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Jeremy D. Kratz, Nataliya V. Uboha, Sam J. Lubner, Daniel L. Mulkerin, Linda Clipson, Yanyao Yi, Menggang Yu, Kristina A. Matkowskyj, Noelle K. LoConte and Dustin A. Deming

Background: Molecular profiles guide the clinical management of metastatic colorectal cancer (mCRC), particularly related to the use of anti–epidermal growth factor receptor (EGFR) antibodies. Tumor sidedness has also been implicated in resistance to these therapies, but has largely been studied in the first-line setting. We examined the role of tumor sidedness and disease bulk in predicting clinical outcomes to anti-EGFR therapy in the treatment-refractory setting. Methods: We identified a retrospective cohort of 62 patients with KRAS wild-type mCRC who received anti-EGFR therapy in the late-line setting. Response was assessed per RECIST 1.1, with bulky disease defined as any single lesion >35 mm in longest cross-sectional diameter or nodal short axis. Primary sidedness was defined in relation to the splenic flexure. Results: Patients with right-sided primary tumors at time of late-line EGFR therapy presented with increased tumor bulk and worsened overall survival (OS) relative to left-sided primary tumors. Tumor bulk, defined as either a categorical or continuous variable, predicted worsened progression-free survival (PFS) and OS, which persisted when controlling for differences in the primary tumor location. Within the right-sided cohort, no objective responses were observed for bulky disease or during treatment with anti-EGFR monotherapy. The nonbulky cohort experienced clinical benefit with anti-EGFR monotherapy, showing similar PFS and an improved response rate compared with sequential chemotherapy. Conclusions: In an effort to expand understanding of the role of primary sidedness in clinical response to anti-EGFR therapy, we identified sidedness and tumor bulk as potential predictive biomarkers of clinical response in late-line mCRC. Future prospective studies of EGFR targeting should consider tumor bulk in addition to molecular profiling in the identification of populations most likely to achieve meaningful clinical benefit.

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Margaret A. Tempero, Mokenge P. Malafa, Mahmoud Al-Hawary, Horacio Asbun, Andrew Bain, Stephen W. Behrman, Al B. Benson III, Ellen Binder, Dana B. Cardin, Charles Cha, E. Gabriela Chiorean, Vincent Chung, Brian Czito, Mary Dillhoff, Efrat Dotan, Cristina R. Ferrone, Jeffrey Hardacre, William G. Hawkins, Joseph Herman, Andrew H. Ko, Srinadh Komanduri, Albert Koong, Noelle LoConte, Andrew M. Lowy, Cassadie Moravek, Eric K. Nakakura, Eileen M. O'Reilly, Jorge Obando, Sushanth Reddy, Courtney Scaife, Sarah Thayer, Colin D. Weekes, Robert A. Wolff, Brian M. Wolpin, Jennifer Burns and Susan Darlow

Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

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Margaret A. Tempero, Mokenge P. Malafa, E. Gabriela Chiorean, Brian Czito, Courtney Scaife, Amol K. Narang, Christos Fountzilas, Brian M. Wolpin, Mahmoud Al-Hawary, Horacio Asbun, Stephen W. Behrman, Al B. Benson III, Ellen Binder, Dana B. Cardin, Charles Cha, Vincent Chung, Mary Dillhoff, Efrat Dotan, Cristina R. Ferrone, George Fisher, Jeffrey Hardacre, William G. Hawkins, Andrew H. Ko, Noelle LoConte, Andrew M. Lowy, Cassadie Moravek, Eric K. Nakakura, Eileen M. O’Reilly, Jorge Obando, Sushanth Reddy, Sarah Thayer, Robert A. Wolff, Jennifer L. Burns and Griselda Zuccarino-Catania

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.