A Decision Support Tool to Optimize Selection of Head and Neck Cancer Patients for Proton Therapy

SIMPLE SUMMARY: A decision support tool was developed to select head and neck cancer patients for proton therapy. The tool uses delineation data to predict expected toxicity risk reduction with proton therapy and can be used before a treatment plan is created. The positive predictive value of the tool is >90%. This tool significantly reduces delays in commencing treatment and avoid redundant photon vs. proton treatment plan comparison. ABSTRACT: Selection of head and neck cancer (HNC) patients for proton therapy (PT) using plan comparison (VMAT vs. IMPT) for each patient is labor-intensive. Our aim was to develop a decision support tool to identify patients with high probability to qualify for PT, at a very early stage (immediately after delineation) to avoid delay in treatment initiation. A total of 151 HNC patients were included, of which 106 (70%) patients qualified for PT. Linear regression models for individual OARs were created to predict the D(mean) to the OARs for VMAT and IMPT plans. The predictors were OAR volume percentages overlapping with target volumes. Then, actual and predicted plan comparison decisions were compared. Actual and predicted OAR D(mean) (VMAT R(2) = 0.953, IMPT R(2) = 0.975) and NTCP values (VMAT R(2) = 0.986, IMPT R(2) = 0.992) were highly correlated. The sensitivity, specificity, PPV and NPV of the decision support tool were 64%, 87%, 92% and 51%, respectively. The expected toxicity reduction with IMPT can be predicted using only the delineation data. The probability of qualifying for PT is >90% when the tool indicates a positive outcome for PT. This tool will contribute significantly to a more effective selection of HNC patients for PT at a much earlier stage, reducing treatment delay

Impact of radiation-induced toxicities on quality of life of patients treated for head and neck cancer

PURPOSE: The aim of this study is to establish the relative impact of physician-rated toxicities and patient-rated symptoms in head and neck cancer (HNC) on quality of life (QOL) and to weigh the various toxicities and symptoms during treatment plan optimization and selection. MATERIALS AND METHODS: This prospective cohort study comprised 1,083 HNC patients (development: 750, validation: 333) treated with definitive radiotherapy with or without chemotherapy. Clinical factors were scored at baseline. Physician-rated and patient-rated outcome measures and QOL (EORTC QLQ-HN35 and QLQ-C30) were prospectively scored at baseline and 6, 12, 18 and 24 months after radiotherapy. The impact of 20 common toxicities and symptoms (related to swallowing, salivary function, speech, pain and general complaints) on QOL (0-100 scale) was established for each time point by combining principal component analysis and multivariable linear regression. RESULTS: Radiation-induced toxicities and symptoms resulted in a significant decline in QOL of patients with 12.4±12.8 points at 6 months to 16.6±17.1 points at 24 months. The multivariable linear models described the QOL points subtracted for each toxicity and symptom after radiotherapy. For example, xerostomia and weight loss had a significant but minor effect (on average -0.5 and -0.6 points) while speech problems and fatigue had a much greater impact (on average -11.9 and -17.4 points) on QOL. R2 goodness-of-fit values for the QOL models ranged from 0.64 (6 months) to 0.72 (24 months). CONCLUSION: The relative impact of physician-rated toxicities and patient-rated symptoms on QOL was quantified and can be used to optimize, compare and select HNC radiotherapy treatment plans, to balance the relevance of toxicities and to achieve the best QOL for individual patients

Effect of painful Ledderhose disease on dynamic plantar foot pressure distribution during walking:a case-control study

Background: Plantar pressure distribution during walking in patients with painful Ledderhose disease is unknown.Research question: Do patients with painful Ledderhose disease have an altered plantar pressure distribution during walking compared to individuals without foot pathologies? It was hypothesized that plantar pressure is shifted away from the painful nodules.Methods: Pedobarography data of 41 patients with painful Ledderhose disease (cases, mean age: 54.2 ± 10.4 years) was collected and compared to pedobarography data from 41 individuals without foot pathologies (controls, mean age: 21.7 ± 2.0 years). Peak Pressure (PP), Maximum Mean Pressure (MMP) and Force-Time Integral (FTI) were calculated for eight regions (heel, medial midfoot, lateral midfoot, medial forefoot, central forefoot, lateral forefoot, hallux and other toes) under the soles of the feet. Differences between cases and controls were calculated and analysed by means of linear (mixed models) regression.Results: Proportional differences in PP, MMP and FTI showed increased values for the cases compared to the controls, especially in the heel, hallux and other toes regions, and decreased values in the medial- and lateral midfoot regions. In naïve regression analysis, being a patient was a predictor for increased- and decreased values for PP, MMP and FTI for several regions. When dependencies in the data were taken into account with linear mixed-model regression analysis, the increased- and decreased values for the patients were most prevalent for FTI at the heel, medial midfoot, hallux and other toes regions.Significance: In patients with painful Ledderhose disease, during walking, a shift of pressure was found towards the proximal and distal foot regions, while offloading the midfoot regions.</p

Quality of life and toxicity guided treatment plan optimisation for head and neck cancer

PURPOSE: To evaluate the feasibility of semi-automatic Quality of Life (QOL)-weighted normal tissue complication probability (NTCP)-guided VMAT treatment plan optimisation in head and neck cancer (HNC) and compare predicted QOL to that obtained with conventional treatment. MATERIALS AND METHODS: This study included 30 HNC patients who were treated with definitive radiotherapy. QOL-weighted NTCP-guided VMAT plans were optimised directly on 80 multivariable NTCP models of 20 common toxicities and symptoms on 4 different time points (6, 12, 18 and 24 months after radiotherapy) and each NTCP model was weighted relative to its impact on QOL. Planning results, NTCP and predicted QOL were compared with the clinical conventional VMAT plans. RESULTS: QOL-weighted NTCP-guided VMAT plans were clinically acceptable, had target coverage equally adequate as the clinical plans, but prioritised sparing of organs at risk (OAR) related to toxicities and symptoms that had the highest impact on QOL. NTCP was reduced for, e.g., dysphagia (-6.1% for ≥ grade 2/ -7.6% for ≥ grade 3) and moderate-to-severe fatigue / speech problems / hoarseness (-0.7%/ -1.5%/ -2.5%) at 6 months, respectively. Concurrently, the average NTCP of toxicities related to salivary function increased with +0.4% to +5.7%. QOL-weighted NTCP-guided plans were produced in less time, were less dependent on the treatment planner experience and yielded more consistent results. The average predicted QOL improved by 0.7, 0.9, 1.0, and 1.1 points on a 0-100 scale (p < 0.001) at 6, 12, 18, and 24 months, respectively, compared to the clinical plans. CONCLUSION: Semi-automatic QOL-weighted NTCP-guided VMAT treatment plan optimisation is feasible. It prioritised sparing of OARs related to high-impact toxicities and symptoms and resulted in a systematic improvement of predicted QOL compared to conventional VMAT

Radiotherapy for Ledderhose disease:Results of the LedRad-study, a prospective multicentre randomised double-blind phase 3 trial

Background and purpose: Radiotherapy is considered a treatment option for Ledderhose disease. However, its benefits have never been confirmed in a randomised controlled trial. Therefore, the LedRad-study was conducted. Materials and methods: The LedRad-study is a prospective multicentre randomised double-blind phase three trial. Patients were randomised to sham-radiotherapy (placebo) or radiotherapy. The primary endpoint was pain reduction at 12 months after treatment, measured with the Numeric Rating Scale (NRS). Secondary endpoints were pain reduction at 6 and 18 months after treatment, quality of life (QoL), walking abilities and toxicity.Results: A total of 84 patients were enrolled. At 12 and 18 months, patients in the radiotherapy group had a lower mean pain score compared to patients in the sham-radiotherapy group (2.5 versus 3.6 (p = 0.03) and 2.1 versus 3.4 (p = 0.008), respectively). Pain relief at 12 months was 74% in the radiotherapy group and 56% in the sham-radiotherapy group (p = 0.002). Multilevel testing for QoL scores showed higher QoL scores in the radiotherapy group compared to the sham-radiotherapy group (p &lt; 0.001). Moreover, patients in the radiotherapy group had a higher mean walking speed and step rate with barefoot speed walking (p = 0.02). Erythema, skin dryness, burning sensations and increased pain were the most frequently reported side effects. These side effects were generally graded as mild (95%) and the majority (87%) were resolved at 18 months follow-up.Conclusion: Radiotherapy for symptomatic Ledderhose disease is an effective treatment resulting in a significant pain reduction, improvement of QoL scores and bare feet walking abilities, in comparison to sham-radiotherapy.</p

A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oropharyngeal Cancer

Purpose: The aim of this study was to generate normal tissue complication probability (NTCP) models in patients treated with either proton beam therapy (PBT) or intensitymodulated radiation therapy (IMRT) for oropharynx cancer and to use a model-based approach to investigate the added value of PBT in preventing treatment complications. Methods and Materials: For patients with advanced-stage oropharynx cancer treated with curative intent (PBT, n = 30; IMRT, n = 175), NTCP models were developed using multivariable logistic regression analysis with backward selection. For PBTtreated patients, an equivalent IMRT plan was generated to serve as a reference to determine the benefit of PBT in terms of NTCP. The models were then applied to the PBT-treated patients to compare predicted and observed clinical outcomes (calibration- in-the-large). Five binary endpoints were analyzed at 6 months after treatment: dysphagia >= grade 2, dysphagia >= grade 3, xerostomia >= grade 2, salivary duct inflammation >= grade 2, and feeding tube dependence. Corresponding toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4. Paired t tests and Wilcoxon rank tests were used to compare mean NTCP results for endpoints between PBT and IMRT. Results: NTCP models developed based on outcomes from all patients were applied to those receiving PBT. NTCP values were calculated for the equivalent IMRT plans for all PBT-treated patients, revealing significantly higher NTCP values with IMRT. PBT was associated with statistically significant reductions in the mean NTCP values for each endpoint at 6 months after treatment, with the largest absolute differences in rates of >= grade 2 dysphagia and >= grade 2 xerostomia. Conclusions: NTCP models predict significant improvements in the probability of short-term, treatment-related toxicity with PBT compared with IMRT for oropharyngeal cancer. This study demonstrates an NTCP model-based approach to compare predicted patient outcomes when randomized data are not available. (C) 2019 Elsevier Inc. All rights reserved

Acute symptoms during the course of head and neck radiotherapy or chemoradiation are strong predictors of late dysphagia

AbstractPurposeTo determine if acute symptoms during definitive radiotherapy (RT) or chemoradiation (CHRT) are prognostic factors for late dysphagia in head and neck cancer (HNC).Material and methodsThis prospective cohort study consisted of 260 HNC patients who received definitive RT or CHRT. The primary endpoint was grade 2–4 swallowing dysfunction at 6months after completing RT (SWALM6). During treatment, acute symptoms, including oral mucositis, xerostomia and dysphagia, were scored, and the scores were accumulated weekly and entered into an existing reference model for SWALM6 that consisted of dose–volume variables only.ResultsBoth acute xerostomia and dysphagia were strong prognostic factors for SWALM6. When acute scores were added as variables to the reference model, model performance increased as the course of treatment progressed: the AUC rose from 0.78 at the baseline to 0.85 in week 6. New models built for weeks 3–6 were significantly better able to identify patients with and without late dysphagia.ConclusionAcute xerostomia and dysphagia during the course of RT are strong prognostic factors for late dysphagia. Including accumulated acute symptom scores on a weekly basis in prediction models for late dysphagia significantly improves the identification of high-risk and low-risk patients at an early stage during treatment and might facilitate individualized treatment adaptation