Season of radiotherapy and outcomes of head & neck cancer patients in the MACH-NC & MARCH meta-analyses.

BACKGROUND: A single institution retrospective study suggested that head and neck squamous cell cancer (HNSCC) patients receiving radiotherapy (RT) during "dark" season (fall/winter) may have better outcomes than those treated during "light" season (spring/summer), possibly secondary to seasonal variations in cell cycle progression. We investigated the impact of season of RT in two large, multi-institutional, prospective datasets of randomized trials. METHODS: Individual patient data from the MACH-NC and MARCH meta-analyses were analyzed. Dark season was defined as mid-radiotherapy date during fall or winter and light the reverse, using equinoxes to separate the two periods. Primary endpoint was progression-free survival (PFS) and secondary endpoint was locoregional failure (LRF). The effect of season was estimated with a Cox model stratified by trial and adjusted on sex, tumor site, stage, and treatment. Planned sensitivity analyses were performed on patients treated around solstices, who received "complete radiotherapy", patients treated with concomitant radio-chemotherapy and on trials performed in Northern countries. RESULTS: 11320 patients from 33 trials of MARCH and 6276 patients from 29 trials of MACH-NC were included. RT during dark season had no benefit on PFS in the MARCH (hazard ratio[HR]: 1.01 [95%CI 0.97;1.05],p=0.72) or MACH-NC dataset (HR:1.00 [95%CI 0.94;1.06],p=1.0. No difference in LRF was observed in the MARCH (HR:1.00 [95%CI 0.94;1.06,p=0.95) or MACH-NC dataset (HR:0.99 [95%CI 0.91; 1.07],p=0.77). Sensitivity analyses showed similar results. CONCLUSION: Season of RT had no impact on PFS or LRF in two large databases of HNSCC.

Fluid Intake in Critically Ill Patients: The "Save Useless Fluids For Intensive Resuscitation" Multicenter Prospective Cohort Study.

OBJECTIVES: Patients at risk of adverse effects related to positive fluid balance could benefit from fluid intake optimization. Less attention is paid to nonresuscitation fluids. We aim to evaluate the heterogeneity of fluid intake at the initial phase of resuscitation. DESIGN: Prospective multicenter cohort study. SETTING: Thirty ICUs across France and one in Spain. PATIENTS: Patients requiring vasopressors and/or invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All fluids administered by vascular or enteral lines were recorded over 24 hours following admission and were classified in four main groups according to their predefined indication: fluids having a well-documented homeostasis goal (resuscitation fluids, rehydration, blood products, and nutrition), drug carriers, maintenance fluids, and fluids for technical needs. Models of regression were constructed to determine fluid intake predicted by patient characteristics. Centers were classified according to tertiles of fluid intake. The cohort included 296 patients. The median total volume of fluids was 3546 mL (interquartile range, 2441-4955 mL), with fluids indisputably required for body fluid homeostasis representing 36% of this total. Saline, glucose-containing high chloride crystalloids, and balanced crystalloids represented 43%, 27%, and 16% of total volume, respectively. Whatever the class of fluids, center of inclusion was the strongest factor associated with volumes. Compared with the first tertile, the difference between the volume predicted by patient characteristics and the volume given was +1.2 ± 2.0 L in tertile 2 and +3.0 ± 2.8 L in tertile 3. CONCLUSIONS: Fluids indisputably required for body fluid homeostasis represent the minority of fluid intake during the 24 hours after ICU admission. Center effect is the strongest factor associated with the volume of fluids. Heterogeneity in practices suggests that optimal strategies for volume and goals of common fluids administration need to be developed.

Prevalence and predictors of elder abuse among older adults attending emergency departments: a prospective cohort study.

INTRODUCTION: Elder abuse is associated with impaired physical and psychological health. It is, however, rarely identified in emergency departments (EDs). The objective was to determine the prevalence and the predictors of elder abuse among older adults visiting EDs. METHODS: This prospective cohort study was conducted in eight Canadian EDs between May and August 2021. Patients were eligible if they were ≥ 65 years old, oriented to time, and with a Canadian Triage and Acuity Scale score 3, 4 or 5. In a private setting, participants were questioned directly about abuse as part of a larger questionnaire exploring ten non-medical problems. We used multivariable logistic regression to identify predictors of elder abuse. RESULTS: A total of 1061 participants were recruited (mean age: 77.1 (SD 7.6) years, female sex: 55.7%, lived alone: 42.5%). Patients mostly attended EDs for pain (19.6%), neurologic (11.3%) or cardiovascular (8.4%) symptoms. The most frequent pre-existing comorbidities were hypertension (67.2%), mental health conditions (33.3%) and cardiac insufficiency (29.6%). Mobility issues outside (41.0%) or inside their home (30.7%) and loneliness (29.4%) were also frequent. Fifty-four (5.1%) participants reported elder abuse, of which 34.3% were aware of available community-based resources. Identified predictors of elder abuse were female sex (OR 2.8 [95%CI 1.4; 5.6]), financial difficulties (OR 3.6 [95%CI 1.8; 7.3]), food insecurity (OR 2.7 [95%CI 1.2; 5.6]), need for a caregiver (OR 2.7 [95%CI 1.5; 5.0]) and at least one pre-existing mental health condition (OR 2.6 [95%CI 1.4; 4.9]). CONCLUSION: When questioned directly, 5.1% of older adults attending EDs reported experiencing abuse. Female sex, functional impairment, social vulnerability, and mental health comorbidities are associated with elder abuse. Given its importance and relatively high prevalence, ED professionals should have a low threshold to ask directly about elder abuse.

RéSUMé: INTRODUCTION: La maltraitance des personnes âgées est associée à une détérioration de la santé physique et psychologique. Elle est cependant rarement identifiée dans les services d'urgence. L'objectif était de déterminer la prévalence et les prédicteurs de l'abus envers les aînés chez les personnes âgées qui consultent dans un service d'urgence. MéTHODES: Cette étude de cohorte prospective a été menée dans huit services d'urgence canadiens entre mai et août 2021. Les patients étaient éligibles s'ils étaient âgés de ≥ 65 ans, s'ils étaient orientés vers le temps et s'ils avaient un score de 3, 4 ou 5 sur l'échelle canadienne de triage et d'acuité. Dans un cadre privé, les participants ont été interrogés directement sur la maltraitance dans le cadre d'un questionnaire plus large explorant 10 problèmes non médicaux. Nous avons utilisé une régression logistique multivariable pour identifier les facteurs prédictifs de la maltraitance envers les personnes âgées. RéSULTATS: Au total, 1 061 participants ont été recrutés (âge moyen : 77,1 (SD 7,6) ans, sexe féminin : 55,7 %, vivant seul : 42,5 %). Les patients se sont surtout rendus aux urgences pour des douleurs (19,6 %), des symptômes neurologiques (11,3 %) ou cardiovasculaires (8,4 %). Les comorbidités préexistantes les plus fréquentes étaient l'hypertension (67,2 %), les problèmes de santé mentale (33,3 %) et l'insuffisance cardiaque (29,6 %). Les problèmes de mobilité à l'extérieur (41,0 %) ou à l'intérieur du domicile (30,7 %) et la solitude (29,4 %) sont également fréquents. Cinquante-quatre (5,1 %) participants ont signalé des cas de maltraitance des personnes âgées, dont 34,3 % connaissaient les ressources communautaires disponibles. Les facteurs prédictifs identifiés de maltraitance envers les personnes âgées étaient le sexe féminin (RC 2,8 [IC 95 % 1,4 ; 5,6]), les difficultés financières (RC 3,6 [IC 95 % 1,8 ; 7,3]), l'insécurité alimentaire (RC 2,7 [IC 95 % 1,2 ; 5,6]), besoin d'un aidant (RC 2,7 [IC 95 % 1,5 ; 5,0]) et au moins un problème de santé mentale préexistant (RC 2,6 [IC 95 % 1,4 ; 4,9]). CONCLUSION: Interrogées directement, 5,1 % des personnes âgées fréquentant les urgences ont déclaré avoir été victimes de maltraitance. Le sexe féminin, les déficits fonctionnels, la vulnérabilité sociale et les problématiques de santé mentale sont associés à la maltraitance des personnes âgées. Compte tenu de son importance et de sa prévalence relativement élevée, les professionnels des urgences ne devraient pas hésiter à poser directement des questions sur la maltraitance aux personnes âgées.

Evaluation of physicians' current practices and awareness regarding the treatment of acute uncomplicated diverticulitis: results of a provincial survey.

OBJECTIVE: International guidelines now recommend nonantibiotic treatment of uncomplicated diverticulitis. We assessed physicians' current management strategies for uncomplicated diverticulitis, their awareness of the updated recommendations, and barriers to practice change. METHODS: A 21-question web-based survey conducted between 09/2022 and 11/2022 was sent to participants through their respective Quebec provincial associations or working groups. Participants included general surgeons, emergency physicians, gastroenterologists and general practitioners. Physicians who did not treat diverticulitis were excluded. The main outcomes were awareness of guideline recommendations on uncomplicated diverticulitis treatment, the use of nonantibiotic management for uncomplicated diverticulitis and identification of perceived barriers to practice change. RESULTS: The participation rate was 15.9%. The 465 participants consisted primarily of general practitioners (41.7%), general surgeons (29.2%) and emergency physicians (17.8%). Eighty-two percent had heard of the nonantibiotic treatment strategy for uncomplicated diverticulitis; 7.5% were "uncomfortable" and 44.6% "somewhat uncomfortable" with this practice. A third (31.8%) of all physicians had no knowledge of the updated guidelines on uncomplicated diverticulitis treatment. Most reported "never" (41.6%) or "rarely" (25.1%) omitting antibiotics for uncomplicated diverticulitis. When informed about nonantibiotic treatment, 28.7% and 51.4% of all physicians, respectively, indicated that this "will" change or "may" change their practice. Common perceived barriers to nonantibiotic treatment were concerns about treatment failure (69.6%), unawareness of updated recommendations (67.0%), difficulty in ensuring proper follow-up (59.0%) and workplace culture (54.9%). CONCLUSION: Physicians' awareness of practice guidelines recommending nonantibiotic treatment for uncomplicated diverticulitis and their application are suboptimal. Knowledge transfer activities, educational interventions and optimization of local protocols are needed to ensure the rational use of antibiotics.

RéSUMé: OBJECTIF: Les lignes directrices internationales recommandent désormais un traitement non antibiotique de la diverticulite non compliquée. Nous avons évalué les stratégies de traitement actuelles des médecins pour la diverticulite non compliquée, leur connaissance des recommandations mises à jour et les obstacles au changement de pratique. MéTHODES: Un sondage en ligne de 21 questions mené entre le 09/2022 et le 11/2022 a été envoyé aux participants par l'intermédiaire de leurs associations ou groupes de travail provinciaux respectifs au Québec. Les participants comprenaient des chirurgiens généraux, des urgentologues, des gastroentérologues et des médecins de famille. Les médecins qui ne traitaient pas de diverticulite ont été exclus. Les principales issues étaient la connaissance des recommandations des lignes directrices sur le traitement de la diverticulite non compliquée, l'utilisation du traitement non antibiotique pour la diverticulite non compliquée et l'identification des obstacles perçus au changement de pratique. RéSULTATS: Le taux de participation était de 15,9 %. Les 465 participants étaient principalement des médecins de famille (41,7 %), des chirurgiens généraux (29,2 %) et des urgentologues (17,8 %). Quatre-vingt-deux pour cent avaient entendu parler de la stratégie de traitement non antibiotique pour la diverticulite non compliquée; 7,5% étaient "inconfortables" et 44,6% "quelque peu inconfortables" avec cette pratique. Un tiers (31,8 %) des médecins ne connaissaient pas les lignes directrices mises à jour sur le traitement de la diverticulite non compliquée. La plupart ont rapporté "jamais" (41,6%) ou "rarement" (25,1%) omettre les antibiotiques pour la diverticulite non compliquée. Lorsqu'ils ont été informés du traitement non antibiotique, 28,7 % et 51,4 % de tous les médecins ont indiqué que cela «changera¼ ou «pourrait changer¼ leur pratique. Les fréquents obstacles au traitement non antibiotique étaient les préoccupations concernant l'échec du traitement (69,6 %), l'ignorance des recommandations mises à jour (67,0 %), la difficulté d'assurer un suivi approprié (59,0 %) et la culture en milieu de travail (54,9 %). CONCLUSIONS: La connaissance des lignes directrices recommandant un traitement non antibiotique pour la diverticulite non compliquée et leur application sont sous-optimales. Des activités de transfert de connaissances, des interventions éducatives et des protocoles locaux sont nécessaires pour assurer l'utilisation rationnelle des antibiotiques.

Sexual Structure Sparing for Prostate Cancer Radiotherapy: A Systematic Review.

CONTEXT: Erectile dysfunction represents a major side effect of prostate cancer (PCa) treatment, negatively impacting men's quality of life. While radiation therapy (RT) advances have enabled the mitigation of both genitourinary and gastrointestinal toxicities, no significant improvement has been showed in sexual quality of life over time. OBJECTIVE: The primary aim of this review was to assess sexual structures' dose-volume parameters associated with the onset of erectile dysfunction. EVIDENCE ACQUISITION: We searched the PubMed database and ClinicalTrials.gov until January 4, 2023. Studies reporting the impact of the dose delivered to sexual structures on sexual function or the feasibility of innovative sexual structure-sparing approaches were deemed eligible. EVIDENCE SYNTHESIS: Sexual-sparing strategies have involved four sexual organs. The mean penile bulb doses exceeding 20 Gy are predictive of erectile dysfunction in modern PCa RT trial. Maintaining a D100% of ≤36 Gy on the internal pudendal arteries showed preservation of erectile function in 88% of patients at 5 yr. Neurovascular bundle sparing appears feasible with magnetic resonance-guided radiation therapy, yet its clinical impact remains unanswered. Doses delivered to the testicles during PCa RT usually remain <2 Gy and generate a decrease in testosterone levels ranging from -4.6% to -17%, unlikely to have any clinical impact. CONCLUSIONS: Current data highlight the technical feasibility of sexual sparing for PCa RT. The proportion of erectile dysfunction attributable to the dose delivered to sexual structures is still largely unknown. While the ability to maintain sexual function over time is impacted by factors such as age or comorbidities, only selected patients are likely to benefit from sexual-sparing RT. PATIENT SUMMARY: Technical advances in radiation therapy (RT) made it possible to significantly lower the dose delivered to sexual structures. While sexual function is known to decline with age, the preservation of sexual structures for prostate cancer RT is likely to be beneficial only in selected patients.

Role of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy (MAC-NPC): an updated individual patient data network meta-analysis.

BACKGROUND: The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis. METHODS: For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained. Both general databases (eg, PubMed and Web of Science) and Chinese medical literature databases were searched. Overall survival was the primary endpoint. A frequentist network meta-analysis approach with a two-step random effect stratified by trial based on hazard ratio Peto estimator was used. Global Cochran Q statistic was used to assess homogeneity and consistency, and p score to rank treatments, with higher scores indicating higher benefit therapies. Treatments were grouped into the following categories: radiotherapy alone, induction chemotherapy followed by radiotherapy, induction chemotherapy without taxanes followed by chemoradiotherapy, induction chemotherapy with taxanes followed by chemoradiotherapy, chemoradiotherapy, chemoradiotherapy followed by adjuvant chemotherapy, and radiotherapy followed by adjuvant chemotherapy. This study is registered with PROSPERO, CRD42016042524. FINDINGS: The network comprised 28 trials and included 8214 patients (6133 [74·7%] were men, 2073 [25·2%] were women, and eight [0·1%] had missing data) enrolled between Jan 1, 1988, and Dec 31, 2016. Median follow-up was 7·6 years (IQR 6·2-13·3). There was no evidence of heterogeneity (p=0·18), and inconsistency was borderline (p=0·10). The three treatments with the highest benefit for overall survival were induction chemotherapy with taxanes followed by chemoradiotherapy (hazard ratio 0·75; 95% CI 0·59-0·96; p score 92%), induction chemotherapy without taxanes followed by chemoradiotherapy (0·81; 0·69-0·95; p score 87%), and chemoradiotherapy followed by adjuvant chemotherapy (0·88; 0·75-1·04; p score 72%), compared with concomitant chemoradiotherapy (p score 46%). INTERPRETATION: The inclusion of new trials modified the conclusion of the previous network meta-analysis. In this updated network meta-analysis, the addition of either induction chemotherapy or adjuvant chemotherapy to chemoradiotherapy improved overall survival over chemoradiotherapy alone in nasopharyngeal carcinoma. FUNDING: Institut National du Cancer and Ligue Nationale Contre le Cancer.

Locoregional treatment of primary tumor in synchronous metastatic head and neck squamous cell carcinomas.

PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas (mHNSCC) are at risk of locoregional progression associated with significant morbidity and mortality. The aim of this study is to assess whether the addition of aggressive locoregional treatment to systemic therapy could be associated with an improved overall survival (OS) compared to systemic therapy alone in upfront mHNSCC patients. MATERIAL AND METHODS: This retrospective study included patients presenting with previously untreated mHNSCC who underwent first-line systemic therapy at a single institution between 1998 and 2018. Locoregional treatment was defined as either exclusive locoregional radiotherapy (RT) or surgery with or without adjuvant RT. RESULTS: One hundred forty-eight patients were included. Eighty patients were treated with systemic therapy alone and 68 patients were treated with a combination of locoregional treatment and systemic therapy. Median overall survival (OS) was 13 months [10.7-15] and median progression free survival (PFS) was 7.7 month [6.5-8.9]. The addition of a locoregional treatment to systemic therapy compared to systemic therapy alone was associated with improved survival (1-year OS, 65.8% vs. 41.1%, p < .001, and 1-year PFS, 42.5% vs. 18.5%, p < .001). Moreover, RT dose equal to 70 Gy was associated with even longer OS compared to a RT dose below 70 Gy and to no locoregional treatment (23.4 vs. 12.7 vs 7.5 months respectively). In a subgroup analysis on 75 patients presenting with a responding or stable metastatic disease after first-line systemic therapy, oropharyngeal primary tumor site and the addition of a locoregional treatment, especially a high radiation dose of 70 Gy, were evidenced as independent prognostic factors for improved OS. CONCLUSION: The addition of a high-dose RT locoregional treatment to systemic therapy is associated with prolonged OS in patients with synchronous mHNSCC and should be discussed for patients who respond to or have a stable disease after first-line systemic therapy.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

BACKGROUND: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. OBJECTIVE: To present the voting results of the APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. RESULTS AND LIMITATIONS: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. TWITTER SUMMARY: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. TAKE-HOME MESSAGE: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.

Post-therapeutic surveillance of HPV-driven oropharyngeal cancers: are we ready to change our practices?

PURPOSE: Although HPV-positive and negative oropharyngeal cancers are two distinct diseases, Post-Therapeutic Surveillance (PTS) modalities are similar. Adjusting PTS strategies to HPV status will represent a massive practice change that raises the issue of its acceptability, by both physicians and patients. METHODS: Two distinct surveys were designed and submitted, respectively, to HPV-positive patients and physicians (surgeons, radiation and medical oncologists) involved in head and neck cancer treatment. RESULTS: 133 patients and 90 physicians have participated to the study. Most patients were reluctant to embrace new PTS options (remote consultations, nurse consultations and smart phone applications). However, 84% of patients would be favorable to use HPV Circulating DNA (HPV Ct DNA) measurement to guide surveillance modalities. 57% of physicians acknowledged that our current PTS strategy is improvable and most of them would accept the use of new monitoring options from the third year of follow-up. 87% of physicians would be interested to participate to a trial comparing the current PTS strategy to a new approach, where monitoring modalities (number of visits, imaging prescription) would depend on HPV Ct DNA level. CONCLUSIONS: Patients and physicians are aware that PTS modalities should depend on HPV status. Their adhesion is a prerequisite to any potential changes. Strategies based on HPV Ct DNA measurement should be assessed within a randomized clinical trial.

A systematic literature review of definitions and classification systems for radiotherapy innovation: A first step towards building a value-based assessment tool for radiation oncology.

INTRODUCTION: Timely access to radiotherapy innovations remains suboptimal, partly because there is no commonly agreed appraisal system suitable for the broad range of radiotherapy interventions. The Health Economics in Radiation Oncology (HERO) programme of ESTRO therefore engaged in building a radiotherapy-specific value-based framework. We report on a first step towards that aim, documenting the available definitions and classification systems for radiotherapy interventions. METHODS: A systematic literature search was carried out in Pubmed and Embase, following PRISMA methodology and using search terms on 'innovation', 'radiotherapy', 'definition' and 'classification'. Data were extracted from articles that met prespecified inclusion criteria. RESULTS: Out of 13,353 articles, 25 met the inclusion criteria, resulting in the identification of 7 definitions of innovation and 15 classification systems applicable to radiation oncology. Iterative appraisal divided the classification systems into two groups. A first group of 11 systems categorized innovations according to the perceived magnitude of innovation, typically 'minor' versus 'major'. The remaining 4 systems categorised innovations according to radiotherapy-specific characteristics, such as the type of radiation equipment or radiobiological properties. Here, commonly used terms as 'technique' or 'treatment' were found to be used in different meanings. DISCUSSION: There is no widely accepted definition or classification system for radiotherapy innovations. The data however suggest that unique properties of radiotherapy interventions can be used to categorise innovations in radiation oncology. Still, there remains a need for clear terminology denoting radiotherapy-specific characteristics. CONCLUSION: Building on this review, the ESTRO-HERO project will define what is required for a radiotherapy-specific value-based assessment tool.

Outcomes after PD-103 versus I-125 for low dose rate prostate brachytherapy monotherapy: An international, multi-institutional study.

BACKGROUND AND PURPOSE: Pd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression. RESULTS: Compared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971). CONCLUSIONS: Pd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125.

A Canadian consensus-based list of urgent and specialized in-hospital trauma care interventions to assess the accuracy of prehospital trauma triage protocols: a modified Delphi study.

BACKGROUND: Injury severity scales have traditionally been used to assess the performance of prehospital trauma triage protocols, but they correlate weakly with the urgent needs of specialized trauma care interventions. This study aimed to develop a list of in-hospital urgent and specialized trauma care interventions that require direct transport to the highest-level trauma centre within the catchment area. METHODS: Based on a list of potential participants we obtained using data on training, experience, geographic location, affiliations and role within key trauma organizations, we recruited multidisciplinary trauma experts (including prehospital, emergency, surgery and intensive care clinicians, epidemiologists and clinician/decision-makers) from across Canada to complete a 3-round modified Delphi survey. We conducted a literature review of the criteria used to define urgent and specialized trauma care, and included all diagnostic and therapeutic interventions presented in previously published studies in the list of interventions to present to the panellists. The final list was determined by our advisory committee, 5 clinicians with experience in trauma care. Participants were asked to rate their level of agreement for potentially including the 38 items as urgent and specialized trauma care interventions on a 9-point Likert scale. Interventions were retained if more than 67% of participants moderately or strongly agreed (7-9 on the Likert scale). Interventions that did not reach consensus were presented again in the subsequent round. RESULTS: Twenty-three panellists were recruited. The response rate was 91%, 96% and 83% for the 3 rounds. After the Delphi process, 30 of the 38 interventions, including endotracheal intubation, blood product administration and angioembolization, and abdominal, thoracic, neurosurgical, spinal and/or orthopedic operations (excluding hip or limb surgery, and toe or finger amputation), were selected. Hospital admission to the intensive care unit and/or for observation of brain, spinal, thoracic or abdominal injuries were also retained. CONCLUSION: We developed a Canadian consensus-based list of urgent and specialized in-hospital trauma care interventions requiring direct transportation to a major trauma centre. This list should help standardize assessments of current protocols and derive new triage tools.

Outcomes following brachytherapy boost for intermediate- and high-risk prostate cancer: A retrospective bicenter study by the SFRO brachytherapy group.

INTRODUCTION: Radiotherapy dose escalation improves biochemical control in intermediate- or high-risk prostate cancer. Brachytherapy boost was shown to further improve biochemical control compared to radiotherapy alone in three randomized trials. The SFRO brachytherapy group sought to evaluate the efficacy and toxicity of BT-boost for intermediate and high-risk prostate cancer in real life, and to determine prognostic factors for efficacy and toxicity. MATERIAL AND METHOD: A retrospective study was conducted, including all patients with intermediate- or high-risk prostate cancer treated with a combination of external beam radiotherapy (EBRT) and high dose-rate brachytherapy boost (HDR-BB), from 2006 until December 2019 at two centers. Patient characteristics, initial disease, treatment and follow-up were collected. RESULTS: 709 patients from two centers were analyzed given a short follow-up in the other centers. Out of those, 277 were intermediate risk (170 favorable and 107 unfavorable) and 432 were high risk. The median EBRT and HDR-BB doses were 46 Gy (35-50) and 14 Gy (10-20). After a median follow-up of 62 months, biochemical control at 5 years was 87.5 % for the overall population, 91 % and 85 % for intermediate- and high-risk cancers, respectively. At 5 years, biochemical and clinical relapse-free survival, metastasis-free survival and local control rates were 83 %, 90 % and 97 % respectively. 5-years overall survival was 94 %. Late grade 2 or higher GU or GI toxicity was found in 36 patients (5 %) and 9 patients (1.3 %). CONCLUSION: This bicenter analysis shows the efficacy and tolerability of HDR-BB as a complement to external radiotherapy. Further improvements such as combination with new hormonal agents or new brachytherapy-radiotherapy fractionation regimens are warranted to improve further the outcomes and therapeutic ratio.

Genomic Classifiers in Personalized Prostate Cancer Radiation Therapy Approaches: A Systematic Review and Future Perspectives Based on International Consensus.

Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research. We performed a systematic review and screened ongoing clinical trials on ClinicalTrials.gov. Based on these results, a multidisciplinary international team of experts received an adapted Delphi method survey. Thirty-one and 30 experts answered round 1 and round 2, respectively. Questions with ≥75% agreement were considered relevant and included in the qualitative synthesis. Evidence for GCs as predictive biomarkers is mainly available to the postoperative RT setting. Validation of GCs as prognostic markers in the definitive RT setting is emerging. Experts used GCs in patients with PCa with extensive metastases (30%), in postoperative settings (27%), and in newly diagnosed PCa (23%). Forty-seven percent of experts do not currently use GCs in clinical practice. Expert consensus demonstrates that GCs are promising tools to improve risk-stratification in primary and oligo-/metastatic patients in addition to existing classifications. Experts were convinced that GCs might guide treatment decisions in terms of RT-field definition and intensification/deintensification in various disease stages. This work confirms the value of GCs and the promising evidence of GC utility in the setting of RT. Additional studies of GCs as prognostic biomarkers are anticipated and form the basis for future studies addressing predictive capabilities of GCs to optimize RT and systemic therapy. The expert consensus points out future directions for GC research in the management of PCa.