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

Aaron T. Wild; Joseph M. Herman; Avani S. Dholakia; Shalini Moningi; Yao Lu; Lauren M. Rosati; Amy Hacker-Prietz; Ryan K. Assadi; Ali M. Saeed; Timothy M. Pawlik; Elizabeth M. Jaffee; Daniel A. Laheru; Phuoc T. Tran; Matthew J. Weiss; Christopher L. Wolfgang; Eric Ford; Stuart A. Grossman; Xiaobu Ye; Susannah G. Ellsworth

doi:10.1016/j.ijrobp.2015.11.026

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

Aaron T. Wild, Joseph M. Herman, Avani S. Dholakia, Shalini Moningi, Yao Lu, Lauren M. Rosati, Amy Hacker-Prietz, Ryan K. Assadi, Ali M. Saeed, Timothy M. Pawlik, Elizabeth M. Jaffee, Daniel A. Laheru, Phuoc T. Tran, Matthew J. Weiss, Christopher L. Wolfgang, Eric Ford, Stuart A. Grossman, Xiaobu Ye, Susannah G. Ellsworth

Radiation Oncology

Research output: Contribution to journal › Article › peer-review

163 Scopus citations

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.

Original language	English (US)
Pages (from-to)	571-579
Number of pages	9
Journal	International Journal of Radiation Oncology Biology Physics
Volume	94
Issue number	3
DOIs	https://doi.org/10.1016/j.ijrobp.2015.11.026
State	Published - 2016

ASJC Scopus subject areas

Radiation
Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

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Wild, A. T., Herman, J. M., Dholakia, A. S., Moningi, S., Lu, Y., Rosati, L. M., Hacker-Prietz, A., Assadi, R. K., Saeed, A. M., Pawlik, T. M., Jaffee, E. M., Laheru, D. A., Tran, P. T., Weiss, M. J., Wolfgang, C. L., Ford, E., Grossman, S. A., Ye, X., & Ellsworth, S. G. (2016). Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients with Unresectable Pancreatic Cancer. International Journal of Radiation Oncology Biology Physics, 94(3), 571-579. https://doi.org/10.1016/j.ijrobp.2015.11.026

Wild, AT, Herman, JM, Dholakia, AS, Moningi, S, Lu, Y, Rosati, LM, Hacker-Prietz, A, Assadi, RK, Saeed, AM, Pawlik, TM, Jaffee, EM, Laheru, DA, Tran, PT, Weiss, MJ, Wolfgang, CL, Ford, E, Grossman, SA, Ye, X & Ellsworth, SG 2016, 'Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients with Unresectable Pancreatic Cancer', International Journal of Radiation Oncology Biology Physics, vol. 94, no. 3, pp. 571-579. https://doi.org/10.1016/j.ijrobp.2015.11.026

@article{4f1053563d734f089286bd048173d081,

title = "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.",

author = "Wild, {Aaron T.} and Herman, {Joseph M.} and Dholakia, {Avani S.} and Shalini Moningi and Yao Lu and Rosati, {Lauren M.} and Amy Hacker-Prietz and Assadi, {Ryan K.} and Saeed, {Ali M.} and Pawlik, {Timothy M.} and Jaffee, {Elizabeth M.} and Laheru, {Daniel A.} and Tran, {Phuoc T.} and Weiss, {Matthew J.} and Wolfgang, {Christopher L.} and Eric Ford and Grossman, {Stuart A.} and Xiaobu Ye and Ellsworth, {Susannah G.}",

note = "Funding Information: This study was funded by the Viragh Family Foundation, the Claudio X. Gonzalez Family Foundation, the Keeling Family Foundation, the DeSanti Family Foundation, and the McKnight Family.",

year = "2016",

doi = "10.1016/j.ijrobp.2015.11.026",

language = "English (US)",

volume = "94",

pages = "571--579",

journal = "International Journal of Radiation Oncology Biology Physics",

issn = "0360-3016",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients with Unresectable Pancreatic Cancer

AU - Wild, Aaron T.

AU - Herman, Joseph M.

AU - Dholakia, Avani S.

AU - Moningi, Shalini

AU - Lu, Yao

AU - Rosati, Lauren M.

AU - Hacker-Prietz, Amy

AU - Assadi, Ryan K.

AU - Saeed, Ali M.

AU - Pawlik, Timothy M.

AU - Jaffee, Elizabeth M.

AU - Laheru, Daniel A.

AU - Tran, Phuoc T.

AU - Weiss, Matthew J.

AU - Wolfgang, Christopher L.

AU - Ford, Eric

AU - Grossman, Stuart A.

AU - Ye, Xiaobu

AU - Ellsworth, Susannah G.

N1 - Funding Information: This study was funded by the Viragh Family Foundation, the Claudio X. Gonzalez Family Foundation, the Keeling Family Foundation, the DeSanti Family Foundation, and the McKnight Family.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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U2 - 10.1016/j.ijrobp.2015.11.026

DO - 10.1016/j.ijrobp.2015.11.026

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AN - SCOPUS:84963726148

SN - 0360-3016

VL - 94

SP - 571

EP - 579

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

IS - 3

ER -

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

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