0331 Daw NC, Billups CA, Rodriguez-Galindo C, et al. (2006). Metastatic osteosarcoma. Cancer; 106:403-412. Goorin AM, Harris MB, Bernstein M, et al. (2002). Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial. J Clin Oncol; 20:426-433. Harris MB, Gieser P, Goorin AM, et al. (1998). Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study. J Clin Oncol; 16:3641-3648. Kager L, Zoubek A, Potschger U, et al. (2003). Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol; 21:2011-2018. Lewis, VO. (2015). Limb salvage in the skeletally immature patient. Current Oncology Reports; 7:285-292. Meyers PA, Schwartz CL, Krailo M, et al. (2005). Osteosarcoma: A randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol; 23:2004-2011. Meyers PA, Schwarz CL, Krailo MD, et al. (2008). Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival a report from the Children s Oncology Group. J Clin Oncol 26(4):633-38. Navid F, Willert JR, McCarville MB, et al. (2008). Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma. Cancer; 113(2):419-25. doi:10.1002/cnrc.23586. Marina N, Smeland S, Bielack S, et al. (2014). MAPIE vs MAP in patients with a Poor Response to preoperative chemotherapy for newly-diagnosed osteosarcoma: Results from EURAMOS-1. CTOS 2014. (abstr) Schwartz CL, Wexler LH, Devidas M, et al. (2004). P9754 therapeutic intensification in nonmetastatic osteosarcoma: A COG trial. Proc Am Soc Clin Oncol 802s, (abstr 8514)
This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, te: DEVELOPMENT CREDITS This practice consensus algorithm is based on majority expert opinion of the Pediatric Osteosarcoma Workgroup at the University of Texas MD Anderson Cancer Center. It was developed using a multidisciplinary approach that included input from the following: Ŧ Core Development Team Najat Daw, M.D. Ŧ Andrea Hayes-Jordan, M.D. Eugenie Kleinerman, M.D. Valerae Lewis, M.D. Ŧ Patrick Lin, M.D. Anita Mahajan, M.D. Mary McAleer, M.D., Ph.D. Bryan Moon, M.D. David Rice, M.D. Janie Rutledge, RN, MS, ANP, OCN Cindy Schwartz, M.D. Ŧ