NEOADJUVANT THERAPY-INDUCED SARCOPENIA IS ASSOCIATED WITH DECREASED OVERALL SURVIVAL IN PANCREATIC DUCTAL ADENOCARCINOMA
Naomi M. Sell*, Carlos Fernandez-del Castillo, Cristina R. Ferrone, Keith Lillemoe, Thomas P. Hank, Colin D. Weekes, Martin Torriani, Colleen G. Buckless, Julie K. Silver, Florian J. Fintelmann, Motaz Qadan
Surgery, Massachusetts General Hospital, Boston, MA
Objective: There is an increased tendency towards use of neoadjuvant therapy (NAT) in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, NAT-related toxicity may exacerbate malnutrition and can lead to progressive weakness, weight loss, and major deconditioning prior to planned surgery. Loss of skeletal muscle mass, or sarcopenia, is known to limit postoperative recovery in patients with PDAC. However, the degree of skeletal muscle loss after NAT and its impact on overall survival (OS) are unknown.
Methods: All patients diagnosed with PDAC who underwent NAT followed by operative resection at a single institution between 01/01/2013 and 12/31/2017 were reviewed. Computed tomography (CT) scans were utilized to measure cross-sectional areas of skeletal muscle at the level of the fourth lumbar vertebra (L4). Skeletal muscle area (SMA) at L4 correlates with whole-body muscle and fat mass. Age-related sarcopenia is defined as loss of 5-8% of skeletal muscle mass over a decade. We defined NAT-related sarcopenia using these data over the NAT time-period. Patients were included if a CT scan was obtained prior to the start of NAT and at the conclusion of NAT before surgical resection.
Results: A total of 346 patients with PDAC underwent neoadjuvant chemotherapy and/or radiation followed by pancreatectomy. Of those, 164 patients had appropriate imaging available for radiographic review. Prior to starting NAT, men had an average SMA of 162.7cm2 and women had an average SMA of 102.7cm2. Following NAT, mean skeletal muscle mass loss was 3.5cm2.
There were 63 patients (38.4%) with ≥5% SMA loss and 44 patients (26.8%) who lost ≥8% SMA over the course of NAT. There was no difference in baseline demographics between patients who did and did not develop sarcopenia (Table 1). A loss of ≥8% SMA was associated with decreased two-year OS compared with the remainder of the group (45.5% vs. 63.3%, p=0.04). A loss of ≥5% SMA was similarly associated with decreased two-year OS (42.9% vs. 68.3%, p=0.001). In addition, there was an association with increased disease recurrence among patients who lost ≥5% SMA (63.5% vs. 45.0%, p=0.02). Finally, patients who lost ≥8% of their SMA had increased lymphovascular invasion rates (32.6% vs. 16.7%, p=0.03) and positive-margin resections (30.2% vs. 15.1%, p=0.03).
On logistic regression, even ≥5% SMA was associated with increased overall mortality (OR 2.42, CI 1.11-5.27, p=0.026, Table 2) and disease recurrence (OR 6.23, CI 2.91-13.3, p<0.001).
Conclusion: Neoadjuvant therapy-induced sarcopenia occurred in over one-third of patients undergoing NAT for PDAC, and was associated with increased disease recurrence and overall mortality, and reduced OS. Prehabilitation during NAT is a potential preventative measure to counteract sarcopenia that warrants further exploration.
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