# Radiation Oncology/Sarcoma/Osteosarcoma

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials

## Epidemiology

* Represent 35% of bone sarcomas.
* Primary distribution in adolescents
* When it occurs in older patients, usually associated with pre-existing condition such as Paget's disease, prior irradiation of bones, multiple hereditary exostosis, or polyostotic fibrous dysplasia
* Hereditary risk factors:
** Hereditary Retinoblastoma (Rb mutated in ~50% osteosarcomas)
** Li-Fraumeni syndrome (p53 mutated in 20-30%)
** Rothmund-Thomson syndrome
* Distribution:
** Distal femur/knee joint ~50%
** Proximal humerus ~25%
** Long tubular bones ~80-90%
** Hands/feet <1%
* Lab findings generally not helpful, though serum alkaline phosphatase elevated in ~50%
* Clinical presentation:
** Night pain
** Typically no effusion in the adjacent joint
** Pathologic fractures rare
* Metastatic disease:
** Approximately 15-20% at diagnosis
** Overwhelmingly in the lung

## Histology

* 90% of osteosarcomas are conventional osteosarcomas; these are intramedullary high grade tumors. Subtypes include:
** osteoblastic
** chondroblastic
** fibroblastic
* 10% include osteosarcoma of the jaw, surface osteosarcomas (paraosteal and periosteal)
* Radiation-induced osteosarcomas may be a linear function of radiation dose and alkylating agents. Risk for most childhood survivors <1%, but higher with genetic predisposition (Retinoblastoma 7%, Ewings' 5%, other bone tumors 2%)

## Radiologic Findings

* Classic appearance on plain x-ray is sunburst pattern which is a mixed lytic sclerotic pattern (vs "onion skinning" in Ewing's sarcoma)
** Increased intramedullary density due to tumor bone or calcified cartilage
** Area of radiolucency due to nonossified tumor
** Cortical destruction
** Extraosseous elevation (Codman's triangle) when tumor lifts the periostium leading to a rim of subperiosteal bone.

## Staging

* Please see the bone staging page

## Treatment

* Biopsy should be performed by an orthopedic surgeon who will ultimately perform the resection
* Treatment is surgical resection, preferentially limb-sparing surgery (distal femur/proximal tibia, shoulder girdle/proximal humerus)
** Surgery alone historically leads to overall survival of <20%.
* Adjuvant chemotherapy plays a key role in preventing distant mets; 4-agent regimens are favored
** Randomized trial by POG showed no difference between neoadjuvant chemotherapy -> surgery -> adjuvant chemotherapy and surgery -> adjuvant chemotherapy; 5-year ERS was ~60%
* Adjuvant RT (including whole lung irradiation) does not appear to benefit survival
** Prior to advent of effective chemo, whole lung xrt was often administered b/c of high rate of pulmonary failure. Data is unclear as to whether there was any benefit to this practice
** Role for RT is mostly limited to life-threatening presentations where adequate surgical removal is unlikely, such as H&N, spine, or pelvis
* Pelvic tumors are typically unresectable, and are treated with RT and chemotherapy
* For metastatic disease, aggressive course is typically advocated, consisting of induction chemotherapy followed by maximal resection of primary and mets, followed by adjuvant chemotherapy

### Primary Radiotherapy

* Blokhin Cancer Center, Russia; 2003 PMID 12583525 "Neoadjuvant chemotherapy and local radiotherapy for high-grade osteosarcoma of the extremities," Mayo Clin Proc 2003; 78(2):147-55.
** 31 pts who refused surgery and underwent induction chemo + conventional xrt (median 60 Gy)
** Local control 56%, OS 61%
** Of pts who had local control, 86% had excellent limb function
* UC San Francisco; 1976 PMID 1064887 "The role of radiation therapy in the treatment of osteosarcoma," Radiology. 1976; 120(1):163-5.
** 70 pts w/ osteosarcoma receiving either primary xrt or surgery b/w 1950-74
** Conclusion: xrt w/o chemo did not add palliative effect or improve OS in operative pt.

### Post-operative Radiation

* Harvard; 2005 (1980-2002) PMID 15667972 "Radiotherapy for local control of osteosarcoma" DeLaney TF, Int J Radiat Oncol Biol Phys. 2005; 61(2):492-8.)
** Retrospective. 41 patients with osteosarcoma (head/face 41%, extremity 20%, spine 20%, pelvis 17%). 5 were radiation-induced. Median age 29. GTR 66%, STR 22%, biopsy 12%. If GTR, received RT for close or +margins. Median 66 Gy delivered (If gross disease >=68 Gy; if SM+ 60-68 Gy, if close SM 55-60 Gy, if radiation-induced sarcoma 10-30 Gy). Some patients pre-op 20 Gy followed by post-op RT. Chemo 85%
** Outcome: 5-year LC 68%; GTR 78% vs. STR 78% vs. biopsy 22% (SS).
** RT: No definitive dose response seen, but doses >55 Gy w/ better local control (71% vs 54%)
** Conclusion: RT can help provide local control if widely negative margins not possible

### Whole Lung Irradiation

* Peru; 1986 PMID 3522504 "Postoperative whole lung irradiation with or without adriamycin in osteogenic sarcoma," Int J Radiat Oncol Biol Phys. 1986; 12(6):907-10.
** 36 patients w/ osteosarcoma of limbs tx'd b/w 1975-78 w/ radical surgery then 20 Gy whole lung irradiation. Most pts received adriamycin.
** All pts ultimately developed lung mets, but whole lung xrt appeared to increase the time to failure.
* Mayo Clinic; 1976 PMID 824047 "Elective whole lung irradiation in the treatment of osteogenic sarcoma," Cancer. 1976 Aug;38(2):939-42.
** 53 pts w/o evidence of pulmonary mets; 2 cohorts (15 Gy prophylactic xrt to whole lung field, or no lung xrt).
** No differences in survival or interval b/w tx and development of pulmonary mets.

## Palliation

Palliative Radiotherapy
* Milan; 1992 (1984-1990) PMID 1429102 -- "Hypofractionated accelerated radiotherapy in osteogenic sarcoma." (Lombardi F, Int J Radiat Oncol Biol Phys. 1992;24(4):761-5.)
** 14 pts receiving RT for palliation to either the primary site (n=6) or skeletal metastases (15 lesions). Received 6 Gy per fraction, 3 fractions per week, for 6 fractions = 36 Gy over 2 weeks.
** Radiographic response in 92%; no local recurrence. Toxicity was often severe.
** Conclusion: "Although effective in inducing remission of osteogenic sarcoma, this irradiation method produced severe damages to normal tissues in a high proportion of patients."