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Simple Summary: The COVID-19 pandemic has resulted in unprecedented changes to the life of patients with cancer. In this study, we aim to evaluate the impact of the COVID-19 pandemic on the mental health and general well-being of patients with colorectal cancer by carrying out a prospective longitudinal questionnaire. We found that around one in four participants reported symptoms of anxiety and poor well-being, with 15% at risk of moderate to severe depression. Amongst others, those who were worried that the COVID-19 pandemic would have an effect on their mental health were most at risk of anxiety, depression, and poor well-being. Screening for the mental health impact of the COVID-19 pandemic on patients is essential to allow timely action from all key stakeholders in order to avoid potentially longer-term detrimental consequences. The COVID-19 pandemic has resulted in unprecedented changes to the lives of patients with cancer. To evaluate the impact of the COVID-19 pandemic on the mental health and well-being of patients with colorectal cancer, we conducted a prospective longitudinal questionnaire study at a UK tertiary cancer centre. In total, 216 participants were included: mean age 65 years, 57% (n = 122) male, 92% (n = 198) of white ethnicity. Amongst participants who completed the screening psychometric questionnaire, 24% (n = 48/203) reported anxiety (GAD-7 ≥ 5), 15% (n = 31/204) depressive symptoms (PHQ-9 ≥ 10), 3% (n = 5/190) probable post-traumatic stress disorder (PC-PTSD-5 ≥ 4), and 31% (n = 66/213) poor well-being (WHO-5 < 50). In the subgroup (n = 95/216, 44%) who consented to and completed a follow-up survey 6 months later, there was a significant increase in the number of participants at risk of depression (4% vs. 13%, p = 0.021). Self-reported concern about the COVID-19 pandemic impacting one's mental health is associated with increased likelihood of anxiety, depression, and poor well-being, in respective multivariate analyses. In conclusion, screening for the mental health impact of the COVID-19 pandemic is essential to ensure timely action from all key stakeholders and to avoid potentially longer-term detrimental consequences. [ABSTRACT FROM AUTHOR]

Background: Metastatic colorectal cancer is one of the commonest causes of cancer and cancer-related deaths.1 The prognosis remains poor and successive treatment options remain limited.2 Many patients will run out of treatment options before they become medically unfit for therapy.3 Cancer drug innovation presents both opportunities and dilemmas as access to innovative cancer medications can be limited by a significant delay between clinical trials, licensing, and positive drug guidance.4,5 Consequently, where no commissioned alternative medicine exists some pharmaceutical companies operate compassionate usage access schemes (Figure 1). These allow cancer treatment with investigational, unlicensed, or off-label medicines as soon as early evidence of potential benefit emerges.6 There is a paucity of information regarding compassionate schemes. This analysis was performed to ascertain real-world data on patients enrolled in these schemes. Methods: Single-centre study conducted at The Christie Hospital, Manchester, UK. We reviewed the process of pharmacy drug set-up and maintenance by undertaking a survey of disease group pharmacists. We undertook a retrospective audit using an electronic patient record of patients who entered into a compassionate scheme between 2018 and 2020. This analysis focused on 27 patients with a diagnosis of metastatic colorectal cancer receiving compassionate medication who possessed the BRAF mutation (mBRAF V600E) or MSI-H status. We analysed 17 mBRAF patients treated with a triplet combination (encorafenib, binimetinib and cetuximab), and subsequently, doublet (encorafenib and cetuximab), as defined by the BEACON study, and 10 MSI-high patients on compassionate nivolumab.7,8 Results: Our survey of compassionate medication across 14 disease groups demonstrated the approval process is lengthy and resource intensive. The average approval time was variable, but pharmacy set-up time could take several days depending on the drug or regimen. However, this is countered by our analysis of 27 meta-static colorectal cancer patients. Most patients were fit (> 88% PS ≤ 1, 50% had no known co-morbidities) and for 62% this represented third- line therapy, in a cancer setting with limited or no treatment options. Patients received 10 cycles of treatment on average before progression or unsuitability, with a mean duration on the treatment of 120 days (15–317) on the triplet/doublet combination and 205 days on nivolumab (range: 1–663), demonstrating benefit. Patient demand was uninhibited by geographical distance (> 30% of patients lived 20+ miles away from the treatment centre) and the possibility of hope and life extension with further treatment. Conclusion: Our audit demonstrates that patients received compassionate drugs that were subsequently commissioned by NHSE, with some benefiting from treatment for a considerable period. This suggests there was both a moral gain and a survival advantage over best supportive care; however, there remains limited real-world data and further research is required. Access to compassionate schemes is controversial and limited as they can be seen to promote healthcare inequity, creating a post-code lottery, as they may not be available in some regions, circumvent existing guidelines or benefit pharmaceutical companies by allowing early data and market access. Compassionate usage recognises a human side to drug development which requires a moral balance between patients. [ABSTRACT FROM AUTHOR]

Tumour-infiltrating CD8+ cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts. We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8+, CD20+, FoxP3+, and CD68+ cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II–III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab. Both trials included patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1. Immune marker predictors were analysed by multiple regression, and the prognostic and predictive values of markers for colorectal cancer recurrence-free interval by Cox regression were assessed using the SCOT cohort for discovery and QUASAR 2 cohort for validation. After exclusion of cases without tissue microarrays and with technical failures, and following quality control, we included 2340 cases from the SCOT trial and 1069 from the QUASAR 2 trial in our analysis. Univariable analysis of associations with recurrence-free interval in cases from the SCOT trial showed a strong prognostic value of intraepithelial CD8 (CD8IE) as a continuous variable (hazard ratio [HR] for 75th vs 25th percentile [75 vs 25] 0·73 [95% CI 0·68–0·79], p=2·5 × 10−16), and of intrastromal FoxP3 (FoxP3IS; 0·71 [0·64–0·78], p=1·5 × 10−13) but not as strongly in the epithelium (FoxP3IE; 0·89 [0·84–0·96], p=1·5 × 10−4). Associations of other markers with recurrence-free interval were moderate. CD8IE and FoxP3IS retained independent prognostic value in bivariable and multivariable analysis, and, compared with either marker alone, a composite marker including both markers (CD8IE-FoxP3IS) was superior when assessed as a continuous variable (adjusted [a]HR75 vs 25 0·70 [95% CI 0·63–0·78], p=5·1 × 10−11) and when categorised into low, intermediate, and high density groups using previously published cutpoints (aHR for intermediate vs high 1·68 [95% CI 1·29–2·20], p=1·3 × 10−4; low vs high 2·58 [1·91–3·49], p=7·9 × 10−10), with performance similar to the gold-standard Immunoscore. The prognostic value of CD8IE-FoxP3IS was confirmed in cases from the QUASAR 2 trial, both as a continuous variable (aHR75 vs 25 0·84 [95% CI 0·73–0·96], p=0·012) and as a categorical variable for low versus high density (aHR 1·80 [95% CI 1·17–2·75], p=0·0071) but not for intermediate versus high (1·30 [0·89–1·88], p=0·17). Combined evaluation of CD8IE and FoxP3IS could help to refine risk stratification in colorectal cancer. Investigation of FoxP3IS cells as an immunotherapy target in colorectal cancer might be merited. Medical Research Council, National Institute for Health Research, Cancer Research UK, Swedish Cancer Society, Roche, and Promedica Foundation. [ABSTRACT FROM AUTHOR]