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.
Alexandra M. Miller and Matthias A. Karajannis
Yi-Nong Chen, Ching-Wen Chiang, Yu-Hsiang Tsai, Wan-Ming Chen, Mingchih Chen, Ben-Chang Shia, Chun-Chi Huang, and Szu-Yuan Wu
Background: Whether preexisting sarcopenia is an independent risk factor for postoperative pneumonia (POP) for patients with oral cavity squamous cell carcinoma (OCSCC) remains unclear. Therefore, we conducted a propensity score–matched population-based cohort study to compare the risk of acute and late POP for patients with sarcopenic and nonsarcopenic OCSCC who underwent curative surgery. Patients and Methods: We included patients with OCSCC who underwent curative surgery and categorized them into 2 groups depending on whether they had preexisting sarcopenia. The patients in the sarcopenic and nonsarcopenic groups were matched at a ratio of 2:1. Results: The matching process yielded 16,257 patients (10,822 without sarcopenia and 5,435 with sarcopenia). In multivariate Cox regression analyses, the adjusted hazard ratio of POP for the group with OCSCC with preexisting sarcopenia was 1.20 (95% CI, 1.14–1.26; P<.0001) compared with the nonsarcopenic group. Among the patients with OCSCC who received curative surgery, those in the sarcopenic group exhibited a higher POP risk than those in the nonsarcopenic group for the following postoperative time periods: 31st to 90th day, 91st day to first year, first to second year, second to third year, third to fourth year, and fourth to fifth year. Conclusions: The high incidence of pneumonia persists for a long time in patients with OCSCC who receive curative surgery; this high incidence may even persist for 5 years after surgery, especially in patients with sarcopenia. For susceptible patients who are at risk for OCSCC, sarcopenia prevention measures (eg, exercise and early nutrition intervention) should be implemented.
Featured Updates to the NCCN Guidelines
Edward M. Schaeffer, Sandy Srinivas, Nabil Adra, Yi An, Daniel Barocas, Rhonda Bitting, Alan Bryce, Brian Chapin, Heather H. Cheng, Anthony Victor D’Amico, Neil Desai, Tanya Dorff, James A. Eastham, Thomas A. Farrington, Xin Gao, Shilpa Gupta, Thomas Guzzo, Joseph E. Ippolito, Michael R. Kuettel, Joshua M. Lang, Tamara Lotan, Rana R. McKay, Todd Morgan, George Netto, Julio M. Pow-Sang, Robert Reiter, Mack Roach III, Tyler Robin, Stan Rosenfeld, Ahmad Shabsigh, Daniel Spratt, Benjamin A. Teply, Jonathan Tward, Richard Valicenti, Jessica Karen Wong, Ryan A. Berardi, Dorothy A. Shead, and Deborah A. Freedman-Cass
The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, recurrent, and metastatic disease. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. These NCCN Guidelines Insights summarizes much of the panel’s discussions for the 4.2022 and 1.2023 updates to the guidelines regarding systemic therapy for metastatic prostate cancer.
Daneng Li, Can-Lan Sun, Heeyoung Kim, Christiana Crook, Ya-Han Zhang, Rebecca Allen, Richard Ballena, Shadman Hyder, Marianna Koczywas, Vincent Chung, Dean Lim, Vani Katheria, William Dale, and Gagandeep Singh
Background: Patient preferences (quantity vs quality of life; present vs future health) have not been investigated in patients with neuroendocrine tumors (NETs). The goal of this cross-sectional study was to evaluate patient values toward treatment goals and competing health outcomes among adults with NETs. Patients and Methods: Patients with well-differentiated, grade 1 or 2, advanced NETs starting a new systemic therapy completed 4 tools: (1) Health Outcomes Tool, which ranks the importance of 4 outcomes (survival, function/independence, freedom from pain, freedom from symptoms); (2) Attitude Scale, which identifies the extent to which patients agree with statements related to health outcomes; (3) Now versus Later Tool, which ranks the relative importance of quality of life (QoL) now versus 1 and 5 years from now; and (4) Prognosis and Treatment Perceptions Questionnaire, which identifies the amount of information the patient prefers to receive about their disease and treatment, the patient’s treatment goal, the patient’s perception of the physician’s treatment goal, and self-reported health status. Results: We recruited 60 patients with NETs (50.0% aged ≥65 years; 96.7% with stage IV disease). Primary tumor locations included the gastrointestinal tract (41.7%), pancreas (30.0%), and lung (21.7%). A plurality of patients reported maintaining independence as their most important health outcome (46.7%), followed by survival (30.0%), freedom from pain (11.7%), and freedom from symptoms (11.7%). A total of 67% of patients agreed with the statement, “I would rather live a shorter life than lose my ability to take care of myself”; 85.0% agreed with the statement, “It is more important to me to maintain my thinking ability than to live as long as possible.” When asked to choose between current QoL versus QoL 1 year or 5 years in the future as more important, 48.3% and 40.0% of patients valued their QoL 1 year and 5 years in the future, respectively, more than their current QoL. Only 51.7% of patients believed their physician’s treatment goals aligned with their own. Conclusions: Adult patients with NETs strongly value independence over survival. More communication between patients with NETs and their physicians is needed to ensure that patient preferences are incorporated into treatment plans.
Christina Teng, Venkatesha, Prunella L. Blinman, and Janette L. Vardy
Background: Chemotherapy-induced peripheral neuropathy (CIPN) can be a debilitating toxicity of oxaliplatin used for treatment of colorectal cancer (CRC). We aimed to assess CIPN symptoms and associations in our colorectal survivorship population and review the impact of neurotoxicity on dose delivery of oxaliplatin. Patients and Methods: Patients attending their first visit to the Sydney Cancer Survivorship Centre following completion of adjuvant treatment for CRC completed comprehensive patient-reported outcome measures, including symptoms, quality of life (QoL), alcohol intake, and exercise habits. Participants scored symptoms of “numbness or pins and needles” in hands or feet from 0 (no trouble at all) to 10 (worst I can imagine). Diagnosis, treatment, and comorbidity details were obtained from medical records. A subset of patients completed serial assessments of PN symptoms at follow-up visits. Results: Data were analyzed from 233 patients (52% male; mean age, 63 years) with CRC attending their first visit at the Sydney Cancer Survivorship Centre. A subset of 104 patients were included in the longitudinal analysis. The odds of patient-reported numbness were significantly higher in patients receiving oxaliplatin (odds ratio, 5.6; 95% CI, 3.2–9.8), with 72.4% of oxaliplatin-treated CRC survivors reporting numbness an average of 5.9 months after chemotherapy. Mean patient-reported numbness was significantly higher in those who received oxaliplatin-containing chemotherapy (mean, 3.31) compared with fluoropyrimidines alone (mean, 1.37) and no chemotherapy (mean, 0.66). Of the patients receiving oxaliplatin, 80% required dose reduction or early cessation, with PN the most common reason reported. QoL in physical, emotional, and functional well-being domains was lower in patients with numbness. We found a weak negative association between numbness score and age, and between (1) numbness and cardiovascular disease and (2) numbers and pain score. Conclusions: CIPN symptoms are common in CRC survivors who have received oxaliplatin and are associated with lower QoL. Neurotoxicity is underreported in clinical trials compared with real-world populations and is a major barrier to oxaliplatin treatment delivery.
Amar Gajjar, Anita Mahajan, Mohamed Abdelbaki, Clarke Anderson, Reuben Antony, Tejus Bale, Ranjit Bindra, Daniel C. Bowers, Kenneth Cohen, Bonnie Cole, Kathleen Dorris, Ralph Ermoian, Andrea Franson, Jeffrey Helgager, Daniel Landi, Chi Lin, Laura Metrock, Ronica Nanda, Joshua Palmer, Sonia Partap, Ashley Plant, Sumit Pruthi, Renee Reynolds, Paul Ruggieri, Duncan Stearns, Phillip Storm, Anthony Wang, Katherine Warren, Nicholas Whipple, Wafik Zaky, Nicole R. McMillian, and Lenora A. Pluchino
Central nervous system (CNS) cancers account for approximately one quarter of all pediatric tumors and are the leading cause of cancer-related death in children. More than 4,000 brain and CNS tumors are diagnosed each year in children and teens, and the incidence rate has remained stagnant in recent years. The most common malignant pediatric CNS tumors are gliomas, embryonal tumors consisting of predominately medulloblastomas, and germ cell tumors. The inaugural version of the NCCN Guidelines for Pediatric Central Nervous System Cancers focuses on the diagnosis and management of patients with pediatric diffuse high-grade gliomas. The information contained in the NCCN Guidelines is designed to help clinicians navigate the complex management of pediatric patients with diffuse high-grade gliomas. The prognosis for these highly aggressive tumors is generally poor, with 5-year survival rates of <20% despite the use of combined modality therapies of surgery, radiation therapy and systemic therapy. Recent advances in molecular profiling has expanded the use of targeted therapies in patients whose tumors harbor certain alterations. However, enrollment in a clinical trial is the preferred treatment for eligible patients.
Ahmed Bilal Khalid, Gerardo Calderon, Shadia I. Jalal, and Greg A. Durm
Background: Immune checkpoint inhibitors (ICIs) have been proven to be very effective in the treatment of multiple cancers. They have a unique side-effect profile distinct from conventional chemotherapy that can manifest as immune-related adverse events (irAEs). With expanding ICI use, clinicians will increasingly encounter irAEs, and thus adequate physician knowledge on their recognition and management is crucial. Methods: To assess physician knowledge of irAEs due to ICIs, an online survey was administered to resident physicians in internal medicine (IM), emergency medicine, and family medicine (FM), as well as to faculty physicians in IM and FM. Results: We sent the survey to 413 physicians and received responses from 155 (38%), of which 110 were residents and 45 were faculty. Pembrolizumab was identified as an ICI by 79% of physicians, nivolumab by 64%, and ipilimumab by 55%. Twenty-five percent incorrectly thought infliximab and adalimumab were ICIs. Most physicians (93%) were able to identify the gastrointestinal tract as an irAE site, whereas only 57% and 67% were able to identify cardiovascular and renal systems as irAE sites, respectively. A total of 59% believed steroids negatively affect efficacy of ICIs and should be used with caution to treat irAEs, 65% incorrectly thought endocrinopathies due to irAEs are usually reversible, and 45% of FM residents considered antibiotics as the mainstay of treatment in ICI-mediated colitis. On a self-rated scale from 0 to 100, the median comfort level for all physicians in recognizing irAEs was 15 and for treatment of irAEs was 10. Conclusions: Significant knowledge gaps exist among residents and faculty physicians across multiple specialties regarding the recognition and treatment of irAEs due to ICIs. Given that these physicians are usually the first point of contact with patients, physician education on identification and treatment of irAEs is needed. Early detection of these toxicities is critical for their resolution.