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Brian De,1,* Sweet Ping Ng,1,2,* Amy Y Liu,1 Santiago Avila,1 Randa Tao,3 Emma B Holliday,1 Zachary Brownlee,4 Ahmed Kaseb,5 Sunyoung Lee,3 Kanwal Raghav,5 Jean-Nicolas Vauthey,6 Bruce D Minsky,1 Joseph M Herman,1 Prajnan Das,1 Grace L Smith,1 Cullen M Taniguchi,1 Sunil Krishnan,7 Christopher H Crane,8 Clemens Grassberger,9 Theodore S Hong,9 Steven H Lin,1 Albert C Koong,1 Radhe Mohan,1 Eugene J Koay1 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Radiation Oncology, Austin Health, Melbourne, Victoria, Australia; 3Department of Radiation Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA; 4Department of Radiation Oncology, Tufts Medical Center, Boston, MA, USA; 5Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 6Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7Department of Radiation Oncology, Mayo Clinic Jacksonville, Jacksonville, FL, USA; 8Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 9Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Eugene J KoayMD Anderson Cancer Center, Department of Radiation Oncology, 1400 Pressler St. Unit 1422, Houston, TX, 77030, USATel + 1 713-563-2381Fax +1 713-563-2331Email EKoay@mdanderson.orgBackground: The immune system plays a crucial role in cancer surveillance. Previous studies have shown that lymphopenia associated with radiotherapy (RT) portends a poor prognosis. We sought to differentiate the effects of proton and photon RT on changes in absolute lymphocyte count (ALC) for patients with hepatocellular carcinoma (HCC).Patients and Methods: Patients with HCC treated with definitive RT from 2006 to 2016 were studied. Serial ALCs were graded according to CTCAE v4.0. Overall survival (OS), disease-free survival, and distant metastasis-free survival were analyzed using the Kaplan–Meier method. Univariable and multivariable Cox-proportional hazards analyses were used to identify predictors of OS. A cohort analysis matched for treatment volume was performed to investigate differences in ALC dynamics between photon and proton therapy.Results: Of 143 patients identified, the median age was 66 (range, 19– 90) years. The treatment modality was photon in 103 (72%) and proton in 40 (28%). Median follow-up was 17 months (95% confidence interval, 13– 25 months). The median time to ALC nadir after initiation of RT was 17 days with a median relative decrease of 67%. Those who received proton RT had a higher median ALC nadir (0.41 vs 0.32 k/μL, p=0.002) and longer median OS (33 vs 13 months, p=0.002) than those who received photon RT. Matched cohort analyses revealed a larger low-dose liver volume in the photon group, which correlated with lower ALC. On multivariable Cox analysis, Grade 3 or higher lymphopenia prior to or after RT, portal venous tumor thrombus, larger planning target volumes, Child-Pugh (CP) Class B, and increased CP score after RT were associated with a higher risk of death, whereas the use of proton therapy was associated with lower risk.Conclusion: Grade 3 or higher lymphopenia may be associated with poorer outcomes in patients receiving RT for HCC. Protons may mitigate lymphopenia compared with photons, potentially due to reduced dose exposure of sites of lymphopoiesis.Keywords: lymphocyte count, circulating lymphocytes, splenic dose, liver dose, overall survival

Purpose: To retrospectively analyze dosimetric parameters of volumetric-modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3D-CRT) delivered to extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue in the stomach (gastric MALT lymphoma) to find out advantages of VMAT and conditions for definite benefits of VMAT. Materials and Methods: Fifty patients with stage I-II gastric MALT lymphoma received VMAT (n = 14) or 3D-CRT (n = 36) between December 2005 and April 2018. Twenty-seven patients were categorized according to whether the planning target volume (PTV) overlaps kidney(s). Dosimetric parameters were analyzed by dose-volume histogram. Results: Radiation dose to the liver was definitely lower with VMAT in terms of mean dose (p = 0.026) and V15 (p = 0.008). The V15 of the left kidney was lower with VMAT (p = 0.065). For those with PTV overlapping kidney(s), the left kidney V15 was significantly lower with VMAT. Furthermore, the closer the distance between the PTV and kidneys, the less the left kidney V15 with VMAT (p = 0.037). Delineation of kidney(s) by integrating all respiratory phases had no additional benefit. Conclusions: VMAT significantly increased monitor units, reduced treatment time and radiation dose to the liver and kidneys. The benefit of VMAT was definite in reducing the left kidney V15, especially in geometrically challenging conditions of overlap or close separation between PTV and kidney(s). [ABSTRACT FROM AUTHOR]