Gastrointestinal Cancer

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SU_10_2094 - A Comparison of Grade 4 Lymphopenia With Proton Versus Photon Radiation Therapy for Esophageal Cancer

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

A Comparison of Grade 4 Lymphopenia With Proton Versus Photon Radiation Therapy for Esophageal Cancer
D. M. Routman1, A. Garant1, S. C. Lester1, C. N. Day2, C. T. Sanhueza3, H. H. Yoon3, M. A. Neben-Wittich1, J. A. Martenson1, M. G. Haddock1, C. L. Hallemeier1, and K. W. Merrell4; 1Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 2Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, 3Department of Medical Oncology, Mayo Clinic, Rochester, MN, 4Mayo Clinic, Rochester, MN

Purpose/Objective(s): Grade 4 lymphopenia (G4L) is associated with worse outcomes such as distant metastasis and overall survival in a number of malignancies treated with radiotherapy (RT), including esophageal cancer (EC). Lymphocytes are highly sensitive to RT with an LD50 of 1-2 Gy. Through a reduction in moderate to low integral radiation dose, proton RT (PRT) may reduce lymphopenia rates relative to photon RT (XRT). We investigated patients (pts) undergoing PRT vs XRT for EC and impact on G4L.

Materials/Methods: Consecutive pts receiving curative intent concurrent RT and chemotherapy between 7/2015 and 12/2017 were identified. Pts with histology besides squamous cell or adenocarcinoma (ACA) and pts receiving a mix of PRT and XRT were excluded. Lymphocyte nadir was defined as the lowest lymphocyte count from time of initiation of RT through the end of RT. G4L was defined according to CTCAE criteria (<200/mm^3). Univariable (UVA) and multivariable (MVA) logistic regression analyses were used to assess for patient and treatment factors potentially associated with odds of lymphopenia. A propensity matched (PM) cohort was created using logistic regression including baseline covariates.

Results: 144 pts met inclusion criteria. Median age was 66 (range 32-85). 85% of pts were male. The majority of pts were Stage II (25%) or III (65%). 5% of pts in each cohort received induction chemo. Concurrent chemotherapy was weekly carboplatin and paclitaxel in 99% of pts. Median RT dose was 50 Gy (range 41.4 to 56.25 Gy). 79 pts received XRT (27% 3D, 73% IMRT) and 65 PRT (100% IMPT). Median clinical target volume was 554 ccs. 84% of patients were candidates for surgery, 62% undergoing resection. The only statistically significant difference between XRT and PRT pts was age, median 64 vs. 68 (p=0.01). Overall, G4L was significantly higher in XRT pts 56% vs 22% for PRT pts (p<0.01). PM resulted in 50 PRT and 50 XRT pts (C-statistic logistic model = 0.690). On UVA and MVA Stage III/IV and RT modality were associated with G4L. RT modality was most strongly associated with G4L, with 60% of XRT pts experiencing G4L as compared to 24% of PRT pts (OR=5.28, p<0.001). Likewise, in a subgroup analysis of pts with ACA undergoing surgical resection (36 XRT, 45 PRT), only RT modality was associated with G4L (56% XRT vs. 14% PRT; OR=7.91, p<0.001).

Conclusion: PRT was associated with a significantly lower risk of G4L in comparison to XRT. Dosimetric analysis is planned to identify DVH parameters mediating this effect. Given prior association of G4L with recurrence risk and ongoing study of immunotherapy in EC, further prospective analysis of G4L is warranted including tumor reactive lymphocyte profiling.

Author Disclosure: D.M. Routman: None. A. Garant: None. S.C. Lester: None. C.N. Day: None. C.T. Sanhueza: None. M.A. Neben-Wittich: None. J.A. Martenson: None. M.G. Haddock: Board Member; ISIORT. C.L. Hallemeier: Research Grant; Mayo Clinic.

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