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Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3–2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days−19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients.

Background\ud There is a considerable global burden of invasive group B streptococcal (GBS) disease. Vaccines are being developed for use in pregnant women to offer protection to neonates.\ud \ud Objective\ud To estimate the potential impact and cost-effectiveness of maternal immunisation against neonatal and maternal invasive GBS disease in the UK.\ud \ud Methods\ud We developed a decision-tree model encompassing GBS-related events in infants and mothers, following a birth cohort with a time horizon equivalent to average life expectancy (81 years). We parameterised the model using contemporary data from disease surveillance and outcomes in GBS survivors. Costs were taken from NHS sources and research studies. Maternal immunisation in combination with risk-based intrapartum antibiotic prophylaxis (IAP) was compared to the current standard practice of risk-based IAP alone from an NHS and Personal Social Services (health-provider) perspective. We estimated the cases averted and cost per QALY gained through vaccination. One-way sensitivity analysis, scenario analysis and probabilistic sensitivity analysis were performed.\ud \ud Results\ud An effective maternal immunisation programme could substantially reduce the burden of GBS disease. The deterministic analysis estimated the threshold cost-effective price for a GBS vaccine to be £54 per dose at £20,000/QALY (£71 per dose at £30,000/QALY). Results were most sensitive to assumptions on disease incidence, sequelae rate and vaccine efficacy. Probabilistic analysis showed 90.66% of iterations fell under the £30,000 threshold at a vaccine price of £55. Inclusion of modest prevention of stillbirths and/or, preterm births, carer health impacts, maternal GBS deaths and 1.5% discounting improved cost-effectiveness compared to the base case. Lowering vaccine strain coverage made the vaccine less cost-effective. A key limitation is that the properties of the final GBS vaccine are unknown.\ud \ud Conclusions\ud Maternal GBS immunisation is expected to be cost-effective, even at a relatively high vaccine price.

Objective\ud To estimate neonatal health benefits and healthcare provider costs of a theoretical Group B streptococcal (GBS) hexavalent maternal vaccination programme in The Gambia, a low-income setting in West Africa.\ud \ud Methods\ud A static decision analytic cost-effectiveness model was developed from the healthcare provider perspective. Demographic data and acute care costs were available from studies in The Gambia undertaken in 2012–2015. Further model parameters were taken from United Nations and World Health Organisation sources, supplemented by data from a global systematic review of GBS and literature searches. As vaccine efficacy is not known, we simulated vaccine efficacy estimates of 50–90%. Costs are reported in US dollars. Cost-effectiveness thresholds of one (US$473, very cost effective) and three (US$1420, cost effective) times Gambian GDP were used.\ud \ud Results\ud Vaccination with a hexavalent vaccine would avert 24 GBS disease cases (55%) and 768 disability adjusted life years compared to current standard of care (no interventions to prevent GBS disease). At vaccine efficacy of 70%, the programme is cost-effective at a maximum vaccine price per dose of 12 US$ (2016 US$), and very cost-effective at a maximum of $3/dose. The total costs of vaccination at $12 is $1,056,962 for one annual cohort of Gambian pregnant women. One-way sensitivity analysis showed that GBS incidence was the most influential parameter on the cost effectiveness ratio.\ud \ud Conclusion\ud The introduction of a hexavalent vaccine would considerably reduce the current burden of GBS disease in The Gambia but to be cost-effective, the vaccine price per dose would need to be $12/dose or less.

TPS4120 Background: Adjuvant chemotherapy (ACT) is routinely offered to patients with high risk (HR) stage II or stage III CRC following potentially curative surgery. Over 50% of stage III and > 80% of stage II patients are cured by surgery alone but are being exposed to unnecessary chemotherapy with short- and long-term side effects. Post-operative ctDNA identifies minimal residual disease (MRD) after surgery in CRC. Our national study, TRACC, compares ctDNA guided versus standard of care (SoC) decision making in patients undergoing ACT. Methods: This is a UK-wide, multi-centre, prospective, two-arm, randomised trial. Patients with HR risk stage II or stage III CRC who have undergone R0 resection and have detectable ctDNA in their pre-surgical sample are eligible. Patients who undergo neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer with detectable ctDNA pre-CRT are also eligible. Patients are randomised in a 1:1 ratio to receive either SoC ACT or ctDNA guided ACT. In the ctDNA guided arm, patients who are ctDNA negative post-operatively have chemotherapy de-escalated i.e., 3 months(m) of Capecitabine and Oxaliplatin (CAPOX) doublet ACT is reduced to 3 m single agent Capecitabine; 6 m single agent Capecitabine reduced to no chemotherapy. In this group, ctDNA is re-tested at 3 months and if detectable, patients receive 3 months of CAPOX. Primary end-point is 3-year disease free survival (DFS). Secondary end-points include overall survival, neurotoxicity, quality of life and health economics. Based on a standard 3-year DFS of 75% in SoC ACT arm, to demonstrate a non-inferiority margin of 1.25, 810 patients are required per arm (85% power, α = 0.1). Stratification is by tumour staging and site of primary tumour. Target accrual is over 4 years. The study opened to recruitment in January 2020 and is supported by the MRC-NIHR Efficacy and Mechanism Evaluation Grant ( NIHR128529 ). Clinical trial information: NCT04050345 .

Group B Streptococcus (GBS) is a leading cause of invasive disease in infants, causing mortality and neurodevelopmental impairment (NDI) in survivors. This article estimates the percentage of survivors of infant GBS disease with NDI., Background Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants