The experience of surgical cancer patients during the COVID-19 pandemic at a large cancer centre in London.

BACKGROUND: The COVID-19 pandemic has had an enormous impact on the experiences of patients across all health disciplines, especially those of cancer patients. The study aimed to understand the experiences of cancer patients who underwent surgery during the first two waves of the pandemic at Guy's Cancer Centre, which is a large tertiary cancer centre in London. METHODS: A mixed-methods approach was adopted for this study. Firstly, a survey was co-designed by the research team and a patient study group. Patients who underwent surgery during the COVID-19 pandemic were invited to take part in this survey. Results were analysed descriptively. Three discussion groups were then conducted to focus on the main themes from the survey findings: communication, COVID-19 risk management and overall experience. These discussion groups were transcribed verbatim and underwent a thematic analysis using the NVivo software package. RESULTS: Out of 1657 patients invited, a total of 250 (15%) participants took part in the survey with a mean age of 66 (SD 12.8) and 52% females. The sample was representative of a wide range of tumour sites and was reflective of those invited to take part. Overall, the experience of the cancer patients was positive. They felt that the safety protocols implemented at the hospital were effective. Communication was considered key, and patients were receptive to a change in the mode of communication from in-person to virtual. CONCLUSIONS: Despite the immense challenges faced by our Cancer Centre, patients undergoing surgery during the first two waves of the COVID-19 pandemic had a generally positive experience with minimal disruptions to their planned surgery and ongoing care. Together with the COVID-19 safety precautions, effective communication between the clinical teams and the patients helped the overall patient experience during their surgical treatment.

Assessing the quality of patient-reported outcome measurements for gynecological cancers: a systematic review.

Aim: To provide perspective on patient-reported outcome measurement (PROM) instruments to adopt in patients diagnosed with gynecological cancers. Methods: A systematic search was conducted to identify PROMs developed for or applied in gynecological cancer populations. PROMs identified in more than one study subsequently underwent assessment according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. Results: Overall, 55 PROMs were identified within the gynecological cancer setting, and 20 were assessed according to COSMIN guidelines. Most PROMs had limited information reported, but a best fit approach was adopted to recommend a number of instruments for use in patients with gynecological cancer. Conclusion: Further study to assess the methodological quality of each PROM utilized in gynecological cancers is warranted to endorse the recommendations of this review.

Gynecological cancers are cancers which occur in the reproductive system of women. The cervical cancer screening program and development of new treatments mean that women with gynecological cancers are now living longer than before. However, these new treatments may have side effects that can affect the quality of life of women with cancer. Many care providers now agree that looking at women's quality of life during their gynecological cancer journey is an important part of their treatment. Patient-reported outcome measurements (PROMs) are questionnaires that the patient completes to measure their symptoms and quality of life. There are a lot of PROMs available to choose from, and it can be difficult to select one that is relevant and understandable for all women with gynecological cancer. This article searched the literature to find all PROMs that can be completed by women with gynecological cancer and then measured each of the PROM's quality. PROM quality was measured by looking at validity (whether the questionnaire measures what it is supposed to measure), reliability (that the questionnaire is not subject to different errors in measuring), and sensitivity (that the questionnaire can measure changes in questionnaire scores over time). Overall, this study found that there were a few PROMs that were of good enough quality to be completed by women with gynecological cancers. These questionnaires are called the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Cervical Cancer Module (EORTC QLQ-CX24), the Functional Assessment of Cancer Therapy - General (FACT-G), European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Endometrial Cancer (EORTC QLQ-EN24), Functional Assessment of Cancer Therapy Gynecologic Oncology Group ­ Neurotoxicity (FACT-GOG/Ntx), Functional Assessment of Cancer Therapy ­ Ovarian (FACT-O) and Female Sexual Function Index (FSFI). Each questionnaire can be filled out by women with different types of gynecological cancer, and the FSFI measures sexual problems that women may experience after cancer treatment.

Is There a Role for Exercise When Treating Patients with Cancer with Immune Checkpoint Inhibitors? A Scoping Review.

The impact of using exercise as a non-pharmacological intervention in patients with cancer receiving immune checkpoint inhibitors (ICIs) is not well known. Our objective was to determine the extent of, and identify gaps within, available literature addressing the effect of exercise on (a) oncological outcomes and (b) quality of life (QoL) in patients with cancer receiving ICIs, and (c) the underlying biological mechanisms for such effects. We conducted searches across EMBASE, APA PsycInfo and Ovid MEDLINE(R). Studies were eligible if they addressed at least one aspect of the objective and were available in the English language. Results were synthesised using a narrative approach and subsequently discussed with multidisciplinary stakeholders. As of the final search on 5 April 2022, 11 eligible studies were identified, of which 8 were preclinical and 3 were clinical. Clinical studies only focused on QoL-related outcomes. When studies were grouped by whether they addressed oncological outcomes (n = 7), QoL (n = 5) or biological mechanisms (n = 7), they were found to be heterogeneous in methodology and findings. Additional evidence, particularly in the clinical setting, is required before robust recommendations about whether, and how, to include exercise alongside ICI treatment can be made.

Cancer staff in an NHS cancer center: infections, vaccination, stress and well-being support during the COVID-19 pandemic.

Aim: To evaluate the impact of the pandemic on the well-being of cancer staff and determine the uptake of opt-in mitigation strategies. Materials & methods: Staff at Guy's Cancer Centre (London, UK) participated in an anonymized survey between May and August 2021. Results: Of 1182 staff, 257 (21.7%) participated. Ethnicity (p = 0.020) and comorbidity burden (p = 0.022) were associated with SARS-CoV-2 infection status. Of 199 respondents, seven (3.6%) were vaccine-hesitant, which was associated with low flu vaccine uptake (p < 0.001). Greater stress was associated with younger age (p = 0.030) and redeployment (p = 0.012). Lack of time and skepticism were barriers to using mental well-being resources. Conclusion: Albeit cautious, numerous trends the authors observed echo those in the published literature. Improved accessibility, awareness and utility of mental well-being resources are required.

COVID-19 is caused by the SARS-CoV-2 virus. The pandemic has applied immense pressure to healthcare workers, putting their physical and mental well-being at risk. However, the impact for cancer staff, specifically, is less known. In a survey of 257 cancer staff at Guy's Cancer Centre (London, UK; May­August 2021), the authors found that staff of particular ethnic groups, or with pre-existing illnesses, appeared more likely to become infected with SARS-CoV-2. Few staff were hesitant about SARS-CoV-2 vaccination, appearing more common among those not receiving the flu vaccine. For many, stress increased over time. However, barriers prevent staff from using mental well-being resources. With findings from larger studies, this work will be useful for strategies protecting cancer staff well-being.

Risk of COVID-19 death in cancer patients: an analysis from Guy's Cancer Centre and King's College Hospital in London.

BACKGROUND: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. METHODS: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. RESULTS: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). CONCLUSIONS: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.

COVID-19 Risk Factors for Cancer Patients: A First Report with Comparator Data from COVID-19 Negative Cancer Patients.

Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1st March and 31st July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.

Update from the ReIMAGINE Prostate Cancer Screening Study NCT04063566: Inviting Men for Prostate Cancer Screening Using Magnetic Resonance Imaging.

ReIMAGINE Screening is a single-centre study assessing the feasibility of biparametric magnetic resonance imaging as a screening tool for prostate cancer. The study outcomes will take us a step towards more accurate and less harmful prostate cancer screening.

Cohort profile: King's Health Partners bladder cancer biobank.

BACKGROUND: Bladder cancer (BC) is the 9th most common cancer worldwide, but little progress has been made in improving patient outcomes over the last 25 years. The King's Health Partners (KHP) BC biobank was established to study unanswered, clinically relevant BC research questions. Donors are recruited from the Urology or Oncology departments of Guy's Hospital (UK) and can be approached for consent at any point during their treatment pathway. At present, patients with bladder cancer are approached to provide their consent to provide blood, urine and bladder tissue. They also give access to medical records and linkage of relevant clinical and pathological data across the course of their disease. Between June 2017 and June 2019, 531 out of 997 BC patients (53.3%) gave consent to donate samples and data to the Biobank. During this period, the Biobank collected fresh frozen tumour samples from 90/178 surgical procedures (of which 73 were biopsies) and had access to fixed, paraffin embedded samples from all patients who gave consent. Blood and urine samples have been collected from 38 patients, all of which were processed into component derivatives within 1 to 2 h of collection. This equates to 193 peripheral blood mononuclear cell vials; 238 plasma vials, 224 serum vials, 414 urine supernatant vials and 104 urine cell pellets. This biobank population is demographically and clinically representative of the KHP catchment area. CONCLUSION: The King's Health Partners BC Biobank has assembled a rich data and tissue repository which is clinically and demographically representative of the local South East London BC population, making it a valuable resource for future BC research.

Frequency of Pathogenic Germline Variants in CDH1, BRCA2, CHEK2, PALB2, BRCA1, and TP53 in Sporadic Lobular Breast Cancer.

BACKGROUND: Invasive lobular breast cancer (ILC) accounts for approximately 15% of invasive breast carcinomas and is commonly associated with lobular carcinoma in situ (LCIS). Both have been shown to have higher familial risks than the more common ductal cancers. However, there are little data on the prevalence of the known high and moderate penetrance breast cancer predisposition genes in ILC. The aim of this study was to assess the frequency of germline variants in CDH1, BRCA2, BRCA1, CHEK2, PALB2, and TP53 in sporadic ILC and LCIS diagnosed in women ages ≤60 years. METHODS: Access Array technology (Fluidigm) was used to amplify all exons of CDH1, BRCA2, BRCA1, TP53, CHEK2, and PALB2 using a custom-made targeted sequencing panel in 1,434 cases of ILC and 368 cases of pure LCIS together with 1,611 controls. RESULTS: Case-control analysis revealed an excess of pathogenic variants in BRCA2, CHEK2, PALB2, and CDH1 in women with ILC. CHEK2 was the only gene that showed an association with pure LCIS [OR = 9.90; 95% confidence interval (CI), 3.42-28.66, P = 1.4 × 10-5] with a larger effect size seen in LCIS compared with ILC (OR = 4.31; 95% CI, 1.61-11.58, P = 1.7 × 10-3). CONCLUSIONS: Eleven percent of patients with ILC ages ≤40 years carried germline variants in known breast cancer susceptibility genes. IMPACT: Women with ILC ages ≤40 years should be offered genetic screening using a panel of genes that includes BRCA2, CHEK2, PALB2, and CDH1.

The acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) inhibits glutathione synthetase in vitro; a clue to the mechanism of 5-oxoprolinuric acidosis?

1. Metabolic acidosis due to accumulation of l-5-oxoproline is a rare, poorly understood, disorder associated with acetaminophen treatment in malnourished patients with chronic morbidity. l-5-Oxoprolinuria signals abnormal functioning of the γ-glutamyl cycle, which recycles and synthesises glutathione. Inhibition of glutathione synthetase (GS) by N-acetyl-p-benzoquinone imine (NAPQI) could contribute to 5-oxoprolinuric acidosis in such patients. We investigated the interaction of NAPQI with GS in vitro. 2. Peptide mapping of co-incubated NAPQI and GS using mass spectrometry demonstrated binding of NAPQI with cysteine-422 of GS, which is known to be essential for GS activity. Computational docking shows that NAPQI is properly positioned for covalent bonding with cysteine-422 via Michael addition and hence supports adduct formation. 3. Co-incubation of 0.77 µM of GS with NAPQI (25-400 µM) decreased enzyme activity by 16-89%. Inhibition correlated strongly with the concentration of NAPQI and was irreversible. 4. NAPQI binds covalently to GS causing irreversible enzyme inhibition in vitro. This is an important novel biochemical observation. It is the first indication that NAPQI may inhibit glutathione synthesis, which is pivotal in NAPQI detoxification. Further studies are required to investigate its biological significance and its role in 5-oxoprolinuric acidosis.