Citations

Background : Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Optimal treatment decisions are challenging, and existing treatment allocation frameworks may not fully reflect the evolving therapeutic landscape or contemporary clinical practices in North America. Methods : Using a modified Delphi process, a multidisciplinary panel of 20 North American experts in hepatology, medical oncology, surgery, radiology, and radiation oncology developed a consensus-based treatment framework for HCC, termed the BEACON-HCC system. The framework was informed by current evidence and expert opinion through iterative discussion and voting. In a pilot study using 29 real-world patient cases, we assessed concordance between external expert recommendations and BEACON-HCC recommendations and Barcelona Clinic Liver Cancer (BCLC) 2025 treatment recommendations. Results : The BEACON-HCC treatment allocation framework diverges from prior frameworks by incorporating nuanced clinical features such as degree of intrahepatic tumor burden and vascular invasion, and adverse tumor prognostic markers, to align treatment allocation with tumor biology and therapeutic potential. Key innovations include the incorporation of emerging modalities such as external beam radiation therapy (EBRT), transarterial radioembolization (TARE), and systemic-locoregional combination therapies. In the pilot exercise, expert treatment decisions showed 96.6% concordance with BEACON-HCC recommendations and 72.4% concordance with BCLC recommendations. Conclusions : BEACON-HCC is a consensus-based framework for treatment allocation that incorporates the expanding range of therapeutic options available to patients in the North American HCC population. Expert treatment decisions showed a high concordance with the BEACON-HCC system; further validation using empiric clinical data is planned through the HCC-Live Consortium.

Among patients with treatment-naive hepatocellular carcinoma, glass microsphere radiation segmentectomy before liver transplant achieved high rates of complete pathologic necrosis, which was positively associated with the number of optimized treatment parameter thresholds.

The treatment landscape for soft tissue sarcomas (STS) is evolving constantly. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for STS specific to surgical management and systemic therapy recommendations for various subtypes.

Radiation segmentectomy is a dynamic image-guided therapy for hepatic malignancies that uses yttrium 90 transarterial radioembolization to deliver high radiation doses to targeted hepatic segments, achieving high and sustained response rates.

This commentary is a call to action for a concerted commitment and effort to transform clinical trials and enable people with cancer to participate in clinical trials closer to home. Three key strategies are identified to address major barriers: confront challenges with the interpretation of US Food and Drug Administration Form 1572 requirements (Statement of Investigator); broaden acceptance of local laboratories and imaging centers; and invest in the creation of effective, sustainable partnerships between research centers and local providers.

PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m 2 ) + gemcitabine (1,000 mg/m 2 ) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.

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.

e16200 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Indoleamine-2,3-dioxygenase (IDO) is an intracellular enzyme expressed by HCC which helps to orchestrate immune suppression within the tumor microenvironment (TME) and may contribute to primary and acquired resistance of PD-(L)1 inhibitors. BMS-986205 is a novel oral drug that potently and selectively inhibits IDO1. This Phase I/II study is evaluating the safety and tolerability of the combination of BMS-986205 and nivolumab as first-line therapy in HCC. Methods: Patients (pts) ≥18y with untreated, unresectable/metastatic HCC received BMS-986205 in combination with nivolumab. A fixed dose of Nivolumab 240mg/m2 IV was administered on Day 1 of each 14-day cycle. BMS-986205 was an oral tablet administered daily; a total of two dose levels (50-100mg) were given to determine dose limiting toxicities (DLT) during the dose-escalation Phase I of the study. Safety was assessed using CTCAE v5.0 criteria, and efficacy was assessed by objective response rate (ORR) using RECIST v1.1 criteria. Secondary objectives included preliminary data on disease control rate (DCR), duration of response (DOR), ORR using immune RECIST criteria (iRECIST), progression free survival (PFS) and overall survival (OS). Results: Here we report the results of the dose escalation cohort. Eight pts were treated with median age 69y [60-76]; 75% male; and PS 0 (3 pts) or 1 (5 pts). Pts were White (62.5%), Asian (25%), and African American (12.5%). Six of 8 pts had underlying viral hepatitis (5 hepatitis C, 1 hepatitis B), and all pts were Child Pugh A at enrollment with median baseline alpha-fetoprotein (AFP) level 41.8 [3.8–917.2]; 4 pts received prior local therapies. A total of 91 cycles of therapy were administered; 2 pts received 27 and 43 cycles of treatment each. Six pts were evaluable for DLT; 2 pts were replaced for DLT assessment due to insufficient dose administered, unrelated to toxicity. No DLTs were observed at either the 50 or 100mg dose of BMS-986205. There were 24 treatment-related adverse events (TRAEs), 4 of which were Grade 3 events; there were no Grade 4-5 events. The most common TRAEs of all grades were AST elevation and ALT elevation in 3 pts, and diarrhea, maculopapular rash and increased alkaline phosphatase in 2 pts each. Grade 3 events were diarrhea and AST elevation (1 pt), and hyperglycemia and pancreatitis requiring treatment discontinuation (1 pt). Eight pts were evaluable for efficacy with best response of partial response in 1 pt (12.5%) and stable disease in 3 pts (37.5%), yielding a DCR of 50%. Median PFS was 8.5 weeks; median OS has not been reached. Conclusions: Combination BMS-986205 and nivolumab showed a manageable safety profile with durable benefit as 1st line therapy in a meaningful subset of patients with unresectable/metastatic HCC. Clinical trial information: NCT03695250.