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.

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.

Relationship between patient and physician-rated xerostomia and dose distribution to the oral cavity and salivary glands for head and neck cancer patients after radiotherapy.

Introduction: Xerostomia is a frequent complication after curative intended radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Assessment of xerostomia is commonly done by the physician. The aim of this study is to investigate the relation between patient and physician-rated xerostomia and to predict the degree of xerostomia from patients with self-reported xerostomia based on delivered doses to the oral cavity, parotid, and submandibular glands. Material and methods: During a 2-year period, consecutive HNSCC patients attending the follow-up clinic were included. All included patients had self-reported xerostomia, and completed the disease-specific EORTC QLQ-H&N35 questionnaire. The physician assessed the degree of xerostomia with the DAHANCA toxicity scale and was blinded for the EORTC score. Oral cavity, parotid, and submandibular glands (OAR) were delineated on the planning CT according to international guidelines. DVH were extracted from treatment plans. Logistic regression tested the relation between mean doses, patient characteristics, and xerostomia scores. Differences between DVH values and scoring of xerostomia were analyzed with a Kruskal-Wallis test. The relation between xerostomia and dose distributions was further investigated using principal component analysis (PCA). Results: In total, 109 patients were included in the study. A weak correlation was seen between patient and physician-rated toxicity (p = .001), however, in general patients reported more toxicity than physicians. For EORTC score ≥2, the multi-variable analysis was significant for doses to the oral cavity, tobacco status and use of xerogenic medication. Neither the DVH analysis nor the PCA found any clear distinction between xerostomia scores for EORTC or DAHANCA and investigated OARs. Conclusion: Patients tended to report higher scores of xerostomia than the physician. PCA indicated a complex relation between doses to the OAR and xerostomia scores, showing e.g., that reducing doses in one organ was on the expense of increased dose to another organ.

Evaluation of tumor-infiltrating lymphocytes and association with prognosis in BRCA-mutated breast cancer.

BACKGROUND: Patients with a BRCA1 or BRCA2 mutation (BRCA-mutated breast cancer) are frequently diagnosed with low differentiated and highly proliferating breast cancer characterized by high amounts of tumor-infiltrating lymphocytes (Tils). Stromal Tils (sTils) are highly prognostic in sporadic triple-negative and HER2 positive breast cancer however, their prognostic importance in BRCA-mutated breast cancers is unknown. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded primary tumor tissue from 411 patients with a germline BRCA1 or BRCA2 mutation and diagnosed with early breast cancer was included. The percentage of sTils was quantified on full HE sections according to guidelines proposed by the Immuno-Oncology Biomarker in Breast Cancer Working Group. Distribution of sTils and associates with patient and tumor characteristics were assessed according to categorical sTils groups defined as low (<10%), intermediate (10-59%) and high (≥60%). Prognostic associations of sTils were evaluated as a continuous variable in univariate and multivariate models. Only follow-up time beyond date of BRCA mutation test was included. RESULTS: A large proportion had high sTils (27% in the full cohort, 36% in BRCA1-mutated, and 44% in ER negative breast cancers). Higher sTils were associated with BRCA1, ER negative breast cancer, high histological grade and medullary histology. In combined analysis for BRCA1 and BRCA2-mutated breast cancers, increasing sTils in 10% intervals were significantly associated with OS (HR 0.92, 95% CI 0.84-1.00, p = .05). For each 10% increment of sTils in BRCA1 breast cancers, a 10% reduction of mortality (adjusted HR 0.90 95% CI 0.81-0.99, p = .03) and a 13% reduction in risk of DFS-event (HR 0.87 95% CI 0.76-1.00, p = .05) was observed even after adjustment for ER status. No significant association with survival was of observed in the BRCA2 subgroup. Test for interaction of sTils and BRCA status was not statistically significant (p = .3). CONCLUSIONS: Breast cancer patients with a germline BRCA mutation had higher sTils than previously reported in sporadic breast cancers, and sTils were associated with favorable survival among BRCA carriers.

NTCP model validation method for DAHANCA patient selection of protons versus photons in head and neck cancer radiotherapy.

Introduction: Prediction models using logistic regression may perform poorly in external patient cohorts. However, there is a need to standardize and validate models for clinical use. The purpose of this project was to describe a method for validation of external NTCP models used for patient selection in the randomized trial of protons versus photons in head and neck cancer radiotherapy, DAHANCA 35. Material and methods: Organs at risk of 588 patients treated primarily with IMRT in the randomized controlled DAHANCA19 trial were retrospectively contoured according to recent international recommendations. Dose metrics were extracted using MatLab and all clinical parameters were retrieved from the DAHANCA database. The model proposed by Christianen et al. to predict physician-rated dysphagia was validated through the closed testing, where change of the model intercept, slope and individual beta's were tested for significant prediction improvements. Results: Six months prevalence of dysphagia in the validation cohort was 33%. The closed testing procedure for physician-rated dysphagia showed that the Christianen et al. model needed an intercept refitting for the best match for the Danish patients. The intercept update increased the risk of dysphagia for the validation cohort by 7.9 ± 2.5% point. For the raw model performance, the Brier score (mean squared residual) was 0.467, which improved significantly with a new intercept to 0.415. Conclusions: The previously published Dutch dysphagia model needed an intercept update to match the Danish patient cohort. The implementation of a closed testing procedure on the current validation cohort allows quick and efficient validation of external NTCP models for patient selection in the future.

Why still in hospital after laparoscopic colorectal surgery within an enhanced recovery programme?

AIM: Enhanced recovery after surgery programmes in elective colorectal surgery have been developed and implemented widely, but a subgroup of patients may still require longer hospital stays than expected. The aim of this study was to identify and describe factors compromising early postoperative recovery by asking 'why is the patient still in hospital today?' after laparoscopic colorectal cancer surgery within an enhanced recovery after surgery programme. METHOD: Patients undergoing elective laparoscopic colorectal cancer resection were evaluated postoperatively with predefined potential reasons for still being in hospital. The primary outcome was 'reason for still being in hospital' on postoperative day 0-4 and secondarily length of stay with a focus on differences between patients with and without a stoma. RESULTS: Ninety-six patients having colorectal cancer surgery were included. The median length of stay for the whole group was 3 days (range 1-14). The four dominant causes for patients without a stoma to be in hospital were lack of gastrointestinal function, lack of early mobilization, lack of normal micturition and nausea. Patients with a stoma stayed in hospital due to stoma training, lack of gastrointestinal function, lack of free micturition and a miscellaneous 'others' group. CONCLUSION: Delayed gastrointestinal function, insufficient mobilization, poor urinary function and stoma care training have been characterized as dominant compromising factors for postoperative recovery. Together with a focus on frailty, future studies should focus on improving early mobilization, prevention and treatment of postoperative urinary retention and improved stoma care training, in order to minimize delay in postoperative recovery and discharge.

Hypoxaemia during recovery after surgery for colorectal cancer: a prospective observational study.

Episodic and ongoing hypoxaemia are well-described after surgery, but, to date, no studies have investigated the occurrence of episodic hypoxaemia following minimally-invasive colorectal surgery performed in an enhanced recovery setting. We aimed to describe the occurrence of postoperative hypoxaemia after minimally-invasive surgery in an enhanced recovery setting, and the association with morphine use, incision site, fluid intake and troponin increase. We performed a prospective observational study of 85 patients undergoing minimally-invasive surgery for colorectal cancer between 25 August 2016 and 17 August 2017. We applied a pulse oximeter with a measurement rate of 1 Hz immediately after surgery either until discharge or until two days after surgery, and recorded the oxygen saturation. We measured troponin I during the first four days after surgery, or until discharge. The median (IQR [range]) length of stay was 3 (2-4 [1-38]) days. Thirty-six percent of patients spent more than 1 h below an oxygen saturation of 90% (4.2% of the day), and with a median (IQR [range]) proportion of 1.3 (0.2-11.1 [0.0-21.4])% of the day spent with an oxygen saturation below 88%. We found no associations between time spent below an oxygen saturation of 88% and morphine use (p = 0.215), fluid intake (p = 0.446), complications (p = 0.808) or extraction site (p = 0.623). Postoperative increases in troponin I were associated both with time spent below an oxygen saturation of 88% (p = 0.026) and hypopnoea episodes (p = 0.003). Even with minimally-invasive surgery and enhanced recovery after surgery, episodic hypoxaemia and hypopnoea episodes are common, but are not associated with morphine use, fluid intake or incision site. Further studies should investigate the relationship between hypoxaemia and troponin increase.

Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing.

BACKGROUND: Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified. METHODS: Fresh-frozen tissue from primary tumours, synchronous liver metastases and adjacent normal liver was collected from 21 patients and analysed by whole-exome sequencing on the Illumina HiSeq 2500 platform. Gene variants designated as 'damaging' or 'potentially damaging' by Ingenuity software were used for the subsequent comparative analysis. BAM files were used as the input for the analysis of CNAs using NEXUS software. RESULTS: Shared mutations between the primary tumours and the synchronous liver metastases varied from 50 to 96%. Mutations in APC, KRAS, NRAS, TP53 or BRAF were concordant between the primary tumours and the metastases. Among the private mutations were well-known driver genes such as PIK3CA and SMAD4. The number of mutations was significantly higher in patients with right- compared to left-sided tumours (102 vs. 66, p = 0.004). Furthermore, right- compared to left-sided tumours had a significantly higher frequency of private mutations (p = 0.023). Similarly, CNAs differed between the primary tumours and the metastases. The difference was mostly comprised of numerical and segmental aberrations. However, novel CNAs were rarely observed in specific CRC-relevant genes. CONCLUSION: The examined primary colorectal tumours and synchronous liver metastases had multiple private mutations, indicating a high degree of inter-tumour heterogeneity in the individual patient. Moreover, the acquirement of novel CNAs from primary tumours to metastases substantiates the need for genomic profiling of metastases in order to tailor metastatic CRC therapies. As for the mutational status of the KRAS, NRAS and BRAF genes, no discordance was observed between the primary tumours and the metastases.

Clinical and molecular characterization of BRCA-associated breast cancer: results from the DBCG.

BACKGROUND: In breast cancer (BC) patients a cancer predisposing BRCA1/2 mutation is associated with adverse tumor characteristics, risk assessment and treatment allocation. We aimed to estimate overall- (OS) and disease-free survival (DFS) according to tumor characteristics and treatment among women who within two years of definitive surgery for primary BC were shown to carry a mutation in BRCA1/2 . MATERIAL AND METHODS: From the clinical database of the Danish Breast Cancer Group we included 141 BRCA1 and 96 BRCA2 BC patients. Estrogen receptor and HER2 status were centrally reviewed on paraffin-embedded tumor tissue. Information on risk reducing surgery was obtained from the Danish Pathology and Patient Registries and included as time-dependent variables in Cox proportional hazard models. RESULTS: Ten-year OS and DFS for BRCA1 BC patients were 78% (95% CI 69-85) and 74% (95% CI 64-81). Ten-year OS and DFS for BRCA2 BC were 88% (95% CI 78-94) and 84% (95% CI 74-91). BRCA1 BC patients as compared to BRCA2 BC patients had a higher risk of BC relapse or non-breast cancer within ten years of follow-up, independent of ER status (adjusted HR 2.78 95% CI 1.28-6.05, p = .01), but BRCA mutation was not associated with OS (adjusted HR 1.98, 95% CI 0.87-4.52, p = .10). In multivariate analysis, including both BRCA1 and BRCA2 carriers, no chemotherapy was associated with a higher risk of death (adjusted OS HR 3.58, 95% CI 1.29-9.97, p = .01) and risk reducing contralateral mastectomy (RRCM) was associated with a significantly reduced risk of death (adjusted OS HR 0.42, 95% CI =0.21-0.84, p = .01). CONCLUSION: Difference in OS between BRCA1 and BRCA2 BC patients could be ascribed to tumor-biology. BRCA1 BC patients may have a shorter ten-year DFS than BRCA2 BC patients. Chemotherapy and risk reducing contralateral mastectomy reduce mortality for both BRCA1 and BRCA2 BC patients.

Prolonged hospital stay and readmission rate in an enhanced recovery after surgery cohort undergoing colorectal cancer surgery.

AIM: The present database study aimed to identify patients with a longer postoperative length of stay (LOS) or patients readmitted and to characterize both groups based on perioperative factors. METHOD: A retrospective review of the Danish Colorectal Cancer Group database and a local database was performed of all patients undergoing elective resection for colorectal cancer in a 25-month period. The primary outcome was the number of patients with a prolonged hospital stay (LOS ≥ 10 days after the primary operation) and readmissions within 30 days after discharge. RESULTS: A total of 372 patients with colon resection and 215 patients with rectal resection were included. Patients undergoing colonic resection had a rate of prolonged hospital stay of 10.6% and a readmission rate of 13.7%; prolonged hospital stay was significantly associated with age ≥ 76 years and those who underwent a conversion from a laparoscopic procedure. Patients undergoing rectal cancer resection had a rate of prolonged hospital stay of 17.7% and a readmission rate of 14.0%; Charlson comorbidity score (CCS) ≥ 2, total mesorectal excision (TME) and laparoscopic conversion were significantly associated with prolonged hospital stay, and American Society of Anesthesiologists (ASA) score ≥ 3, TME and a duration of surgery ≥ 300 min were significantly associated with readmission. CONCLUSION: In patients with colon cancer, older age and conversion to open surgery were associated with prolonged hospital stay. In patients with rectal cancer, CCS ≥ 2, TME and conversion were associated with prolonged hospital stay, and a preoperative ASA score ≥ 3, TME and a duration of surgery ≥ 300 min were associated with readmission.

Influence of experience and qualification on PET-based target volume delineation. When there is no expert--ask your colleague.

BACKGROUND AND PURPOSE: The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. In contrast to automatic contouring, research on visual-manual delineation is scarce. The present study investigates the dependency of manual delineation on experience and qualification. PATIENTS AND METHODS: A total of 44 international interdisciplinary observers each defined a [(18)F]fluorodeoxyglucose (FDG)-PET based gross tumor volume (GTV) using the same PET/CT scan from a patient with lung cancer. The observers were "experts" (E; n = 3), "experienced interdisciplinary pairs" (EP; 9 teams of radiation oncologist (RO) + nuclear medicine physician (NP)), "single field specialists" (SFS; n = 13), and "students" (S; n = 10). Five automatic delineation methods (AM) were also included. Volume sizes and concordance indices within the groups (pCI) and relative to the experts (eCI) were calculated. RESULTS: E (pCI = 0.67) and EP (pCI = 0.53) showed a significantly higher agreement within the groups as compared to SFS (pCI = 0.43, p = 0.03, and p = 0.006). In relation to the experts, EP (eCI = 0.55) showed better concordance compared to SFS (eCI = 0.49) or S (eCI = 0.47). The intermethod variability of the AM (pCI = 0.44) was similar to that of SFS and S, showing poorer agreement with the experts (eCI = 0.35). CONCLUSION: The results suggest that interdisciplinary cooperation could be beneficial for consistent contouring. Joint delineation by a radiation oncologist and a nuclear medicine physician showed remarkable agreement and better concordance with the experts compared to other specialists. The relevant intermethod variability of the automatic algorithms underlines the need for further standardization and optimization in this field.

Methanogenic community changes, and emissions of methane and other gases, during storage of acidified and untreated pig slurry.

AIMS: Acidification with concentrated H(2)SO(4) is a novel strategy to reduce NH(3) emissions from livestock slurry. It was recently found that also CH(4) emissions from acidified slurry are reduced. This study investigated the microbiological basis and temporal stability of these effects. METHODS AND RESULTS: Pig slurry from two farms, acidified by different techniques or untreated, was stored for 83 days in a pilot-scale facility. Methanogens were characterized before and after storage by T-RFLP and qPCR targeting mcrA. Emissions of NH(3) and CH(4) during storage were quantified. Acidified slurry pH was nearly constant at values of 5·5 and 6·5. Ammonia losses were reduced by 84 and 49%, respectively, while CH(4) emission with both acidification techniques was reduced by >90%. T-RFLP fingerprints showed little effect of acidification or storage time. A major T-RF of 105 bp could represent methanogens related to Thermoplasmata (Tp). No treatment effects on gene copy numbers were seen with universal methanogen primers, whereas effects were found with Tp-specific primers. CONCLUSION: Methane emissions were reduced >90% during storage. Thermoplasmata-related methanogens could be involved in CH(4) emissions from pig slurry. SIGNIFICANCE AND IMPACT OF THE STUDY: The effect of acidification on CH(4) emissions during storage of pig slurry was quantified for the first time. Acidification with sulphuric acid holds promise as a novel greenhouse gas mitigation strategy for confined livestock production.

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.

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.

Seroepidemiology of mumps in Europe (1996-2008): why do outbreaks occur in highly vaccinated populations?

Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5-12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01-0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4-8 years between doses (OR 0·08, 95% CI 0·01-0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4-8 years between doses.

Pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor efavirenz among HIV-infected Ugandans.

BACKGROUND: Pharmacokinetic variability of the nonnucleoside reverse transcriptase inhibitor efavirenz has been documented, and high variation in trough concentrations or clearance has been found to be a risk for virological failure. Africans population exhibits greater variability in efavirenz concentrations than other ethnic groups, and so a better understanding of the pharmacokinetics of the drug is needed in this population. This study characterized efavirenz pharmacokinetics in HIV-infected Ugandans. METHODS: Efavirenz plasma concentrations were obtained for 66 HIV-infected Ugandans initiating efavirenz- based regimens, with blood samples collected at eight time-points over 24 h on day 1 of treatment, and at a further eight time-points on day 14. Noncompartmental analysis was used to describe the pharmacokinetics of efavirenz. RESULTS: The mean steady-state minimum plasma concentration (C(min) ) of efavirenz was 2.9 µg/mL, the mean area under the curve (AUC) was 278.5 h µg/mL, and mean efavirenz clearance was 7.4 L/h. Although overall mean clearance did not change over the 2 weeks, 41.9% of participants showed an average 95.8% increase in clearance. On day 14, the maximum concentration (C(max) ) of efavirenz was >4 µg/mL in 96.6% of participants, while C(min) was <1 µg/mL in only 4.5%. Overall, 69% of participants experienced adverse central nervous system (CNS) symptoms attributable to efavirenz during the 2-week period, and 95% of these participants were found to have efavirenz plasma concentrations >4 µg/mL, although only half maintained a high concentration until at least 8 h after dosing. CONCLUSION: The findings of this study show that HIV-infected patients on efavirenz may exhibit autoinduction to various extents, and this needs to be taken into consideration in the clinical management of individual patients. Efavirenz CNS toxicity during the initial phase of treatment may be related to C(max) , regardless of the sampling time.