Towards a European prospective data registry for particle therapy.

The evidence for the value of particle therapy (PT) is still sparse. While randomized trials remain a cornerstone for robust comparisons with photon-based radiotherapy, data registries collecting real-world data can play a crucial role in building evidence for new developments. This Perspective describes how the European Particle Therapy Network (EPTN) is actively working on establishing a prospective data registry encompassing all patients undergoing PT in European centers. Several obstacles and hurdles are discussed, for instance harmonization of nomenclature and structure of technical and dosimetric data and data protection issues. A preferred approach is the adoption of a federated data registry model with transparent and agile governance to meet European requirements for data protection, transfer, and processing. Funding of the registry, especially for operation after the initial setup process, remains a major challenge.

Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial.

BACKGROUND: Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC. METHODS: In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy. Randomisation was done using an interactive response technology system and was stratified by investigator's choice of radiotherapy regimen, tumour site and p16 status, and disease stage, with participants randomly assigned in blocks of four per stratum. Participants, investigators, and sponsor personnel were masked to treatment assignments. Local pharmacists were aware of assignments to support treatment preparation. Pembrolizumab and placebo were administered intravenously once every 3 weeks for up to 17 doses (one before chemoradiotherapy, two during chemoradiotherapy, 14 as maintenance therapy). Chemoradiotherapy included cisplatin (100 mg/m2) administered intravenously once every 3 weeks for two or three doses and accelerated or standard fractionation radiotherapy (70 Gy delivered in 35 fractions). The primary endpoint was event-free survival analysed in all randomly assigned participants. Safety was analysed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03040999, and is active but not recruiting. FINDINGS: Between April 19, 2017, and May 2, 2019, 804 participants were randomly assigned to the pembrolizumab group (n=402) or the placebo group (n=402). 660 (82%) of 804 participants were male, 144 (18%) were female, and 622 (77%) were White. Median study follow-up was 47·7 months (IQR 42·1-52·3). Median event-free survival was not reached (95% CI 44·7 months-not reached) in the pembrolizumab group and 46·6 months (27·5-not reached) in the placebo group (hazard ratio 0·83 [95% CI 0·68-1·03]; log-rank p=0·043 [significance threshold, p≤0·024]). 367 (92%) of 398 participants treated in the pembrolizumab group and 352 (88%) of 398 participants treated in the placebo group had grade 3 or worse adverse events. The most common grade 3 or worse adverse events were decreased neutrophil count (108 [27%] of 398 participants in the pembrolizumab group vs 100 [25%] of 398 participants in the placebo group), stomatitis (80 [20%] vs 69 [17%]), anaemia (80 [20%] vs 61 [15%]), dysphagia (76 [19%] vs 62 [16%]), and decreased lymphocyte count (76 [19%] vs 81 [20%]). Serious adverse events occurred in 245 (62%) participants in the pembrolizumab group versus 197 (49%) participants in the placebo group, most commonly pneumonia (43 [11%] vs 25 [6%]), acute kidney injury (33 [8%] vs 30 [8%]), and febrile neutropenia (24 [6%] vs seven [2%]). Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group (one participant each from aspiration pneumonia, end-stage renal disease, pneumonia, and sclerosing cholangitis) and six (2%) participants in the placebo group (three participants from pharyngeal haemorrhage and one participant each from mouth haemorrhage, post-procedural haemorrhage, and sepsis). INTERPRETATION: Pembrolizumab plus chemoradiotherapy did not significantly improve event-free survival compared with chemoradiotherapy alone in a molecularly unselected, locally advanced HNSCC population. No new safety signals were seen. Locally advanced HNSCC remains a challenging disease that requires better treatment approaches. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

Translational frontiers and clinical opportunities of immunologically-fitted radiotherapy.

Ionising radiations can have a wide range of impacts on tumour-immune interactions, which are being studied with the greatest interest and at an accelerating pace by the medical community. Despite its undeniable immunostimulatory potential, it clearly appears that radiotherapy as it is prescribed and delivered nowadays often alters the host's immunity towards a suboptimal state. This may impair the full recovery of a sustained and efficient anti-tumour immunosurveillance post-treatment. An emerging concept is arising from this awareness and consists in re-considering the way of designing radiation treatment plannings, notably by taking into account the individualised risks of deleterious radio-induced immune alteration that can be deciphered from the planned beam trajectory through lymphocyte-rich organs. In this review, we critically appraise key aspects to consider while planning immunologically-fitted radiotherapy, including the challenges linked to the identification of new dose constraints to immune-rich structures. We also discuss how pharmacological immunomodulation could be advantageously used in combination with radiotherapy to compensate for the radio-induced loss, for example with (i) agonists of interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 or IL-21, similarly to G-CSF being used for the prophylaxis of severe chemo-induced neutropenia, or with (ii) myeloid-derived suppressive cells (MDSC) blockers.

Deep-Learning for Rapid Estimation of the Out-of-Field Dose in External Beam Photon Radiation Therapy - A Proof of Concept.

PURPOSE: The dose deposited outside of the treatment field during external photon beam radiation therapy treatment, also known as out-of-field dose, is the subject of extensive study as it may be associated with a higher risk of developing a second cancer and could have deleterious effects on the immune system that compromise the efficiency of combined radio-immunotherapy treatments. Out-of-field dose estimation tools developed today in research, including Monte Carlo simulations and analytical methods, are not suited to the requirements of clinical implementation because of their lack of versatility and their cumbersome application. We propose a proof of concept based on deep learning for out-of-field dose map estimation that addresses these limitations. METHODS AND MATERIALS: For this purpose, a 3D U-Net, considering as inputs the in-field dose, as computed by the treatment planning system, and the patient's anatomy, was trained to predict out-of-field dose maps. The cohort used for learning and performance evaluation included 3151 pediatric patients from the FCCSS database, treated in 5 clinical centers, whose whole-body dose maps were previously estimated with an empirical analytical method. The test set, composed of 433 patients, was split into 5 subdata sets, each containing patients treated with devices unseen during the training phase. Root mean square deviation evaluated only on nonzero voxels located in the out-of-field areas was computed as performance metric. RESULTS: Root mean square deviations of 0.28 and 0.41 cGy/Gy were obtained for the training and validation data sets, respectively. Values of 0.27, 0.26, 0.28, 0.30, and 0.45 cGy/Gy were achieved for the 6 MV linear accelerator, 16 MV linear accelerator, Alcyon cobalt irradiator, Mobiletron cobalt irradiator, and betatron device test sets, respectively. CONCLUSIONS: This proof-of-concept approach using a convolutional neural network has demonstrated unprecedented generalizability for this task, although it remains limited, and brings us closer to an implementation compatible with clinical routine.

Long-term health-related quality of life in head and neck cancer survivors: A large multinational study.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

A multi-centric dataset on patient-individual pathological lymph node involvement in head and neck squamous cell carcinoma.

Dataset: We provide a dataset on lymph node metastases in 968 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC). All patients received neck dissection and we report the number of metastatic versus investigated lymph nodes per lymph node level (LNL) for every individual patient. Additionally, clinicopathological factors including T-category, primary tumor subsite (ICD-O-3 code), age, and sex are reported for all patients. The data is provided as three datasets: Dataset 1 contains 373 HNSCC patients treated at Centre Léon Bérard (CLB), France, with primary tumor location in the oral cavity, oropharynx, hypopharynx, and larynx. Dataset 2 contains 332 HNSCC patients treated at the Inselspital, Bern University Hospital (ISB), Switzerland with primary tumor location in the oral cavity, oropharynx, hypopharynx, and larynx. For these patients, additional information is provided including lateralization of the primary tumor, size and location of the largest metastases, and clinical involvement based on computed tomography (CT), magnetic resonance imaging (MRI), and/or 18FDG-positron emission tomography (PET/CT) imaging. Dataset 3 consists of 263 oropharyngeal SCC patients underlying a previous publication by Bauwens et al. [1], which were treated at CLB. For these patients, additional information including HPV status, lateralization of the primary tumor and clinically diagnosed lymph node involvement is provided. Reuse Potential: The data may be used to quantify the probability of occult lymph node metastases in each LNL, depending on an individual patient's characteristics of the primary tumor and the location of clinically diagnosed lymph node metastases. As such, the data may contribute to further personalize the elective treatment of the neck for HNSCC patients, i.e. definition of the elective clinical target volume (CTV-N) in radiotherapy (RT) and the extent of neck dissection (ND) in surgery. There exists only one similar publicly available dataset that reports clinical involvement per LNL in 287 oropharyngeal SCC patients [2]. The data presented in this article substantially extends the available data, it additionally includes pathologically assessed involvement per LNL, and it provides data for multiple subsites in the head and neck region.

Evaluation of different algorithms for automatic segmentation of head-and-neck lymph nodes on CT images.

PURPOSE: To investigate the performance of 4 atlas-based (multi-ABAS) and 2 deep learning (DL) solutions for head-and-neck (HN) elective nodes (CTVn) automatic segmentation (AS) on CT images. MATERIAL AND METHODS: Bilateral CTVn levels of 69 HN cancer patients were delineated on contrast-enhanced planning CT. Ten and 49 patients were used for atlas library and for training a mono-centric DL model, respectively. The remaining 20 patients were used for testing. Additionally, three commercial multi-ABAS methods and one commercial multi-centric DL solution were investigated. Quantitative evaluation was assessed using volumetric Dice Similarity Coefficient (DSC) and 95-percentile Hausdorff distance (HD95%). Blind evaluation was performed for 3 solutions by 4 physicians. One recorded the time needed for manual corrections. A dosimetric study was finally conducted using automated planning. RESULTS: Overall DL solutions had better DSC and HD95% results than multi-ABAS methods. No statistically significant difference was found between the 2 DL solutions. However, the contours provided by multi-centric DL solution were preferred by all physicians and were also faster to correct (1.1 min vs 4.17 min, on average). Manual corrections for multi-ABAS contours took on average 6.52 min Overall, decreased contour accuracy was observed from CTVn2 to CTVn3 and to CTVn4. Using the AS contours in treatment planning resulted in underdosage of the elective target volume. CONCLUSION: Among all methods, the multi-centric DL method showed the highest delineation accuracy and was better rated by experts. Manual corrections remain necessary to avoid elective target underdosage. Finally, AS contours help reducing the workload of manual delineation task.

Biomarkers of radioresistance in head and neck squamous cell carcinomas.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality. Although HNSCC is mainly caused by tobacco and alcohol consumption, infection by Human Papilloma Virus (HPV) has been also associated with the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCC) during the past decades. HPV-positive HNSCC is characterized by a higher radiosensitivity compared to HPV-negative tumor. While several clinical trials are evaluating de-escaladed radiation doses strategies in HPV-positive HNSCC, molecular mechanisms associated with relative radioresistance in HPV-negative HNSCC are still broadly unknown. Our goal was to review recently proposed biomarkers of radioresistance in this setting, which may be useful for stratifying tumor's patient according to predicted level of radioresistance. CONCLUSIONS: most of biomarkers of radioresistance in HPV-negative HNSCC are identified using a hypothesis-driven approach, based on molecular mechanisms known to play a key role during carcinogenesis, compared to an unsupervised data-driven approach regardless the biological rational. DNA repair and hypoxia are the two most widely investigated biological and targetable pathways related to radioresistance in HNSCC. The better understanding of molecular mechanisms and biomarkers of radioresistance in HPV-negative HNSCC could help for the development of radiosensitization strategies, based on targetable biomarkers, in radioresistant tumors as well as de-escalation radiation dose strategies, based on biological level of radioresistance, in radiosensitive tumors.

International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.

Salivary gland cancers in elderly patients: challenges and therapeutic strategies.

Salivary gland carcinomas (SGCs) are the most heterogeneous subgroup of head and neck malignant tumors, accounting for more than 20 subtypes. The median age of SGC diagnosis is expected to rise in the following decades, leading to crucial clinical challenges in geriatric oncology. Elderly patients, in comparison with patients aged below 65 years, are generally considered less amenable to receiving state-of-the-art curative treatments for localized disease, such as surgery and radiation/particle therapy. In the advanced setting, chemotherapy regimens are often dampened by the consideration of cardiovascular and renal comorbidities. Nevertheless, the elderly population encompasses a broad spectrum of functionalities. In the last decades, some screening tools (e.g. the G8 questionnaire) have been developed to identify those subjects who should receive a multidimensional geriatric assessment, to answer the question about the feasibility of complex treatments. In the present article, we discuss the most frequent SGC histologies diagnosed in the elderly population and the relative 5-years survival outcomes based on the most recent data from the Surveillance, Epidemiology, and End Results (SEER) Program. Moreover, we review the therapeutic strategies currently available for locoregionally advanced and metastatic disease, taking into account the recent advances in precision oncology. The synergy between the Multidisciplinary Tumor Board and the Geriatrician aims to shape the most appropriate treatment pathway for each elderly patient, focusing on global functionality instead of the sole chronological age.

Comparison of atlas-based and deep learning methods for organs at risk delineation on head-and-neck CT images using an automated treatment planning system.

BACKGROUND AND PURPOSE: To investigate the performance of head-and-neck (HN) organs-at-risk (OAR) automatic segmentation (AS) using four atlas-based (ABAS) and two deep learning (DL) solutions. MATERIAL AND METHODS: All patients underwent iodine contrast-enhanced planning CT. Fourteen OAR were manually delineated. DL.1 and DL.2 solutions were trained with 63 mono-centric patients and > 1000 multi-centric patients, respectively. Ten and 15 patients with varied anatomies were selected for the atlas library and for testing, respectively. The evaluation was based on geometric indices (DICE coefficient and 95th percentile-Hausdorff Distance (HD95%)), time needed for manual corrections and clinical dosimetric endpoints obtained using automated treatment planning. RESULTS: Both DICE and HD95% results indicated that DL algorithms generally performed better compared with ABAS algorithms for automatic segmentation of HN OAR. However, the hybrid-ABAS (ABAS.3) algorithm sometimes provided the highest agreement to the reference contours compared with the 2 DL. Compared with DL.2 and ABAS.3, DL.1 contours were the fastest to correct. For the 3 solutions, the differences in dose distributions obtained using AS contours and AS + manually corrected contours were not statistically significant. High dose differences could be observed when OAR contours were at short distances to the targets. However, this was not always interrelated. CONCLUSION: DL methods generally showed higher delineation accuracy compared with ABAS methods for AS segmentation of HN OAR. Most ABAS contours had high conformity to the reference but were more time consuming than DL algorithms, especially when considering the computing time and the time spent on manual corrections.

18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization.

Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is utilized for staging and treatment planning of head and neck squamous cell carcinomas (HNSCC). Some older publications on the prognostic relevance showed inconclusive results, most probably due to small study sizes. This study evaluates the prognostic and potentially predictive value of FDG-PET in a large multi-center analysis. Methods: Original analysis of individual FDG-PET and patient data from 16 international centers (8 institutional datasets, 8 public repositories) with 1104 patients. All patients received curative intent radiotherapy/chemoradiation (CRT) and pre-treatment FDG-PET imaging. Primary tumors were semi-automatically delineated for calculation of SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Cox regression analyses were performed for event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Results: FDG-PET parameters were associated with patient outcome in the whole cohort regarding clinical endpoints (EFS, OS, LRC, FFDM), in uni- and multivariate Cox regression analyses. Several previously published cut-off values were successfully validated. Subgroup analyses identified tumor- and human papillomavirus (HPV) specific parameters. In HPV positive oropharynx cancer (OPC) SUVmax was well suited to identify patients with excellent LRC for organ preservation. Patients with SUVmax of 14 or less were unlikely to develop loco-regional recurrence after definitive CRT. In contrast FDG PET parameters deliver only limited prognostic information in laryngeal cancer. Conclusion: FDG-PET parameters bear considerable prognostic value in HNSCC and potential predictive value in subgroups of patients, especially regarding treatment de-intensification and organ-preservation. The potential predictive value needs further validation in appropriate control groups. Further research on advanced imaging approaches including radiomics or artificial intelligence methods should implement the identified cut-off values as benchmark routine imaging parameters.

A dataset on patient-individual lymph node involvement in oropharyngeal squamous cell carcinoma.

Dataset: We provide a dataset on lymph node level (LNL) involvement in 287 patients with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC). For each patient, ipsilateral and contralateral LNL involvement for levels I to VII is reported together with clinicopathological factors including TNM-stage, primary tumor subsite, tumor lateralization, HPV status, sex, age, smoking status, and primary treatment. LNL involvement was assessed individually based on available diagnostic modalities (PET, MRI, CT, fine needle aspiration) by reviewing pathology and radiology reports together with the radiological images. The data is shared as a CSV-table with rows of patients and columns of patient/tumor-specific information and the involvement of individual LNL based on the respective diagnostic modalities. Reuse potential: Patterns of lymphatic progression have never been reported on a patient-individual basis in as much detail as provided in this dataset. The data can be used to build quantitative models for lymphatic tumor progression to estimate the probability of occult metastases in LNLs. This may in turn allow for further personalization of the elective clinical target volume definition in radiotherapy and the extent of neck dissection for surgically treated patients. The data can be pooled with other data to build large multi-institutional datasets on lymphatic metastatic progression in the future. Co-submission: This paper supports the original scientific article by Roman Ludwig, Jean-Marc Hoffmann, Bertrand Pouymayou, Grégoire Morand, Martina Broglie Däppen, Matthias Guckenberger, Vincent Grégoire, Panagiotis Balermpas, Jan Unkelbach, "Detailed patient-individual reporting of lymph node involvement in oropharyngeal squamous cell carcinoma with an online interface", Radiotherapy & Oncology [1].

Correction: Brochet et al. A Quantitative Comparison between Shannon and Tsallis-Havrda-Charvat Entropies Applied to Cancer Outcome Prediction. Entropy 2022, 24, 436.

Alexandre Huat, Sébastien Thureau, David Pasquier, Isabelle Gardin, Romain Modzelewski, David Gibon, Juliette Thariat and Vincent Grégoire were not included as authors in the original publication [...].

A Quantitative Comparison between Shannon and Tsallis-Havrda-Charvat Entropies Applied to Cancer Outcome Prediction.

In this paper, we propose to quantitatively compare loss functions based on parameterized Tsallis-Havrda-Charvat entropy and classical Shannon entropy for the training of a deep network in the case of small datasets which are usually encountered in medical applications. Shannon cross-entropy is widely used as a loss function for most neural networks applied to the segmentation, classification and detection of images. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy. In this work, we compare these two entropies through a medical application for predicting recurrence in patients with head-neck and lung cancers after treatment. Based on both CT images and patient information, a multitask deep neural network is proposed to perform a recurrence prediction task using cross-entropy as a loss function and an image reconstruction task. Tsallis-Havrda-Charvat cross-entropy is a parameterized cross-entropy with the parameter α. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy for α=1. The influence of this parameter on the final prediction results is studied. In this paper, the experiments are conducted on two datasets including in total 580 patients, of whom 434 suffered from head-neck cancers and 146 from lung cancers. The results show that Tsallis-Havrda-Charvat entropy can achieve better performance in terms of prediction accuracy with some values of α.

Unmet Needs and Perspectives in Oral Cancer Prevention.

Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover, this range highlights differences in the clinical definition of OPMD, variation in follow-up periods, and molecular and biological heterogeneity of OPMD. Finally, while treatment of OPMD may improve outcome, standard therapy has been shown to be ineffective to prevent OSCC development in patients with OPMD. In this perspective paper, several experts discuss the main challenges in oral cancer prevention, in particular the need to (i) to define an OPMD classification system by integrating new pathological and molecular characteristics, aiming (ii) to better identify OPMD at high risk of malignant transformation, and (iii) to develop treatment strategies to eradicate OPMD or prevent malignant transformation.

Indications of external beams radiation for thyroid cancer.

PURPOSE OF REVIEW: The use of external beam radiation therapy (EBRT) for the treatment of the different histologic subtypes of thyroid cancer is a matter of debate. This article provides an up-to-date review on the current evidence concerning the benefits of EBRT in thyroid cancer in specific indications. RECENT FINDINGS: Based on retrospective studies, adjuvant EBRT lessens the risk of locoregional recurrence in locally advanced differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) with high-risk features. The effect of EBRT on overall survival remains uncertain. EBRT should also be part of the multimodality treatment in anaplastic thyroid cancer (ATC), as it improves survival rates in incompletely resected ATC. SUMMARY: The role of EBRT in thyroid cancer remains unclear. To date, no randomized control studies are available. Retrospective data showed improved outcomes in patients with high-risk features for locoregional recurrence.

Detailed patient-individual reporting of lymph node involvement in oropharyngeal squamous cell carcinoma with an online interface.

PURPOSE/OBJECTIVE: Whereas the prevalence of lymph node level (LNL) involvement in head & neck squamous cell carcinomas (HNSCC) has been reported, the details of lymphatic progression patterns are insufficiently quantified. In this study, we investigate how the risk of metastases in each LNL depends on the involvement of upstream LNLs, T-category, HPV status and other risk factors. MATERIALS/METHODS: We retrospectively analyzed patients with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) treated at a single institution, resulting in a dataset of 287 patients. For all patients, involvement of LNLs I-VII was recorded individually based on available diagnostic modalities (PET, MRI, CT, FNA) together with clinicopathological factors. To analyze the dataset, a web-based graphical user interface (GUI) was developed, which allows querying the number of patients with a certain combination of co-involved LNLs and tumor characteristics. RESULTS: The full dataset and GUI is part of the publication. Selected findings are: Ipsilateral level IV was involved in 27% of patients with level II and III involvement, but only in 2% of patients with level II but not III involvement. Prevalence of involvement of ipsilateral levels II, III, IV, V was 79%, 34%, 7%, 3% for early T-category patients (T1/T2) and 85%, 50%, 17%, 9% for late T-category (T3/T4), quantifying increasing involvement with T-category. Contralateral levels II, III, IV were involved in 41%, 19%, 4% and 12%, 3%, 2% for tumors with and without midline extension, respectively. T-stage dependence of LNL involvement was more pronounced in HPV negative than positive tumors, but overall involvement was similar. Ipsilateral level VII was involved in 14% and 6% of patients with primary tumors in the tonsil and the base of tongue, respectively. CONCLUSIONS: Detailed quantification of LNL involvement in HNSCC depending on involvement of upstream LNLs and clinicopathological factors may allow for further personalization of CTV-N definition in the future.

Current practice in proton therapy delivery in adult cancer patients across Europe.

BACKGROUND AND PURPOSE: Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres. MATERIALS AND METHODS: We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT. RESULTS: Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%). CONCLUSION: Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT.