Highlights of the NCCN Oncology Research Program
An Infant-Type Hemispheric Glioma With SOX5::ALK: A Novel Fusion
Chia Chin Tsai, Man-Hsu Huang, Chia-Lang Fang, Kevin Li-Chun Hsieh, Tsung-Han Hsieh, Wan-Ling Ho, Hsi Chang, Min-Lan Tsai, Yu-Chien Kao, James S. Miser, Tai-Tong Wong, Min-Yu Su, and Yen-Lin Liu
Infant-type hemispheric glioma (IHG) is a rare pediatric brain tumor with variable response to chemotherapy and radiotherapy. Molecular insights into IHG can be useful in identifying potentially active targeted therapy. A male fetus was found to have congenital hydrocephalus at the gestational age of 37 weeks. Fetal MRI showed a 2.6 × 2.0-cm tumor located at the frontal horn of the left lateral ventricle, involving the left basal nuclei and thalamus. Tumor biopsy at the age of 2 days revealed an IHG consisting of spindle tumor cells with strong expression of GFAP and ALK. Targeted RNA sequencing detected a novel fusion gene of SOX5::ALK. After initial chemotherapy with cyclophosphamide, carboplatin, and etoposide for 2 cycles, the tumor size progressed markedly and the patient underwent a subtotal resection of brain tumor followed by treatment with lorlatinib, an ALK tyrosine kinase inhibitor with central nervous system (CNS) activity. After 3 months of treatment, reduction of tumor size was observed. After 14 months of treatment, partial response was achieved, and the infant had normal growth and development. In conclusion, we identified a case of congenital IHG with a novel SOX5::ALK fusion that had progressed after chemotherapy and showed partial response and clinical benefit after treatment with the CNS-active ALK inhibitor lorlatinib.
Navigating the Management of Chronic Phase CML in the Era of Generic BCR::ABL1 Tyrosine Kinase Inhibitors
Fadi G. Haddad and Hagop Kantarjian
Over the past several years, advances in research, treatment, and market dynamics have impacted treatment strategies in chronic myeloid leukemia in chronic phase (CML-CP). They include the broader availability of cost-effective generic imatinib, and soon other generic second-generation tyrosine kinase inhibitors (TKIs). Access to affordable generics means that all patients with CML-CP should have access to safe and highly effective lifelong therapies. When overall survival is the treatment endpoint, imatinib provides a good treatment value. Second-generation TKIs may be the best frontline strategy when treatment-free remission is the goal. Recent studies have shown maintained efficacy and reduced toxicity when TKIs are used at reduced dosing. Reduced-dose schedules of second-generation TKIs (which are less toxic and induce faster deep molecular responses) may render generic second-generation TKIs a more attractive treatment option. Adjusting the dose of TKI in the presence of mild-to-moderate, or even severe but reversible, adverse events may be preferable to switching to a different TKI. The selection of second-line and beyond therapies depends on the evolving patterns observed with frontline treatment. Dose-adjusted ponatinib schedules have demonstrated improved efficacy and safety in patients resistant to second-generation TKIs or those with T315I-mutated disease. For asciminib, longer-term follow-up is needed to better evaluate its safety and efficacy compared with ponatinib. Allogeneic stem cell transplantation represents a valid alternative to newer-generation TKIs, with a better treatment value when TKIs are priced at >$40,000/year.
NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024
Featured Updates to the NCCN Guidelines
Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Ajjai Alva, Hilary Bagshaw, Michael Baine, Kathryn Beckermann, Maria I. Carlo, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Arpita Desai, Yasser Ged, Saby George, John L. Gore, Andrew Gunn, Naomi Haas, Michael Johnson, Payal Kapur, Jennifer King, Christos Kyriakopoulos, Elaine T. Lam, Primo N. Lara, Clayton Lau, Bryan Lewis, David C. Madoff, Brandon Manley, M. Dror Michaelson, Amir Mortazavi, Lee Ponsky, Sundhar Ramalingam, Brian Shuch, Zachary L. Smith, Jeffrey Sosman, Randy Sweis, Matthew Zibelman, Ryan Schonfeld, MaryElizabeth Stein, and Lisa A. Gurski
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.
Patient-Centered Decision-Making in Metastatic Breast Cancer Care Delivery: A Call to Action
Gabrielle B. Rocque, Manali I. Patel, Lauren P. Wallner, Stacy C. Bailey, Rebekkah Schear, Christine M. Gunn, Jamil Rivers, Rozanne Wilson, Emily C. Freeman, Trudy L. Buckingham, Suepattra G. May, and Arif H. Kamal
Thank You to 2023 JNCCN Reviewers
Value of Size and Malignant Features of Lateral Lymph Nodes in Risk Stratification at Lateral Local Recurrence of Rectal Cancer: A National Cohort Study
Eline G.M. van Geffen, Tania C. Sluckin, Sanne-Marije J.A. Hazen, Karin Horsthuis, Regina G.H. Beets-Tan, Susan van Dieren, Corrie A.M. Marijnen, Pieter J. Tanis, and Miranda Kusters
Background: Patients with rectal cancer who have enlarged lateral lymph nodes (LLNs) have an increased risk of lateral local recurrence (LLR). However, little is known about prognostic implications of malignant features (internal heterogeneity, irregular margins, loss of fatty hilum, and round shape) on MRI and number of enlarged LLNs, in addition to LLN size. Methods: Of the 3,057 patients with rectal cancer included in this national, retrospective, cross-sectional cohort study, 284 with a cT3–4 tumor located ≤8 cm from the anorectal junction who received neoadjuvant treatment and who had visible LLNs on MRI were selected. Imaging was reassessed by trained radiologists. LLNs were categorized based on size. Influence of malignant features and the number of LLNs on LLR was investigated. Results: Of 284 patients with at least 1 visible LLN, 122 (43%) had an enlarged node (≥7.0 mm) and 157 (55%) had malignant features. Of the 122 patients with enlarged nodes, 25 had multiple (≥2). In patients with a single enlarged node (n=97), a single malignant feature was associated with a 4-year LLR rate of 0% and multiple malignant features was associated with a rate of 17% (P=.060). In the group with multiple malignant features, their disappearance on restaging was associated with an LLR rate of 13% compared with an LLR rate of 20% for persistent malignant features (P=.532). The presence of intermediate-size LLNs (5.0–6.9 mm) with at least 1 malignant feature was associated with a 4-year LLR rate of 8%; the 4-year LLR rate was 13% when the malignant features persisted on restaging MRI (P=.409). Patients with multiple enlarged LLNs had a 4-year LLR rate of 28% compared with 11% for those with a single enlarged LLN (P=.059). Conclusions: The presence of multiple enlarged LLNs (≥7.0 mm), as well as multiple malignant features in an enlarged node contribute to the risk of developing an LLR. These radiologic features can be used for clinical decision-making regarding the potential benefit of LLN dissection.
Associations Among Optimal Lung Cancer Treatment, Clinical Outcomes, and Health Care Utilization in Patients Who Underwent Comprehensive Genomic Profiling
Adam C. Powell, Elifnur Yay Donderici, Nicole J. Zhang, Shaun P. Forbes, Julie Wiedower, Amy C. McNeal, and Mark D. Hiatt
Background: Although immune checkpoint inhibitor immunotherapies are contraindicated as first-line treatment of advanced non–small cell lung cancer (NSCLC) in patients with ALK rearrangement and EGFR mutation, many receive them. The purpose of this study was to examine the association between optimal first-line treatment in this population and clinical outcomes. Methods: Claims and genomic data from patients with advanced or metastatic NSCLC were extracted from a nationally representative GuardantINFORM dataset. Patients who had their first claim mentioning advanced or metastatic NSCLC between March 2019 and February 2020 and had ALK rearrangement or EGFR mutation detected by comprehensive genomic profiling were included in this study. Patients were classified as having received optimal or suboptimal first-line treatment. Claims were reviewed to determine real-world time to next treatment, real-world time to discontinuation, and health services utilization (emergency department, inpatient, and outpatient) in the 12 months following first-line treatment initiation. Survival analyses were conducted using Kaplan-Meier plots and Cox proportional hazard models. Health services utilization was compared between the groups using t tests and negative binomial models. Results: Of the 359 patients included, 280 (78.0%) received optimal first-line treatment. Optimally treated patients had longer median real-world time to next treatment (11.2 vs 4.4 months; P<.01) and real-world time to discontinuation (10.4 vs 1.9 months; P<.01). The optimal group had significantly fewer emergency department presentations (0.76 vs 1.27; P<.01) and outpatient visits (22.9 vs 42.7; P<.01) than the suboptimal group but did not significantly differ in inpatient utilization. Adjusted utilization analysis yielded similar findings. Conclusions: Patients with NSCLC who received optimal treatment, as determined by comprehensive genomic profiling using next-generation sequencing–based circulating tumor DNA testing (Guardant360), had significantly superior clinical and utilization outcomes, reinforcing existing guidelines recommending profiling at the onset of treatment.
Development of a Strategic Initiative at MD Anderson Cancer Center to Improve Outcomes in Immune-Related Adverse Events
Sarah E. Fayle, Nicolas L. Palaskas, Bilal A. Siddiqui, Jennifer L. McQuade, Jamie S. Lin, Sumit K. Subudhi, Anisha B. Patel, Robert R. Jenq, Amishi Y. Shah, Amy R. Spelman, Mianen Sun, Bettina H. Marble, and Yinghong Wang
Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for many cancer types. The clinical use of ICIs is increasing rapidly, including in combinations associated with increased risk of toxicities, termed “immune-related adverse events” (irAEs). Therefore, MD Anderson Cancer Center (MDACC) in Houston, Texas has proactively responded by developing a priority endeavor known as the Immuno-Oncology Toxicity (IOTOX) initiative. This strategic initiative aims to facilitate the seamless integration of key domains: (1) standardized clinical practice and innovative decision toolsets; (2) patient and provider education; and (3) a comprehensive clinical and translational research platform. The ultimate goal of this initiative is to develop and disseminate clinical best practices and biologic insights into irAEs to improve outcomes of patients with irAEs at MDACC and in the wider oncology community.