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Purpose: To report on quality assurance (QA) and protocol adherence (PA) in a multicentre phase III trial for head and neck cancer, evaluate patterns of protocol deviations and investigate the effect of PA on study outcomes., Methods: All 221 patients from the ARTFORCE trial (NCT01504815) were included in this study. Pre- and per-treatment QA measures included protocol guidelines, a dummy run, early case reviews and trial meetings. FDG-PET-guided dose painting and scheduled adaptive radiotherapy were reviewed in patients in the experimental arm (eRT). Patient and disease characteristics, as well as institutes' accrual rate and timing were examined for correlation with PA. Cox regression was used to determine the impact of PA on outcome., Results: The dummy run was completed in all nine institutes and early case reviews were completed in five out of nine institutes that contributed 190 out of 221 patients. Among all patients randomized to eRT, 64 % had at least one deviation of the experimental trial components. Protocol deviations were significantly correlated with the institute patients were treated at (Cramer'sV 0.34-0.48). Despite early identification of institute-specific deviations in QA, these continued during the trial. No significant associations were seen between deviations and accrual timing or rate (P ≥ 0.26). Within eRT, no significant relation was observed between experimental PA and locoregional control (LRC), the primary endpoint of the trial (P≥.15)., Conclusions: Despite QA, protocol deviations persisted during the trial, which were mostly institute-specific. However, deviations of the experimental treatment strategy did not significantly impact LRC and therefore the trial conclusion., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Anna Liza M.P. de Leeuw; PhD-student at the Antoni van Leeuwenhoek hospital. Jordi Giralt; Radiation oncologist at the Vall d'Hebron Unniversity Hospital. Yungan Tao; Radiation oncologist at the Institut Gustave roussy. Sergi Benavente; Radiation oncologist at the Vall d'Hebron Unniversity Hospital. Thanh-Vân France Nguyen; Radiation oncologist at the Institut Gustave roussy. Frank J.P. Hoebers; Radiation oncologist at the Maastro Center. Ann Hoeben; Clinical oncologist at the Maastro Center. Chris H.J. Terhaard; retired radiation oncologist at the University Medical Center Utrecht. Lip Wai Lee; Radiation oncologist at the Christie NHS Foundation Trust. Signe Friesland; Radiation oncologist at the Karolinska Comprehensive Cancer Center. Roel J.H.M. Steenbakkers; Radiation oncologist at the University Medical Center Groningen. Lisa Tans; Radiation oncologist at the Erasmus Medical Center. Simon R. van Kranen; Postdoc at the Antoni van Leeuwenhoek hospital. Jeroen B van de Kamer; Medical physicist at the Antoni van Leeuwenhoek hospital. Harry Bartelink; retired radiation oncologist at the Antoni van Leeuwenhoek hospital. Coen R.N. Rasch; Professor at Leiden University; Radiation oncologist at the Leiden University Medical Center; Jan-Jakob Sonke; Professor by special appointment at University of Amsterdam; senior group leader at Antoni van Leeuwenhoek hospital; ownership of patent/license fees/copyright at Elekta AB; member of the international advisory board at Physics, medicine and biology; editorial board member of Physics & Imaging in Radiation Oncology. Olga Hamming-Vrieze; Radiation oncologist at Antoni van Leeuwenhoek hospital]., (Copyright © 2024. Published by Elsevier B.V.)

Background/objectives: Studies have shown that dose to the parotid gland stem cell rich (SCR) regions should be reduced to lower the risk of xerostomia after radiotherapy (RT). This study aimed to assess whether stem cell sparing (SCS)-RT can be adopted in routine clinical practice., Methods: Multiple planning studies were performed to compare SCS-RT with standard (ST)-RT using 30 head and neck cancer patients. Shifts in mean dose to the SCR regions (D mean,SCR ) and other organs at risk and their estimated impact on normal tissue complication probability (NTCP) for side-effects were compared using Wilcoxon signed-rank test. A multicenter study was performed (eight institutions, three patients) to test the generalizability of SCS-RT using the Friedman test., Results: Using photons, D mean,SCR was reduced with median 4.1/3.5 Gy for ipsilateral/contralateral ( p < 0.001). The largest reductions were when the SCR regions overlapped less with target volumes. Subsequently, NTCPs for xerostomia decreased ( p < 0.001). Using protons, D mean,SCR was also reduced (2.2/1.9 Gy for ipsilateral/contralateral, p < 0.002). Nevertheless, SCS-RT did not further decrease NTCPs for xerostomia ( p > 0.17). Target coverage and prevention of other side-effects were not compromised. However, increased mean oral cavity dose was observed in some patients. Lastly, in the multicenter study D mean,SCR could be reduced by slightly adjusting the standard optimization. Contralateral D mean,SCR reductions differed between centers ( p = 0.01), which was attributed to differences in ST-RT plans., Conclusions: Stem cell sparing radiotherapy can be clinically introduced by making small adjustments to the optimization strategy and can reduce the risk of xerostomia.

The use of artificial intelligence (AI) holds great promise for radiation oncology, with many applications being reported in the literature, including some of which are already in clinical use. These are mainly in areas where AI provides benefits in efficiency (such as automatic segmentation and treatment planning). Prediction models that directly impact patient decision-making are far less mature in terms of their application in clinical practice. Part of the limited clinical uptake of these models may be explained by the need for broader knowledge, among practising clinicians within the medical community, about the processes of AI development. This lack of understanding could lead to low commitment to AI research, widespread scepticism, and low levels of trust. This attitude towards AI may be further negatively impacted by the perception that deep learning is a "black box" with inherently low transparency. Thus, there is an unmet need to train current and future clinicians in the development and application of AI in medicine. Improving clinicians' AI-related knowledge and skills is necessary to enhance multidisciplinary collaboration between data scientists and physicians, that is, involving a clinician in the loop during AI development. Increased knowledge may also positively affect the acceptance and trust of AI. This paper describes the necessary steps involved in AI research and development, and thus identifies the possibilities, limitations, challenges, and opportunities, as seen from the perspective of a practising radiation oncologist. It offers the clinician with limited knowledge and experience in AI valuable tools to evaluate research papers related to an AI model application., Competing Interests: Dr R.H.M. reported receiving personal fees from ViewRay, AstraZeneca, Novartis, Varian Medical Systems, and Sio Capital and grants from ViewRay outside the submitted work. Dr D.S.B. reported serving as an associate editor for HemOnc.org and her institution received support for research from the American Association for Cancer Research outside the submitted work. No disclosures relevant for this submitted work were reported by the other authors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Background and Purpose: This multicenter randomized phase III trial evaluated whether locoregional control of patients with LAHNSCC could be improved by fluorodeoxyglucose-positron emission tomography (FDG-PET)-guided dose-escalation while minimizing the risk of increasing toxicity using a dose-redistribution and scheduled adaptation strategy., Materials and Methods: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10thfraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/m 2 cisplatin. Primary endpoints were 2-year locoregional control (LRC) and toxicity. Primary analysis was based on the intention-to-treat principle., Results: Due to slow accrual, the study was prematurely closed (at 84 %) after randomizing 221 eligible patients between 2012 and 2019 to receive rRT (N = 109) or cRT (N = 112). The 2-year LRC estimate difference of 81 % (95 %CI 74-89 %) vs. 74 % (66-83 %) in the rRT and cRT arm, respectively, was not found statistically significant (HR 0.75, 95 %CI 0.43-1.31,P=.31). Toxicity prevalence and incidence rates were similar between trial arms, with exception for a significant increased grade ≥ 3 pharyngolaryngeal stenoses incidence rate in the rRT arm (0 versus 4 %,P=.05). In post-hoc subgroup analyses, rRT improved LRC for patients with N0-1 disease (HR 0.21, 95 %CI 0.05-0.93) and oropharyngeal cancer (0.31, 0.10-0.95), regardless of HPV., Conclusion: Adaptive and dose redistributed radiotherapy enabled dose-escalation with similar toxicity rates compared to conventional radiotherapy. While FDG-PET-guided dose-escalation did overall not lead to significant tumor control or survival improvements, post-hoc results showed improved locoregional control for patients with N0-1 disease or oropharyngeal cancer treated with rRT., Competing Interests: Declaration of competing interest Funding information: European commission FP7 project (Nr 257144) The authors declare that they have no further known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Elective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life., Methods/design: This is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment., Discussion: If this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background and Purpose: Prior to radiotherapy (RT), teeth with poor prognosis that pose a risk for post-RT osteoradionecrosis (ORN) are removed. To allow enough time for adequate wound healing prior to RT, decisions are made based on the estimated radiation dose. This study aimed to gain insight into (1) the overall number of teeth extracted and (2) the patient and tumor characteristics associated with the number of redundantly extracted teeth., Materials and Methods: Patients with head and neck cancer (HNC), treated with RT between 2015 and 2019, were included in this cross-sectional study. For each extracted tooth the radiation dose was calculated retrospectively. The cut-off point for valid extraction was set at ≥ 40 Gy in accordance with the national protocol. Potential factors for doses ≥ 40 Gy were identified, including age, sex, tumor location, tumor (T) and nodal stage (N), overall tumor stage and number of teeth extracted., Results: A total of 1759 teeth were removed from 358 patients. Of these 1759 teeth, 1274 (74%) appeared to have been removed redundantly, based on the mean dose (D mean ) of < 40 Gy. Using the maximum dose (D max ) of < 40 Gy, 1080 teeth (61%) appeared to have been removed redundantly. Tumor location and N-classification emerged as the most important associative variables in the multivariable regression analysis., Conclusion: To our knowledge this is the first study to provide insight into the amount of teeth redundantly extracted prior to RT and represents a step forward in de-escalating the damage to the masticatory system prior to RT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Head and neck cancer (HNC) patients treated with radiotherapy often suffer from radiation-induced toxicities. Normal Tissue Complication Probability (NTCP) modeling can be used to determine the probability to develop these toxicities based on patient, tumor, treatment and dose characteristics. Since the currently used NTCP models are developed using supervised methods that discard unlabeled patient data, we assessed whether the addition of unlabeled patient data by using semi-supervised modeling would gain predictive performance., Materials and Methods: The semi-supervised method of self-training was compared to supervised regression methods with and without prior multiple imputation by chained equation (MICE). The models were developed for the most common toxicity outcomes in HNC patients, xerostomia (dry mouth) and dysphagia (difficulty swallowing), measured at six months after treatment, in a development cohort of 750 HNC patients. The models were externally validated in a validation cohort of 395 HNC patients. Model performance was assessed by discrimination and calibration., Results: MICE and self-training did not improve performance in terms of discrimination or calibration at external validation compared to current regression models. In addition, the relative performance of the different models did not change upon a decrease in the amount of (labeled) data available for model development. Models using ridge regression outperformed the logistic models for the dysphagia outcome., Conclusion: Since there was no apparent gain in the addition of unlabeled patient data by using the semi-supervised method of self-training or MICE, the supervised regression models would still be preferred in current NTCP modeling for HNC patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.A. Langendijk reports a relationship with Dutch Cancer Society: funding grants. J.A. Langendijk reports his department has research contracts with IBA, RaySearch, Siemens, Elekta, Leoni, and Mirada. J.A. Langendijk reports a relationship with Global Scientific Advisory Board of IBA, RayCare International Advisory Board of RaySearch that includes: board membership, consulting or advisory, and speaking and lecture fees. J.A. Langendijk reports a relationship with Netherlands Society for Radiation Oncology that includes: board membership. Funding AL is funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement N° 825162. This dissemination reflects only the author's view and the Commission is not responsible for any use that may be made of the information it contains., (© 2023 The Authors.)

Background: Radiotherapy induced impairment of cognitive function can lead to a reduced quality of life. The aim of this study was to describe the implementation and compliance of standardized neurocognitive assessment. In addition, the first results of cognitive changes for patients receiving a radiation dose to the brain are described., Materials and Methods: Patients that received radiation dose to the brain (neuro, head and neck and prophylactic cranial irradiation between April-2019 and Dec-2021 were included. Three neuro cognitive tests were performed a verbal learning and memory test, the Hopkins Verbal Learning Test; a verbal fluency test, the Controlled Oral Word Association Test and a speed and cognitive flexibility test, the Trail Making Test A&B. Tests were performed before the start of radiation, 6 months (6 m) and 1 year (1y) after irradiation. The Reliable Change Index (RCI) between baseline and follow-up was calculated using reference data from literature., Results: 644 patients performed the neurocognitive tests at baseline, 346 at 6 months and 205 at 1y after RT, with compliance rates of 90.4%, 85.6%, and 75.3%, respectively. Reasons for non-compliance were: 1. Patient did not attend appointment (49%), 2. Patient was unable to perform the test due to illness (12%), 3. Patient refused the test (8 %), 4. Various causes, (31%). A semi-automated analysis was developed to evaluate the test results. In total, 26% of patients showed a significant decline in at least one of variables at 1y and 11% on at least 2 variables at 1y. However, an increase in cognitive performance was observed in 49% (≥1 variable) and 22% (≥2 variables)., Conclusion: Standardized neurocognitive testing within the radiotherapy clinic was successfully implemented, with a high patient compliance. A semi-automatic method to evaluate cognitive changes after treatment was defined. Data collection is ongoing, long term follow-up (up to 5 years after treatment) and dose-effect analysis will be performed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Over the past decades, the therapeutic landscape has markedly changed for patients with metastatic solid cancer, yet few studies have evaluated its effect on population-based survival. The objective of this study was to evaluate the change in survival of patients with de novo metastatic solid cancers during the last 30 years., Methods: For this retrospective study, data from almost 2 million patients diagnosed with a solid cancer between January 1, 1989, and December 31, 2018, were obtained from the Netherlands Cancer Registry, with follow-up until January 31, 2021. We classified patients as with or without de novo metastatic disease (M1 or M0, respectively) at diagnosis and determined the proportion with M1 disease over time. Changes in age-standardized net survival were calculated as the difference in the 1- and 5-year survival rates of patients diagnosed in 1989-1993 and 2014-2018., Results: Different cancers showed divergent trends in the proportion of M1 disease and increases in net survival for M1 disease (approximately 0-50 percentage points at both 1 and 5 years). Patients with gastrointestinal stromal tumors saw the largest increases in 5-year survival, but we also observed substantial 5-year survival increases for patients with neuroendocrine tumors, melanoma, prostate cancer, and breast cancer., Conclusion: Over 30 years, the survival of patients with de novo M1 disease modestly and unevenly increased among cancers. Metastatic cancer still remains a very lethal disease. Next to better treatment options, we call for better preventive measures and early detection to reduce the incidence of metastatic disease., (© The Author(s) 2023. Published by Oxford University Press.)

Background: This study aims to investigate the relationship between cancer cachexia and oropharyngeal dysphagia (OD) in patients with head and neck cancer (HNC) prior to chemoradiotherapy or bioradiotherapy (CRT/BRT)., Methods: A prospective cohort study with patients with HNC undergoing CRT/BRT (2018-2021) was conducted. Body composition and skeletal muscle function were evaluated using bioelectrical impedance analysis, handgrip strength, and the short physical performance battery (SPPB). The M. D. Anderson Dysphagia Inventory (MDADI), Eating Assessment Tool (EAT)-10 questionnaire, and patient characteristics were collected. A standardized videofluoroscopic swallowing study was offered to patients., Results: Sixty-six patients were included. Twenty-six patients scored EAT-10 ≥ 3 and seventeen were cachectic. ACE-27 score >1, cachexia, abnormal SPPB-derived repeated chair-stand test, lower MDADI scores, and higher overall stage grouping showed potential predictive value (p ≤ 0.10) for EAT-10 ≥ 3. Using multivariable regression analysis, only cachexia remained a significant predictor of EAT-10 ≥ 3 (HR 9.000 [95%CI 2.483-32.619], p = 0.001)., Conclusion: Cachexia independently predicted the presence of patient-reported OD., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Normal-tissue complication probability (NTCP) models predict complication risk in patients receiving radiotherapy, considering radiation dose to healthy tissues, and are used to select patients for proton therapy, based on their expected reduction in risk after proton therapy versus photon radiotherapy (ΔNTCP). Recommended model evaluation measures include area under the receiver operating characteristic curve (AUC), overall calibration (CITL), and calibration slope (CS), whose precise relation to patient selection is still unclear. We investigated how each measure relates to patient selection outcomes., Methods: The model validation and consequent patient selection process was simulated within empirical head and neck cancer patient data. By manipulating performance measures independently via model perturbations, the relation between model performance and patient selection was studied., Results: Small reductions in AUC (-0.02) yielded mean changes in ΔNTCP between 0.9-3.2 %, and single-model patient selection differences between 2-19 %. Deviations (-0.2 or +0.2) in CITL or CS yielded mean changes in ΔNTCP between 0.3-1.4 %, and single-model patient selection differences between 1-10 %., Conclusions: Each measure independently impacts ΔNTCP and patient selection and should thus be assessed in a representative sufficiently large external sample. Our suggested practical model selection approach is considering the model with the highest AUC, and recalibrating it if needed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.A. Langendijk reports a relationship with Dutch Cancer Society: funding grants. J.A. Langendijk reports his department has research contracts with IBA, RaySearch, Siemens, Elekta, Leoni, and Mirada. J.A. Langendijk reports a relationship with Global Scientific Advisory Board of IBA, RayCare International Advisory Board of RaySearch that includes: board membership, consulting or advisory, and speaking and lecture fees. J.A. Langendijk reports a relationship with Netherlands Society for Radiation Oncology that includes: board membership. J.B. Reitsma and E. Schuit are involved as methodologist in the development of indication protocols for patient selection for proton therapy in the Netherlands. Conflicts of Interest J.B. Reitsma: Involvement as methodologist in the development of indication protocols for patient selection for proton therapy in the Netherlands. J.A. Langendijk: Department has research contracts with IBA, RaySearch, Siemens, Elekta, Leoni, and Mirada. Received grants from Dutch Cancer Society and EU. Member of Global Scientific Advisory Board of IBA. Member of RayCare International Advisory Board of RaySearch. Chair of the Netherlands Society for Radiation Oncology. E. Schuit: Involvement as methodologist in the development of indication protocols for patient selection for proton therapy in the Netherlands., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study aimed to assess the prognostic value of intratumoral CD57+ cells in head and neck squamous cell carcinoma (HNSCC) and to examine the reproducibility of these analyses using QuPath. Pretreatment biopsies of 159 patients with HPV-negative, stage III/IV HNSCC treated with chemoradiotherapy were immunohistochemically stained for CD57. The number of CD57+ cells per mm 2 tumor epithelium was quantified by two independent observers and by QuPath, software for digital pathology image analysis. Concordance between the observers and QuPath was assessed by intraclass correlation coefficients (ICC). The correlation between CD57 and clinicopathological characteristics was assessed; associations with clinical outcome were estimated using Cox proportional hazard analysis and visualized using Kaplan-Meier curves. The patient cohort had a 3-year OS of 65.8% with a median follow-up of 54 months. The number of CD57+ cells/mm 2 tumor tissue did not correlate to OS, DFS, or LRC. N stage predicted prognosis (OS: HR 0.43, p = 0.008; DFS: HR 0.41, p = 0.003; LRC: HR 0.24, p = 0.007), as did WHO performance state (OS: HR 0.48, p = 0.028; LRC: 0.33, p = 0.039). Quantification by QuPath showed moderate to good concordance with two human observers (ICCs 0.836, CI 0.805-0.863, and 0.741, CI 0.692-0.783, respectively). In conclusion, the presence of CD57+ TILs did not correlate to prognosis in advanced stage, HPV-negative HNSCC patients treated with chemoradiotherapy. Substantial concordance between human observers and QuPath was found, confirming a promising future role for digital, algorithm driven image analysis., (© 2022. The Author(s).)

Purpose: Prior to radiotherapy combined with chemotherapy (CRT) or biotherapy (BRT) for oropharyngeal squamous cell carcinoma (OPSCC), teeth with poor prognosis that pose a risk for post-RT osteoradionecrosis (ORN) are removed. The effect of tooth loss on body weight loss and tube feeding (TF) dependency during CRT/BRT is unknown. This study aimed to evaluate the effect of incomplete dentition, tooth extractions prior to CRT/BRT, and the subsequent loss of functional units on (1) weight loss during CRT/BRT and (2) the need for TF during CRT/BRT for OPSCC., Methods: OPSCC patients treated with CRT/BRT between 2013 and 2016 were included in this retrospective cohort study. Dental status was determined during the dental assessment at first visit and after tooth extractions prior to the start of CRT/BRT. Weight loss during CRT/BRT was scored dichotomously, comparing weight loss > 5% to stable or increased weight. Potential factors associated with weight loss were identified, including patient, tumor, and treatment characteristics., Results: Seventy-seven OPSCC patients were included. Forty patients (52%) experienced weight loss > 5% during CRT/BRT. Extractions were performed in 66% of the OPSCC patients. The mean number of extracted teeth was 4.1 ± 5.6 per patient. Tooth extractions prior to CRT/BRT were associated with weight loss > 5% during CRT/BRT (HR 1.130 (95% CI 1.011-1.262), p = 0.031). None of the dental status-related parameters showed any significant associative value for TF during CRT/BRT., Conclusions: Pre-CRT/BRT tooth extractions intended to reduce the risk of ORN, are a risk factor for weight loss during CRT/BRT for OPSCC., Trial Registration Number: This study was approved by the medical ethics committee of the MUMC + (METC 2020-1589) on July 28, 2020., (© 2022. The Author(s).)

Background: Inevitably, the emergence of COVID-19 has impacted non-COVID care. Because timely diagnosis and treatment are essential, especially for patients with head and neck cancer (HNC) with fast-growing tumours in a functionally and aesthetically important area, we wished to quantify the impact of the COVID-19 pandemic on HNC care in the Netherlands., Material and Methods: This population-based study covered all, in total 8468, newly diagnosed primary HNC cases in the Netherlands in 2018, 2019 and 2020. We compared incidence, patient and tumour characteristics, primary treatment characteristics, and time-to-treatment in the first COVID-19 year 2020 with corresponding periods in 2018 and 2019 (i.e. pre-COVID)., Results: The incidence of HNC was nearly 25% less during the first wave (n = 433) than in 2019 (n = 595) and 2018 (n = 598). In April and May 2020, the incidence of oral cavity and laryngeal carcinomas was significantly lower than in pre-COVID years. There were no shifts in tumour stage or alterations in initial treatment modalities. Regardless of the first treatment modality and specific period, the median number of days between first visit to a HNC centre and start of treatment was significantly shorter during the COVID-19 year (26-28 days) than pre-COVID (31-32 days, p < 0.001)., Conclusion: The incidence of HNC during the Netherlands' first COVID-19 wave was significantly lower than expected. The expected increase in incidence during the remainder of 2020 was not observed. Despite the overloaded healthcare system, the standard treatment for HNC patients could be delivered within a shorter time interval., Competing Interests: Conflict of interest None., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: Patients who receive chemoradiotherapy or bioradiotherapy (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates interfering with oral intake, causing tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds 4 weeks. We aimed to develop and externally validate a prediction model to identify patients who need TF ≥ 4 weeks and would benefit from prophylactic gastrostomy insertion., Methods: A retrospective multicenter cohort study was performed in four tertiary head and neck cancer centers in the Netherlands. The prediction model was developed using data from University Medical Center Utrecht and the Netherlands Cancer Institute and externally validated using data from Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF dependency ≥4 weeks initiated during CRT/BRT or within 30 days after CRT/BRT completion. Potential predictors were extracted from electronic health records and radiotherapy dose-volume parameters were calculated., Results: The developmental and validation cohort included 409 and 334 patients respectively. Multivariable analysis showed predictive value for pretreatment weight change, texture modified diet at baseline, ECOG performance status, tumor site, N classification, mean radiation dose to the contralateral parotid gland and oral cavity. The area under the receiver operating characteristics curve for this model was 0.73 and after external validation 0.62. Positive and negative predictive value for a risk of 90% or higher for TF dependency ≥4 weeks were 81.8% and 42.3% respectively., Conclusions: We developed and externally validated a prediction model to estimate TF-dependency ≥4 weeks in LAHNSCC patients treated with CRT/BRT. This model can be used to guide personalized decision-making on prophylactic gastrostomy insertion in clinical practice., Competing Interests: Conflict of interest Anna C.H. Willemsen, Annemieke Kok, Jan Paul de Boer, Remco de Bree, Chantal M.L. Driessen, Johannes H.A.M. Kaanders, Rebecca T. Karsten, Sander M.J. van Kuijk, Roy I. Lalisang, Arash Navran, Susanne R. Pereboom, Annemie M.W.J. Schols, Chris H.J. Terhaard, and Ann Hoeben declare that they have no conflict of interest. Laura W.J. Baijens. Consulting or advisory role: Phagenesis Limited, member of the Independent FEES Review Committee for the PhINEST study. Lot A. Devriese. Consulting or advisory role: MSD, Bristol Myers Squibb. Frank J.P. Hoebers. Consulting or advisory role: Bristol Myers Squibb. Carla M.L. van Herpen. Consulting or advisory role: Bayer, Bristol Myers Squibb, MSD, Regeneron, TRK Fusion Cancer Medical. Research Funding: Astra Zeneca, Bristol Myers Squibb, MSD, Merck, Ipsen, Novartis, Sanofi, France., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives/hypothesis: To further improve the quality of head and neck cancer (HNC) care, we developed a composite measure defined as "textbook outcome" (TO)., Methods: We analyzed a retrospective cohort of patients after curvative-intent primary surgery, radiotherapy (RT), or chemoradiation (CRT) for HNC between 2015 and 2018 at the Netherlands Cancer Institute. TO was defined as 1) the start of treatment within 30 days, 2a) satisfactory pathologic outcomes, without 30-day postoperative complications, for the surgically treated group, and 2b), for RT and CRT patients, no unexpected or prolonged hospitalization and toxicity after the completion of treatment as planned., Results: In total, 392 patients with HNC were included. An overall TO was achieved in 9.6% of patients after surgery, 20.6% after RT, and 2.2% after CRT. Two indicators (margins >5 mm and start treatment <30 days) reduced TO radically for both groups., Conclusion: TO can aid the evaluation of the quality of care for HNC patients and guide improvement processes., Level of Evidence: 3 Laryngoscope, 132:78-87, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: The prognostic advantage of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) resulted in the initiation of treatment de-intensification studies. Two randomized controlled trials (RCTs) reported inferior survival of HPV-positive OPSCC treated with radiotherapy plus cetuximab compared to standard of care radiotherapy plus cisplatin. In this study we investigated whether the important role of cisplatin in the treatment of HPV-positive OPSCCs would also emerge from causal inference analyses of real-world data., Material and Methods: A retrospective cohort of 263 advanced-stage OPSCC-patients from 5 European clinics was studied, treated with radiotherapy (RT) alone or cisplatin-based chemoradiotherapy (CRT) based on standard clinical indications. Causal inference was applied to adjust for treatment assignment, thereby simulating a randomized setting. Average treatment effect of concurrent cisplatin on overall survival (OS) probability was estimated using Bayesian Additive Regression Trees (BART) and Bayesian logistic regression., Results: Significantly better survival probabilities were found for HPV-positive OPSCC treated with CRT compared to RT alone (3-year OS probability 0.961 versus 0.798, p = 0.008)., Conclusion: This study using causal inference of retrospective patient data confirms the important role of cisplatin in the treatment of HPV-positive OPSCC. Causal inference analyses of real-world data complements the evidence from the published RCTs., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive chemoradiation (CRT) for proximal esophageal cancer., Materials and Methods: Patients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses., Results: In 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8-61.5 months), 58% (95% CI 48-66), and 49% (95% CI 40-57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31-48), and 45% (95% CI 36-54). Three- and five-year risk of LRR were 26% (95% CI 19-33), and 30% (95% CI 22-38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached)., Conclusion: In patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years., Competing Interests: Declaration of competing interest JV has served as a consultant for AstraZeneca, MSD, Pierre Fabre, and Servier, and has received institutional research funding from Servier. All outside the submitted work. SG has received institutional research funding from Roche, Pfizer, Novartis, and Eli Lilly. All outside the submitted work. CM had research collaborations with IBA, Siemens, Raystation, and Mirada. All outside the submitted work. VT has received honoraria/travel grants from Roche, Novartis, Pfizer, Lilly, and Accord Healthcare, and has received institutional research funding from AstraZeneca, Roche, Pfizer, Novartis, Eisai, and Lilly. All outside the submitted work. The other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Malnutrition in head and neck cancer (HNC) patients is associated with increased morbidity and mortality. The purpose of this study is two-fold: to identify the risk of malnutrition in patients with oropharyngeal dysphagia (OD) secondary to HNC, and to determine the relationship between the risk of malnutrition versus tumor characteristics, treatment modality, time interval (between the end of oncological treatment and swallowing assessment date), level of oral intake, body mass index (BMI), aspiration, pharyngeal pooling, and OD-related quality of life (QoL)., Methods: The Short Nutritional Assessment Questionnaire (SNAQ) was used to screen patients for the risk of malnutrition. Patients underwent a standardized swallowing examination protocol including an endoscopic evaluation of swallowing., Results: Seventy-five dysphagic HNC patients were included. Forty-eight percent of the patients presented a high risk of malnutrition using SNAQ. The majority of the patients (81.3%) was on a total oral diet. Moreover, BMI did not appear to be a reliable measure to screen for malnutrition as a normal BMI was often associated with an increased risk of malnutrition on the SNAQ. In contrast, patients who were underweight or overweight did not show an association with a high risk of malnutrition. With the exception of BMI, no other patient and tumor characteristics were found to be associated with the risk of malnutrition., Conclusions: This study emphasizes the importance of early nutritional screening in dysphagic HNC patients, as almost half of these patients presented a high risk of malnutrition. Malnutrition screening using SNAQ can identify HNC patients with OD who are at risk of malnutrition and subsequently need to be referred to a dietician for additional nutritional assessment, diagnosis of malnutrition, and nutritional support, even when their BMI is within normal range., Competing Interests: Declaration of competing interest Dr. L.W.J. Baijens reports personal fees from Phagenesis Limited, The Elms Courtyard, Bromesberrow, Ledbury, HR8 1RZ UK outside the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) patients have high relapse and mortality rates. Imaging-based decision support may improve outcomes by optimising personalised treatment, and support patient risk stratification. We propose a multifactorial prognostic model including radiomics features to improve risk stratification for advanced HNSCC, compared to TNM eighth edition, the gold standard., Patient and Methods: Data of 666 retrospective- and 143 prospective-stage III-IVA/B HNSCC patients were collected. A multivariable Cox proportional-hazards model was trained to predict overall survival (OS) using diagnostic CT-based radiomics features extracted from the primary tumour. Separate analyses were performed using TNM8, tumour volume, clinical and biological variables, and combinations thereof with radiomics features. Patient risk stratification in three groups was assessed through Kaplan-Meier (KM) curves. A log-rank test was performed for significance ( p -value < 0.05). The prognostic accuracy was reported through the concordance index (CI)., Results: A model combining an 11-feature radiomics signature, clinical and biological variables, TNM8, and volume could significantly stratify the validation cohort into three risk groups ( p < 0∙01, CI of 0.79 as validation)., Conclusion: A combination of radiomics features with other predictors can predict OS very accurately for advanced HNSCC patients and improves on the current gold standard of TNM8.

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., Competing Interests: Conflicts of Interest: Steven J. Frank, MD, is an Associate Editor of the International Journal of Particle Therapy. The authors have no other relevant conflicts of interest to disclose., (©Copyright 2021 The Author(s) 2020.)

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., Competing Interests: Conflicts of Interest: J. A. Langendijk is Member of the International Scientific Advisory Committees of IBA and RaySearch; consultant for IBA, honorarium paid to UMCG Research BV. The department of Radiation Oncology has Research Agreement/Grant Support from Siemens, IBA, Elekta, Leonie, RaySearch, and Mirada., (©Copyright 2021 The Author(s).)

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., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Despite advances in treatments, 30% to 50% of stage III-IV head and neck squamous cell carcinoma (HNSCC) patients relapse within 2 years after treatment. The Big Data to Decide (BD2Decide) project aimed to build a database for prognostic prediction modeling., Methods: Stage III-IV HNSCC patients with locoregionally advanced HNSCC treated with curative intent (1537) were included. Whole transcriptomics and radiomics analyses were performed using pretreatment tumor samples and computed tomography/magnetic resonance imaging scans, respectively., Results: The entire cohort was composed of 71% male (1097)and 29% female (440): oral cavity (429, 28%), oropharynx (624, 41%), larynx (314, 20%), and hypopharynx (170, 11%); median follow-up 50.5 months. Transcriptomics and imaging data were available for 1284 (83%) and 1239 (80%) cases, respectively; 1047 (68%) patients shared both., Conclusions: This annotated database represents the HNSCC largest available repository and will enable to develop/validate a decision support system integrating multiscale data to explore through classical and machine learning models their prognostic role., (© 2020 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Cancer cachexia is highly prevalent in advanced non-small cell lung cancer (NSCLC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC), and compromises treatment tolerance and overall survival (OS). NSCLC and LAHNSCC patients share similar risk factors, and receive comparable anti-cancer treatment regimens. The aim of this study was to determine the predictive value of body composition assessed by bioelectrical impedance analysis (BIA) and handgrip strength (HGS) (baseline and early changes during therapy) on OS in NSCLC and LAHNSCC patients treated with platinum-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (BRT). To elucidate potential underlying determinants of early changes in body composition and HGS, specific (fat and fat free) mass loss patterns of squamous NSCLC (sNSCLC) were compared to human papilloma virus negative (HPV-) LAHNSCC patients treated with CRT. Methods: Between 2013 and 2016, BIA and HGS were performed at baseline and after 3 weeks of CRT/BRT in LAHNSCC and NSCLC patients treated with curative intent. Results: Two hundred thirty-three patients were included for baseline measurements. Fat free mass index (FFMI) and HGS<10th percentile of reference values at baseline were both prognostic for poor OS in NSCLC and LAHNSCC [HR 1.64 [95%CI 1.13-2.39], p = 0.01 and HR 2.30 [95%CI 1.33-3.97], p = 0.003, respectively], independent of Charlson Comorbidity Index, cancer site, and gross tumor volume. Early fat mass (FM) loss during CRT was predictive for poor OS in sNSCLC ( n = 64) [HR 3.80 [95%CI 1.79-8.06] p ≤ 0.001] but not in HPV- LAHNSCC ( n = 61). In patients with significant weight loss (>2%) in the first 3 weeks of CRT (sNSCLC n = 24, HPV- LAHNSCC n = 23), the FM change was -1.4 ± 14.5% and -8.7 ± 9.0% in sNSCLC and HPV- LAHNSCC patients, respectively ( p < 0.05). Fat fee mass change was -5.6 ± 6.3% and -4.0 ± 4.3% for sNSCLC and HPV- LAHNSCC, respectively ( p = 0.31). Conclusion: FFMI and HGS<10th percentile at baseline are independent prognostic factors for poor OS in NSCLC and LAHNSCC patients treated with CRT/BRT. The specific composition of mass loss during first 3 weeks of CRT significantly differs between sNSCLC and HPV- LAHNSCC patients. Early FM loss was prognostic in sNSCLC only., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Willemsen, Degens, Baijens, Dingemans, Hoeben, Hoebers, De Ruysscher and Schols.)

Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of this study was to compare the treatment outcomes of contemporary CRT regimens. Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model. Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9-77.2 months). Median OS (21.9 months; 95% CI: 16.9-27.0 months) was comparable between treatment groups (logrank p  = .88), confirmed in the fully adjusted and PS weighted model ( p  > .05). Grades 3-5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31-10.87; p  = .01). The occurrence of grades 3-5 late toxicities was not different between treatment groups. Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC.

Background & Aims: Chemoradiation and bioradiation (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often comes with high toxicity rates, interfering with oral intake and leading to temporary tube feeding (TF) dependency. High-quality scientific evidence for indicators of prophylactic gastrostomy insertion is not available. The aim of this retrospective cohort study was to develop a prediction model to identify patients who need prophylactic gastrostomy insertion, defined as the expected use of TF for at least four weeks., Methods: Four-hundred-fifty LAHNSCC patients receiving CRT/BRT with curative intent between 2013 and 2016 were included in the study. Primary outcome was TF-dependency for four weeks or longer. Patient, tumor, and treatment characteristics were extracted from the medical records and their effects on the use of TF were analyzed using univariable and multivariable analysis. The prediction model was internally validated using bootstrapping techniques., Results: Sixty-five percent (294/450 patients) required TF for four weeks or longer. Variables included in the model were: body mass index and adjusted diet at start of CRT/BRT, percentage weight change at baseline, World Health Organization performance status, tumor subsite, TNM-classification, CRT/BRT, mean radiation dose on the contralateral submandibular and parotid gland. The corrected Area Under the Curve after internal validation was 72.3%, indicating good discriminative properties of the prediction model., Conclusions: We developed and internally validated a prediction model that is intended to estimate TF-dependency for at least four weeks in LAHNSCC patients treated with CRT/BRT. This model can be used as a tool to support personalized decision making on prophylactic gastrostomy insertion., Competing Interests: Conflict of Interest None declared., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Normal Tissue Complication Probability (NTCP) models can be used for treatment plan optimisation and patient selection for emerging treatment techniques. We discuss and suggest methodological approaches to address key challenges in NTCP model development and validation, including: missing data, non-linear response relationships, multicollinearity between predictors, overfitting, generalisability and the prediction of multiple complication grades at multiple time points. The methodological approaches chosen are aimed to improve the accuracy, transparency and robustness of future NTCP-models. We demonstrate our methodological approaches using clinical data., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an internal image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting., Materials and Methods: Ninety-five radiotherapy planning FDG-PET/CT-scans of patients with head and neck cancer were analyzed using the Bland-Altman method to evaluate differences in FDG-uptake in the cervical spinal cord and the mediastinal blood pool. Non-linear regression analysis was used to determine the optimal MTV using the gross tumor volume (GTV) as ground truth and a spatial overlap-index as statistical validation metric. Reproducibility was evaluated using the Bland-Altman method and external validation was performed in an independent dataset consisting of 62 patients., Results: Bland-Altman's analyses demonstrated equivalence of FDG-uptake in the mediastinal blood pool and the cervical spinal cord. Reproducibility of the models improved when using SUR instead of SUV. These results were confirmed in the validation cohort., Conclusion: The use of the tumor to cervical spinal cord SUR instead of SUV improves the reproducibility of a model to determine the MTV on FDG-PET/CT in a multicenter setting. This study indicates that SUR may be preferred over SUV based approaches., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Monitoring and effectively improving oncologic integrated care requires dashboard information based on quality registrations. The dashboard includes evidence-based quality indicators (QIs) that measure quality of care. This study aimed to assess the quality of current integrated head and neck cancer care with QIs, the variation between Dutch hospitals, and the influence of patient and hospital characteristics. Methods: Previously, 39 QIs were developed with input from medical specialists, allied health professionals, and patients' perspectives. QI scores were calculated with data from 1,667 curatively treated patients in 8 hospitals. QIs with a sample size of >400 patients were included to calculate reliable QI scores. We used multilevel analysis to explain the variation. Results: Current care varied from 29% for the QI about a case manager being present to discuss the treatment plan to 100% for the QI about the availability of a treatment plan. Variation between hospitals was small for the QI about patients discussed in multidisciplinary team meetings (adherence: 95%, range 88%-98%), but large for the QI about malnutrition screening (adherence: 50%, range 2%-100%). Higher QI scores were associated with lower performance status, advanced tumor stage, and tumor in the oral cavity or oropharynx at the patient level, and with more curatively treated patients (volume) at hospital level. Conclusions: Although the quality registration was only recently launched, it already visualizes hospital variation in current care. Four determinants were found to be influential: tumor stage, performance status, tumor site, and volume. More data are needed to assure stable results for use in quality improvement., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Background: Pain is still a burden for many patients with cancer. A recent trial showed the superiority of methadone over fentanyl in neuropathic pain, and we expect that this finding could influence the number of patients treated with methadone., Methods: We performed a randomized controlled noninferiority trial in patients with nociceptive pain. Eighty-two strong-opioid-naïve patients with head and neck cancer with substantial pain (pain numeric rating scale [NRS] score ≥ 4) due to radiation therapy were included. Forty-two patients were treated with methadone, and 40 with fentanyl. Patients were evaluated at 1, 3, and 5 weeks. The primary outcomes were reduction in average pain and clinical success (50% pain decrease). We set the predefined noninferiority margin at 1 on the NRS and 10% clinical success. Secondary outcomes were pain interference, global perceived effect (GPE), side effects, and opioid escalation index., Results: Noninferiority was shown for decrease in NRS for maximum and mean pain scores at 1 and 3 weeks. Noninferiority was shown for clinical success at 1 week only. The opioid escalation index was lower in the methadone group at 3 and 5 weeks as compared to fentanyl (1.44 vs. 1.99, P = 0.004; and 1.50 vs. 2.32, P = 0.013). The pain interference in the methadone group was significantly decreased at 3 weeks only. GPE and side effects were not different., Conclusion: This is the first study to show noninferiority of methadone compared to fentanyl at 1 and 3 weeks in the treatment of radiation-induced nociceptive pain in patients with head and neck cancer., (© 2017 World Institute of Pain.)

Background: Audit and feedback on professional practice and health care outcomes are the most often used interventions to change behaviour of professionals and improve quality of health care. However, limited information is available regarding preferred feedback for patients, professionals and health insurers., Objective: Investigate the (differences in) preferences of receiving feedback between stakeholders, using the Dutch Head and Neck Audit as an example., Methods: A total of 37 patients, medical specialists, allied health professionals and health insurers were interviewed using semi-structured interviews. Questions focussed on: "Why," "On what aspects" and "How" do you prefer to receive feedback on professional practice and health care outcomes?, Results: All stakeholders mentioned that feedback can improve health care by creating awareness, enabling self-reflection and reflection on peers or colleagues, and by benchmarking to others. Patients prefer feedback on the actual professional practice that matches the health care received, whereas medical specialists and health insurers are interested mainly in health care outcomes. All stakeholders largely prefer a bar graph. Patients prefer a pie chart for patient-reported outcomes and experiences, while Kaplan-Meier survival curves are preferred by medical specialists. Feedback should be simple with firstly an overview, and 1-4 times a year sent by e-mail. Finally, patients and health professionals are cautious with regard to transparency of audit data., Conclusions: This exploratory study shows how feedback preferences differ between stakeholders. Therefore, tailored reports are recommended. Using this information, effects of audit and feedback can be improved by adapting the feedback format and contents to the preferences of stakeholders., (© 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.)

Objective: The aim of the study was to investigate the accuracy of dual-energy computed tomography (DECT) compared with magnetic resonance (MR) imaging for the detection of edema of the mandible., Materials and Methods: Fifteen adult Göttingen mini pigs received irradiation to the mandible with an equivalent dose of 0, 25, 50, or 70 Gy. Six months after irradiation, all animals underwent DECT and MR imaging of the mandible. Magnetic resonance short tau inversion recovery (STIR) was used for the grading of the bone marrow edema (0-3). Dual-energy CT (80 and 140 kVp) was performed, and virtual noncalcium (VNCa) images were calculated., Results: Increased signal intensity at STIR was found in the higher radiation groups. An increase of signal intensity in MR imaging was accompanied by a significant increase in the Hounsfield unit value of the VNCa images of the bone marrow (STIR: 0, 1, 2, 3; mean Hounsfield unit: -103, -90, -76, -34, respectively; P < 0.05; R = 0.388)., Conclusions: The VNCa images derived from DECT are able to demonstrate bone marrow edema in radiation-induced bone changes in the mandible.

Background and Purpose: In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs)., Material and Methods: Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT)., Results: When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D 2 ) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org., Conclusions: In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)