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Title: SU-F-J-187: The Statistical NTCP and TCP Models in the Proton Therapy

Abstract

Purpose: The statistical models (SM) are typically used as a subjective description of a population for which there is only limited sample data, and especially in cases where the relationship between variables is known. The normal tissue complications and tumor control are frequently stochastic effects in the Radiotherapy (RT). Based on probabilistic treatments, it recently has been formulated new NTCP and TCP models for the RT. Investigating the particular requirements for their clinical use in the proton therapy (PT) is the goal of this work. Methods: The SM can be used as phenomenological or mechanistic models. The former way allows fitting real data and getting theirparameters. In the latter one, we should do efforts for determining the parameters through the acceptable estimations, measurements, and/or simulation experiments. Experimental methodologies for determination of the parameters have been developed from the fraction cells surviving the proton irradiation curves in tumor and OAR, and precise RBE models are used for calculating the variable of effective dose. As the executions of these methodologies have a high costs, so we have developed computer tools enable to perform simulation experiments as complement to limitations of the real ones. Results: The requirements for the use of the SMmore » in the PT, such as validation and improvement of the elaborated and existent methodologies for determining the SM parameters and effective dose respectively, were determined. Conclusion: The SM realistically simulates the main processes in the PT, and for this reason these can be implemented in this therapy, which are simples, computable and they have other advantages over some current models. It has been determined some negative aspects for some currently used probabilistic models in the RT, like the LKB NTCP and others derived from logistic functions; which can be improved with the proposed methods in this study.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7]
  1. Princeton Radiation Oncology, Princeton Radiation Oncology (United States)
  2. Theoretical and Computational Methods Working Group of IMAG, Santiago de Cuba (Cuba)
  3. National Cancer Institute, Rockville, MD (United States)
  4. MD Anderson Cancer Center, Houston, TX (United States)
  5. Northwestern University, Chicago, IL (United States)
  6. Provincial Hospital of Santiago de Cuba, Santiago de Cuba (Cuba)
  7. Faculty of Electrics of the University of Oriente, Santiago de Cuba (Cuba)
Publication Date:
OSTI Identifier:
22634783
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; ANIMAL TISSUES; COMPLEMENT; IRRADIATION; NEOPLASMS; PROBABILISTIC ESTIMATION; PROTON BEAMS; RADIATION DOSES; RADIOTHERAPY; SIMULATION; STOCHASTIC PROCESSES; VALIDATION

Citation Formats

Jang, S, Frometa, T, Pyakuryal, A, Sio, T, Piseaux, R, Acosta, S, and Ocana, K. SU-F-J-187: The Statistical NTCP and TCP Models in the Proton Therapy. United States: N. p., 2016. Web. doi:10.1118/1.4956095.
Jang, S, Frometa, T, Pyakuryal, A, Sio, T, Piseaux, R, Acosta, S, & Ocana, K. SU-F-J-187: The Statistical NTCP and TCP Models in the Proton Therapy. United States. doi:10.1118/1.4956095.
Jang, S, Frometa, T, Pyakuryal, A, Sio, T, Piseaux, R, Acosta, S, and Ocana, K. 2016. "SU-F-J-187: The Statistical NTCP and TCP Models in the Proton Therapy". United States. doi:10.1118/1.4956095.
@article{osti_22634783,
title = {SU-F-J-187: The Statistical NTCP and TCP Models in the Proton Therapy},
author = {Jang, S and Frometa, T and Pyakuryal, A and Sio, T and Piseaux, R and Acosta, S and Ocana, K},
abstractNote = {Purpose: The statistical models (SM) are typically used as a subjective description of a population for which there is only limited sample data, and especially in cases where the relationship between variables is known. The normal tissue complications and tumor control are frequently stochastic effects in the Radiotherapy (RT). Based on probabilistic treatments, it recently has been formulated new NTCP and TCP models for the RT. Investigating the particular requirements for their clinical use in the proton therapy (PT) is the goal of this work. Methods: The SM can be used as phenomenological or mechanistic models. The former way allows fitting real data and getting theirparameters. In the latter one, we should do efforts for determining the parameters through the acceptable estimations, measurements, and/or simulation experiments. Experimental methodologies for determination of the parameters have been developed from the fraction cells surviving the proton irradiation curves in tumor and OAR, and precise RBE models are used for calculating the variable of effective dose. As the executions of these methodologies have a high costs, so we have developed computer tools enable to perform simulation experiments as complement to limitations of the real ones. Results: The requirements for the use of the SM in the PT, such as validation and improvement of the elaborated and existent methodologies for determining the SM parameters and effective dose respectively, were determined. Conclusion: The SM realistically simulates the main processes in the PT, and for this reason these can be implemented in this therapy, which are simples, computable and they have other advantages over some current models. It has been determined some negative aspects for some currently used probabilistic models in the RT, like the LKB NTCP and others derived from logistic functions; which can be improved with the proposed methods in this study.},
doi = {10.1118/1.4956095},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • 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 ofmore » 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.« less
  • Purpose: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. Methods and Materials: The data from 6 patients who had previously been treated with HT were used. A three-beam IMPT technique was optimized in the Hyperion treatment planning system, simulating a 'beam scanning' technique. HT was planned using the tomotherapy treatment planning system. Both techniques were optimized to simultaneously deliver 66 Gy in 30 fractions to planning target volume (PTV1; GTV and enlarged nodes) and 54 Gy to PTV2 subclinical, electively treated nodes. Normal tissue complication probability calculationmore » was performed for the parotids and larynx. Results: Very similar PTVs coverage and homogeneity of the target dose distribution for IMPT and HT were found. The conformity index was significantly lower for protons than for photons (1.19 vs. 1.42, respectively). The mean dose to the ipsilateral and contralateral parotid glands decreased by 6.4 Gy and 5.6 Gy, respectively, with IMPT. The volume of mucosa and esophagus receiving {>=}20 Gy and {>=}30 Gy with IMPT was significantly lower than with HT. The average volume of larynx receiving {>=}50 Gy was significantly lower with HT, while for thyroid, it was comparable. The volume receiving {>=}30, {>=}20, and {>=}10 Gy in total body volume decreased with IMPT by 14.5%, 19.4%, and 23.1%, respectively. The normal tissue complication probability for the parotid glands was significantly lower with IMPT for all sets of parameters; however, we also estimated an almost full recovery of the contralateral parotid with HT. The normal tissue complication probability for the larynx was not significantly different between the two irradiation techniques. Conclusion: Excellent target coverage, homogeneity within the PTVs, and sparing of the organs at risk were reached with both modalities. IMPT allows for better sparing of most organs at risk at medium-to-low doses.« less
  • 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 evaluate models for normal-tissue-complication probability (NTCP) on describing the dose-volume effect in rat thoracolumbar spinal cord. Methods and materials: Single-dose irradiation of four field lengths (4, 1.5, 1.0, and 0.5 cm) was evaluated by the endpoints paresis and white-matter necrosis. The resulting dose-response data were used to rank phenomenological and tissue architecture NTCP models. Results: The 0.5-cm field length showed a steep increase in radiation tolerance. Statistical analysis of the model fits, which included evaluation of goodness of fit (GOF) and confidence intervals, resulted in the rejection of all the models considered. Excluding the smallest field length, themore » Schultheiss (D{sub 50} = 21.5 Gy, k = 26.5), the relative seriality (D{sub 50} = 21.4 Gy, s = 1.6, {gamma}{sub 50} = 6.3), and the critical element (D{sub 50,FSU} = 26.6 Gy, {gamma}{sub 50,FSU} = 2.3, n 1.3) model gave the best fit. Conclusion: A thorough statistical analysis resulted in a serial or critical-element behavior for the field lengths of 1.0 cm and greater. Including the 0.5-cm field length, the radiation response markedly diverged from serial properties, but none of the models applied acceptably described this dose-response relationship. This study suggests that the commonly assumed serial behavior of the spinal cord might be valid for daily use in external- beam irradiation.« less
  • Purpose: To evaluate several existing dose-volume effect models for their ability to describe the occurrence of white matter necrosis in rat spinal cord after irradiation with small proton beams. Methods and materials: A large number of dose-volume effect models has been fitted to data on the occurrence of white matter necrosis after irradiation with small proton beams. The fitting was done with the maximum likelihood method. For each model, the goodness of fit was calculated. An empirical tolerance dose-volume (eTDV) model was designed to describe data obtained after uniform irradiation. Results: The eTDV model, the critical element model, and criticalmore » volume model with inclusion of the repair-by-migration principle described by Shirato, were able to describe the data obtained after irradiation with uniform dose distributions of varying sizes. However, none of the models under investigation was able to describe all the data. Extension of the developed empirical model with a repair mechanism with a limited range resulted in a good description of the tolerance doses. Conclusions: In the rat spinal cord, a nonlocal repair mechanism, acting from nonirradiated to irradiated tissue, plays an important role in the (prevention of the) occurrence of white matter necrosis after irradiation. Models that take into account this effect need to be developed.« less