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TOPLINE:

In patients with localized pancreatic ductal adenocarcinoma (PDAC), failure to undergo resection following neoadjuvant chemotherapy is common and associated with worse survival. Researchers identified few risk factors associated with failing to undergo surgical resection but did highlight weight loss during neoadjuvant therapy as one significant factor.

METHODOLOGY:

• Surgical resection after neoadjuvant therapy offers significant survival benefits in patients with PDAC, so it is crucial to identify and address factors that lead patients to forgo surgery.
• To evaluate risk factors associated with forgoing surgical resection following neoadjuvant chemotherapy, researchers conducted a secondary analysis of a phase 2 study, in which two chemotherapy regimens were compared in 102 patients with resectable PDAC.
• Overall, 73 patients (71.6%) had a successful pancreatectomy, while 29 patients (28.4%) did not undergo surgical resection. The reasons varied, with distant progression during neoadjuvant therapy (n = 11) and therapy-related toxicity (n = 9) being the most common factors, but occult metastatic disease (n = 3), patient preference (n = 2), complications during surgery (n = 1) also playing a role.

TAKEAWAY:

• Patients who underwent surgical resection had a longer median overall survival (23.8 vs 10.8 months) and 2-year survival rate (49.3% vs 24.2%; adjusted hazard ratio, 0.55).
• Weight loss during neoadjuvant chemotherapy was associated with 66% lower odds of undergoing surgical resection (odds ratio [OR], 0.34; 95% CI, 0.11-0.93).
• City size also appeared to be a factor, but one the researchers considered "unexpected and difficult to explain." Patients in midsize cities were much more likely to undergo surgery than those in small (OR, 0.24) or large (OR, 0.28) cities.
• Patients who did not undergo surgical resection also received fewer planned cycles of neoadjuvant chemotherapy (mean dose density, 0.84 for resection vs 0.56 for no resection; P < .001). Many other factors — age, sex, race, body mass index, performance status, insurance type, geographic region, treatment arm, tumor location, chemotherapy delays or modifications, and hospital characteristics — were not associated with failure to undergo surgical resection.

IN PRACTICE:

In the current analysis, the researchers confirmed that patients who do not undergo surgery after starting neoadjuvant therapy experience worse overall survival but "identified few predictive factors" to explain this attrition. Weight loss during neoadjuvant therapy was one key factor "independently associated with reduced odds of undergoing surgical resection," the authors wrote, adding that "further research must focus on risk factors for severe toxicities during [neoadjuvant therapy] that preclude surgical resection."

SOURCE:

This study, led by Jordan M. Cloyd, MD, The Ohio State University Wexner Medical Center, was published online on April 29 in Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

An attempt at a subset analysis of the nine patients who experienced attrition due to toxicity was limited by the small sample size. The study used any weight loss during chemotherapy rather than specific amounts or percentage. Changes in imaging results and performance status during the study period were not documented. Data on CA 19-9 levels, an important prognostic marker and predictor of resectability, were not available.

DISCLOSURES:

National Cancer Institute of the National Institutes of Health supported this study. One author disclosed financial ties to multiple pharmaceutical and biotechnology companies. Other authors declared no competing interests.