Nick C Levinsky1, Mackenzie C Morris1, Koffi Wima1, Jeffrey J Sussman1, Syed A Ahmad1, Jordan M Cloyd2, Charles Kimbrough2, Keith Fournier3, Andrew Lee3, Sean Dineen4, Sophie Dessureault4, Jula Veerapong5, Joel M Baumgartner5, Callisia Clarke6, Mohammad Y Zaidi7, Charles A Staley7, Shishir K Maithel7, Jennifer Leiting8, Travis Grotz8, Laura Lambert9, Ryan J Hendrix9, Sean Ronnekleiv-Kelly10, Courtney Pokrzywa10, Mustafa Raoof11, Oliver S Eng11, Fabian M Johnston12, Jonathan Greer12, Sameer H Patel13. 1. Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way ML-0558, Cincinnati, OH, 45267-0558, USA. 2. Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. 3. Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Department of Gastrointestinal Oncology, Moffitt Cancer Center, Department of Oncologic Sciences, Morsani College of Medicine, Tampa, FL, USA. 5. Division of Surgical Oncology, Department of Surgery, University of California, San Diego, CA, USA. 6. Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. 7. Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA. 8. Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA. 9. Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA. 10. Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA. 11. Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA. 12. Department of Surgery, Johns Hopkins University, Baltimore, MD, USA. 13. Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way ML-0558, Cincinnati, OH, 45267-0558, USA. patel5se@ucmail.uc.edu.
Abstract
BACKGROUND: Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC. METHODS: The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed. RESULTS: Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p < 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI > 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA. CONCLUSION: While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved.
BACKGROUND:Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC. METHODS: The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed. RESULTS: Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p < 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI > 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA. CONCLUSION: While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved.
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