Ovarian Cancer Awareness Month

Ovarian Cancer Awareness Month | n.d |  Ovarian Cancer Awareness Month

March is Ovarian Cancer Awareness Month, ovarian cancer is the biggest gynaecological killer of women in the UK women, with UK survival rates among the worst in Europe.

Three quarters of women are diagnosed once the cancer has already spread, making treatment more difficult. This is why awareness is so important, to drive forward improvements in diagnosis, treatment and survival.

Ovarian cancer charities in the UK, we are all working to increase awareness of the disease, with women and GPs, in order to save lives (Source: Ovarian Cancer Awareness Month).

See also:

Ovarian Cancer Action 

The Eve Appeal 

Target Ovarian Cancer

Ovacome 

NIHR Signal: Prolonging anticoagulant treatment after abdominal cancer surgery reduces clot risk

NIHR Signal | February 2019 | Prolonging anticoagulant treatment after abdominal cancer surgery reduces clot risk

An National Institute for Health Research (NIHR) Signal spotlights a Cochrane Review of seven randomised controlled trials that studied the effects of prolonging anticoagulant treatment after abdominal cancer surgery. The Review found extending treatment reduces the clot risk. 

Why was this study needed?

Every year about 1 in 1,000 people in the UK develop a venous thromboembolism (VTE). Either a blood clot in the deep veins (deep vein thrombosis) or in the lungs (pulmonary embolism). VTE is more common in people with cancer and following major surgery. Over half of all cases follow recent hospitalisation. VTE used to be a leading cause of preventable death in hospital.

It is now routine practice to give drug treatment to prevent blood clots while people recover in hospital after abdominal or pelvic surgery. But observational studies indicate that patients may remain at increased risk for up to four or six weeks after surgery.

The Cochrane review aimed to resolve the uncertainty by combining data from recent high-quality studies to see whether there is a place for a longer course of anticoagulation after abdominal or pelvic surgery.

What did this study do?

This Cochrane review includes seven randomised controlled trials of extended LMWH treatment, given for at least 14 days after abdominal or pelvic surgery compared with shorter treatment as an inpatient only. The 1,728 patients had either open or keyhole surgery. Five trials recruited patients specifically with cancer and two included surgery for either cancer or benign conditions.

Venous thromboembolism was confirmed by an objective test (such as venography). Most studies were of LMWH for around 28 days, with only one study treating for 14 days only. Studies using other anticoagulants or mechanical measures (e.g. compression stockings) were excluded.

Overall the evidence was rated as moderate quality. Sources of bias included lack of detail about randomisation methods, whether participants and assessors were blinded to group assignment and incomplete reporting of outcomes. Nevertheless, the results were similar across studies, and this increases confidence in the conclusions.

What did it find?

• Extended LMWH reduced the risk of VTE up to 30 days after surgery, which occurred in 5.3% of the intervention group compared with 13.2% of the control group.
• The findings were similar in the subgroup of patients who received open surgery: 6% experienced VTE after extended treatment vs 13.8% of the control group.
• Extended LMWH also reduced the risk of deep vein thrombosis in general, and specifically thrombosis in the upper thigh or pelvic veins.
• Extended treatment did not affect the risk of minor or major bleeds up to three months after surgery.

What does current guidance say on this issue?

The NICE guideline on reducing risk of hospital-acquired venous thromboembolism (published 2018) recommends using LMWH (or an alternative drug, fondaparinux sodium) for a minimum of seven days for people undergoing abdominal surgery, taking into account individual patient factors and according to clinical judgement.

NICE recommends considering extending VTE prophylaxis to 28 days postoperatively for people who have had major cancer surgery in the abdomen.

What are the implications?

These results suggest that extended VTE prophylaxis after abdominal or pelvic surgery is beneficial, especially in cancer surgery.  This is in agreement with evidence in orthopaedic surgery and with current NICE guidance in cancer surgery.

It is difficult to be certain whether the findings apply to patients following non-cancer surgery as two trials that included these patient groups didn’t separate their results.

Newer oral anticoagulant drugs may provide similar benefits, but these were not tested in the studies included. (Source: NIHR)

 

Read the full Signal at NIHR 

Full reference:

Felder, S. et al |2018| Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery| Cochrane Database of Systematic Reviews| 11| Art. No.: CD004318|  DOI: 10.1002/14651858.CD004318.pub3

BACKGROUND: This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. OBJECTIVES: To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE.

SEARCH METHODS: We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies.

SELECTION CRITERIA: We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (more than or equal to fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation.

DATA COLLECTION AND ANALYSIS: Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis.

MAIN RESULTS: We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH .For the secondary outcome of all DVT, seven studies, n is equal to 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT. We found a similar reduction when analysis was limited to incidence in proximal DVT. The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis. No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively. Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity.

AUTHORS’ CONCLUSIONS: Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

To access the Cochrane Review in full contact the Library 

The skeletal impact of cancer therapies

Bedatsova, L. & Drake, M. T. | 2019| The skeletal impact of cancer therapies | British Journal of Clinical Pharmacology | https://doi.org/10.1111/bcp.13866

A new article published in the British Journal of Clinical Pharmacology looks at the skeletal impact of cancer therapies.

Abstract

Both cancer and therapies used in the treatment of cancer can have significant deleterious effects on the skeleton, increasing the risks for both bone loss and fracture development. While advancements in cancer therapies have resulted in enhanced cancer survivorship for patients with many types of malignancies, it is increasingly recognized that efforts to reduce bone loss and limit fractures must be considered for nearly all patients undergoing cancer therapy in order to diminish the anticipated future skeletal consequences. To date, most studies examining the impact of cancer therapies on skeletal outcomes have focused on endocrine‐associated cancers of the breast and prostate, with more recent advances in our understanding of bone loss and fracture risk in other malignancies. Pharmacologic efforts to limit the adverse effects of cancer therapies on bone have nearly universally employed anti‐resorptive approaches, although studies have frequently relied on surrogate outcomes such as changes in bone mineral density or bone turnover markers, rather than on fractures or other skeletal‐related events, as primary study endpoints. Compounding current deficiencies for the provision of optimal care is the recognition that despite clearly written and straightforward society‐based guidelines, vulnerable eligible patients are very often neither identified nor provided with appropriate treatments to limit the skeletal impact of their cancer therapies.

The full article is available from the British Journal of Clinical Pharmacology

[NICE Technology appraisal guidance] Encorafenib with binimetinib for unresectable or metastatic BRAF V600 mutation-positive melanoma

NICE | February 2019 | Encorafenib with binimetinib for unresectable or metastatic BRAF V600 mutation-positive melanoma

Evidence-based recommendations on encorafenib (Braftovi) with binimetinib (Mektovi) for treating unresectable or metastatic BRAF V600 mutation-positive melanoma in adults.

Full details from NICE 

[NICE Technology appraisal guidance] Abemaciclib with an aromatase inhibitor for previously untreated, hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer

NICE | February 2019| Abemaciclib with an aromatase inhibitor for previously untreated, hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer

Evidence-based recommendations on abemaciclib (Verzenios) for treating locally advanced or metastatic, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in adults who have not had endocrine-based therapy before.

Full details from NICE 

[NICE] Dabrafenib with trametinib for treating advanced metastatic BRAF V600E mutation-positive non-small-cell lung cancer (terminated appraisal)

NICE | February 2019 | Dabrafenib with trametinib for treating advanced metastatic BRAF V600E mutation-positive non-small-cell lung cancer (terminated appraisal)

NICE is unable to make a recommendation about the use in the NHS of dabrafenib with trametinib for treating advanced metastatic BRAF V600E mutation-positive non-small-cell lung cancer because no evidence submission was received from Novartis. We will review this decision if the company decides to make a submission (Source: NICE).

Full details from NICE 

New drive to improve care and save lives

Professor Sir Mike Richards has launched a major overhaul of cancer screening as part the NHS Long Term Plan’s renewed drive to improve care and save lives | via NHS England

Early detection of cancer, while the condition is easier to treat, is central to the plan which aims to prevent tens of thousands more deaths each year. Sir Mike Richards, who was the NHS’ first cancer director and is the former CQC chief inspector of hospitals, is leading an independent review of national screening programmes.

He will recommend how they should be upgraded to ensure they remain world leading and that patients benefit from new technologies and treatments.

As part of his work, Sir Mike wants to hear views and ideas from staff, patients and other groups to inform recommendations for the future of cancer screening.

Sir Mike is seeking feedback on a number of areas including:

• Future management, delivery and oversight of screening programmes
• How to ensure maximum screening uptake across the country and particularly in vulnerable and minority groups
• Opportunities for the use of AI and other technology to help with cancer screening
• Feedback on current and future IT and equipment
• Having the right number of staff with the right training to deliver the programmes
• Views on what screening should look like in ten years’ time

Full story at NHS England

BMJ Best Practice update: Laryngeal cancer

BMJ Best Practice | February 2019 | Laryngeal cancer

There has been an update to BMJ Best Practice on Laryngeal cancer

Full details from BMJ Best Practice

Sheffield research: New compound could help treat ovarian cancer

University of Sheffield | February 2019 | New compound could help treat ovarian cancer

Two departments at the University of Sheffield have collaborated to explore new drug types that could work against types of treatment resistant cancers. 

Researchers from the Department of Chemistry and the Department of  Biomedical Science have screened new compounds made in the lab against a “panel” of cancers that were sensitive and resistant to standard cancer therapy.

The study’s lead author Professor Jim Thomas, of the Department of Chemistry, said: “Many cancer cells – about 20 per cent – become resistant to common treatments by learning to ignore the internal signals that tell them to undergo programed cell death, known as apoptosis.

“We have identified a compound that kills cancer cells that avoids the need for apoptosis, and so the usual resistance mechanism doesn’t work against our compound.

“The compound is as potent as common current chemotherapeutics, but crucially retains its potency against treatment-resistant cancers. By looking at the cellular response from the cancers we found the new drug lead works by two different mechanisms simultaneously, making it much more difficult for cancers to develop resistance toward them during treatment.

“We think this compound could be particularly effective against ovarian cancer.” (Source: University of Sheffield)

Read the news release in full from University of Sheffield 

Abstract 

Drug resistance to platinum chemotherapeutics targeting DNA often involves abrogation of apoptosis and has emerged as a significant challenge in modern, non-targeted chemotherapy. Consequently, there is great interest in the anti-cancer properties of metal complexes—particularly those that interact with DNA—and mechanisms of consequent cell death. Herein we compare a parent cytotoxic complex, [Ru(phen)₂(tpphz)]²⁺ [phen = 1,10-phenanthroline, tpphz = tetrapyridyl[3,2-a:2′,3′-c:3″,2″-h:2‴,3‴-j]phenazine], with a mononuclear analogue with a modified intercalating ligand, [Ru(phen)₂(taptp)]²⁺ [taptp = 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene], and two structurally related dinuclear, tpphz-bridged, heterometallic complexes, RuRe and RuPt. All three of these structural changes result in a switch from intercalation to groove-binding DNA interaction and concomitant reduction in cytotoxic potency, but no significant change in relative cytotoxicity toward platinum-resistant A2780CIS cancer cells, indicating that the DNA interaction mode is not critical for the mechanism of platinum resistance. All variants exhibited a light-switch effect, which for the first time was exploited to investigate timing of cell death by live-cell microscopy. Surprisingly, cell death occurred rapidly as a consequence of oncosis, characterized by loss of cytoplasmic volume control, absence of significant mitochondrial membrane potential loss, and lack of activation of apoptotic cell death markers. Importantly, a novel, quantitative proteomic analysis of the A2780 cell genome following exposure of the cells to either mononuclear complex reveals changes in protein expression associated with global cell responses to oxidative stress and DNA replication/repair cellular pathways. This combination of multiple targeting modalities and induction of a non-apoptotic death mechanism makes these complexes highly promising chemotherapeutic cytotoxicity leads.

The Library can provide the full article to Rotherham NHS Staff, request here 

Leeds research: Smoking may limit body’s ability to fight skin cancer

University of Leeds | February 2019 | Leeds research: Smoking may limit body’s ability to fight skin cancer

A study of more than 700 melanoma patients, mainly from the north of England, provides evidence to suggest that smoking may blight the immune response against melanoma and reduce survival.

The study led by experts at the University of Leeds found that people diagnosed with melanoma who also smoked/ had history of smoking are 40 per cent less likely to survive their melanoma than non-smokers within a decade of diagnosis.

In a subset of 156 patients who had the most genetic indicators for immune cells, smokers were around four and a half times less likely to survive from the cancer than people who had never smoked.

Lead author Julia Newton-Bishop, Professor of Dermatology at the University of Leeds, said: “The immune system is like an orchestra, with multiple pieces. This research suggests that smoking might disrupt how it works together in tune, allowing the musicians to continue playing but possibly in a more disorganised way.

“The result is that smokers could still mount an immune response to try and destroy the melanoma, but it appears to have been less effective than in never-smokers, and smokers were less likely to survive their cancer.

“Based on these findings, stopping smoking should be strongly recommended for people diagnosed with melanoma.” (Source: University of Leeds)

Read the press release from the University of Leeds 

This study was funded by Cancer Research UK and has been published in the journal Cancer Research

Pozniak, J. et al.| 2019| Genetic and environmental determinants of immune response to cutaneous melanoma| Cancer Research| DOI: 10.1158/0008-5472.CAN-18-2864