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The treatment of relapsed multiple myeloma is based in part on the degree of previous exposure and resistance to commonly used drug classes. For patients with a first relapse, an anti-CD38 antibody–based combination is preferred unless patients have already received these agents, in which case a carfilzomib-based option can be an excellent choice. For patients with more refractory disease, a bispecific antibody is an emerging choice, but CAR T-cell therapy should also be considered for some patients; other options include salvage autologous transplantation, recycling of previous therapies, and selinexor-based therapies. Emerging new classes of drugs in development are poised to broaden the treatment possibilities for relapsed disease.

In 2021, the WHO revised its classification of central nervous system (CNS) tumors, which has resulted in changes to both the diagnostic and treatment landscapes. At the NCCN 2023 Annual Conference, this tumor board–style presentation featured 4 case studies to demonstrate an evidence-based approach to the treatment of patients with various WHO-defined types of diffuse glioma. The NCCN Guidelines have been updated to reflect the WHO reclassification of CNS tumors and provide treatment recommendations accordingly.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is characterized by the accumulation of abnormal lymphocytes in the blood, bone marrow, and lymphoid tissues, leading to a weakened immune system and an increased risk of infections for patients. The NCCN Guidelines for CLL/SLL underscore the need for a comprehensive evaluation of multiple factors to determine the most appropriate treatment approach for each patient. For frontline therapy, the selection process should consider the patient’s IGHV status, del(17p)/TP53 mutation status, age, and comorbidities. In choosing subsequent therapy, prior therapy, comorbidities, and resistance mutations should be considered. With no clear evidence of a functional cure, it is important to enroll patients in clinical trials when available.

Excellent long-term outcomes are being achieved with contemporary treatment strategies for localized rectal cancer. A “watch-and-wait” nonoperative strategy seems to be a safe option for patients experiencing a complete clinical response. Total neoadjuvant therapy (TNT) has shown many advantages over standard chemoradiotherapy, although the optimal sequencing—with induction or consolidation chemotherapy—is still debated. The use of FOLFIRINOX can boost the benefit of TNT. Of note, in the small subset of patients whose tumors have mismatch repair deficiency, checkpoint inhibition has led to responses in most patients, eliminating the need for further treatment.

Esophageal squamous cell carcinoma is an aggressive malignancy with histologic variability depending on where in the world it is diagnosed, with most of these cancers occurring in China and other parts of Asia. Previous studies with cytotoxic chemotherapy combinations led to a plateau median overall survival of approximately 10 to 12 months, as well as a need for more effective treatment options. Cytotoxic chemotherapy served as the control arm in 3 studies that evaluated the safety and efficacy of immunotherapy + chemotherapy versus chemotherapy alone; in all 3 prospective randomized trials, the addition of immunotherapy resulted in a survival benefit in the first-line relapsed/metastatic setting. Data support these immunotherapy regimens as new standard-of-care systemic therapy options for unresectable, locally advanced, recurrent or metastatic esophageal cancers, and these regimens have now been incorporated into the NCCN Guidelines.

The NCCN Guidelines for Lung Cancer Screening have evolved over time to reflect the latest evidence and expert consensus. These NCCN Guidelines have played a significant role in shaping clinical practice and policy, leading to increased payer coverage for lung cancer screening and decreasing lung cancer mortality. Continued research and advancements in early detection methods, along with the implementation of effective screening programs, will be crucial in the ongoing effort to reduce lung cancer mortality and improve the overall quality of life for patients affected by this disease.

For many patients, sleep disorders (particularly insomnia), cancer-related fatigue, and cancer-related cognitive impairment are common and distressing symptoms of cancer and its treatment. At the NCCN 2023 Annual Conference, a panel of experts began with a personal account of a cancer survivor’s experience and discussed approaches to assess and manage these adverse effects of cancer and its treatment.

The use of next-generation tyrosine kinase inhibitors has led to improved progression-free survival for patients with metastatic non–small cell lung cancer (NSCLC) and those with EGFR-mutant and ALK-positive tumors. Newer therapeutics can now target KRAS G12C mutations, EGFR exon 20 insertions, and ERBB2 (HER2) mutations. Patients with metastatic NSCLC should undergo molecular testing for these mutations as well as for BRAF mutations; MET exon 14 skipping alterations; and ROS1, RET, and NTRK gene rearrangements (fusions). Novel targeted therapeutics are emerging at a fast pace.

Hepatobiliary cancers are aggressive tumors that affect the liver and biliary tract and are responsible for nearly 550,000 deaths per year. The most common malignancy is hepatocellular carcinoma, and risk factors include viral hepatitis infection, nonalcoholic steatohepatitis, and excessive alcohol use. Other etiologies include Wilson’s disease, α1-antitrypsin deficiency, and cryptogenic cirrhosis. Clinicians should be aware of underlying conditions and how they influence treatment decisions.