Obesity and cancer outcome : The Lancet

Obesity and cancer outcome : The Lancet

Obesity and cancer outcome

The Lancet

 

12 million Americans are cancer survivors and a staggering two-thirds of Americans are currently considered overweight or obese. On April 3, the National Cancer Policy Forum of the US Institute of Medicine released a welcome report entitled The Role of Obesity in Cancer Survival and Recurrence. Many epidemiological studies have identified obesity as a factor in cancer risk and prognosis. Obesity is associated with higher cancer incidence, recurrence, progression, and death. The report emphasises how little is still known about the precise cellular mechanisms that link obesity with cancer.

Adipose tissue can behave as an endocrine organ by generating hormones, growth factors, and cytokines that can disrupt regulation of cell growth and survival—the hallmark of malignancy. Knowing the precise cellular targets involved in this interplay could lead to targeted therapeutic approaches for controlling both cancer and obesity. For example, appropriate animal models could allow investigation of mechanisms of obesity and diabetes in precise genetic models of human cancers.

What is not yet known is whether weight management changes the prognosis and outcome in different cancers. The simple solution of tracking individuals' BMI and bodyweight during clinical trials to analyse effect on cancer outcomes needs to become standard practice. Another area of clinical controversy is related to proper chemotherapy dosing in obese cancer patients. Total body-surface area is used to calculate the chemotherapy dose, which does not take into account the body's composition (such as an individual's fat percentage). This approach often leads to suboptimum doses of chemotherapy.

But the most important lesson of this report comes from the basic science of obesity-associated cancer risk. Our population-level responses—which have largely failed—are based on a far too simplistic understanding of how obesity contributes to cancer. To address this challenge demands not more poorly thought out intervention trials. 

 Instead, we need greater understanding of the biological mechanisms underpinning cancer and obesity.

Screening of symptomatic women for ovarian cancer: 4 articles (correspondence -RECAP OF LINKS) : The Lancet Oncology : Volume 13, Number 4, 1 April 2012

Blogger's Note: with some exceptions, the Lancet is a subscriber based journal ($$$), registration (free) may be required to view abstracts and/or articles

The Lancet Oncology : Volume 13, Number 4, 1 April 2012

e137 - open access

Screening of symptomatic women for ovarian cancer

Christopher P Crum

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e137 - open access

Screening of symptomatic women for ovarian cancer

Alicia A Tone, David G Huntsman, Dianne M Miller

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e138 - open access

Screening of symptomatic women for ovarian cancer

Aleksandra Gentry-Maharaj, Jatinderpal Kalsi, Matthew Burnell, Ranjit Manchanda, Usha Menon

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e139 - open access (authors' response)

Screening of symptomatic women for ovarian cancer – Authors' reply

Lucy Gilbert, Olga Basso, for the DOvE Study Group

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Commentary: Primary care and diagnosis of cancer : The Lancet Oncology

Primary care and diagnosis of cancer : The Lancet Oncology

"..........These findings raise several questions. Do modes of cancer presentation vary systematically between different groups of patients? Are general practitioners more reluctant to refer young or non-white patients for investigation of possible cancer? Are participants in these groups less willing to accept a referral to investigate possible cancer? Lyratzopoulos and colleagues' study will raise concerns for those involved in diagnosing and treating patients with cancer. This descriptive study suggests several hypotheses concerning pathways to accessing cancer care that deserve to be tested prospectively in future research."

The Lancet Oncology: Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial

The Lancet Oncology, Early Online Publication,  

7 March 2012

doi:10.1016/S1470-2045(12)70075-XCite or Link Using DOI

 Feature

The Women's Health Initiative

Women who use the oestrogen-only form of hormone replacement therapy (HRT) appear less likely to develop breast cancer in the longer term, according to new research published in The Lancet Oncology. A follow-up study of over 7500 women from the Women's Health Initiative trial who took oestrogen for about 6 years and then stopped has found that they are over 20% less likely to develop breast cancer and remain significantly less likely to die from the disease than those who never used HRT, a period of nearly 5 years after stopping treatment. The findings are discussed further in a Comment.

 Summary

Background

By contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort.

Methods

Between 1993 and 1998, the WHI enrolled 10 739  postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50—79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0·625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00000611.

Findings

After a median follow-up of 11·8 years (IQR 9·1—12·9), the use of oestrogen for a median of 5·9 years (2·5—7·3) was associated with lower incidence of invasive breast cancer (151 cases, 0·27% per year) compared with placebo (199 cases, 0·35% per year; HR 0·77, 95% CI 0·62—0·95; p=0·02) with no difference (p=0·76) between intervention phase (0·79, 0·61—1·02) and post-intervention phase effects (0·75, 0·51—1·09).

In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0·01) or a family history of breast cancer (p=0·02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0·009% per year) compared with controls (16 deaths, 0·024% per year; HR 0·37, 95% CI 0·13—0·91; p=0·03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0·046% per year) than did controls (50 deaths, 0·076%; HR 0·62, 95% CI 0·39—0·97; p=0·04).

Interpretation

Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer.

Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study : The Lancet Oncology

open access: Editorial - Ovarian cancer: breaking the silence : The Lancet Oncology (references Avastin studies and NEJM)

Ovarian cancer: breaking the silence

The Lancet Oncology

 

"The heterogeneous nature of cancer makes it a very difficult disease to manage. Although great progress has been made against many types of cancer (as highlighted by recent mortality data from the American Cancer Society), treatment of others has shown little change in the past few decades. Ovarian cancer, for example, has traditionally lagged behind: recent research, however, is starting to provide a better outlook for women with this cancer. Two phase 3 clinical trials published in December, 2011, in the New England Journal of Medicine (GOG018 and ICON7) showed that women with newly diagnosed advanced ovarian cancer given concomitant bevacizumab with a paclitaxel and carboplatin chemotherapy regimen following surgery, and then maintenance bevacizumab, had significantly longer progression-free survival compared with those who received chemotherapy alone. On the basis of these results, on Dec 19, 2011, the European Medicines Agency approved bevacizumab for first-line treatment of ovarian cancer, although it is uncertain whether the US FDA will follow suit....."

"Ovarian cancer is the seventh most common cancer in women worldwide, with nearly a quarter of a million women diagnosed every year. 5-year survival is just 30%, a figure that has not changed for the past 30 years—this contrasts with breast cancer, in which 5-year survival has improved from 50% to 80% over the same period."

TheLancet.com - 9/11 (key paper included - free access - mortality/survivors/World Trade Center)

9/11

Published September 1, 2011

Executive summary

This issue of The Lancet allows reflections on the events of 9/11, and particularly explores some of the research, review, and opinion pieces on the short-term and long-term physical, mental, and public health consequences of the terrorist attacks. The research papers report not only US domestic health effects but also some of the international consequences. Respiratory illnesses and post-traumatic stress disorder are known to be increased in those who survived the World Trade Center disaster, but data reported in this issue show that 9 years after the attacks, rescue and recovery workers continue to have substantial physical and mental health problems. No excess overall mortality is shown, although high levels of exposure to injury or to the dust cloud are linked to increased risk of all-cause and heart-disease-related mortality. An excess of cancer cases is reported in firefighters who survived the disaster which may have implications for policy on eligibility for compensation. New data on battlefield ethics and casualties in civilians and coalition soldiers in Iraq are presented, while Arab-Muslim refugee health in the USA and public health preparedness are reviewed.

one key paper from this Lancet issue (full free access):

The Lancet, Volume 378, Issue 9794, Pages 879 - 887, 3 September 2011

doi:10.1016/S0140-6736(11)60966-5

Mortality among survivors of the Sept 11, 2001, World Trade Center disaster: results from the World Trade Center Health Registry cohort

abstract - The Lancet Oncology : Evolution of platinum resistance in high-grade serous ovarian cancer

Drug advertising in The Lancet : The Lancet

Cancer survivors: still room for improvement : The Lancet Oncology

abstract: Mucinous carcinomas of the ovary and colorectum: different organ, same dilemma : The Lancet Oncology

Mucinous carcinomas of the ovary and colorectum: different organ, same dilemma

Dr Linda E Kelemen ScD a d , Martin Köbel MD b c

Summary

Mucinous carcinomas are uncommon histological types that affect several organ sites. 

 

Primary mucinous carcinomas of the ovary are distinct from other ovarian carcinoma types, but they can pose a particular challenge for correct diagnosis from metastases, which most usually originate from the colorectum. 

 

Correct diagnosis is the mainstay of treatment, because standard practice states that protocols are tailored to the primary organ site. Little is known of mutational alterations in primary and metastatic mucinous carcinomas of the ovary, and few markers exist that can discriminate between them. 

 

We reviewed commonalities between ovarian and colorectal mucinous carcinomas with respect to aetiology, molecular alterations, differential diagnosis, and implications for treatment. 

 

Although primary mucinous carcinomas of the ovary and colorectum share similar mutational patterns and unfavourable outcomes at advanced stage, compared with their non-mucinous counterparts, important differences exist with respect to mucin localisation and specific molecular alterations.  

 

Technologies—eg, next-generation sequencing—could aid identification of additional driver molecular changes that will help clarify the relation between mucinous carcinomas from different organ sites. Perhaps, then, we can consider moving towards testing and adoption of therapeutic approaches tailored to molecular characteristics of mucinous carcinomas, irrespective of organ site, so patients' survival can be optimised.

The making of a modern medic : The Lancet

"...In the past, medical students were selected on the basis of academic knowledge; it was hoped that traits such as communication skills and sound ethics would develop organically throughout the training process. Now, medical students are increasingly selected on the basis of possession of good social skills—many UK medical schools test prospective students' communication skills, and the USA is considering changing their entrance exam to test would-be students' attitudes. Further, teaching at medical school focuses on the legal, moral, and communication attributes that doctors are expected to have, and this focus continues into a doctor's training years. But do these processes produce the professional doctors that the public deserves?...."cont'd

Health of lesbian, gay, bisexual, and transgender populations : The Lancet

"In later adulthood, LGBT are less likely to have a partner or children to provide them with health and social care, resulting in their greater dependence on friends, caregivers, and LGBT organisations. There has been clinical concern about rates of diabetes, ovarian disease, and stroke among transgender older people potentially as a result of long-term hormone treatments...."

Editorial: New guidelines for early detection of ovarian cancer : The Lancet

"....NICE advises primary care professionals to measure serum concentrations of the protein CA125 if a woman (especially if older than 50 years) presents on a persistent or frequent basis with abdominal distension, feeling full or loss of appetite, pelvic or abdominal pain, or increased urinary frequency. If the blood test is positive, an ultrasound of the abdomen or pelvis should be done and, if ovarian cancer is suggested, the woman should be referred to a specialist...."

Guiding the guidelines : The Lancet

...Clinical Practice Guidelines We Can Trust is the tandem document from the IOM—tandem in the sense that one of these standards states that a systematic review must precede guideline formulation. The IOM points out that the database of the Guidelines International Network includes more than 3700 guidelines from 39 countries. The standards were formulated to overcome common deficiencies—particularly in bias and how bias is handled—in existing guidelines. These deficiencies include the variable quality of evidence, poorly done systematic reviews, methodology that is not transparent, a development group that does not reflect all stakeholders, and unmanaged conflicts of interest. The IOM recommends that before the development group is formed, conflicts of interest need to be fully disclosed—and their definition includes financial, intellectual, and institutional interests. The prospective panel members should also explain how any conflicts they might have could influence the guideline process. The IOM is clear in some specific areas: members of the group need to divest relevant financial investments they or family members hold, and not take part in advisory boards or marketing activities with relevant companies. Additionally, the chair and co-chairs should have no conflicts of interest, members with conflicts should form a minority, and funders should have no role in guideline development. Overall, tough talk from the IOM—but much needed talk. Apart from expert members in the group, the standards include involvement of patients or their representatives.

Commentary: Early versus delayed treatment of relapsed ovarian cancer : The Lancet (re: Rustin trial early vs delayed treatments/survival)

full free access The Lancet: Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial : The Lancet Oncology

abstract/full access: Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data : The Lancet

Note: Full access to article is free after registration (free)


"Background

Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival.  

Methods Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995—2007, with follow-up to Dec 31, 2007.

An epidemic of loneliness : The Lancet (essay)

Expansion of cancer care and control in countries of low and middle income: a call to action : The Lancet

Note: includes a number of easy to read charts/comparisons