Despite the use of first-line therapies like fluoropyrimidine and platinum-based cytotoxic chemotherapy, gastric cancer (GC) continues to carry a poor prognosis. Recent subgroup analyses of first-line phase III trials have demonstrated that patients with microsatellite instability–high (MSI-H) metastatic GC derive significant improvement in survival rates when immune checkpoint inhibitors (ICIs) are combined with chemotherapy compared with chemotherapy alone. However, it remains to be seen whether the success of ICIs in the metastatic setting can be translated into earlier stages of GC with resectable disease. We report 6 cases of locally advanced, nonmetastatic MSI-H GC that all demonstrated favorable response following treatment with pembrolizumab in addition to neoadjuvant chemotherapy. With the exception of immune-related colitis in one patient, pembrolizumab was well-tolerated. To our knowledge, this is the first reported US case series of patients treated with an ICI in combination with neoadjuvant chemotherapy for advanced, nonmetastatic, resectable or unresectable MSI-H GC.
Louisa Liu, Yanghee Woo, Massimo D’Apuzzo, Laleh Melstrom, Mustafa Raoof, Yu Liang, Michelle Afkhami, Stanley R. Hamilton, and Joseph Chao
Rebecca A. Vanderwall, Alison Schwartz, Lindsay Kipnis, Catherine M. Skefos, Samantha M. Stokes, Nizar Bhulani, Michelle Weitz, Rebecca Gelman, Judy E. Garber, and Huma Q. Rana
Background: Cancer family history is a vital part of cancer genetic counseling (GC) and genetic testing (GT), but increasing indications for germline cancer GT necessitate less labor-intensive models of collection. We evaluated the impact of GC on patient pedigrees generated by an electronic cancer family history questionnaire (eCFHQ). Methods: An Institutional Review Board–approved review of pedigrees collected through an eCFHQ was conducted. Paired pre-GC and post-GC pedigrees (n=1,113 each group) were analyzed independently by cancer genetic counselors for changes in patient-reported clinical history and to determine whether the pedigrees met NCCN GT criteria. Discrepancy in meeting NCCN GT criteria between pre-GC and post-GC pedigrees was the outcome variable of logistic regressions, with patient and family history characteristics as covariates. Results: Overall, 780 (70%) patients had cancer (affected), 869 (78%) were female, and the median age was 57 years (interquartile range, 45–66 years; range, 21–91 years). Of the 1,113 pairs of pre-GC and post-GC pedigrees analyzed, 85 (8%) were blank, 933 (84%) were not discrepant, and 95 (9%) were discrepant in meeting any NCCN GT criteria. Of the discrepant pedigrees, n=79 (83%) became eligible for testing by at least one of the NCCN GT criteria after GC. Patients with discrepant pedigrees were more likely to report no or unknown history of GT (odds ratio [OR], 4.54; 95% CI, 1.66–18.70; P=.01, and OR, 18.47; 95% CI, 5.04–88.73; P<.0001, respectively) and belonged to racially and/or ethnically underrepresented groups (OR, 1.91; 95% CI, 1.08–3.25; P=.02). Conclusions: For most patients (84%), a standalone eCFHQ was sufficient to determine whether NCCN GT criteria were met. More research is needed on the performance of the eCFHQ in diverse patient populations.
Featured Updates to the NCCN Guidelines
Thomas W. Flaig, Philippe E. Spiess, Michael Abern, Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Kevin Chan, Sam Chang, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Harry W. Herr, Jean Hoffman-Censits, Amar Kishan, Shilajit Kundu, Subodh M. Lele, Ronac Mamtani, Vitaly Margulis, Omar Y. Mian, Jeff Michalski, Jeffrey S. Montgomery, Lakshminarayanan Nandagopal, Lance C. Pagliaro, Mamta Parikh, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Mark A. Preston, Kyle Richards, Wade J. Sexton, Arlene O. Siefker-Radtke, Matthew Tollefson, Jonathan Tward, Jonathan L. Wright, Mary A. Dwyer, Carly J. Cassara, and Lisa A. Gurski
The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non–muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non–muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody–drug conjugates for metastatic bladder cancer.
Bharathi Muthusamy, Pradnya D. Patil, and Nathan A. Pennell
Despite remarkable treatment advancements in patients with advanced non–small cell lung cancer (NSCLC), recurrence rates for those with resectable, early-stage disease remains high. Immune checkpoint inhibitors and targeted therapies are 2 promising treatment modalities that may improve survival outcomes for patients with resected NSCLC when moved from the advanced stage to the curable setting. There are many clinical studies that have evaluated or are currently evaluating immunotherapy or targeted therapy in the perioperative setting, and recent trials such as CheckMate 816, ADAURA, and IMpower010 have led to new approvals and demonstrated the promise of this approach. This review discusses recent and ongoing neoadjuvant and adjuvant systemic therapy trials in NSCLC, and where the field may be going in the near future.
Caitlin A. Hester, Giampaolo Perri, Laura R. Prakash, Jessica E. Maxwell, Naruhiko Ikoma, Michael P. Kim, Ching-Wei D. Tzeng, Brandon Smaglo, Robert Wolff, Milind Javle, Michael J. Overman, Jeffrey E. Lee, and Matthew H.G. Katz
Background: This study aimed to determine the clinical relevance of putative radiographic and serologic metrics of chemotherapy response in patients with localized pancreatic cancer (LPC) who do not undergo pancreatectomy. Studies evaluating the response of LPC to systemic chemotherapy have focused on histopathologic analyses of resected specimens, but such specimens are not available for patients who do not undergo resection. We previously showed that changes in tumor volume and CA 19-9 levels provide a clinical readout of histopathologic response to preoperative therapy. Methods: Our institutional database was searched for patients with LPC who were treated with first-line chemotherapy between January 2010 and December 2017 and did not undergo pancreatectomy. Radiographic response was measured using RECIST 1.1 and tumor volume. The volume of the primary tumor was compared between pretreatment and posttreatment images. The percentage change in tumor volume (%Δvol) was calculated as a percentage of the pretreatment volume. Serologic response was measured by comparing pretreatment and posttreatment CA 19-9 levels. We established 3 response groups by combining these metrics: (1) best responders with a decline in %Δvol in the top quartile and in CA 19-9, (2) nonresponders with an increase in %Δvol and in CA 19-9, and (3) other patients. Results: This study included 329 patients. Individually, %Δvol and change in CA 19-9 were associated with overall survival (OS) (P≤.1), but RECIST 1.1 was not. In all, 73 patients (22%) were best responders, 42 (13%) were nonresponders, and there were 214 (65%) others. Best responders lived significantly longer than nonresponders and others (median OS, 24 vs 12 vs 17 months, respectively; P<.01). A multivariable model adjusting for type of chemotherapy regimen, number of chemotherapy doses, and receipt of radiotherapy showed that best responders had longer OS than did the other cohorts (hazard ratio [HR], 0.35; 95% CI, 0.21–0.58 for best responders, and HR, 0.55; 95% CI, 0.37–0.83 for others). Conclusions: Changes in tumor volume and serum levels of CA 19-9—but not RECIST 1.1—represent reliable metrics of response to systemic chemotherapy. They can be used to counsel patients and families on survival expectations even if pancreatectomy is not performed.
Brooke E. Wilson, Sallie-Anne Pearson, Michael B. Barton, and Eitan Amir
Background: It is unknown how often regional differences in oncology trials are observed. Based on our study findings, we quantified regional variation in registration studies in oncology and developed a question guide to help clinicians evaluate regional differences. Methods: Using FDA archives, we identified registration studies in solid tumor malignancies from 2010 to 2020. We extracted the baseline study characteristics and participating countries and determined whether the primary publication reported a regional subgroup analysis. For studies presenting outcomes stratified by region, we extracted the stratified hazard ratios (HRs) and extracted or calculated the test for heterogeneity. We performed a random effects meta-analysis and a pairwise comparison to determine whether outcomes differed between high-income versus mixed-income regions. Results: We included 147 studies in our final analysis. Studies supporting FDA drug approval have become increasingly multinational over time (β = 0.5; P=.04). The median proportion of countries from high-income groups was 81.2% (range, 44%–100%), with no participation from low-income countries in our cohort. Regional subgroup analysis was presented for 78 studies (53%). Regional heterogeneity was found in 17.8% (8/45) and 18% (8/44) of studies presenting an overall survival (OS) and progression-free survival endpoint, respectively. After grouping regions by income level, we found no difference in OS outcomes in high-income regions compared with mixed-income regions (n=20; HR, 0.95; 95% CI, 0.84–1.07). To determine whether regional variation is genuine, clinicians should evaluate the data according to the following 5 questions: (1) Are the regional groupings logical? (2) Is the regional difference on an absolute or relative scale? (3) Is the regional difference consistent and plausible? (4) Is the regional difference statistically significant? (5) Is there a clinical explanation? Conclusions: As registration studies in oncology become increasingly international, regional variations in trial outcomes may be detected. The question guide herein will help clinicians determine whether regional variations are likely to be clinically meaningful or statistical anomalies.
Robert I Haddad, Lindsay Bischoff, Douglas Ball, Victor Bernet, Erik Blomain, Naifa Lamki Busaidy, Michael Campbell, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Whitney S. Goldner, Theresa Guo, Megan Haymart, Shelby Holt, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Dominick M. Lamonica, Susan Mandel, Stephanie Markovina, Bryan McIver, Christopher D. Raeburn, Rod Rezaee, John A. Ridge, Mara Y. Roth, Randall P. Scheri, Jatin P. Shah, Jennifer A. Sipos, Rebecca Sippel, Cord Sturgeon, Thomas N. Wang, Lori J. Wirth, Richard J. Wong, Michael Yeh, Carly J. Cassara, and Susan Darlow
Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).