González, Ricardo

AbstractIntegration and mining of bioimaging data remains a challenge and lags behind the rapidly expanding digital pathology field. We introduce Hourglass, an open‐access analytical framework that streamlines biology‐driven visualization, interrogation, and statistical assessment of multiparametric datasets. Cognizant of tissue and clinical heterogeneity, Hourglass systematically organizes observations across spatial and global levels and within patient subgroups. Applied to an extensive bioimaging dataset, Hourglass promptly consolidated a breadth of known interleukin‐6 (IL‐6) functions via its downstream effector STAT3 and uncovered a so‐far unknown sexual dimorphism in the IL‐6/STAT3‐linked intratumoral T‐cell response in human pancreatic cancer. As an R package and cross‐platform application, Hourglass facilitates knowledge extraction from multi‐layered bioimaging datasets for users with or without computational proficiency and provides unique and widely accessible analytical means to harness insights hidden within heterogeneous tissues at the sample and patient level. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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.

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.

Background In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). Methods Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. Results Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re‐resection (61.9%). The 5‐year OS rate varied significantly based on the pattern of failure ( P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [ P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [ P < .001]). The 5‐year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. Conclusions Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease‐free survivors were identified after surgery for second LR in patients selected for this intervention.

Abstract Background Schwannomas are rare tumours that pose a significant management challenge in the abdomen, retroperitoneum and pelvis. No data are available to inform management strategy. Methods A collaborative international cohort study, across specialist sarcoma units, was conducted to include adults presenting between 2000 and 2017 with histopathologically confirmed schwannomas within the abdomen, retroperitoneum or pelvis. Results Of 485 patients across 12 centres, 38 (7·8 per cent) were discharged without follow-up, 199 (41·0 per cent) underwent early resection and 248 (51·1 per cent) had radiological monitoring. Of these 248 patients, 96 (38·7 per cent) eventually had surgery, giving an overall resection rate of 60·8 per cent (295 of 485). At baseline, median tumour volume was 90·1 (i.q.r. 26·5–262·0) cm3. The estimated growth rate was 10·5 (95 per cent c.i. 9·4 to 11·6) per cent per year, and was consistent in the short term (within 2 years of diagnosis) and long term (beyond 2 years) (ρ = 0·405, P = 0·021). A decision to operate was more common in symptomatic patients (P &lt; 0·001) and for rapidly growing tumours (growth rate more than 20 per cent per year) (P = 0·025). R0/R1 resection was achieved in 91·6 per cent of patients (263 of 287). Kaplan–Meier long-term recurrence rates after R0/R1 resection were 2·3 and 6·7 per cent at 3 and 5 years respectively. Conclusion Specific recommendations include: indications for early surgery, prediction of growth from radiological monitoring, promotion of selective submacroscopic resection and cessation of postoperative imaging surveillance.

Abstract Purpose: The role of surgery for first relapse locally recurrent retroperitoneal sarcoma (RPS-LR1) is uncertain. We report outcomes of the largest RPS-LR1 series and propose a new prognostic nomogram. Experimental Design: Patients with consecutive RPS-LR1 without distant metastases who underwent resection at 22 centers (2002–2011) were included. Endpoints were disease-free and overall survival (DFS, OS) and crude-cumulative-incidence (CCI) of local/distant recurrence from second surgery. Nomograms predicting DFS and OS from second surgery were developed and validated (calibration plots); discrimination was assessed (Harrell C index). Results: Of 684 patients identified, full prognostic variable data were available for 602. Initial surgery for primary RPS was performed at our institutions in 188 patients (31%) and elsewhere in 414 (69%). At a median follow-up of 119 months [Interquartile range (IQR), 80–169] from initial surgery and 75 months (IQR 50–105) from second surgery, 6-year DFS and OS were 19.2% [95% confidence interval (CI), 16.0–23.0%] and 54.1% (95% CI, 49.8–58.8%), respectively. Recurrence patterns and survival probability were histology-specific, with liposarcoma subtypes having the highest 6-year CCI of second local recurrence (LR, 60.2%–70.9%) and leiomyosarcoma (LMS) having higher 6-year CCI of distant metastasis (DM, 36.3%). Nomograms included age at second surgery, multifocality, grade, completeness of second surgery, histology, chemotherapy/radiotherapy at first surgery, and number of organs resected at first surgery. OS and DFS nomograms showed good calibration and discriminative ability (C index 0.70 and 0.67, respectively). Conclusions: We developed nomograms to predict DFS and OS for patients undergoing RPS-LR1 resection. Nomograms provide individualized, disease-relevant estimations of survival for RPS-LR1 patients and assist in clinical decisions.