Purpose/Objective(s): To determine whether radiation to the spleen with concurrent chemotherapy is associated with lymphopenia and ultimately worse survival outcomes in patients with locally advanced pancreatic cancer.

Materials/Methods: Retrospective review of 92 pancreatic cancer patients treated at Massachusetts General Hospital with neoadjuvant FOLFIRINOX for 8 cycles followed by consolidative pre-operative RT (median dose 50.4 Gy) with concurrent capecitabine and surgical resection (39%) from 2010-2016. Absolute lymphocyte count (ALC) was recorded at baseline, post-chemotherapy and post-RT. Basic clinical and demographic variables were collected for all patients. DVH parameters were collected for both spleen and liver.

Results: Median ALC was similar before and after neoadjuvant chemotherapy (1.4 vs. 1.3; p=0.23), but declined significantly after chemo-RT (1.4 vs. 0.6, p<0.001). Median hemoglobin (HgB, 12.9 vs. 11.6, p<0.001) and platelets (223.5 vs. 156.0, p<0.001) also significantly declined after chemo-RT. On multivariable logistic regression, higher risk of post-RT grade IV lymphopenia was associated with lower baseline ALC count (p=0.001), female gender (p=0.001), no surgical resection (p=0.03), and larger spleen volume (p=0.003). On multivariable Cox regression, at a median follow-up of 13.5 months, improved overall survival was associated with having a surgical resection (p=0.001), younger age (p=0.02), and lower spleen V5 (p=0.003), but not gender, pre/post-RT ALC or any other spleen/liver DVH parameters.

Conclusion: Chemo-RT for pancreatic cancer is associated with a significant decline in ALC. Gender, baseline ALC and spleen volume predict for post-treatment ALC. In our series, in the setting of FOLFIRINOX and improved rates of resection, ALC was not associated with overall survival. Table 1: Change in blood count over the course of treatment

	Baseline	Post-Chemo	Post-RT	Baseline vs. Post Chemo	Post-Chemo vs. Post-RT	Baseline vs. Post-RT
Lymphopenia
	71 (77%	68 (74%)	22 (24%)	P=0.72	P<0.001	P<0.001
Grade III	18 (20%)	22 (24%)	38 (41%)
Grade IV	3 (3%)	2 (2%)	32 (35%)
ANC, median (IQR)	4.3 (3.2, 6.2)	4.2 (3.0, 5.9)	2.9 (2.3, 3.9)	P=0.29	P<0.001	P<0.001
ALC, median (IQR)	1.4 (1.0, 2.0)	1.3 (1.0, 1.6)	0.6 (0.4, 0.9)	P=0.23	P<0.001	P<0.001
ANC/ALC ratio, median (IQR)	3.1 (2.0, 5.3)	3.2 (2.2, 5.1)	5.2 (3.4, 8.6)	P=0.80	P<0001	P<0.001
WBC, median (IQR)	6.8 (5.2, 9.0)	6.5 (4.9, 8.6)	4.5 (3.5, 5.3)	P=0.23	P<0.001	P<0.001
HgB, median (IQR)	12.9 (12.1, 13.9)	11.3 (10.3, 12.2)	11.6 (10.1, 12.8)	P<0.001	P=0.21	P<0.001
Platelets, median (IQR)	223.5 (169.0, 298.5)	172.5 (127.5, 217.5)	156 (114.5, 200.0)	P<0.001	P=0.094	P<0.001