Purpose: Response Evaluation Criteria in Solid Tumors (RECIST) are insensitive in evaluating imatinib-treated gastrointestinal stromal tumors (GISTs). Response by Choi criteria, a 10% decrease in size or a 15% decrease in density on contrast-enhanced CT, correlated well in a small training set of patients who showed response as measured by positron emission tomography, and was more predictive of time to tumor progression (TTP) than response by RECIST. This study was designed to validate these observations in an independent data set. Patients and Methods: Fifty-eight patients with imatinib-treated GISTs were evaluated by RECIST and Choi criteria. TTP was compared with TTP in the training set. Patients were analyzed initially with follow-up to 28 months, extended to 60 months for survival analysis. Results: Patients who met Choi response criteria on CT at 2 months had significantly better TTP than those who did not (P = .0002), whereas response group by RECIST was not significantly correlated with TTP. Even when the 98 patients from both sets were analyzed together, the response group by RECIST did not correlate significantly with TTP, whereas response group by Choi criteria did correlate significantly with TTP. Disease-specific survival (DSS) was also significantly correlated with response group by Choi criteria (P = .04), but not with response group by RECIST. Conclusion: Choi response criteria are reproducible, more sensitive, and more precise than RECIST in assessing the response of GISTs to imatinib mesylate. Response by Choi criteria, unlike response by RECIST, correlates significantly with TTP and DSS. Response by Choi criteria should be incorporated routinely into future studies of GIST therapy. We should desist using RECIST, at least in GIST.

Background Immunotherapies, specifically those based on immune checkpoint inhibitors, have shown promising activity in multiple tumor types. Other than mifamurtide (MEPACT®) for osteosarcoma approved by European Medicines Agency, there are no approved immunotherapies for sarcomas. Methods We analyzed medical records of patients with advanced sarcoma who were referred to Phase 1 clinic at MD Anderson and received an immunotherapy (checkpoint inhibitors, vaccines, or cytokine based therapies). Clinical parameters including demographics, clinical history, toxicity, and response were abstracted. Results Among 50 patients enrolled in immunotherapy trials (Bone 10; Soft-tissue 40) we found 14 different subtypes of sarcomas. Royal Marsden Hospital (RMH) prognostic score was <2 (86%). Performance status (PS) was 0–1 in 48 patients (96%); median number of prior therapies was 3 (0–12). Immunotherapy consisted of checkpoint inhibitors (82%: PD1 = 7, PD-L1 = 11, CTLA4 = 22, other = 1) of which 42% were combinations, as well as vaccines (14%), and cytokines (4%). Median overall survival (OS) was 13.4 months (11.2 months: not reached). Median progression free survival (PFS) was 2.4 months (95% CI = 1.9–3.2 months). Best response was partial response (PR) in 2 patients with alveolar soft part sarcoma (ASPS) and stable disease (SD) in 11 patients (3 GIST, 3 liposarcomas (2 DDLS, 1 WDLS), 2 ASPS, 2 leiomyo, 1 osteo). PFS was 34% (23%, at 50%) at 3 months, 16% (8%, 30%) at 6 months, and 6% (2%, 20%) at 1 year. Pseudo-progression followed by stable disease was observed in 2 patients (4%). Grade 3/4 adverse events included rash (10%), fever (6%), fatigue (6%), and nausea/vomiting (6%). Conclusion Immunotherapies were well tolerated in advanced sarcoma patients enrolled in trials. All four ASPS patients had clinical benefit with checkpoint inhibitors and this was the only subtype experiencing partial response. Further evaluation of checkpoint inhibitors in ASPS is warranted.

Background: Patients with advanced solitary fibrous tumors (SFTs) have a poor prognosis; treatment options for recurrent disease are particularly limited. Several novel targeted agents have recently shown promise against advanced SFTs, but the relative efficacy of new agents is difficult to assess because data on the efficacy of conventional chemotherapy for SFTs are limited. We thus sought to estimate the efficacy of conventional chemotherapy for SFTs by reviewing data on tumor response to therapy and progression-free survival from SFT patients who received this therapy. Methods: We retrospectively analyzed the clinical outcomes of 21 patients with grossly measurable, advanced SFTs (unresectable metastatic disease or potentially resectable primary tumors) who received conventional chemotherapy and follow-up at The University of Texas MD Anderson Cancer Center between January 1994 and June 2007. Best tumor response to therapy was assessed using the Response Evaluation Criteria In Solid Tumors 1.1. The Kaplan-Meier method was used to estimate median progression-free survival (PFS) duration. Results: Of 21 patients, 4 received more than 1 regimen of chemotherapy, for a total of 25 treatments. Doxorubicin-based chemotherapy was given in 15 cases (60%), gemcitabine-based therapy in 5 cases (20%), and paclitaxel in 5 cases (20%). First-line chemotherapy was delivered in 18 cases (72%). No patients had a complete or partial response, 16 (89%) had stable disease, and 2 (11%) had disease progression. Five patients (28%) maintained stable disease for at least 6 months after first-line treatment. The median PFS duration was 4.6 months. The median overall survival from diagnosis was 10.3 years. Conclusion: Conventional chemotherapy is effective in controlling or stabilizing locally advanced and metastatic SFTs. Our findings can serve as a reference for tumor response and clinical outcomes in the assessment of novel treatments for SFTs.

Purpose: Desmoplastic small round cell tumor (DSRCT), which harbors EWSR1-WT1 t(11;22)(p13:q12) chromosomal translocation, is an aggressive malignancy that typically presents as intra-abdominal sarcomatosis in young males. Given its rarity, optimal treatment has not been defined. Experimental Design: We conducted a retrospective study of 187 patients with DSRCT treated at MD Anderson Cancer Center over 2 decades. Univariate and multivariate regression analyses were performed. We determined whether chemotherapy, complete cytoreductive surgery (CCS), hyperthermic intraperitoneal cisplatin (HIPEC), and/or whole abdominal radiation (WART) improve overall survival (OS) in patients with DSRCT. Critically, because our institutional practice limits HIPEC and WART to patients with less extensive, potentially resectable disease that had benefited from neoadjuvant chemotherapy, a time-variant analysis was performed to evaluate those adjunct treatment modalities. Results: The pre-2003 5-year OS rate of 5% has substantially improved to 25% with the advent of newer chemotherapies and better surgical and radiotherapy techniques (HR, 0.47; 95% CI, 0.29–0.75). Chemotherapy response (log rank P = 0.004) and CCS (log rank P < 0.0001) were associated with improved survival. Although WART and HIPEC lacked statistical significance, our study was not powered to detect their potential impact upon OS. Conclusions: Improved 3- and 5-year OS were observed following multidisciplinary treatment that includes Ewing sarcoma (ES)-based chemotherapy and complete tumor cytoreductive surgery, but few if any patients are cured. Prospective randomized studies will be required to prove whether HIPEC or WART are important. In the meantime, chemotherapy and CCS remain the cornerstone of treatment and provide a solid foundation to evaluate new biologically targeted therapies. Clin Cancer Res; 24(19); 4865–73. ©2018 AACR.

The largest studies of chemotherapy for bone sarcomas are in the pediatric population. Although increasing age is often found to be an adverse prognostic factor in these clinical trials, few studies are aimed at assessing regimens specifically in the adult population. Osteosarcoma and Ewing sarcoma have peak incidences in the pediatric and young adult population but also occur in adults. Chondrosarcoma and giant cell tumor of bone are generally found in adults. In this review, we describe the current status of our knowledge about treating adults with cancers of bone origin. We also describe our experience treating patients in the adult Sarcoma Medical Oncology group at The University of Texas MD Anderson Cancer Center.