Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels
Radiation esophagitis (RE) is a common adverse event associated with radiotherapy for non–small cell lung cancer (NSCLC). While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-02-01
|
| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523317303534 |
| _version_ | 1818128240447848448 |
|---|---|
| author | Peter G. Hawkins Philip S. Boonstra Stephen T. Hobson James A. Hayman Randall K. Ten Haken Martha M. Matuszak Paul Stanton Gregory P. Kalemkerian Theodore S. Lawrence Matthew J. Schipper Feng-Ming (Spring) Kong Shruti Jolly |
| author_facet | Peter G. Hawkins Philip S. Boonstra Stephen T. Hobson James A. Hayman Randall K. Ten Haken Martha M. Matuszak Paul Stanton Gregory P. Kalemkerian Theodore S. Lawrence Matthew J. Schipper Feng-Ming (Spring) Kong Shruti Jolly |
| author_sort | Peter G. Hawkins |
| collection | DOAJ |
| description | Radiation esophagitis (RE) is a common adverse event associated with radiotherapy for non–small cell lung cancer (NSCLC). While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc) and generalized equivalent uniform dose (gEUD)], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC) and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc) and 0.727 (gEUD). Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs) of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning. |
| first_indexed | 2024-12-11T07:30:06Z |
| format | Article |
| id | doaj.art-807aa9f845534e57980033eb1a73c236 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 1944-7124 |
| language | English |
| last_indexed | 2024-12-11T07:30:06Z |
| publishDate | 2018-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-807aa9f845534e57980033eb1a73c2362022-12-22T01:15:50ZengElsevierTranslational Oncology1936-52331944-71242018-02-0111110210810.1016/j.tranon.2017.11.005Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine LevelsPeter G. Hawkins0Philip S. Boonstra1Stephen T. Hobson2James A. Hayman3Randall K. Ten Haken4Martha M. Matuszak5Paul Stanton6Gregory P. Kalemkerian7Theodore S. Lawrence8Matthew J. Schipper9Feng-Ming (Spring) Kong10Shruti Jolly11Department of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States of AmericaDepartment of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Internal Medicine, Division of Medical Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaDepartment of Radiation Oncology, Indiana University, 535 Barnhill Drive, Indianapolis, IN 46202, United States of AmericaDepartment of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, United States of AmericaRadiation esophagitis (RE) is a common adverse event associated with radiotherapy for non–small cell lung cancer (NSCLC). While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc) and generalized equivalent uniform dose (gEUD)], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC) and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc) and 0.727 (gEUD). Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs) of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning.http://www.sciencedirect.com/science/article/pii/S1936523317303534 |
| spellingShingle | Peter G. Hawkins Philip S. Boonstra Stephen T. Hobson James A. Hayman Randall K. Ten Haken Martha M. Matuszak Paul Stanton Gregory P. Kalemkerian Theodore S. Lawrence Matthew J. Schipper Feng-Ming (Spring) Kong Shruti Jolly Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels Translational Oncology |
| title | Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels |
| title_full | Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels |
| title_fullStr | Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels |
| title_full_unstemmed | Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels |
| title_short | Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels |
| title_sort | prediction of radiation esophagitis in non small cell lung cancer using clinical factors dosimetric parameters and pretreatment cytokine levels |
| url | http://www.sciencedirect.com/science/article/pii/S1936523317303534 |
| work_keys_str_mv | AT peterghawkins predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT philipsboonstra predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT stephenthobson predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT jamesahayman predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT randallktenhaken predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT marthammatuszak predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT paulstanton predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT gregorypkalemkerian predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT theodoreslawrence predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT matthewjschipper predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT fengmingspringkong predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels AT shrutijolly predictionofradiationesophagitisinnonsmallcelllungcancerusingclinicalfactorsdosimetricparametersandpretreatmentcytokinelevels |