The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair–deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers’ tissue of origin.

/pdf/mismatch-repair-deficiency-predicts-response-of-solid-tumors-2mgnsq9rdf.pdf

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor.

https://escholarship.org/content/qt7gf847t7/qt7gf847t7.pdf?t=qaejdd

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Summary Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015–35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015–35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries—a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015–35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015–35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015–35 (–$14·9 billion in low-income countries; –$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (–$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(15)00222-3.pdf

Expanding global access to radiotherapy

http://static.guim.co.uk/ni/1432986420413/Ann-Oncol-2015.pdf

A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS)

Global colorectal cancer burden in 2020 and projections to 2040

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(20)30217-5.pdf

Cancer guidelines during the COVID-19 pandemic.

COVID-19: consequences for higher education.

Cancer care in the time of COVID-19.

Pink Ribbons, Inc

www.thelancet.com/oncology Vol 17 May 2016 e182 UK Chancellor of the Exchequer, George Osborne, made a surprise announcement during last week’s budget. From 2018, drinks in which the sugar content exceeds 8 grams per 100 millilitres will be liable to a levy, equivalent to 24 pence per litre. As things stand, this will aff ect the regular versions of Coca-Cola, Pepsi Cola, and Red Bull. Drinks with a sugar content of 5–8 grams per 100 millilitres will be taxed at the equivalent of 18 pence per litre. Fruit juices and milk-based drinks will be exempt (although some of these contain far more sugar than a typical soft drink). The Government expects the tax to raise £520 million in the fi rst year, money which will be spent on school sports to encourage healthier behaviour. The focus on fizzy drinks may be driven by expediency—these are highly visible items which provide no nutritional benefit. A tax on confectionery or processed food would be tricky to formulate. Besides, the main target is British children and teenagers, around one-third of whom are overweight or obese. According to some estimates, every day the average 11–18 year old in the UK consumes roughly three times their recommended quantity of sugar. Soft drinks appear to be this group’s single largest source of sugar. “Overweight and obese children are more likely to be overweight and obese adults, and that increases your risk of up to ten different cancers”, said Chit Selvarajah of Cancer Research UK, London, UK. A report commissioned by the organisation suggested that if current trends continue, the UK will face some 670 000 new cases of cancer caused by obesity over the next 20 years. “It is brilliant to see bold action from the Government on this issue—it is a really important first step in terms of addressing childhood obesity”, Selvarajah told The Lancet Oncology. S imon Capewel l f rom the Faculty of Public Health, (London, UK), expressed qualms over the structure of the levy. “Industry will work very hard to reduce sugar content to 1% less than the cut-off point”, he explained. “A tax graded gram-by-gram would exert steady pressure on them to reduce the sugar content down towards zero”. But he welcomed the measure. “The Government has stated very publicly that they have looked at the evidence of harm from sugar and been persuaded, and it is extremely symbolic, important, and powerful that they have put the levy on drinks manufacturers”, Capewell concluded.

Talha Khan Burki

Papers

Cancer guidelines during the COVID-19 pandemic.

COVID-19: consequences for higher education.

Cancer care in the time of COVID-19.

Pink Ribbons, Inc

Sugar tax in the UK