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Craig Horbinski, Louis Burt Nabors, Jana Portnow, Joachim Baehring, Ankush Bhatia, Orin Bloch, Steven Brem, Nicholas Butowski, Donald M. Cannon, Samuel Chao, Milan G. Chheda, Andrew J. Fabiano, Peter Forsyth, Pierre Gigilio, Jona Hattangadi-Gluth, Matthias Holdhoff, Larry Junck, Thomas Kaley, Ryan Merrell, Maciej M. Mrugala, Seema Nagpal, Lucien A. Nedzi, Kathryn Nevel, Phioanh L. Nghiemphu, Ian Parney, Toral R. Patel, Katherine Peters, Vinay K. Puduvalli, Jason Rockhill, Chad Rusthoven, Nicole Shonka, Lode J. Swinnen, Stephanie Weiss, Patrick Yung Wen, Nicole E. Willmarth, Mary Anne Bergman, and Susan Darlow

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2–3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2–4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non–AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS 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 most recent recommendations regarding molecular profiling of gliomas.

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Bin-Yi Xiao, Xuan Zhang, Tai-Yuan Cao, Dan-Dan Li, Wu Jiang, Ling-Heng Kong, Jing-Hua Tang, Kai Han, Chen-Zhi Zhang, Wei-Jian Mei, Jian Xiao, Zhi-Zhong Pan, Yun-Feng Li, Xiao-Shi Zhang, and Pei-Rong Ding

Background: Our study aimed to evaluate the efficacy and feasibility of neoadjuvant anti–PD-1 treatment for localized mismatch repair–deficient (dMMR) colorectal cancer (CRC). Patients and Methods: The study cohort included patients with localized dMMR CRC who received PD-1 inhibitors as neoadjuvant therapy from 3 medical centers in Southern China. Main eligibility criteria included age between 18 and 75 years, ECOG performance status of 0 or 1, and receipt of ≥2 doses of PD-1 inhibitors. Results: A total of 73 patients were included. Most of the tumors were locally advanced, including 19 (26.0%) T4a and 29 (39.7%) T4b. Most patients (79.5%) received PD-1 inhibitor monotherapy. Objective response per radiologic assessment was achieved in 62 (84.9%) patients, including 17 (23.3%) with complete response (CR) and 45 (61.6%) with partial response, with a median time to response of 9.6 weeks. Patients with T4a/4b disease had a similar response rate as those with T2–3 disease (84.0% vs 85.4%; P=.999). As of writing, a total of 50 patients have undergone surgery. Pathologic CR was achieved in most (57.1%) patients and remained high (59.5%) even among the 38 patients with T4a/4b disease. The 17 patients with CR did not undergo surgery and adopted a watch-and-wait strategy. After a median follow-up of 17.2 months (range, 3.4–45.1 months), the overall median recurrence-free and overall survivals were not reached. Among patients undergoing surgery or achieving CR, the 2-year tumor-specific disease-free and overall survival rates were both 100%. During neoadjuvant treatment, grade 3–4 adverse events occurred in 8 patients; 4 required acute intervention. Severe postoperative complications were recorded in 4 patients, 3 of whom required a second surgery. Conclusions: Neoadjuvant therapy with PD-1 blockade is highly effective for localized dMMR CRC, with an acceptable safety profile and low recurrence rate. This treatment holds promise for becoming the new standard of care for localized dMMR CRCs.

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Soledad Jorge, Shatreen Masshoor, Heidi J. Gray, Elizabeth M. Swisher, and Kemi M. Doll

Background: Significant disparities exist in recruitment of minorities to clinical trials, with much of the prior literature focused on race/ethnicity only. Limited English proficiency (LEP) is a known barrier in healthcare that may also drive disparities in trial enrollment. We sought to determine participation rates in gynecologic oncology trials among patients with LEP and to explore barriers to their participation. Methods: In a retrospective cohort study, electronic health record data from >2,700 patients treated over 2 years at one academic gynecologic oncology practice were abstracted and the primary exposure of having LEP was identified. The primary outcome was enrollment in a clinical trial. Demographic, financial, clinical, and healthcare access–related covariates were also abstracted and considered as potential confounders in a multivariable logistic regression model. Age, race, ethnicity, and insurance status were further examined for evidence of effect modification. In addition, a survey was administered to all gynecologic oncology research staff and gynecologic oncology providers (n=25) to assess barriers to research participation among patients with LEP. Results: Clinical trial enrollment was 7.5% among fluent English speakers and 2.2% among patients with LEP (risk ratio, 0.29; 95% CI, 0.11–0.78; P=.007), and remained significantly lower in patients with LEP after adjusting for the identified confounders of Hispanic ethnicity and insurance payer (odds ratio, 0.34; 95% CI, 0.12–0.97; P=.043). There was a trend toward race and LEP interaction: Asian patients were equally likely to participate in research regardless of language fluency, whereas White and Black patients with LEP were less likely to participate than non-LEP patients in both groups (P=.07). Providers reported that the most significant barriers to enrollment of patients with LEP in research were unavailability of translated consent forms and increased time needed to enroll patients. Conclusions: Patients with LEP were 3.4 times less likely to participate in gynecologic oncology trials than fluent English speakers. De-aggregation of race, ethnicity, and language proficiency yielded important information about enrollment disparities. These findings offer avenues for future interventions to correct disparities.

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Krisda H. Chaiyachati, Diana Krause, Jessica Sugalski, Evan M. Graboyes, and Lawrence N. Shulman

Background: Addressing patients’ social determinants of health is a national priority for cancer treatment centers. Transportation insecurity is one major challenge for patients undergoing active cancer treatment, and missing treatments can result in worse cancer treatment outcomes, including worse morbidity and mortality. How cancer treatment centers are addressing transportation insecurity is understudied. Methods: In January and February 2022, the NCCN Best Practices Committee conducted a survey of NCCN’s 31 Member Institutions (currently 32 member institutions as of April 2022) to assess how centers were addressing patient transportation insecurity: how they screen for transportation insecurity, coordinate transportation, and fund transportation initiatives, and their plans to address transportation insecurity in the future. Results: A total of 25 of 31 (81%) NCCN Member Institutions responded to the survey, of which 24 (96%) reported supporting the transportation needs of their patients through screening, coordinating, and/or funding transportation. Patients’ transportation needs were most often identified by social workers (96%), clinicians (83%), or patients self-declaring their needs (79%). Few centers (33%) used routine screening approaches (eg, universal screening of social risk factors) to systematically identify transportation needs, and 54% used the support of technology platforms or a vendor to coordinate transportation. Transportation was predominantly funded via some combination of philanthropy (88%), grants (63%), internal dollars (63%), and reimbursement from insurance companies (58%). Over the next 12 months, many centers were either going to continue their current transportation programs in their current state (60%) or expand existing programs (32%). Conclusions: Many NCCN Member Institutions are addressing the transportation needs of their patients. Current efforts are heterogeneous. Few centers have systematic, routine screening approaches, and funding relies on philanthropy more so than institutional dollars or reimbursement from insurers. Opportunities exist to establish more structured, scalable, and sustainable programs for patients’ transportation needs.

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Shaji K. Kumar, Natalie S. Callander, Kehinde Adekola, Larry D. Anderson Jr., Muhamed Baljevic, Erica Campagnaro, Jorge J. Castillo, Caitlin Costello, Christopher D’Angelo, Srinivas Devarakonda, Noura Elsedawy, Alfred Garfall, Kelly Godby, Jens Hillengass, Leona Holmberg, Myo Htut, Carol Ann Huff, Malin Hultcrantz, Yubin Kang, Sarah Larson, Hans C. Lee, Michaela Liedtke, Thomas Martin, James Omel, Aaron Rosenberg, Douglas Sborov, Jason Valent, Ryan Berardi, and Rashmi Kumar

Primary systemic light chain amyloidosis (SLCA) is characterized by production of light chains that get converted to amyloid fibrils with an affinity for visceral organs and causing organ dysfunction. The therapy for SLCA is directed to recovering the function of the affected organs by targeting the abnormal plasma cell clone and slowing deposition of amyloid fibrils. The NCCN Guidelines for SLCA provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated SLCA.

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Eleonora Pelle, Taymeyah Al-Toubah, Brian Morse, and Jonathan Strosberg

von Hippel-Lindau (VHL) disease is a rare autosomal-dominant hereditary disease characterized by mutation of the VHL gene. This gene encodes for the VHL protein, which regulates the activity of HIF-α, a transcription factor involved in the cellular response to hypoxia. Mutations in VHL lead to the accumulation of HIF-α and, consequently, the engagement of hypoxia-sensitive genes with tumorigenic effects. VHL disease is associated with the development of tumors in multiple organs, including pancreatic neuroendocrine tumors (pNETs). Belzutifan is an HIF-α inhibitor; however, it has not been previously evaluated in patients with metastatic or treatment-refractory pNETs. This report presents a 43-year-old woman with VHL-associated metastatic pNET treated with belzutifan after progression on multiple systemic therapies. She began treatment with belzutifan and experienced partial radiographic response within 1 month of treatment. Other than asymptomatic anemia, no adverse effects developed during 5 months of ongoing therapy. Belzutifan is an inhibitor of HIF-2α that targets the underlying pathophysiology of VHL-associated pNETs. Our case report describes exceptional activity in a metastatic pNET arising from VHL.

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Marieke Pape, Steven C. Kuijper, Pauline A.J. Vissers, Laurens V. Beerepoot, Geert-Jan Creemers, Hanneke W.M. van Laarhoven, and Rob H.A. Verhoeven

Background: In recent years, clinical trials have shown improved survival of patients with metastatic esophageal or gastric cancer. The number of patients participating in clinical trials is limited, and survival improvements observed from clinical trials are unrepresentative for the full population. The aim of our study was to assess trends in survival for the best-case, typical, and worst-case scenarios in patients with metastatic esophageal or gastric cancer. Methods: We selected patients with metastatic esophageal or gastric cancer diagnosed between 2006 and 2020 from the nationwide Netherlands Cancer Registry. Survival was calculated for different percentiles of the survival curve for each incidence year (eg, the 10th percentile [p10] represents the top 10% of patients with the best survival): p10 (best-case), p25 (upper-typical), p50 (median), p75 (lower-typical), and p90 (worst-case). Weighted linear regression analyses were performed to test whether changes in survival were significant. Results: The overall median survival between 2006 and 2020 remained unchanged for patients with esophageal cancer (n=10,448; from 5.2 to 5.2 months, respectively; P=.06) and improved for patients with gastric cancer (n=10,512; from 3.5 to 4.3 months, respectively; P=.001). For patients with esophageal cancer, survival for the best-case scenario (p10; best 10% of patients) significantly improved from 17.2 to 21.0 months (P=.006). For patients with gastric cancer, survival significantly improved for the best-case scenario (p10) from 15.9 to 23.5 months (P<.001) and the upper-typical scenario (p25) scenario improved from 7.9 to 9.9 months (P<.001). Conclusions: Despite significant survival improvements in clinical trials, survival improvements were not observed for the majority of patients treated in daily clinical practice. An increase in survival was only observed for patients with the best prognosis.

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Alexandra M. Miller and Matthias A. Karajannis

Most pediatric central nervous system (CNS) tumors are located in eloquent anatomic areas, making surgical resection and, in some cases, even biopsy risky or impossible. This diagnostic predicament coupled with the move toward molecular classification for diagnosis has exposed an urgent need to develop a minimally invasive means to obtain diagnostic information. In non-CNS solid tumors, the detection of circulating tumor DNA (ctDNA) in plasma and other bodily fluids has been incorporated into routine practice and clinical trial design for selection of molecular targeted therapy and longitudinal monitoring. For primary CNS tumors, however, detection of ctDNA in plasma has been challenging. This is likely related at least in part to anatomic factors such as the blood–brain barrier. Due to the proximity of primary CNS tumors to the cerebrospinal fluid (CSF) space, our group and others have turned to CSF as a rich alternative source of ctDNA. Although multiple studies at this time have demonstrated the feasibility of CSF ctDNA detection across multiple types of pediatric CNS tumors, the optimal role and utility of CSF ctDNA in the clinical setting has not been established. This review discusses the work-to-date on CSF ctDNA liquid biopsy in pediatric CNS tumors and the associated technical challenges, and reviews the promising opportunities that lie ahead for integration of CSF ctDNA liquid biopsy into clinical care and clinical trial design.