Model-based calculation of thyroid gland normal tissue complication probability in head and neck cancer patients after radiation therapy.

AIM: Primary hypothyroidism is one of the late complications that can occur after radiation therapy for malignant tumors in the head and neck region. The aim of this retrospective study was to show the validity of the Lyman-Kutcher-Burman (LKB) normal tissue complication model for thyroid gland based on clinical results. METHODS: Thyroid function was evaluated by measuring thyroid-stimulating hormone and free thyroxine serum levels before radiation therapy, 3 months after the beginning of radiation therapy, and afterwards at each follow-up visit. Cumulative incidence was calculated using the Kaplan-Meier method. Dose-volume histogram, total dose, fractionation schedule, total duration of the treatment, and other parameters were used for normal tissue complication probability calculation based on the LKB model. The model was evaluated after fitting with the three sets of parameters for grade 2 hypothyroidism: 1) "Emami," where n = 0.22; m = 0.26, and D50 = 80 Gy; 2) "mean dose," where n = 1; m = 0.27, and D50 = 60 Gy; and 3) "Lyman EUD," where n = 0.49; m = 0.24, and D50 = 60 Gy. A value 3.0 Gy was used for α/ß ratio RESULTS: Eighty-three patients treated with volumetric modulated arc therapy for head and neck cancers at the University Hospital Martin, Slovakia, from January 2014 to July 2017, were included in the retrospective study. Median follow-up was 1.2 years. Cumulative incidence of hypothyroidism grade 2 or higher after 12 and 24 months was 9.6 and 22.0%, respectively. Normal tissue complication probability values calculated with mean dose and Lyman EUD parameters showed the best correlation with our clinical findings. CONCLUSION: Empirically based modelling of normal tissue complication probability was valid for our cohort of patients. With carefully chosen parameters, the LKB model can be used for predicting the normal tissue complication probability value.

Impact of Modern Low Dose Involved Site Radiation Therapy on Normal Tissue Toxicity in Cervicothoracic Non-Hodgkin Lymphomas: A Biophysical Study.

This biophysical study aimed to determine fitting parameters for the Lyman-Kutcher-Burman (LKB) dose-response model for normal tissue complication probability (NTCP) calculations of acute side effects and to investigate the impact of reduced radiation doses on the probability of their occurrence in supradiaphragmatic non-Hodgkin lymphoma (NHL) irradiation. A cohort of 114 patients with NHL in the cervicothoracic region, treated between 2015 and 2021 at the University Hospitals of Münster, Hamburg, and Essen, with involved site radiation therapy (ISRT), were included. Among them, 68 patients with aggressive NHL (a-NHL) received consolidative radiation therapy with 24-54 Gy following (R-)CHOP chemotherapy. Additionally, 46 patients with indolent NHL (i-NHL) underwent radiotherapy with 22.5-45.0 Gy. Two treatment plans were prospectively created for each patient (a-NHL: 30.0/40.0 Gy; i-NHL: 24.0/30.0 Gy). NTCP were then calculated using the optimized LKB model. The adapted dose-response models properly predicted the patient's probability of developing acute side effects when receiving doses ≤ 50 Gy. In addition, it was shown that reduced radiation doses can influence the NTCP of acute side effects depending on the aggressiveness of NHL significantly. This study provided a foundation to prospectively assess the probability of adverse side effects among today's reduced radiation doses in the treatment of NHL.

Ipsilateral lung normal tissue complication probability parameters for different dose calculation algorithms in radiotherapy of breast cancer.

PURPOSE: Different dose calculation algorithms (DCAs) predict different dose distributions for the same treatment. Awareness of optimal model parameters is vital for estimating normal tissue complication probability (NTCP) for different algorithms. The aim is to determine the NTCP parameter values for different DCAs in left-sided breast radiotherapy, using the Lyman-Kutcher-Burman (LKB) model. MATERIALS AND METHODS: First, the methodology recommended by International Atomic Energy Agency TEC-DOC 1583 was used to establish the accuracy of dose calculations of different DCAs including: Monte Carlo (MC) and collapsed cone algorithms implemented in Monaco, pencil beam convolution (PBC) and analytical anisotropic algorithm (AAA) implemented in Eclipse, and superposition and Clarkson algorithms implemented in PCRT3D treatment planning systems (TPSs). Then, treatment planning of 15 patients with left-sided breast cancer was performed by the mentioned DCAs and NTCP of the left-lung normal tissue were calculated for each patient individually, using the LKB model. For the PB algorithm, the NTCP parameters were taken from previously published values and new model parameters obtained for each DCA, using the iterative least squares methods. RESULTS: For all cases and DCAs, NTCP computation with the same model parameters resulted in >15% deviation in NTCP values. The new NTCP model parameters were classified according to the algorithm type. Thus, the discrepancy of NTCP computations was reduced up to 5% after utilizing adjusted model parameters. CONCLUSIONS: This paper confirms that the NTCP values for a given treatment type are different for the different DCAs. Thus, it is essential to introduce appropriate NTCP parameter values according to DCA adopted in TPS, to obtain a more precise estimation of lung NTCP. Hence, new parameter values, classified according to the DCAs, must be determined before introducing NTCP estimation in clinical practice.

Lyman-Kutcher-Burman normal tissue complication probability modeling for radiation-induced esophagitis in non-small cell lung cancer patients receiving proton radiotherapy.

PURPOSE: To develop and test an Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model to predict radiation-induced esophagitis (RE) in non-small cell lung cancer (NSCLC) patients receiving passive-scattering proton therapy (PSPT). MATERIAL AND METHODS: We retrospectively reviewed 328 NSCLC patients receiving PSPT at our institution. Esophagitis severity was graded by physicians according to the Common Toxicity Criteria for Adverse Events version 3.0, and the primary endpoint was grade ≥2 RE within 6 months from the first treatment. LKB model parameters (n, m, and TD50) were determined using maximum likelihood estimation. Overall performance of the model was quantified by Nagelkerke's R2 and the scaled Brier score. Discriminative ability was evaluated using the area under the receiver operating curve (AUC), and calibration was assessed with the Hosmer-Lemeshow goodness-of-fit test. Bootstrap internal validation was performed to assess the model uncertainty and generalizability. RESULTS: Grade 2-3 RE was observed in 136 (41.5%) patients, and no grade 4-5 RE was reported. The optimal LKB parameters were: n = 0.24, m = 0.51, and TD50 = 44.83 Gy (relative biological effectiveness). The optimism-corrected AUC was 0.783, and the Hosmer-Lemeshow test showed significant agreement between predicted and observed morbidity. Bootstrap validation verified that the model was robust to similar future populations. CONCLUSION: Our LKB NTCP model to predict grade ≥2 RE in NSCLC patients who received PSPT showed good predictive performance and robustness to similar future populations, and a smaller volume effect than the previously observed in photon-treated populations. External validation of the model is warranted.

Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation.

BACKGROUND: Palliative thoracic radiotherapy is an effective technique to alleviate symptoms of disease burden in advanced-stage lung cancer patients. Previous randomized controlled studies demonstrated a survival benefit in patients with good performance status at radiation doses of 35Gy10 or greater but with an increased incidence of esophagitis. The objective of this planning study was to assess the potential impact of esophageal-sparing IMRT (ES-IMRT) compared to the current standard of care using parallel-opposed pair beams (POP). METHODS: In this study, 15 patients with lung cancer treated to a dose of 30Gy in 10 fractions between August 2015 and January 2016 were identified. Radiation treatment plans were optimized using ES-IMRT by limiting the max esophagus point dose to 24Gy. Using published Lyman-Kutcher-Burman normal tissue complication probabilities (LKB-NTCP) models, both plans were evaluated for the likelihood of esophagitis (≥ grade 2) and pneumonitis (≥ grade 2). RESULTS: Using ES-IMRT, the median esophageal and lung mean doses reduced from 16 and 8Gy to 7 and 7Gy, respectively. Using the LKB models, the theoretical probability of symptomatic esophagitis and pneumonitis reduced from 13 to 2%, and from 5 to 3%, respectively. The median normalize total dose (NTD mean) accounting for fraction size for the GTV and PTV of the clinically approved POP plans compared to the ES-IMRT plans were similar. CONCLUSION: Advanced radiotherapy techniques such as ES-IMRT may have clinical utility in reducing treatment-related toxicity in advanced lung cancer patients. Our data suggests that the rate of esophagitis can be reduced without compromising local control.

Dose volume histogram analysis and comparison of different radiobiological models using in-house developed software.

The purpose of this study is to compare Lyman-Kutcher-Burman (LKB) model versus Niemierko model for normal tissue complication probability (NTCP) calculation and Niemierko model versus Poisson-based model for tumor control probability (TCP) calculation in the ranking of different treatment plans for a patient undergoing radiotherapy. The standard normal tissue tolerance data were used to test the NTCP models. LKB model can reproduce the same complication probability data of normal tissue response on radiation, whereas Niemierko model cannot reproduce the same complication probability. Both Poisson-based and Niemierko models equally reproduce the same standard TCP data in testing of TCP. In case of clinical data generated from treatment planning system, NTCP calculated using LKB model was found to be different from that calculated using Niemierko model. When the fractionation effect was considered in LKB model, the calculated values of NTCPs were different but comparable with those of Niemierko model. In case of TCP calculation using these models, Poisson-based model calculated marginally higher control probability as compared to Niemierko model.