Current treatment of osteosarcoma includes surgical resection of all gross disease in conjunction with systemic chemotherapy to control micro-metastatic disease. This yields a 5-year event free survival (EFS) of approximately 70% for patients with localized osteosarcoma while patients with metastatic or recurrent disease fare poorly with overall survival rates of less than 20%. Areas covered: This review outlines the current and future approach towards the treatment of osteosarcoma. A literature search was performed utilizing PubMed. Several recent clinical trials are reviewed in detail, as is innovative research evaluating novel agents and surgical techniques which hold promise. Expert commentary: The outcome for patients with osteosarcoma has not changed in several decades. This plateau in survival rates highlights the need for a novel approach towards research. There remains a great deal of interest in utilizing the very high risk population of recurrent osteosarcoma patients to rapidly and sequentially evaluate novel agents to determine if any of these agents hold promise. Several phase II studies are ongoing or in development that offer hope based on intriguing preclinical data. Furthermore, initiatives in obtaining specimens to further explore the genetic and immunological profile behind osteosarcoma will be essential towards identifying novel pathways and targets to exploit.

BACKGROUND.Correlations between various patient, tumor, and treatment characteristics and complications in patients undergoing combined modality treatment for primary lower extremity soft‐tissue sarcomas were investigated.METHODS.Using the M. D. Anderson Radiation Oncology database, the records of the subset of patients treated with combined radiation and limb‐sparing surgery for primary lower extremity soft‐tissue sarcomas were retrospectively reviewed from the years 1960 to 2003.RESULTS.In all, 412 patients were identified. With a median follow‐up of 9.3 years, there were a total of 113 (27%) acute wound complications and 41 (13% at 20 years) chronic radiation‐related limb complications. Preoperative radiation and tumor sizes >5 cm were associated with an increased risk of acute wound complications (34% preoperative vs. 16% postoperative, P < .001; and 31% >5 cm vs. 17% ≤5 cm, P = .005). At 20 years the radiation‐related complication rate was higher in patients with a groin or thigh tumor location (16% vs. 4% other; P = .008), prior acute wound complications (20% vs. 10% no surgical complication), and a radiation dose ≥60 grays (Gy) (18% vs. 9% for dose < 60 Gy; P = .04). Five fractures occurred, resulting in a crude overall fracture rate of 1.2%.CONCLUSIONS.Patients treated with preoperative radiation for larger tumors are more likely to have acute surgical wound complications. Acute wound complications followed by postoperative radiation are associated with chronic radiation‐related limb problems, as are higher radiation dose and proximal tumor location. The fracture rate is so low that prophylactic fixation is not warranted. Cancer 2006. © 2006 American Cancer Society.

Limited clinical activity has been seen in osteosarcoma (OS) patients treated with immune checkpoint inhibitors (ICI). To gain insights into the immunogenic potential of these tumors, we conducted whole genome, RNA, and T-cell receptor sequencing, immunohistochemistry and reverse phase protein array profiling (RPPA) on OS specimens from 48 pediatric and adult patients with primary, relapsed, and metastatic OS. Median immune infiltrate level was lower than in other tumor types where ICI are effective, with concomitant low T-cell receptor clonalities. Neoantigen expression in OS was lacking and significantly associated with high levels of nonsense-mediated decay (NMD). Samples with low immune infiltrate had higher number of deleted genes while those with high immune infiltrate expressed higher levels of adaptive resistance pathways. PARP2 expression levels were significantly negatively associated with the immune infiltrate. Together, these data reveal multiple immunosuppressive features of OS and suggest immunotherapeutic opportunities in OS patients.

Therapeutic Study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

IMPORTANCE Consensus is lacking as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases.OBJECTIVE To assess the relative efficacy of high-dose, single-fraction stereotactic body radiotherapy (SBRT) vs standard multifraction radiotherapy (MFRT) for alleviation of pain in patients with mostly nonspine bone metastases. DESIGN, SETTING, AND PARTICIPANTSThis prospective, randomized, single-institution phase 2 noninferiority trial conducted at a tertiary cancer care center enrolled 160 patients with radiologically confirmed painful bone metastases from September 19, 2014, through June 19, 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for Ն4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions. MAIN OUTCOMES AND MEASURESThe primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (Ն2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. We hypothesized that SBRT was noninferior to MFRT. RESULTSIn this phase 2 noninferiority trial of 96 men and 64 women (mean [SD] age, 62.4 [10.4] years), 81 patients received SBRT and 79 received MFRT. Among evaluable patients who received treatment per protocol, the single-fraction group had more pain responders than the MFRT group (complete response + partial response) at 2 weeks (34 of 55 [62%] vs 19 of 52 [36%]) (P = .01), 3 months (31 of 43 [72%] vs 17 of 35 [49%]) (P = .03), and 9 months (17 of 22 [77%] vs 12 of 26 [46%]) (P = .03). No differences were found in treatment-related toxic effects or quality-of-life scores after SBRT vs MFRT; local control rates at 1 and 2 years were higher in patients receiving single-fraction SBRT.CONCLUSIONS AND RELEVANCE Delivering high-dose, single-fraction SBRT seems to be an effective treatment option for patients with painful bone metastases. Among evaluable patients, SBRT had higher rates of pain response (complete response + partial response) than did MFRT and thus should be considered for patients expected to have relatively long survival.