Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study #Covid19RftLks

COVIDSurg Collaborative | 2021| Effect of Covid-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study | The Lancet Oncology | https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00493-9/fulltext

This international study prospectively enrolled patients with a decision for curative surgery awaiting surgery during the SARS-CoV-2 pandemic and tracked their care pathways prospectively. It included data from the 15 most common solid cancer types across all country-income settings, providing wide generalisability to global policy. The analysis allowed a direct comparison of full and moderate lockdowns to light restrictions, accounting for their dynamic nature, where different patients from the same country were exposed to different lockdown states.

Their findings indicate that during full lockdowns, one in seven patients did not receive their planned operation, all of whom had a pandemic-related reason for non-operation. This finding was robust, and consistent in sensitivity analyses. In a secondary analysis, awaiting surgery in a full lockdown for greater than 6 weeks was associated with an increased likelihood of non-operation (Source: COVIDSurg Collaborative).

Summary

Background

Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.

Methods

This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.

Findings

Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays.

Interpretation

Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.

Funding

National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.

Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an interrnational, prospective, cohort study [primary paper]

Benefits from changes to kidney cancer drug treatment

University of Leeds | September 2021 | Benefits from changes to kidney cancer drug treatment

13 000 people are diagnosed with kidney cancer every year in the UK, making it the seventh most common UK cancer.

A trial, run through the Clinical Trials Research Unit at the University of Leeds, has examined the implications of administering drugs to treat kidney cancer over a 48-week period, instead of the standard 12 weeks. The trial was designed to so that two treatment schedules could be formally compared with each other in terms of treatment toxicity/side effects. The study showed a significant reduction in serious side effects with the modified schedule (33 per cent) compared to the standard schedule (53 per cent). 

As a result the proportion of patients experiencing serious side effects during treatment dropped by a fifth (20 per cent).

How long patients lived and the amount of tumour shrinkage looked similar in both groups, but due to the size of the study, the trial could not definitively prove this.

The findings have been prevented at the recent Annual Conference of the European Society for Medical Oncology (ESMO) held in Paris 16–21 September 2021 (Source: University of Leeds).

Adapted from this press release from the University of Leeds Benefits from changes to kidney cancer drug treatment

Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010)

Felip, E. et al | 2021 | Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial | The Lancet | https://doi.org/10.1016/S0140-6736(21)02098-5

Summary

Background

Novel adjuvant strategies are needed to optimise outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). We aimed to evaluate adjuvant atezolizumab versus best supportive care after adjuvant platinum-based chemotherapy in these patients.

Methods

IMpower010 was a randomised, multicentre, open-label, phase 3 study done at 227 sites in 22 countries and regions. Eligible patients were 18 years or older with completely resected stage IB (tumours more than or equal to 4 cm) to IIIA NSCLC per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system (7th edition). Patients were randomly assigned (1:1) by a permuted-block method (block size of four) to receive adjuvant atezolizumab (1200 mg every 21 days; for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence) after adjuvant platinum-based chemotherapy (one to four cycles). The primary endpoint, investigator-assessed disease-free survival, was tested hierarchically first in the stage II–IIIA population subgroup whose tumours expressed PD-L1 on 1 per cent or more of tumour cells (SP263), then all patients in the stage II–IIIA population, and finally the intention-to-treat (ITT) population (stage IB–IIIA). Safety was evaluated in all patients who were randomly assigned and received atezolizumab or best supportive care. IMpower010 is registered with ClinicalTrials.gov, NCT02486718 (active, not recruiting).

Findings

Between Oct 7, 2015, and Sept 19, 2018, 1280 patients were enrolled after complete resection. 1269 received adjuvant chemotherapy, of whom 1005 patients were eligible for randomisation to atezolizumab (n equal to 507) or best supportive care (n=498); 495 in each group received treatment. After a median follow-up of 32·2 months (IQR 27·4–38·3) in the stage II–IIIA population, atezolizumab treatment improved disease-free survival compared with best supportive care in patients in the stage II–IIIA population whose tumours expressed PD-L1 on 1 per cent or more of tumour cells (HR 0·66; 95 per cent CI 0·50–0·88; p equal to0·0039) and in all patients in the stage II–IIIA population (0·79; 0·64–0·96; p equal to0·020). In the ITT population, HR for disease-free survival was 0·81 (0·67–0·99; p equal to 0·040). Atezolizumab-related grade 3 and 4 adverse events occurred in 53 (11 per cent) of 495 patients and grade 5 events in four patients (1 per cent).

Interpretation

IMpower010 showed a disease-free survival benefit with atezolizumab versus best supportive care after adjuvant chemotherapy in patients with resected stage II–IIIA NSCLC, with pronounced benefit in the subgroup whose tumours expressed PD-L1 on 1 per cent or more of tumour cells, and no new safety signals. Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC.

Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial [abstract only]

Rotherham NHS staff can request this article from the Library & Knowledge Service

NIHR: New drug shows promise in slowing growth of bowel cancer

NIHR | September 2021 | New drug shows promise in slowing growth of bowel cancer

This NIHR Alert summarises the findings of a piece of research ,where a therapeutic agent (Adavosertib) was tested as maintenance therapy following induction chemotherapy for patients with bowel cancer. The drug could delay tumour regrowth among patients with an aggressive sub-type of inoperable bowel cancer who have limited treatment options. 

The authors found that, among those who had a complete break, the cancer started to grow somewhat sooner than in those on continued maintenance therapy, but that maintenance therapy did not lead to an increase in how long people lived. 

The paper has now been published in the Journal of Clinical Oncology

Seligmann, J.F., et al | 2021 | Inhibition of WEE1 Is Effective in TP53– and RAS-Mutant Metastatic Colorectal Cancer: A Randomized Trial (FOCUS4-C) Comparing Adavosertib (AZD1775) With Active Monitoring | Journal of Clinical Oncology | DOI: 10.1200/JCO.21.01435 

Abstract

Purpose

Outcomes in RAS-mutant metastatic colorectal cancer (mCRC) remain poor and patients have limited therapeutic options. Adavosertib is the first small-molecule inhibitor of WEE1 kinase. We hypothesized that aberrations in DNA replication seen in mCRC with both RAS and TP53 mutations would sensitize tumors to WEE1 inhibition.

Methods

Patients with newly diagnosed mCRC were registered into FOCUS4 and tested for TP53 and RAS mutations. Those with both mutations who were stable or responding after 16 weeks of chemotherapy were randomly assigned 2:1 between adavosertib and active monitoring (AM). Adavosertib (250 mg or 300 mg) was taken orally once on days 1-5 and days 8-12 of a 3-week cycle. The primary outcome was progression-free survival (PFS), with a target hazard ratio (HR) of 0.5 and 80% power with a one-sided 0.025 significance level.

Results

FOCUS 4-C was conducted between April 2017 and Mar 2020 during which time 718 patients were registered; 247 (34 per cent) were RAS/TP53-mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib equal to 44; AM equal to 25). Adavosertib was associated with a PFS improvement over AM (median 3.61 v 1.87 months; HR equal to 0.35; 95 per cent) were RAS/TP53-mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib equal to 44; AM equal to 25). CI, 0.18 to 0.68; P  .0022). Overall survival (OS) was not improved with adavosertib versus AM (median 14.0 v 12.8 months; HR equal to 0.92; 95 per cent) were RAS/TP53-mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib equal to 44; AM equal to 25). CI, 0.44 to 1.94; P equal to .93). In prespecified subgroup analysis, adavosertib activity was greater in left-sided tumors (HR equal to 0.24; 95 per cent) were RAS/TP53-mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib equal to 44; AM equal to 25). CI, 0.11 to 0.51), versus right-sided (HR equal to 1.02; 95 per cent) were RAS/TP53-mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib equal to 44; AM equal to 25). CI, 0.41 to 2.56; interaction P equal to .043). Adavosertib was well-tolerated; grade 3 toxicities were diarrhea (9 per cent), nausea (5 per cent), and neutropenia (7 per cent).

Conclusion

In this phase II randomized trial, adavosertib improved PFS compared with AM and demonstrates potential as a well-tolerated therapy for RAS/TP53-mutant mCRC. Further testing is required in this sizable population of unmet need.

Full news release is available from NIHR

Severe mental illness: inequalities in cancer screening uptake

Public Health England | September 2021 | Severe mental illness: inequalities in cancer screening uptake

This report from PHE highlights that people with a recorded diagnosis of SMI are more likely than the general population to experience poor physical health and to die prematurely.

People with SMI in England:

• die on average 15 to 20 years younger than the general population
• are 4.7 times more likely to die under the age of 75 than people without SMI

• cancer is the leading cause of premature mortality among adults with SMI

While international research suggests that the incidence of most cancers is similar among people with and without SMI. However, among people with a cancer diagnosis, those who also have SMI are more likely to die from the cancer (the case fatality is higher).

Comparing the uptake of NHS bowel, breast and cervical cancer screening services between people with and without severe mental illness.

Severe mental illness (SMI): inequalities in cancer screening uptake report

New screening pathways could improve NHS England’s bowel cancer programme

NIHR | 13 September 2021 | New screening pathways could improve NHS England’s bowel cancer programme

 NHS England’s Bowel Cancer Screening Programme aims to find warning signs in people aged 60 to 74. This population are invited to take a faecal immunochemical test (FIT) every two years. FIT measures blood in faeces and people with levels above a certain threshold are invited to have their bowel tissue examined for signs of cancer. Growths which could become cancerous (polyps) are removed and cancers prevented.

The research team set out to

1. Explore the relationship between FIT results and bowel pathology using truncated regression, in both a univariate and multiple regression model, with demographic factors including age, sex and area-based socioeconomic status; and
2. Use these results to estimate proportions of bowel abnormalities the screening programme would fail to diagnose at different FIT thresholds (false negative rates);
3. Generate hypotheses for fuller exploitation of quantitative FIT measures.

Researchers were surprised to find that the FIT threshold for further investigation is set at a point that may miss more than half of bowel cancer cases. This highlights a need to improve the NHS screening programme.

They suggest that the programme could make better use of FIT’s ability to provide the exact concentration of blood in faeces (rather than only whether it is above or below a cutoff level).

A new, multi-threshold strategy would mean referring people different follow-up according to their results. Screening intervals could be varied, and different ways of examining the bowel could be used (for example, sigmoidoscopy examines only the lower bowel). This could reduce the number of cancers missed while minimising the demand on services (Source: NIHR & Li et al, 2021).

Full details are available from NIHR

Primary paper Faecal immunochemical testing in bowel cancer screening: Estimating outcomes for different diagnostic policies

Li, S.J. et al | 2021| Faecal immunochemical testing in bowel cancer screening: Estimating outcomes for different diagnostic policies| Journal of Medical Screening | 28 | 3 P .277-285. doi:10.1177/0969141320980501

Abstract

Objectives

The National Health Service Bowel Cancer Screening Programme (NHS BCSP) in England has replaced guaiac faecal occult blood testing by faecal immunochemical testing (FIT). There is interest in fully exploiting FIT measures to improve bowel cancer (CRC) screening strategies. In this paper, we estimate the relationship of the quantitative haemoglobin concentration provided by FIT in faecal samples with underlying pathology. From this we estimate thresholds required for given levels of sensitivity to CRC and high-risk adenomas (HRA).

Methods

Data were collected from a pilot study of FIT in England in 2014, in which 27,238 participants completed a FIT. Those with a faecal haemoglobin concentration (f-Hb) of at least 20 µg/g were referred for further investigation, usually colonoscopy. Truncated regression models were used to explore the relationship between bowel pathology and FIT results. Regression results were applied to estimate sensitivity to different abnormalities for a number of thresholds.

Results

Participants with CRC and HRA had significantly higher f-Hb, and this remained unchanged after adjusting for age and sex. While a threshold of 20 μg/g was estimated to capture 82.2 per cent of CRC and 64.0 per cent of HRA, this would refer 7.8 per cent of participants for colonoscopy. The current programme threshold used in England of 120 μg/g was estimated to identify 47.8 per cent of CRC and 25.0 per cent of HRA.

Conclusions

Under the current diagnostic policy of dichotomising FIT results, a very low threshold would be required to achieve high sensitivity to CRC and HRA, which would place further strain on colonoscopy resources. The NHS BCSP in England might benefit from a diagnostic policy that makes greater use of the quantitative nature of FIT.

1. Exploring the relationship between FIT results and bowel pathology using truncated regression, in both a univariate and multiple regression model, with demographic factors including age, sex and area-based socioeconomic status; and
2. Using these results to estimate proportions of bowel abnormalities the screening programme would fail to diagnose at different FIT thresholds (false negative rates);
3. Generating hypotheses for fuller exploitation of quantitative FIT measures.

NIHR: UK lung cancer trial shows screening at-risk groups lowers mortality rates

NIHR | September 2021 | UK lung cancer trial shows screening at-risk groups lowers mortality rates

This NIHR Alert summarises the findings of a piece of recent screening trial in the UK, the trial looked at the first lung cancer computed tomography (CT) screening trial in the UK.

This paper enhances our knowledge of lung cancer CT screening, including effects on mortality (lung cancer mortality and all-cause mortality), as well as on stage of the disease and on pulmonary nodule classification. As the UK lung cancer screening trial (UKLS) had only a single screen, this study adds considerably to knowledge of the pattern of lung cancer incidence and mortality post-screening. The associated meta-analysis, which includes the UKLS trial, provides the most up to date international view of lung cancer mortality in lung cancer CT screening studies (Source: Field et al, 2021).

NIHR UK lung cancer trial shows screening at-risk groups lowers mortality rates

Primary paper Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis

Artificial intelligence and cancer diagnosis: caution needed

Venkatesan, P. | 2021| Artificial intelligence and cancer diagnosis: caution needed | The Lancet Oncology | DOI: https://doi.org/10.1016/S1470-2045(21)00533-7

The use of artificial intelligence (AI; computer-based algorithms that mimic human cognition) offers the promise to transform clinical medicine and health care in the near future. The concept of using machines to complement or replace human workers and decrease workloads is an attractive one, particularly now when the COVID-19 pandemic has greatly increased the global burden of health care and created a backlog in the care of other conditions, including in the oncology setting.

Contact the Library & Knowledge Service for a copy of this article

NICE (draft guidance) recommends apalutamide for treating prostate cancer

NICE |  September 2021 | NICE draft guidance recommends apalutamide for treating prostate cancer

NICE has recently (8 September 2021) published final draft guidance which now recommends apalutamide (also called Erleada and made by Janssen) plus androgen deprivation therapy for treating prostate cancer in adults.

The positive recommendations follow an improved discount to the price of apalutamide offered by the company.

The draft guidance looks at treating prostate cancer in adults which no longer responds to hormone therapy and who are at high risk of the cancer spreading to other parts of their body, or is still sensitive to hormone therapy but has already spread.

Apalutamide is a type of drug called an androgen receptor inhibitor which works by blocking the effect of testosterone on prostate cancer cells.  

For both types of prostate cancer where apalutamide has been recommended, the clinical trial results suggest apalutamide plus androgen deprivation therapy increases the time until the disease gets worse and how long people with these types of prostate cancer live.

It is estimated that around 8 000 people with hormone-sensitive or hormone-relapsed prostate cancer will now be eligible for treatment with apalutamide (Source: NICE).

Full details are available from NICE

NHS launches world first trial for new cancer test

NHS England | September 2021 | NHS launches world first trial for new cancer test

The NHS will today (13 September 2021) launch the world’s largest trial of a revolutionary new blood test that can detect more than 50 types of cancer before symptoms appear.

The first people invited to take part will have blood samples taken at mobile testing clinics in retail parks and other convenient community locations.

The Galleri blood test checks for the earliest signs of cancer in the blood and the NHS-Galleri trial, the first of its kind, aims to recruit 140 000 volunteers in eight areas of England to see how well the test works in the NHS.

The simple test has been shown to be particularly effective at finding cancers that are typically difficult to identify early – such as head and neck, bowel, lung, pancreatic, and throat cancers.

It works by finding chemical changes in fragments of genetic code-cell-free DNA (cfDNA) that leak from tumours into the bloodstream. The NHS is already sending out letters inviting tens of thousands of people from different backgrounds and ethnicities aged between 50 and 77 to take part.

Participants, who must not have had a cancer diagnosis in the last three years, will be asked to give a blood sample at a locally based mobile clinic and they will then be invited back after 12 months, and again at two years, to give further samples. The trial is part of the NHS’s efforts to increase the proportion of cancers detected early by the end of the Long Term Plan.

This quick and simple blood test could mark the beginning of a revolution in cancer detection and treatment here and around the world.

By finding cancer before signs and symptoms even appear, we have the best chance of treating it and we can give people the best possible chance of survival.

NHS chief executive Amanda Pritchard

NHS launches world first trial for new cancer test [news release]