Lymphopenia and spleen dose for patients with inoperable pancreatic cancer receiving ablative 5-fraction radiation therapy.
Authors: Chuong Michael David , Herrera Roberto , Carvallo Nicolas , Rubens Muni B. , Kotecha Rupesh , Hall Matthew , Mittauer Kathryn , Bassiri-Gharb Nema , Gutierrez Alonso , Kaiser Adeel 
Published: January 2024

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Background: Treatment-induced lymphopenia in pancreatic ductal adenocarcinoma (PDAC) patients after radiation therapy (RT) may negatively impact overall survival (OS). While non-ablative RT (NA-RT) is routine for borderline resectable (BRPC) and locally advanced (LAPC) PDAC, ablative RT (A-RT) has garnered increasing interest based on data suggesting improved clinical outcomes including OS. Absolute lymphocyte count (ALC) changes after A-RT and the potential association with spleen dose in this setting have not been previously described. Methods: We performed a single-institution retrospective analysis of BRPC, LAPC, and medically inoperable PDAC patients to evaluate ALC values 1 month before vs. 1-3 months after A-RT. All were treated with 5-fraction A-RT on a 0.35 T MR-Linac; the spleen was not considered an organ-at-risk during treatment planning. Lymphopenia was assessed using CTCAE version 5.0. Results: 101 patients were evaluated with median age 71 years (range 35-94 years), median maximum tumor size of 3.6 cm (range, 1.3-6.8 cm), and frequently tumor in the pancreas head (84.2%). Most had LAPC (61.4%) followed by BRPC (28.7%). Induction chemotherapy (ICT) was routine (89.1%), most commonly FOLFIRINOX (61.4%) with a median ICT duration of 5.2 months (range, 0.2-14.0 months). Median prescribed dose was 50 Gy (range, 40-50 Gy). The median mean spleen dose was 2.75 Gy (range, 0.38-16.79 Gy). The median spleen V5Gy, V10Gy, V15Gy, and V20Gy were 12.8% (range, 0 - 77.5%), 1.9% (range, 0 - 66.2%), 0% (range, 0 - 54.5%), and 0% (range, 0 - 39.2%), respectively. The median ALC at a median 25.5 days before A-RT was 1.39 no./mL (range, 0.24 - 3.00 no./mL), and this decreased to 0.85 no./mL (range, 0.20-2.45 no./mL) a median 6 weeks after A-RT. Grade 2 lymphopenia (G2L) prior to vs. after A-RT was 6.9% vs. 27.7% (p<0.001). Grade 3 lymphopenia (G3L) prior to vs. after A-RT was 1.0% vs. 13.9% (p<0.001). No grade 4+ lymphopenia was observed. Significant factors on multivariable analysis (MVA) for G2L were age (OR: 1.05, 95% CI 1.01-1.09, p=0.019), male vs. female (OR: 0.30, 95% CI:0.11-0.82, p=0.019), and T1-3 vs. T4 (OR: 0.27, 95% CI: 0.10-0.71, p=0.007); ICT duration, target volume dose/volume, and spleen dose were not significant on univariate analysis (UVA). No factors were significant on UVA for G3L, but a trend was observed for T1-3 vs. T4 (OR: 3.5, 95% CI: 0.91-13.42, p=0.067) and spleen V5Gy (OR: 1.44, 95% CI: 0.85-3.26, p=0.065). Conclusions: To our knowledge, this is the first study to evaluate spleen dose and ALC changes after A-RT for PDAC. We observed a similar incidence of grade 2+ lymphopenia compared to prior 5-fraction NA-RT studies. There was a trend towards significance of higher spleen V5Gy being associated with a higher probability of G3L. We are evaluating whether grade 2+ lymphopenia is associated with long-term clinical outcomes after A-RT for inoperable PDAC.