Older women with breast cancer chose less aggressive treatment when they used a decision aid

NIHR | March 2022 | Older women with breast cancer chose less aggressive treatment when they used a decision aid

New research funded by the National Institute for Health Research (NIHR) explored the impact of decision aids among women over 70 who were diagnosed with breast cancer. The women either had a consultation using the decision aid or without it (standard care). Researchers found women in the centres using the decision aids were less likely to have surgery or chemotherapy.

The women were followed for an average of 3 years. Using the decision aid had little impact on their chances of being alive at 3 years. This suggests that the decision aids were well-targeted and used with women for whom the treatment choice would make least difference to their length of life.

The study found women who used decision aids were better informed about their treatment options. There was little difference in quality of life between women who used the decision aids and those who did not. (Source: NIHR)

Full Alert is available from NIHR Older women with breast cancer chose less aggressive treatment when they used a decision aid

The Alert highlights research and the findings of a recent paper: Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices 

Earlier decisions on breast and ovarian surgery reduce cancer in women at high risk

Marcinkute, R. et al | 2021| Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers | Journal of Medical Genetics | Published Online First: 10 February 2021. doi: 10.1136/jmedgenet-2020-107356

This NIHR Alert summarises the recent findings of a longitudinal study that followed more than 800 women who carry the BRCA1 or BRCA2 genes who have an increased risk of developing ovarian and breast cancers (as well as other cancers). After testing positive for these genes, the individuals were followed up twenty years later, where more than half (57.9 per cent) had a risk reducing mastectomy, and 77 per cent had elected for a bilateral salpingo-oophorectomy (RRSO).

Abstract

Background Women testing positive for BRCA1/2 pathogenic variants have high lifetime risks of breast cancer (BC) and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy BRCA1/2 carriers.

Methods Women were prospectively followed up from positive genetic test (GT) result to censor date. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk.

Results In total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range equal to 0.01–24.3; total equal to4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9 per cent and RRSO uptake was 78.6 per cent. The median time from GT to RRM was 18.4 months, and from GT to RRSO–10.0 months. Annual BC incidence in the study population was 1.28 per cent. Relative BC risk reduction (RRM versus non-RRM) was 94 per cent. Risk reduction of ovarian cancer (RRSO versus non-RRSO) was 100 per cent.

Conclusion Over a 24-year period, we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC.

Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers [abstract only]

NIHR Alert Earlier decisions on breast and ovarian surgery reduce cancer in women at high risk

Rotherham NHS staff can request this article from their Library

NIHR: Catching cancer early: how research could help us improve

This NIHR collection explores recent NIHR-supported research into the early detection of cancer. Some studies address the needs of specific groups, others look at new approaches to screening. The Collection brings together messages from research that has been highlighted in accessible summaries of evidence – NIHR Alerts – over the past year. 

• Addressing the needs of different groups to improve cancer screening
• Innovative ways to improve early detection of cancer
• Alterations to existing screening programmes

Catching cancer early: how research could help us improve

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

Algorithms as good as doctors at predicting death in advanced cancer

NIHR | April  2021 | Algorithms as good as doctors at predicting death in advanced cancer

This Alert from the NIHR looks at two pieces of research funded by NIHR, and led by Marie Curie Palliative Care Research Department at University College London (UCL), whihc compared five digital prognosis tools clinician judgement in over 1 800 adults with incurable cancer in England and Wales. The experts conducted interviews with 29 patients who had recently been referred to community, hopsital and hospice palliative care services, 20 caregivers and 32 clinicians.

Both papers, now published in PLoS One report that algorithms can be as accurate as clinicians’ judgements for predicting how long terminally ill people with advanced cancer have left to live.  at least two of the studied algorithms were equally as good as the combined judgement of an experienced doctor and nurse in predicting whether patients would live for days, weeks or months.

The lead researcher- Professor Paddy Stone, from the Marie Curie Palliative Care Research Department at UCL- explained that although the best algorithms were as accurate as expert clinician judgement, the overall accuracy was only just over 60 per cent. The research concludes that while prognosis algorithms are currently no more accurate than clinicians’ judgments they may be helpful in other ways such as providing a supplementary second opinion or helping less experienced staff navigate difficult conversations with patients and their loved ones about their prognosis and end of life plans.

Professor Stone explained how important and valuable an accurate prognosis is for a terminally ill patient’s care: “ Knowing whether one only has days, weeks or a few short months remaining can help prepare for the end of life and to focus on achieving the best possible quality of life.  (Source: NIHR).

NIHR Algorithms as good as doctors at predicting death in advanced cancer

Primary papers

Prognostic tools or clinical predictions: Which are better in palliative care?

The Prognosis in Palliative care Study II (PiPS2): A prospective observational validation study of a prognostic tool with an embedded qualitative evaluation

NIHR: To improve team decision-making in cancer care: streamline workload, shorten meetings, address logistics and keep a gender balance on the team

NIHR | March 2021 | To improve team decision-making in cancer care: streamline workload, shorten meetings, address logistics and keep a gender balance on the team

A multi-disciplinary approach to decision making in cancer care is recognised as being the ‘gold-standard’, although evidence of its effectiveness remains unclear. Authors of this study set out to test, for the first time, the functional perspective of group DM in cancer MDTs, operationalized as two specific hypotheses: (H1) the interaction process, the internal factors, external circumstances, and case complexity will impact on the quality of DM for patients; and (H2) there will be a difference in the interaction process, internal and external factors, and quality of DM between the first and second half of a MDT meeting. The researchers followed three MDTs at university hospitals in Greater London and Derbyshire. Each MDT comprised around 14-15 members and specialised in breast, colorectal and gynaecological cancers. Between 2015-16, the researchers videoed 30 meetings in which more than 800 patients were discussed. Some patients had complex cancer; others had suspected cancer or benign disease (Source: NIHR & Soukop, et al. 2021).

Key findings:

• decision-making was better in larger teams, in those which had a balance of genders, and when more complex cases were being discussed (since these discussions involved more team members). Question-and-answer style communication was helpful
• barriers to decision-making during the meetings included antagonism, tension, and lack of acknowledgement of other members’ contributions; gender imbalance; and logistical issues with administration, equipment and meeting attendance
• time and workload pressures hindered decision-making. The longer the meeting, and the more cases discussed, the worse the quality of decision-making and communication. The optimal number of patients discussed was 20. Beyond that, the quality of decision-making went down with every treatment recommendation made and negative reactions increased.
• first versus second half of the meeting had different challenges. Patients discussed in the first half of the meeting had more complex needs. In the second half, cases were more straightforward, but less time was spent discussing them as team members became tired. They also started to leave so the remaining group had less broad expertise.

Following the research, the team recommend:

• Streamlining MDT workload to help reduce the time all MDT members spend in the meetings. Only patients with complex needs requiring input from various specialists should be discussed. The MeDiC tool may help to select patients.
• A maximum limit on the number of cases discussed at a single meeting.
• A mandatory short break during the meeting.
• Better preparation to smooth out logistical issues ahead of meetings, for example, using a checklist to ensure all information is readily available.
• An MDT meeting chair who does not contribute to the clinical discussion could steer the team through the workload by reducing tensions, promoting positive interaction and communication, and ensuring a more uniform decision-making process.
• Staff selection for MDTs should factor in gender. (Source: NIHR)

Abstract

Background

Multidisciplinary teams (MDT) formulate expert informed treatment recommendations for people with cancer. We set out to examine how the factors proposed by the functional perspective of group decision making (DM), that is, interaction process, internal factors (factors emanating from within the group such as group size), external circumstances (factors coming from the outside of the team), and case‐complexity affect the quality of MDT decision making.

Methods

This was a cross‐sectional observational study. Three cancer MDTs were recruited with 44 members overall and 30 of their weekly meetings filmed. Validated observational instruments were used to measure quality of DM, interactions, and complexity of 822 case discussions.

Results

The full regression model with the variables proposed by the functional perspective was significant, R² = 0.52, F(20, 801) = 43.47, P < .001, adjusted R² = 0.51. Positive predictors of DM quality were asking questions (P = .001), providing answers (P = .001), team size (P = .007), gender balance (P = .003), and clinical complexity (P = .001), while negative socioemotional reactions (P = .007), gender imbalance (P = .003), logistical issues (P = .001), time‐workload pressures (P = .002), and time spent in the meeting (P = .001) were negative predictors. Second half of the meetings also saw significant decrease in the DM quality (P = .001), interactions (P = .001), group size (P = .003), and clinical complexity (P = .001), and an increase in negative socioemotional reactions (P = .001) and time‐workload pressures (P = .001).

Discussion

To the best of our knowledge, this is the first study to attempt to assess the factors proposed by the functional perspective in cancer MDTs. One novel finding is the effect of sociocognitive factors on team DM quality, while another is the cognitive‐catch 22 effect: while the case discussions are significantly simpler in the second half of the meeting, there is significantly less time left to discuss the remaining cases, further adding to the cognitive taxation in teams who are now rapidly attempting to close their time‐workload gap. Implications are discussed in relation to quality and safety.

Image source: Soukup, et al. 2021

Graphical representation of the functional perspective of group decision making as applied to cancer multidisciplinary team meetings. Note. Reprinted with permission from Soukup, 2017.⁵²

NIHR Alert To improve team decision-making in cancer care: streamline workload, shorten meetings, address logistics and keep a gender balance on the team

The full paper: Soukup T, and others. A multicentre cross‐sectional observational study of cancer multidisciplinary teams: Analysis of team decision making. Cancer Medicine. 2020;9:7083–7099

New oncology collaboration established to drive forward translational cancer research

NIHR | February 2021 | New oncology collaboration established to drive forward translational cancer research

The National Institute for Health Research has announced the NIHR Oncology Translational Research Collaboration (TRC), it unites leading cancer researchers from across the NIHR’s Biomedical Research Centres (BRC) to drive forward innovative research in key areas including early diagnosis, surgery, immunotherapy and radiotherapy. Through working in partnership, the Oncology TRC will be able to carry out research that requires real collaborative effort, and would not be possible by centres working alone. It will also complement research undertaken by other cancer research networks.

Full details about the TRC are available from NIHR

To find out more about the Oncology TRC, visit its page on the NIHR website or contact nocri@nihr.ac.uk to find out how you can work with the collaboration. 

NIHR: How radiotherapy research has helped safe and effective treatment for cancer patients throughout the COVID-19 pandemic #covid19rftlks #worldcancerday

NIHR | 4 February 2021| How radiotherapy research has helped safe and effective treatment for cancer patients throughout the COVID-19 pandemic

Today 4 February 2021 is World Cancer Day, the NIHR highlights how thanks to radiotherapy research, patients with breast cancer can continue to receive safe and effective treatment in a reduced number of visits to hospital, helping to keep them safe from Covid-19 (@NIHRResearch).

In this piece Professor John Wadsley explains how, research that demonstrates a week’s treatment of radiotherapy is as safe and effective as undergoing a course of more treatments over a period of three weeks, was used to inform treatment for patients with breast cancer during the first wave of the pandemic.

Radiotherapy treatment usually requires multiple visits to hospital, typically five days a week for three to seven weeks. At the onset of the pandemic there were major concerns about the safety of bringing potentially vulnerable patients into hospital for so many visits, and the capacity within radiotherapy departments to continue delivering treatments due to staff sickness or having to isolate.

Researchers from the FAST- Forward trial, wherein more than 4000 patients from 97 UK hospitals over 2.5 years, each allocated to one of three treatment groups – the standard 15 treatment schedule or one of two, had already tested whether a course of five treatments over one week was as safe and effective. Patients in all groups were carefully followed up to check for any evidence of cancer recurrence and for any late side effects from the treatment. The findings from the FAST- Forward trial are published in The Lancet

The full article can be read from NIHR Research

Related:

University of Leeds Dramatic changes to radiotherapy treatments due to COVID-19

NIHR: First-line chemotherapy for ovarian cancer given once every three weeks may preserve quality of life

NIHR | November 2020| First-line chemotherapy for ovarian cancer given once every three weeks may preserve quality of life

NIHR’s latest evidence feature focuses on research that studied the chemotherapy treatment women with a new diagnosis of ovarian cancer receive, this type of cancer is usually treated every three weeks with chemotherapy containing the medicines carboplatin and paclitaxel. Although a recent Japanese studied reported better outcomes without reducing quality of life for weekly chemotherapy, the researchers behind this study found that patients who received weekly paclitaxel had poorer quality of life during treatment. They were also more likely to have nerve damage that lasted up to 18 months.

Taken together with the lack of progression-free survival benefit, their findings do not support routine use of weekly paclitaxel-containing regimens in the management of newly diagnosed ovarian cancer.

What’s new?

1438 women with ovarian cancer were asked about their quality of life at regular intervals for up to five years after starting treatment. They completed written questionnaires on factors such as emotional well-being, fatigue and nerve pain.

Nine months after patients entered the trial, the researchers found:

• Patient well-being fell during chemotherapy but then improved over the following months regardless of which treatment was given
• When researchers looked at well-being scores during and after treatment, those on weekly treatment experienced lower quality of life compared to those receiving treatment every three weeks
• Nerve damage caused by paclitaxel was worse in the weekly treatment arms and persisted for longer. It started later than in women receiving chemotherapy every three weeks
• Patients having weekly treatment reported slightly increased levels of fatigue compared to those treated every three weeks but this was not significant.

Although survival was similar for patients on all treatment plans, well-being data shows a different story. The study suggested weekly schedules were harder for patients to tolerate and caused long-lasting toxicity compared to less frequent chemotherapy.

The researchers believe that three-weekly chemotherapy should remain the standard of care for most newly-diagnosed ovarian cancer patients.

It is not known why paclitaxel causes nerve damage. The researchers in this study believe long-lasting nerve damage and numbness are likely because the total amount of paclitaxel given is higher for people taking weekly treatment (Source: NIHR)

Primary paper:

Blagden, S.P. (2020) et al. Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial| The Lancet Oncology|21|P. 969-977

NIHR: International trial shows single-dose radiotherapy as effective for treating breast cancer

National Institute Health Research |August 2020 | International trial shows single-dose radiotherapy as effective for treating breast cancer

A pioneering breast cancer therapy requiring just one shot of radiotherapy rather than conventional weeks-long treatment, has proven to be as effective for most women in treating the disease, finds research funded and supported by NIHR.

Results of the large international randomised trial, published in the BMJ, confirm the long-term effectiveness of Targeted Intraoperative Radiotherapy (TARGIT-IORT): a breast cancer treatment which is increasingly available throughout the world. 

TARGIT-IORT is delivered immediately after lumpectomy (tumour removal), via a small ball-shaped device placed inside the breast, directly where the cancer had been. The single-dose treatment lasts for around 20 to 30 minutes and replaces the need for extra hospital visits, benefiting both patient safety and well-being.

Researchers compared this technique to conventional external beam radiotherapy (EBRT), delivered from outside the body via a linear accelerator radiotherapy machine. This consists of daily treatment sessions, known as fractions, to the whole breast, over three to six weeks. EBRT is given over a few minutes, but requires 15 to 30 hospital visits, which could be a significant distance from where the patient lives.

At the five-year follow up, recurrence risk of localised breast cancer was 2.1% for TARGIT-IORT compared to 0.95% for EBRT showing TARGIT-IORT to be non-inferior to EBRT. There were 14 fewer deaths for the TARGIT-IORT group.

Significantly, at long-term follow up (average 8.6 years, maximum 18.9 years) there was no statistically significant difference found in any of the breast cancer outcomes, and a substantial reduction in deaths from causes other than breast cancer with TARGIT-IORT.

Researchers say they hope the treatment can be made more available to patients (Source: NIHR)

Full news release from NIHR

BMJ (2020)| Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial |370|m2836 |

Abstract

Objective To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

Design Prospective, open label, randomised controlled clinical trial.

Setting 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

Participants 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

Interventions Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).

Main outcome measures Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.

Results Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).

Conclusion For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.

The research findings are published in the BMJ, available here