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Osteosarcoma and Radiation therapy

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osteosarcoma is radio-resistant tumor.but chemoradiation is effective tool to

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Osteosarcoma and Radiation therapy

  1. 1. OSTEOSARCOMA Dr. AADITYA PRAKASH DNB Resident, Radiation Oncology BMCHRC, Jaipur
  2. 2. INTRODUCTION • Osteosarcoma is most common primary bone cancer (35%). • Osteosarcoma is most common radiation induced sarcoma. • Osteosarcoma has a bimodal distribution as a function of age, with cases arising during the teenage years as well as cases associated with other conditions (Paget Disease, fibrous dysplasia) that arise in an older (age >65 yrs) population. • Osteosarcoma is more common in boys (> girls) and in blacks (> whites).
  3. 3. INTRODUCTION • Osteosarcoma arises most frequently in the appendicular skeleton (80% of cases) at the metaphyseal portions of the distal femur, tibia, and humerus. • Osteosarcoma broadly classified in 3 histologic subtypes:-intramedullary, surface and extra-skeletal. • High grade intramedullary osteosarcoma (conventional /classic) refers to the most common (80% of all cases) variant of osteosarcoma, which typically presents within areas of rapidly proliferating skeletal bone. • Osteosarcoma is associated with Li-Fraumeni syndrome (germline inactivation of p53) as well as retinoblastoma.
  4. 4. INTRODUCTION • Other types of less common osteosarcomas include telangiectatic, small cell, juxtacortical, periosteal, and high-grade surface sarcomas. • Juxtacortical osteosarcoma refers to a set of more rare osteosarcoma variants that arise adjacent to the outer surface of cortical bone. • Osteosarcoma spreads hematogenously, with the lung being most common metastatic site.
  5. 5. CLINICAL PRESENTATION • Pts with osteosarcoma typically present with localized bone pain (often associated with an injury) of several months duration and a soft tissue mass/swelling. • Osteosarcoma is derived from bone-forming mesenchyme, and is described as a malignant sarcomatous stroma associated with the production of osteoid bone.
  6. 6. DISTRIBUTION OF PRIMARY & SECONDARIES
  7. 7. PROGNOSTIC FACTORS (NCCN) • TUMOR SITE AND SIZE • PATIENT AGE • PRESENCE & LOCATION METASTASES • HISTOLOGICAL RESPONSE TO CHEMOTHERAPY • GENDER • TYPE OF SURGERY & SURGICAL MARGINS • BMI ( COG ) COSS EOI RCT
  8. 8. WORKUP/STAGING • HISTORY AND PHYSICAL EXAMINATION • MRI +/- CT OF PRIMARY SITE • CHEST CT SCAN • PET SCAN AND /OR BONE SCAN • MRI or CT OF SKELETAL METASTATIC SITES • LDH • ALP
  9. 9. • The elevated periosteal reaction cause Codman’s triangle to form. • In osteosarcoma, periosteal new bone formation, with the blastic component shows bony sunburst pattern.
  10. 10. Musculoskeletal Tumor Society (MSTS) staging system
  11. 11. TREATMENT OF OSTEOSARCOMA SURGERY • Complete en bloc resection of tumor is the mainstay of local treatment of osteosarcoma. • Surgical resection is performed either by amputation or a limb- sparing approach and has a 5% local failure rate. • For extremity lesions, limb preservation is preferred and can be accomplished in the majority of cases.
  12. 12. SURGERY • Pelvic tumors require a hemipelvectomy for en bloc resection. • Adjuvant radiation has been used to improve outcomes in patients with incomplete resections of pelvic tumors. • Spinal tumors are difficult to resect with negative margins. Typically, an en bloc resection with vertebrectomy is performed, combined with mechanical stabilization. • Postoperative radiation therapy used when negative margins cannot be obtained, particularly when there is microscopic dural involvement.
  13. 13. CHEMOTHERAPY • Chemotherapy plays an important role for all patients with intermediate- and high-grade tumors. • Eilber et al.:- 1. 59 patients with nonmetastatic osteosarcoma randomized to surgery followed by observation versus adjuvant chemotherapy. 2. DFS at 2 years was 55% with chemotherapy and 20% with observation (p < .01). 3. OS was also superior at 2 years: 80% versus 48% with and without chemotherapy, respectively (p < .01).
  14. 14. CHEMOTHERAPY • Link et al.:- 1. 36 patients with nonmetastatic, high-grade osteosarcoma randomized to observation versus adjuvant chemotherapy after primary surgery. 2. DFS at 2 years was 66% with chemotherapy and 17% with observation (p < .001).
  15. 15. CHEMOTHERAPY • POG 8651 randomized patients with nonmetastatic, high-grade osteosarcoma to neoadjuvant chemotherapy followed by surgery or surgery followed by the same chemotherapy. • 5-year relapse-free survival was not statistically different between the two groups (65% vs. 61%, respectively), nor was the rate of limb salvage (55% vs. 50%, respectively). • This trial did not show improved outcomes with neoadjuvant chemotherapy, it did show equivalence and established a benchmark for comparison with future trials.
  16. 16. Memorial Sloan-Kettering Cancer Center T10 regimen is frequently used for nonprotocol patients :- high-dose methotrexate, doxorubicin, bleomycin, cyclophosphamide, and actinomycin D. EURAMOS I (AOST 0331):- This ongoing trial is evaluating the benefit of additional chemotherapy after preoperative and postoperative chemotherapy consisting of methotrexate, doxorubicin, and cisplatin. Patients with a poor response to preoperative chemotherapy are randomized to the addition of ifosfamide and etoposide, whereas those with a good response to preoperative chemotherapy are randomized to the addition of interferon.
  17. 17. RADIATION THERAPY INDICATION • Unresectable primary tumors • Incompletely resected tumors with positive margins • Patients who refuse surgery • For palliation of symptomatic metastases
  18. 18. Radiation Therapy Techniques • 3-D treatment planning with the aid of presurgical and postsurgical imaging is used to define gross tumor volumes and areas of subclinical disease. • Typically, a 2-cm margin is used for axial tumors, which can be extended to 4 to 5 cm for extremity tumors. • These margins can be restricted at natural tissue and fascial boundaries. • The radiation technique used, either 3D-CRT or IMRT, should be tailored to the individual patient. • Dose to uninvolved organs should be minimized to prevent late organ dysfunction, as should the integral dose to minimize risk of secondary malignancy.
  19. 19. DOSE • 60 Gy in 2-Gy fractions used for microscopically involved margins • 66 Gy is used for macroscopic residual disease and • 70 Gy is used for inoperable tumors. • Chemotherapy should not be interrupted to deliver local radiation therapy. • Radiation can be given concurrently but is usually delivered after chemotherapy due to increased acute toxicity with concurrent administration.
  20. 20. Cooperative Osteosarcoma Study Group (COSS) • Total of 175 pts with histologically proven osteosarcoma irradiated over the period of 1980−2007. 100 pts were eligible for analysis. • The median age was 18 (3–66) years. • Indication for RT was :- a primary tumor in 66, a local recurrence in 11, and metastases in 23 pts. 94 pts got external photon therapy; 2 pts, proton therapy; 2 pts, neutron therapy; and 2 pts, intraoperative RT. • In addition, a group of 17 pts received bone-targeted radionuclide therapy by samarium-153-EDTMP-therapy alone or in combination with external RT. • The median dose for external RT was 55.8 Gy (30–120). All the pts received chemotherapy in accordance with different COSS-protocols. • The median follow-up :- 1.5 (0.2–23) years.
  21. 21. Cooperative Osteosarcoma Study Group (COSS) • Survival and local control rates at 5 years were calculated. • The overall survival rate after biopsy was 41% at 5 years, while the overall survival rates after RT for the whole group, for treatment of primary tumors, local recurrence, and metastases were 36%, 55%, 15%, and 0% respectively. • Local control for the whole group was 30%. Local control rates for combined surgery and RT were significantly better than those for RT alone (48% vs. 22%, p = 0.002). • Local control for treatment of primary tumors, local recurrence, and metastases were 40%, 17%, and 0% respectively. • Local control for pts given an addition of samarium-153-EDTMP was poor, though not statistically significant . A dose of over 60 Gy had no significant effect on local control.
  22. 22. Schwarz et al. • Reported on an analysis of 100 patients treated with radiation therapy in the COSS registry. • Local control and overall survival for the whole group were 30% and 36%, respectively, at 5 years. • Local control was significantly better when surgery was combined with radiation compared to radiation alone: 48% vs. 22%, respectively (p = .002)
  23. 23. Machak et al. • Reported on a series of 187 patients with nonmetastatic osteosarcoma treated with induction chemotherapy. • 31 patients refused surgery and were treated with radiation to a mean dose of 60 Gy. • Local control was related to response to induction chemotherapy. There were no local recurrences in 11 patients who had a good response to chemotherapy. • However, local progression-free survival was 31% at 3 years and 0% at 5 years for nonresponders.
  24. 24. De Laney et al. • Reported on 41 pts with osteosarcoma who were either not resected or were excised with close or positive margins and who underwent RT with external beam photons (median dose of 66 Gy (10–80 Gy)) and/or protons at the Massachusetts General Hospital (MGH). • Local control rates, according to the extent of resection, were 78.4% for gross total resection, 77.8% for subtotal resection, and 40% for biopsy only.
  25. 25. OTHER MODALITIES • Intraoperative radiation therapy has been used to deliver dose directly to close or involved surgical margins. • Radionuclide therapy with rhenium, strontium and samarium has been used for palliation of extensive bone metastases with good effects. • Radium-223 dichloride is bone seeking radiopharmaceutical ,under investigation for treatment of metastatic or recurrent osteosarcoma. This agent is approved in US for treating bone mets assoc. with castration resistant prostate cancer.
  26. 26. EXTRACORPOREAL IRRADIATION (ECI) • It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor from the bone ,irradiation, and re-implantation back in the body. • First reported by Spira et al in 1968, there are limited reports available in the literature. • ECI has several potential advantages.:- 1. The affected bone segment is removed from the body and irradiated and therefore, avoidance of radiation injury to the un-irradiated bone, muscles, joint, and other healthy tissues of the body. 2. The delivery of very high doses of radiation to tumor bearing bone by ECI, which is otherwise not possible in the intact bone. These higher doses in the range of 50-300 Gy, are lethal to the remaining tumor cells and therefore, reduce the risk of recurrence. 3. It provides an anatomically size-matched graft for biological reconstruction. 4. It is cost effective as compared to the prosthetic devices. 5. It has psychological advantage as patients feel that their own bone is being used as prosthesis.
  27. 27. Davidson et al (2005) • Reported a series of 50 patients with different malignant bone tumor mainly ESFT (21 patients) and OS (16 patients) using en bloc resection and ECI (50 Gy). • The mean time of ECI process was 35 min. With a mean follow-up of 38 months (range 12-92), 84% patients were alive without any disease and only 8% developed LR. The mean MSTS score was 77.
  28. 28. Poffyn et al (2011) • Recently published a retrospective analysis of 107 patients with 108 malignant or locally aggressive bone tumors treated by ECI with 300 Gy, and re-implantation of the bone as an orthotopic autograft. • At 5 year follow-up, there was no LR and 64% of patients had well healed graft. The 0% LR rate could be due to relatively very high dose of ECI (300 Gy) used in their study.
  29. 29. • radiological images and operative photographs of a 10 year old boy diagnosed with osteosarcoma of lower end of right femur that underwent extracorporeal irradiation (ECI). • (a) (plain radiograph) and • (b) (reconstructed computed tomography scan) showing the tumor at the lower end of femur. • (c) the resected bone segment from which the tumor has been removed. The same was packaged and sent for ECI. • (d) the operated limb after the resection of the bone segment
  30. 30. THANK YOU

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