Panayiotis Mavroidis1, Alex Price2, David Fried2, Mark Kostich2, Robert Amdur3, William Mendenhall3, Chihray Liu4, Shiva Das2, Lawrence B Marks2, Bhishamjit Chera5. 1. Department of Radiation Oncology, University of North Carolina, Chapel Hill, United States. Electronic address: panayiotis_mavroidis@med.unc.edu. 2. Department of Radiation Oncology, University of North Carolina, Chapel Hill, United States. 3. Department of Radiation Oncology, University of Florida Hospitals, Gainesville, United States; Shands Cancer Center, University of Florida Hospitals, Gainesville, United States. 4. Department of Radiation Oncology, University of Florida Hospitals, Gainesville, United States. 5. Department of Radiation Oncology, University of North Carolina, Chapel Hill, United States; Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, United States.
Abstract
BACKGROUND AND PURPOSE: The aim is to determine the radiobiological parameters of four popular normal tissue complication probability (NTCP) models that describe the dose-response relations of salivary glands and pharyngeal constrictors to the severity of patient reported xerostomia and dysphagia, respectively 6 and 12months post chemo-radiotherapy, furthermore, to evaluate the goodness-of-fit of the NTCP models for different combinations of glands and constrictors. MATERIAL AND METHODS: Forty-three patients were treated on a prospective multi-institutional phase II study (ClinicalTrials.gov, NCT01530997) assessing the efficacy of de-intensified chemoradiotherapy in patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma. All patients received 60Gy intensity modulated radiotherapy with concurrent weekly intravenous cisplatinum. All patients reported severity of their xerostomia and dysphagia (pre- and post-treatment) using the patient reported outcome version of the CTCAE (PRO-CTCAE). A change in severity (from baseline) of ≥2 was considered clinically meaningful. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS), Logit, and Relative Seriality Logit (RSL) NTCP models were used to fit the patients' dose/volume data to changes in PRO-CTCAE severity of xerostomia and dysphagia (from baseline to 6 and 12months post-treatment). The correlation of the models with the patient outcomes was performed for different combinations of salivary glands and different sections of pharyngeal constrictors. The goodness-of-fit of the different models was assessed through the area under the receiver operating characteristic curve (AUC), maximum of the log-likelihood function, normal error distribution and Akaike information criterion (AIC). RESULTS: The dose/volume metrics of the combined contralateral (parotid+submandibular) glands appear to correlate best with xerostomia, at both 6- and 12-months. Among the different sections of pharyngeal constrictors, the dose/volume metrics of the superior pharyngeal constrictors appear to correlate best with dysphagia at 6months. The AUC values ranged from 0.72 to 0.85 in the case of xerostomia and 0.73 to 0.74 in the case of dysphagia over the different models. The four NTCP models showed similar goodness-of-fit. The differences in AIC between the different models were less than 2 and ranged within 0.7 and 0.8 in the cases of xerostomia and dysphagia, respectively. The calculated parameters of the LKB model were D50=26.9Gy, m=0.63, n=1.0 for the combined contralateral glands at 12months and D50=62.0Gy, m=0.10, n=0.49 for the superior pharyngeal constrictors at 6months. CONCLUSIONS: The values of the parameters of four NTCP models were determined for salivary glands and pharyngeal constrictors. All four models could fit the clinical data equally well. The NTCP predictions of the combined contralateral glands and superior pharyngeal constrictors showed the best correlation with the patient reported outcomes of xerostomia and dysphagia, respectively.
BACKGROUND AND PURPOSE: The aim is to determine the radiobiological parameters of four popular normal tissue complication probability (NTCP) models that describe the dose-response relations of salivary glands and pharyngeal constrictors to the severity of patient reported xerostomia and dysphagia, respectively 6 and 12months post chemo-radiotherapy, furthermore, to evaluate the goodness-of-fit of the NTCP models for different combinations of glands and constrictors. MATERIAL AND METHODS: Forty-three patients were treated on a prospective multi-institutional phase II study (ClinicalTrials.gov, NCT01530997) assessing the efficacy of de-intensified chemoradiotherapy in patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma. All patients received 60Gy intensity modulated radiotherapy with concurrent weekly intravenous cisplatinum. All patients reported severity of their xerostomia and dysphagia (pre- and post-treatment) using the patient reported outcome version of the CTCAE (PRO-CTCAE). A change in severity (from baseline) of ≥2 was considered clinically meaningful. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS), Logit, and Relative Seriality Logit (RSL) NTCP models were used to fit the patients' dose/volume data to changes in PRO-CTCAE severity of xerostomia and dysphagia (from baseline to 6 and 12months post-treatment). The correlation of the models with the patient outcomes was performed for different combinations of salivary glands and different sections of pharyngeal constrictors. The goodness-of-fit of the different models was assessed through the area under the receiver operating characteristic curve (AUC), maximum of the log-likelihood function, normal error distribution and Akaike information criterion (AIC). RESULTS: The dose/volume metrics of the combined contralateral (parotid+submandibular) glands appear to correlate best with xerostomia, at both 6- and 12-months. Among the different sections of pharyngeal constrictors, the dose/volume metrics of the superior pharyngeal constrictors appear to correlate best with dysphagia at 6months. The AUC values ranged from 0.72 to 0.85 in the case of xerostomia and 0.73 to 0.74 in the case of dysphagia over the different models. The four NTCP models showed similar goodness-of-fit. The differences in AIC between the different models were less than 2 and ranged within 0.7 and 0.8 in the cases of xerostomia and dysphagia, respectively. The calculated parameters of the LKB model were D50=26.9Gy, m=0.63, n=1.0 for the combined contralateral glands at 12months and D50=62.0Gy, m=0.10, n=0.49 for the superior pharyngeal constrictors at 6months. CONCLUSIONS: The values of the parameters of four NTCP models were determined for salivary glands and pharyngeal constrictors. All four models could fit the clinical data equally well. The NTCP predictions of the combined contralateral glands and superior pharyngeal constrictors showed the best correlation with the patient reported outcomes of xerostomia and dysphagia, respectively.
Authors: Brett A Miles; Marshall R Posner; Vishal Gupta; Marita S Teng; Richard L Bakst; Mike Yao; Kryzsztof J Misiukiewicz; Raymond L Chai; Sonam Sharma; William H Westra; Seunghee Kim-Schulze; Bheesham Dayal; Stanislaw Sobotka; Andrew G Sikora; Peter M Som; Eric M Genden Journal: Oncologist Date: 2021-03-18
Authors: Travis P Schrank; Nicholas Lenze; Lee P Landess; Alan Hoyle; Joel Parker; Asim Lal; Siddharth Sheth; Bhishamjit S Chera; Samip N Patel; Trevor G Hackman; M Ben Major; Natalia Issaeva; Wendell G Yarbrough Journal: Cancer Date: 2021-04-05 Impact factor: 6.921
Authors: Camil Ciprian Mireștean; Roxana Irina Iancu; Dragoș Petru Teodor Iancu Journal: Int J Environ Res Public Health Date: 2022-03-22 Impact factor: 3.390
Authors: Panayiotis Mavroidis; Kevin A Pearlstein; John Dooley; Jasmine Sun; Srinivas Saripalli; Shiva K Das; Andrew Z Wang; Ronald C Chen Journal: Radiat Oncol Date: 2018-02-02 Impact factor: 3.481