Petersen, Ivy A.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

AbstractBackgroundCompared to other sarcomas, myxoid liposarcoma (ML) is known to be radiosensitive, with improved oncologic outcomes. Although these tumors “shrink” following radiotherapy, there is a paucity of data examining the degree of radiosensitivity and oncologic outcome. The purpose of the study was to evaluate pre‐ and postradiotherapy tumor volume to determine if size reduction impacts outcome.MethodsWe reviewed 62 patients with ML undergoing surgical resection combined with preoperative radiotherapy, with pre‐ and postradiotherapy MRI. This included 34 (55%) males, with a mean age of 47 ± 14 years. All tumors were deep to the fascia, and 12 (19%) patients had tumors with a >5% round‐cell component.ResultsThe mean volume reduction was 54% ± 29%. Compared to patients with >25% volume reduction, patients with reduction ≤25% had worse 10‐year disease specific survival (86% vs. 37%, p < 0.01), in addition to an increased risk of metastatic disease (HR 4.63, p < 0.01) and death due to disease (HR 4.52, p < 0.01).ConclusionLack of volume reduction is a risk factor for metastatic disease and subsequent death due to disease in patients with extremity ML treated with combined preoperative radiotherapy and surgery. This data could be used to stratify patients for adjuvant therapies and follow‐up intervals.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

Background: Contemporary breast cancer radiotherapy (RT) results in variable cardiac radiation exposure. While cardiomyocytes are radio-resistant, radiation induces coronary microvascular endothelial damage and inflammation which may ultimately lead to myocardial inflammation, ischemia and fibrosis and put patients at risk for heart failure (HF) and particularly, HF with preserved ejection fraction (HFpEF). Methods: Community based (Olmsted County, MN), HF case-control study of contemporary (1999-2014) breast cancer RT patients with CT-based RT planning for precise mean cardiac radiation dose (MCRD) calculation. HF cases (n=66) and controls (n=129) were matched (1:2) for age at RT, HF risk factors, tumor side and chemotherapy use. Matched controls and cases had identical follow-up (index interval). Proportion of HF and clinical characteristics in categories of MCRD were reported (table) and conditional logistic regression was used to estimate the HF odds ratio (OR) associated with MCRD as a continuous variable. Results: Of the 66 HF cases, 46 (70%) had HFpEF and 20 (30%) had HF with reduced ejection fraction (HFrEF). The proportion of patients with HF (any) or HFpEF increased and proportion with HFrEF tended to increase with increasing MCRD. The prevalence of HF risk factors (hypertension, diabetes, coronary disease) at time of RT did not vary by MCRD while left sided tumor, cancer stage and adriamycin use increased with increasing MCRD. The OR per 1 unit increase in log MCRD was 3.71 (1.98, 6.94) for total HF (p<0.001), 4.91 (1.93, 9.09) for HFpEF (p<0.001) and 2.78 (0.91, 8.47) for HFrEF (p=0.07). The mean index interval was 5.0±3.2 years. Conclusion: Cardiac radiation incident to contemporary breast RT increases the risk of HF, and particularly HFpEF over a short post-RT interval. These data may guide use of proton beam therapy in breast cancer. These data also provide support for the role of coronary microvascular compromise in the pathophysiology of HFpEF.

11550 Background: RPS often have local recurrence (LR) after surgery. Preoperative radiation (RT) to 50.4 Gy can reduce LR risk but is not uniformly effective, especially after (+) margin resections. Therefore, we conducted a multi-institutional, prospective Phase II study to assess efficacy and tolerability of preop IMPT with selective dose escalation to 63 GyRBE to the posterior RPS margin (clinical target volume [CTV] 2) at high risk for (+) margins to further reduce the risk of LR. This dose was tolerable in a prior phase I study (DeLaney T et al, 2017, PMID:28740917). Methods: Primary RPS patients (pts) >18 years received preop IMPT, 50.4 GyRBE in 28 fractions (fx) of 1.8 GyRBE to CTV1 (tumor plus adjacent tissue at risk of subclinical disease) with SIB to CTV2 to 63.0 GyRBE in 28 fx of 2.25 GyRBE. Pts with high-grade tumors could get chemotherapy(CTX) prior to IMPT. To avoid treatment delay, 11 fx of IMRT x-rays could be substituted for IMPT. Pts had restaging and surgery 4-8 weeks after IMPT. Primary study endpoint was local tumor control. Secondary endpoints included clinical and pathologic response, surgical margin status, and disease-free and overall survival. Results: We accrued 60 pts from January 2016 to February 2021. Histology: 35 liposarcoma(LPS) (19 dediff and 16 well diff), 22 leiomyosarcoma(LMS), and 3 undifferentiated pleomorphic sarcoma. IMPT was delivered per protocol in all pts. 51 pts have had surgery, 5 are awaiting surgery, and 4 had no surgery due to metastases(DM) on preop imaging. 22 pts had (+) margins. 2 pts had > 75% necrosis. With 23-month median (range 1-52 months) follow-up after start of RT, there were two LRs. A dediff LPS pt had a well diff LPS LR 26 months postop, resected, and is disease-free. A renal vein/IVC LMS pt treated with CTX and IMPT had LR and DM 4 months postop and died from disease. Surgical Clavien-Dindo morbidity scores: 0(21), 1(9), 2(8), 3a (4), 3b(4), 4a(2), 4(b)1, 5(2); the periop deaths were from sepsis(pneumonia) and duodenal ulcer. The grade 3-4 periop morbidity included abscess(3), treated by catheter(2) or operative(1) drainage, prolonged hospital stays (2 pts with IVC LMS), small bowel obstruction (1), and late sigmoid colon anastomotic failure (1). Readmissions for lymphopenia(1), pneumoperitoneum (1), and volume overload (1). One late neuropathy was seen in a Type II diabetic pt with transient postop weakness after femoral nerve dissection who later had significant lower extremity weakness 3.75 years postop. Study was amended to reduce IMPT dose in diabetic pts. Conclusions: Preoperative IMPT with selective dose escalation to 63 GyRBE to the high risk posterior RPS margin is feasible. Early local control results with this approach appear promising. Some peri-operative morbidity was noted but appears to be in the expected range for RPS resections. Clinical trial information: NCT01659203.

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

AbstractBackground and ObjectivesDescribe patient‐reported functional outcomes for hand and foot sarcoma survivors treated with limb‐sparing surgery and radiation therapy (LSS + RT).MethodsFifty‐four patients with hand/wrist and foot/ankle sarcomas treated with LSS + RT from 1991 to 2015 were identified. Survivors ≥18 years old without subsequent amputation completed self‐assessed functional surveys: Toronto upper extremity salvage score (TESS‐UE) and Michigan hand outcomes (MHQ) surveys for hand; TESS lower extremity (TESS‐LE) and Foot and Ankle Outcomes (FAOS) surveys for foot. Scoring scales: 0–100, MHQ and TESS; ‐26 to 56 and 25‐59, FAOS core and shoe comfort, respectively. Higher scores denote superior function.ResultsFive‐year local tumor control was 88%. Fourteen of 24 hand (58%) and 14/18 foot (78%) survivors completed surveys. Mean TESS‐UE and MHQ scores were 89.4 and 72.8, respectively. Mean TESS‐LE, core FAOS, and shoe comfort scores were 92.4, 46.19, and 53.1, respectively. No factors correlated with outcomes. TESS‐UE and MHQ scores strongly correlated (r = .87). TESS‐LE and FAOS scores were associated with a poor correlation (r = .02 and r = .69).ConclusionsThe largest patient‐reported functional outcomes analysis for hand and foot sarcoma survivors treated with LSS + RT demonstrates excellent local tumor control and acceptable functional outcomes. Further exploration of optimal functional assessment tools is needed given the potential scope differences.