ASO Author Reflections: Does Adjuvant Therapy Confer a Survival Benefit in Patients Receiving Neoadjuvant Chemotherapy f
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ASO AUTHOR REFLECTIONS
ASO Author Reflections: Does Adjuvant Therapy Confer a Survival Benefit in Patients Receiving Neoadjuvant Chemotherapy for Pancreatic Cancer? A CA19-9 Analysis Hao Liu, MD PhD, and Amer Zureikat, MD Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
PAST Pancreatic resection followed by adjuvant therapy (AT) is the current standard of care for pancreatic adenocarcinoma (PDAC). However, a significant proportion of patients are unable to receive or complete AT due to postoperative morbidity.1 This, coupled to the realization that PDAC is a systemic disease at diagnosis, has led to increasing interest in a neoadjuvant therapy (NAT) approach. NAT can downstage tumors, increase R0 resection rates, treat micrometastatic disease, and allow a greater proportion of patients to complete multimodality treatment.2 Despite the enthusiasm for NAT, consensus on the optimal perioperative chemotherapy strategy in localized PDAC remains under debate. Specifically, it is unclear whether patients who receive NAT will benefit from additional AT. PRESENT We proposed that CA19-9 response to NAT can serve as a surrogate for systemic chemotherapy response in patients with elevated CA19-9 levels, and may guide the need for further AT following resection.3 Our results suggest that the magnitude of CA19-9 response during NAT may predict additional survival benefit (or lack thereof) from AT. We demonstrated that AT was not associated with additional survival benefit when a large CA19-9 decline (normalization and decrease of [ 50%) was observed
during NAT. Conversely, AT was only associated with a survival benefit in patients with a suboptimal CA19-9 response (no normalization and decrease \ 50%) during NAT. Although these findings require validation, they provide new insight into the role of NAT and AT in optimizing survival in PDAC. FUTURE The future of personalized PDAC management depends on the ability to measure and predict treatment response. Rather than focusing on specific regimens or duration of NAT, our data suggest that CA19-9 response may guide how much systemic therapy is needed for localized pancreatic cancer. CA19-9 however has limitations; it is not expressed in patients with certain Lewis antigen phenotypes and can be influenced by the presence of obstructive jaundice. Other potential biomarkers of response are needed, including tumor genetics and heterogeneity, circulating tumor cells, and circulating tumor DNA.4 The tumor microenvironment (TME) may also influence PDAC treatment response. Stromal marker biophysical properties, vascular perfusion characteristics, tumor-infiltrating immune cell function, and tumor microenvironment metabolites are all are being investigated and show great promise.5 Further studies are needed to validate those novel markers and incorporate them with CA19-9 to guide multimodality treatment of pancreatic cancer. DISCLOSURES
The authors declare no conflicts of interest.
REFERENCES Ó Society of Surgical Oncology 2020 First Received: 19 April 2020
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