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Title: SU-D-204-05: Fitting Four NTCP Models to Treatment Outcome Data of Salivary Glands Recorded Six Months After Radiation Therapy for Head and Neck Tumors

Abstract

Purpose: To estimate the radiobiological parameters of four popular NTCP models that describe the dose-response relations of salivary glands to the severity of patient reported dry mouth 6 months post chemo-radiotherapy. To identify the glands, which best correlate with the manifestation of those clinical endpoints. Finally, to evaluate the goodness-of-fit of the NTCP models. Methods: Forty-three patients were treated on a prospective multiinstitutional phase II study for oropharyngeal squamous cell carcinoma. All the patients received 60 Gy IMRT and they reported symptoms using the novel patient reported outcome version of the CTCAE. We derived the individual patient dosimetric data of the parotid and submandibular glands (SMG) as separate structures as well as combinations. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS), Logit and Relative Logit (RL) NTCP models were used to fit the patients data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC) and the Odds Ratio methods. Results: The AUC values were highest for the contralateral parotid for Grade ≥ 2 (0.762 for the LKB, RS, Logit and 0.753 for the RL). For the salivary glands the AUC values were: 0.725 for the LKB, RS, Logit and 0.721 for the RL.more » For the contralateral SMG the AUC values were: 0.721 for LKB, 0.714 for Logit and 0.712 for RS and RL. The Odds Ratio for the contralateral parotid was 5.8 (1.3–25.5) for all the four NTCP models for the radiobiological dose threshold of 21Gy. Conclusion: It was shown that all the examined NTCP models could fit the clinical data well with very similar accuracy. The contralateral parotid gland appears to correlated best with the clinical endpoints of severe/very severe dry mouth. An EQD2Gy dose of 21Gy appears to be a safe threshold to be used as a constraint in treatment planning.« less

Authors:
; ; ; ; ; ;  [1]; ;  [2];  [3]
  1. University North Carolina, Chapel Hill, NC (United States)
  2. University of Florida, Gainesville, FL (United States)
  3. University of North Carolina, Raleigh, NC (United States)
Publication Date:
OSTI Identifier:
22624363
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ACCURACY; CARCINOMAS; HEAD; NECK; ORAL CAVITY; PATIENTS; PLANNING; RADIATION DOSES; RADIOTHERAPY; SALIVARY GLANDS; SYMPTOMS

Citation Formats

Mavroidis, P, Price, A, Kostich, M, Green, R, Das, S, Marks, L, Chera, B, Amdur, R, Mendenhall, W, and Sheets, N. SU-D-204-05: Fitting Four NTCP Models to Treatment Outcome Data of Salivary Glands Recorded Six Months After Radiation Therapy for Head and Neck Tumors. United States: N. p., 2016. Web. doi:10.1118/1.4955610.
Mavroidis, P, Price, A, Kostich, M, Green, R, Das, S, Marks, L, Chera, B, Amdur, R, Mendenhall, W, & Sheets, N. SU-D-204-05: Fitting Four NTCP Models to Treatment Outcome Data of Salivary Glands Recorded Six Months After Radiation Therapy for Head and Neck Tumors. United States. doi:10.1118/1.4955610.
Mavroidis, P, Price, A, Kostich, M, Green, R, Das, S, Marks, L, Chera, B, Amdur, R, Mendenhall, W, and Sheets, N. 2016. "SU-D-204-05: Fitting Four NTCP Models to Treatment Outcome Data of Salivary Glands Recorded Six Months After Radiation Therapy for Head and Neck Tumors". United States. doi:10.1118/1.4955610.
@article{osti_22624363,
title = {SU-D-204-05: Fitting Four NTCP Models to Treatment Outcome Data of Salivary Glands Recorded Six Months After Radiation Therapy for Head and Neck Tumors},
author = {Mavroidis, P and Price, A and Kostich, M and Green, R and Das, S and Marks, L and Chera, B and Amdur, R and Mendenhall, W and Sheets, N},
abstractNote = {Purpose: To estimate the radiobiological parameters of four popular NTCP models that describe the dose-response relations of salivary glands to the severity of patient reported dry mouth 6 months post chemo-radiotherapy. To identify the glands, which best correlate with the manifestation of those clinical endpoints. Finally, to evaluate the goodness-of-fit of the NTCP models. Methods: Forty-three patients were treated on a prospective multiinstitutional phase II study for oropharyngeal squamous cell carcinoma. All the patients received 60 Gy IMRT and they reported symptoms using the novel patient reported outcome version of the CTCAE. We derived the individual patient dosimetric data of the parotid and submandibular glands (SMG) as separate structures as well as combinations. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS), Logit and Relative Logit (RL) NTCP models were used to fit the patients data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC) and the Odds Ratio methods. Results: The AUC values were highest for the contralateral parotid for Grade ≥ 2 (0.762 for the LKB, RS, Logit and 0.753 for the RL). For the salivary glands the AUC values were: 0.725 for the LKB, RS, Logit and 0.721 for the RL. For the contralateral SMG the AUC values were: 0.721 for LKB, 0.714 for Logit and 0.712 for RS and RL. The Odds Ratio for the contralateral parotid was 5.8 (1.3–25.5) for all the four NTCP models for the radiobiological dose threshold of 21Gy. Conclusion: It was shown that all the examined NTCP models could fit the clinical data well with very similar accuracy. The contralateral parotid gland appears to correlated best with the clinical endpoints of severe/very severe dry mouth. An EQD2Gy dose of 21Gy appears to be a safe threshold to be used as a constraint in treatment planning.},
doi = {10.1118/1.4955610},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose: To estimate the radiobiological parameters of four NTCP models that describe the dose-response relations of pharyngeal constrictors and proximal esophagus regarding the severity of patient reported swallowing problems 6 months post chemo-radiotherapy. To identify the section/structure that best correlates with the manifestation of the clinical endpoints. Finally, to compare the goodness-of-fit of those models. Methods: Forty-three patients were treated on a prospective multi-institutional phase II study for oropharyngeal squamous cell carcinoma. All the patients received 60 Gy IMRT and they reported symptoms using the novel patient reported outcome version of the CTCAE. We derived the individual patient dosimetric datamore » of superior, medium and inferior sections of pharyngeal constrictors (SPC, MPC and IPC), superior and inferior sections of esophagus (SES and IES) as separate structures as well as combinations. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS), Logit and Relative Logit (RL) NTCP models were used to fit the patient data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC) and the Odds Ratio methods. Results: The AUC values were highest for the SPC for Grade ≥ 2 (0.719 for the RS and RL models, and 0.716 for LKB and Logit). For Grade ≥ 1, the respective values were 0.699 for RS, LKB and Logit and 0.676 for RL. For MPC the AUC values varied between 0.463–0.477, for IPC between 0.396–0.458, for SES between 0.556–0.613 and for IES between 0.410–0.519. The Odds Ratio for the SPC was 15.6 (1.7–146.4) for RS, LKB and Logit for NTCP of 55%. Conclusion: All the examined NTCP models could fit the clinical data with similar accuracy. The SPC appear to correlate best with the clinical endpoints of swallowing problems. A prospective study could establish the use of NTCP values of SPC as a constraint in treatment planning.« less
  • Purpose: To investigate the correlation between different dosimetric indices of salivary glands (as separate or combined structures) to patient-reported dry mouth 6 months post radiotherapy using the novel patient reported outcome version of the CTCAE (PRO-CTCAE). Methods: Forty-three patients with oropharyngeal squamous cell carcinoma were treated on a prospective multi-institutional study. All patients received de-intensified 60 Gy intensity modulated radiotherapy. Dosimetric constraints were used for the salivary glands (e.g. mean dose to the contralateral-parotid < 26 Gy). We investigated correlations of individual patient dosimetric data of the parotid and submandibular glands (as separate or combined structures) to their self-reported 6more » month post-treatment dry mouth responses. Moderate dry mouth responses were most prevalent and were used as the clinical endpoint indicating response. The correlation of Dmean, Dmax and a range of dosevolume (VD) points were assessed through the area under the Receiver Operating Characteristic curve (ROC) and Odds Ratios (OR). Results: Patients reporting non/mild dry mouth response (N=22) had average Dmean = 19.6 ± 6.2Gy to the contralateral-parotid compared to an average Dmean = 28.0 ± 8.3Gy and an AUC = 0.758 for the patients reporting moderate/severe/very severe dry mouth (N=21). Analysis of the range of VD’s for patients who had reported dry mouth showed that for the contralateral-parotid the indices V18 through V22 had the highest area under the curves (AUC) (0.762 – 0.772) compared to a more traditional dosimetric index V30, which had an AUC = 0.732. The highest AUC was observed for the combination of contralateral parotid and contralateral submandibular glands, for which V16 through V28 had AUC = 0.801 – 0.834. Conclusion: Patients who report moderate/severe/very severe dry mouth 6 months post radiotherapy had on average higher Dmean. The V16-V28 of the combination of the contralateral glands showed the highest correlation with the clinical endpoint.« less
  • The natural history of chronic radiation esophagitis occurring in previously normal esophagus is still unknown. The authors describe here the long-term outcome of chronic esophagitis arising after neck irradiation for oropharynx and larynx carcinomas in 13 consecutive adult patients. The first clinical signs of radiation esophagitis were dysphagia or impossibility of oral intake, which appeared within 26 months (range 2--120 months) after the end of radiation for pyriform fossae carcinoma (N = 5), tonsil carcinoma (N = 2), larynx carcinoma (N = 2), pharynx carcinoma (N = 2), base of the tongue (N = 1), and thyroid carcinomas (N =more » 1). During upper endoscopy, an esophageal stenosis was found in 11 cases and was associated with ulceration in three cases. An isolated esophageal ulceration was present in only two cases. Chronic radiation esophagitis diagnosis was confirmed by histology and surgery in seven cases. In the last six cases, diagnosis was supported by the absence of first cancer relapses within a median follow-up of two years (16 months to nine years) and by endoscopic findings. Seven patients received parenteral or enteral nutrition. Ten patients were treated by peroral dilatations. These treatments allowed nearly normal oral diet in 11/13 patients. Only one patient was lost of follow-up after 20 months. Four patients died from chronic radiation esophagitis. One of these patients died from massive hemorrhage after peroral dilatation. Four patients died of a second carcinoma with no first cancer recurrence. Four patients were alive after six months to nine years of follow-up. Moderate dysphagia was still present, allowing nearly normal oral feeding. In conclusion, chronic radiation esophagitis is a severe disease with an underestimated frequency. In this study, peroral dilatations appeared to be necessary and were not associated with an increased morbidity. 21 refs., 1 tab.« less
  • Purpose: The aim of this study was to compare changes in salivary gland function after intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (RT), with or without Amifostine, for tumors of the head-and-neck region using quantitative salivary gland scintigraphy (QSGS). Methods and Materials: A total of 75 patients received pre- and post-therapeutic QSGS to quantify the salivary gland function. In all, 251 salivary glands were independently evaluated. Changes in the maximum uptake ({delta}U) and relative excretion rate ({delta}F) both pre- and post-RT were determined to characterize radiation-induced changes in the salivary gland function. In addition, dose-response curves were calculated. Results: In allmore » groups, maximum uptake and relative excretion rate were reduced after RT ({delta}U {<=}0 and {delta}F {<=}0). The reduction was significantly lower for IMRT than for conventional RT. For the parotid glands, the reduction was smaller for the IMRT-low than for the IMRT-high group. For the Amifostine-high and the conventional group the difference was significant only for one parameter ({delta}U, parotid and submandibular glands, p < 0.05). In contrast to this, the difference between the Amifostine-low and the conventional group was always significant or at least showed a clear trend for both changes in U and F. In regard to the endpoint 'reduction of the salivary gland excretion rate of more than 50%,' the dose-response curves yielded D{sub 50}-values of 34.2 {+-} 12.2 Gy for the conventionally treated group and 36.8 {+-} 2.9 Gy for the IMRT group. For the Amifostine group, an increased D{sub 50}-values of 46.3 {+-} 2.3 Gy was obtained. Conclusion: Intensity-modulated RT can significantly reduce the loss of parotid gland function when respecting a certain dose threshold. Conventional RT plus Amifostine prevents reduced salivary gland function only in the patient group treated with <40.6 Gy.« less
  • Purpose: To estimate the correlation between different dosimetric indices and the clinical outcome, which was recorded at different time points after the treatment, regarding the structure of salivary glands in head and neck cancer radiotherapy. Methods: 218 salivary glands from patients with head and neck tumours treated at IPOCFG from 2007 to 2013 were included in this study. The follow up of those patients consisted on weekly medical visits during the treatment that take about seven weeks. After that the patients had consults every three months. Treatment complications were graded using the RTOG/EORTC guidelines. The response of the salivary glandsmore » (both parotids, oral cavity and both submandibular glands) was analyzed for six time periods: 7th week, 3rd, 7th, 12th, 18th and 24th months after the start of the radiotherapy. The total dose distributions, converted to a fractionation scheme of 2Gy fractional doses, were used to calculate the DVHs and dose-response plots of salivary glands. Results: The small differences obtained between the mean DVHs showed that patients should be grouped into: with complications (G1+G2) and without complications (G0). The mean dose/2Gy was 22.2±13.2 Gy (G0) and 33.2±8.0 Gy (G1+G2) for the 7th week, 31.9±9.6 Gy (G0) and 34.6±6.8 Gy (G1+G2) for the 12th month and, 32.9±9.3 Gy (G0) and 37.2±8.5 Gy (G1+G2) for the 24th month. The dose-response plots for the 7th week and 24th month were similar to the dose-response curves published in the literature. Conclusion: In some cases, there were not major differences between the mean DVHs of the groups with and without complications in the salivary glands, when comparing them at different time periods. More radiobiological analysis should thus be made to estimate the clinical impact of those differences.« less