LKB Model Research Articles

Dosimetric and radiobiological comparison of IMRT, VMAT, and helical tomotherapy planning techniques in hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases.

To compare treatment planning and dosimetric outcomes for hippocampal sparing whole brain radiotherapy (WBRT) with the simultaneous integrated boost (SIB) in brain metastasis (BM) patients using tumour control probability (TCP) and normal tissue complication probability (NTCP) formalism between IMRT, VMAT, and HT techniques. In this retrospective study, the treatment data of 20 BM patients who typically received whole brain radiation with SIB treatment were used. Prescription doses of 30Gy and 36Gy was delivered in 10 fractions for WBRT and SIB, respectively. Niemierko and LKB models were applied for calculating TCP and NTCP. All the plans were evaluated for the RTOG 0933 protocol criteria and found acceptable. Additionally, the homogeneity of the PTV boost is 0.07 ± 0.01, 0.1 ± 0.04, and 0.08 ± 0.02 for IMRT, VMAT, and HT, respectively (P < 0.05). The percentage of TCP for the PTV boost was 99.99 ± 0.003, 99.98 ± 0.004, and 99.99 ± 0.002 of IMRT, VMAT, and HT, respectively, (P < 0.005). The NTCP value of the lenses was higher with the VMAT plan as compared to IMRT and HT Plans. The hippocampal NTCP values are equal in all three planning proficiencies. The techniques like IMRT, VMAT, and HT can reduce the dose received by hippocampus to the dosimetric threshold during the delivery of WBRT with hippocampal sparing and can simultaneously boost multiple metastases. Overall, the high-quality dose distribution, TCP, and NTCP comparison between all three planning techniques show that the HT technique has better results when compared to the VMAT and IMRT techniques.

NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT

PurposeThis study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6–24 months after radiotherapy for oropharynx cancer. MethodsThe treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. ResultsXerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58–0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. ConclusionsBased on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2–3 the risk for radiation induced xerostomia that is observed at 6–24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6–24 months post-RT by 2.0–2.3 times.

Prostate Cancer Volumetric Arc Therapy (VMAT) Analysis

Aim: The purpose of this study was to derive radiobiological parameters from the dose volume histogram of patients that undergone prostate cancer radiotherapy via the VMAT technique. Material and Methods: A total of twenty-two cases of prostate cancer of 70.2 and 81 Gy were selected for this study. Radiobiological parameters were evaluated by the Poisson equation for the tumor and LKB model for organs at risk. Results: For prostate tumor, the average TCP was 96.28, 86.45, 68.57 for α/β of 1.2, 3.0, and 10, respectively. The average EUD was 37.98 Gy, 59.23 Gy, 21.19 Gy, 20.65 Gy, 16.32 Gy, and 21.87 Gy for bladder, rectum, right femoral head, left femoral head, small bowel, and large bowel respectively. The average NTCP was 7.6 % for the rectum and negligible for other organs at risk. Conclusion: NTCP for critical organs and TCP for prostate cancer can be determined via dose volume histogram.

Machine learning for normal tissue complication probability prediction: Predictive power with versatility and easy implementation.

A popular Normal tissue Complication (NTCP) model deployed to predict radiotherapy (RT) toxicity is the Lyman-Burman Kutcher (LKB) model of tissue complication. Despite the LKB model's popularity, it can suffer from numerical instability and considers only the generalized mean dose (GMD) to an organ. Machine learning (ML) algorithms can potentially offer superior predictive power of the LKB model, and with fewer drawbacks. Here we examine the numerical characteristics and predictive power of the LKB model and compare these with those of ML. Both an LKB model and ML models were used to predict G2 Xerostomia on patients following RT for head and neck cancer, using the dose volume histogram of parotid glands as the input feature. Model speed, convergence characteristics and predictive power was evaluated on an independent training set. We found that only global optimization algorithms could guarantee a convergent and predictive LKB model. At the same time our results showed that ML models remained unconditionally convergent and predictive, while staying robust to gradient descent optimization. ML models outperform LKB in Brier score and accuracy but compare to LKB in ROC-AUC. We have demonstrated that ML models can quantify NTCP better than or as well as LKB models, even for a toxicity that the LKB model is particularly well suited to predict. ML models can offer this performance while offering fundamental advantages in model convergence, speed, and flexibility, and so could offer an alternative to the LKB model that could potentially be used in clinical RT planning decisions.

A Dosimetric and Radiobiological Comparison of Intensity Modulated Radiotherapy, Volumetric Modulated Arc Therapy and Helical Tomotherapy Planning Techniques in Synchronous Bilateral Breast Cancer

The present investigation intends to identify the optimal radiotherapy treatment plan for synchronous bilateral breast cancer (SBBC) using dosimetric and radiobiological indexes for three techniques, namely, helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT). Twenty SBBC treated female patients treatment planning data (average age of 52.5 years) were used as the sample for the present study. Three different plans were created using 50 Gy in a 25 fraction dose regime. Poisson, Niemierko, and LKB models were applied for calculating normal tissue complication probability (NTCP) and tumour control probability (TCP). The target average dose comparison between IMRT with HT and VMAT with HT was highly substantial (P=0.001). The percentage of TCP for IMRT, VMAT, and HT in the Poisson model were 93.70±0.28, 94.68±0.30, and 94.34±0.57, respectively (p<0.05). The dose maximum was lower for the whole lung in the HT plan, with an average dose of 49.31Gy±3.9 (p<0.009). The NTCP values of both Niemierko and LKB models were lower for the heart, lungs, and liver for the IMRT plan. The sparing of organs at risk was higher in the HT plan dosimetrically, and the TCP was higher in the three techniques. The comparison between the three techniques shows that the IMRT and HT techniques could be considered for treating SBBC.

Dosimetric predictors and Lyman normal tissue complication probability model of hematological toxicity in cervical cancer patients with treated with pelvic irradiation.

PurposeTo identify dosimetric parameters associated with acute hematological toxicity (HT) and identify the corresponding normal tissue complication probability (NTCP) model in cervical cancer patients receiving helical tomotherapy (Tomo) or fixed‐field intensity‐modulated radiation therapy (ff‐IMRT) in combination with chemotherapy, that is, concurrent chemoradiotherapy (CCRT) using the Lyman–Kutcher–Burman normal tissue complication probability (LKB‐NTCP) model.MethodsData were collected from 232 cervical cancer patients who received Tomo or ff‐IMRT from 2015 to 2018. The pelvic bone marrow (PBM) (including the ilium, pubes, ischia, acetabula, proximal femora, and lumbosacral spine) was contoured from the superior boundary (usually the lumbar 5 vertebra) of the planning target volume (PTV) to the proximal end of the femoral head (the lower edge of the ischial tubercle). The parameters of the LKB model predicting ≥grade 2 hematological toxicity (Radiation Therapy Oncology Group [RTOG] grading criteria) (TD 50(1), m, and n) were determined using maximum likelihood analyses. Univariate and multivariate logistic regression analyses were used to identify correlations between dose–volume parameters and the clinical factors of HT.ResultsIn total, 212 (91.37%) patients experienced ≥grade 2 hematological toxicity. The fitted normal tissue complication probability model parameters were TD 50(1) = 38.90 Gy (95%CI, [36.94, 40.96]), m = 0.13 (95%CI [0.12, 0.16]), and n = 0.04 (95%CI [0.02, 0.05]). Per the univariate analysis, the NTCP (the use of LKB‐NTCP with the set of model parameters found, p = 0.023), maximal PBM dose (p = 0.01), mean PBM dose (p = 0.021), radiation dose (p = 0.001), and V 16–53 (p < 0. 05) were associated with ≥grade 2 HT. The NTCP (the use of LKB‐NTCP with the set of model parameters found, p = 0.023; AUC = 0.87), V 16, V 17, and V 18 ≥ 79.65%, 75.68%, and 72.65%, respectively (p < 0.01, AUC = 0.66∼0.68), V 35 and V 36 ≥ 30.35% and 28.56%, respectively (p < 0.05; AUC = 0.71), and V 47 ≥ 13.43% (p = 0.045; AUC = 0.80) were significant predictors of ≥grade 2 hematological toxicity from the multivariate logistic regression analysis.ConclusionsThe volume of the PBM of patients treated with concurrent chemoradiotherapy and subjected to both low‐dose (V 16–18) and high‐dose (V 35,36 and V 47) irradiation was associated with hematological toxicity, depending on the fractional volumes receiving the variable degree of dosage. The NTCP were stronger predictors of toxicity than V 16–18, V 35, 36, and V 47. Hence, avoiding radiation hot spots on the PBM could reduce the incidence of severe HT.

Dosimetric validation of two different radiobiological models for parotid gland functionality of tongue cancer

AbstractObjectiveThe aim of this study was to investigate the normal tissue complication probability (NTCP) for parotid gland of ca tongue patients from two different radiobiological models and to establish a dosimetric validity.MethodsLyman–Kutcher–Burman (LKB) model and linear quadratic (LQ) model were considered for determination of NTCP and tolerance dose (TD5/5 and TD50/5) for the parotid gland of 67 number of ca tongue patients who were treated with the volumetric arc therapy (VMAT) technique. An in‐house developed software on Excel (VBA) was used for this study.ResultsThe equivalent uniform dose (EUD) was linearly proportional to the effective volume (veff) for parotid glands and there was a strong correlation between EUD and veff. At EUD = 46 to 47 Gy, the NTCP of parotid was 0.5 for both the models. The tolerance doses, TD5/5 (veff) and TD50/5 (veff) were exponentially reduced with increase of veff for LKB model; whereas these parameters were volume‐independent in the LQ model. TD5/5 (veff) and TD50/5 (veff) were 31.98 Gy and 45.98 Gy respectively for all 67 patients in the LQ model. Below TD50/5, NTCP of LKB model was less than the NTCP , calculated from LQ model.ConclusionOne may consider radiobiological LQ model for estimation of clinical tolerance dose for OARs. Due to lack of clinical data, there are inaccuracy in determination of NTCP from LQ model. If sufficient number of tolerance data for partial volumes are available, the prediction of NTCP would be more confident.

Prediction of Pituitary Gland Complications by LKB and Log-Logistic Radiobiological Models in 3D Conformal Radiation Therapy of Head and Neck Tumors

Introduction: The pituitary gland is frequently irradiated during radiation therapy of head and neck tumors which can influence the quality of life of the patients after radiation therapy. This study aimed to estimate the normal tissue complication probability (NTCP) for the pituitary gland in head and neck cancers using two radiobiological models. Material and Methods: 53 patients including 20 cases with nasopharyngeal cancer and 33 cases with brain tumor were studied. The dosimetric properties of each plan including minimum, mean and maximum doses were extracted from the dose-volume histogram curve. For estimation of pituitary gland response for each patient, the BIOPLAN software was used to calculate NTCP by LKB model and Matlab software was applied to calculate NTCP by equivalent uniform dose (EUD) model. Models’ parameters including TD50, , and‘a’ were extracted from a previous study of radiobiological modeling of pituitary gland response to radiation therapy. For statistical analysis, the T-test was used to compare two models. Results: The average mean doses of 30.42 and 51.29 (Gy) of the pituitary gland were obtained for nasopharyngeal and brain tumor patients, respectively. The average NTCPs of the pituitary gland for nasopharyngeal patients estimated by LKB and Log-logistic models were 3.84 and 3.91%, respectively. In brain tumors, the average NTCP was 16.33% for LKB and 16.41% for Log-logistic models. The results showed that the log-logistic and LKB models provided comparable results and no statistically significant difference (P-value< 0.05) was found between two models. Conclusion: The NTCP results indicated that the average NTCP of the pituitary gland for nasopharyngeal patients was approximately four times lower than that of brain tumors. Finally, implementation of follow up studies and modeling investigations are recommended for accurate estimation of pituitary gland complications following radiation therapy.

Dose-response relationships of intestinal organs and excessive mucus discharge after gynaecological radiotherapy.

BackgroundThe study aims to determine possible dose-volume response relationships between the rectum, sigmoid colon and small intestine and the ‘excessive mucus discharge’ syndrome after pelvic radiotherapy for gynaecological cancer.Methods and materialsFrom a larger cohort, 98 gynaecological cancer survivors were included in this study. These survivors, who were followed for 2 to 14 years, received external beam radiation therapy but not brachytherapy and not did not have stoma. Thirteen of the 98 developed excessive mucus discharge syndrome. Three self-assessed symptoms were weighted together to produce a score interpreted as ‘excessive mucus discharge’ syndrome based on the factor loadings from factor analysis. The dose-volume histograms (DVHs) for rectum, sigmoid colon, small intestine for each survivor were exported from the treatment planning systems. The dose-volume response relationships for excessive mucus discharge and each organ at risk were estimated by fitting the data to the Probit, RS, LKB and gEUD models.ResultsThe small intestine was found to have steep dose-response curves, having estimated dose-response parameters: γ50: 1.28, 1.23, 1.32, D50: 61.6, 63.1, 60.2 for Probit, RS and LKB respectively. The sigmoid colon (AUC: 0.68) and the small intestine (AUC: 0.65) had the highest AUC values. For the small intestine, the DVHs for survivors with and without excessive mucus discharge were well separated for low to intermediate doses; this was not true for the sigmoid colon. Based on all results, we interpret the results for the small intestine to reflect a relevant link.ConclusionAn association was found between the mean dose to the small intestine and the occurrence of ‘excessive mucus discharge’. When trying to reduce and even eliminate the incidence of ‘excessive mucus discharge’, it would be useful and important to separately delineate the small intestine and implement the dose-response estimations reported in the study.

Proposals of models for new formulations of the current complication-free cure (P+) and uncomplicated tumor control probability (UTCP) concepts, and total normal tissue complication probability of late complications

This study proposes phenomenological models for total normal tissue complication probability (TNTCP) and NTCP0. NTCP0 is a new acronym for reformulating the current complication-free cure (P+) and uncomplicated tumor control probability (UTCP) concepts, and TNTCP will reformulate the current NTCP involving multiple organs at risks. The current probabilistic concepts are incoherently formulated with mathematical operations of tumor control probability (TCP) and normal tissue complication probability (NTCP) that are associated with different stochastic processes and random variables. NTCP0 is equal to NTCP0 (normal tissue non-complication probability) that is calculated as the ratio of a number of patients of a population without late complications and a total of them. As a cumulative distribution function (CDF) of late complications, TNTCP = sum(NTCPi), where NTCPi is the NTCP of the ith late complication. TNTCP is also a new acronym, and the probabilistic complement of NTCP0, then NTCP0 = 100% − TNTCP. The NTCP0/TNTCP (D(d)) proposing models are based on the relationship between the NTCP0/TNTCP and total dose (D = n×d; where d = dose per fraction, and n = number of fractions). TNTCP(D) model will be correlated with LKB model (the normal CDF) that is an increasing function; and NTCP0(D) model with a decreasing function, which additionally will define clear limits of three possible regions for NTCP0: 0 and 100% deterministic, and a stochastic. These models are function D, which is widely used for characterizing radiation therapies.

Normal Tissue Complication Probability (NTCP) modeling and validation of quantitative analysis of normal tissue effects in the clinic (QUANTEC) guideline using quality of life questionnaire for parotid gland during head and neck radiotherapy

Introduction: Radiation therapy is the main treatment method for head and neck cancers, which comprise 3–5% of all cancers. A major side effect of this treatment is complication of the parotid glands, i.e. xerostomia, which occurs at relatively low doses. This complication leads to mouth dryness which is the most common problem for head and neck cancer survivors. There are different grades of xerostomia and severe xerostomia is defined as a long-term reduction in the function of salivary gland to less than 25% relative to the pre-radiotherapy baseline value. The grading of xerostomia is usually assessed by patient self-reports carried out by the quality of life questionnaire (QoL), designed based on indigenous criteria and internationally recognized protocols. In recent years several studies have focused on normal tissue complication probability (NTCP) modeling of xerostomia using quality of life questionnaires with or without functional analysis based on various standard model parameters. Lyman (LKB) model is commonly used to predict the normal tissue complication probability (NTCP). This model uses the patient’s calculated dose volume histogram of (DVH) of an organ at risk (OAR) and the dose response curve parameters. The quantitative analysis of normal tissue effects in the clinic (QUANTEC) effort is to refine the guidelines based on 3D dose/volume and outcome data. According to QUANTEC guideline to limit the severity of xerostomia, maximum dose received by one or both of parotid glands should be 20 Gy and 25 Gy (20/25 Gy), respectively. The aim of this study was to evaluate the NTCP model parameters for all grades of acute parotid complications using the LKB model during head and neck conformal radiotherapy treatment and using a QoL questionnaire. Materials and Methods: 50 patients with head and neck cancer who have been referred for radiotherapy to Milad Hospital in Isfahan, Iran, were selected. QoL questionnaire datasets of patients with squamous cell carcinoma and lymph node cancers beside the parotids were within the radiation field were analyzed. The European organization for research and treatment of cancer (EORTC) QLQ HN35 was used in three stages (before, during and at the end of treatment). Prescribed dose per fraction was modified to 2 Gy/fraction equivalent dose for each patients. The LKB model with DVH reduction to form the equivalent uniform dose (EUD), known as LEUD was used. The model parameters of TD50 (Tolerance Dose 50%) and m was assessed by fitting the patient reported complication data to the normal tissue complication probability (NTCP) curve. Results: One patient (2%) at stage 2 and 5 patients (10%) at stage 3 experienced grade 3 xerostomia. The dose-response curves (LKB model) for occurrence of xerostomia was fitted to the QoL data which were collected at stages 2 and 3. These parameters were TD50 =23.3Gy, m =1 and TD50 =21.6 Gy, m =1 at stage 2 and stage 3, respectively. Conclusion: The agreement between the NTCP modeling based on QoL questionnaire data and the QUANTEC guidelines, confirms the cutoff values of 20/25 Gy to spare the parotid gland.

Comparison between artificial neural network and radiobiological modeling for prediction of thyroid gland complications of after radiotherapy

Introduction: Hypothyroidism is one of the frequent side effects of radiotherapy of head and neck cancers, breast cancer, and Hodgkin's lymphoma. It is recommended to estimate the normal tissue complication probability of thyroid gland using radiobiological modeling during treatment planning. Moreover, the use of artificial neural network is also proposed as a new method for this aim. The purpose of this study is to compare the results of the radiobiological modeling with the artificial neural network. Materials and Methods: Thyroid dose-volume histograms from a dataset of 44 consecutive patients treated with 3D- CRT for head-and-neck cancers and breast cancer were extracted. Dose-volumetric and radiobiological parameters of thyroid gland including the minimum dose, the maximum dose, the mean dose, TD50, EUD, m, n, and NTCP values calculated by LKB model were used as the input variables of the artificial neural network (ANN) method. The results of each method were then compared with each other. Evaluation of the two methods was estimated using the root- mean-square error (RMSE) and the coefficient of determination (R2). Results: The values for simulation results were RMSE = 0.008 and R2 = 0.99. Using error estimation criteria, results obtained by the ANN method showed the potential prediction of this method for complications of thyroid gland as same as the radiobiological modeling method. Conclusion: Artificial neural network (ANN) can be used in modeling and patients could hopefully benefit from its individualized estimation of normal tissue complications in the clinic.

A prospective radiobiological study of acute esophagitis and swallowing dysfunction in head-and-neck radiotherapy

Introduction: Esophagitis is one of the main causes of swallowing dysfunction after radiation therapy (RT) for head and neck cancer (HNC).It significantly affects patients’ quality of life as well as having a potentially negative impact on their long term survival. However, little has been investigated on the dose-response and normal tissue complication probability (NTCP) of esophagitis in the cervical esophagus (CE), although it is often at risk in neck irradiation. The aim of this study was to investigate the incidence and dose-response relation for acute esophagitis in HNC patients undergoing 3D conformal RT. Materials and Methods: This prospective study consisted of 50 HNC patients. The main studied endpoint was grade 2 or higher acute esophagitis according to the Common Terminology Criteria for Adverse Events v.4 scoring criteria within 9 weeks after the start of RT, assessed using the EORTC QLQ-H&N-35 questionnaire. The mean dose and dose-volume parameters were analyzed for CE and eight other swallowing-related structures including: superior, middle and inferior pharyngeal constrictor muscles (SPCM, MPCM and IPCM, respectively), esophagus inlet muscle (EIM), supraglottic larynx (SGL), base of tongue (BT), glottic larynx and cricopharyngeal muscle. Then, due to the lack of model parameters for acute esophagitis in the CE, the ability of four sets of LKB model parameters available for predicting the NTCP of this endpoint for middle and lower esophagus was evaluated based on the mean CE dose in these patients. Results: Forty three patients (86%) experienced grade ≥ 2 acute esophagitis in the follow-up period (no grades 4 or 5). The V30 of the SPCM, V30-V40 of the MPCM, V50 of the EIM, V40-V55 of the CE, V60 of the BT, and V20-V40 of the SGL, and the mean doses of these six structures, correlated with swallowing dysfunction. The mean dose to the CE was the most significant parameter. The LKB model parameters TD50= 47 Gy, m= 0.36, n= 0.069 showed the current best fit to the observed NTCP. Conclusion: The mean dose and V40-V55 to the CE were significantly associated with swallowing dysfunction. The high number of patients who experienced swallowing complications in this study adds evidence to the necessity of advanced treatment planning and delivery techniques that offer dose optimization to reduce esophagitis in HNC RT. Better LKB model parameters for predicting swallowing dysfunction due to CE dose are also required.

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans

Purpose: The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy.Materials and methods: Fourteen pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value.Results: Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < .05, using the three NTCP concepts. However, applying the same TD50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better.Conclusions: Treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Because estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD50/5, a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient’s plan.

Comparison of three and four-field radiotherapy technique and the effect of laryngeal shield on vocal and spinal cord radiation dose in radiotherapy of non-laryngeal head and neck tumors

Abstract Introduction: Due to the effect of radiation on both the tumor and the surrounding normal tissues, the side effects of radiation in normal tissues are expected. One of the important complications in the head and neck radiotherapy is the doses reached to the larynx and spinal cord of patients with non-laryngeal head and neck tumors. Materials and Methods: In this study, CT scan images of 25 patients with non-laryngeal tumors including; lymph nodes, tongue, oropharynx and nasopharynx were used. A three-field and a four-field treatment planning with and without laryngeal shield in 3D CRT technique were planned for each patient. Subsequently, the values of Dmin, Dmean, Dmax and Dose Volume Histogram from the treatment planning system and NTCP values of spinal cord and larynx were calculated with BIOPLAN and MATLAB software for all patients. Results: Statistical results showed that mean values of doses of larynx in both three and four-field methods were significantly different between with and without shield groups. Comparison of absorbed dose didn’t show any difference between the three and four field methods (P&gt;0.05). Using Shield, just the mean and minimum doses of spinal cord decreased in both three and four fields. The NTCP of the spinal cord and larynx by three and four-field methods with shield in the LKB and EUD models significantly are less than that of the three and four fields without shields, and in the four-field method NTCP of larynx is less than three radiation field. Conclusion: The results of this study indicate that there is no significant difference in doses reached to larynx and spinal cord between the treatments techniques, but laryngeal shield reduce dose and NTCP values in larynx considerably.

PO-0855: Use of the LKB model to fit urethral strictures for prostate patients treated with HDRB

PO-0855: Use of the LKB model to fit urethral strictures for prostate patients treated with HDRB

An integrated strategy of biological and physical constraints in biological optimization for cervical carcinoma

BackgroundFor cervical carcinoma cases, this study aimed to evaluate the quality of intensity-modulated radiation therapy (IMRT) plans optimized by biological constraints. Furthermore, a new integrated strategy in biological planning module was proposed and verified.MethodsTwenty patients of advanced stage cervical carcinoma were enrolled in this study. For each patient, dose volume optimization (DVO), biological model optimization (BMO) and integrated strategy optimization (ISO) plans were created using same treatment parameters. Different biological models were also used for organ at risk (OAR) in BMO plans, which include the LKB and Poisson models. Next, BMO plans were compared with their corresponding DVO plans, in order to evaluate BMO plan quality. ISO plans were also compared with DVO and BMO plans, in order to verify the performance of the integrated strategy.ResultsBMO plans produced slightly inhomogeneity and less coverage of planning target volume (PTV) (V95=96.79, HI = 0.10: p < 0.01). However, the tumor control probability (TCP) value, both from DVO and BMO plans, were comparable. For the OARs, BMO plans produced lower normal tissue complication probability (NTCP) of rectum (NTCP = 0.11) and bladder (NTCP = 0.14) than in the corresponding DVO plans (NTCP = 0.19 and 0.18 for rectum and bladder; p < 0.01 for rectum and p = 0.03 for bladder). V95, D98, CI and HI values that were produced by ISO plans (V95 = 98.31, D98 = 54.18Gy, CI = 0.76, HI = 0.09) were greatly better than BMO plans (V95 = 96.79, D98 = 53.42Gy, CI = 0.71, HI = 0.10) with significant differences. Furthermore, ISO plans produced lower NTCP values of rectum (NTCP = 0.14) and bladder (NTCP = 0.16) than DVO plans (NTCP = 0.19 and 0.18 for rectum and bladder, respectively) with significant differences.ConclusionsBMO plans produced lower NTCP values of OARs compared to DVO plans for cervical carcinoma cases, and resulted in slightly less target coverage and homogeneity. The integrated strategy, proposed in this study, could improve the coverage, conformity and homogeneity of PTV greater than the BMO plans, as well as reduce the NTCP values of OARs greater than the DVO plans.

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

BackgroundPalliative 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).MethodsIn 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).ResultsUsing 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.ConclusionAdvanced 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.

Sci‐Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques ‐ 03: The Potential Benefit Of Esophageal Sparing During Palliative Radiotherapy For Lung Cancer

Puropose:Palliative radiotherapy is an effective technique to alleviate systems of disease burden in late‐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 1%, and from 5 to 3%, respectively. The median NTD mean for the GTV and PTV of the clinically approved POP plans compared to the ES‐IMRT plans were similar.Conclusions: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 tumour control.

SU‐F‐T‐132: Variable RBE Models Predict Possible Underestimation of Vaginal Dose for Anal Cancer Patients Treated Using Single‐Field Proton Treatments

Purpose:Anal cancer patients treated using a posterior proton beam may be at risk of vaginal wall injury due to the increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the beam distal edge. We investigate the vaginal dose received.Methods:Five patients treated for anal cancer with proton pencil beam scanning were considered, all treated to a prescription dose of 54 Gy(RBE) over 28–30 fractions. Dose and LET distributions were calculated using the Monte Carlo simulation toolkit TOPAS. In addition to the standard assumption of a fixed RBE of 1.1, variable RBE was considered via the application of published models. Dose volume histograms (DVHs) were extracted for the planning treatment volume (PTV) and vagina, the latter being used to calculate the vaginal normal tissue complication probability (NTCP).Results:Compared to the assumption of a fixed RBE of 1.1, the variable RBE model predicts a dose increase of approximately 3.3 ± 1.7 Gy at the end of beam range. NTCP parameters for the vagina are incomplete in the current literature, however, inferring value ranges from the existing data we use D50 = 50 Gy and LKB model parameters a=1–2 and m=0.2–0.4. We estimate the NTCP for the vagina to be 37–48% and 42–47% for the fixed and variable RBE cases, respectively. Additionally, a difference in the dose distribution was observed between the analytical calculation and Monte Carlo methods. We find that the target dose is overestimated on average by approximately 1–2%.Conclusion:For patients treated with posterior beams, the vaginal wall may coincide with the distal end of the proton beam and may receive a substantial increase in dose if variable RBE models are applied compared to using the current clinical standard of RBE equal to 1.1. This could potentially lead to underestimating toxicities when treating with protons.