The impact of the SARS-CoV-2 pandemic upon pancreatic cancer treatment (CONTACT Study): A UK national observational cohort study

Background: The SARS-CoV-2 pandemic has had an unprecedented impact on healthcare systems, and cancer patients were amongst the most vulnerable. CONTACT is a national multidisciplinary study assessing the impact of the SARS-CoV-2 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). Method(s): A novel, mixed prospective and retrospective design, with retrospective case identification of both cohorts, and trainee-performed data collection. The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID cohort (07/01/ 2019-03/03/2019) were compared to a cohort diagnosed during the first wave of SARS-CoV-2 in the UK ('COVID' cohort, 16/03/2020-10/05/ 2020), with 12-month follow-up. Result(s): Among 984 patients (pre-COVID: N=483, COVID: N=501), across 96 hospitals, the COVID cohort were less likely to receive staging investigations other than CT scan (148/501, 29.5% vs 180/486, 37.2%;p=0.01). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (42/77, 54.5% vs 72/94, 76.6%, p=0.001) and increase in the proportion recommended neoadjuvant therapy (35/77, 45.5% vs 22/94, 23.4%, p=0.002). Among patients within a non-curative pathway, fewer patients were recommended (201/424, 47.4% vs 223/389, 57.3%, p=0.004) or received palliative therapy (87/424, 20.5% vs 103/389, 26.5%, p=0.045). Ultimately, fewer patients in the COVID cohort underwent resection surgery (29/501, 6.4% vs 45/483, 9.3%, OR 0.64, 95%CI: 0.37- 0.97, p=0.036), whilst more patients received no treatment whatsoever (347/ 501, 69.3% vs 286/483, 59.2% p=0.009). There was no difference in median survival between the COVID and pre-COVID cohorts, (105 days, IQR: 86-124 vs 130 days, IQR: 108-157, p=0.093). Conclusion(s): The CONTACT study confirms alarming reduction in the staging and treatment provided to patients with PDAC diagnosed during the SARS-CoV-2 pandemic. Restoration of cancer services to pre-pandemic standards must be urgently addressed.

Identification of a microbiome signature predicting immune checkpoint inhibitor outcomes across multiple cancer types in the MITRE study

Background: The gut microbiome is implicated as a biomarker of response to immune checkpoint inhibitors (ICIs), based on preclinical mouse models and preliminary observations in limited patient series. Furthermore, early reports suggest faecal microbial transfer may have therapeutic potential, converting ICI nonresponders to responders. So far, identification of specific responsible bacterial taxa has been inconsistent between published studies, which limits future application. By culturing and metagenomic sequencing of stool sample bacteria, our group has identified a unique microbiome signature, which appears to be predictive of response to ICIs across all key published series as well as our own melanoma patient series (Robinson M et al, J Immunother Cancer 2020;8(suppl 3):A404). Because the patient numbers in all published series remain low, we are now further exploring and validating this microbiome signature in a larger scale study across several different cancer types. Methods: MITRE (Microbiome Immunotherapy Toxicity and Response Evaluation) is a UK NIHR portfolio multi-centre prospective study funded jointly by Cancer Research UK and Microbiotica (NCT04107168) Up to 1800 patients receiving ICIs will be recruited over a 5-year period. In the first stage 1: anti-PD1 monotherapy, cohort 2: antiPD1+anti-CTLA-4 combination), renal cancer (cohort 3: anti-PD(L)1+kinase inhibitor, cohort 4: anti-PD1+anti-CTLA-4 combination) and nonsmall cell lung cancer (cohort 5: anti-PD(L)1 monotherapy, cohort 6: antiPD(L)1+chemotherapy+anti-angiogenic) are being recruited, 50 patients to each cohort. A cohort-specific, simulation-based power calculation will then be performed, guiding subsequent recruitment. Stool and blood are collected prior to treatment, at 3, 6 and 12 months, or disease progression (whichever is sooner), as well as after any grade >3 immunerelated adverse events. Patients collect and freeze their own stool samples which are cultured and subjected to shotgun metagenomic sequencing. Plasma, whole blood buffy coat, RNA and PBMCs are being stored for correlative studies. Any tumour, or organ biopsies, taken prior to and during treatment are also being collected. Clinical data collection includes treatment, disease response (using RECIST criteria) and toxicity. The primary outcome measure is 1 year progression-free survival. Patients are also asked to invite a household member to be part of the study control group. Recruitment started in July 2020 The Covid-19 pandemic hindered recruitment last year, but the protocol was amended to incorporate a Covid-19 substudy (to document testing, infection and vaccination) and adapt processes for remote trial delivery as much as possible. As of February 2021, 7 sites have opened, 17 patients and 5 household controls have been recruited.

The impact of COVID-19 on clinical cancer care: An individual-patient level analysis

Background: At the outset of the COVID-19 pandemic, concerns for the safety of patients receiving anti-cancer treatment coupled with pressures on healthcare services prompted review of standard clinical care pathways in the UK. Revised consensus treatment guidelines were generated. Individual patient-level data regarding actual treatment modifications implemented in clinical practice are lacking. Methods: All anti-cancer treatment plans of patients with breast, lung, renal, hepatopancreatobiliary, CNS cancers and melanoma attending a single academic cancer centre in the UK between 16 March and 31 May 2020 were reviewed and any modifications to standard practice were documented. The effect of patient (age, ECOG performance status [PS], sex) and cancer (site, stage, treatment intent) characteristics on likelihood of treatment modifications were analysed using univariable and multivariable models. Results: Treatment plans for 925 patients were reviewed: median patient age was 63 (range 19-97);66% were female;73% were PS 0-1;45% were on a curative pathway. Overall, 47% of all patients had one or more modifications made to their treatment plans: 53% of surgeries (primarily being delayed);41% of radiotherapy (primarily reduced fractions delivered);39% of systemic therapy prescriptions. 96-100% of all systemic therapy modifications resulted in treatment deescalation, excluding endocrine therapy used as a bridge to defer primary breast cancer surgery. Biological therapy was predominantly interrupted (49%), immunotherapy was mostly omitted entirely (36%), and chemotherapy varied between interruptions (39%) or omissions (31%). Relative to the likelihood of modification to chemotherapy, surgery was significantly more likely to be modified (OR 1.69 95%CI 1.20-2.38). Chemotherapy, radiotherapy, biological therapy and immunotherapy were all modified to a similar degree. Multivariate analysis identified PS ≥2 (OR 1.79, 95% CI 1.18- 2.75), but not patient age, as a predictor of treatment modification. Some tumour types were less likely to undergo any modification: stage 1-3 lung (OR 0.13, 95%CI 0.04-0.37), stage 4 lung (OR 0.26 95%CI 0.24-0.60) and stage 4 renal cancer (OR 0.22 95%CI 0.09-0.52). Conclusions: This single centre analysis demonstrated almost half of cancer patients had their treatment modified, the overwhelming majority resulting in treatment de-escalation. The impact of the treatment modifications on overall cancer patient outcomes remains to be determined.

SARS-CoV-2 Infection and Antibody Seroprevalence among UK Healthcare Professionals Working with Cancer Patients during the First Wave of the COVID-19 Pandemic.

AIMS: The proportion of UK oncology healthcare professionals (HCPs) infected with SARS-CoV-2 during the COVID-19 pandemic's first wave is unknown. The primary aim of this study was to determine the SARS-CoV-2 infection and seroprevalence rates among HCPs. MATERIALS AND METHODS: Patient-facing oncology HCPs working at three large UK hospitals during the COVID-19 pandemic's first wave underwent polymerase chain reaction (PCR) and antibody testing [Luminex and point-of-care (POC) tests] on two occasions 28 days apart (June-July 2020). RESULTS: In total, 434 HCPs were recruited: nurses (58.3%), doctors (21.2%), radiographers (10.4%), administrators (10.1%); 26.3% reported prior symptoms suggestive of SARS-CoV-2. All participants were PCR negative during the study, but 18.4% were Luminex seropositive on day 1, of whom 42.5% were POC seropositive. Nurses had the highest seropositive prevalence trend (21.3%, P = 0.2). Thirty-eight per cent of seropositive HCPs reported previous SARS-CoV-2 symptoms: 1.9 times higher odds than seronegative HCPs (P = 0.01). Of 400 participants retested on day 28, 13.3% were Luminex seropositive (92.5% previously, 7.5% newly). Thirty-two per cent of initially seropositive HCPs were seronegative on day 28. CONCLUSION: In this large cohort of PCR-negative patient-facing oncology HCPs, almost one in five were SARS-CoV-2 antibody positive at the start of the pandemic's first wave. Our findings that one in three seropositive HCPs retested 28 days later became seronegative support regular SARS-CoV-2 PCR and antibody testing until widespread immunity is achieved by effective vaccination.

Detection of breastmilk antibodies targeting SARS-CoV-2 nucleocapsid, spike and receptor-binding-domain antigens.

A 40-year-old female was found to have strongly neutralizing SARS-CoV-2 breastmilk IgA and IgG antibodies reactive against multiple SARS-CoV-2 antigens at 2.5 months after documented infection with SARS-CoV-2. At 6.5 months following the infection, she remained positive for breastmilk and serum SARS-CoV-2 neutralizing antibodies. Holder breast milk pasteurization did not diminish SARS-CoV-2 antibody titres but it reduced its neutralizing capacity, while serum heat inactivation had no negative effect on SARS-CoV-2 serum antibody levels and neutralizing capacity. Current data on SARS-CoV-2 and breastmilk are reviewed.