Publications by authors named "Johannes A Langendijk"

358 Publications

Radiotherapy as nose preservation treatment strategy for cancer of the nasal vestibule: the Dutch experience.

Radiother Oncol 2021 Sep 3. Epub 2021 Sep 3.

Department of Radiation Oncology, Radboud University Medical Center, Geert Grooteplein Zuid 32, 6525 GA Nijmegen, The Netherlands.

Background And Purpose: Primary radiotherapy is often preferred for early-stage cancer of the nasal vestibule (CNV), combining high disease control with preservation of nasal anatomy. However, due to practice variation and an absence of comparative trials, no consensus exists on preference for brachytherapy (BT) or external beam radiotherapy (EBRT). We compared these modalities in terms of disease control, nose preservation rates and toxicity.

Materials And Methods: Medical records of 225 patients with T1-T2 squamous cell carcinoma of the nasal vestibule treated with 3D image-guided primary radiotherapy between Jan 2010 and Dec 2016 in 6 Dutch institutions were reviewed retrospectively.

Results: 153 of 225 patients were treated with BT, 65 with EBRT and 7 with other modalities. Median follow-up was 46 months. Overall 3-year local control (LC) and regional control (RC) were 87% and 89%. Five-year disease-specific survival (DSS) and overall survival (OS) were 94% and 82%. Three-year survival with preserved nose (SPN) was 76%. BT provided higher 3-year LC (95% vs 71%, p<0·01) and SPN compared with EBRT (82% vs 61%, p<0·01). Multivariable and propensity-score-matched cohort analyses confirmed better outcomes after BT. No difference was seen in DSS or OS. Five-year incidence of CTCAE 5.0 grade ≥2 toxicity was higher after BT (20% vs 3%, p=0·03) and consisted mostly of radiation ulcers. 50% of all late toxicity recovered.

Conclusion: In this largest-to-date multicenter analysis of T1-T2 CNV, BT achieved superior LC and SPN compared with EBRT. Grade 1-2 radiation ulcers occurred more frequently after brachytherapy, but were transient in half the cases. Considering these results, BT can be recommended as first-line treatment for T1-T2 CNV.
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http://dx.doi.org/10.1016/j.radonc.2021.08.018DOI Listing
September 2021

Associations between testosterone and patient reported sexual outcomes among male and female head and neck cancer patients before and six months after treatment: A pilot study.

Oral Oncol 2021 Aug 27;121:105505. Epub 2021 Aug 27.

Department of Sexology and Psychosomatic OBGYN, Amsterdam Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.

Objectives: To investigate associations between testosterone and patient reported sexual problems and need for sexual care in head and neck cancer patients at time of diagnosis and 6 months after treatment.

Patients And Methods: Data and samples were used of 40 patients (20 men, 20 women) before and 6 months after treatment. Outcome measures were total testosterone level (TT) and free testosterone index (FTI), testosterone insufficiency (TI), the EORTC QLQ-HN35 Sexuality subscale, the subscales of the International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), and the Sexuality subscale of the Short-Form Supportive Care Needs Survey (SCNS-SF34).

Results: In men, higher FTI before treatment was significantly associated with better IIEF Orgasm (p = 0.020) and at 6 months follow-up with IIEF Desire (p = 0.019). Before treatment, insufficient testosterone was present in 5 males (25%) and in 3 at follow-up (15%) (2 patients who had TI before treatment plus one). In women, higher TT at follow-up was significantly associated with better EORTC Sexuality (p = 0.031) and FSFI Satisfaction (p = 0.020); FTI at follow-up was associated with FSFI Satisfaction (p = 0.012). Before treatment, TI was present in 2 women (10%) and in 3 (15%) at follow-up (the same 2 patients plus one).

Conclusion: This pilot study showed that testosterone seems to be associated with patient reported sexual outcomes among male and female head and neck cancer patients. It is estimated that 10-25% of HNC patients may have testosterone insufficiency before treatment and/or at 6 months after treatment.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105505DOI Listing
August 2021

High DNMT1 Is Associated With Worse Local Control in Early-Stage Laryngeal Squamous Cell Carcinoma.

Laryngoscope 2021 Aug 24. Epub 2021 Aug 24.

Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Objectives/hypothesis: Early-stage laryngeal squamous cell carcinoma (LSCC) has yielded local control rates of 75% after radiotherapy. DNA methylation, in which DNA methyltransferases play an important role, has influence on tumorigenesis. In this study, we investigated the association between the expression of DNA methyltransferase 1 (DNMT1) and local control in early-stage LSCC treated with radiotherapy.

Study Design: Retrospective cohort study.

Methods: We analyzed a well-defined homogeneous series of 125 LSCC patients treated with radiotherapy with curative intent. The association of immunohistochemical expression of DNMT1 with local control was evaluated using Cox proportional hazard regression models.

Results: With a median follow-up of 58 months, 29 local recurrences (23%) were observed. On univariate analysis, worse local control was associated with high DNMT1 expression (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.10-6.01). Also, higher T-stage (HR 2.48, 95% CI 1.06-5.80) and positive N-status (HR 2.62, 95% CI 1.06-6.47) were associated with worse local control. Multivariate Cox regression demonstrated that high DNMT1 (HR 2.81; 95% CI 1.20-6.58) was independently associated with worse local control.

Conclusions: We found an association between high DNMT1 expression and worse local control in a homogeneous well-defined cohort of early-stage LSCC patients treated with definitive radiotherapy. The association between DNA methylation status as determined by DNMT1 expression and local control suggests that DNMT1 acts as a potential prognostic tumor marker in treatment decision-making in early-stage laryngeal carcinoma.

Level Of Evidence: NA Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29833DOI Listing
August 2021

Validation of separate multi-atlases for auto segmentation of cardiac substructures in CT-scans acquired in deep inspiration breath hold and free breathing.

Radiother Oncol 2021 Jul 31;163:46-54. Epub 2021 Jul 31.

Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.

Background And Purpose: Developing NTCP-models for cardiac complications after breast cancer (BC) radiotherapy requires cardiac dose-volume parameters for many patients. These can be obtained by using multi-atlas based automatic segmentation (MABAS) of cardiac structures in planning CT scans. We investigated the relevance of separate multi-atlases for deep inspiration breath hold (DIBH) and free breathing (FB) CT scans.

Materials And Methods: BC patients scanned in DIBH (n = 10) and in FB (n = 20) were selected to create separate multi-atlases consisting of expert panel delineations of the whole heart, atria and ventricles. The accuracy of atlas-generated contours was validated with expert delineations in independent datasets (n = 10 for DIBH and FB) and reported as Dice coefficients, contour distances and dose-volume differences in relation to interobserver variability of manual contours. Dependency of MABAS contouring accuracy on breathing technique was assessed by validation of a FB atlas in DIBH patients and vice versa (cross-validation).

Results: For all structures the FB and DIBH atlases resulted in Dice coefficients with their respective reference contours ≥ 0.8 and average contour distances ≤ 2 mm smaller than slice thickness of (CTs). No significant differences were found for dose-volume parameters in volumes receiving relevant dose levels (WH, LV and RV). Accuracy of the DIBH atlas was at least similar to, and for the ventricles better than, the interobserver variation in manual delineation. Cross-validation between breathing techniques showed a reduced MABAS performance.

Conclusion: Multi-atlas accuracy was at least similar to interobserver delineation variation. Separate atlases for scans made in DIBH and FB could benefit atlas performance because accuracy depends on breathing technique.
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http://dx.doi.org/10.1016/j.radonc.2021.07.025DOI Listing
July 2021

Assessment of a diaphragm override strategy for robustly optimized proton therapy planning for esophageal cancer patients.

Med Phys 2021 Jul 20. Epub 2021 Jul 20.

Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Purpose: To ensure target coverage in the treatment of esophageal cancer, a density override to the region of diaphragm motion can be applied in the optimization process. Here, we evaluate the benefit of this approach during robust optimization for intensity modulated proton therapy (IMPT) planning.

Materials And Methods: For 10 esophageal cancer patients, two robustly optimized IMPT plans were created either using (WDO) or not using (NDO) a diaphragm density override of 1.05 g/cm during plan optimization. The override was applied to the excursion of the diaphragm between exhale and inhale. Initial robustness evaluation was performed for plan acceptance (setup errors of 8 mm, range errors of ±3%), and subsequently, on all weekly repeated 4DCTs (setup errors of 2 mm, range errors of ±3%). Target coverage and hotspots were analyzed on the resulting voxel-wise minimum (Vw ) and voxel-wise maximum (Vw ) dose distributions.

Results: The nominal dose distributions were similar for both WDO and NDO plans. However, visual inspection of the Vw of the WDO plans showed hotspots behind the right diaphragm override region. For one patient, target coverage and hotspots improved by applying the diaphragm override. We found no differences in target coverage in the weekly evaluations between the two approaches.

Conclusion: The diaphragm override approach did not result in a clinical benefit in terms of planning and interfractional robustness. Therefore, we do not see added value in employing this approach as a default option during robust optimization for IMPT planning in esophageal cancer.
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http://dx.doi.org/10.1002/mp.15114DOI Listing
July 2021

National Protocol for Model-Based Selection for Proton Therapy in Head and Neck Cancer.

Int J Part Ther 2021 25;8(1):354-365. Epub 2021 Jun 25.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

In the Netherlands, the model-based approach is used to identify patients with head and neck cancer who may benefit most from proton therapy in terms of prevention of late radiation-induced side effects in comparison with photon therapy. To this purpose, a National Indication Protocol Proton therapy for Head and Neck Cancer patients (NIPP-HNC) was developed, which has been approved by the health care authorities. When patients qualify according to the guidelines of the NIPP-HNC, proton therapy is fully reimbursed. This article describes the procedures that were followed to develop this NIPP-HNC and provides all necessary information to introduce model-based selection for patients with head and neck cancer into routine clinical practice.
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http://dx.doi.org/10.14338/IJPT-20-00089.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270079PMC
June 2021

A Systematic Review of Proton Therapy for the Management of Nasopharyngeal Cancer.

Int J Part Ther 2021 25;8(1):119-130. Epub 2021 Jun 25.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose: With improved technology, more patients with nasopharyngeal cancer (NPC) are receiving definitive treatment with proton therapy, which allows greater sparing of dose to normal tissues without compromising efficacy. As there is no randomized data, the purpose of this study was to systematically review the available literature on proton therapy in this setting, focusing on the toxicity endpoints.

Materials And Methods: A systematic search using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was conducted in 5 databases: PubMed, Embase, SCOPUS, Web of Science, and the Cochrane Central Register of Controlled Trials. A total of 491 studies were found on the topic of NPC and proton therapy. Following independent study selection by 2 investigators, 9 studies were found to have sufficient focus and relevance to be incorporated into the systematic review.

Results: All 9 studies were retrospective and examined only NPC patients except for one that also included paranasal sinus cancer. One study was a reirradiation study. Four studies used 3D or double scatter technique, while all others used intensity-modulated proton therapy. Oncologic outcomes were similar to intensity-modulated radiation therapy (IMRT) rates, with 2-year local and regional progression-free survival (LRFS) ranging from 84% to 100%, 2-year progression-free survival (PFS) ranging from 75% to 88.9%, and 2-year overall survival (OS) ranging from 88% to 95% in the up-front setting. Four comparison studies with IMRT found significantly lower feeding tube rates (20% versus 65%,  = .015; and 14% versus 85%,  < .001) with proton therapy as well as lower mucositis (G2 46% versus 70%,  = .019; and G3 11% versus 76%,  = .0002). All other acute and late effects were largely improved with proton therapy but not statistically significant.

Conclusions: NPC patients receiving proton therapy maintain good outcomes with improved toxicity profile, likely due to sparing of dose to normal structures. Prospective studies are ongoing to better quantify the magnitude.
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http://dx.doi.org/10.14338/IJPT-20-00082.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270076PMC
June 2021

PTCOG Head and Neck Subcommittee Consensus Guidelines on Particle Therapy for the Management of Head and Neck Tumors.

Int J Part Ther 2021 25;8(1):84-94. Epub 2021 Jun 25.

The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: Radiation therapy is a standard modality in the treatment for cancers of the head and neck, but is associated with significant short- and long-term side effects. Proton therapy, with its unique physical characteristics, can deliver less dose to normal tissues, resulting in fewer side effects. Proton therapy is currently being used for the treatment of head and neck cancer, with increasing clinical evidence supporting its use. However, barriers to wider adoption include access, cost, and the need for higher-level evidence.

Methods: The clinical evidence for the use of proton therapy in the treatment of head and neck cancer are reviewed here, including indications, advantages, and challenges.

Results: The Particle Therapy Cooperative Group Head and Neck Subcommittee task group provides consensus guidelines for the use of proton therapy for head and neck cancer.

Conclusion: This report can be used as a guide for clinical use, to understand clinical trials, and to inform future research efforts.
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http://dx.doi.org/10.14338/IJPT-20-00071.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270078PMC
June 2021

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

Radiother Oncol 2021 Jul 5;162:85-90. Epub 2021 Jul 5.

Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

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.
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http://dx.doi.org/10.1016/j.radonc.2021.06.035DOI Listing
July 2021

Frailty and restrictions in geriatric domains are associated with surgical complications but not with radiation-induced acute toxicity in head and neck cancer patients: A prospective study.

Oral Oncol 2021 Jul 7;118:105329. Epub 2021 Jun 7.

Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, PO box 30.001, 9700 RB, Groningen, the Netherlands.

Objectives: We aimed to evaluate the association between frailty screening and geriatric assessment (GA) on short term adverse events in patients treated for head and neck cancer (HNC) for the first time in a prospective study.

Materials And Methods: Newly diagnosed HNC patients undergoing curative treatment were prospectively included in OncoLifeS, a data biobank. Prior to the start of treatment, frailty was assessed with a GA, Groningen Frailty Indicator (GFI) and Geriatric-8 (G8). The GA included comorbidity (Adult Comorbidity Evaluation - 27), nutritional status (Malnutrition Universal Screening Tool), functional status ((instrumental) Activities of Daily Living), mobility (Timed Up & Go), psychological (Geriatric Depression Scale 15) and cognitive (Mini Mental State Examination) measures. Clinically relevant postoperative complications (Clavien-Dindo ≥ grade 2) and acute radiation-induced toxicity (Common Terminology Criteria for Adverse Events version 4.0 ≥ grade 2) were defined as outcome measures. Univariable and multivariable logistic regression analyses were performed, yielding odds ratios (ORs) and 95% confidence intervals (95%CIs).

Results: Of the 369 included patients, 259 patients were eligible for analysis. Postoperative complications occurred in 41/148 (27.7%) patients and acute radiation-induced toxicity was present in 86/160 (53.7%) patients. Number of deficit domains of GA (OR = 1.71, 95%CI = 1.14-2.56), GFI (OR = 2.54, 95%CI = 1.02-6.31) and G8 (OR5.59, 95%CI = 2.14-14.60) were associated with postoperative complications, but not with radiation-induced toxicity.

Conclusion: Frailty and restrictions in geriatric domains were associated with postoperative complications, but not with radiation-induced acute toxicity in curatively treated HNC patients. The results of this prospective study further emphasizes the importance of geriatric evaluation, particularly before surgery.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105329DOI Listing
July 2021

Range probing as a quality control tool for CBCT-based synthetic CTs: In vivo application for head and neck cancer patients.

Med Phys 2021 Aug 11;48(8):4498-4505. Epub 2021 Jul 11.

Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Purpose: Cone-beam CT (CBCT)-based synthetic CTs (sCT) produced with a deep convolutional neural network (DCNN) show high image quality, suggesting their potential usability in adaptive proton therapy workflows. However, the nature of such workflows involving DCNNs prevents the user from having direct control over their output. Therefore, quality control (QC) tools that monitor the sCTs and detect failures or outliers in the generated images are needed. This work evaluates the potential of using a range-probing (RP)-based QC tool to verify sCTs generated by a DCNN. Such a RP QC tool experimentally assesses the CT number accuracy in sCTs.

Methods: A RP QC dataset consisting of repeat CTs (rCT), CBCTs, and RP acquisitions of seven head and neck cancer patients was retrospectively assessed. CBCT-based sCTs were generated using a DCNN. The CT number accuracy in the sCTs was evaluated by computing relative range errors between measured RP fields and RP field simulations based on rCT and sCT images.

Results: Mean relative range errors showed agreement between measured and simulated RP fields, ranging from -1.2% to 1.5% in rCTs, and from -0.7% to 2.7% in sCTs.

Conclusions: The agreement between measured and simulated RP fields suggests the suitability of sCTs for proton dose calculations. This outcome brings sCTs generated by DCNNs closer toward clinical implementation within adaptive proton therapy treatment workflows. The proposed RP QC tool allows for CT number accuracy assessment in sCTs and can provide means of in vivo range verification.
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http://dx.doi.org/10.1002/mp.15020DOI Listing
August 2021

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

Int J Radiat Oncol Biol Phys 2021 10 26;111(2):456-467. Epub 2021 May 26.

Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

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 evident time pattern and less pronounced differences in mean scores between subgroups, although differences were still significant (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 subgroups 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.
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http://dx.doi.org/10.1016/j.ijrobp.2021.05.114DOI Listing
October 2021

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

Radiother Oncol 2021 07 21;160:61-68. Epub 2021 Apr 21.

University of Groningen, University Medical Center Groningen, Department of Radiation Oncology, Groningen, the Netherlands.

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 D 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.
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http://dx.doi.org/10.1016/j.radonc.2021.04.012DOI Listing
July 2021

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

Radiother Oncol 2021 07 20;160:47-53. Epub 2021 Apr 20.

Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.

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 1083 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. R 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.
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http://dx.doi.org/10.1016/j.radonc.2021.04.011DOI Listing
July 2021

Unilateral versus bilateral nodal irradiation: Current evidence in the treatment of squamous cell carcinoma of the head and neck.

Head Neck 2021 09 19;43(9):2807-2821. Epub 2021 Apr 19.

International Head and Neck Scientific Group, Udine, Italy.

Cancers of the head and neck region often present with nodal involvement. There is a long-standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guidelines for the selection and delineation of the elective lymph nodes were published in the early 2000s and were updated recently. However, diagnostic imaging techniques have improved the accuracy and reliability of nodal staging and as a result, small metastases that used to remain undetected and were thus in the past included in the elective nodal volume, will now be included in high-dose volumes. Furthermore, the elective nodal areas are situated close to the parotid glands, the submandibular glands and the swallowing muscles. Therefore, irradiation of a smaller, more selected volume of the elective nodes could reduce treatment-related toxicity. Several researchers consider the current bilateral elective neck irradiation strategies an overtreatment and show growing interest in a unilateral nodal irradiation in selected patients. The aim of this article is to give an overview of the current evidence about the indications and benefits of unilateral nodal irradiation and the use of SPECT/CT-guided nodal irradiation in squamous cell carcinomas of the head and neck.
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http://dx.doi.org/10.1002/hed.26713DOI Listing
September 2021

The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

Int J Radiat Oncol Biol Phys 2021 08 10;110(5):1350-1359. Epub 2021 Mar 10.

Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address:

Purpose: Radiation-induced acute coronary events (ACEs) may occur as a treatment-related late adverse effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remain to be determined. The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in patients with BC treated with radiation therapy.

Methods And Materials: The study cohort consisted of 910 patients with BC treated with postoperative radiation therapy after breast-conserving surgery. In total, 163 patients had an atherosclerotic plaque in the LAD. The endpoint was the occurrence of an ACE after treatment. For each individual patient, the mean heart dose, volume of the left ventricle receiving ≥5 Gy (LV-V5), mean LAD dose, and mean dose to calcified atherosclerotic plaques in the LAD, if present, were acquired based on planning computed tomography scans. Cox regression analysis was used to analyze the effects on the cumulative incidence of ACEs.

Results: The median follow-up time was 9.2 years (range, 0.1-14.3 years). In total, 38 patients (4.2%) developed an ACE during follow-up. For patients with an atherosclerotic plaque (n = 163), the mean dose to the atherosclerotic plaque was the strongest predictor for ACEs, even after correction for cardiovascular risk factors (hazard ratio [HR], 1.269; 95% CI, 1.090-1.477; P = .002). The LV-V5 was associated with ACEs in patients without atherosclerotic plaques in the LAD (n = 680) (HR, 1.021; 95% CI, 1.003-1.039; P = .023).

Conclusions: The results of this study suggest that radiation dose to pre-existing calcified atherosclerotic plaques in the LAD is strongly associated with the development of ACEs in patients with BC.
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http://dx.doi.org/10.1016/j.ijrobp.2021.03.004DOI Listing
August 2021

Sleep quality trajectories from head and neck cancer diagnosis to six months after treatment.

Oral Oncol 2021 04 12;115:105211. Epub 2021 Feb 12.

Department of Clinical, Neuro- and Developmental Psychology, Faculty of Behavioral and Movement Sciences & Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands; Cancer Center Amsterdam Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Otolaryngology - Head and Neck Surgery, Amsterdam, the Netherlands. Electronic address:

Objectives: Patients with head and neck cancer (HNC) often report disturbances in their sleep quality, impairing their quality of life. This study aims to examine the trajectories of sleep quality from diagnosis up to 6-month after treatment, as well as the pre-treatment risk factors for poor sleep trajectories.

Materials And Methods: Sleep quality (Pittsburgh sleep quality index) was measured shortly after diagnosis (pre-treatment), and at 3 and 6 months after finishing treatment. Patients were categorized into 5 trajectory groups. We examined the association of sleep quality trajectories with sociodemographic and clinical characteristics, coping style, HNC symptoms, and psychological distress.

Results: Among 412 included patients, about a half either had a persistent good sleep (37.6%) or an improving (16.5%) trajectory. About a third had a persistent poor sleep (21.8%) or worsening (10.9%) sleep trajectory. The remaining patients (13.1%), alternated between good and poor sleep. Using persistent good sleep as a reference outcome, persistent poor sleepers were more likely to be woman (odds ratio [OR] = 1.98, 95% confidence interval [CI] 1.01-3.90), use painkillers prior to treatment (OR = 2.52, 95% CI 1.33-4.77), and have more pre-treatment anxiety symptoms (OR = 1.26, 95% CI 1.15-1.38).

Conclusion: Unfavorable sleep quality trajectories are prevalent among HNC patients from pre-treatment to 6-month after treatment. A periodic sleep evaluation starting shortly after HNC diagnosis is necessary to identify persistent sleep problems, especially among high-risk group.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105211DOI Listing
April 2021

Radiation-Induced Myocardial Fibrosis in Long-Term Esophageal Cancer Survivors.

Int J Radiat Oncol Biol Phys 2021 07 10;110(4):1013-1021. Epub 2021 Feb 10.

Department of Radiology, University Medical Center, Groningen, Netherlands.

Purpose: Radiation-induced cardiac toxicity is a potential lethal complication. The aim of this study was to assess whether there is a dose-dependent relationship between radiation dose and myocardial fibrosis in patients who received neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC).

Methods And Materials: Forty patients with EC treated with a transthoracic esophagectomy with (n = 20) or without (n = 20) nCRT (CROSS study regimen) were included. Cardiovascular magnetic resonance imaging (1.5 Tesla) for left ventricular (LV) function, late gadolinium enhancement, and T1 mapping were performed. Extracellular volume (ECV), as a surrogate for collagen burden, was measured for all LV segments separately. The dose-response relationship between ECV and mean radiation dose per LV myocardial segment was evaluated using a mixed-model analysis.

Results: Seventeen nCRT and 16 control patients were suitable for analysis. The mean time after treatment was 67.6 ± 8.1 (nCRT) and 122 ± 35 (controls) months (P = .02). In nCRT patients, we found a significantly higher mean global ECV of 28.2% compared with 24.0% in the controls (P < .001). After nCRT, LV myocardial segments with elevated ECV had received significantly higher radiation doses. In addition, a linear dose-effect relation was found with a 0.136% point increase of ECV for each Gy (P < .001). There were no differences in LV function measures and late gadolinium enhancement between both groups.

Conclusions: Myocardial ECV was significantly higher in long-term EC survivors after nCRT compared with surgery only. Moreover, this ECV increase was linear with the radiation dose per LV segment, indicating radiation-induced myocardial fibrosis.
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http://dx.doi.org/10.1016/j.ijrobp.2021.02.007DOI Listing
July 2021

International Recommendations on Reirradiation by Intensity Modulated Radiation Therapy for Locally Recurrent Nasopharyngeal Carcinoma.

Int J Radiat Oncol Biol Phys 2021 07 9;110(3):682-695. Epub 2021 Feb 9.

Department of Clinical Oncology, University of Hong Kong Shenzhen Hospital and University of Hong Kong, Hong Kong, China. Electronic address:

Purpose: Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions.

Methods And Materials: A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement.

Results: The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints).

Conclusion: This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.041DOI Listing
July 2021

Risk of ischaemic cerebrovascular events in head and neck cancer patients is associated with carotid artery radiation dose.

Radiother Oncol 2021 04 3;157:182-187. Epub 2021 Feb 3.

Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.

Background And Purpose: Radiotherapy in the head and neck area may cause vascular damage to the carotid arteries, increasing the risk of anterior circulation ischaemic cerebrovascular events (ICVEs). However, limited data exists on the relationship between radiation dose to the carotid arteries and risk of ICVE. The purpose of this study was therefore to determine the relationship between radiation dose to the carotid arteries and anterior circulation ICVE risk.

Materials And Methods: A retrospective analysis of a prospective study cohort of 750 head and neck cancer patients treated with definitive (chemo)radiotherapy was performed. Carotid arteries were delineated, and dose-volume parameters of the treatment plans were calculated. ICVEs were scored prospectively and checked retrospectively by analysing all patient records. Cox proportional hazards analysis was performed to analyse the dose-effect relationships.

Results: The median follow-up period was 3.4 years, 27 patients experienced an ICVE and the 5-year cumulative risk was 4.6%. ICVE risk was significantly associated with dose to the carotid arteries. Multivariable analysis showed that the absolute volume (cm) of the carotid arteries that received at least a radiation dose of 10 Gy was the most important prognostic factor for ICVE (HR = 1.11, AUC = 0.68, p < 0.001).

Conclusion: This is the first large prospective cohort study that demonstrates an independent dose-effect relationship between radiation dose to the carotid arteries and the risk of ICVE. These findings may be used to identify patients at risk for ICVE after radiotherapy who may benefit from primary or secondary preventive measures.
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http://dx.doi.org/10.1016/j.radonc.2021.01.026DOI Listing
April 2021

Comprehensive toxicity risk profiling in radiation therapy for head and neck cancer: A new concept for individually optimised treatment.

Radiother Oncol 2021 04 3;157:147-154. Epub 2021 Feb 3.

Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.

Background And Purpose: A comprehensive individual toxicity risk profile is needed to improve radiation treatment optimisation, minimising toxicity burden, in head and neck cancer (HNC) patients. We aimed to develop and externally validate NTCP models for various toxicities at multiple time points.

Materials And Methods: Using logistic regression, we determined the relationship between normal tissue irradiation and the risk of 22 toxicities at ten time points during and after treatment in 750 HNC patients. The toxicities involved swallowing, salivary, mucosal, speech, pain and general complaints. Studied predictors included patient, tumour and treatment characteristics and dose parameters of 28 organs. The resulting NTCP models were externally validated in 395 HNC patients.

Results: The NTCP models involved 14 organs that were associated with at least one toxicity. The oral cavity was the predominant organ, associated with 12 toxicities. Other important organs included the parotid and submandibular glands, buccal mucosa and swallowing muscles. In addition, baseline toxicity, treatment modality, and tumour site were common predictors of toxicity. The median discrimination performance (AUC) of the models was 0.71 (interquartile range: 0.68-0.75) at internal validation and 0.67 (interquartile range: 0.62-0.71) at external validation.

Conclusion: We established a comprehensive individual toxicity risk profile that provides essential insight into how radiation exposure of various organs translates into multiple acute and late toxicities. This comprehensive understanding of radiation-induced toxicities enables a new radiation treatment optimisation concept that balances multiple toxicity risks simultaneously and minimises the overall toxicity burden for an individual HNC patient who needs to undergo radiation treatment.
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http://dx.doi.org/10.1016/j.radonc.2021.01.024DOI Listing
April 2021

Towards the clinical implementation of intensity-modulated proton therapy for thoracic indications with moderate motion: Robust optimised plan evaluation by means of patient and machine specific information.

Radiother Oncol 2021 04 3;157:210-218. Epub 2021 Feb 3.

Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands; Division for Medical Radiation Physics, Carl von Ossietzky University Oldenburg, Germany.

Purpose: Compared to volumetric modulated arc therapy (VMAT), clinical benefits are anticipated when treating thoracic tumours with intensity-modulated proton therapy (IMPT). However, the current concern of plan robustness as a result of motion hampers its wide clinical implementation. To define an optimal protocol to treat lung and oesophageal cancers, we present a comprehensive evaluation of IMPT planning strategies, based on patient 4DCTs and machine log files.

Materials And Methods: For ten lung and ten oesophageal cancer patients, a planning 4DCT and weekly repeated 4DCTs were collected. For these twenty patients, the CTV volume and motion were assessed based on the 4DCTs. In addition to clinical VMAT plans, layered rescanned 3D and 4D robust optimised IMPT plans (IMPT_3D and IMPT_4D respectively) were generated, and approved clinically, for all patients. The IMPT plans were then delivered in dry runs at our proton facility to obtain log files, and subsequently evaluated through our 4D robustness evaluation method (4DREM). With this method, for each evaluated plan, fourteen 4D accumulated scenario doses were obtained, representing 14 possible fractionated treatment courses.

Results: From VMAT to IMPT_3D, nominal D(lungs-GTV) decreased 2.75 ± 0.56 Gy and 3.76 ± 0.92 Gy over all lung and oesophageal cancer patients, respectively. A more pronounced reduction was verified for D(heart): 5.38 ± 7.36 Gy (lung cases) and 9.51 ± 2.25 Gy (oesophagus cases). Target coverage robustness of IMPT_3D was sufficient for 18/20 patients. Averaged dose in critical structures over all 4DREM scenarios changed only slightly for both IMPT_3D and IMPT_4D. Relative to IMPT_3D, no gain in IMPT_4D was observed.

Conclusion: The dosimetric superiority of IMPT over VMAT has been established. For most thoracic tumours, our IMPT_3D planning protocol showed to be robust and clinically suitable. Nevertheless, accurate patient positioning and adapting to anatomical variations over the course of treatment remain compulsory.
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http://dx.doi.org/10.1016/j.radonc.2021.01.014DOI Listing
April 2021

Trends in the Management of Non-Vestibular Skull Base and Intracranial Schwannomas.

Cancer Manag Res 2021 18;13:463-478. Epub 2021 Jan 18.

International Head and Neck Scientific Group, Padua, Italy.

The aim of this review is to analyze the latest trends in the management of non-vestibular skull base and intracranial schwannomas in order to optimize tumor control and quality of life. Non-vestibular cranial nerve schwannomas are rare lesions, representing 5-10% of cranial nerve schwannomas. Management decisions should be individualized depending on tumor size, location and associated functional deficits. Generally, large sized schwannomas exerting significant mass effect with increased intracranial pressure are treated surgically. In some cases, even after optimal skull base resection, it is not possible to achieve a gross total resection because tumor location and extent and/or to reduce morbidity. Thus, subtotal resection followed by stereotactic radiosurgery or fractioned radiotherapy offers an alternative approach. In certain cases, stereotactic radiosurgery or radiotherapy alone achieves good tumor control rates and less morbidity to gross total resection. Finally, given the slow growth rate of most of these tumors, observation with periodic radiographic follow-up approach is also a reasonable alternative for small tumors with few, if any, symptoms.
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http://dx.doi.org/10.2147/CMAR.S287410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822088PMC
January 2021

Assessment of manual adjustment performed in clinical practice following deep learning contouring for head and neck organs at risk in radiotherapy.

Phys Imaging Radiat Oncol 2020 Oct 14;16:54-60. Epub 2020 Oct 14.

Mirada Medical Ltd., Oxford, United Kingdom.

Background And Purpose: Auto-contouring performance has been widely studied in development and commissioning studies in radiotherapy, and its impact on clinical workflow assessed in that context. This study aimed to evaluate the manual adjustment of auto-contouring in routine clinical practice and to identify improvements regarding the auto-contouring model and clinical user interaction, to improve the efficiency of auto-contouring.

Materials And Methods: A total of 103 clinical head and neck cancer cases, contoured using a commercial deep-learning contouring system and subsequently checked and edited for clinical use were retrospectively taken from clinical data over a twelve-month period (April 2019-April 2020). The amount of adjustment performed was calculated, and all cases were registered to a common reference frame for assessment purposes. The median, 10th and 90th percentile of adjustment were calculated and displayed using 3D renderings of structures to visually assess systematic and random adjustment. Results were also compared to inter-observer variation reported previously. Assessment was performed for both the whole structures and for regional sub-structures, and according to the radiation therapy technologist (RTT) who edited the contour.

Results: The median amount of adjustment was low for all structures (<2 mm), although large local adjustment was observed for some structures. The median was systematically greater or equal to zero, indicating that the auto-contouring tends to under-segment the desired contour.

Conclusion: Auto-contouring performance assessment in routine clinical practice has identified systematic improvements required technically, but also highlighted the need for continued RTT training to ensure adherence to guidelines.
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http://dx.doi.org/10.1016/j.phro.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807591PMC
October 2020

Technical Note: First report on an in vivo range probing quality control procedure for scanned proton beam therapy in head and neck cancer patients.

Med Phys 2021 Mar 6;48(3):1372-1380. Epub 2021 Feb 6.

Department of Radiation Oncology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

Purpose: The capability of proton therapy to provide highly conformal dose distributions is impaired by range uncertainties. The aim of this work is to apply range probing (RP), a form of a proton radiography-based quality control (QC) procedure for range accuracy assessment in head and neck cancer (HNC) patients in a clinical setting.

Methods And Materials: This study included seven HNC patients. RP acquisition was performed using a multi-layer ionization chamber (MLIC). Per patient, two RP frames were acquired within the first two weeks of treatment, on days when a repeated CT scan was obtained. Per RP frame, integral depth dose (IDD) curves of 81 spots around the treatment isocenter were acquired. Range errors are determined as a discrepancy between calculated IDDs in the treatment planning system and measured residual ranges by the MLIC. Range errors are presented relative to the water equivalent path length of individual proton spots. In addition to reporting results for complete measurement frames, an analysis, excluding range error contributions due to anatomical changes, is presented.

Results: Discrepancies between measured and calculated ranges are smaller when performing RP calculations on the day-specific patient anatomy rather than the planning CT. The patient-specific range evaluation shows an agreement between calculated and measured ranges for spots in anatomically consistent areas within 3% (1.5 standard deviation).

Conclusions: The results of an RP-based QC procedure implemented in the clinical practice for HNC patients have been demonstrated. The agreement of measured and simulated proton ranges confirms the 3% uncertainty margin for robust optimization. Anatomical variations show a predominant effect on range accuracy, motivating efforts towards the implementation of adaptive radiotherapy.
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http://dx.doi.org/10.1002/mp.14713DOI Listing
March 2021

Model-based comparison of organ at risk protection between VMAT and robustly optimised IMPT plans.

Z Med Phys 2021 Feb 22;31(1):5-15. Epub 2020 Dec 22.

West German Proton Therapy Centre Essen (WPE), Essen, Germany; West German Cancer Centre (WTZ), Essen, Germany; Department of Particle Therapy, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK), Germany.

The comparison between intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT) plans, based on models of normal tissue complication probabilities (NTCP), can support the choice of radiation modality. IMPT irradiation plans for 50 patients with head and neck tumours originally treated with photon therapy have been robustly optimised against density and setup uncertainties. The dose distribution has been calculated with a Monte Carlo (MC) algorithm. The comparison of the plans was based on dose-volume parameters in organs at risk (OARs) and NTCP-calculations for xerostomia, sticky saliva, dysphagia and tube feeding using Langendijk's model-based approach. While the dose distribution in the target volumes is similar, the IMPT plans show better protection of OARs. Therefore, it is not the high dose confirmation that constitutes the advantage of protons, but it is the reduction of the mid-to-low dose levels compared to photons. This work investigates to what extent the advantages of proton radiation are beneficial for the patient's post-therapeutic quality of life (QoL). As a result, approximately one third of the patients examined benefit significantly from proton therapy with regard to possible late side effects. Clinical data is needed to confirm the model-based calculations.
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http://dx.doi.org/10.1016/j.zemedi.2020.09.003DOI Listing
February 2021

Metastatic Squamous Cell Carcinoma to the Cervical Lymph Nodes From an Unknown Primary Cancer: Management in the HPV Era.

Front Oncol 2020 10;10:593164. Epub 2020 Nov 10.

International Head and Neck Scientific Group, Padua, Italy.

Background: Patients with metastases in the lymph nodes of the neck and no obvious primary tumor, neck cancer with unknown primary (NCUP), represent a management challenge. A majority of patients have metastatic squamous cell carcinoma (SCC), although other histologies do occur.

Methods: We comprehensively reviewed the literature, compared available guidelines, and conferred with an international team of experts.

Results: Positron emission tomography-computed tomography (PET-CT) and fine needle aspiration (FNA) under ultrasound guidance increase accuracy of diagnosis. Immunohistochemistry (IHC), determination of human papilloma virus (HPV) status, by p16 staining or by hybridization (ISH), and next-generation gene sequencing can guide us regarding probable primary sites and tumor biology. Narrow Band Imaging (NBI) has been introduced for the early detection of subtle mucosal lesions. Direct laryngoscopy (DL) and tonsillectomy have long been procedures used in the search for a primary site. More recently, TransOral Robotic Surgery (TORS) or Transoral LASER Microsurgery (TLM) have been introduced for lingual tonsillectomy.

Conclusions: New technologies have been developed which can better detect, diagnose, and treat occult primary tumors. Decisions regarding therapy are based on the primary tumor site (if discovered) and N stage. Options include neck dissection with or without postoperative adjuvant therapy, primary irradiation, or combined chemotherapy with irradiation. The preferred treatment of patients whose primary remains unidentified is controversial.
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http://dx.doi.org/10.3389/fonc.2020.593164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685177PMC
November 2020

Roadmap: proton therapy physics and biology.

Phys Med Biol 2020 Nov 23. Epub 2020 Nov 23.

Department of Radiation Medicine, Paul Scherrer Institute, CH-5232 Villigen PSI, Villigen, SWITZERLAND.

The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200,000 patients have been treated with proton beams worldwide and the number of operating proton therapy facilities will soon reach one hundred. Proton therapy has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While proton therapy has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of proton therapy cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effects differ from photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because proton therapy treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in proton therapy categorized into four different themes, "improving efficiency", "improving planning and delivery", "improving imaging", and "improving patient selection".
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http://dx.doi.org/10.1088/1361-6560/abcd16DOI Listing
November 2020

Proton therapy for selected low grade glioma patients in the Netherlands.

Radiother Oncol 2021 01 14;154:283-290. Epub 2020 Nov 14.

University of Groningen, University Medical Center Groningen, Department of Radiation Oncology, the Netherlands.

Proton therapy offers an attractive alternative to conventional photon-based radiotherapy in low grade glioma patients, delivering radiotherapy with equivalent efficacy to the tumour with less radiation exposure to the brain. In the Netherlands, patients with favourable prognosis based on tumour and patient characteristics can be offered proton therapy. Radiation-induced neurocognitive function decline is a major concern in these long surviving patients. Although level 1 evidence of superior clinical outcome with proton therapy is lacking, the Dutch National Health Care Institute concluded that there is scientific evidence to assume that proton therapy can have clinical benefit by reducing radiation-induced brain damage. Based on this decision, proton therapy is standard insured care for selected low grade glioma patients. Patients with other intracranial tumours can also qualify for proton therapy, based on the same criteria. In this paper, the evidence and considerations that led to this decision are summarised. Additionally, the eligibility criteria for proton therapy and the steps taken to obtain high-quality data on treatment outcome are discussed.
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http://dx.doi.org/10.1016/j.radonc.2020.11.004DOI Listing
January 2021
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