Kyuwan Lee, Aleksi Iukuridze, Tianhui He, Alysia Bosworth, Lanie Lindenfeld, Jennifer Berano Teh, Meagan Echevarria, Sophia Albanese, Liezl Atencio, Rusha Bhandari, F. Lennie Wong, Andrew S. Artz, Tanya Siddiqi, Liana Nikolaenko, Jasmine Zain, Matthew Mei, Geoffrey Shouse, Leslie L. Popplewell, Alex F. Herrera, L. Elizabeth Budde, Stephen J. Forman, and Saro H. Armenian
Background: The purpose of this study was to examine the association between baseline skeletal muscle measurements, acute toxicity (immune effector cell–associated neurotoxicity syndrome [ICANS], cytokine release syndrome), and treatment efficacy in patients undergoing CAR T-cell therapy for B-lineage lymphoma. Patients and Methods: Skeletal muscle measurements were obtained from automated CT measurements in 226 consecutive patients who received CAR T-cell therapy between 2015 and 2021. The Kaplan-Meier method was used to examine progression-free survival (PFS) and overall survival (OS) at 1-year. Multivariable regression was used to calculate the hazard ratio (HR) with 95% confidence intervals, adjusted for covariates. Results: The median age of the cohort was 63.1 years (range, 18.5–82.4 years), and most patients were male (66%) and had primary refractory disease (58%). Patients with abnormally low skeletal muscle at baseline were at greater risk of ICANS (HR, 1.74; 95% CI, 1.05–2.87) and had longer length of hospitalization (mean 27.7 vs 22.9 days; P<.05) compared with those with normal muscle mass. Abnormal skeletal muscle was independently associated with risk of disease progression (HR, 1.70; 95% CI, 1.11–2.57) and worse survival (HR, 2.44; 95% CI, 1.49–4.00) at 1 year compared with normal skeletal muscle. Individuals who had abnormal skeletal muscle and high lactate dehydrogenase (LDH) levels at baseline had poor 1-year PFS (17%) and OS (12%) compared with those with normal skeletal muscle and LDH levels (72% and 82%, respectively; P<.001). Patients who had abnormal skeletal muscle and LDH levels had a 5-fold risk (HR, 5.34; 95% CI, 2.97–9.62) of disease progression and a 10-fold risk (HR, 9.73; 95% CI, 4.81–19.70) of death (reference: normal skeletal muscle, normal LDH), independent of prior lines of therapy, extent of residual disease at time of CAR T-cell therapy, functional status, or product. Conclusions: This information can be used for risk stratification prior to CAR T-cell therapy or to implement prehabilitation and nutritional optimization before lymphodepletion as well as thereafter. These efforts will be complementary to ongoing efforts toward sustained efficacy after CAR T-cell therapy.
Jaffer A. Ajani, Thomas A. D’Amico, David J. Bentrem, David Cooke, Carlos Corvera, Prajnan Das, Peter C. Enzinger, Thomas Enzler, Farhood Farjah, Hans Gerdes, Michael Gibson, Patrick Grierson, Wayne L. Hofstetter, David H. Ilson, Shadia Jalal, Rajesh N. Keswani, Sunnie Kim, Lawrence R. Kleinberg, Samuel Klempner, Jill Lacy, Frank Licciardi, Quan P. Ly, Kristina A. Matkowskyj, Michael McNamara, Aaron Miller, Sarbajit Mukherjee, Mary F. Mulcahy, Darryl Outlaw, Kyle A. Perry, Jose Pimiento, George A. Poultsides, Scott Reznik, Robert E. Roses, Vivian E. Strong, Stacey Su, Hanlin L. Wang, Georgia Wiesner, Christopher G. Willett, Danny Yakoub, Harry Yoon, Nicole R. McMillian, and Lenora A. Pluchino
Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.
Samuel L. Cytryn and Yelena Y. Janjigian
HER2 is overexpressed in approximately 20% of esophagogastric cancer (EGC) cases. The addition of the anti-HER2 antibody, trastuzumab, to chemotherapy in 2010 was the first targeted treatment to demonstrate an improvement in survival. The aggressive nature and heterogeneous biology of EGC have posed a particular challenge and resulted in numerous negative trials without a change in standard of care for more than a decade. However, with the incorporation of dual HER2 and PD-1 blockade as well as the advent of a new, potent antibody–drug conjugate, trastuzumab deruxtecan, there have been 2 new FDA approvals for this patient population within the past 2 years. Consequently, the management and landscape of HER2-positive EGC is rapidly changing and increasingly optimistic.
Ahmed A. Hussein, Umar Iqbal, Zhe Jing, Yousuf Ramahi, Holly Houenstein, Stephanie Newman, Blake Peterson, Katarina Krajacic, Adeena Samoni, Bo Xu, Norbert Sule, Gissou Azabdaftari, Eric C. Kauffman, James L. Mohler, Michael Kuettel, and Khurshid A. Guru
Background: We sought to investigate the impact of an NCCN-compliant multidisciplinary conference on treatment decisions of patients with localized prostate cancer. Methods: A retrospective review of our quality assurance localized prostate cancer database was performed. All patients with localized prostate cancer who sought a second opinion at Roswell Park Comprehensive Cancer Center between 2009 and 2019 were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Multivariable regression models were fit to evaluate variables associated with concordance between community recommendations, LPCC recommendations, and treatment received by patients. Results: A total of 1,164 patients were identified, of whom 26% had NCCN very low-/low-risk, 27% had favorable intermediate-risk, 25% had unfavorable intermediate-risk, and 22% had high-/very high-risk prostate cancer. Pathology changed in 11% of patients after genitourinary pathologist review, which caused disease reclassification in 9%. Concordance between community and LPCC recommendations occurred in 78%, with lowest concordance for androgen deprivation therapy (21%) and radiotherapy (53%). Concordance between community recommendations and treatment received occurred in 65%, with lowest concordance for androgen deprivation therapy and radiotherapy; among those who were recommended radiotherapy as the only option by their community urologist, only 26% received it. Concordance between LPCC recommendations and treatment received occurred in 92%. Conclusions: Community recommendations differed from the multidisciplinary NCCN-compliant recommendations in 22% of patients, primarily for radiotherapy. Multidisciplinary recommendations matched the treatment received in 92% of patients compared with 65% for community recommendations.