BACKGROUND:The standard treatment for older patients (aged ≥70 years) with localised, unresectable head and neck squamous-cell carcinoma is standard fractionated radiotherapy (SF-RT). However, its high toxicity and multiple fractions lead physicians to deliver tailored hypofractionated split-course radiotherapy (HSC-RT). The aim of the study was to compare these two radiotherapy methods in older patients. METHODS:This non-inferiority, multicentre, open-label, randomised controlled trial was done in 30 treating centres (cancer centres, university and general hospitals, and private clinics) across France and Monaco. Patients aged 70 years or older, assessed as frail by geriatric evaluation, with stage II-IV head and neck squamous-cell carcinoma and in curative intent were randomly assigned (1:1) to receive either SF-RT (70 Gy, 35 fractions over 7 weeks) or HSC-RT (55 Gy, 20 fractions, two courses of 2 weeks with 2 weeks stop). Randomisation was done by minimisation, and physicians and patients were not masked to the treatment group. The primary endpoint was the proportion of patients alive with complete locoregional response at 6 months, analysed in all randomly assigned patients (intention-to-treat population). The non-inferiority margin was set at 16%. The study was sponsored by the Groupe d'Oncologie Radiothérapie Tête et Cou (GORTEC) and is registered with ClinicalTrials.gov, NCT01864850. FINDINGS:Between Oct 21, 2013, and Aug 22, 2018, 102 patients were randomly assigned to the HSC-RT group and 100 patients to the SF-RT group. One patient in the HSC-RT group refused treatment and follow-up and so was excluded, resulting in 101 patients in the HSC-RT group. Median age was 82 years (IQR 77-86); 145 (72%) were male and 56 (28%) were female. Median follow-up for overall survival was 56·6 months (IQR 41-69). In the intent-to-treat population, 35 (35%) of 101 patients were alive with complete locoregional response at 6 months in the HSC-RT group versus 33 (33%) of 100 patients in the SF-RT group (difference +2%, 95% CI -11 to 15). In the per-protocol population, 35 (36%) of 97 patients were alive with complete locoregional response at 6 months in the HSC-RT group versus 33 (35%) of 95 patients in the SF-RT group (difference +1%, -12 to 15). Median overall survival was 13·0 months (95% CI 10·3 to 17·0) in the HSC-RT group versus 18·9 months (14·3 to 30·9) in the SF-RT group (hazard ratio 1·32, 95% CI 0·97 to 1·81). Eight patients died between radiotherapy start and 30 days after radiotherapy end (five [5%] in the HSC-RT group and three [3%] in the SF-RT group). One patient in the HSC-RT group had a grade 4 adverse event (kidney failure), as did four in the SF-RT group (two mucositis, one septic shock, and one hemiplegia). Acute adverse events grade 3-5 occurred in 33 (36%) of 91 patients in the HSC-RT group and in 44 (47%) of 93 patients in the SF-RT group (p=0·13; difference -11%, 95% CI -25 to 3). INTERPRETATION:Compared with SF-RT, HSC-RT did not decrease the 6-month complete locoregional response rate and could be an option for frail older patients. However, given the survival results, it should only be offered to patients deemed unsuitable for SF-RT after geriatric assessment. FUNDING:French programme PAIR-VADS 2011 (sponsored by the French National Cancer Institute, Fondation ARC, and Ligue Contre le Cancer), GEMLUC, and GEFLUC.
Managing unresectable metastatic colorectal cancer (mCRC) requires a comprehensive strategy. While chemotherapy, anti-angiogenic, and anti-epidermal growth factor receptor (EGFR) agents are available, strategy trials are needed to optimize their use and sequencing. The STRATEGIC-1 phase III trial (NCT01910610) was designed to determine the optimal treatment sequence in patients with untreated, unresectable wild-type RAS/BRAFV600E mCRC. Patients were randomized (1:1) to FOLFIRI-cetuximab then mFOLFOX6-bevacizumab (arm A) or OPTIMOX-bevacizumab then FOLFIRI-bevacizumab followed by EGFR monoclonal antibody +/- irinotecan (arm B). The primary endpoint was the duration of disease control (DDC). Secondary endpoints were overall survival (OS), time to failure of strategy (TFS), progression-free survival (PFS), overall response rate (ORR), salvage surgery rate, safety, and health-related quality of life (HRQoL). Overall, 263 patients (arm A:131, arm B:132) were randomized. After 68.4 months of median follow-up (95% CI, 76.5-98.0), the median DDC was 22.8 months (95% CI, 20.4-28.8) in arm A and 23.5 months (95% CI, 17.9-26.3) in arm B (HR = 1.01, 95% CI, 0.76-1.34; log-rank P = 0.945). The median OS was 40.4 months (95% CI, 32.4-51.1) in arm A and 34.4 months (95% CI, 27.5-42.2) in arm B (HR = 1.30, 95% CI, 0.99-1.72). The ORR was higher in arm A (82.4% versus 65.4%) in the first-line group but not in the second-line group (20.7% versus 16.4%). Adverse events were consistent with the well-known safety profiles. STRATEGIC-1 did not meet its primary endpoint and was inconclusive in identifying the optimal treatment strategy in wild-type RAS/BRAFV600E mCRC.
BACKGROUND:This cadaveric study aimed to assess the biomechanical impact of functional hallux limitus (FHLim), identified using the functional stretch test, on first metatarsophalangeal joint (MTP1) mobility and joint pressures, as well as on the first cuneometatarsal joint (C1M1). A secondary objective was to evaluate the effect of retrotalar pulley section of the flexor hallucis longus (FHL) tendon on these parameters. METHODS:Seventeen cadaveric feet from 9 donors were analyzed. Each specimen was assessed in a resting position and during a functional stretch test, defined as passive hallux dorsiflexion performed with the ankle maintained in dorsiflexion to reproduce functional loading conditions. MTP1 mobility and intraarticular pressures at the MTP1 and C1M1 joints were measured before and after sectioning of the FHL retrotalar pulley. RESULTS:Maximum dorsiflexion mobilities in stretch test position in the FHLim group were significantly increased after pulley section (P < .001). Increased MTP1 pressure was found in the stretch test position in case of FHLim compared with controls in the neutral position (P = .02), and in the 20° dorsiflexion position (P = .02). There was a greater differential pressure in C1M1 joint before/after sectioning of the pulley in the FHLim group, whatever the position of the MTP1 in stretch test (P < .05). The amount of pressure reduction in MTP1 joint after pulley section in dorsiflexion was correlated with the severity of maximal dorsiflexion deficit in the stretch test position before pulley section (r = 0.51; P = .04). CONCLUSION:In this cadaveric model, FHL tenodesis at the retrotalar pulley restricted functional MTP1 dorsiflexion and increased joint pressures. Retrotalar pulley section corrected this biomechanical constraint and normalized MTP1 pressures relative to controls, supporting its role as a contributing mechanism in functional hallux limitus. CLINICAL RELEVANCE:This cadaveric study provides direct biomechanical evidence linking FHL retrotalar pulley impingement to elevated MTP1 joint pressures, supporting pulley release as a rational surgical target in functional hallux limitus.
This page contains three documents related to the work the STRINGS team has developed on mapping research related to the Sustainable Development Goals (SDGs): 1. A document explaining the methodology used to create search queries for identifying documents related to SDGs 1-16. 2. An Excel file containing the search queries themselves. 3. An additional Excel file containing country-SDG level data used in the paper "Countries’ research priorities in relation to the Sustainable Development Goals".The procedure for creating SDG queries was developed for the STRINGS project. For both the project and the paper, the procedure to identify SDG-related publications does not rely exclusively on search queries. We apply each SDG query to research areas obtained from a publication-level clustering algorithm, based on direct backward and forward citations. This enables us to select research areas related to SDGs and include all the publications contributing to that area. This approach has several advantages, including the ability to include publications that do not use SDG-related language in their abstract or title but still contribute to SDG-related research. For further insights, the platform, data, and thresholds used to understand which research areas are associated with an SDG are openly available here.In the STRINGS report, you can explore applications to map and characterize publications and patents related to the SDGs. Additionally, the paper "Countries’ research priorities in relation to the Sustainable Development Goals" provides a country-level analysis of the alignment between research priorities and SDG challenges.
