Neoadjuvant Therapy Safe, Effective for Elderly Patients With Pancreatic Ductal Adenocarcinoma
Key findings
- This study evaluated the safety and efficacy of multimodal therapy of pancreatic ductal adenocarcinoma (PDAC) in older patients (those ≥75 years old), using three analyses representing different points in the continuum of PDAC care
- In a cohort of patients with non-metastatic PDAC who initiated FOLFIRINOX, there was no significant difference in the rate of proceeding to surgical exploration or the rate of tumor resectability between 40 older patients and 214 younger adults
- In a propensity score–matched cohort, 48 older patients who underwent neoadjuvant chemotherapy followed by surgical resection had significantly longer overall and recurrence-free survival than 48 older counterparts who had upfront surgical resection
- There was no significant difference in postoperative complication rates in the cohort described above or a propensity score–matched cohort of 54 older vs. 54 younger patients who had neoadjuvant therapy, with or without radiation, followed by surgery
- An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC
Several recent studies at high-volume surgical centers have confirmed the safety of surgical resection for elderly patients with pancreatic ductal adenocarcinoma (PDAC). Similarly, the administration of adjuvant chemotherapy has proved feasible for elderly patients with high-performance status.
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Now, researchers at Massachusetts General Hospital have demonstrated the safety and feasibility of delivering neoadjuvant chemotherapy followed by surgical resection in elderly patients with PDAC.
Guoliang Qiao, MD, PhD, a research fellow in the Department of Surgery, Motaz Qadan, MD, PhD, a pancreatic and liver surgeon at Mass General and deputy clinical director of the Mass General Cancer Center; the Gapontsev Family endowed chair in Surgical Oncology at Harvard Medical School, and colleagues report in the Annals of Surgery.
Methods
The researchers retrospectively provided three analyses of patients representing different points in the continuum of PDAC care. Older patients were defined as those ≥75 years of age. These were:
- Analysis 1—Comparison of 40 older patients vs. 214 younger patients who started FOLFIRINOX for non-metastatic PDAC between January 1, 2015, and September 30, 2020, including those who did not undergo later operative exploration.
- Analysis 2—Propensity score–matched comparison of 54 older vs. 54 younger patients who received neoadjuvant therapy (most often FOLFIRINOX), with or without radiation, followed by surgery at Mass General from March 1, 2007, to December 30, 2017.
- Analysis 3— Propensity score–matched comparison of 48 older patients who underwent neoadjuvant therapy followed by surgical resection vs. 48 older patients who had upfront surgery for PDAC between March 1, 2010, and December 31, 2017, at Mass General or between January 1, 2013, and December 31, 2016, at the University Medical Center Schleswig–Holstein in Germany.
In a propensity score–matched cohort, groups are matched on important covariates that may influence outcomes, to reduce the potential selection bias inherent in a non-randomized retrospective study.
Analysis 1
Compared with younger adults, older patients were significantly more likely to:
- Have a toxicity-related emergency room visit
- Require inpatient admission
- Be unable to complete the intended eight cycles of neoadjuvant FOLFIRINOX
However, older patients were not so deconditioned by neoadjuvant chemotherapy that they missed the opportunity to undergo surgery. Their surgical exploration and tumor resection rates were similar to those of younger adults.
Survival in Analyses 2 and 3
Median results for older patients who underwent neoadjuvant therapy followed by surgical resection were the following:
Compared with younger adults
- Significantly shorter overall survival (16.43 vs. 30.83 months; P=0.002)
- Similar recurrence-free survival (7.65 vs. 11.83 months; P=0.215)
Compared with older patients who underwent upfront surgical resection
- Better overall survival (15.78 vs. 11.51 months; P=0.037)
- Better recurrence-free survival (8.81 vs. 7.10 months; P=0.046)
Postoperative Complications in Analyses 2 and 3
The researchers reviewed rates of postoperative pancreatic fistula, delayed gastric emptying, biliary fistula, post-pancreatectomy hemorrhage, peripancreatic fluid collection, infectious complications, sepsis, pulmonary complications, cardiac complications, and surgical site infection.
In cohorts 2 and 3, there were no significant differences in the rates of major or minor postoperative complications between the groups being compared.
Support for Neoadjuvant Therapy
A recognized benefit of the chemotherapy-first strategy is to ensure delivery of much needed multimodal therapy, which is frequently omitted following surgery due to complications. This study adds to the support for offering an aggressive approach to older adults undergoing multimodal treatment of PDAC.
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