Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET.

BACKGROUND: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. METHODS: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. DISCUSSION: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Effects of diluted effluent on aquatic macroinvertebrate communities at the McClean Lake uranium operation in northern Saskatchewan.

Diluted treated effluent from the McClean Lake uranium mill in northern Saskatchewan is released into Vulture Lake, which flows into the east basin of McClean Lake; this input could potentially cause a variety of disturbances to the aquatic systems. This study aimed to determine the potential effects of diluted effluent exposure (metals and major ions) on benthic macroinvertebrates in Vulture Lake and McClean Lake. Two monitoring locations located in Vulture Lake and eight in McClean Lake were used for collection water, sediment, and benthic macroinvertebrates. Complementary surface water bioassays were performed with larvae of the midge Chironomus dilutus using lake water from selected sites. Results indicated that total macroinvertebrate abundance and Margalef index (MI) did not follow the diluted effluent pattern. In addition, while the MI from artificial substrate samplers showed higher values in Vulture Lake and lower values at McClean Lake sites 4 and 5 (closer to effluent diffuser), the values recorded for sediment grab samples registered lower indices in Vulture Lake and higher values for sites 4 and 5. The final model from a Generalized Additive Modelling (GAM) approach suggested that electrical conductivity (EC), selenium (Se), and chloride (Cl) in water, and total organic carbon (TOC) and cadmium (Cd) in sediment are key variables that collectively may have influenced macroinvertebrate community composition at the study sites. Finally, across all test endpoints in the bioassays, exposure to lake water from Vulture Lake and McClean Lake had no statistically significant effects on C. dilutus.

Prehabilitation services for people diagnosed with cancer in Scotland - Current practice, barriers and challenges to implementation.

BACKGROUND: Prehabilitation is the practice of enhancing a patient's functional and psychological capacity before treatment commences. It is of interest in the cancer context because of the impact of treatments on quality of life and cancer survivorship. This work aims to document current practice, barriers and challenges to implementing prehabilitation to inform the development of a national framework. METHODS: A mixed-methods approach was applied: an on-line survey was sent to stakeholders in cancer care across Scotland, supplemented by in-depth interviews. Key domains explored were the perceived importance of prehabilitation, availability, delivery and content of services, outcome measures, referral processes and funding. FINDINGS: A total of 295 survey responses were obtained and 11 interviews completed. Perceived importance of prehabilitation was rated highly. There was uncertainty over the definition of prehabilitation and most respondents did not know if local services were available. Where services were described, a range of health professionals were involved, different outcome measures were utilised and frequency of referrals varied. Respondents highlighted short time frames between referral and treatment, concerns about patient engagement, the evidence base for action and funding priorities. Respondents also commented on which context a referral should be made and to whom, and the need for equity of service across the country. CONCLUSIONS: The current work found clear evidence of the perceived importance of prehabilitation in cancer patients. However, issues and key gaps were identified within current services (including issues arising from COVID-19) which must be addressed to enable wide-spread development and implementation of equitable programmes.

A thermal stressor, propranolol and long-term memory formation in freshly collected Lymnaea.

A heat stressor (1 h at 30°C) in Lymnaea stagnalis before operant conditioning training of aerial respiration is sufficient to enhance long-term memory (LTM) formation in 'average' cognitive ability, laboratory-reared, inbred snails. However, in freshly collected outbred snails, the same heat stressor blocks LTM formation in 'smart' cognitive phenotype but not in average cognitive phenotype strains. Here, we hypothesize that (1) preventing the stress associated with the heat stressor before training allows LTM to form in the smart phenotype strains; and (2) alleviating the stress before a memory recall session allows a formed LTM to be recalled in the smart phenotype strains. We found that an injection of propranolol, which mitigates the stressor, before snails experience the heat stressor enabled two strains of the smart phenotype snails to form LTM, consistent with our first hypothesis. However, the injection of propranolol before a memory test session did not alleviate a memory recall block in the smart phenotype snails. Thus, our second hypothesis was not supported. Therefore, smart cognitive phenotype snails encountering a heat stressor have an inability to form LTM, but this inability can be overcome by the pre-injection of propranolol.

VOCCluster: Untargeted Metabolomics Feature Clustering Approach for Clinical Breath Gas Chromatography/Mass Spectrometry Data.

Metabolic profiling of breath analysis involves processing, alignment, scaling, and clustering of thousands of features extracted from gas chromatography/mass spectrometry (GC/MS) data from hundreds of participants. The multistep data processing is complicated, operator error-prone, and time-consuming. Automated algorithmic clustering methods that are able to cluster features in a fast and reliable way are necessary. These accelerate metabolic profiling and discovery platforms for next-generation medical diagnostic tools. Our unsupervised clustering technique, VOCCluster, prototyped in Python, handles features of deconvolved GC/MS breath data. VOCCluster was created from a heuristic ontology based on the observation of experts undertaking data processing with a suite of software packages. VOCCluster identifies and clusters groups of volatile organic compounds (VOCs) from deconvolved GC/MS breath with similar mass spectra and retention index profiles. VOCCluster was used to cluster more than 15 000 features extracted from 74 GC/MS clinical breath samples obtained from participants with cancer before and after a radiation therapy. Results were evaluated against a panel of ground truth compounds and compared to other clustering methods (DBSCAN and OPTICS) that were used in previous metabolomics studies. VOCCluster was able to cluster those features into 1081 groups (including endogenous and exogenous compounds and instrumental artifacts) with an accuracy rate of 96% (±0.04 at 95% confidence interval).

Juveniles of Lymnaea 'smart' snails do not perseverate and have the capacity to form LTM.

Previously, it was concluded that the nervous systems of juvenile snails were not capable of mediating long-term memory (LTM). However, exposure and training of those juvenile snails in the presence of a predator cue significantly altered their ability to learn and form LTM. In addition, there are some strains of Lymnaea which have been identified as 'smart'. These snails form LTM significantly better than the lab-bred strain. Here, we show that juveniles of two smart snail strains not only are capable of associative learning but also have the capacity to form LTM following a single 0.5 h training session. We also show that freshly collected 'wild' 'average' juveniles are also not able to form LTM. Thus, the smart snail phenotype in these strains is expressed in juveniles.

Strain-specific differences of the effects of stress on memory in Lymnaea.

Stress alters the ability to form, recall and maintain memory according to the Yerkes-Dodson/Hebb (YDH) law. The effects of environmentally relevant stressors, such as low environmental calcium and crowding, on learning and memory have previously been described in a laboratory-reared 'average' strain of Lymnaea stagnalis (i.e. the Dutch strain) as well as two strains of freshly collected L. stagnalis with enhanced memory formation abilities (i.e. 'smart' snails). Here, we use L. stagnalis to study the effects of other environmentally relevant stressors on memory formation in two other strains of freshly collected snails, one 'smart' and one 'average'. The stressors we examined are thermal, resource restriction combined with food odour, predator detection and, for the first time, tissue injury (shell damage). We show that the same stressor has significantly different effects on memory formation depending on whether snails are 'smart' or 'average'. Specifically, our data suggest that a stressor or a combination of stressors act to enhance memory in 'average' snails but obstruct memory formation in 'smart' snails. These results are consistent with the YDH law and our hypothesis that 'smart' snails are more easily stressed than 'average' snails.

A traffic light approach for treatment and supportive care stratification in lung cancer.

PURPOSE OF REVIEW: Comprehensive supportive care interventions for patients with lung cancer are being investigated in a range of ways, including: early palliative care, prehabilitation and rehabilitation. We review recent literature on supportive care and propose a traffic light system to individualise comprehensive supportive care. Green for those very likely to receive anti-cancer treatment, red for those very unlikely to receive anti-cancer treatment and orange where the chance of accessing treatment is uncertain. Comprehensive supportive care can be individualised based on the group a particular patient is in. RECENT FINDINGS: Lung cancer outcomes are improving with the availability of increasingly efficacious treatments; however, treatment rates for advanced disease remain low. In this review, we discuss how person-centred outcomes could be improved, how outcomes can be prognosticated and how the 'host' can be staged as well as the cancer. Recent data suggests that early comprehensive supportive care improves quality of life, reduces time spent in hospital and may affect survival. SUMMARY: Comprehensive supportive care is likely to improve quality of life in patients with advanced lung cancer. Further work is needed to see if it can improve treatment rates and survival.

Prognostic Biomarkers of Systemic Inflammation in Non-Small Cell Lung Cancer: A Narrative Review of Challenges and Opportunities.

Non-small cell lung cancer (NSCLC) is a common malignancy and is associated with poor survival outcomes. Biomarkers of systemic inflammation derived from blood tests collected as part of routine clinical care offer prognostic information for patients with NSCLC that may assist clinical decision making. They are an attractive tool, as they are inexpensive, easily measured, and reproducible in a variety of healthcare settings. Despite the wealth of evidence available to support them, these inflammatory biomarkers are not yet routinely used in clinical practice. In this narrative review, the key inflammatory indices reported in the literature and their prognostic significance in NSCLC are described. Key challenges limiting their clinical application are highlighted, including the need to define the optimal biomarker of systemic inflammation, a lack of understanding of the systemic inflammatory landscape of NSCLC as a heterogenous disease, and the lack of clinical relevance in reported outcomes. These challenges may be overcome with standardised recording and reporting of inflammatory biomarkers, clinicopathological factors, and survival outcomes. This will require a collaborative approach, to which this field of research lends itself. This work may be aided by the rise of data-driven research, including the potential to utilise modern electronic patient records and advanced data-analysis techniques.

Systematic review of the efficacy of stereotactic ablative radiotherapy for oligoprogressive disease in metastatic cancer.

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) for the treatment of oligometastatic disease can improve survival and delay the requirement for systemic therapy. The benefits of SABR in oligoprogressive disease are less well-defined. Here, we evaluate the available evidence investigating the efficacy of SABR in the treatment of oligoprogressive disease. METHODS: A systematic review was carried out following PRISMA guidelines. Medline and Embase databases were searched using the terms "stereotactic radiotherapy" OR "SABR" OR "Stereotactic Ablative Body Radiotherapy" OR "SBRT" OR "SRT" AND "oligoprogression" in May 2022, June 2023, and February 2024. Studies were excluded where: SABR was used as a radical treatment, a specific oligoprogressive cohort could not be identified, publication was as a conference abstract or where fewer than 10 patients were recruited. Studies treating only brain metastases were also excluded. The site of primary tumour, oligoprogressive sites, rates of overall survival (OS), progression free survival (PFS), local control (LC) and time to next systemic therapy were collected. RESULTS: Thirty-three full text studies were included. These consisted of single centre and multi-institutional observational studies, case series and phase II trials. Twenty-two studies were related to a specific tumour type: 12 urological cancer (9 prostate, 3 renal cancer), 6 non-small cell lung cancer, 2 colorectal cancer, 2 breast cancer and 11 were studies covering multiple tumour sites (5 studies involving SABR to a single organ and 6 studies involving SABR to multi-organ). Median PFS was >6 months in patients with oligoprogressive prostate, non-small cell lung cancer and renal cancer patients. CONCLUSIONS: SABR appears to have clinical benefit in oligoprogresssive prostate, lung, and renal patients. However, the optimal management of patients with oligoprogressive disease is still somewhat uncertain due to lack of prospective data. This will hopefully become clearer in the near future with the publication of further randomised trials.

Exposure to the insecticide, imidacloprid, impairs predator-recognition learning in damselfly larvae.

Many aquatic organisms use chemosensory information to learn about local predation threats, but contaminants in their environment may impair such cognitive processes. Neonicotinoids are a class of water-soluble systemic insecticides that have become a major concern in aquatic systems. In this study, we explored how a 10-day exposure to various concentrations (0, 0.1, 1.0, or 10.0 µg/L) of the neonicotinoid imidacloprid affects the learned recognition of predator odour by non-target damselfly larvae (Lestes spp). Unexposed larvae and those exposed to the low concentration (0.1 µg/L) demonstrated an appropriate learned response to a novel predator odour following a conditioning with the odour paired with chemical alarm cues. However, such learning failed to occur for larvae that were exposed to imidacloprid concentrations of 1.0 and 10.0 µg/L. Thus, either the cognitive processing of the chemical information was impaired or the chemistry of one or both of the conditioning cues was altered, making them ineffective for learning. In a second experiment, we found evidence for this latter hypothesis. In the absence of background imidacloprid exposure, larvae did not show significant learned responses to the predator odour when the conditioning cues were mixed with imidacloprid (initial pulse solution of 3.0 µg/L) at the start of conditioning (reaching a final concentration of 0.01 µg/L). These findings indicate that even low levels of imidacloprid can have important implications for chemosensory cognition of non-target species in aquatic environments.

Sub-lethal effects of the insecticide, imidacloprid, on the responses of damselfly larvae to chemosensory cues indicating predation risk.

Insecticides, including the widely used neonicotinoids, can affect both pest and non-target species. In addition to lethal effects, these insecticides at sub-lethal levels may cause disruption to sensory perception and processing leading to behavioural impairments. In this laboratory experiment, we investigated the effects of a 10-day exposure to the neonicotinoid insecticide, imidacloprid, on the behaviour of larvae of the damselfly, Lestes congener. In tests of baseline activity, imidacloprid concentrations of 1.0 and 10.0 µg/L caused significant reductions in foraging behaviour. Moreover, in response to chemical cues that indicate a potential risk to the larvae, imidacloprid caused the loss of an appropriate antipredator response (reduced foraging) depending on the concentration and duration of exposure. Imidacloprid at 0.1 µg/L caused the loss of responses toward the odour of a beetle (Dytiscus spp.) predator after 10 days of exposure, whereas 1.0 µg/L caused lost responses toward both the predator odour and injured conspecific cues (i.e., alarm cues) and after only 2 days of exposure. However, at 10.0 µg/L, larvae responded appropriately to both cues throughout the duration of the study, suggesting compensatory responses to imidacloprid at higher concentrations. Hence, the lack of appropriate responses at 1.0 µg/L likely resulted from a cognitive impairment rather than chemical alteration of these important chemosensory cues. In the natural environment, such effects will likely cause decreased survivorship in predator encounters. Hence, imidacloprid exposure, even at low concentrations, could have adverse consequences for chemosensory ecology of this damselfly species.

Early prehabilitation in suspected locally advanced and metastatic lung cancer.

OBJECTIVES: The most common treatment for locally advanced and metastatic lung cancer is best supportive care. Patients with lung cancer are often comorbid with a high symptom burden. We wanted to assess whether early prehabilitation was feasible in patients with likely lung cancer. METHODS: Patients were offered prehabilitation if they were attending the new patient respiratory clinic, had a CT scan suggesting stage III or IV lung cancer and undergoing further investigations. Patients receiving palliative care were ineligible. All prehabilitation patients were referred to a palliative medicine physician, registered dietitian and rehabilitation physiotherapist. RESULTS: 50 patients underwent prehabilitation between June 2021 and August 2022. The median age was 72 years (range 54-89 years). 48 patients had lung cancer. 84% of patients attended all three interventions.Half of the palliative care consultations focused on pain. Half of the patients seen had a change in medication. 25% of patients' weights were stable, 32% required a food-first strategy and 33% required oral nutritional supplements. 57% of patients discussed managing breathlessness with the physiotherapist. CONCLUSIONS: Early prehabilitation is feasible alongside the investigation of locally advanced and metastatic lung cancer. Further work will aim to assess its impact on admission to the hospital, survival and treatment rates.

Early prehabilitation reduces admissions and time in hospital in patients with newly diagnosed lung cancer.

OBJECTIVES: Lung cancer is the leading cause of cancer death in the UK. Prehabilitation aims to maximise patient fitness and minimise the negative impact of anticancer treatment. What constitutes prehabilitation before non-surgical anticancer treatment is not well established. We present data from a pilot project of Early prehabilitation In lung Cancer. METHODS: All new patients with likely advanced lung cancer were offered prehabilitation at respiratory clinic, if fit for further investigation. Prehabilitation included assessment and appropriate intervention from a consultant in palliative medicine, registered dietitian and rehabilitation physiotherapist. Four objective endpoints were identified, namely admissions to hospital, time spent in the hospital, treatment rates and overall survival. Outcomes were to be compared with 178 prehab eligible historical controls diagnosed from 2019 to 2021. RESULTS: From July 2021 to June 2023, 65 patients underwent prehabilitation and 72% of patients underwent all 3 interventions. 54 patients had a stage 3 or 4 lung cancer. In the prehab group, fewer patients attended Accident and Emergency (31.5 vs 37.4 attendances per 100 patients) and fewer were admitted (51.9 vs 67.9) when compared with historical controls. Those receiving prehab spent a lot less time in the hospital (129.7 vs 543.5 days per 100 patients) with shorter admissions (2.5 vs 8 days). Systemic anticancer treatment rates increased in the short term but were broadly similar overall. Median survival was higher in the prehabilitation group (0.73 vs 0.41 years, p=0.046). CONCLUSIONS: Early prehabilitation appears to reduce time spent in the hospital. It may improve survival. Further work is required to understand its full effect on treatment rates.

The care of older patients with cancer across the United Kingdom in 2024: A narrative review by the International Society of Geriatric Oncology UK Country Group.

The worldwide population is ageing, alongside an increase in cancer incidence rates. Over the past 10 years, there has been huge progress in the field of oncology with earlier diagnosis and an expansion of treatment options, leading to a growing number of older people living with cancer. That has meant that caring for older patients with cancer is now part of day-to-day oncology practices. This cohort often has geriatric syndromes and a higher prevalence of frailty and complex needs and preparing our clinical services to optimise care for these patients is essential. Whilst it is widely accepted that comprehensive geriatric assessments are of benefit to patients, only a small proportion of patients can access these through specialised teams during their cancer care. In the past few years there has been significant progress in this field throughout the United Kingdom (UK). The goal of this review is to inform other health care systems how to learn from what has been done in the UK. This paper provides an update from our previous review in 2020, detailing the new services being implemented and made available to patients and an expansion in the number of new pilot teams and research projects/trials throughout the four nations of the UK.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study.

PURPOSE: Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. METHODS: In Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. RESULTS: Response rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. CONCLUSIONS: This Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.

Body weight and composition endpoints in cancer cachexia clinical trials: Systematic Review 4 of the cachexia endpoints series.

Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.

Agricultural Use of Insecticides Alters Homeostatic Behaviors and Cognitive Ability in Lymnaea stagnalis.

Lymnaea stagnalis is an ecologically important, stress-sensitive, freshwater mollusk that is at risk for exposure to insecticides via agricultural practices. We provide insight into the impact insecticides have on L. stagnalis by comparing specific behaviors including feeding, locomotion, shell regeneration, and cognition between snails collected at two different sites: one contaminated by insecticides and one not. We hypothesized that each of the behaviors would be altered in the insecticide-exposed snails and that similar alterations would be induced when control snails were exposed to the contaminated environment. We found no significant differences in locomotion, feeding, and shell regeneration of insecticide-exposed L. stagnalis compared with nonexposed individuals. Significant changes in feeding and shell repair were observed in nonexposed snails inhabiting insecticide-contaminated pond water. Most importantly, snails maintained and trained in insecticide-contaminated pond water did not form configural learning, but this cognitive deficit was reversed when these snails were maintained in insecticide-free pond water. Our findings conclude that insecticides have a primarily negative impact on this higher form of cognition in L. stagnalis. Environ Toxicol Chem 2023;42:2466-2477. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer.

BACKGROUND: Pembrolizumab monotherapy for non-small-cell lung cancer (NSCLC) expressing PD-L1 ≥ 50% doubles five-year survival rates compared to chemotherapy. However, immune-related adverse events (irAEs) can cause severe, long-term toxicity necessitating high-dose steroids and/or treatment cessation. Interestingly, patients experiencing irAEs demonstrate better survival outcomes. Biomarkers of systemic inflammation, including the Scottish Inflammatory Prognostic Score (SIPS), also predict survival in this patient group. This study examines the relationship between inflammatory status, irAEs, and survival outcomes in NSCLC. METHODS: A retrospective analysis was conducted on patients with NSCLC expressing PD-L1 ≥ 50% receiving first-line pembrolizumab monotherapy at a large cancer centre in Scotland. Regression analyses were conducted to examine the relationship between SIPS, irAEs, and survival. RESULTS: 83/262 eligible patients (32%) experienced an irAE. Dermatological, endocrine, gastrointestinal, and hepatic, but not pulmonary, irAEs were associated with prolonged PFS and OS (p <= 0.011). Mild irAEs were associated with better PFS and OS in all patients, including on time-dependent analyses (HR0.61 [95% CI 0.41-0.90], p = 0.014 and HR0.41 [95% CI 0.26-0.63], p < 0.001, respectively). SIPS predicted PFS (HR 1.60 [95% CI 1.34-1.90], p < 0.001) and OS (HR 1.69 [95% CI 1.41-2.02], p < 0.001). SIPS predicted the occurrence of any irAE in all patients (p = 0.011), but not on 24-week landmark analyses (p = 0.174). The occurrence of irAEs predicted favourable outcomes regardless of the baseline inflammatory status (p = 0.015). CONCLUSION: The occurrence of certain irAEs is associated with a survival benefit in patients with NSCLC expressing PD-L1 ≥ 50% receiving pembrolizumab. We find that the association between low levels of systemic inflammation and the risk of irAEs is confounded by their independent prognostic value.

Nutritional status and symptom burden in advanced non-small cell lung cancer: results of the dietetic assessment and intervention in lung cancer (DAIL) trial.

INTRODUCTION: European Society for Clinical Nutrition and Metabolism guidelines recommend that patients with cancer should be screened for malnutrition at diagnosis. The dietetic assessment and intervention in lung cancer study investigated the nutritional status of patients with non-small cell lung cancer (NSCLC) and the need for dietetic intervention. METHODS: In this observational cohort pilot study, patients with stage 3b and 4 NSCLC were assessed prior to starting first line systemic anticancer therapy (SACT) with a range of measurements and questionnaires. We report the outcomes related to the Patient Generated Subjective Global Assessment tool (PG-SGA), RESULTS: 96 patients were consented between April 2017 and August 2019. The PG-SGA identified that 78% of patients required specialist nutritional advice; with 52% patients having a critical need for dietetic input and symptom management. Results were dominated by symptom scores. As a screening test, one or more symptoms or recent weight loss history had a sensitivity of 88% (95% CI 78.44% to 94.36%) and specificity of 95.24% (95% CI 76.18% to 99.88%) for need for dietetic intervention. CONCLUSION: A large proportion of patients with NSCLC have a high symptom burden and are at risk of malnutrition prior to starting SACT and would benefit from dietetic review. It is imperative that oncologists and healthcare professionals discuss weight loss history and symptoms with lung cancer patients to correct nutritional deficiencies and resolve symptoms prior to starting treatment.