Paul Cordero

Background/Objectives: Up to 95% of cancer patients report sleep disturbances or disorders. These can potentially influence cancer development and outcomes. This study aimed to review the existing literature to understand the patient experience of cancer-related sleep impairment across indications and treatments, to improve awareness and inform disease treatment/management. Methods: A targeted literature review of published qualitative studies exploring sleep impairment in oncology was conducted in MEDLINE, Embase, and PsycINFO. Concepts were extracted from the reviewed articles, and patient quotes or author descriptions/interpretations were subject to secondary analysis using semantic, qualitative, directed content analysis techniques via ATLAS.ti. Results informed the development of a patient-centric conceptual model. Results: From 482 identified publications, 22 publications were selected for in-depth review and concept extraction, collectively including 531 patients across 25 different oncology indications. Cancer-related sleep impairment frequently affected patients living with cancer, who reported difficulty obtaining good quality sleep, including difficulty falling asleep and staying asleep. Sleep problems were triggered by the emotional anxiety of life with cancer, cancer-related symptoms, treatments and side effects, and external factors. Poor sleep greatly impacted daily life for patients, with difficulties in daily life causing further sleep impairment, in a cyclical relationship. Conclusions: This study determined that there is an unmet need for treatment of sleep impairment in oncology to improve patient outcomes. The holistic conceptual model developed in this study can provide an important basis for selecting, developing, or modifying outcome measures to assess relevant sleep outcomes, facilitating discussion between patients and clinicians and improving disease treatment/management.

The literature on the qualitative experiences of patients with non-Hodgkin lymphoma (NHL) is limited. Qualitative interviews were conducted to investigate participants’ experiences with two types of NHL (diffuse large B-cell lymphoma [n = 20] and mantle cell lymphoma [n = 10]) and evaluate the comprehensiveness of patient-reported outcome (PRO) measures. Fatigue, tiredness, body aches, night sweats, lethargy, headache, appetite loss, altered taste, and weakness were the most frequent and bothersome symptoms. Key impacts were decreased physical performance, restricted activity, sadness, distress, fear of recurrence, and worry about future. Most participants expressed positive opinions about the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) (n = 22/28), EORTC QLQ-NHL-High Grade Module 29 (EORTC QLQ-NHL-HG29) (n = 12/16), EORTC QLQ-NHL-Low Grade Module 20 (EORTC QLQ-NHL-LG20) (n = 8/12), and Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) (n = 10/14), considering them relevant to their experiences (22/27, 13/15, 9/13, and 10/12, respectively). All measures adequately captured their experiences with NHL (QLQ-C30: n = 26/26, NHL-HG29: n = 14/14, NHL-LG20: n = 11/11, and FACT-Lym: n = 12/13). These findings provide a valuable framework for informing the selection of appropriate PRO measures in NHL clinical trials and identifying potentially meaningful trial endpoints.

Background and aims: YAQ001 is a novel, highly engineered, non-absorbable, gut-restricted, multiporous, carbon bead adsorbent. Pre-clinical studies and a clinical trial confirmed its therapeutic potential and safety in patients with cirrhosis. The aims of this sub study were to evaluate the effect of YAQ001 on the gut microbiome and its association with biomarkers of gut permeability and systemic inflammation. Methods: In total, 28-patients with cirrhosis were randomized (double-blind) to receive YAQ001 (4g once daily) or Placebo. Gut microbiome and biomarkers of inflammation and gut permeability were assessed at baseline, after 4 and 12-weeks. Changes in biomarkers and relationship with microbiome composition and gene profiling were assessed. The effect of YAQ001 on Klebsiella pneumoniae bacterial biofilms was also assessed using an in vitro gut epithelial model. Results: Alpha and beta diversity at different time points were unaltered. YAQ001 increased the abundance of bacteria associated with improved gut health such as Adlercreutzia equolifaciens (pKlebsiella pneumonia and Streptococcus mutans (pKlebsiella pneumoniae biofilms in vitro . Conclusions: The results show that YAQ001 impacts positively on the composition of the microbiome, significantly reduces its virulence, antibiotic resistance genes and biofilm formation, which is associated with modulation of gut permeability and systemic inflammation. Impact and implications: YAQ001 exerts its therapeutic effect by favorably modulating the gut ecosystem in cirrhosis. It selectively increases beneficial gut bacteria while suppressing pathogenic taxa linked to adverse outcomes. Beyond composition, YAQ001 reduces microbial virulence by limiting the production of invasive toxins and lowers the abundance of antibiotic-resistance genes. In vitro models also demonstrated its efficacy in inhibiting biofilm formation by key pathogens. In summary, this multifaceted modulation of the microbiome led to tangible clinical improvements, notably enhanced gut barrier function and reduced systemic inflammation. The data support further development of YAQ001 as a novel microbiome therapeutic. Highlights: In patients with cirrhosis, YAQ001 specifically enhanced beneficial gut bacteria while suppressing pathogenic bacteria linked to adverse clinical outcomes. YAQ001 significantly reduced the genetic expression of critical virulence factors, including siderophores, fimbriae, and lipopolysaccharides, thereby diminishing the potential for microbial invasion and inflammation. YAQ001 administration led to a significant decrease in the abundance of antibiotic resistance genes within the gut microbiome, potentially restoring therapeutic efficacy of antibiotics. In vitro studies demonstrated that YAQ001 effectively prevents the formation of Klebsiella pneumoniae biofilms, a key mechanism of bacterial persistence and chronic infection. The beneficial microbial shifts were directly associated with clinically relevant improvements in biomarkers of gut permeability and systemic inflammation.

Background and objective: Typical endpoints in cancer clinical trials focus on standardized efficacy endpoints, such as overall survival. Pain is not always assessed, although it is a highly prevalent and distressing aspect of patients’ cancer experience and plays a critical role in health-related quality of life. To inform future pain measurement strategies in oncology, this targeted literature review of pain-related qualitative publications in oncology aimed to characterize and explore the patient experience of pain, and its impact on how patients feel and function. Methods: A review of publications in MEDLINE, Embase and PsycINFO from 2018 to 2023 was conducted. Patient quotes or author descriptions/interpretations were extracted and analyzed with directed content analysis techniques, using ATLAS.ti v9. Data were synthesized to inform the development of a conceptual model. Results: Twenty-eight publications, with data from 534 patients across different oncology indications and geographies, were reviewed. Pain was triggered by disease symptoms and treatment, including surgical procedures, chemotherapy, and radiation. Pain was most often daily, severe, and chronic in nature. Characterizations of pain varied, but most often “sharp”/“stabbing”/“shooting” pain was described across different treatment stages. Pain had an extensive impact on emotional wellbeing, activities of daily living, physical, physiological and social functioning, sleep and work. Unmet needs included difficulty communicating pain needs to healthcare practitioners and fear/distrust of opioid pain medication. Conclusions: This research provides a patient-centric model conceptualizing the patient experience of cancer-related pain. The findings highlight the burden and all-encompassing impact of cancer-related pain, demonstrating the importance of assessing pain in oncology clinical trials.

Introduction Traditionally, treatment endpoints in oncology have focused on increasing overall survival and progression-free survival. Although fatigue may be a meaningful outcome measure across different cancers, it is assessed less frequently. To explore the impact of fatigue on patients with cancer, confirm the importance of fatigue measurement and inform future measurement strategies in oncology, we aimed to characterise the patient experience of fatigue and the associated impact on how patients feel and function, including aspects of health-related quality of life (HRQoL). Methods A targeted literature review of published fatigue-related qualitative publications in oncology was conducted in MEDLINE, Embase and PsycINFO, limited to studies published between 2018 and 2023. Concepts were extracted from the qualitative literature and patient quotes or author descriptions/interpretations were subject to secondary analysis using semantic, qualitative, directed content analysis techniques via ATLAS.ti v9. The literature review informed the development of a preliminary patient-centric conceptual model of fatigue in oncology. Results Of 1210 identified publications, 26 were selected for data extraction, including 512 patients living with 28 different oncology indications across geographies. Frequently reported fatigue triggers included treatments and cancer itself. Patients used various fatigue descriptors, including low/lack/loss of energy, tiredness and exhaustion, across disease stages. Physiological and cognitive manifestations of fatigue were reported, and fatigue episodes were described as unpredictable and of variable severity, duration and frequency. Cancer-related fatigue had a substantial negative effect on patients’ QoL, including emotional, physical, physiological, social, activities of daily living, sleep and work impacts. Unmet needs included poor support from healthcare professionals (HCPs). Conclusions This review demonstrated that fatigue is an impactful symptom across oncology indications and provides the first holistic conceptual model of cancer-related fatigue across disease stages and treatments. Future research should review clinical outcome assessments (COA) that may be fit-for-purpose for measuring fatigue in oncology clinical trials.

Introduction: Subcutaneous (SC) administration of the anti-CD38 antibody isatuximab (Isa) by an on-body delivery system (OBDS), plus pomalidomide-dexamethasone, has demonstrated safety and efficacy comparable to intravenous (IV) administration, with no infusion reactions and excellent local tolerability in multiple myeloma (MM) patients. We report here results of a nurse survey designed to evaluate convenience of treatment with SC Isa, via OBDS, for healthcare providers and MM patients.Methods: A newly developed, expert-vetted questionnaire was used to survey nurses with experience in SC administration to MM patients enrolled in clinical trials. Results on extent of agreement with pre-vetted statements were expressed as percentages of respondents. Free-text answers were analyzed for each respondent and grouped by topic.Results: All surveyed nurses (N=12) agreed that OBDS administration improved efficiency and was easy to learn and administer with a low level of physical burden, leading to a preference for OBDS over IV Isa administration and facilitating a positive treatment experience for the patients. Compared with IV dosing, the OBDS improved patient comfort and could reduce time spent in the clinic. As agreed by most nurses, main advantages for patients included no needle visibility, short treatment duration, and a generally well-tolerated and painless SC injection.Conclusions: Our findings show a high level of confidence among nurses in SC Isa administration via OBDS, due to the ease of use, tolerability, and time savings achieved with hands-free OBDS injections. Our findings suggest applicability of the OBDS for convenient SC Isa administration to MM patients in routine clinical practice.

While patient-reported outcome measures are regularly incorporated into phase 3 clinical trials, they have been infrequently used in early phase trials. However, the patient’s perspective is vital to fully understanding dose toxicity and selecting an optimal dose. This viewpoint paper reviews the rationale for and practical approach to collecting patient-reported outcome data in early phase oncology drug development and the rationale for electronic collection.

Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit obesity during adulthood. Here, we aim to determine the influence of the Mc4r gene on the liver of mice subjected to perinatal diet-induced obesity. Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO). At 21 days, offspring were genotyped, weaned onto a control diet, and sacrificed at 6 months old. Offspring phenotypic characteristics, plasma biochemical profile, liver histology, and hepatic gene expression were analyzed. Mc4r_ko offspring showed higher body, liver and adipose tissue weights respect to the wild type animals. Histological examination showed mild hepatic steatosis in offspring group C_KO. The expression of hepatic genes involved in regulating inflammation, fibrosis, and immune cell infiltration were upregulated by the absence of the Mc4r gene. These results demonstrate that maternal obesogenic feeding during the perinatal period programs offspring obesity development with involvement of the Mc4r system.