Cancer overtakes cardiovascular disease as UK’s No. 1 killer – but only among men

Cardiovascular disease still primary cause of death among women

Cancer has overtaken cardiovascular disease, which includes heart disease and stroke, as the UK’s No 1 killer- but only among men, reveals research published online in the journal Heart. Cardiovascular disease is still the most common cause of death among women, and kills more young women than breast cancer, the figures show.

The researchers used the latest nationally available data (2012-13) for each of the four UK countries and the Cardiovascular Disease Statistics 2014 report compiled for the British Heart Foundation (BHF) to quantify the prevalence of cardiovascular disease, and find out how it’s treated, how much it costs, and how many deaths it causes. Cardiovascular disease includes coronary heart disease, stroke, high blood pressure, circulatory system disease, and other vascular/arterial disease.

The researchers analysed entries to the Clinical Practice Research Datalink GOLD database, the world’s largest repository of anonymised records for primary care, plus information from the family doctor (GP) quality improvement scheme known as QOF, and figures on episodes of inpatient hospital care. The analysis indicated that just short of 2.3 million people were living with some form of coronary heart disease in 2012. Around half a million were living with heart failure and a further 1.1 million were living with abnormal heart rhythm (atrial fibrillation).

England had the lowest prevalence of all cardiovascular conditions out of the four UK countries. But there were regional variations, with higher rates of cardiovascular disease in the North of England than in the South of the country. Scotland had the highest prevalence of coronary heart disease, stroke, and peripheral vascular disease, while Wales had the highest prevalence of high blood pressure, heart failure, and atrial fibrillation.

For the first time since the middle of the 20th century, cancer overtook cardiovascular disease as the primary cause of death in 2012. The proportion of deaths attributable to cancer was 29% while cardiovascular disease accounted for 28%.

But this was only true of men; cardiovascular disease still killed more women than cancer.

Almost one in three deaths (32%) in men were caused by cancer compared with 29% for cardiovascular disease. The equivalent figures were 27% and 28%, respectively, for women.

Cardiovascular disease accounted for a total of nearly 42,000 premature deaths (before the age of 75) in 2012, accounting for more than one in four premature deaths in men and around one in five (18%) in women. But it still killed more young women than did breast cancer.

Once again, there were wide regional variations in death rates. There were higher rates in Scotland (347/100,000 of the population) and the North of England (320/100,000), and lower rates in the South of England. The City of Glasgow topped the league table for death rates from cardiovascular disease for all ages, including premature deaths.

The number of surgical procedures and drugs prescribed to treat and prevent cardiovascular disease has risen substantially over the past two decades, and in 2012-13 the NHS spent just under £7 billion in England alone on cardiovascular disease, the largest chunk of which was spent on hospital care.The equivalent cost in Wales was £442.3 million, £393 million in Northern Ireland, and more than £750 million in Scotland.

Cardiovascular disease remains a substantial burden to the UK, both in terms of health and economic costs,” write the researchers, highlighting the “stark regional inequalities in the mortality and prevalence of cardiovascular disease.”

In a linked editorial, Dr Adam Timmis, of the NIHR Cardiovascular Biomedical Research Unit at Barts Health, London, describes the more than 40% drop in cardiovascular disease death rates since 1960 as “among the greatest public health triumphs in the past 50 years.” But the continuing North-South divide is a “stain on the UK’s public health record,” he writes.

The BHF report provides a timely reminder that in young women too cardiovascular disease kills more women than breast cancer. Most of these deaths in young women are caused by myocardial infarction heart attack which is largely preventable through modification of risk factors,” he points out.

And if the national effort put into the detection of breast cancer could be matched in protecting young women against myocardial infarction many more lives would probably be saved,” he insists.

Bhatnagar et al. The epidemiology of cardiovascular disease in the UK 2014. Heart. 2015; doi:10.1136/heartjnl-2015-307516 [Article]

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Increased overall survival for advanced stage non-small cell lung cancer patients is associated with availability of less toxic chemotherapy

A 10-year population-based study shows that increased availability of better systemic chemo- and targeted-therapies for patients with advanced non-small cell lung cancer (NSCLC) coincides with increased usage of these therapies. This in turn leads to a significant increase in overall survival.

Researchers from the British Columbia Cancer Agency, Vancouver, Canada, performed a retrospective chart review of all patients referred to the agency with advanced stage (IIIB or IV) lung cancer and grouped the patients into 4 one-year time frame cohorts; one termed “baseline” and three other groups that each started 6-months after a new second-line agent (docetaxel, erlotinib and pemetrexed) was made commercially available and put into practice. In British Columbia, Canada, the implementation of the second-line agents docetaxel, erlotinib and pemetrexed occurred in December 2000, October 2005 and June 2007, respectively. Cohort 1 (January to December 1998) with 555 patients was the baseline and cohort 2 (May 2001-April 2002) had 613 patients, cohort 3 (March 2006-February 2007) had 688 patients and Cohort 4 (November 2007-Ocotober 2008) had 750 patients.

The results published in the August Issue of the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer, show that the usage of second-line therapy increased significantly over time. At baseline only 21% of the patients received second-line therapy but in Cohorts 2 and 3 this increased to 27% and 37% respectively, and by Cohort 4 more than half, 55%, received second-line therapy. The most common agent in Cohort 1 was docetaxel (48%) but by Cohort 4 erlotinib (EGFR TKIs) and pemetrexed were used 50% and 26% of the time. The research also found that the proportion of patients who received at least first-line systemic chemotherapy also increased over the four time points from 16% in Cohort 1 to 23%, 34% and 33% for Cohorts 2-4, respectively.

The median overall survival of the patients who did not receive any chemotherapy did not change over the four time points; 3.9, 4.0, 3.1 and 3.2 months (p=0.136), however for those that did receive chemotherapy survival increased significantly, 9.4. 9.8 11.0 and 11.8 months (p=0.023). Examination of the entire population showed that the median overall survival of those not receiving chemotherapy was 3.51 months, whereas those receiving first-line therapy was 7.9 months and for those receiving second-line or beyond therapy the survival was 17 months (p<0.001).

The authors note that “The benefits of chemotherapy and specifically second-line treatment on patient outcomes are substantial, even in a widely mixed population of patients, which confirms the advances seen in clinical trial populations over the past decade“. Likewise, “As the options for treatment of NSCLC expand we anticipate that the outlook for lung cancer will continue to improve.”

Ho et al., (2014). Less Toxic Chemotherapy Improves Uptake of All Lines of Chemotherapy in Advanced Non–Small-Cell Lung Cancer: A 10-Year Retrospective Population-Based Review. J. Thoracic Oncol., 9: 1180-1186, doi: 10.1097/JTO.0000000000000225 [Abstract]

Prostate cancer in younger men — More frequent and aggressive?

Early onset prostate cancer is a newly identified, more aggressive subtype often linked to genetic mutations.

The number of younger men diagnosed with prostate cancer has increased nearly 6-fold in the last 20 years, and the disease is more likely to be aggressive in these younger men, according to a new analysis from researchers at the University of Michigan Comprehensive Cancer Center.

Typically, prostate cancer occurs more frequently as men age into their 70s or 80s. Many prostate cancers are slow-growing and many older men diagnosed with early stage prostate cancer will end up dying from causes other than prostate cancer.

But, the researchers found, when prostate cancer strikes at a younger age, it’s likely because the tumor is growing quickly. “Early onset prostate cancer tends to be aggressive, striking down men in the prime of their life. These fast-growing tumors in young men might be entirely missed by screening because the timeframe is short before they start to show clinical symptoms,” says Kathleen A. Cooney, M.D., professor of internal medicine and urology at the University of Michigan.

Peter Rich was 59 when he was diagnosed with stage 4 prostate cancer. His Prostate-Specific Antigen (PSA)  levels were relatively low, but the disease had already spread to his ribs, spine and lymph nodes.

To think of mortality was devastating. It was like any major loss – shock and numbness,” says Rich, who had to retire from his job as a school social worker because of his cancer treatment. Rich was diagnosed six years ago. Average survival for stage 4 disease is generally less than three years.”What we both said when we got the diagnosis was, well, that’s not acceptable,” Rich says of himself and his wife, Carol. “I’m a fighter.”

Cooney and Scott Tomlins, M.D., Ph.D., assistant professor of pathology at U-M, are leading a new study supported by the U.S. Department of Defense to look at DNA of both normal and cancerous prostate tissue of men diagnosed with advanced prostate cancer before age 61. They will be looking at whether these younger men are more likely to have inherited genetic mutations. For more information on this study, contact the U-M Cancer AnswerLine at 800-865-1125.

Men with a family history of prostate cancer have a two- to three-times greater chance of being diagnosed with prostate cancer. That risk increases for young men with multiple affected relatives. Prostate cancer runs in Rich’s family. Like Rich, his brother was diagnosed in his 50s, and a cousin and uncle had prostate cancer as well.

The new analysis, which appears in Nature Reviews: Urology, found that men with early onset prostate cancer had more genetic variants than men diagnosed with prostate cancer at a later age. The researchers suggest that genetic counseling or increased surveillance in younger men with a family history of prostate cancer may be warranted.

American men have a 16 percent risk of developing prostate cancer in their lifetime, but only a 3 percent lifetime risk of dying from it. The challenge, Cooney says, is understanding which subset of prostate cancers are most likely to be aggressive and deadly.

The unexpectedly poor prognosis of advanced stage early onset prostate cancer supports the idea that a new clinical subtype might exist in the subset of men with early onset prostate cancer. This subtype is more aggressive and requires more specialty expertise, including genetic sequencing,” Cooney says.

Salinas et al., (2014). Prostate cancer in young men: an important clinical entity. Nat. Rev. Urology11:317–323 doi:10.1038/nrurol.2014.91 [abstract]

Guidelines address long-term needs of prostate cancer survivors

New American Cancer Society Prostate Cancer Survivorship Care guidelines released today outline posttreatment clinical follow-up care for the myriad of long-term and late effects an estimated 2.8 million prostate cancer survivors in the United States may face.

The guidelines are based on recommendations set forth by an American Cancer Society expert panel convened as part of the work of the National Cancer Survivorship Resource Center, a project of the ACS. They are designed to promote optimal health and quality of life for the posttreatment prostate cancer survivor by facilitating the delivery of comprehensive posttreatment care by primary care clinicians.

Prostate cancer survivors represent more than four in ten male cancer survivors and one in five of all cancer survivors in the United States. While guidelines exist for treatment and surveillance for recurrent disease, availability of guidelines for long-term posttreatment care is limited. The American Cancer Society Prostate Cancer Survivorship Care guidelines were developed using a combined approach of evidence synthesis and expert consensus. They address health promotion, surveillance for recurrence and screening for second primary cancers, and the assessment and management of physical and psychosocial long-term and late effects resulting from prostate cancer and its treatment. A key challenge to the development of the guidelines was the limited availability of published evidence informing the clinical management of prostate cancer survivors after treatment.

Among the recommendations:

  • Since information needs evolve as patients transition from treatment through various stages of survivorship, survivor and caregiver information needs should be assessed regularly, with information and support services provided or referred to as necessary.
  • Primary care clinicians should provide regular evaluations of survivors to determine appropriate levels of participation in health promotion and lifestyle modification programs.
  • Primary care clinicians should conduct routine assessments of body mass index among survivors across the prostate cancer survivorship continuum, with recommendations for limiting consumption of high-calorie foods and beverages for survivors who are overweight or obese.
  • Primary care clinicians should educate survivors regarding the association between physical activity and lower overall and prostate cancer-specific mortality and improved quality of life.
  • Since smoking after treatment of prostate cancer increases the risk of cancer recurrence and second cancers, primary care clinicians should assess for tobacco use and offer or refer survivors to cessation counseling and resources.
  • While existing evidence is not definitive with regard to frequency of monitoring for recurrence using PSA testing, a leading clinical practice guideline, The NCCN guidelines for prostate cancer treatment recommend measuring serum PSA levels every 6 to 12 months for the first 5 years after definitive treatment, and then to recheck annually.
  • Clinicians should be aware of a small increased risk of second primary cancers after radiation therapy compared with men receiving surgery. While evidence does not support increased frequency or intensity of screening, adherence to routine ACS screening guidelines for the early detection of any new cancers is recommended.
  • Survivors should be assessed for physical (e.g.: urinary, sexual, bowel) and psychosocial effects of prostate cancer and its treatment; the focus of assessment should be tailored to the type of cancer treatment received and current disease state to trigger appropriate self-management and clinical management strategies for support and therapy.
  • Estimates indicate that as many as 30% of patients with prostate cancer experience clinically relevant general distress, 25% have increased anxiety, and nearly 10% experience major depressive disorder. These guidelines affirm early identification, treatment, and ongoing assessment for psychological distress as important aspects of prostate cancer survivorship care.

We are hopeful that the hard work that went into the development of these much-needed guidelines will pay off in improved care for the approximately 240,000 men diagnosed with prostate cancer every year,” said Rebecca Cowens-Alvarado, MPH, principal investigator for the National Cancer Survivorship Resource Center, director of Cancer Control Mission Strategy at the American Cancer Society and co-author of the report. “The adoption of these guidelines will be a critical step forward to improve the delivery of prostate cancer survivorship care.”

Additional Information:

Skolarus et al., (2014). American Cancer Society Prostate Cancer Survivorship Care Guidelines. CA: A Cancer Journal for Clinicians. doi: 10.3322/caac.21234 [pdf]

Survey sheds light on common clinical practice for incompletely resected lung cancer

A landmark survey of more than 700 specialists provides crucial real-world insight into the treatments most oncologists choose for lung cancer patients whose tumour has been incompletely resected, an expert from the European Society for Medical Oncology (ESMO) says.

Jean Yves Douillard, from the ICO Institut de Cancerologie de l’Ouest René Gauducheau, France, Chair of the ESMO Educational Committee, was commenting on a paper published in the journal Lung Cancer. In the study, researchers led by Raffaele Califano of The Christie NHS Foundation Trust, Manchester, UK, surveyed 768 oncologists from 41 European countries about the treatments they offered patients who had “R1 resected” non-small-cell lung cancer.

R1 resection is a term used by oncologists to indicate that it is possible to find microscopic evidence of cancer cells remaining after a cancer has been surgically removed.

We know that incomplete resection, or R1 resection, is associated with a higher risk of relapse but there are currently no strong evidence-based recommendations on how to treat these patients after surgery,” Douillard says.

This study is important since it provides a good overview on how the problem is handled in clinical practice all over Europe by practitioners who treat lung cancer.”

Overall, 83% of experts surveyed were medical oncologists –specialists trained to treat cancer using chemotherapy, targeted therapies, immunotherapy and other medications.

Of the respondents, 91.4% prescribed chemotherapy, mostly cisplatin/vinorelbine or cisplatin/gemcitabine. The survey showed that the majority of doctors (85%) discussed with the patient the fact that there was limited clinical evidence to guide treatment options. Almost 50% of participants prescribed radiotherapy, with radiation oncologists most likely to offer this treatment approach.

Treating physicians clearly believe in what they do, and try to provide the best for their patients,” says Douillard. “According to the survey, however, practice is heterogeneous and varies according to the specialty of the treating physician—whether they are radiation oncologists or medical oncologists. This is why treatment decisions are best made by multidisciplinary teams.”

The evidence gathered in this survey is supported by the recommendations of the 2nd ESMO Consensus Conference on Lung Cancer held in 2013, Douillard notes. That group of worldwide recognised experts recommended adjuvant chemotherapy and adjuvant radiation in R1 resected patients.

The authors of the latest paper call for prospective trials to be undertaken to provide stronger evidence to guide post-surgery treatment in this situation. Douillard agrees that such trials would be informative.

However, trials of adjuvant treatment in R1 resected lung cancer would be very difficult to design and perform, as this is fortunately an infrequent occurrence. R1 resection would also need to be clearly defined in such studies, as it actually represents a quite heterogeneous group.”

Based on evidence from clinical trials in resected patients in whom all tumour cells have been completely removed, there is a rationale for using both chemotherapy and radiotherapy in R1-resected non-small-cell lung cancer,” Douillard says.

As the authors of this survey state, definitive proof would come from a randomised clinical trial, although such studies would be difficult to perform.”

Additional Information:

Califano et al., (2014). Use of adjuvant chemotherapy (CT) and radiotherapy (RT) in incompletely resected (R1) early stage Non-Small Cell Lung Cancer (NSCLC): A European survey conducted by the European Society for Medical Oncology (ESMO) Young Oncologists Committee. Lung Cancer85(1):74–80 [Abstract][pdf]

Older people not receiving adequate access to cancer care

Older people all around the globe are being denied proper access to cancer care, according to an editorial by Queen’s University Belfast academic, Professor Mark Lawler of the Centre for Cancer Research and Cell Biology.

In an editorial in the BMJ (British Medical Journal) Professor Lawler said: “there is increasing evidence from around the world that elderly patients are being ‘undertreated’, leading to a ‘survival gap’ between older and younger patients.

We need a fundamental change in cancer policy for the elderly patient. Our current practices are essentially ageist, as we are making judgements based on how old the patient is rather than on their capacity to be entered into clinical trials or to receive potentially curative therapy. It is disappointing that we see different principles being applied for older patients when compared to younger patients, with these differences leading to poorer outcomes in the elderly patient population.”

Professor Lawler’s findings are published in an editorial in the BMJ entitled, ‘Ageism In Cancer Care: We Need to Change The Mindset‘. It states the need to redress the disparities in the policy on cancer for older patients, citing a recent position paper from the European Organisation for Research and Treatment of Cancer, the Alliance for Clinical Trials in Oncology and the International Society of Geriatric Oncology recommending that clinical trials should be without an upper age limit.

A high proportion of older women with a certain form of breast cancer (‘triple negative’) receive less chemotherapy than their younger counterparts – despite evidence of the treatment’s efficacy in this patient cohort, the authors claim.

They also point out that more than 70 per cent of deaths caused by prostate cancer occur in men aged over 75 years, who usually have more aggressive disease. Few older patients, however, receive treatment for localised prostate cancer, and in most cases they are denied access to chemotherapy for advanced disease, they add.

Colorectal cancer is another disease of older people, yet the evidence again suggests that optimal treatment is not being provided to this patient cohort,” Professor Lawler continues.

The paper sets its argument within the context of an ageing society – both locally and globally. Estimates for the UK suggest that 76 per cent of cancers in men and 70 per cent of cancers in women will occur in the over-65 population by 2030.

In the US, the number of over-65s is set to double at least, from around 40 million in 2009 to 89 million in 2050. Cancer is mainly a disease of the elderly. Given our ageing demographic, the paper argues, this will lead to an exponential increase in the number of cancer deaths unless we change our approach towards the elderly cancer patient.

The International Cancer Benchmarking Partnership – a collaboration that compares clinical outcomes between Australia, Canada, Denmark, England, Northern Ireland, Norway, Sweden and Wales – has indicated decreased survival for patients older than 65 years. A EUROCARE 5 study confirmed this trend, suggesting that the survival gap was widening between older and younger patients in Europe.

The evidence provided highlights the ‘urgent need’ for a ‘geriacentric’ strategy that maximises clinical trial activity in older patients, makes existing treatments more available and develops new approaches that are well tolerated in older people, the paper says in its closing comments.

Professor Lawler concludes: “Such a strategy will also have to ensure that the principle of early diagnosis (underpinning more effective and less aggressive treatment) is applied in older patients as well as in their younger counterparts. Only then can we truly deliver a comprehensive cancer service to the elderly population in our society.

Lawler et al., (2014). Ageism in cancer care: We need to change our mindset. BMJ348:g16  doi: http://dx.doi.org/10.1136/bmj.g1614 [Abstract]

Advances in nanotechnology’s fight against cancer

As cancer maintains its standing as the second leading cause of death in the U.S., researchers have continued their quest for safer and more effective treatments. Among the most promising advances has been the rise of nanomedicine, the application of tiny materials and devices whose sizes are measured in the billionths of a meter to detect, diagnose and treat disease.

A new research review co-authored by a UCLA professor provides one of the most comprehensive assessments to date of research on nanomedicine-based approaches to treating cancer and offers insight into how researchers can best position nanomedicine-based cancer treatments for FDA approval.

The article, by Dean Ho, professor of oral biology and medicine at the UCLA School of Dentistry, and Edward Chow, assistant professor at the Cancer Science Institute of Singapore and the National University of Singapore, was published online by the peer-reviewed journal Science Translational Medicine. Ho and Chow describe the paths that nanotechnology-enabled therapies could take — and the regulatory and funding obstacles they could encounter — as they progress through safety and efficacy studies.

“Manufacturing, safety and toxicity studies that will be accepted by the Food and Drug Administration before clinical studies are just some of the considerations that continue to be addressed by the nanomedicine field,” said Chow, the paper’s co-corresponding author.

Compared with other available therapies, nanomedicine has proven to be especially promising in fighting cancer. In preclinical trials, nanomaterials have produced safer and more effective imaging and drug delivery, and they have enabled researchers to precisely target tumors while sparing patients’ healthy tissue. In addition, nanotechnology has significantly improved the sensitivity of magnetic resonance imaging, making hard-to-find cancers easier to detect.

“A broad spectrum of innovative vehicles is being developed by the cancer nanomedicine community for targeted drug delivery and imaging systems,” said Dr. Ho, the paper’s corresponding author and co-director of the Jane and Jerry Weintraub Center for Reconstructive Biotechnology at the UCLA School of Dentistry. “It is important to address regulatory issues, overcome manufacturing challenges and outline a strategy for implementing nanomedicine therapies — both individually and in combination — to help achieve widespread acceptance for the clinical use of cancer nanomedicine.”

Ho’s team previously pioneered the development of a nanodiamond-doxorubicin compound named NDX. In preclinical studies conducted with Chow, NDX was found to be safer and more effective than unmodified doxorubicin, a clinical standard, for treating breast, liver and other cancer models.

Ho and Chow’s new report features multiple studies in which the use of nanoparticles was translated from the preclinical to the clinical stage. In several of the highlighted studies, nanotechnology-modified drugs showed improvements over conventional, drug-only approaches because of their ability to overcome drug resistance (which occurs when tumors reject the drug and stop responding to treatment), to more effective tumor reduction, among other advantages.

The authors also describe how algorithm-based methods that rapidly determine the best drug combinations, and computation-based methods that draw information from databases of drug interactions and side effects, to help rationally design drug combinations could potentially be paired with nanomedicine to deliver multiple nano-therapies together to further improve the potency and safety of cancer treatments.

“This research review by Dr. Ho and his colleagues lays the groundwork for nanomedicine to become a widely accepted cancer therapy,” said Dr. No-Hee Park, dean of the UCLA School of Dentistry. “This blueprint for navigating the process from bench research to mainstream clinical use is invaluable to the nanotechnology community.”

Dr. Ho, also a professor of bioengineering and a member of the Jonsson Comprehensive Cancer Center and California NanoSystems Institute, noted that nanomedicine regulation is still in its early stages, but the clinical use of existing nanoparticle drugs, such as the protein-modified breast cancer drug Abraxane, is a promising start.

“The FDA’s approval of Abraxane provides a strong foundation for the continued acceleration of new cancer nanomedicine therapies and imaging solutions in the fight against cancer,” Ho said.

Chow and Ho (2013). Cancer Nanomedicine: From drug delivery to imaging. Sci. Transl. Med., 5, 216rv4, DOI: 10.1126/scitranslmed.3005872 [Abstract]