DIET QUALITY LINKED TO PANCREATIC CANCER RISK

In a large new study of older Americans, researchers find that people with the healthiest eating habits are about 15 percent less likely to develop pancreatic cancer than those with the poorest diets.

In the analysis of data on more than 500,000 Americans over age 50, men in particular, especially those who were overweight or obese, appeared to benefit most from a high quality diet.

"It is important to note that our findings are based on overall diet and not individual foods. A combination of many foods contributed to the observed association between greater compliance with the Dietary Guidelines and lower risk of pancreatic cancer," lead author Hannah Arem of the National Cancer Institute in Bethesda, Maryland, told Reuters Health in an email.

Though pancreatic cancer is rare - about 1.5 percent of Americans will develop the disease during their lifetimes - it is one of the most aggressive and lethal cancers. Only about six percent of people with pancreatic cancer are still alive five years after diagnosis, according to Arem.

Past studies looking at the relationship between diet and risk for pancreatic cancer have tended to focus on individual foods and found few connections, according to her team's report, published in the Journal of the National Cancer Institute.

To examine links between overall diet and cancer risk, Arem and her colleagues used the government-designed Healthy Eating Index published in 2005 (HEI-2005) as a basis for rating the overall quality of people's diets.

They applied those criteria to responses from 537,218 men and women who were part of the American Association for Retired Persons Diet and Health Study. Between 1995 and 1996, participants filled out diet questionnaires about how often they ate items on a list of 124 foods.

Arem's team then divided participants into five groups based on how closely their diets met HEI-2005 recommendations for consuming healthy foods such as fruits, vegetables and whole grains and limiting unhealthy ones, like red meat and junk foods.

Scores on the index range from 0 (no guidelines met) to 100 (all guidelines met), with high scores indicating the healthiest eating patterns.

Using state cancer registries and Social Security Administration data, the researchers followed participants for about 10 years and found that 2,383 people developed pancreatic cancer.

About 22 percent of the pancreatic cancer cases were among people with the lowest HEI-2005 scores, while 19 percent were in people with the highest scores. Overall, that translates to a 15 percent lower risk among those with the healthiest diets.

Among men who were overweight or obese, however, those with healthy eating scores in the top-fifth group were 28 percent less likely than their counterparts in the bottom-fifth to develop pancreatic cancer. The same effect was not seen among overweight women.

When the researchers adjusted for other factors linked to pancreatic cancer risk, including smoking, alcohol consumption and diabetes, the effects of diet quality remained the same.

Arem's team also looked at specific subgroups of foods and found that people who ate the greatest amounts of certain healthy foods, such as dark-green and orange vegetables, legumes, whole grains and low-fat milk had lowered risk for pancreatic cancer.

The researchers point out in their report, though, that other recent reviews of the literature have not found similar results for people who ate lots of fruits and vegetables, for example.

"Our study showed an association between diet and pancreatic cancer risk, rather than cause and effect. In general, maintaining a healthy diet has many health benefits," Arem said.

Dr. Rachel Ballard-Barbash, also of the National Cancer Institute, and her colleagues also note in an editorial accompanying the new study that attempts to link individual foods or nutrients to cancer risk have yielded conflicting results.

While some understanding about the relationship between diet and certain cancers has been gained, that "knowledge has not yet translated into noticeable reductions in the incidence of the major cancers with diet-related etiology," they write.

Dr. Alfred Neugut, who studies digestive cancers and epidemiology but was not involved in the current research, agreed there are still a lot of unknowns about the links between diet and cancer.

"If you go out of your way to have a healthy diet, then you're probably going out of your way to be healthy in other ways," Neugut, a professor of medicine at Columbia Presbyterian Medical Center in New York, told Reuters Health. So it's difficult to tease out whether it's really the diet alone that explains the decreased risk seen in the new study.

"It's always safe to say that it's prudent to eat a healthy diet," he said. But, he added, "I would say that diet and cancer is a topic that, despite huge numbers of studies and huge amounts of money invested, has eluded any dramatic findings."

Source: Reuters

LOOKING FOR LESSONS IN CANCER´S "MIRACLE" RESPONDERS

Nearly every oncologist can tell the story of cancer patients who beat the odds, responding so well to treatment that they continued to live many years disease-free, while most of their peers worsened and eventually died.

Dr. David Solit decided to find out why.

Solit, an oncologist at Memorial Sloan-Kettering Cancer Center in New York City, delved into the case of a woman with advanced bladder cancer who volunteered for a 45-patient study of the Novartis drug Afinitor. He discovered that a combination of two gene mutations made her particularly receptive to the treatment.

"Every other patient died, but she's without evidence of disease for more than three years now," said Solit.

Over the past century, such patients - sometimes called "outliers" or "super responders" - have stood out by staging remarkable recoveries, or long-term benefit, from cancer drugs that provide little or no help to others. Little heed has been paid to them because there was no way to know why they fared so well. In most cases, the drugs that helped them were abandoned because they helped too few patients.

Now, armed with huge advances in genetic sequencing technology and growing knowledge of the genetic underpinnings of cancer, a handful of top academic centers are taking a new look at outlier patients. The research may lead to new uses for well-known treatments as it becomes clearer why particular patients respond so well, or even revive drugs left for dead if the right patient population for the treatment can be identified.

"These experiences have always been out there, where somebody's grandmother was told she had two months to live and they tried something and she bounced back," said Dr. Bill Hahn, an oncologist with the Dana-Farber Cancer Institute. "But nobody ever understood why grandma responded in such a really amazing way."

The Bethesda, Maryland-based National Cancer Institute (NCI) and academic researchers it sponsors have just launched "super responder" initiatives to match patients having little-known gene mutations to drugs already shown to help others with the same mutations, even if their tumors are for a variety of organs.

New York's Sloan-Kettering, prompted largely by Solit's research, aims to create an "outlier" clinic devoted to explaining exceptional responses. Other projects are underway at Houston's MD Anderson Cancer Center and Boston's Dana-Farber.

Drugmakers are cautious, if only because they are sufficiently busy trying to develop new medicines against some 300 identified cancer gene mutations. With the priority on developing drugs that will help large numbers of patients, they are reluctant, at least for now, to look backward to salvage failed drug studies.

"We've tried to develop our drugs very specifically so we actually develop the drug for the right population of patients" in the first place, said Sandra Horning, a senior oncology executive at Roche's Genentech unit.

But Harold Varmus, director of the NCI, says drugmakers stand to benefit hugely from outlier research.

"(Drugmakers) are struggling now," Varmus said. "They know there's a lot of genetic damage in tumors, but they don't know which kind of genetic damage represents the best target for developing new drugs."

GENOME SEQUENCING AS STEP ONE

Fueling the research is new technology that has brought the cost of sequencing the human genome down from tens of millions of dollars to about $5,000. The cost of such analysis is expected to drop to as little as $1,000 in the next few years.

"It will be cheaper to do your whole genome sequencing than to get an MRI scan," said Dr. Christopher Austin, director of the National Center for Advancing Translational Sciences. "When that happens, identifying whether a mutation is making you an exceptional responder will be much easier."

Austin expects special-responder research will eventually link individual gene mutations to totally different ailments beyond cancer, allowing drugmakers to broaden the use of their medicines.

A tumor sample from Solit's patient underwent whole genome sequencing - meaning all genes within it were analyzed for mutations, or variations, in the repeat stretches of compounds called bases that make up the genetic code.

"She had 17,000 mutations in her tumor that were not found in her normal cells," Solit said. After months of analyzing 140 mutations that were considered suspects, two of them - genes named TSC1 and NF2 - stood out.

"It was like, 'Wow,' that's why the patient was unique, and why even though Afinitor was generally disappointing in the bladder cancer trial, it was the right drug for her," Solit said. "It was the combination of both mutations that probably led to her complete response," especially the TSC1 mutation.

Zeroing in on the two genes - among more than 20,000 human genes that make proteins - would not have been possible even five years ago, Solit said. "Maybe we would have looked at one gene and if that didn't show anything we'd look at another. Now we can sequence the entire genome and look at every gene, every needle in the haystack, at the same time."

By linking the TSC1 mutation to bladder cancer, Solit has discovered a new "biomarker," or suspected link, to the disease, while simultaneously identifying a possible appropriate drug for patients with any type of cancer who have that mutation.

The next step, he said, is to develop a diagnostic test for the TSC1 mutation and use it to screen patients being treated at his hospital for all varieties of cancer.

"We hope by year's end to be routinely doing TSC1 testing on large numbers of patients," Solit said. "The mutation could be important across tumor types."

Once a small group of patients with the mutation is identified, they would all be treated with Afinitor - which is now approved for cancers of the breast, kidney and pancreas - regardless of the type of cancer.

"If I was sitting in a pharmaceutical firm and I read about David Solit's case, I would say, 'Gee, this is a remarkable change: the mutations that can be found are reasonable targets for developing drugs,'" the NCI's Varmus said.

RESURRECTING DRUGS, FINDING NEW USES

Hundreds of drugs have been abandoned over the years after failing clinical trials, although many had their own exceptional responders.

Some of those drugs could be resurrected, and newer ones could be saved, if the genetic links are established, Solit said. He sees Roche's Avastin as a candidate for study for new, or more targeted, uses as well.

With annual sales of more than $6 billion, Avastin is approved to treat cancers of the colon, lung and kidney.

The U.S. Food and Drug Administration in late 2011 withdrew its approval of Avastin for breast cancer, three years after clearing it for the condition. Subsequent research showed the drug was not effective enough to justify its risks, even though some women had strong responses to the medicine.

Philippe Bishop, a senior research executive at Roche's Genentech unit, said exceptional responses have been seen in patients taking Avastin for breast cancer and other cancers, but no specific genetic reason has been identified.

To get a clearer picture, the company last year started an online study called Invite, in which patients who have taken Avastin are asked to donate a saliva sample for genetic analysis, and to complete a survey that can help assess whether they had an exceptional response to Avastin.

"We're trying to correlate what makes them unique and maybe what part of their genetic makeup makes them do so well," Bishop said, adding that exceptional response would be defined as being alive for a long time without their disease getting worse.

MD Anderson, meanwhile, is encouraging its doctors to submit tumor samples from exceptional responders in past drug trials for a detailed genetic analysis.

"We're looking at data from several dozen trials in a variety of cancers," said senior researcher Dr. Funda Meric-Bernstam.

She noted exceptional responders also include patients who fare exceptionally poorly in trials, in terms of side effects or development of drug resistance. "They are the flip side of the coin, so we want to know why their tumor outsmarted the drug." That information could help in designing drugs that sidestep side effects and produce more-prolonged benefit.

Novartis, like Genentech and other drugmakers, designs its cancer studies around patients with a single pre-identified cancer-gene mutation.

But research chief Mark Fishman said the Swiss drugmaker has also begun routinely sequencing tumors of the patients for another 300 known cancer-gene mutations before they enter early-stage studies, an extra step that could help explain eventual exceptional responses to its drugs.

"In any given patient, if we analyze only one gene we may not have a complete enough picture of the cancer because sometimes you have a time bomb sitting in another gene," Fishman said. Such interaction of cancer genes is a main reason drugs no longer work - why the cancer recurs - after an initial period of effectiveness from a drug, he said.

Dana-Farber's Hahn said he knows of no trials that have pulled together patients having the same gene mutation as one already tied to a special response to a given drug. But Dana-Farber, the NCI and Sloan-Kettering have such studies on their drawing boards, he said.

The research centers will have to work together nationally and overseas to find patients with the shared mutations, Hahn said. "Even if there are only one or two in individual hospitals, you can put them together and do a trial that has a reasonable number of patients."

An NCI initiative is attempting to recover tumor samples from exceptional responders in up to 200 U.S. drug trials it has supported. It will sequence them to find "actionable mutations" that can be targeted for improved treatment.

"This is an incredibly promising opportunity," Varmus said, "for us to take advantage of our new skills and analyze what's really wrong with the cancer cell, and figure out if we have some ways to destroy that cell."

Source: Reuters

CANCER BIGGEST KILLER OF HISPANIC TEXANS

More Hispanic Texans die from cancer than any other cause, according to a new report by the Comparative Effectiveness Research on Cancer in Texas research group.

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The report documents cancer as the leading cause of death among Hispanic Texans under the age of 76. Only three percent of Hispanic Texans are older than 75.

Texas's Hispanic population has more than doubled since 1990. Texans of Hispanic ethnicity now comprise 38 percent of the state's population.

The findings are published in a September 2013 special issue of the Texas Public Health Journal, available online at http://txcercit.org/.

Based on data from the Texas Cancer Registry, Medicare claims records and state vital statistics, researchers compared rates and trends for cancer in Hispanics to those for non-Hispanic whites in Texas. Key findings include:

       Hispanic Texans are less likely to be screened for breast or colon cancer.

       Hispanics have lower rates of new cancer diagnoses for breast, colon and lung cancer.

       Of the cancers diagnosed in Hispanics, fewer were in the earliest, most treatable stages -- those typically detected through screening. Breast cancer at the most advanced stage was diagnosed at a 12 percent higher rate.

       Cancers more common among Hispanics were stomach and liver cancer in men and stomach, liver and cervical cancer in women. Such cancers can arise from untreated infections.

       Overall mortality from all cancer was lower among Hispanics with the exception of stomach and liver cancer.

       Survival after a diagnosis of cancer is superior for Hispanics compared to non-Hispanic whites.

These findings were based on 10 years of data about the diagnoses of new cancer cases and 21 years of data about cancer deaths.

The CERCIT researchers noted one puzzling contradiction. Even though cancers tend to be more advanced when diagnosed in Hispanics, death rates were lower than in the white population. This phenomenon, known as the Hispanic Paradox, has been noted before by other researchers looking at disease and survival rates across the spectrum. Hispanic Americans tend to survive illness and live longer than white Americans with the same diseases even though the Hispanics have less education, income and access to health care.

Foreign-born Hispanics had lower mortality rates than those born in the United States, according to analyses of regional differences within the state.

Source: Science Daily 

CASE REPORT SHOWS TATTOOS MAY HIDE MELANOMA

Melanoma may be hiding in pigmented tattoos, according to a new case report published in JAMA Dermatology. Clinicians from Germany recently published a case report detailing a young white man with a malignant melanoma that developed on a nevus within a large tattoo.

The clinicians, led by Laura Pohl, MD, of Laserklinik Karlsruhe, Germany, reported the case in the hope that other colleagues may help them to gather additional information on similar cases of melanoma developing within tattoos, in addition to the 16 cases already reported in English literature.

“Pigmented lesions in decorative tattoos cause diagnostic difficulties at a clinical and dermoscopic level. In cases of laser removal of tattoos, hidden suspicious nevi may be revealed gradually,” the researchers stated.

According to background information in the case, “the number of decorative tattoos has been increasing, as has the demand for their removal by laser devices.” In this case, a man aged 29 years presented to the clinic for removal of large tattoos that covered most of his chest and arms.

Upon examination of his skin, the clinicians noticed a nevus on his shoulder and advised that it be excised. However, the patient refused excision.

With informed consent, the clinicians began removal of the tattoos in March 2002 with a Q-switched Nd:YAG laser, switching to a Q-switched alexandrite laser after loss of response after 43 sessions.

By November 2009, the clinicians refused to continue laser removal of the tattoo without excision of the nevus. The patient consented.

“At that time, dermoscopy findings showed characteristics of an early melanoma,” the clinicians wrote. “The excisional biopsy results showed the lesion to be a Clark level II malignant melanoma with a Breslow thickness of 0.45 mm.”

Based on their experience with this case, the Dr. Pohl and colleagues made several recommendations. First, skin examination should take place prior to laser tattoo removal, and, if suspicious nevi are found, treatment should be withheld until excision occurs. In addition, clinicians should continue to conduct skin examinations throughout the process of laser tattoo removal. Finally, the clinicians recommended that tattoos never be placed on a pigmented lesion in the skin.

Source:

http://www.cancernetwork.com/melanoma-skin-cancer/content/article/10165/2153265