McCarter, Martin D.

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/Aims: Barrett’s esophagus (BE), defined by the presence of intestinal metaplasia (IM) on histology, is thought to be the only identifiable precursor lesion for esophageal adenocarcinoma (EAC). Recent studies have suggested the possibility of an alternate, non-IM associated EAC that is a more aggressive form of EAC with worse survival. Among EAC patients, we aimed to compare survival of patients with and without IM at the time of diagnosis. Methods: This was a retrospective cohort study of all patients with histologic confirmed EAC evaluated at a tertiary care center from 2013 to 2019. Cases were categorized according to the presence or absence of IM on histologic specimens (Group I—IM-EAC and Group II—non-IM-EAC). We compared demographic characteristics, clinical stage, therapy, and survival between the 2 groups using the Chi-square and ANOVA tests (for categorical and continuous variables, respectively). We used Cox proportional hazards regression to determine the association of IM with overall survival, adjusting for sex, age at diagnosis, tumor location, histologic grade, and clinical stage. Results: A total of 475 patients were included in this analysis (mean age 64.8 years [SD 10.8], 89% white) and 109 (23.0%) had no evidence of IM. Compared with IM-EAC (Group I), individuals in the non-IM-EAC group were younger ( P = .01) and had a greater proportion of patients diagnosed with advanced disease (49.5 vs 20.2% for stage 4, P < .001). These patients were less likely to undergo endoscopic therapy alone (0.92% vs 29.78%, P < .001) or surgery alone (0 vs 9.84%, P = .001). On multivariable analysis, the presence of IM-EAC was associated with improved overall survival compared to non-IM-EAC (HR 0.69, 95% CI 0.49-0.96). Additional factors associated with poor survival was increasing stage of diagnosis (HR 6.49: 95% CI 3.77-11.15 for stage 4, HR 2.19: 95% CI 1.25-3.84 for stage 3, HR 2.04: 95% CI 0.98-4.25 for stage 2 compared to stage 1) and more advanced histologic stage (HR 2.00, 95% CI 1.26-3.19) for poorly/undifferentiated compared to well differentiated). Conclusions: EAC without the presence of IM on histology was associated with worse survival compared to those with IM. Future prospective studies with detailed molecular sequencing are required to clarify if 2 separate phenotypes of EAC exist (IM-EAC and non-IM-EAC). If confirmed, this may have significant implications for screening and management strategies.

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.

INTRODUCTION: Using the National Cancer Database, we assessed the relationship between facility overall esophageal adenocarcinoma (EAC) case volume and survival. METHODS: We categorized facilities into volume quintiles based on annual EAC patient volume and performed a multivariable Cox proportional hazards regression between facility patient volume and survival. RESULTS: In a cohort of 116,675 patients, facilities with higher vs lower (≥25 vs 1–4 cases) annual EAC patient volume demonstrated improved survival (adjusted hazard ratio: 0.80. 95% confidence interval: 0.70–0.91). DISCUSSION: This robust volume-outcome effect calls for centralization of care for EAC patients at high annual case volume facilities.

Purpose The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year of adjuvant imatinib prolonged recurrence-free survival (RFS) after resection of primary GI stromal tumor (GIST). We sought to determine the pathologic and molecular factors associated with patient outcome. Patients and Methods There were 328 patients assigned to the placebo arm and 317 to the imatinib arm. Median patient follow-up was 74 months. There were 645 tumor specimens available for mitotic rate or mutation analysis. Results RFS remained superior in the imatinib arm (hazard ratio, 0.6; 95% CI, 0.43 to 0.75; Cox model–adjusted P < .001). On multivariable analysis of patients in the placebo arm, large tumor size, small bowel location, and high mitotic rate were associated with lower RFS, whereas tumor genotype was not significantly associated with RFS. Multivariable analysis of patients in the imatinib arm yielded similar findings. When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Adjuvant imatinib did not seem to alter overall survival. Conclusion Our findings show that tumor size, location, and mitotic rate, but not tumor genotype, are associated with the natural history of GIST. Patients with KIT exon 11 deletions assigned to 1 year of adjuvant imatinib had a longer RFS.