The Impact of COVID-19 on Systemic Anti-Cancer Treatment Delivery in Scotland

Understanding the impact of the COVID19 pandemic on systemic anti-cancer therapy delivery (SACT) is crucial for a full appreciation of the short and long-term consequences for cancer patients and for planning future cancer care. In this article we report real-time national SACT delivery data from NHS Scotland. We demonstrate an initial rapid reduction in patient attendance for SACT of 28.7% with a subsequent rapid and full recovery following service re-design. Regional variation in the magnitude of impact on SACT delivery was observed, but nadirs occurred at the same time and the rate of recovery was similar across all regions. This recovery reected a co-ordinated national approach and associated patient and clinician support structures which facilitated the creation of COVID-19 protected areas for SACT delivery in Scottish cancer centres and enabled rapid sharing of successful and innovative strategies. The data shows that these actions have limited the disadvantage to cancer patients.

Early studies suggested that cancer patients were at increased risk of SARS-CoV-2 infection and that SACT was associated with severe COVID-19 outcomes (2). Additionally, delivery of SACT while maintaining social distancing is challenging. Patient attendance for treatment increases the risk of transmission of infection for both patients and staff. These factors led to uncertainty for cancer clinicians (3).
In response, the UK National Institute of Clinical Excellence (NICE) produced a guideline regarding the delivery of systemic anticancer treatments , while in Scotland, the Scottish Government introduced new interim governance arrangements and clinical guidance for cancer medicines (4,5).
UK cancer units adapted and clinicians consulted with patients regarding the potential risk of continuing treatment. Focus turned to immunosuppressive regimes and immune checkpoint inhibitors due to the risk of neutropenia and cytokine storm respectively (6). Ultimately, these adaptations led to a reduction in delivery of SACT. In England and Northern Ireland, data suggested patient attendances for SACT reduced initially by 45-66%, (7).
The need for evidence to guide decisions led to the development of prospective observational studies such as, the UK Coronavirus Cancer Monitoring Project (UKCCMP) (8). UKCCMP has rapidly collected data with weekly reports provided to 96 participating centres.
The UKCCMP alongside the US COVID-19 and Cancer Consortium (CCC19) (9) have recently demonstrated that outcomes in cancer patients with COVID-19 is largely driven by age, gender and comorbidity. No detrimental effect of SACT was observed on patient outcomes. These new data provide welcome reassurance that SACT including chemotherapy, should be offered to patients if possible. However, these studies had short follow-up time and their retrospective nature led to high proportions of missing data and incomplete adjustment for confounders, and consequently many unanswered questions (10).
Knowledge of the extent of the impact COVID-19 on cancer treatment delivery is important for future planning, and to minimise disadvantage to patients in the event of a resurgence of infection. In this rapid short report, we present real-time nationwide data from Scotland on cancer patient attendance for SACT during the COVID19 pandemic. We demonstrate the impact on a regional and national level and discuss reasons for patterns seen and conclusions for future SACT delivery during the ongoing COVID-19 pandemic.

Methods
Cancer care in NHS Scotland is delivered across 14 geographic health boards and co-ordinated by 3 Regional networks; North of Scotland Cancer Alliance (NCA, population 1,396,780), West of Scotland Cancer Network (WoSCAN, population 3,158,940), and South East Cancer Network (SCAN, population 1,509,500). In all Health boards SACT is prescribed using the same electronic prescribing system, ChemoCare® (CIS Oncology Ltd, Belfast, UK). This enables data on the numbers of patients attending for SACT to be extracted rapidly and in real time.
Following the UK wide lockdown on 23 rd March 2020, patient attendance numbers were collated weekly from each health board and grouped by the responsible regional Cancer Network, for discussion and review at national level. Patient attendance for six weeks prior to lockdown were collected for comparison.

Results
Adult patient attendances for SACT in NHS Scotland showed a sudden decrease that was not seen in previous years, in the week preceding the UK lockdown. This decrease continued until the week beginning 13 th April 2020 ( Figure 1A). A decrease of 28.7% was seen in the period 2 nd March to 19 th April 2020, by comparison to average weekly attendance in the six week period 20 th January to 1 st March ( Figure 1B).
Subsequently a recovery from this point is observed with patient attendances returning towards pre-COVID levels by the week beginning 20 th July at -7.5% by comparison to average weekly attendance in the 6 week period 20th January -1st March ( Figure 1A&B). Comparing to 2019, attendance in April 2020 decreased by 17.2%, and in June 2020 by 3.1% ( Figure 1D).
Our national data also enable us to explore regional variation between the three cancer networks (Figure1C). Interestingly, a similar fall in patient attendances was seen in SCAN and in NCA, but a greater and more rapid decrease in WoSCAN. The rate of recovery in all regions appears similar.
On assessment of the impact of route, intravenous (IV), subcutaneous (SC) and oral (PO) administration of SACT were all reduced. The greatest decrease was seen for IV and SC, while PO SACT was largely maintained (data not shown).This pattern is the same for all regional networks.

Discussion
In this report we demonstrate the impact of COVID-19 on SACT delivery in Scotland. The initial decrease observed re ects uncertainty of the risks associated with SACT at the beginning of the pandemic. This timing pre-dates the UK lockdown indicating an awareness of early, small cohort data from other countries. The subsequent rapid recovery re ects Scottish government interim governance arrangements for cancer medicines that enabled evidence based, co-ordinated and transparent quick adaptions to practice based on clinical consensus, and the creation of COVID-19 protected SACT delivery in Scottish cancer centres. Subsequently, larger observational studies, including UKCCMP provided weekly distribution of real-time data to UK investigators and provided reassurance that SACT should be offered to patients if possible. This generated con dence to sustain recovery of SACT delivery in NHS Scotland. Overall these actions, as our data shows, have been important in limiting the disadvantage to cancer patients.
A differing impact on SACT delivery was observed at a regional level, with a greater initial decrease seen in WoSCAN. This may re ect the highest incidence of COVID-19 in Scotland being observed in 2 of the 4 health boards (NHS Greater Glasgow and Clyde and NHS Lanarkshire), that together comprise 73% of the WoSCAN population. Despite differences in the extent and rate of decrease between regions, the rate of recovery in all regions appears similar. A key reason for this is likely to be the co-ordinated national recovery approach.
The lesser impact seen on oral SACT may be explained by the drugs mechanism of action and less need for hospital attendance which may have encouraged clinicians and patients to continue treatment.
The high quality and granularity of NHS Scotland cancer data is enabling further research to allow a deeper understanding of the impact of SACT in different tumour types. This includes reporting short term outcomes to allow rapid investigation of the impact of COVID-19 and associated response and recovery cancer pathway modi cations.
A re-surgence of SARS-CoV-2 infection is predicted as lockdown restrictions are lifted. The ability to learn from experience will form a key part of future strategies aimed at avoiding any subsequent decrease in patient attendance for SACT if a COVID-19 resurgence occurs . It is evident that not all regions of the United Kingdom have been affected equally in terms of COVID-19 incidence [8]. Similarly the impact of SACT delivery may differ according to administration route. The impact of COVID-19 upon cancer referrals, diagnostic services, and other treatment modalities will also impact SACT delivery, and may disproportionally affect some tumour types. This is the subject of ongoing analysis to ensure the observed recovery in SACT in NHS Scotland is sustained.