TPS3645 Background: Pre-clinical studies of aerosol gemcitabine (GCB) in mice and dogs with osteosarcoma (OS) lung metastases demonstrated therapeutic efficacy. Aerosol GCB administered once weekly proved to be safe in adults with lung cancer. Direct delivery of GCB to the lungs via inhalation may offer higher drug concentration in the tumor with fewer side effects. We initiated a Phase I study to evaluate the feasibility and safety of aerosol GCB treatment in patients >12 years with solid tumors and lung metastases (2015-0720- NCT03093909). Methods: Eligibility criteria: 1) Diagnosis of solid tumor with lung metastases, 2) willing to comply with protocol therapy, 3) adequate organ function, 4) patient age > 12 and < 50 years, 5) good performance status, 6) resolution of all acute toxic effects of any prior anti-cancer therapy, and 7) no radiotherapy within 2 weeks. Patients who previously received systemic GCB are eligible. Objectives: To determine the maximum tolerated dose (MTD) and toxicities of aerosol GCB, to evaluate for drug spillover into the circulation, and to preliminarily assess the anti-tumor activity. Correlative studies include effect of aerosol GCB on immune cell infiltration in the lung, autophagy, apoptosis, heat shock protein 27, evidence of DNA strand breaks (gH2AX) and expression of human equilibrative nucleoside transporter-1.Aerosol GCB is administered via a breath-induced nebulizer twice a week in 28-day cycles. A maximum of 6 dose levels will be studied; the starting dose is 0.75 mg/kg twice weekly. If no progressive disease or unacceptable treatment-related toxicity, patients may continue for 12 cycles. The study uses the accelerated titration method for the first 2 dose levels then the 3+3 design for the remaining dose levels. After determining the MTD, we will evaluate the defined MTD in an expansion cohort of 14 patients with relapsed OS. Symptoms, pulse oximetry, and pulmonary function are assessed prior to each nebulized dose using remote spirometry that allows raw numbers and flow-volume curves to be uploaded and transmitted via bluetooth to an android tablet provided to patients. Data is transmitted to a web portal and captured in a HIPAA-compliant web-based database (REDCap) that is accessible to the research team. Results: To date, the study enrolled 4 patients and accrual is ongoing at dose level 3. Conclusions: This study will provide information on the feasibility and safety of aerosol GCB. If proven to be feasible and safe, it can potentially offer a novel approach to treat metastatic OS to the lungs while minimizing systemic toxicity. Clinical trial information: NCT03093909 .

Osteosarcoma was initially resistant to chemotherapy that worked for Ewing sarcoma and rhabdomyosarcoma as well as other chemotherapeutic agents available in the 1960s. In the early 1970s, responses of osteosarcoma to adriamycin were reported, and at about the same time, so were responses of osteosarcoma to high-dose methotrexate. These agents were introduced into adjuvant therapy due to the dire prognosis associated with apparently localized osteosarcoma. After initial questions regarding the role of chemotherapy delayed its uniform acceptance, there is now general agreement that chemotherapy is primarily responsible for the cure of patients with osteosarcoma when combined with surgical elimination of the primary tumor. Advances with combination chemotherapy later adding cisplatin and ifosfamide have improved ultimate survival. The history of the development of effective chemotherapy combinations at Memorial Sloan Kettering Cancer Center, UT MD Anderson Cancer Center, and the Rizzoli Institute are highlighted, and recent large cooperative group studies are reviewed in the context of those findings.

Background. Despite the dose-dependent response rate of sarcomas to doxorubicin, clinicians limit its cumulative dose due to cardiotoxicity. This study evaluates early evidence of cardiotoxicity in patients treated with high-dose doxorubicin given as a continuous infusion. Methods. Data was collected on patients who received 90 mg/m2 doxorubicin as a continuous infusion and 10 gm/m2 ifosfamide for up to 6 cycles as part of a phase II study. Cardiotoxicity was assessed with serial echocardiograms or multigated acquisition scans and serum brain natriuretic peptide and troponin levels. Tumor responses were determined by serial radiographic imaging per RECIST. Result. Out of the 48 patients enrolled, no patient developed heart failure symptoms; however, 4 out of the 38 (10%) patients with serial left ventricular ejection fraction assessments developed subclinical cardiotoxicity (asymptomatic drop in LVEF ≥ 10%). Twenty-three patients received all six 72-hour cycles of doxorubicin with a mean cumulative dose of 540 mg/m2. Among these patients, 4% (n=1) developed subclinical cardiotoxicity. In the advanced disease group (n=39), patients with a complete or partial response received a higher mean cumulative dose than those with stable disease (p<0.033). Conclusions. Doxorubicin cardiotoxicity can be limited by administering doxorubicin as a continuous infusion, allowing higher cumulative dosing to maximize efficacy.

Background. The prognosis and clinical characteristics of head and neck synovial sarcomas (HNSS) are unclear. Herein, we present an update using a cohort of patients treated at our institution.Methods. We performed a retrospective chart review of 44 patients diagnosed with primary HNSS between March 1990 and June 2012. Overall survival (OS) and progression-free survival (PFS) curves were estimated and hazard ratios (HRs) were calculated.Results. The entire cohort’s median PFS was 4.6 years, and 20 of the 44 (45%) patients developed either local or distant recurrence. Tumor size ≥ 5 cm (p=0.008, HR = 4.69; 95% CI = 1.34–16.38) and a primary presentation in the soft tissues of the neck (p=0.04, HR = 2.41; 95% CI = 1.003–5.82) were associated with significantly worse PFS. The OS and PFS of patients who received definitive local therapy versus those who received additional adjuvant systemic therapy did not differ significantly.Conclusion. Despite the treatment challenges associated with HNSS, our cohort of patients had a better prognosis than one might expect in this unfavorable anatomical location. Our findings suggest that tumor size and site are predictive of PFS and that wide surgical excision is of vital importance, since traditional cytotoxic chemotherapy has limited efficacy at this site.

Dr. Gianni Bonadonna is internationally recognized as one of the foremost medical oncologists of the 20th century. He is best known for his pioneering work in the development of adjuvant chemotherapy for breast cancer, but he was also the father of sarcoma chemotherapy. The first investigator to study the new chemotherapeutic agent adriamycin in the late 1960s, he noted activity against sarcomas. This article, focusing on adjuvant chemotherapy, adriamycin, and sarcomas, memorializes his achievements and their progeny.

Oncologists who treat sarcomas are frequently asked by their patients about the cause of their cancer. Until now, with the exception of Li-Fraumeni syndrome, 1 Li FP Fraumeni Jr, JF Soft-tissue sarcomas, breast cancer, and other neoplasms: a familial syndrome?. Ann Intern Med. 1969; 71: 747-752 Crossref PubMed Scopus (1162) Google Scholar hereditary retinoblastoma, 2 Knudson Jr, AG Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971; 68: 820-823 Crossref PubMed Scopus (5546) Google Scholar and neurofibromatosis, which could be excluded by history and physical examination, the answer was usually: “almost all cases of sarcomas are not hereditary”. A genetic study by Mandy Ballinger and colleagues 3 Ballinger ML Goode DL Ray-Coquard I et al. for the International Sarcoma Kindred StudyMonogenic and polygenic determinants of sarcoma risk: an international genetic study. Lancet Oncol. 2016; (published online Aug 4.)http://dx.doi.org/10.1016/S1470-2045(16)30147-4 PubMed Google Scholar reported in The Lancet Oncology, now throws this answer into a different light. In one of the most important studies on sarcomas in recent years, the investigators performed targeted exon sequencing on 72 genes, selected because of associations with increased cancer risk, in 1162 patients in four sarcoma cohorts, and using a case–control rare variant burden analysis found that about half of the patients had an excess of pathogenic (and potentially aetiological) germline variants. Monogenic and polygenic determinants of sarcoma risk: an international genetic studyAbout half of patients with sarcoma have putatively pathogenic monogenic and polygenic variation in known and novel cancer genes, with implications for risk management and treatment. Full-Text PDF

11069 Background: ARMS is considered to be one of the most aggressive pediatric malignancies. Adults with ARMS notoriously experience inferior outcomes. Our goal was to define our adult population with ARMS and review their outcomes on front-line systemic therapies. Methods: Adult ARMS pts over the age of 18 years (y) treated at MDACC from 2004 to 2015 were identified from our registry. Descriptive statistics and survival analysis were performed via multivariate analysis. Results: 43 pts were identified. Median age at diagnosis was 31 y (range (R) 18 to 69 y). 51% were male. 26 pts (60%) were Caucasian, 10 pts (23%) were Latino, 5 pts (12%) were Asian and 2 pts (5%) were African-American. The most common primary site was the parameningeal space (25 pts; 58%). The majority were classified with IRSG stage IV (37%) or III disease (47%). The majority were classified with group IV (37%) or III (56%). By COG clinical risk, 27 pts (63%) and 16 pts (37%) were intermediate and high, respectively. N1 disease was noted in 31 pts (72%). M1 disease was observed in 16 pts (37%). 36 pts (84%) had an unfavorable primary site. 60% of pts had primary tumors > 5 cm. FOXO1 fusions were present in 30 pts (70%), negative in 4 pts (9%), and not evaluated in 9 (21%). Most common chemotherapy regimens employed doxorubicin (26 pts; 49%), actinomycin-D (12 pts; 28%), both (3 pts; 7%), or other (2 pts; 5%). A median of 8 cycles (R: 1 – 20 cycles) were received. RECIST Responses included CR (21%), PR (26%), and SD (7%). 30 pts (70%) received radiation therapy for local control. Median OS was 32 months (R: 2 to 97 months). By multivariate analysis, m status (P = 0.007) and clinical risk (P = 0.007) were associated with statistically significant differences in survival. An inferior OS was noted in pts receiving doxorubicin-based chemotherapy (P = 0.037), though an associated increase in absolute tumor size was noted in this group (P = 0.057). Only 21% of pts were disease free at last follow up or death.Conclusions: Adults with ARMS represent a poorly defined group with an unmet need for improved treatment. Clinical trials are needed to improve the outcomes for this rare population of patients.

10564 Background: Synovial Sarcoma (SS) is one of the more common subtypes of soft tissue sarcomas, comprising 8-10% of this entity. It is well known that SS responds well to adriamycin/ifosfamide (AI) therapies, however responses to gemcitabine/docetaxel (GT) combination have not been well documented, although commonly used in practice. This study aimed to evaluate response to GT in patients with SS. Methods: We retrospectively reviewed medical records of patients diagnosed with SS from 2000 to 2012. All patients had confirmed SS by pathology review. Only patients who were metastatic and treated with GT concurrently were included. Results: The study included 51 patients with metastatic disease who received GT concurrently. Majority of patients were white (69%), with a mean age of 42 years (SD 15) when receiving GT. Median time from initial diagnosis to first metastasis was 15 months. Median overall survival from first metastasis was 2.3 years (95% CI 1.8-3.0 years). The majority of patients (96%) had received A and/or I prior to GT therapy, and 86% had documented disease progression prior to start of GT. 21% of patients were taken off GT due to side effects or other reasons. 79% were taken off due to progressive disease. As best response, 10% of patients (n=4) had: complete response (CR) (n=1), near CR (n=1) or partial response (PR) (n=2). 33% (n=14) had stable disease, and 57% (n=24) had disease progression (DP). 9 patients had missing data. Overall 43% may have derived some clinical benefit, and 57% had DP. Median duration of GT therapy was 2 cycles (range 1-3); median of 1.7 months (range 1.2-3.0) in patients who progressed; 4 cycles (range 2-8), median 3.0 months (range 1.6-10.0) in patients with SD, and 8 cycles (range 6-11); median 6.1 months (range 4.7-10.5) in patients with CR/near CR/PR. Conclusions: This data shows some efficacy of GT in metastatic SS. Rare responses were seen, and due to limited availability of other active agents in this disease it may not be unreasonable to consider GT after other lines of therapy, (such as A/I, dacarbazine, pazopanib) have been used.

9616 Background: AI is multi-day regimen of highly emetogenic chemotherapy, with high incidence of delayed N/V. Fosa, NK1 receptor antagonist (RA), administered IV as single dose (FDA-approved), with 5HT3RA and dexamethasone has improved the control of emesis. However, delayed N/V still remains problematic. Purpose of the study was to examine the effects of fosa administered IV on day 1 vs days 1 and 4 on N/V and the effect on ifosfamide (Ifex) and its active metabolites, due to potential drug interactions via CYP450. Methods: Sarcoma pts, planned to receive AI, were randomized 1:1 to Arm A (single- dose Fosa on day 1) or Arm B (2-doses, on days 1 and 4). Within each arm, patients were randomized to Group-1: Fosa in cycle-1 (C-1) and no Fosa in cycle-2 (C-2), and group-2: no Fosa in C-1 and Fosa in C-2. Blood samples were drawn for levels of Ifex/metabolites to be analyzed at the end of study. All pts could receive 2 doses of Fosa during cycles 3-6. Pts were monitored for N/V with daily symptom diary and FLIE (functional living index -- emesis) score (days 1, 5 and 10). Results: Of 47 pts, 40 eligible pts were randomized. There were 13 men and 27 women, with median age of 45 years (range, 19-65) and KPS of 90 (80-100). At present, 34 pts have completed 2 CT cycles. As shown below, Fosa administered as 2 doses resulted in significantly better control of delayed N/V as compared to single-dose or the control cycle. Furthermore, in cycle-3 the higher CR rate for N/V was maintained with 2 doses. Treatment with Fosa (one or two doses) was well tolerated with no enhanced neurological toxicity. Conclusions: The results of this study showed for the first time that Fosa administered as 2 doses is well tolerated and more effective in the control of delayed N/V than single dose or no Fosa with 5HT3RA + Dexa in pts receiving multi-day CT. Clinical trial information: NCT01490060.Complete response (CR*) in C-1 and C-2. Study groups No. of pts Day 1 N (%) Days 2-5 N (%) Days 1-10 N (%) Single-dose 18 13 (72) 2 (11) 2 (11) Two-doses 16 10 (63) 8 (50) 6 (38) Control (no Fosa) 34 27 (79) 6 (18) 4 (12) P value ** 0.44 0.015 0.06 * CR: No emetic episodes and no rescue medications. ** Chi-square test.

Abstract Abstract 2086 Background: Anemia in patients with malignancies can be multifactorial including anemia of chronic disease (ACD), also known as anemia of inflammation (AI), and chemotherapy (CT)-induced anemia (CIA) from myelosuppression. Although, exact mechanism for ACD is not known, induction of hepcidin, a key iron-regulatory hormone, by Interleukin (IL)-6 and other pro-inflammatory cytokines with resulting hypoferremia and limitation of iron supply to the bone marrow appear to be major contributors to pathogenesis of anemia. Hepcidin reduces iron levels by inducing degradation of the cellular iron exporter, ferroportin. The objective of this study was to examine the levels of various cytokines/regulators that may play role in ACD. Methods: Chemo-naïve patients with sarcoma scheduled to initiate first-line doxorubicin-based chemotherapy had blood samples drawn at baseline, and following chemotherapy (post cycles1, 3 and 6) for analysis of pro-inflammatory cytokines/other biomarkers of anemia. Serum samples were analyzed for IL-1β, IL-6, TNF-α, Hepcidin, hemojuvelin, ferroportin, soluble transferrin receptor (sTFR), and C-reactive protein (CRP) using ELISA techniques (R&D Diagnostics, Uscn Life Science Inc, or Abnova). Correlations between these biomarkers and Hgb levels at baseline and during the study period were calculated by linear regression analysis (SAS 9.2). Results: Of the 49 patients enrolled on to the clinical trial, there were 26 (53%) women and 23 (47%) men, with median age 45 years (range 19–65 years). Twenty-five percent of the patients had Hgb less than 12g/dL (range, 8.9–15.9 g/dL) prior to CT. At baseline, 50% of the pts had hypoferremia with low serum iron and transferrin saturation <20%. Baseline serum levels of IL-6 (r= −0.73, p<0.0001), hepcidin (r= −0.46, p=0.005), CRP (r= −0.46, p=0.003), sTFR (r= −0.32, p=0.064) inversely correlated with hemoglobin levels prior to CT, supporting their role in ACD. During CT (median 4, range; 1–6 cycles), Hgb declined in all pts with 55% requiring PRBC transfusions (77% of pts starting with baseline Hgb < 12 g/dL vs 47% of pts with baseline Hgb > 12 g/dL). Interestingly, as shown below, Hepcidin, IL-6, and sTFR all significantly negatively correlated with Hgb levels during CT. No significant correlation was found for IL-1β, TNF-α, ferroportin, or hemojuvelin levels with Hgb. Conclusions: IL-6 and Hepcidin pathway appears to play an important role in anemia in cancer patients before and during CT. Treatment with novel agents targeting this pathway may provide effective strategies for prevention and treatment of ACD and CIA. Disclosures: Vadhan-Raj: JNJ: Research Funding.

10035 Background: Major barriers to durable remission in cancer are drug-resistant clones and tumor stem cells. We sought to harness and enhance endogenous antitumor immunity by combining imatinib with peginterferon α-2b (PegIntron; PegIFNa2b) in GIST. Methods: Patients (pts) with primary tumor ≥6 cm or metastatic imatinib-sensitive GIST were enrolled. Patients received imatinib at 400mg/d for KIT exon 11 mutation GIST and 800 mg/d for the rest, started 3–5 d before PegIFNa2b. The first cohort (3 pts) received PegIFNa2b at 4 mcg/kg/wk and developed granulocytopenia, so the dose was reduced to 3 mcg/kg/wk × 4 doses then 1.5 mcg/kg/wk × 18. Partial response (PR) is judged by ≥25% decrease in SUV (PET-CT criteria), ≥10% decrease in size or ≥15% decrease in density (HU) (Choi criteria), and RECIST. Progression-free survival (PFS) was assessed. Genotyping, cytokine panel, and flow cytometry phenotyping of peripheral lymphocytes at specific time points were performed. This is a case report from chart review. Results: 8 pts were enrolled (age: 42–89 years). The combination treatment was well tolerated; grade 3 skin rash/dermatitis occurred in 2 pts. All 8 pts showed PR by Choi and RECIST criteria, and 7 pts showed PR and 1 inevaluable (not FDG avid) by PET-CT. The oldest pt died of unrelated causes while in remission. PFS of 7 evaluable pts ranges from 365 to >900 days, 6 pts exceeded historical controls and 1 will reach it in 1 month (PFS of historical control of KIT exon 11 mutation GIST is 687 days, KIT exon 9 mutation 200 days, and wild type 82 days). A pt with wild type GIST initially achieving a PR, later progressed (day 365). When PegIFNa2b was restarted, a second PR was induced, with 1 target lesion showing SUV reduction from 22.8 to 9.5, and another from 28 to 18.2. PegIFNa2b resulted in a surge of CD45RO+CD4+ and CD45RO+CD8+ memory T cell subsets and induction of interferon γ producing lymphocytes. Conclusions: Combination of imatinib and PegIFNa2b showed promising efficacy in 8 GIST pts. Induction of a second PR after progression (due to imatinib resistance) by re-initiation of PegIFNa2b is unprecedented. The trial was closed early in anticipation of a larger future study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck

e20501 Background: PPAS is a rare sarcoma whose prognosis is often poor despite surgery. The optimal treatment strategy for the management of PPAS is unknown. Methods: We analyzed the clinical outcome and treatment responses of all patients (pts) with available records evaluated at our institution for treatment of histopathologically confirmed PPAS between 1998 and 2009. Descriptive statistics were performed from the data obtained to determine recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and response rate. Results: We identified 13 pts (M:F = 10:3; mean age 53 yrs [19-73]). 7 pts had completely resected or potentially resectable disease at presentation. 6 pts had metastatic disease involving the lung (n = 6), bone (n = 1), abdomen (n = 1) and brain (n = 1). All 7 pts with completely resected or potentially resectable disease underwent definitive surgery with gross total resection and also received chemotherapy (n = 3), radiotherapy (n = 1) or both (n = 3) in either neoadjuvant or adjuvant settings. Pts were treated with doxorubicin 75 mg/m2 and ifosfamide 10 gm/m2 every 3 weeks (n = 4) or doxorubicin 75 mg/m2 and dacarbazine 1,000 mg/m2 every 3 weeks (n = 2). For the 6 pts with metastatic disease, all received chemotherapy, with doxorubicin 75 mg/m2 and ifosfamide 10 gm/m2 (n = 5) or doxorubicin 75 mg/m2 and dacarbazine 1,000 mg/m2 (n = 1) as first- or second-line therapy. For pts treated with curative intent, 1/7 (17%) developed local recurrence at 55.8 months, and 1/7 (17%) developed distant disease at 6.5 months. 67% of pts remain disease free at a median follow-up period of 53.7 months (6.5-100.8). All remain alive to date. For metastatic pts treated with palliative intent, the median PFS was 7.2 months (1.5-11.2) and OS was 22.1 months (6.3-43.6). For pts with measurable disease who received doxorubicin-based chemotherapy, best response was CR 1/9 (11%), PR 1/9 (11%), SD 4/9 (44%), and PD 3/9 (33%). Conclusions: For PPAS pts with potentially resectable disease, multidisciplinary therapy with the addition of chemotherapy and/or radiotherapy can produce long-term disease control. Doxorubicin-based chemotherapy may have a potential role in the systemic management of locally advanced and metastatic PPAS. No significant financial relationships to disclose.

BACKGROUND:The current study was performed to evaluate outcomes in patients with osteosarcoma of the head and neck (OHN) who were treated with surgery with or without radiotherapy (RT). METHODS:Between 1960 and 2007, 119 patients with OHN underwent macroscopic total resection with or without RT. The median age of the patients was 33 years (range, 7-77 years). Of these 119 patients 92 (77%) underwent surgery alone whereas 27 (23%) patients were treated with combined modality treatment (CMT) comprised of surgery and RT (median dose, 60 Gray [Gy]; range, 50-66 Gy). RESULTS:The median follow-up was 5.8 years. Overall survival (OS) rates at 5 years and 10 years were 63% and 55%, respectively. Corresponding disease-specific survival (DSS) rates were 67% and 61%, respectively. Stratified analysis by resection margin status demonstrated that CMT compared with surgery alone improved OS (80% vs 31%; P = .02) and DSS (80% vs 35%; P = .02) for patients with positive/uncertain resection margins. Multivariate analysis indicated that CMT for patients with positive/uncertain resection margins improved OS (P < .0001). A total of 44 (37%) patients experienced local disease recurrence (LR) and 25 (21%) developed distant metastases (DM). There was no difference noted with regard to DSS if disease recurrence was isolated (LR vs DM: 26% vs 29%, respectively, at 5 years; P = .48) The use of CMT versus surgery alone improved local control (LC) (75% vs 24%; P = .006) for patients with positive/uncertain resection margins. The rate of surgical complications was 28% at 5 years. The rates of RT-associated complications were 40% and 47% at 5 years and 10 years, respectively. CONCLUSIONS:The results of the current study indicated that RT in addition to surgery improves OS, DSS, and LC for patients with OHN who have positive/uncertain resection margins.

10511 Purpose: To evaluate outcomes for patients with osteosarcoma of the jaw/craniofacial bones treated with surgery or combined modality therapy (CMT) consisting of surgery and radiation therapy (RT). Methods: Retrospective analysis was performed on data for 119 patients with osteosarcoma of jaw/craniofacial bones who underwent definitive resection with or without RT between 1960 and 2007. Median age was 33 years (range, 7–77 years). Ninety-two (77%) underwent surgery alone while 27 (23%) were treated with CMT. Median RT dose was 60 Gy (range, 50–66 Gy). Kaplan-Meier method was used to calculate the actuarial curves for survival (OS), disease-specific survival (DSS), local recurrence (LR), distant metastatic relapse (DM), and complication rates; and the log-rank statistic was used to test for significance of differences between curves. Results: Median follow-up was 5.8 years (range, 0.25 to 44.5 years). The OS rates at 5 and 10 years were 63% and 55%, respectively. Corresponding DSS rates were 67% and 61% respectively. Surgical margin status (positive/uncertain vs. negative) was adversely prognostic for OS (p=0.0001) and DSS (0.0001). Stratified analysis by margin status showed that CMT compared to surgery alone improved OS (80% vs. 31%, p=0.02) and DSS (80% vs. 35%, p=0.02) for patients with positive/uncertain margins. Multivariate analysis showed that CMT for patients with positive/uncertain margins improved OS (p<0.0001). Forty-four patients (40%) experience LR and 25 (21%) developed DM. There was no difference in DSS if relapse was isolated LR vs. DM (26% vs. 29%, respectively at 5 years, p=0.48) Local control (LC) rates were 59% and 57% at 5 and 10 years, respectively. The use of CMT vs. surgery alone significantly improved LC for patients with positive/uncertain margins (75% vs. 24%, p=0.006). The rate of surgical complications was 28% at 5 years. Rates of RT-associated complications were 40% and 47% at 5 and 10 years, respectively. Conclusions: RT in addition to surgery improves OS, DSS, and LC for patients with osteosarcoma of the jaw/craniofacial bones who have positive/uncertain surgical margins. Complication rates from surgery and RT are high, but LR is lethal in this disease. Morbidity risks must be weighed against the need to eradicate disease with primary local managmement. No significant financial relationships to disclose.

The objective of the current study was to analyze the potential treatment‐related mortality in long‐term survivors of soft‐tissue sarcoma (STS) treated with radiotherapy (RT) and conservation surgery.