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Abstract Low anterior resection (LAR) and abdominoperineal resection (APR) are the two main surgical procedures after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. APR is associated with poorer prognosis; however existing data do not consider intensified CRT (5-Fluorouracil (5-FU)/Oxaliplatin + radiation) protocols. Clinicopathological data of patients treated with APR and LAR from the CAO/ARO/AIO-04 trial were analysed in terms of prognostic parameters and quality of life (QoL). Based on higher response rate after intensified CRT, subgroup analyses were performed. Data from n = 1173 patients were assessed. APR after preoperative CRT was associated with a significantly worse overall survival (p = 0.0056), disease-free survival (p

Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options, emphasizing the urgent need for effective therapies. The predominant driver in PDAC is mutated KRAS proto‐oncogene, KRA, present in 90% of patients. The emergence of direct KRAS inhibitors presents a promising avenue for treatment, particularly those targeting the KRASG12C mutated allele, which show encouraging results in clinical trials. However, the development of resistance necessitates exploring potent combination therapies. Our objective was to identify effective KRASG12C‐inhibitor combination therapies through unbiased drug screening. Results revealed synergistic effects with son of sevenless homolog 1 (SOS1) inhibitors, tyrosine‐protein phosphatase non‐receptor type 11 (PTPN11)/Src homology region 2 domain‐containing phosphatase‐2 (SHP2) inhibitors, and broad‐spectrum multi‐kinase inhibitors. Validation in a novel and unique KRASG12C‐mutated patient‐derived organoid model confirmed the described hits from the screening experiment. Our findings propose strategies to enhance KRASG12C‐inhibitor efficacy, guiding clinical trial design and molecular tumor boards.

Context: Understanding Paralympic athletes' perspectives on the importance of sleep is the first step toward developing effective sleep hygiene (SH) strategies. We aim to describe and compare the knowledge about SH and sleep behaviors practiced by medalists and nonmedalists Paralympic athletes at the Tokyo 2020 Paralympic Games and between sexes (female vs male), identify whether the coaching staff encourages SH, and the perspective of these athletes on the importance of SH. Methods: 98 Paralympic athletes responded to the Sleep Beliefs Scale and the Athlete Sleep Behavior Questionnaire-BR. Results: Medalists (68%) and nonmedalists (78%) Paralympic athletes had low knowledge about SH (60% vs 55%; P =.20), with no difference between groups. The Athlete Sleep Behavior Questionnaire-BR score (48.7 [5.9]) for all Paralympic athletes (n = 98) indicated high practice of maladaptive sleep behaviors. Male athletes had significantly worse sleep behaviors than female athletes (49.1 [6.0] vs 39.5 [7.2]; P <.01) and less knowledge about behaviors that can affect sleep (64% vs 72%; P <.05), 26% of Paralympic athletes considered SH practices necessary, and the frequency of coaching staff encouraging SH was higher among medalists Paralympic athletes compared to nonmedalists athletes (29% vs 13%, P =.04). Conclusions: Most Paralympic athletes have inadequate sleep behaviors and knowledge about SH. There was no difference between knowledge about SH and sleep behaviors between medalists and nonmedalists Paralympic athletes, although medalists athletes were more encouraged to practice SH. Male Paralympic athletes had worse sleep behaviors and worse knowledge about SH than female athletes. [ABSTRACT FROM AUTHOR]