Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer

Abstract

Purpose Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC). Methods and Materials Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 × Gy 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival. Results Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm3) than in CRT (344.6 cm3; P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm3 vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310–3.237; P=.002). Conclusions SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling studies. Given the association of severe RIL with survival in LAPC, further study of the effect of radiation technique on immune status is warranted.

Is a Pathological Complete Response Following Neoadjuvant Chemoradiation Associated With Prolonged Survival in Patients With Pancreatic Cancer?

“…This may decrease the potential of systemic progression and improve quality of life 42 . The expanded timing of CRT, however, allows better opportunity to develop and test new radiosensitizing therapeutics that may improve treatment effects 43 . At this time, both SBRT and CRT are valid modalities with different benefits and do not appear in our cohort to independently impact survival.…”

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy

“…For instance, altered RT fractionation using shorter courses with stereotactic body radiation therapy (SBRT) for pancreatic cancer over 2 weeks has been associated with significantly less radiation-induced lymphopenia than standard chemoradiation therapy (CRT) over 5 weeks[6]. Radiation target volume has also been identified as an important factor with greater treated volumes associated with lower posttreatment lymphocyte counts in non-small cell lung cancer[7].…”

Comparison of proton therapy and intensity modulated photon radiotherapy for locally advanced non-small cell lung cancer: considerations for optimal trial design

“…The increased conformity of proton therapy spares circulating lymphocytes through decreased radiation exposure and fractionation to major blood pools, such as the heart. Other research has shown that lymphopenia and post treatment circulating lymphocyte levels are independent predictors of survival (22,23). These collective findings suggest that proton therapy may improve outcomes through lymphocyte sparing.…”