Browsing by Author "Mohan, Radhe"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Lymphocyte Depletion Rate as a Biomarker of Radiation Dose to Circulating Lymphocytes During Fractionated Partial-Body Radiation Therapy
    (Elsevier, 2022-04-08) Ellsworth, Susannah G.; Yalamanchali, Anirudh; Lautenschlaeger, Tim; Grossman, Stuart A.; Grassberger, Clemens; Lin, Steven H.; Mohan, Radhe; Radiation Oncology, School of Medicine
    Purpose: Radiation causes exponential depletion of circulating lymphocyte populations; in turn, radiation-induced lymphopenia is associated with worse survival for many solid tumors, possibly owing to attenuated antitumor immune responses. Identifying reliable and reproducible methods of calculating the radiation dose to circulating immune cells may facilitate development of techniques to reduce the risk and severity of radiation-induced toxic effects to circulating lymphocytes. Methods and materials: Patient-specific lymphocyte loss rates were derived from a clinical data set including 684 adult patients with solid tumors. Multivariable linear regression was used to model the relationship between the lymphocyte loss rate and physical parameters of the radiation plan that determine circulating blood dose. Results: During partial-body radiation, lymphocyte loss rates are determined by physical parameters of the radiation plan that reflect radiation exposure to circulating cells, including target volume size, dose per fraction squared, and anatomic site treated. Differences in observed versus predicted lymphocyte loss rates may be partly explained by variations in concurrent chemotherapy regimens. Conclusions: We describe a novel method of using patient-specific lymphocyte loss kinetics to approximate the effective radiation dose to circulating lymphocytes during focal fractionated photon radiation therapy. Clinical applications of these findings include the early identification of patients at particularly high risk of severe radiation-induced lymphopenia based on physical parameters of the radiation therapy plan.
  • Thumbnail Image
    Item
    Patient-Specific Lymphocyte Loss Kinetics as Biomarker of Spleen Dose in Patients Undergoing Radiation Therapy for Upper Abdominal Malignancies
    (Elsevier, 2020-08-10) Yalamanchali, Anirudh; Zhang, Hong; Huang, Ke Colin; Mohan, Radhe; Lin, Steven H.; Zhu, Cong; Grossman, Stuart A.; Jin, Jian-Yue; Ellsworth, Susannah G.; Radiation Oncology, School of Medicine
    Purpose: Radiation therapy (RT)-induced lymphopenia (RIL) is linked with inferior survival in esophageal and pancreatic cancers. Previous work has demonstrated a correlation between spleen dose and RIL risk. The present study correlates spleen dose-volume parameters with fractional lymphocyte loss rate (FLL) and total percent change in absolute lymphocyte count (%ΔALC) and suggests spleen dose constraints to reduce RIL risk. Methods and materials: This registry-based study included 140 patients who underwent RT for pancreatic (n = 67), gastroesophageal (n = 61), or biliary tract (n = 12) adenocarcinoma. Patient-specific parameters of lymphocyte loss kinetics, including FLL and %ΔALC, were calculated based on serial ALCs obtained during RT. Spearman's rho was used to correlate spleen dose-volume parameters with %ΔALC, end-treatment ALC, and FLL. Multivariable logistic regression was used to identify predictors of ≥grade 3 and grade 4 RIL. Results: Spleen dose-volume parameters, including mean spleen dose (MSD), all correlated with %ΔALC, end-treatment ALC, and FLL. Controlling for baseline ALC and planning target volume (PTV), an increase in any spleen dose-volume parameter increased the odds of developing ≥grade 3 lymphopenia. Each 1-Gy increase in MSD increased the odds of ≥grade 3 RIL by 18.6%, and each 100-cm3 increase in PTV increased the odds of ≥grade 3 lymphopenia by 20%. Patients with baseline ALC < 1500 cells/μL had a high risk of ≥grade 3 RIL regardless of MSD or PTV. FLL was an equally good predictor of ≥grade 3 lymphopenia as any spleen dose-volume parameter. Conclusions: In patients undergoing RT for upper abdominal malignancies, higher spleen dose is associated with higher per-fraction lymphocyte loss rates, higher total %ΔALC, and increased odds of severe lymphopenia. Spleen dose constraints should be individualized based on baseline ALC and PTV size to minimize RIL risk, although our findings require validation in larger, ideally prospective data sets.
  • Thumbnail Image
    Item
    Proton therapy reduces the likelihood of high-grade radiation-induced lymphopenia in glioblastoma patients: phase II randomized study of protons vs photons
    (Oxford University Press, 2021-02-25) Mohan, Radhe; Liu, Amy Y.; Brown, Paul D.; Mahajan, Anita; Dinh, Jeffrey; Chung, Caroline; McAvoy, Sarah; McAleer, Mary Frances; Lin, Steven H.; Li, Jing; Ghia, Amol J.; Zhu, Cong; Sulman, Erik P.; de Groot, John F.; Heimberger, Amy B.; McGovern, Susan L.; Grassberger, Clemens; Shih, Helen; Ellsworth, Susannah; Grosshans, David R.; Radiation Oncology, School of Medicine
    Background: We investigated differences in radiation-induced grade 3+ lymphopenia (G3+L), defined as an absolute lymphocyte count (ALC) nadir of <500 cells/µL, after proton therapy (PT) or X-ray (photon) therapy (XRT) for patients with glioblastoma (GBM). Methods: Patients enrolled in a randomized phase II trial received PT (n = 28) or XRT (n = 56) concomitantly with temozolomide. ALC was measured before, weekly during, and within 1 month after radiotherapy. Whole-brain mean dose (WBMD) and brain dose-volume indices were extracted from planned dose distributions. Univariate and multivariate logistic regression analyses were used to identify independent predictive variables. The resulting model was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Rates of G3+L were lower in men (7/47 [15%]) versus women (19/37 [51%]) (P < 0.001), and for PT (4/28 [14%]) versus XRT (22/56 [39%]) (P = 0.024). G3+L was significantly associated with baseline ALC, WBMD, and brain volumes receiving 5‒40 Gy(relative biological effectiveness [RBE]) or higher (ie, V5 through V40). Stepwise multivariate logistic regression analysis identified being female (odds ratio [OR] 6.2, 95% confidence interval [CI]: 1.95‒22.4, P = 0.003), baseline ALC (OR 0.18, 95% CI: 0.05‒0.51, P = 0.003), and whole-brain V20 (OR 1.07, 95% CI: 1.03‒1.13, P = 0.002) as the strongest predictors. ROC analysis yielded an area under the curve of 0.86 (95% CI: 0.79-0.94) for the final G3+L prediction model. Conclusions: Sex, baseline ALC, and whole-brain V20 were the strongest predictors of G3+L for patients with GBM treated with radiation and temozolomide. PT reduced brain volumes receiving low and intermediate doses and, consequently, reduced G3+L.
  • Thumbnail Image
    Item
    Radiation-Induced Lymphopenia Risks of Photon Versus Proton Therapy for Esophageal Cancer Patients
    (Elsevier, 2021-04-07) Ebrahimi, Saba; Lim, Gino; Liu, Amy; Lin, Steven H.; Ellsworth, Susannah G.; Grassberger, Clemens; Mohan, Radhe; Cao, Wenhua; Radiation Oncology, School of Medicine
    Purpose: To assess possible differences in radiation-induced lymphocyte depletion for esophageal cancer patients being treated with the following 3 treatment modalities: intensity-modulated radiation therapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT). Methods and materials: We used 2 prediction models to estimate lymphocyte depletion based on dose distributions. Model I used a piecewise linear relationship between lymphocyte survival and voxel-by-voxel dose. Model II assumes that lymphocytes deplete exponentially as a function of total delivered dose. The models can be fitted using the weekly absolute lymphocyte counts measurements collected throughout treatment. We randomly selected 45 esophageal cancer patients treated with IMRT, PSPT, or IMPT at our institution (15 per modality) to demonstrate the fitness of the 2 models. A different group of 10 esophageal cancer patients who had received PSPT were included in this study of in silico simulations of multiple modalities. One IMRT and one IMPT plan were created, using our standards of practice for each modality, as competing plans to the existing PSPT plan for each patient. We fitted the models by PSPT plans used in treatment and predicted absolute lymphocyte counts for IMRT and IMPT plans. Results: Model validation on each modality group of patients showed good agreement between measured and predicted absolute lymphocyte counts nadirs with mean squared errors from 0.003 to 0.023 among the modalities and models. In the simulation study of IMRT and IMPT on the 10 PSPT patients, the average predicted absolute lymphocyte count (ALC) nadirs were 0.27, 0.35, and 0.37 K/μL after IMRT, PSPT, and IMPT treatments using Model I, respectively, and 0.14, 0.22, and 0.33 K/μL using Model II. Conclusions: Proton plans carried a lower predicted risk of lymphopenia after the treatment course than did photon plans. Moreover, IMPT plans outperformed PSPT in terms of predicted lymphocyte preservation.
  • Thumbnail Image
    Item
    Workshop Report for Cancer Research: Defining the Shades of Gy: Utilizing the Biological Consequences of Radiotherapy in the Development of New Treatment Approaches—Meeting Viewpoint
    (AACR, 2018-05) Ahmed, Mansoor M.; Coleman, C. Norman; Mendonca, Marc; Bentzen, Soren; Vikram, Bhadrasain; Seltzer, Stephen M.; Goodhead, Dudley; Obcemea, Ceferino; Mohan, Radhe; Prise, Kevin M.; Capala, Jacek; Citrin, Deborah; Kao, Gary; Aryankalayil, Molykutty; Eke, Iris; Buchsbaum, Jeffrey C.; Prasanna, Pataje G. S.; Liu, Fei-Fei; Le, Quynh-Thu; Teicher, Beverly; Kirsch, David G.; Smart, DeeDee; Tepper, Joel; Formenti, Silvia; Haas-Kogan, Daphne; Raben, David; Mitchell, James; Radiation Oncology, School of Medicine
    The ability to physically target radiotherapy using image-guidance is continually improving with photons and particle therapy that include protons and heavier ions such as carbon. The unit of dose deposited is the gray (Gy); however, particle therapies produce different patterns of ionizations, and there is evidence that the biological effects of radiation depend on dose size, schedule, and type of radiation. This National Cancer Institute (NCI)–sponsored workshop addressed the potential of using radiation-induced biological perturbations in addition to physical dose, Gy, as a transformational approach to quantifying radiation.