Assessment of residual geometrical errors of clinical target volumes and their impact on dose accumulation for head and neck radiotherapy

PURPOSE: To assess the residual geometrical errors (dr) and their impact on the clinical target volumes (CTV) dose coverage for head and neck cancer (HNC) proton therapy patients.METHODS: We analysed 28 HNC patients treated with 70 Gy (RBE) and 54.25 Gy (RBE) to the therapeutic CTV70 and prophylactic CTV54.25, respectively. Daily cone beam CTs were converted to high quality synthetic CTs (sCTs). The CTVs from the nominal CT were propagated to the corresponding sCTs using a hybrid deformable image registration (propagated CTVs) in RayStation 11B. For 11 patients, all propagated CTVs were reviewed by our HNC radiation oncologist (physician corrected CTVs). The residual geometrical error dr was quantified as a function of the daily CTVs volume overlap with the nominal plan CTV. The errors dr(propagated CTVs) and dr(physician corrected CTVs) and the difference in dice similarity coefficients (ΔDSC) were determined. Using clinical plans, dose coverage and the tumor control probability (TCP) for the nominal, accumulated and voxel-wise minimum scenarios were determined.RESULTS: The difference in the residual geometrical error dr (propagated CTVs - physician corrected CTVs) and mean DSC (|ΔDSC|mean) were minor: Δdr(CTV70) = 0.16 mm, Δdr(CTV54.25) = 0.26 mm, |ΔDSC|mean &lt; 0.9%. For all 28 patients, dr(CTV70) = 1.91 mm and dr(CTV54.25) = 1.90 mm. However, CTV54.25 above and below the cricoid cartilage differed substantially (1.00 mm c.f. 3.93 mm). The CTV54.25 coverage below the cricoid was then almost always lower, although the TCP of the accumulated dose was higher than the TCP of the voxel-wise minimum dose.CONCLUSIONS: Setup uncertainty setting of 2 mm is possible. The feasibility of using propagated CTVs for error determination is demonstrated.</p

Assessment of residual geometrical errors of clinical target volumes and their impact on dose accumulation for head and neck radiotherapy

Purpose: To assess the residual geometrical errors (dr) and their impact on the clinical target volumes (CTV) dose coverage for head and neck cancer (HNC) proton therapy patients.Methods: We analysed 28 HNC patients treated with 70 Gy (RBE) and 54.25 Gy (RBE) to the therapeutic CTV70 and prophylactic CTV54.25, respectively. Daily cone beam CTs were converted to high quality synthetic CTs (sCTs). The CTVs from the nominal CT were propagated to the corresponding sCTs using a hybrid deformable image registration (propagated CTVs) in RayStation 11B. For 11 patients, all propagated CTVs were reviewed by our HNC radiation oncologist (physician corrected CTVs).The residual geometrical error dr was quantified as a function of the daily CTVs volume overlap with the nominal plan CTV. The errors dr(propagated CTVs) and dr(physician corrected CTVs) and the difference in dice similarity coefficients (ΔDSC) were determined. Using clinical plans, dose coverage and the tumor control probability (TCP) for the nominal, accumulated and voxel-wise minimum scenarios were determined.Results: The difference in the residual geometrical error dr (propagated CTVs – physician corrected CTVs) and mean DSC (|ΔDSC|mean) were minor: Δdr(CTV70) = 0.16 mm, Δdr(CTV54.25) = 0.26 mm, |ΔDSC|mean &lt; 0.9%. For all 28 patients, dr(CTV70) = 1.91 mm and dr(CTV54.25) = 1.90 mm. However, CTV54.25 above and below the cricoid cartilage differed substantially (1.00 mm c.f. 3.93 mm). The CTV54.25 coverage below the cricoid was then almost always lower, although the TCP of the accumulated dose was higher than the TCP of the voxel-wise minimum dose.Conclusions: Setup uncertainty setting of 2 mm is possible. The feasibility of using propagated CTVs for error determination is demonstrated.</p

A novel semi auto-segmentation method for accurate dose and NTCP evaluation in adaptive head and neck radiotherapy

Background and purpose: Accurate segmentation of organs-at-risk (OARs) is crucial but tedious and time-consuming in adaptive radiotherapy (ART). The purpose of this work was to automate head and neck OAR-segmentation on repeat CT (rCT) by an optimal combination of human and auto-segmentation for accurate prediction of Normal Tissue Complication Probability (NTCP). Materials and methods: Human segmentation (HS) of 3 observers, deformable image registration (DIR) based contour propagation and deep learning contouring (DLC) were carried out to segment 15 OARs on 15 rCTs. The original treatment plan was re-calculated on rCT to obtain mean dose (D-mean) and con-sequent NTCP-predictions. The average Dmean and NTCP-predictions of the three observers were referred to as the gold standard to calculate the absolute difference of D-mean and NTCP-predictions (vertical bar AD(mean)vertical bar and vertical bar ANTCP vertical bar). Results: The average vertical bar AD(mean)vertical bar of parotid glands in HS was 1.40 Gy, lower than that obtained with DIR and DLC (3.64 Gy, p < 0.001 and 3.72 Gy, p < 0.001, respectively). DLC showed the highest vertical bar AD(mean)vertical bar in middle Pharyngeal Constrictor Muscle (PCM) (5.13 Gy, p = 0.01). DIR showed second highest vertical bar AD(mean)vertical bar in the cricopharyngeal inlet (2.85 Gy, p = 0.01). The semi auto-segmentation (SAS) adopted HS, DIR and DLC for segmentation of parotid glands, PCM and all other OARs, respectively. The 90th percentile vertical bar ANTCP vertical bar was 2.19%, 2.24%, 1.10% and 1.50% for DIR, DLC, HS and SAS respectively. Conclusions: Human segmentation of the parotid glands remains necessary for accurate interpretation of mean dose and NTCP during ART. Proposed semi auto-segmentation allows NTCP-predictions within 1.5% accuracy for 90% of the cases. (C) 2021 The Author(s). Published by Elsevier B.V

An efficient strategy to select head and neck cancer patients for adaptive radiotherapy

BACKGROUND AND PURPOSE: Adaptive radiotherapy (ART) is workload intensive but only benefits a subgroup of patients. We aimed to develop an efficient strategy to select candidates for ART in the first two weeks of head and neck cancer (HNC) radiotherapy.MATERIALS AND METHODS: This study retrospectively enrolled 110 HNC patients who underwent modern photon radiotherapy with at least 5 weekly in-treatment re-scan CTs. A semi auto-segmentation method was applied to obtain the weekly mean dose (D mean) to OARs. A comprehensive NTCP-profile was applied to obtain NTCP's. The difference between planning and actual values of D mean (ΔD mean) and dichotomized difference of clinical relevance (BIOΔNTCP) were used for modelling to determine the cut-off maximum ΔD mean of OARs in week 1 and 2 (maxΔD mean_1 and maxΔD mean_2). Four strategies to select candidates for ART, using cut-off maxΔD mean were compared. RESULTS: The Spearman's rank correlation test showed significant positive correlation between maxΔD mean and BIOΔNTCP (p-value &lt;0.001). For major BIOΔNTCP (&gt;5%) of acute and late toxicity, 10.9% and 4.5% of the patients were true candidates for ART. Strategy C using both cut-off maxΔD mean_1 (3.01 and 5.14 Gy) and cut-off maxΔD mean_2 (3.41 and 5.30 Gy) showed the best sensitivity, specificity, positive and negative predictive values (0.92, 0.82, 0.38, 0.99 for acute toxicity and 1.00, 0.92, 0.38, 1.00 for late toxicity, respectively). CONCLUSIONS: We propose an efficient selection strategy for ART that is able to classify the subgroup of patients with &gt;5% BIOΔNTCP for late toxicity using imaging in the first two treatment weeks.</p

Impact of sarcopenia on acute radiation-induced toxicity in head and neck cancer patients

Background and purpose: Sarcopenia is related to late radiation-induced toxicities and worse survival in head and neck cancer (HNC) patients. This study tested the hypothesis that sarcopenia improves the performance of current normal tissue complication probability (NTCP) models of radiation-induced acute toxicity in HNC patients. Material/methods: This was a retrospective analysis in a prospective cohort of HNC patients treated from January 2007 to December 2018 with (chemo)radiotherapy. Planning CT scans were used for evaluating skeletal muscle mass. Characteristics of sarcopenic and non-sarcopenic patients were compared. The impact of sarcopenia was analysed by adding sarcopenia to the linear predictors of current NTCP models predicting physician- and patient-rated acute toxicities. Results: The cut-off values of sarcopenia in the study population (n = 977) were established at skeletal muscle index = 2, p = 3 dysphagia (week 3-6 during RT, p 0.99). Conclusion: Sarcopenia in HNC patients was an independent prognostic factor for radiation-induced physician-rated acute grade >= 3 dysphagia, which might be explained by its impact on swallowing muscles. However, addition of sarcopenia did not improve the NTCP model performance. (c) 2022 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 170 (2022) 122-128 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Development of advanced preselection tools to reduce redundant plan comparisons in model-based selection of head and neck cancer patients for proton therapy

PURPOSE: In the Netherlands, head and neck cancer (HNC) patients are selected for proton therapy (PT) based on estimated normal tissue complication probability differences (ΔNTCP) between photons and protons, which requires a plan comparison (VMAT vs. IMPT). We aimed to develop tools to improve patient selection for plan comparisons. METHODS: This prospective study consisted of 141 consecutive patients in which a plan comparison was done. IMPT plans of patients not qualifying for PT were classified as 'redundant'. To prevent redundant IMPT planning, 5 methods that were primarily based on regression models were developed to predict IMPT Dmean to OARs, by using data from VMAT plans and volumetric data from delineated targets and OARs. Then, actual and predicted plan comparison outcomes were compared. The endpoint was being selected for proton therapy. RESULTS: Seventy out of 141 patients (49.6%) qualified for PT. Using the developed preselection tools, redundant IMPT planning could have been prevented in 49-68% of the remaining 71 patients not qualifying for PT (=specificity) when the sensitivity of all methods was fixed to 100%, i.e., no false negative cases (positive predictive value range: 57-68%, negative predictive value: 100%). CONCLUSION: The advanced preselection tools, which uses volume and VMAT dose data, prevented labour intensive creation of IMPT plans in up to 68% of non-qualifying patients for PT. No patients qualifying for PT would have been incorrectly denied a plan comparison. This method contributes significantly to a more cost-effective model-based selection of HNC patients for PT

Patient-Reported Toxicity and Quality-of-Life Profiles in Patients With Head and Neck Cancer Treated With Definitive Radiation Therapy or Chemoradiation

Purpose: Radiation therapy is an effective but burdensome treatment for head and neck cancer (HNC). We aimed to characterize the severity and time pattern of patient-reported symptoms and quality of life in a large cohort of patients with HNC treated with definitive radiation therapy, with or without systemic treatment. Methods and Materials: A total of 859 patients with HNC treated between 2007 and 2017 prospectively completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Head and Neck Cancer module (QLQ-HN35) and Core Quality of Life Questionnaire (QLQ-C30) at regular intervals during and after treatment for up to 5 years. Patients were classified into 3 subgroups: early larynx cancer, infrahyoideal cancer, and suprahyoideal cancer. Outcome scales of both questionnaires were quantified per subgroup and time point by means of average scores and the frequency distribution of categorized severity (none, mild, moderate, and severe). Time patterns and symptom severity were characterized. Toxicity profiles were compared using linear mixed model analysis. Additional toxicity profiles based on age, human papillomavirus status, treatment modality, smoking status, tumor site, and treatment period were characterized as well. Results: The study population consisted of 157 patients with early larynx cancer, 304 with infrahyoideal cancer, and 398 with suprahyoideal cancer. The overall questionnaire response rate was 83%. Generally, the EORTC QLQ-HN35 symptoms reported showed a clear time pattern, with increasing scores during treatment followed by a gradual recovery in the first 2 years. Distinct toxicity profiles were seen across subgroups (P < .001), with generally less severe symptom scores in the early larynx subgroup. The EORTC QLQ-C30 functioning, quality-of-life, and general symptoms reported showed a less evi- dent time pattern and less pronounced differences in mean scores between subgroups, although differences were still signifi- cant (P < .001). Differences in mean scores were most pronounced for role functioning, appetite loss, fatigue, and pain. Conclusions: We established patient-reported toxicity and quality-of-life profiles that showed different patterns for 3 sub-groups of patients with HNC. These profiles provide detailed information on the severity and persistence of various symptoms as experienced by patients during and after definitive radiation therapy. These profiles can be used to inform treatment of future patients and may serve as a benchmark for future studies. (C) 2021 The Authors. Published by Elsevier Inc

Proton therapy of a pregnant patient with nasopharyngeal carcinoma

Background and purpose: Radiotherapy during pregnancy is rarely administered due to lack of data and practical challenges. This is the first detailed report of proton therapy as cancer treatment for a pregnant patient with nasopharyngeal carcinoma. Materials and methods: Pencil beam scanning proton therapy was prescribed to a pregnant patient to a total dose of 70 Gy (RBE) to the therapeutic CTV and 54.25 Gy to the prophylactic CTV, delivered in 35 fractions with a simultaneous integrated boost technique. Results: Phantom measurements showed a thirty-fold decrease in fetal radiation dose when using proton compared to photon therapy, with a total fetal dose of 5.5 mSv for the complete proton treatment, compared to 185 and 298 mSv for the photon treatment with and without lead shielding, respectively. After adminstering proton therapy during pregnancy, at 39 weeks of gestation, a healthy boy with a birthweight on the 83th percentile was delivered. Pediatric follow-up at 2 months of age of the offspring showed normal growth and age-adequate motor development with no signs of neurological problems. MR follow-up of the tumor 3 months after the end of treatment showed complete remission. Conclusion: This case demonstrates the potential of proton therapy for treatment during pregnancy. Compared to photon therapy, proton therapy can significantly limit fetal dose, while simultaneously offering a more optimized treatment to the patient

Volledigheid en toxiciteit van adjuvante chemotherapie bij patiënten met colorectaal carcinoom: een retrospectieve analyse van 78 patiënten

Background: Colorectal cancer is one of the most common malignancies in the Netherlands, with over 10.000 new patients every year. Patients with high risk colorectal cancer are treated with adjuvant chemotherapy after surgical resection of the primary tumor. This chemotherapy consists of eight cycles capecitabine monotherapy or eight cycles capecitabine combined with oxaliplatin (CapOx). The toxicity of this treatment often is a limiting factor for the completion of the treatment. Current insights are based on patient populations from trials with strict in- and exclusion criteria. Purpose: This study is conducted to gain insight about the toxicity that occurs during chemotherapeutic treatment in patient populations in the daily practice. The primary goal is to evaluate the proportion of patients that complete the treatment as planned. Secondary goals are to identify the consequences of the toxicity for the treatment (delay, dose reduction and withdrawal) and to evaluate the reasons for changing or early withdrawal of the treatment. Methods: The study is a retrospective analysis of patients who started adjuvant treatment for colorectal carcinoma in the Isala Klinieken between January 2009 and June 2012. The toxicity is graded according the ‘Common Terminology Criteria for Adverse Events, version 4.03’ (June 2010). The proportion of patients that complete the treatment as planned were compared between capecitabine monotherapy and CapOx. The forms of toxicity were compared between chemotherapy (CapOx vs capecitabine monotherapy), sex (male vs female) and age (<65 vs ≥65). Results: A total of 78 patients were included, 63 received CapOx , the other 15 received capecitabine monotherapy. Only 8 (12.7%) patients treated with CapOx completed treatment as planned. Of the patients treated with capecitabine monotherapie 4 (26.7%) completed the treatment. The most common forms of toxicity (grade 1-4) in the patients treated with CapOx, were neurotoxicity (92.2%), nausea (79.4%) and anaemia (74.6%). Hand-foot-syndrome (60.0%), diarrhoea (53.3%) and nausea (40.0%) were the most common forms of toxicity in patients treated with capecitabine. The most common grade 3/4 toxicity in patients treated with CapOx were nausea (14.3%) and neurotoxicity (12.7%). Diarrhoea (26.6%) and nausea (20.0%) were most common in patients treated with capecitabine monotherapy. Grade 1-4 bone marrow toxicity, neurotoxicity and nausea were significantly higher with CapOx compared to capecitabine monotherapy. Grade 1-4 thrombocytopenia was significantly higher in men compared to women, grade 3 hand-foot-syndrome was significantly higher in women. Grade 1-4 nausea was significantly higher in older patients compared to younger patients. Conclusion: Compared with two fase III studies (Cassidy et al, 2008 and Schmoll et al, 2007), the proportion of patients in our study that complete the treatment as planned was low. The toxicity is comparable with data from other studies. A possible explanation for the low proportion of patients that complete the treatment, is that the oncologists in our hospital consider a different definition of unacceptable toxicity such as occurrence of combinations of low grade toxicities within one patient. Another explanation could be that other forms of toxicity, which are not well documented play a roll in altering the treatment.

Assessment of residual geometrical errors of clinical target volumes and their impact on dose accumulation for head and neck radiotherapy

Purpose: To assess the residual geometrical errors (dr) and their impact on the clinical target volumes (CTV) dose coverage for head and neck cancer (HNC) proton therapy patients.Methods: We analysed 28 HNC patients treated with 70 Gy (RBE) and 54.25 Gy (RBE) to the therapeutic CTV70 and prophylactic CTV54.25, respectively. Daily cone beam CTs were converted to high quality synthetic CTs (sCTs). The CTVs from the nominal CT were propagated to the corresponding sCTs using a hybrid deformable image registration (propagated CTVs) in RayStation 11B. For 11 patients, all propagated CTVs were reviewed by our HNC radiation oncologist (physician corrected CTVs).The residual geometrical error dr was quantified as a function of the daily CTVs volume overlap with the nominal plan CTV. The errors dr(propagated CTVs) and dr(physician corrected CTVs) and the difference in dice similarity coefficients (ΔDSC) were determined. Using clinical plans, dose coverage and the tumor control probability (TCP) for the nominal, accumulated and voxel-wise minimum scenarios were determined.Results: The difference in the residual geometrical error dr (propagated CTVs – physician corrected CTVs) and mean DSC (|ΔDSC|mean) were minor: Δdr(CTV70) = 0.16 mm, Δdr(CTV54.25) = 0.26 mm, |ΔDSC|mean &lt; 0.9%. For all 28 patients, dr(CTV70) = 1.91 mm and dr(CTV54.25) = 1.90 mm. However, CTV54.25 above and below the cricoid cartilage differed substantially (1.00 mm c.f. 3.93 mm). The CTV54.25 coverage below the cricoid was then almost always lower, although the TCP of the accumulated dose was higher than the TCP of the voxel-wise minimum dose.Conclusions: Setup uncertainty setting of 2 mm is possible. The feasibility of using propagated CTVs for error determination is demonstrated.</p