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Article ; Online: RE: Venkatesulu et al. (Letter to the Editor).

Ellsworth, Susannah G / Mohan, Radhe / Lin, Steven H

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2023 Volume 181, Page(s) 109490

Language	English
Publishing date	2023-02-02
Publishing country	Ireland
Document type	Letter
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2023.109490
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Article: Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors.

Ellsworth, Susannah G

Advances in radiation oncology

2018 Volume 3, Issue 4, Page(s) 512–519

Abstract: Purpose: Radiation-induced lymphopenia (RIL) is the result of direct toxicity to circulating lymphocytes as they traverse the irradiated field, occurs in 40% to 70% of patients who undergo conventional external beam radiation therapy, and is associated ... ...

Abstract	Purpose: Radiation-induced lymphopenia (RIL) is the result of direct toxicity to circulating lymphocytes as they traverse the irradiated field, occurs in 40% to 70% of patients who undergo conventional external beam radiation therapy, and is associated with worse outcomes in multiple solid tumors. As immunotherapy strategies evolve, a better understanding of radiation's effects on the immune system is needed in order to develop rational methods of combining RT with immunotherapy. Methods and materials: This paper is a review of the available literature on the clinical significance and dosimetric predictors of radiation-induced toxicity to the immune system. Results: An association between severe RIL and inferior survival has been described in multiple solid tumors, including glioma, lung cancer, and pancreatic cancer. RIL risk is correlated with field size, dose per fraction, and fraction number. SBRT and proton therapy techniques are associated with lower RIL risk. Conclusions: The immune system should be considered an organ at risk during RT, and absolute lymphocyte count is an important biomarker of RT-induced immunotoxicity. Radiation dose and technique affect the risk and severity of RIL. Further research is needed to accurately characterize RT-induced immunotoxicity and develop strategies to prevent or mitigate this clinically significant side effect.
Language	English
Publishing date	2018-10-23
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2452-1094
ISSN	2452-1094
DOI	10.1016/j.adro.2018.08.014
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Article ; Online: Neoadjuvant mFOLFIRINOX vs mFOLFIRINOX Plus Radiotherapy in Patients With Borderline Resectable Pancreatic Cancer-The A021501 Trial.

Grossberg, Aaron J / Jethwa, Krishan R / Ellsworth, Susannah G

JAMA oncology

2022 Volume 9, Issue 2, Page(s) 275

MeSH term(s)	Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Fluorouracil/therapeutic use ; Neoadjuvant Therapy ; Pancreatic Neoplasms/radiotherapy ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms
Chemical Substances	Fluorouracil (U3P01618RT)
Language	English
Publishing date	2022-12-01
Publishing country	United States
Document type	Clinical Trial ; Letter ; Comment
ISSN	2374-2445
ISSN (online)	2374-2445
DOI	10.1001/jamaoncol.2022.6135
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Article ; Online: In Regard to Schaub et al.

Long, David E / Ellsworth, Susannah G

International journal of radiation oncology, biology, physics

2019 Volume 103, Issue 5, Page(s) 1284–1285

MeSH term(s)	Chemical and Drug Induced Liver Injury ; Humans ; Liver Cirrhosis ; Liver Neoplasms ; Radiometry
Language	English
Publishing date	2019-03-13
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2018.12.013
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Zs.A 1218: Show issues

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Article ; Online: RE: Valstar et al., "The tubarial salivary glands: A potential new organ at risk for radiotherapy".

Ellsworth, Susannah G / Winkfield, Karen M / Greenberger, Joel S

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2020 Volume 154, Page(s) 312–313

MeSH term(s)	Humans ; Radiation Oncology ; Radiotherapy Dosage ; Salivary Glands
Language	English
Publishing date	2020-12-11
Publishing country	Ireland
Document type	Letter ; Comment
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2020.12.002
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Article ; Online: Declarations of Independence: How Embedded Multicollinearity Errors Affect Dosimetric and Other Complex Analyses in Radiation Oncology.

Ellsworth, Susannah G / van Rossum, Peter S N / Mohan, Radhe / Lin, Steven H / Grassberger, Clemens / Hobbs, Brian

International journal of radiation oncology, biology, physics

2023 Volume 117, Issue 5, Page(s) 1054–1062

Abstract: The statistical technique of multiple regression, commonly referred to as "multivariable regression," is often used in clinical research to quantify the relationships between multiple predictor variables and a single outcome variable of interest. The ... ...

Abstract	The statistical technique of multiple regression, commonly referred to as "multivariable regression," is often used in clinical research to quantify the relationships between multiple predictor variables and a single outcome variable of interest. The foundational theory underpinning multivariable regression assumes that all predictor variables are independent of one another. In other words, the effect of each independent variable is measured by its contribution to the regression equation while all other variables remain unchanged. In the presence of correlations between two or more variables, however, it is impossible to change one variable without a consequent change in the variable(s) it is linked to. This condition, known as "multicollinearity," can introduce errors into multivariable regression models by affecting estimates of the regression coefficients that quantify the relationship between individual predictor variables and the outcome variable. Errors that arise due to violations of the multicollinearity assumption are of special interest to radiation oncology researchers. Because of high levels of correlation among variables derived from points along individual organ dose-volume histogram (DVH) curves, as well as strong intercorrelations among dose-volume parameters in neighboring organs, dosimetric analyses are particularly subject to multicollinearity errors. For example, dose-volume parameters for the heart are strongly correlated not only with other points along the heart DVH curve but are likely also correlated with dose-volume parameters in neighboring organs such as the lung. In this paper, we describe the problem of multicollinearity in accessible terms and discuss examples of violations of the multicollinearity assumption within the radiation oncology literature. Finally, we provide recommendations regarding best practices for identifying and managing multicollinearity in complex data sets.
MeSH term(s)	Humans ; Radiation Oncology ; Multivariate Analysis ; Lung
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2023.06.015
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Article ; Online: Functional liver-image guided hepatic therapy (FLIGHT): A technique to maximize hepatic functional reserve.

Furukawa, Yukie / Long, David E / Ellsworth, Susannah G

Medical dosimetry : official journal of the American Association of Medical Dosimetrists

2019 Volume 45, Issue 2, Page(s) 117–120

Abstract: Introduction: Radiation planning approaches for liver radiation often do not consider the regional variation that can exist in liver function. This study dosimetrically compares functional liver image-guided hepatic therapy (FLIGHT) to standard ... ...

Abstract	Introduction: Radiation planning approaches for liver radiation often do not consider the regional variation that can exist in liver function. This study dosimetrically compares functional liver image-guided hepatic therapy (FLIGHT) to standard stereotactic body radiation therapy (SBRT) plans. In the FLIGHT plans, functional data from hepatobiliary iminodiacetic acid (HIDA) single photon emission computed tomography (SPECT) scans serve as a road map to guide beam arrangement. While meeting the same target volume coverage, plans are optimized to reduce dose to high-functioning liver. Materials and methods: The study included 10 patients with hepatocellular carcinoma (HCC) with baseline HIDA SPECT imaging. Standard SBRT plans which did not systematically incorporate these scans had previously been completed on all 10 plans. Retrospectively, FLIGHT plans were created based on the use of contours of relative liver function from the HIDA SPECT as avoidance structures. Resulting dose to each relative functional liver structure was examined and compared qualitatively and using Wilcoxin rank-sum tests. Target coverage, doses to organs at risk (OARs), conformity index (CI), and gradient index (GI) were also evaluated. Results: While maintaining the same target coverage, FLIGHT plans reduced the mean dose to the high functioning liver by a median of 3.0 Gy (range 0.7 to 4.6 Gy), which represented a 31.4% mean reduction compared to standard planning. FLIGHT plans reduced the volume of high functioning liver receiving 15 Gy by a mean of 59.3 cc (range 7 to 170 cc), for a mean reduction of 41.9%. The mean dose to areas of liver function defined by 25% to 100% and 50% to 100% maximum was reduced with FLIGHT from 10.5 Gy to 8.5 Gy and from 10.5 Gy to 7.5 Gy, respectively (p < 0.005 for both comparisons). The FLIGHT plans' mean CI and GI did not differ significantly from the standard plans' (p = 0.721 and 0.169, respectively). Conclusion: FLIGHT SBRT allows for field design and plan optimization individualized to a patient's baseline regional liver function to maximize hepatic functional reserve. This personalized approach is achieved without compromising target coverage or OAR sparing.
MeSH term(s)	Aged ; Carcinoma, Hepatocellular/radiotherapy ; Female ; Humans ; Liver Function Tests ; Liver Neoplasms/radiotherapy ; Male ; Middle Aged ; Radiosurgery ; Radiotherapy Planning, Computer-Assisted ; Single Photon Emission Computed Tomography Computed Tomography
Language	English
Publishing date	2019-08-19
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	645065-9
ISSN	1873-4022 ; 0958-3947 ; 0739-0211
ISSN (online)	1873-4022
ISSN	0958-3947 ; 0739-0211
DOI	10.1016/j.meddos.2019.07.007
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Zs.A 2448: Show issues

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Article: Lymphocyte Depletion Rate as a Biomarker of Radiation Dose to Circulating Lymphocytes During Fractionated Partial-Body Radiation Therapy.

Ellsworth, Susannah G / Yalamanchali, Anirudh / Lautenschlaeger, Tim / Grossman, Stuart A / Grassberger, Clemens / Lin, Steven H / Mohan, Radhe

Advances in radiation oncology

2022 Volume 7, Issue 5, Page(s) 100959

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2022-04-08
Publishing country	United States
Document type	Journal Article
ISSN	2452-1094
ISSN	2452-1094
DOI	10.1016/j.adro.2022.100959
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Article ; Online: Demographic factors associated with missed follow-up among solid tumor patients treated at a large multi-site academic institution.

Freije, Samantha L / Holmes, Jordan A / Rachidi, Saleh / Ellsworth, Susannah G / Zellars, Richard C / Lautenschlaeger, Tim

Future oncology (London, England)

2020 Volume 16, Issue 32, Page(s) 2635–2643

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Continental Population Groups/statistics & numerical data ; Demography ; Female ; Health Care Surveys ; Healthcare Disparities ; Humans ; Male ; Medicaid ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Neoplasms/therapy ; United States
Language	English
Publishing date	2020-09-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2020-0425
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Article ; Online: Radiation-Induced Lymphopenia Risks of Photon Versus Proton Therapy for Esophageal Cancer Patients.

Ebrahimi, Saba / Lim, Gino / Liu, Amy / Lin, Steven H / Ellsworth, Susannah G / Grassberger, Clemens / Mohan, Radhe / Cao, Wenhua

International journal of particle therapy

2021 Volume 8, Issue 2, Page(s) 17–27

Abstract: 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 ( ... ...

Abstract	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.
Language	English
Publishing date	2021-04-07
Publishing country	United States
Document type	Journal Article
ISSN	2331-5180
ISSN (online)	2331-5180
DOI	10.14338/IJPT-20-00086
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