Splenic radiation during pancreatic cancer radiotherapy: Are we throwing the baby out with the bath water?

Abstract

354 Background: Lymphopenia is commonly seen following chemoradiation and is associated with a poor prognosis. We conducted this study to determine if the severity of lymphopenia is dependent on the radiation dose and the fractional volume of spleen irradiated unintentionally during definitive chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC were treated with induction chemotherapy (FOLFIRINOX or gemcitabine- based regimens) followed by chemoradiation (CRT; median 50.4 Gy with concurrent capecitabine) from 1/2006 to 12/2012. Absolute lymphocyte count (ALC) was recorded at baseline, prior to CRT and 2-10 weeks after the end of CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and the percentage of splenic volume receiving at least 5 Gy (V5), 10 Gy (V10), 15 Gy (V15) and 20 Gy (V20) dose. Overall survival (OS) was analyzed using Cox model and multivariate logistic regression was used to assess the development of post CRT severe lymphopenia (ALC < 0.5 K/UL) using baseline and treatment factors. Results: Median post-CRT ALC (0.68 K/UL, range 0.13 to 2.72) was significantly lower than both baseline (1.42 K/UL, range 0.34- 3.97; p < 0.0001) and pre-CRT ALC (1.32 K/UL, range 0.36- 4.82; p < 0.0001). Post-CRT ALC < 0.5 K/UL was associated with inferior OS on univariate (16.8 vs. 21.2 months, p = 0.004) and multivariate analysis (HR = 1.9, p = 0.002).The MSD was 8.8 Gy and log MSD showed a significant negative correlation (r = -0.18, p = 0.02) with post-CRT ALC. Median V5, V10, V15 and V20 were 34%, 21%, 13% and 8% respectively. Median V10 (32.6 vs. 16%, p = 0.04), V15 (23.2 vs. 9.5%, p = 0.03) and V20 (15.4 vs. 4.6%, p = 0.02) were significantly higher in patients with severe lymphopenia. On multivariate logistic regression analysis, baseline lymphopenia (ALC < 1 K/UL; p = 0.003, OR = 4.6) and MSD (p = 0.03, OR = 7.3) were independent predictors for the development of severe post-CRT lymphopenia. Conclusions: LAPC patients receiving high MSD during CRT are at increased risk of developing severe lymphopenia, which is an independent predictor of poor OS. Routine assessment of splenic DVHs prior to acceptance of treatment plans may minimize this risk.