Acute toxicities in proton therapy for head and neck cancer - A matched analysis of the DAHANCA 35 feasibility study.

Background and purpose: As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods: 62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. Results: Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01-3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3-1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period. Conclusion: Proton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.

European Society of Radiotherapy and Oncology (ESTRO) strategy 2024-2026: Growth and diversification in a rapidly changing world.

In 2019, the European Society of Radiotherapy and Oncology (ESTRO) published its 2030 Vision "Radiation Oncology, Optimal Health, For All, Together". However, in 2020, the global pandemic, coinciding with the Society's 40th anniversary, had long-term consequences on global behaviours and on the financial environment for scientific associations worldwide. In 2022, ESTRO conducted a survey among its members, revealing their strong appreciation for networking opportunities and the creation of high-quality interdisciplinary scientific content. In response to the survey findings and to address the evolving landscape following the COVID pandemic, ESTRO initiated a strategic review process to respond to, and refocus on, the opportunities and challenges ahead. This paper, marking a turning point in ESTRO's strategy for achieving its Vision 2030 in a post-pandemic era, describes the 2022-23 strategic review process, discussions, and consequent recommendations. The comprehensive strategic review process involved: (i) pre-meeting preparations with surveys and strategic documents; (ii) a carefully themed three-day retreat in Brussels incorporating a blend of plenary sessions, workshops focusing on ESTRO's role, value creation and capture, strategic objectives; and (iii) a post-retreat phase including qualitative analysis and development of action plans. The strategic review emphasized the need for adaptive tactics for scientific associations to remain current and productive in the face of changing global conditions. The development of key strategic goals for the years 2024-2026 focused on improving research impact, strengthening and diversifying ESTRO's educational offerings and fostering proactive and mutually beneficial partnerships. The Board approved these objectives, alongside prioritising digital innovation, financial sustainability, and community engagement for ESTRO's continued growth and development. In essence, ESTRO aims to advocate, empower, expand, and diversify its community, with the overarching goal of enhancing cancer care for patients in Europe, and beyond.

Considerations for study design in the DAHANCA 35 trial of protons versus photons for head and neck cancer.

Proton radiotherapy offers a dosimetric advantage compared to photon therapy in sparing normal tissue, but the clinical evidence for toxicity reductions in the treatment of head and neck cancer is limited. The Danish Head and Neck Cancer Group (DAHANCA) has initiated the DAHANCA 35 randomised trial to clarify the value of proton therapy (NCT04607694). The DAHANCA 35 trial is performed in an enriched population of patients selected by an anticipated benefit of proton therapy to reduce the risk of late dysphagia or xerostomia based on normal tissue complication probability (NTCP) modelling. We present our considerations on the trial design and a test of the selection procedure conducted before initiating the randomised study.

Like Frying Multiple Eggs in One Pan: a Qualitative Study Exploring the Understanding of Inter-speciality Training in Cancer Care.

H igh-quality cancer care is a key priority worldwide. Caring for people affected by cancer requires a range of specific knowledge, skills and experience to deliver the complex care regimens both within the hospital and within the community environment. In June 2022, the European Cancer Organisation along with 33 European cancer societies began working together to develop a curriculum for inter-speciality training for healthcare professionals across Europe. As part of the project, this research consisted of a qualitative survey distributed to the European Union societies via email. The aim of this paper is to disseminate the qualitative findings from healthcare professionals across Europe. Questionnaires were sent out to a convenience sample of 219 healthcare professionals and patient advocates with a response rate of 55% (n = 115). The findings identified that there were four key themes: 'What is inter-speciality training?', 'Barriers and challenges', 'Support throughout the cancer journey' and 'New ways of working'. These results are part of a larger needs analysis and scoping review to inform the development of a core competency framework which will be part of an inter-speciality curriculum for specialist cancer doctors, nurses and other healthcare professionals across Europe. Healthcare professionals will be able to access education and training through the virtual learning environment and workshops and by clinical rotations to other specialties.

Early Mortality after Radical Radiotherapy in Head and Neck Cancer - A Nationwide Analysis from the Danish Head and Neck Cancer Group (DAHANCA) Database.

AIMS: Curative-intent radiotherapy (RT) or chemoradiation (CRT) of squamous cell carcinoma of the head and neck (HNSCC) produces high survival rates, but is associated with substantial toxicity. However, there are no commonly accepted quality metrics for early mortality in radiation oncology. To assess the applicability of early mortality as a clinical quality indicator, this study investigated the temporal distribution, risk factors and trends of 90- and 180-day overall and non-cancer mortality in a nationwide cohort of HNSCC patients treated with RT/CRT. MATERIALS AND METHODS: Information on all HNSCC patients treated with curative-intent RT/CRT in Denmark between 2000 and 2017 was obtained from the national Danish Head and Neck Cancer Group clinical database. Deaths in patients with residual or recurrent disease after RT/CRT were classified as cancer-related. Possible risk factors were investigated using logistic regression analysis. RESULTS: Data from 11 419 patients were extracted. In total, 90- and 180-day mortality risks were 3.1% and 7.1%, respectively. There was a uniform temporal distribution of 180-day mortality. In multivariable analysis, increasing age, stage, performance status, earlier treatment year and hypopharyngeal cancer were significantly associated with an increased risk (P < 0.05). Risk factor estimates were comparable for 90- versus 180-day mortality as well as for overall versus non-cancer mortality. Between 2000 and 2017 there was a significant decrease in 180-day mortality, which was driven by a reduction in cancer-related events. CONCLUSION: The distribution of 180-day overall and non-cancer mortality did not indicate a well-defined early high-risk period. Moreover, risk factor estimates were highly similar across risk periods and groups. Taken together, our findings question the applicability of early mortality as a standard metric for treatment-associated toxicity.

Prediction of radiation-induced mucositis of H&N cancer patients based on a large patient cohort.

PURPOSE/OBJECTIVE: Radiation-induced mucositis is a severe acute side effect, which can jeopardize treatment compliance and cause weight loss during treatment. The study aimed to develop robust models to predict the risk of severe mucositis. MATERIALS/METHODS: Mucosal toxicity scores were prospectively recorded for 802 consecutive Head and Neck (H&N) cancer patients and dichotomised into non-severe event (grade 0-2) and severe event (grade 3+) groups. Two different model approaches were utilised to evaluate the robustness of the models. These used LASSO and Best Subset selection combined with 10-fold cross-validation performed on two-thirds of the patient cohort using principal component analysis of DVHs. The remaining one-third of the patients were used for validation. Model performance was tested through calibration plot and model performance metrics. RESULTS: The main predicted risk factors were treatment acceleration and the first two principal dose components, which reflect the mean dose and the balance between high and low doses to the oral cavity. For the LASSO model, gender and current smoker status were also included in the model. The AUC values of the two models on the validation cohort were 0.797 (95%CI: 0.741-0.857) and 0.808 (95%CI: 0.749-0.859), respectively. The two models predicted very similar risk values with an internal Pearson coefficient of 0.954, indicating their robustness. CONCLUSIONS: Robust prediction models of the risk of severe mucositis have been developed based on information from the entire dose distribution for a large cohort of patients consisting of all patients treated H&N for within our institution over a five year period.

Surgeons' posture and muscle strain during laparoscopic and robotic surgery.

BACKGROUND: It is assumed that conventional laparoscopy (LAP) and robotic-assisted laparoscopic surgery (RALS) differ in terms of the surgeon's comfort. This study compared muscle workload, work posture and perceived physical exertion of surgeons performing LAP or RALS. METHODS: Colorectal surgeons with experience in advanced LAP and RALS performed one of each operation. Bipolar surface electromyography (EMG) recordings were made from forearm, shoulder and neck muscles, and expressed relative to EMG maximum (%EMGmax ). The static, median and peak levels of muscle activity were calculated, and an exposure variation analysis undertaken. Postural observations were carried out every 10 min, and ratings of perceived physical exertion before and after surgery were recorded. RESULTS: The study included 13 surgeons. Surgeons performing LAP showed higher static, median, and peak forearm muscle activity than those undertaking RALS. Muscle activity at peak level was higher during RALS than LAP. Exposure variation analysis demonstrated long-lasting periods of low-level intensity muscle activity in the shoulders for LAP, in the forearms for RALS, and in the neck for both procedures. Postural observations revealed a greater need for a change in work posture when performing LAP compared with RALS. Perceived physical exertion was no different between the surgical modalities. CONCLUSION: Minimally invasive surgery requires long-term static muscle activity with a high physical workload for surgeons. RALS is less demanding on posture.

ANTECEDENTES: Se asume que la cirugía laparoscópica (laparoscopic, LAP) y la cirugía laparoscópica asistida por robot (robotic-assisted laparoscopic surgery, RALS) difieren en cuanto a la comodidad del cirujano. En este estudio se comparó la carga de trabajo muscular, la postura de trabajo y el esfuerzo físico percibido por los cirujanos al realizar LAP o RALS. MÉTODOS: Trece cirujanos colorrectales con experiencia en LAP avanzada y RALS realizaron una operación con cada uno de los abordajes. Se registró la electromiografía de superficie bipolar en los músculos del antebrazo, del hombro y del cuello, y se expresó en relación con el EMG máximo (% EMGmax). Se calculó el nivel de actividad muscular estático, mediano y pico, y se realizó un análisis de variación de la exposición. Las observaciones posturales se llevaron a cabo cada diez minutos y se registraron las valoraciones del esfuerzo físico percibido antes y después de la cirugía. RESULTADOS: La práctica de LAP mostró una mayor actividad muscular estática, mediana y pico del antebrazo en comparación con la práctica de RALS. El hombro izquierdo mostró la mayor actividad muscular en RALS a nivel máximo. El análisis de variación de exposición demostró periodos prolongados de actividad muscular de baja intensidad para LAP en los hombros, para RALS en los antebrazos y para ambos en el cuello. Las observaciones posturales mostraron una mayor necesidad de un cambio en la postura de trabajo al realizar LAP en comparación con RALS. El esfuerzo físico percibido no fue diferente entre ambas modalidades quirúrgicas. CONCLUSIÓN: La cirugía mínimamente invasiva requiere una actividad muscular estática prolongada con una alta carga de trabajo físico para los cirujanos. RALS es menos exigente en el aspecto postural.

Osteoradionecrosis of the mandible after radiotherapy for head and neck cancer: risk factors and dose-volume correlations.

Background: The project aimed at determining the incidence of mandibular osteoradionecrosis (ORN) after radiotherapy, possible risk factors, and mandibular dose-volume effects in a large cohort of head and neck cancer patients (HNC). Methods: The cohort consisted of 1224 HNC patients treated with 66-68 Gy in 2007-2015 predominantly with IMRT. ORN cases were defined from clinical observations at follow-up and through hospital code diagnostics after oral-maxillofacial surgery and cross-checked with the national Danish Head and Neck Cancer database. In a nested case-control study, patients with ORN cases were matched with two controls (1:2) and pre-RT dental procedures including surgery to the mandible were documented. Multivariable Cox regression analysis was applied using demographic and treatment variables including dental procedures, smoking and tumor characteristics, and combined with dosimetric data. Mean mandibular dose (Dmean) was pre-selected for the multivariable model. Results: ORN was recorded in 56 cases (4.6%) with a median time to event of 10.9 months (range 1.8-89.7) after RT, 90% occurred within 37.4 months. Median follow-up time was 22 months (0.3-95). Average Dmean was significantly higher in the ORN event cohort and significant dose-volume differences were observed for population mean DVH doses between 30 Gy and 60 Gy. In univariable analysis, smoking (HR = 1.69; CI 1.14-2.5), pre-RT surgery/tooth extraction (HR = 2.76; 1.48-5.14), and several dosimetric parameters including Dmean (HR = 1.05, 1.02-1.08) were all significantly associated with ORN. Dmean and surgery/tooth extraction remained significant predictors of ORN in multivariable analysis, HR = 1.04 (CI 1.01-1.07) and HR = 2.09 (CI 1.1-3.98), respectively, while smoking only retained its significance in an interaction analysis with pre-RT dental procedures. Conclusion: The onset of ORN of the mandible was early (median 10.8 months) and the incidence low (4.6%) after IMRT in HNC cancer patients. Surgery to the mandible and pre-RT tooth extraction, tobacco smoking, and treatment dose were associated with the development of ORN.