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Abstract

Liver transplant and resection are preferable for the management of hepatocellular carcinoma, but ultimately, tumor location, biology, and patient condition dictate treatment decisions. At the NCCN 2022 Annual Conference, a panel of experts used 3 case studies to develop an evidence-based approach to the treatment of similar patients with hepatocellular carcinoma. Moderated by Daniel B. Brown, MD, FSIR, the session focused on current research regarding liver-directed and systemic therapy options.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org.

An association between diabetes mellitus and pancreatic ductal adenocarcinoma (PDA) has long been recognized. This article assesses the effect of the baseline hemoglobin-A1c (HbA1c) value on the clinical outcomes of patients with PDA. HbA1c values were prospectively collected on 656 consecutive patients presenting to a pancreas multidisciplinary cancer clinic from 2009 to 2012. Patients were diagnosed with benign pancreatic disease (BPD) or biopsy-confirmed resectable (R), borderline/locally advanced (BL), or metastatic (M) PDA. Excluded were those with prior treatment for PDA or a history of chronic diabetes mellitus (>1-year or unknown duration), resulting in a final cohort of 284 patients. Of 284 patients, 44 had benign disease, 62 had R-PDA, 115 had BL-PDA, and 63 had M-PDA. Patients with malignant disease (R-, BL-, and M-PDA) collectively had a higher average HbA1c value than patients with BPD (6.1% vs 5.6%; P<.001). Among patients with PDA (n=240), HbA1c values of 6.5% or greater were significantly associated with inferior overall survival (OS) compared with patients with HbA1c values less than 6.5% (hazard ratio [HR], 1.74; OS, 10.2 vs 13.0 months; P=.007), along with other known prognostic factors, such as age of 65 years or older, ECOG performance status of 1 or greater, carbohydrate antigen 19-9 level greater than 90, tumor size larger than 3 cm, and disease stage. HbA1c values of 6.5% or greater remained in the final predictive model using backward elimination (HR, 1.46; P=.097), indicating that HbA1c values of 6.5% or greater influence OS of patients with PDA even when accounting for other known prognostic factors. HbA1c level at presentation is significantly higher in patients with PDA than patients with BPD and seems to affect survival.

The prognosis for patients with newly diagnosed acute lymphoblastic leukemia (ALL) has improved with the use of more intensive chemotherapy regimens, tyrosine kinase inhibitors, targeted agents, and allogeneic hematopoietic cell transplantation. However, the management of relapsed or refractory (R/R) ALL remains challenging and prognosis is poor. The NCCN Guidelines for ALL provide recommendations on standard treatment approaches based on current evidence. These NCCN Guidelines Insights summarize treatment recommendations for R/R ALL and highlight important updates, and provide a summary of the panel's discussion and underlying data supporting the most recent recommendations for R/R ALL management.