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Radiation Therapy for Bone Tumors

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Radiation Therapy for Bone Tumors

  1. 1. Mayur Mayank 22.02.2014
  2. 2. Primary bone tumors are rare malignancies. They account for <0.2% of all neoplasms. Most common amongst them are : Osteosarcoma – 35% Chondrosarcoma – 30% Ewing’s sarcoma – 16% Most common tumors of the bone are secondary tumors metastasizing from some other primary.
  3. 3. Enneking Staging system AJCC Staging system
  5. 5. Osteosarcomas are highly radio resistant tumors and the management basically comprises of surgery and chemotherapy. Radiation therapy has limited role to play in the management of osteosarcomas.
  6. 6. Appropriate approach is to facilitate a limb saving surgery. It can be done upfront in small diseases In case of high disease burden, neo adjuvant chemotherapy is given followed by limb conserving surgery (whenever feasible).
  7. 7. Response to neo adjuvant chemotherapy has prognostic significance. It is the amount of necrosis in the post operative specimen which gives a measure of the response to NACT Huvo’s Grading > 90% necrosis - Good response < 90% necrosis - Poor response
  8. 8. The role of radiotherapy in the routine management of extremity osteosarcoma is virtually nonexistent today. Radiotherapy has been reported to improve local control of borderline or unresectable extremity osteosarcoma, vertebral osteosarcoma and pelvic osteosarcoma. It has also been used to successfully treat osteosarcomas of the mandible.
  9. 9. Patients who refuse surgery/medically inoperable Margin positive disease after surgery/Close margins after surgery Sites not amenable for surgery : Pelvis Jaw Palliation
  10. 10. 1. Definitive : Unresectable disease 2. Adjuvant : After R1 or R2 resection 3. Palliative
  11. 11. Patient positioning and immobilization : Depends on the site to be treated Immobilization should be done adequately so that the fields are adequately reproducible. The lesion should be positioned such that the entrance and exit of the beam(s) do not expose contralateral limbs or other tissues unnecessarily.
  12. 12. Techniques : 2D conventional 3D Conformal Radiation therapy IMRT Proton beam therapy
  13. 13. Fields and borders : From initial tumor Axial : 2 cms margin dimensions on the pre operative imaging Extremity : 4-5 cms margin Strip of skin to be spared to prevent lymphoedema To restrict fields at anatomical barriers Dosage : 60 Gy in 30 # for microscopically involved margins 66 Gy in 33 # for macroscopic disease 70 Gy in 35 # for inoperable disease
  15. 15. Extracorporeal and Intraoperative RT : The extracorporeal technique includes en bloc resection of the tumor and surrounding soft tissues, irradiation of the specimen, and reimplantation, often with the aid of prostheses. In IORT, the operative field is exposed and radiotherapy is administered. No resection of the tumor is performed.
  16. 16. Palliative : Palliative RT for pain management In cases of big lesion causing mass effects Samarium 153 Whole lung irradiation - with the recognition of the other advantages of systemic therapy, prophylactic lung irradiation has fallen out of favour.
  17. 17. Depends on the site which has been irradiated The normal tissue constraints of the particular site should be kept into consideration while planning fields. Also, patients receive systemic chemotherapy which causes side effects : Doxorubicin can cause cardiomyopathy and radiation recall.
  19. 19. In contrast to Osteosarcomas, The Ewing’s Sarcoma family of tumors are sensitive to radiation. Historically, Radiation therapy was the treatment of choice for these tumors However, in view of increased toxicity and better survival with combined modality of treatment, the role of radiation therapy has declined.
  20. 20. Presently, based on studies done by the IESS, POG and CESS trials, the treatment comprises of systemic chemotherapy followed by adequate local control of the disease. Local control : Surgery Radiation therapy
  21. 21. Induction Chemotherapy 12 TO 24WKS VAC/IE Local Control Maintenance • Surgery • Radiotherapy • Chemotherapy AT 12WK/18WK UP TO 1YEAR
  23. 23. Local control : Definitive Radiation therapy Neo adjuvant Radiation therapy Adjuvant Radiation therapy Metastatic disease : Pain control Symptomatic management
  24. 24. Pre operative / Definitive : Large inoperable tumors Tumors involving the proximal humerus and upper scapula since limb reconstruction is difficult and shoulder morbidity may be substantial. Patients with lesions of the skull, facial bones, or vertebrae difficulty in achieving negative margins without substantial functional deficit Pelvic bone tumors
  25. 25. Adjuvant RT In case of initially bulky tumors – can be given pre operative or post operative – for better local control Microscopic or Macroscopic margin positivity Inadequate margins Adjuvant hemithorax irradiation
  26. 26. Adjuvant Hemithorax Irradiation : improves outcomes in patients with high-risk chest wall primary tumors close or involved margins initial pleural effusion pleural infiltration, and intraoperative contamination of the pleural space HEMITHORAX IRRADIATION FOR EWING TUMORS OF THE CHEST WALL Int. J. Radiation Oncology Biol. Phys., Vol. 54, No. 3, pp. 830–838, 2002
  27. 27. Historically, Ewing’s sarcoma was thought to be a tumor arising from the bone marrow. The treatment protocol consisted of treating the entire length of the bone. An analysis of the RT fields for the Intergroup Ewing's Sarcoma Study Group (IESS) trial I suggested that most relapses were at the site of initially bulky tumor.
  28. 28. POG 8346 trial was the first trial which used “tailored field RT” with reduced portals. IESS III was the first cooperative group trial to include tailored RT ports, and the first to be carried out with modern MRI imaging of the primary site and CT-based treatment planning
  29. 29. FIG. Changes in treatment volume. (A) Field encompassing the entire length of the medullary cavity for a tumor involving the proximal left humerus. (B) Tailored field encompassing only the proximal aspect of the leg for a limited tumor of the left tibia.
  30. 30. Patient positioning and immobilization : Depends on the site to be treated Immobilization should be done adequately so that the fields are adequately reproducible. The lesion should be positioned such that the entrance and exit of the beam(s) do not expose contralateral limbs or other tissues unnecessarily.
  31. 31. Techniques : 2D conventional 3D Conformal Radiation therapy IMRT Proton beam therapy
  32. 32. Current recommendations for RT Initial clinical target volume to include the original bone and soft tissue tumor with a 2.0 cm margin The initial clinical target volume is treated to 45 Gy in 25 fractions Boost field to encompass the post-chemotherapy gross soft tissue tumor as well as all of the originally involved bone with a margin of 1.5 cms. 10.8 Gy in 6 fractions in patients undergoing definitive RT and to 5.4 Gy in three fractions for patients undergoing adjuvant RT for microscopic residual disease after surgery (with boost up to 10.8 Gy for any sites of gross disease after surgery).
  33. 33. Additional margin expansions on these volumes are used for the planning target volume expansion to account for any variability in daily setup 0.5cms-1cms depending on the institutional protocol
  34. 34. Some centers (University of Florida) use Hyperfractionated therapy 1.2Gy per fraction, twice daily, 6 hours apart This has shown adequate local control Less long term toxicity Limited field sizes with hyperfractionated highenergy RT could minimize long-term complications and provide superior functional outcomes.
  35. 35. Normal tissue considerations : Epiphyseal growth plates - Avoided in order to minimize treatment induced limb shortening Circumferential irradiation of a limb - Avoided to reduce the risk of limb edema and fibrosis Gonadal avoidance or additional shielding (for the testes) - important to retain fertility Nail beds should be excluded from the radiated field when possible Pelvic tumors – Bladder distention prior to treatment can reduce the amount of small bowel in the radiated field To avoid radiation to significant portions of the bladder in patients receiving ifosfamide to reduce the risk of hemorrhagic cystitis
  36. 36. Long bone fracture : The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. For bone hypoplasia : Dose - 35 Gy was the most significant threshold• Volume significant effect in the young population (<5 yrs)
  37. 37. Newer modalities of radiation delivery are preferable to reduce the toxicity 3D Conformal radiation therapy IMRT Proton beam therapy Heavy ion treatment
  38. 38. Reference : Uptodate
  39. 39. Reference : Uptodate
  40. 40. SEQUELAE OF TREATMENT Acute effects Desquamation of the skin, myelosuppression, mucositis, diarrhea, nausea, and cystitis. Patients receiving whole lung irradiation are at risk for radiation pneumonitis. Acute reactions are usually self-limited and subside within 10 to 14 days of RT completion
  41. 41. Late effects : Younger, prepubertal children are at greatest risk for radiationinduced arrest of bone growth. Sparing of uninvolved epiphyseal plates minimizes limb shortening after RT of extremity lesions. RT doses above 60 Gy are associated with markedly increased rates of soft tissue induration and fibrosis High-dose circumferential irradiation of an extremity is associated with edema, fibrosis, and compromised limb function . This can be avoided by sparing of an adequate strip of tissue. Weight-bearing bones are at risk for pathologic fractures. The highest risk is within the first 18 months of RT completion
  42. 42. Second malignancy after RT • With protocols utilizing lower doses of RT and tailored RT fields suggest that the magnitude of the risk is somewhat lower. • Cumulative risk at 15yrs = 6 – 6.7% ( CESS-81 & CESS-86; IJROBP:1997; 39) • No secondary sarcomas seen at doses <48 Gy ( Kutterch et al; JCO:1996, 14 )
  43. 43. RT for metastatic disease : Control of local disease Pulmonary metastatsis Bone and soft tissue metastasis
  44. 44. Pulmonary metastasis : Bilateral lung irradiation : Low-dose bilateral lung irradiation (15 to 18 Gy, in 1.5 to 2.0 Gy fractions) with a focal boost dose to a total of 40 to 50 Gy to large deposits is recommended for patients with pulmonary metastases who have had a good response to chemotherapy. Reduced pulmonary relapse and improved event-free survival, and the low rate of pulmonary toxicity, it is suggested to give bilateral low-dose lung irradiation (15 to 18 Gy) even if all lesions are resected or completely respond to chemotherapy
  45. 45. Superior border : 3cm above the middle 1/3 rd of clavicle Inferior border Below the xiphisternum / level of L1 (to include anterior and posterior costophrenic angles) Lateral borders : Lateral border of areola of nipple
  46. 46. Bone and Soft tissue metastasis : Palliative RT can be considered for symptom management
  48. 48. Dedifferentiated chondrosarcoma : treated as osteosarcoma Mesenchymal chondrosarcoma : treated as Ewing's sarcoma For low grade histology's treatment is with surgery/RT. Indications for RT: Inaccessible tumor Where clear margins are not achievable. Recurrence Dose : 50-70 Gy/ 200cGY/#/5days/week. 5 year survival – RT alone – low grade 48% high grade 22%.
  50. 50. The role of radiation therapy in the management of bone tumors depends on the histology of the tumor and the resectability. Surgery forms the mainstay of management of most of the tumors of the bone. However, radiation therapy has a significant role to play in inoperable or incompletely excised tumors for adequate local contol.
  51. 51. The newer modalities of delivering radiation therapy and “tailored field” radiation therapy approach has led to significant decrease in the toxicity. The toxicities are also contributed by the chemotherapy used for the treatment of the tumor and cumulative effect of both should be considered while planning a treatment.
  52. 52. THANK YOU !!!