Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

Next generation pan-cancer blood proteome profiling using proximity extension assay.

A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.

End-of-life care for people with advanced dementia and pain: a qualitative study in Swedish nursing homes.

BACKGROUND: Of the Swedish people with advanced dementia, the majority die in nursing homes. Unresolved pain can occur in people with a terminal illness such as dementia. However, pain management in people with advanced dementia is often suboptimal and inadequate, with fewer palliative care interventions than offered to cancer patients. Although they are largely responsible for the care of these people, few studies have addressed the experiences of registered nurses in this respect. Therefore, the aim of this study was to describe the experiences of nurses in caring for people with advanced dementia and pain at the end of life. METHODS: The study had a descriptive explorative design. Individual qualitative, semi-structured interviews were carried out with 13 nurses from 12 nursing homes in Sweden. The results were analysed using thematic content analysis. RESULTS: The nurses described communicative, relational and organisational challenges. One major issue involved difficulties communicating with the person with advanced dementia, resulting in uncertain pain assessment. Other difficulties involved the differentiation of pain from anxiety, the balance of benefits and risks with morphine administration, and the creation of good relationships with healthcare personnel and the persons' relatives. Relatives can greatly affect the assessment and management of pain, both because of their ability to interpret pain behaviour and by questioning the care given. Good pain management was facilitated by good communication and relationships with healthcare staff and relatives, extensive professional nursing experience, and already knowing the person with advanced dementia. CONCLUSIONS: This study highlights the need for nursing homes to employ specialist nurses who have been trained in the appropriate knowledge and skills to deal with the challenges of end-of-life care for people with advanced dementia and pain. Additionally, there should be resources and strategies available for providing information to family members and for involving them in the decision-making process, as they are often unfamiliar with the multitude of considerations involved in decisions such as whether to administer morphine or not.