Thyroid Cancer Fight

Cancer sufferer prepares for his part in toughest race on earth - Health and Family - Yorkshire Post

2012-02-09T09:23:00.001-06:00

By Catherine Scott
Published on Wednesday 8 February 2012 10:42

Dean Clifford is used to pushing himself to the limit.

His hobby is summiting unclimbed mountains, but now he is taking on his biggest challenge yet.

Two years ago Dean, 39, from York was diagnosed with thyroid cancer which had spread to his lungs and skull.

He had just returned from a climbing expedition to Kyrgyzstan where he got to name two previously unclimbed mountains.

“It was a couple of weeks after we got back and my wife said that I had a lump on my neck, I thought it had been there for ages but she suggested that I get it checked out.”

Dean’s doctors wasn’t unduly worried but decided to send him for an ultrasound scan which revealed a lump the size of an apple in his throat.

“I had absolutely no idea. I felt fine and had no discomfort.”

When the tumour was removed from Dean’s thyroid it was found to be malignant and had also spread to his lungs and skull.

“I had to undergo four lots of radiotherapy which meant I had to spend four days in isolation at St James’s each time.”

Dean is so grateful for all the treatment he has received in Leeds and York that he decided he wanted to give something back. And what better way than tackling what has been dubbed the toughest foot race in the world, the Marathon des Sables.

“I am used to pushing myself both mentally and physically and I suppose this is the ultimate.”

Dean is running two marathons a week in preparation for the event in April. It will see him run the equivalent of nearly a marathon a day for six days across the Sahara Desert.

He is more than aware of the challenges ahead but feels it is something he needs to do.

“Temperatures could in excess of 40 degrees and we have to carry everything on our backs so I have been practising running marathons with a backpack on which is tough.

“But we are training in winter so nothing can prepare me for the heat I am going to experience and all the risks that brings with it, such as dehydration.

“I have done running before but nothing like this endurance event. The risk is that if you set off too quickly then by day three or four you have nothing left. It really is a case of pushing yourself to the limit both mentally and physically. I’m used to that but even my wife says I have gone a bit far this time.”

Dean, a plumbing and heating engineer, has been in training with a friend who has done the Marathon des Sables eight times and so has been giving him some top tips.

“A lot of people don’t even managed to finish the event and for others it is just a case of getting to the end. But I am competitive and I am aware this is a race. I want to finish but I don’t want to have walked the whole way.”

As well as the dehydration, other dangers include snakes and scorpions as Dean will be sleeping under a tarpaulin in the desert.

“We have to carry a venom pack with us at all times in case we get bitten,” he says.

Dean is aiming to raise at least £3,000 for Cancer Research UK.

“While I have been getting treatment for my cancer I have seen so many people much poorlier than me. I just want to raise some money to help the research into cancer.”

Dean still has to undergo scans to see whether his cancer has returned.

“I have another scan at the end of February as they think the tumour in my lungs might have started to grow again.

“But whatever they find I am still going to take part in the Marathon des Sables.”

Anyone who wants to sponsor Dean should visit www.justgiving.com/dean-clifford

Race equivalent to six marathons

The Marathon des Sables is a race across 151 miles of the Sahara Desert run over six days – the equivalent of nearly six regular marathons. Temperatures reach in excess of 40 degrees and in addition to that, competitors have to carry everything they will need for the duration (apart from a tent) on their backs in a rucksack (food, clothes, medical kit, sleeping bag etc). Water is rationed and handed out at each checkpoint. It is run ever year and has been dubbed the toughest foot race on earth. While some take part to win, others compete just to complete it.

www.sahara marathon.co.uk

Certain Cancer Drugs May Have Fatal Side Effects: Analysis - US News and World Report

2012-02-06T19:29:00.000-06:00

Certain Cancer Drugs May Have Fatal Side Effects: Analysis

Risk is very small, but doctors, patients should be made aware, investigators say

February 6, 2012 RSS Feed Print

MONDAY, Feb. 6 (HealthDay News) -- Treatment with three relatively new cancer drugs may be linked to a slightly increased risk of death, a new analysis suggests.

While the risk is low, it should be taken into account by doctors and patients, according to Dana-Farber Cancer Institute scientists and colleagues.

The investigators analyzed the findings of 10 clinical trials that included nearly 4,700 patients treated with sorafenib (Nexavar) for kidney and liver cancer; sunitinib (Sutent) for kidney cancer and gastrointestinal stromal tumor; or pazopanib (Votrient) for kidney cancer.

These so-called "targeted" drugs are used to stop the growth or spread of cancer by blocking the vascular endothelial growth factor tyrosine kinase receptors in cancer cells, the researchers explained in a Dana-Farber news release.

The analysis of the clinical trials revealed that the incidence of fatal complications was 1.5 percent in patients who received any of the three drugs, compared with 0.7 percent in patients who received standard treatments or placebos.

Bleeding, heart attack and heart failure were the most common fatal side effects noted in the clinical trials. In addition, liver failure was also reported, according to the report published in the Feb. 6 edition of the Journal of Clinical Oncology.

"There is no doubt for the average patient, these drugs have benefits and are [U.S. Food and Drug Administration]-approved for these indications," study leader Dr. Toni Choueiri said in the news release. "While the absolute incidence of these fatal side effects is very small, the relative risks are higher and patients and practitioners need to be aware of it."

More information

The U.S. National Cancer Institute has more about targeted cancer therapies.

Exercise a Good Pick-Me-Up After Cancer Treatment: Study

2012-02-02T08:18:00.001-06:00

Exercise a Good Pick-Me-Up After Cancer Treatment: Study

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WEDNESDAY, Feb. 1 (HealthDay News) -- Exercise can improve the health, energy and well-being of cancer patients after they've completed their main cancer treatment, a new review finds.

University of Hong Kong researchers analyzed the results of 34 clinical trials that examined the effects of physical activity among adult patients with breast, prostate, gynecologic, colorectal, gastric or lung cancer.

The study was published online Feb. 1 in BMJ.

There were an average of 93 patients in each trial, which included aerobic, resistance and strength training. The patients' average age was 55, and the training lasted roughly 13 weeks.

Breast cancer patients showed improvements in blood sugar control, body mass index (BMI) and body weight, physical functions such as lower limb strength, mental health problems such as fatigue and depression, and quality of life.

Patients with other types of cancer who were physically active experienced improvements in BMI and body weight, physical function such as oxygen consumption and hand-grip strength, depression and quality of life.

Different types and levels of exercise had specific effects. For example, breast cancer patients found that aerobic exercise plus resistance was much more effective on physical fitness, emotional fitness, overall well-being and fears about breast cancer than aerobic activity alone.

The researchers also found that younger patients seemed to gain more benefit from exercise, but said this finding was not entirely conclusive because younger patients could exercise for longer periods of time.

The findings show that "quality of life was a clear significant benefit of physical activity and that clinically, there were important positive effects on physical functions and quality of life," the researchers concluded in a journal news release.

More information

The U.S. National Cancer Institute has more about cancer survivorship.

SOURCE: BMJ, news release, Jan. 31, 2012

BioNews - Cancer drugs may boost breast cancer stem cell growth

2012-01-31T10:53:00.001-06:00

31 January 2012

By Maria Botcharova

Appeared in BioNews 642

Two breast cancer drugs, Avastin and Sutent, may inadvertently aid cancer growth, a study in mice suggests. The drugs, designed to reduce the blood supply to tumours, were found to encourage cancer stem cell growth, potentially fuelling the spread of the cancer. The study, published in PNAS, may explain why patients treated with Avastin are at risk of relapsing and why these drugs fail to improve overall survival rate despite initially slowing the tumour's growth.
In the study, scientists at the University of Michigan treated mice that had breast cancer with Avastin and Sutent (chemical names bevacizumab and sunitinib). The drugs stop new blood vessels forming, a process called angiogenesis, so that the supply of food and oxygen to the tumour is reduced.

The cancer stem cells in the tumours of the treated mice were mostly found in pockets of low oxygen concentration, created, paradoxically, by the reduction in oxygen delivery. Cancer stem cells fuel the spread and growth of a tumour and are difficult to eliminate with radiotherapy and chemotherapy.

However, Dr Max Wicha, who led the study, suggests that such anti-angiogenic drugs may still be important in cancer therapy if used in conjunction with other drugs. 'These agents will need to be combined with cancer stem cell inhibitors, an approach now being explored in the laboratory', he said.

Avastin is currently licensed to treat breast cancer in the UK yet not available on the NHS. The UK's National Institute for Health and Clinical Excellence advised against its use in February 2011, finding insufficient evidence that it prolongs life. The drug was approved by the US Food and Drug Administration for breast cancer in 2008, but this decision was revoked in November 2011. Sutent is not prescribed for breast cancer in the UK or the USA.

Despite the negative findings on Avastin, two studies this week have suggested that it may be useful in treatment during the early stages of breast cancer. Separate studies, performed on 1,200 and 1,900 women, and both published in the New England Journal of Medicine, looked at the use of the drug prior to surgery. They both found that Avastin significantly reduced or even eliminated the tumour, making it easier to operate on. These were initial findings - the longer-term survival rate of women given Avastin pre-operatively is as yet unknown.

SOURCES & REFERENCES

Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia

PNAS | 23 January 2012

Avastin fights early breast cancer in 2 studies: Will it be re-approved?

CBS News | 26 January 2012

Avastin, Sutent increase breast cancer stem cells, U-M study shows

EurekAlert! | 25 January 2012

Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer

NEJM | 26 January 2012

Breast Cancer Survival - Why Avastin And Sutent Don't Help

Medical News Today | 26 January 2012

Lab Paradox May Explain Avastin's Effects

Med Page Today | 26 January 2012

Neoadjuvant Chemotherapy and Bevacizumab for HER2-Negative Breast Cancer

Nebraskans Can Help Fight Cancer by Sharing Daffodils « Nebraska Region

2012-01-19T09:21:00.001-06:00

People all across Nebraska can fight back against cancer and share hope for those facing the disease by supporting the American Cancer Society Daffodil Days®. This longstanding program, which involves offering daffodils to donors every spring in appreciation for their contributions, is about more than just giving beautiful flowers; it is an opportunity to share hope for a world with less cancer and more birthdays, where cancer never steals another year from anyone’s life. For a donation of $10 everyone can support the fight against cancer. As the first flower of spring, the daffodil is the American Cancer Society’s symbol of hope for a world free of cancer.
An important part of Daffodil Days is the Gift of Hope – a bouquet of 10 daffodil stems in a vase, delivered anonymously to cancer patient within the community. The Gift of Hope helps brighten a patient’s day and fosters a relationship, ensuring the patient’s and caregiver’s knowledge that the Society is helping them get well by being in their corner around the clock to guide them through every step of their cancer experience.
A special part of this year’s Daffodil Day, Shar N. Hope, is a limited-edition Boyds® by Enesco® bear designed exclusively for the American Cancer Society Daffodil Days Bear and a Bunch™. She is available for a donation of $25 and comes with a bouquet of 10 daffodil stems.
Anyone wishing to order daffodils should call their nearest American Cancer Society office no later than February 20. For a donation of $10, supporters will receive a bouquet of fresh-cut daffodils and, more importantly, the knowledge that they are helping fight cancer. The flowers will arrive and may be picked up in mid-March.
Dollars raised through Daffodil Days provide the Society with much-needed funds to save lives by helping people stay well by preventing cancer or detecting it early; helping people get well by being there for them during and after a cancer diagnosis; by finding cures through investment in groundbreaking discovery; and by fighting back by rallying lawmakers to pass laws to defeat cancer and by rallying communities worldwide to join the fight.
For more information about Daffodil Days, or to place your order, contact your nearest American Cancer Society office:
Omaha – 402-393-5803
Lincoln – 402-423-4893
Kearney – 308-237-1631

Study finds that tumor cells can prevent cancer spread

2012-01-19T09:13:00.001-06:00

Paradoxical discovery finds that a group of cells known as pericytes help prevent metastasis

BOSTON – A new study finds that a group of little-explored cells in the tumor microenvironment likely serve as important gatekeepers against cancer progression and metastasis. Published in the January 17 issue of Cancer Cell, these findings suggest that anti-angiogenic therapies – which shrink cancer by cutting off tumors' blood supply – may inadvertently be making tumors more aggressive and likely to spread.
One approach to treating cancer targets angiogenesis, or blood vessel growth. In this new investigation, senior author Raghu Kalluri, MD, PhD, Chief of the Division of Matrix Biology at Beth Israel Deaconess Medical Center (BIDMC) and Professor of Medicine at Harvard Medical School (HMS), wanted to find out if targeting a specific cell type, the pericyte, could inhibit tumor growth in the same way that other antiangiogenic drugs do. Pericytes are an important part of tissue vasculature, covering blood vessels and supporting their growth.
Kalluri and his colleagues began by creating mice genetically engineered to support drug-induced depletion of pericytes in growing tumors. They then deleted pericytes in implanted mouse breast cancer tumors, decreasing pericyte numbers by 60 percent. Compared with wild-type controls, they saw a 30 percent decrease in tumor volumes over 25 days. However, contrary to conventional clinical wisdom, the investigators found that the number of secondary lung tumors in the engineered mice had increased threefold compared to the control mice, indicating that the tumors had metastasized.
"If you just looked at tumor growth, the results were good," says Kalluri. "But when you looked at the whole picture, inhibiting tumor vessels was not controlling cancer progression. The cancer was, in fact, spreading."
To understand the mechanism behind this increased metastasis, Kalluri and his team examined the tumor's microenvironment to find out what changes were taking place at the molecular level. They found a fivefold percentage increase in hypoxic areas in tumors lacking pericytes. "This suggested to us that without supportive pericytes, the vasculature inside the tumor was becoming weak and leaky—even more so than it already is inside most tumors—and this was reducing the flow of oxygen to the tumor," explains Kalluri.
"Cancer cells respond to hypoxia by launching genetic survival programs," he adds. To that end, the investigators found evidence of epithelial-to-mesenchymal transition (EMT), a change that makes the cells more mobile, so they can travel through those leaky vessels to new locations, and makes them behave more like stem cells, so they are better able to survive. Experiments that demonstrated fivefold increases in protein markers of EMT showed that the cells had undergone the change. The team also found a fivefold increase in activation of Met, a receptor molecule that promotes cell migration and growth.
Importantly, the team found that these molecular changes occurred inside the smaller, pericyte-depleted tumors that had increased incidences of secondary tumors in the lungs in the mouse models. "This suggested that smaller tumors are shedding more cancer cells into the blood and causing more metastasis," says Kalluri. "We showed that a big tumor with good pericyte coverage is less metastatic than a smaller tumor of the same type with less pericyte coverage."
Because cancer therapies such as Imatinib, Sunitinib and others have been shown to decrease pericytes in tumors, the researchers' next step was to perform the same experiments in mice with primary tumors, only this time, using Imatinib and Sunitinib rather than genetic programs to decrease pericyte numbers. And while both Imatinib and Sunitinib caused a 70 percent pericyte depletion, the end results, stayed the same: metastasis increased threefold. "We showed that a big tumor with good pericyte coverage is less metastatic than a smaller tumor of the same type with less pericyte coverage," says Kalluri, who corroborated these findings in multiple types of cancer by repeating these same experiments with implanted renal cell carcinoma and melanoma tumors.
Additional experiments showed that combining pericyte-depleting drugs with the Met-inhibiting drug helped suppress EMT and metastasis.
Finally, to determine if the findings were relevant to patients, the scientists examined 130 breast cancer tumor samples of varying cancer stages and tumor sizes and compared pericyte levels with prognosis. They found that samples with low numbers of pericytes in tumor vasculature and high levels of Met expression correlated with the most deeply invasive cancers, distant metastasis and 5- and 10- year survival rates lower than 20 percent.
"These results are quite provocative and will influence clinical programs designed to target tumor angiogenesis," says Ronald A. DePinho, president of the University of Texas MD Anderson Cancer Center. "These impressive studies will inform and refine potential therapeutic approaches for many cancers."
Meanwhile, for Kalluri, the work suggests that certain assumptions about cancer must be revisited. "We must go back and audit the tumor and find out which cells play a protective role versus which cells promote growth and aggression," says Kalluri. "Not everything is black and white. There are some cells inside a tumor that are actually good in certain contexts."

###

Collaborators in this study include BIDMC investigators Vesselina Cooke and Valerie LeBleu (co-first authors) Doruk Keskin, Zainab Khan, Joyce O'Connell, Yingqi Teng, Michael Duncan, Liang Xie, Genta Maeda, Sylvia Vong, and Hikaru Sugimoto. Additional investigators Rafael Rocha, Aline Damascena, and Ricardo Brentani collaborated from Hospital A. C. Camargo in the National Institute of Oncogenomics of Brazil.
This study was supported by the National Institutes of Health (NIH). Kalluri is a Champalimaud investigator funded by the Champalimaud metastasis programme. Cooke is funded by a Ruth Kirschstein Post-doctoral fellowship. LeBleu is funded by an NIH training grant in gastroenterology. Duncan is funded by an NIH training grant in cancer biology, an NIH supplemental grant to support diversity, and a United Negro College Fund-Merck Postdoctoral Science Research Fellowship. Sugimoto is funded by an NIH research training grant in cardiovascular medicine. O'Connell is funded by the Department of Defense Breast Cancer Predoctoral Traineeship Award.
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is a clinical partner of the Joslin Diabetes Center and a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

The Press Association: Some cancer drugs might aid tumours

2012-01-19T09:13:00.000-06:00

Cancer drugs that shrink tumours by cutting off their blood supply may end up helping them to spread, a study suggests.
Drugs such as Glivec and Sutent reduce the size of tumours but could also make them more aggressive and mobile, it is claimed.
A little-studied group of cells called pericytes that provide structural support to blood vessels act as "gatekeepers" to pen in cancer, scientists have discovered.
Pericytes are wiped out by some advanced cancer drugs that prevent the growth of tumour-nourishing blood vessels, the research shows. As a result tumours find it easier to "metastasise", or spread around the body.
Tests on mice showed that both Glivec and Sutent depleted pericytes by 70% while metastasis rates tripled.
Glivec, the brand name of the drug imatinib, and Sutent (sunitinib) have both been shown in trials to increase patient survival by a significant degree.
However, the research raises the possibility that ultimately they might help cancers become more deadly. Metastasis to vital organs such as the liver or brain is the chief reason why people die from cancer.
The US scientists, whose work is reported in the journal Cancer Cell, began by removing pericytes from breast cancer tumours in genetically engineered mice.
They saw a 30% decrease in tumour volumes over 25 days, but also a three-fold increase in the number of secondary tumours growing in the animals' lungs.
Dr Joanna Owens, science information manager at Cancer Research UK, said: "This research helps us understand more about how they work in different patients, and refine clinical practice. These types of drugs are only used after extensive trials that demonstrate a clear benefit for some patients."

Effect of moisturizers on prevention of hand-foot syndrome associated with capecitabine plus oxaliplatin. - ASCO

2012-01-19T09:12:00.000-06:00

Effect of moisturizers on prevention of hand-foot syndrome associated with capecitabine plus oxaliplatin.

Sub-category:

Multidisciplinary Treatment

Category:

Cancers of the Colon and Rectum

Meeting:

2012 Gastrointestinal Cancers Symposium

Session Type and Session Title:

General Poster Session C: Cancers of the Colon and Rectum

Abstract No:

681

Citation:

J Clin Oncol 30, 2012 (suppl 4; abstr 681)

Author(s):

Kazuyoshi Kawakami, Mitsukuni Suenaga, Takashi Yokokawa, Kazuo Sugita, Yutaro Mae, Eri Nakamoto, Hiroshi Imada, Nobuyuki Mizunuma, Toshiharu Yamaguchi, Toshihiro Hama; Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan; Department of Medical Oncology, Cancer Institute Hospital, Tokyo, Japan; Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Japan; Department of Pharmacy, Cancer Institute Hospital, Tokyo, Japan; Cancer Institute Hospital, Tokyo, Japan
Abstract Disclosures

Abstract:

Background: Capecitabine plus oxaliplatin (XELOX) has been established as first-line treatment for patients with metastatic colorectal cancer. Hand-foot syndrome (HFS) is the most common toxicity associated with capecitabine, and the mechanism of which remains to be clarified. Appropriate management of HFS for continuing treatment is needed to ensure improved survival. In this study, we evaluated the efficacy of our candidate moisturizers for HFS, considering its compliance in each patient at a single institute. Methods: Patients who received XELOX for metastatic colorectal cancer at the Japanese Foundation for Cancer Research, Cancer Institute Hospital, between Apr 1 2010 and Apr 30 2011 were included in this study. Pharmacists conducted the skin care for HFS using moisturizers: heparinoid ointment, a mixture of vitamin A oil and white petrolatums (1:1). All HFS events were graded according to NCI–CTC, version 4.0. The relationship between accumulated dose of capecitabine and incidence of HFS events stratified by frequency of daily moisturizers application was analyzed by using the Kaplan-Meier method. P value of <0.05 was considered significant. Results: Moisturizers were applied two or more times a day in 45 patients (Good compliance group) and once a daily in 28 patients (Poor compliance group). In terms of incidence of grade ≥1 HFS, no significant differences were observed between good compliance group and poor compliance group (p = 0.764). Incidence of grade ≥2 HFS was observed slightly higher in the poor compliance group than in the good compliance group, though the differences were not statistically significant (p = 0.286). Conclusions: The onset of capecitabine-associated HFS is independent of frequency of using moisturizers. However, more frequent application of moisturizers appeared to have a possibility to prevent severe HFS. Assessment for compliance with the moisturizers is important as well as patient-compliance-instruction by pharmacist.

Associated Presentation(s):

1. Effect of moisturizers on prevention of hand-foot syndrome associated with capecitabine plus oxaliplatin.
Meeting: 2012 Gastrointestinal Cancers Symposium
Presenter: Kazuyoshi Kawakami
Session: General Poster Session C: Cancers of the Colon and Rectum (General Poster Session)

Other Abstracts in this Sub-Category:

		1. Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies. Meeting: 2012 Gastrointestinal Cancers Symposium Abstract No: LBA385 First Author: Axel Grothey Category: Cancers of the Colon and Rectum - Multidisciplinary Treatment
		2. Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with metastatic (MET) chemotherapy refractory K-RAS wild-type (WT) colorectal carcinoma (CRC): The NCIC Clinical Trials Group and AGITG CO.20 trial. Meeting: 2012 Gastrointestinal Cancers Symposium Abstract No: 386 First Author: Lillian L. Siu Category: Cancers of the Colon and Rectum - Multidisciplinary Treatment
		3. Final results from study 181: Randomized phase III study of FOLFIRI with or without panitumumab (pmab) for the treatment of second-line metastatic colorectal cancer (mCRC). Meeting: 2012 Gastrointestinal Cancers Symposium Abstract No: 387 First Author: Alberto F. Sobrero Category: Cancers of the Colon and Rectum - Multidisciplinary Treatment
		More...

Abstracts by Kazuyoshi Kawakami:

		1. Effect of moisturizers on prevention of hand-foot syndrome associated with capecitabine plus oxaliplatin. Meeting: 2012 Gastrointestinal Cancers Symposium Abstract No: 681 First Author: Kazuyoshi Kawakami Category: Cancers of the Colon and Rectum - Multidisciplinary Treatment
		2. Prognostic role of Thymidylate Synthase (TS) gene polymorphisms in gastric cancer patients treated with surgery and adjuvant chemotherapy Meeting: 2005 ASCO Annual Meeting Abstract No: 4044 First Author: K. Kawakami Category: Gastrointestinal (Noncolorectal) Cancer - Esophageal, Gastric, or Small Bowel
		3. Loss of heterozygosity at the TS locus affects tumor response and survival in individuals heterozygous for a TS promoter polymorphism Meeting: 2003 ASCO Annual Meeting Abstract No: 492 First Author: K. Uchida Category: Developmental Therapeutics - Experimental Therapeutics - Pharmacogenomics
		More...

Presentations by Kazuyoshi Kawakami:

		1. Effect of moisturizers on prevention of hand-foot syndrome associated with capecitabine plus oxaliplatin. Meeting: 2012 Gastrointestinal Cancers Symposium Presenter: Kazuyoshi Kawakami Session: General Poster Session C: Cancers of the Colon and Rectum (General Poster Session)
		More...

Educational Book Manuscripts by Kazuyoshi Kawakami:

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Medical researchers unsure why thyroid cancer cases on the rise - USATODAY.com

2012-01-17T09:17:00.000-06:00

INDIANAPOLIS – Thyroid cancer, which affects about 11 people per 100,000 each year, seems to be on the rise. It's a trend that baffles medical researchers.

National Cancer Institute statistics suggest that in recent years the number of cases of this often curable cancer has increased by about 6.5%. Over a decade, that has added up to make thyroid cancer the fastest-increasing cancer, says Tod Huntley, an otolaryngologist and head and neck surgeon with the Center for Ear, Nose, Throat and Allergy in Indianapolis.

"Ten years ago, if I saw four new thyroid cancer patients a year, it would have been a lot," says G. Irene Minor, a radiation oncologist with Indiana University Health Central Indiana Cancer Center. "Now sometimes I see that many in a month, and I have seen three in a week."

Thyroid cancer is more common in women younger than 45, Minor said. Doctors don't know why that's the case, but thyroid problems in general — such as hyper- or hypo-thyroidism — are more common in women.

The thyroid helps regulate heart rate, blood pressure, body temperature and weight. Thyroid cancer is three times more common in women than men.

Why is it more prevalent?

Experts remain divided on the cause of the increase.

Some attribute it to better screening. Many smaller tumors are picked up on ultrasounds or scans done for other reasons, says Michael Moore, a head and neck surgeon with Indiana University Simon Cancer Center.

Autopsies conducted on people who died for non-thyroid-related reasons reveal that as many as 80% of people older than 60 have a thyroid lump or malignancy that went undiagnosed, Moore says.

Some think that better screening alone can't explain the increase in thyroid cancer. A recent study showed that the increase is not just in smaller tumors, which might have to do with detection, but also in larger ones, Huntley says.

"There is definitely something going on," he says. "How much is due to increased surveillance and detection and how much is due to an actual biological change in disease prevalence, we don't know, but we know it's both."

Obesity, radiation exposure and diets low in fruits and vegetables are three potential culprits, Huntley says. People who are overweight have a 20% increase in thyroid cancer; those who are obese have a 53% increase. The more dental X-rays a person has, the higher the risk, studies show.

Often, thyroid cancer has no symptoms but is diagnosed when a person or his physician notices a lump in the neck. When symptoms do occur they can include difficulty swallowing or the sensation of a lump in the throat or voice changes.

Amber Skipper, 29, who was diagnosed with thyroid cancer, had felt something in her neck but thought it was a swollen lymph node. She had been prone to bronchitis and fatigue, but she attributed that to being a working mother with two small children.

When she learned she had cancer, she vowed to fight it. Numbers were on her side. The five-year survival rate for thyroid cancer is 97%.

In October 2010, Skipper, of Westfield, Ind., had her thyroid and many lymph nodes removed and underwent treatment with radioactive iodine. She now takes a daily replacement thyroid hormone pill.

Separated from family

Because the iodine is radioactive, Skipper had to be isolated from her family for seven days. She ached to see her two young daughters, now 4 and 2, as well as her husband, Ryan, who would leave her food outside her door.

Argentina's president, Cristina Fernandez, recently had her thyroid removed for what doctors thought was a cancerous nodule. Only after the operation did they decide the mass was not cancer.

In the year since her operation, Skipper started eating more organic foods and taking vitamins. Doctors may not be able to tell her why she got cancer, but she wants to make sure she stays healthy. She also decided to become a medical assistant to help others who are sick.

Her second iodine isolation, which lasted two days, was harder than the first. Her daughters were old enough to miss her.

At the end, she got the answer she wanted: She is cancer-free.

Says Huntley: "If you had to pick a cancer, this is what you would pick."

Cleveland Clinic researcher discovers genetic cause of thyroid cancer

2011-12-24T10:30:00.000-06:00

Genetic analysis revises treatment recommendations related to thyroid cancer

Friday, December 23, 2011, Cleveland: Cleveland Clinic researchers have discovered three genes that increase the risk of thyroid cancer, which is has the largest incidence increase in cancers among both men and women.

Research led by Charis Eng, M.D., Ph.D., Chair and founding Director of the Genomic Medicine Institute of Cleveland Clinic's Lerner Research Institute, included nearly 3,000 patients with Cowden syndrome (CS) or CS-like disease, which is related to an increased risk of breast and thyroid cancer.

Mutations in the PTEN gene are the foundation of Cowden syndrome. PTEN is a tumor suppressor gene, helping to direct the growth and division of cells. Inherited mutations in the PTEN gene have been found in approximately 80 percent of Cowden syndrome patients. These mutations prevent the PTEN protein from effectively regulating cell survival and division, which can lead to the formation of tumors.

"Our investigation into the genetics behind thyroid disease raises important details relevant to diagnosis and treatment," said Dr. Eng. "We hope to promote the earliest diagnosis and most targeted treatment possible."

The conclusions of this research, published in the Journal of Clinical Endocrinology & Metabolism, found that all six patients under age 18 had pathogenic PTEN mutations. The researchers recommend that the thyroids of children with PTEN mutation-causing CS-related disease receive increased surveillance.

Children with thyroid cancer are recommended to have testing for PTEN mutations, which could warrant surveillance for additional cancers or maladies. In contrast, alterations in the SDH and KLLN genes did not associate with thyroid cancer in children.

PTEN gene testing in the setting of genetic counseling is already routinely practiced, and has been a powerful gene-enabled diagnostic test which then personalizes clinical screening and treatment. Once SDH and KLLN findings are independently validated, the tests could be implemented as a clinical routine test as well. Importantly, these three genes belong to different cell pathways so that specific molecular-targeted treatments can be utilized depending on which gene is involved.

CureToday.com: Winter 2011 Article - "Patients on Angiogenesis Inhibitors Should Be Monitored for Heart Issues"

2011-12-23T11:12:00.001-06:00

Patients on Angiogenesis Inhibitors (Including Sutent - jhh) Should Be Monitored for Heart Issues

BY KATHY LATOUR
PUBLISHED DECEMBER 21, 2011

Researchers studying the side effects of new cancer treatments have determined that patients taking a class of drugs that target the VEGF pathway should be monitored for cardiac issues that include high blood pressure, heart attack and congestive heart failure.

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The issue is not to stop the drugs’ use but to make oncologists aware that patients taking these drugs need monitoring, says Javid Moslehi, MD, co-director of the Cardio-Oncology Program at the Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston.

VEGF, or vascular endothelial growth factor, is a protein released more abundantly by tumors, which signals the growth of blood vessels to feed the tumor, a process called angiogenesis. The increasing numbers of angiogenesis inhibitors in development have made this an important area of research, Moslehi says. During the past seven years, four drugs that target the VEGF pathway have been approved by the Food and Drug Administration for use in a number of cancers, including brain, colon, lung, kidney, liver and gastrointestinal tumors. In addition to Avastin (bevacizumab), the FDA has approved Nexavar (sorafenib), Sutent (sunitinib) and Votrient (pazopanib).

“It has been recognized that these drugs cause hypertension,” Moslehi says, “but it was often ignored because they were treating the patient for cancer. But hypertension can be a long-term issue and lead to a number of cardiovascular diseases, including heart failure and stroke.”

A study reported earlier this year in the Journal of Clinical Oncology examined five randomized trials, which compared 3,784 women with metastatic breast cancer who received chemotherapy regimens containing Avastin with women given regimens that did not include the drug.

“This analysis showed a significant increase in [risk for] high-grade congestive heart failure in women taking Avastin—almost five times higher,” says Toni Choueiri, MD, assistant professor of medicine at Harvard Medical School and lead researcher. “This is clinically significant.” Only 1.6 percent of women taking Avastin actually had high-grade congestive heart failure, so while it’s important to note there is a significantly increased risk, there is still a low incidence overall.

In the study, Choueiri points to research on mice indicating that those lacking the VEGF gene have thinned myocardial walls. “What we know is that VEGF may have cardioprotective effects, and when you block it you may get a certain cardiac toxicity,” Choueiri says, adding that physicians may not have attributed symptoms associated with heart failure to Avastin since symptoms could be attributed to other causes, particularly in the breast cancer population where women may have received other treatments recognized as having cardiac toxicity. For this reason, he says, incidents may not have been cited in the studies.

Moslehi and Choueiri point to the trial process for the newer drugs as a time to identify potential cardiac side effects, learn how they can be managed and determine whether they are reversible.

In October, Moslehi and colleagues published a letter in The New England Journal of Medicine that indicated in certain cases that the heart failure seen with Nexavar and Sutent is reversible. “But more studies are needed that prospectively examine these unwarranted side effects.”

Moslehi and Choueiri have joined forces and combined their expertise—cardiology and oncology—to examine the effects of VEGF inhibitors on the cardiovascular system.

“Ultimately, treating the cardiovascular effects of novel chemotherapies requires a team effort between various physicians working together for the benefit of the patient,” Moslehi says.

Health News - Removal of lymph nodes during surgery for thyroid cancer may be beneficial

2011-12-21T09:20:00.000-06:00

Procedure may reduce recurrence rates, lower tumor marker levels

By Rachel Champeau

Papillary thyroid cancer accounts for the majority of all thyroid malignancies, which primarily impact women. A new study indicates that routinely removing lymph nodes in the neck in these cancer patients may help prevent the disease from coming back.

When thyroid cancer metastasizes, lymph nodes in the neck may be affected, but these lymph-node tumors can be tiny and may not be detected by ultrasounds done before surgery to remove the diseased thyroid — or even during the procedure itself.

In an international academic study published in the December issue of the journal Surgery, UCLA researchers and colleagues demonstrate that routine removal of neck lymph nodes during initial thyroid surgery for papillary cancer may lead to lower disease recurrence rates and lower levels of thyroglobulin, a thyroid tumor marker that can be an indicator of disease when elevated.

Although it is standard procedure in some cancer centers, there has been debate in the worldwide surgical community about the benefits of routinely removing neck lymph nodes, a procedure known as prophylactic central neck lymph-node dissection, or CLND.

"We found that re-operation rates due to cancer were lower in patients who had routine removal of these lymph nodes, which suggests a more thorough surgical clearance of disease," said the study's senior author, Dr. Michael Yeh, an associate professor of surgery at the David Geffen School of Medicine at UCLA. "Our findings may help add to growing evidence that this additional procedure, performed during initial thyroid surgery, may be helpful in management of papillary thyroid cancer."

For the study, researchers examined data on 606 patients who received care in one of three endocrine surgical units in the U.S., England and Australia. Patients were divided into two groups: Group A patients had undergone total thyroid removal alone; Group B patients had undergone both thyroid removal and dissection of central neck lymph nodes. Patients were followed for an average of three-and-a-half years following surgery.

The standard pre-operative evaluation of all patients included a fine-needle biopsy of the primary thyroid tumor and determination of neck lymph-node disease status through physical examination and ultrasound of the neck.

The rate of disease recurrence in the entire study population was 6.9 percent. The researchers found that the need for central neck re-operation was significantly lower among patients who had undergone the routine initial central neck lymph-node dissection, compared with those who had undergone only thyroid removal (1.5 percent vs. 6.1 percent).

Stimulated thyroglobulin levels were also lower among patients in Group B, which may demonstrate a more thorough clearing of disease in the patients who had both thyroid and neck lymph-node removal procedures, the researchers said.

"This significant reduction in the need for further surgery in the critical central area of the neck is important, since it reduces risk to the many vital structures housed here, such as the nerves supplying the voice," said study co-author Dr. Mark Sywak of the University of Sydney in Australia.

UCLA's Yeh noted that blood thyroglobulin levels are a useful and sensitive measure in tracking disease recurrence, especially when many tumors in this area are too tiny to be detected using a physical exam or ultrasound.

Rates of temporarily low calcium levels, a common side effect, were significantly higher in Group B patients (9.7 percent), who had neck lymph nodes removed, than in Group A patients (4.1 percent) who had thyroid-removal surgery alone. The rate of long-term complications was low for both groups — about 1 percent.

The researchers said the next step may be to conduct a prospective, randomized clinical trial to further assess the impact of routinely removing central neck lymph nodes during initial surgery for papillary thyroid cancer.

The study took place at UCLA Medical Center; the University of Sydney, Australia; and Hammersmith Hospital at Imperial College London.

Other study authors included Aleksandra Popadich, James C. Lee, Stan Sidhu, Leigh Delbridge and Mark Sywak from the University of Sydney endocrine surgical unit; Olga Levin and Kevin Ro, both students at the David Geffen School of Medicine at UCLA; Stephanie Smooke-Praw from the department of medicine at the Geffen School of Medicine; Maisam Fazel, Asit Arora, Neil S. Tolley and F. Fausto Palazzo from the department of thyroid and endocrine surgery at Hammersmith Hospital in London; and Diana L. Learoyd from the department of endocrinology at Royal North Shore Hospital in New South Wales, Australia.

Clinical Trial Update following Cycles 39 and 40

2011-12-16T11:35:00.000-06:00

Hi, Everyone - I made my 12-weekly visit to St. Louis on December 14 for my quarterly poking and prodding. I got good news again - no new tumors and no growth in the existing ones. Yea! There was no shrinkage, but the point of the study is to try for no growth.

They are now calling me a Progression Free Survivor (PFS). Rather an impressive-sounding label, isn't it? I got no new details about how the study is going from St. Louis, not even hints, but my Lincoln oncologist told me that I'm the longest surviving person with this type of cancer that he's ever heard of. I hope they say that at my funeral in about 40 years!

The side effects, etc., have been about the same but I'm getting used to them after 4-and-a-half years on Sutent. (That doesn't mean I still don't look for ways to minimize them!)

Christopher flew down with me this trip, which was nice. He's a senior and Washington University in St. Louis is a school he's interested in. They seem to be interested in him as well. He came down to be interviewed by their admissions department. He left feeling pretty good about how things went. It would be nice if it went so well that they offered him lots and lots of financial aid to attend, but we'll have to wait and see.

While Christopher was interviewed in one room, a few other admission people came out and talked to me about him. They were all familiar with his activities and academics, oddly enough. They wanted to talk to me mainly about Show Choir and Band and how he managed to do both while taking as many AP classes as he did. They were really impressed that he chose to take summer classes to free up time during the school year for those other activities. (And here I thought it was just to avoid mowing the lawn!)

He's been admitted to the U of Nebraska and Nebraska Wesleyan here in Lincoln as well as Iowa State (which should make his mother's side of the family happy). There are a few other schools he's applied to but hasn't heard back from. I'm not sure to what college he's leaning at the moment, but he has plenty of time to make a decision.

Sara and Matthew are both fine. Matthew's been singing a lot this month with the Lincoln Boys Choir, among other things. He's about ready for everything to be over though. His final concert is Sunday, December 18, at 5:00 at St. Paul Church, for all you Lincoln people.

My next trip will be March 7. I bet the daffodils will be up down there by then.

Thanks again for all your continuing prayers and support. Hope you all have a very Merry Christmas and a Great 2012!

John

BRAF addiction of thyroid cancers makes them therapeutically vulnerable

2011-11-23T08:57:00.001-06:00

BRAF addiction of thyroid cancers makes them therapeutically vulnerable

Papillary carcinoma is the most common form of thyroid cancer. Approximately one quarter of these carcinomas have mutations in the BRAF gene. The prevalence of such mutations is even greater in high-grade carcinomas, particularly those that are refractory to standard treatment, which is radioactive iodine (RAI). A team of researchers led by James Fagin, at Memorial Sloan-Kettering Cancer Center, New York, has now identified a way to potentially exploit the expression of BRAF by such cancers for therapeutic purposes.
Despite the prevalence of BRAF mutations in papillary carcinoma it has remained unclear how dependent thyroid cancers are on BRAF expression. Fagin and colleagues first showed that thyroid tumors in mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas were exquisitely dependent on BRAF for viability. Of therapeutic significance, treating thyroid tumor–bearing mice with drugs that inhibited the BRAF signaling pathway rendered the tumor cells susceptible to a therapeutic dose of RAI. Fagin and colleagues therefore suggest that their data provide rationale for clinical trials testing whether such drugs can restore the efficacy of RAI therapy in patients with papillary thyroid carcinomas expressing BRAF mutations.

###

TITLE: Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation
AUTHOR CONTACT:
James A. Fagin
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Phone: 646-888-2136; Fax: 646-422-0890; E-mail: faginj@mskcc.org.

Overcoming Thyroid Cancer Resistance | www.dailyrx.com

2011-11-22T09:24:00.000-06:00

Overcoming Thyroid Cancer Resistance

BRAF mutations may restore RAI efficacy in papillary carcinomas

Reviewed By: Joseph V. Madia, MD

By: Laurie Stoneham

Published: Nov 21, 2011 11:18 am

(dailyRx)
Thyroid cancer is usually successfully treated with surgery. The problem is - this is one of the cancers that tends to reappear. New research has uncovered a means for overcoming a common obstacle in treating thyroid cancer.
BRAF gene mutations occur in about 25 percent of thyroid cancers, particularly high-grade tumors that often become resistant to standard treatments with radioactive iodine (RAI). Researchers have found that targeting the BRAF mutations may help these tumors become more responsive to therapy.

Work with your healthcare team to develop a comprehensive cancer care plan.

Researchers, led by James Fagin, M.D., chief of Endocrinology Service at Memorial Sloan-Kettering Cancer Center, have found a way to work with BRAF mutations in papillary carcinoma, the most common type of thyroid cancer.
Dr. Fagin and his team first discovered that thyroid cancers were what they called "exquisitely dependent on BRAF for viability."
Next, the team treated mice with thyroid tumors with drugs that blocked the BRAF signaling pathway. They found that this therapy made the tumor cells more responsive to therapeutic doses of RAI.
Researchers suggest this data provides enough evidence for clinical trials to be conducted which will focus on restoring RAI therapy efficacy in patients with papillary thyroid cancers who have BRAF mutations.
This research was published in November, 2011 edition of Journal of Clinical Investigation.

Cancer

Cancer is diagnosed in over 12 million people each year, kills over 7 million and one out of every three people will be diagnosed with an invasive cancer at some point in their lifetime in the United States. Cancer is a group of diseases classified by abnormal and uncontrolled cellular growth in a particular organ or tissue type in the body.
Cancer is caused by a multitude of factors including genetics and infections, but a majority of cancers can be attributed to environmental causes, such as smoking, and being exposed to carcinogens or radiation.

Cancer will produce symptoms that affect the organ it is located in, such as coughing and shortness of breath from a lung cancer, constipation and bloody stools from colon cancer, or headaches and cognitive problems from a brain cancer. Other cancers such as leukemia and blood cancers may produce flu-like symptoms and sudden infections. Some cancers may be discovered by physical evidence, such as feeling a lump in breast cancer.
Treatment is usually one of, or a combination of, surgery, radiation therapy, and chemotherapy. Newer treatments such as hormonal drugs and targeted drugs (Herceptin in breast cancer, Erbitux in colon cancer, Avastin in several) are making cancer treatment even more specific to the patient and the disease. Diagnosis is based off of physical examination and several imaging techniques such as MRI, PET scan laparoscopy and when a pathologist examines a piece of cancerous tissue.

EU regulators back AstraZeneca thyroid cancer drug - Yahoo!

2011-11-18T10:38:00.000-06:00

EU regulators back AstraZeneca thyroid cancer drug

Reuters – 6 hours ago

LONDON (Reuters) - European drug regulators have recommended AstraZeneca's new thyroid cancer pill Caprelsa, or vandetanib, for approval, giving a boost to a drug which has suffered past setbacks.
The Anglo-Swedish drugmaker said in a statement on Friday its application for a marketing authorisation for Caprelsa received a positive opinion from the European Medicines Agency for the treatment of advanced and non-operable medullary thyroid cancer.
Vandetanib was once seen as a potential $1 billion (631 million pounds)-plus blockbuster for AstraZeneca, but suffered a major setback after failing to extend survival in patients with lung cancer.
The drug is now targeted at the niche market of treating patients with non-operable advanced medullary thyroid cancer (MTC), which accounts for about 4 percent of thyroid cancers.
U.S. drug regulators approved it for MTC in April.
Analysts on average now expect sales of Caprelsa to reach $112 million by 2016, according to consensus forecasts on Thomson Reuters Pharma.
AstraZeneca said the European agency came to its decision after reviewing data from Phase III clinical trials of the drug, which included a double-blind trial of 331 patients with advanced MTC that had spread to other parts of the body, and showed a 54 percent reduction in risk for disease progression with Caprelsa compared to placebo.
Thyroid cancer affects around 48,000 people a year in Europe and kills around 6,300, of which between 5 to 10 percent have MTC.
Advanced MTC has a poor prognosis and clinical outcomes for patients with this disease have not changed substantially in the past 20 years. Currently there are no approved therapies in Europe for this advanced stage of the disease.
(Editing by Mike Nesbit and Ben Hirschler)

Mortality Greatest With Recurrence of Papillary Type Thyroid Cancer : IMNG Oncology Report

2011-11-17T10:29:00.001-06:00

Mortality Greatest With Recurrence of Papillary Type Thyroid Cancer

By: CAROLINE HELWICK, Oncology Report Digital Network

SAN FRANCISCO – Thyroid cancer recurs in almost 40% of elderly patients, and while recurrence is accompanied by an increased mortality risk, this seems to be confined to the subset of patients with papillary thyroid cancer, according to researchers from Penn State Milton S. Hershey Medical Center in Hershey, Pa.

"Elderly patients with follicular disease and recurrence did not have a significantly different risk of death compared to patients without recurrences," said lead author Melissa M. Boltz, D.O., who presented the findings at the annual clinical congress of the American College of Surgeons.

About half of patients who develop recurrent disease will die from this, but little is known about the risk of recurrence. "We questioned whether the implications could be different for the elderly population," she said.

The researchers focused on recurrent well-differentiated thyroid cancer (WDTC) in patients aged 65 years or older and assessed its impact on 1-year and 5-year survival, controlling for patient-, disease-, and treatment-related variables.

From the SEER (Surveillance Epidemiology and End Results), Medicare-linked database, they identified 2,883 patients with primary WDTC treated between 1995 and 2007. They documented recurrence through billing codes, evidence of I-131 treatment, thyroid imaging, or the performance of additional thyroid procedures beyond 6 months of diagnosis.

Of these, 1,126 patients (39%) developed recurrent disease, and the recurrent group was not demographically different from the group of patients without recurrence. The majority recurred within the first 2 years of initial treatment, after which the probability of developing recurrence was never more than 45% over 10 years, Dr. Boltz said.

Risk factors associated with recurrence included older age, advanced stage, lack of surgical treatment, and regional disease, she reported.

Regional disease was present in 44% of the recurrent group, vs. only 24% of the nonrecurrent group, and thyroidectomy was performed on 33% vs. 60%, respectively.

At 10 years, of the total thyroid cancer population, 662 (23%) died of some form of cancer with thyroid cancer as the cause of death in 273 (41%).

"In the 1-year landmark analysis, patients with recurrence had a higher risk for cancer-specific mortality within 10 years, versus those without recurrence, and the trend was similar at the 5-year landmark," Dr. Boltz noted.

By histology, patients who recurred with papillary thyroid cancer were significantly more likely to die of thyroid cancer as compared to papillary thyroid cancer patients not experiencing recurrence. Papillary patients who were older, had regional or distant disease, and who did not undergo surgery were also at increased risk for cancer-specific death.

The hazard ratios for thyroid cancer death for papillary thyroid cancer patients were as follows:

• Recurrence: HR, 1.96 (P less than .001).

• Age, 5-year increases: HR, 1.46 (P less than .001).

• Regional disease: HR, 4.90 (P less than .001).

• Distant disease: HR, 16.97 (P less than .001).

• No surgery: HR, 7.98 (P less than .001).

• Treatment other than surgery: HR, 3.47 (P less than 0.001).

In contrast, patients with follicular thyroid cancer had an increase in cancer-specific mortality only in relation to the presence of distant disease (HR, 17.78; P less than 0.001). Older age was also associated with an increase in cancer-specific mortality (HR, 1.24; P = 0.04), but disease recurrence was not (HR 0.58; P = 0.16).

"Unlike papillary cancer, follicular cancer recurrence did not contribute to cancer-specific mortality. The only risks were related to older age and advanced stage," Dr. Boltz reported.

Dr. Boltz cautioned that this study pertained to elderly Medicare patients, and the results should not be generalized to a younger population, in which thyroid cancer is more prevalent.

Dr. Boltz reported no relevant conflicts of interest.

MedWire News - Oncology - Polymorphisms may identify sunitinib poor responders

2011-10-28T09:50:00.001-05:00

By Laura Dean

24 October 2011

Lancet Oncol 2011; Advance online publication

MedWire News: Polymorphisms in the genes encoding vascular endothelial growth factor receptor 3 (VEGFR3) and cytochrome P450 3A5 (CYP3A5) may partially account for the absence of response and low tolerability to sunitinib observed in some patients with renal-cell carcinoma (RCC), researchers report.

"These data suggest that alternative treatment approaches for patients with these genetic variants should be promoted," write Cristina Rodríguez-Antona (Spanish National Cancer Center, Madrid) and colleagues in The Lancet Oncology.

The researchers explain that sunitinib is a tyrosine kinase inhibitor with proven efficacy in RCC, but around 20% of patients do not respond, while around 32% need dose reductions due to toxicity.

In the present study, Rodríguez-Antona and team aimed to identify polymorphisms as potential markers of sunitinib outcome, focusing on genetic variants that could alter the pharmacokinetics and pharmacodynamics of this drug.

They genotyped 101 RCC patients for 16 single nucleotide polymorphisms (SNPs) in nine genes: VEGFR2, VEGFR3, platelet-derived growth factor receptor α (PDGFR-α), VEGF-A, interleukin 8 (IL-8), CYP3A4, CYP3A5, ATP-binding cassette B1 (ABCB1), and ABCB2.

The researchers then assessed associations between each SNP and efficacy and toxicity of sunitinib using multivariable analyses adjusted for clinical factors associated with survival or toxicity.

After a median follow-up period of 21.2 months, the median progression-free survival (PFS) among 89 patients included the efficacy analysis was 12.3 months.

Objective response was assessed in 78 patients with measurable disease; one (1%) patient had a complete response, 36 (46%) had a partial response, 26 (33%) had stable disease, and 15 (19%) had progressive disease.

The analysis showed that two VEGFR3 missense SNPs, rs307826 and rs307821, were significantly associated with reduced PFS with sunitinib. Indeed, median PFS for people with the wild-type (AA) allele at rs307826 was 13.7 months, compared with 3.6 months for heterozygous (AG) individuals. The corresponding values for the rs307821 wild-type (GG) and heterozygous (GT) alleles were 13.7 months and 6.7 months, respectively.

Although not statistically significant, SNPs in ABCB1, ABCG2, and VEGFR2(rs1128503, rs2231142, and rs1870377) also showed a tendency to have worse response to sunitinib in terms of PFS or overall survival.

In terms of toxicity, the CYP3A5*1 (rs776746) high-metabolizing genotype (AG) was significantly associated with a 3.75-fold increased risk for dose reductions due to toxicity.

The researchers conclude that if their findings are independently validated in further studies, "these genetic variants could provide the basis for individualized renal cancer treatment."

In a related commentary, Brian Rini (Cleveland Clinic Taussig Cancer Institute, Ohio, USA) said: "An ideal predictive biomarker is one that is easily and unambiguously measured and reliably separates patients who will benefit from a specific approach from patients who will benefit from an alternative approach. [The present data] thus represent a small but important step toward truly targeted therapy for patients with renal-cell carcinoma."

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Using Gene Therapy to Make Thyroid Tumors More Susceptible to Radioiodine Therapy

2011-10-28T08:56:00.001-05:00

Newswise — Falls Church, Virginia. Oct. 27, 2011 – Some forms of differentiated thyroid cancer (DTC) respond to treatment with radioactive iodine, which is taken up by the thyroid gland, destroying the cancerous cells. However patients with two forms of thyroid cancer, radioiodine-refractory DTC and anaplastic thyroid cancer (ATC), do not benefit from radioiodine therapy, and other treatment options are limited.

Christine Spitzweg, MD, and colleagues from Ludwig-Maximilians-University, Munich, Germany, are exploring a novel therapeutic approach intended to modify the genetic make-up of radioiodine-refractory forms of thyroid cancer to make them more susceptible to the anti-cancer effects of radioiodine therapy. Using a non-viral gene delivery system based on nanoparticle vectors, the researchers are able to introduce the gene for the sodium iodide symporter (NIS) into radioiodine-refractory tumor cells, enhancing their uptake of therapeutic radioiodine.

The vectors contain the NIS gene, a protective polymer, and a synthetic peptide that targets the particle to an epidermal growth factor receptor (EGFR) present at varying levels on the surface of thyroid tumor cells. The researchers mixed the thyroid tumor cells with the nanoparticles. In a parallel experiment, the researchers created a similar nanoparticle complex that lacked the EGFR-specific targeting peptide.

According to data presented today at the 81st Annual Meeting of the American Thyroid Association, tumor cell lines containing higher levels of EGFR incorporated more of the nanoparticle complexes. The tumor cell lines that exhibited the most efficient nanoparticle transduction had a 7-10 fold increase in iodide uptake when the nanoparticles contained the EGFR targeting peptide compared to experiments using the complexes lacking the EGFR targeting peptide.

Preliminary tests of this therapeutic approach in mice indicate that a tumor-selective gene delivery strategy can enhance radioiodine uptake by refractory DTC and ATC tumors.

About the ATA Annual Meeting
The 81st Annual Meeting of the American Thyroid Association will be held October 26-30, 2011 at the Renaissance Esmeralda Resort & Spa in Indian Wells (near Palm Springs), California. This four day creative and innovative scientific program, chaired by Drs. Anthony Hollenberg and Martha Zeiger, has carefully balanced clinical and basic science sessions on the latest advances in thyroidology. The ATA meeting is designed to offer continuing education for endocrinologists, internists, surgeons, basic scientists, nuclear medicine scientists, pathologists, endocrine fellows and nurses, physician assistants and other health care professionals. Visit www.thyroid.org for more information.

About the ATA
The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization with over 1,400 members from 43 countries around the world. Celebrating its 88th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology and Clinical Thyroidology for Patients; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease. Visitwww.thyroid.org for more information.

Researchers explore novel therapeutic approach for thyroid cancer

2011-10-28T08:46:00.001-05:00

Some forms of differentiated thyroid cancer (DTC) respond to treatment with radioactive iodine, which is taken up by the thyroid gland, destroying the cancerous cells. However patients with two forms of thyroid cancer, radioiodine-refractory DTC and anaplastic thyroid cancer (ATC), do not benefit from radioiodine therapy, and other treatment options are limited.
Christine Spitzweg, MD, and colleagues from Ludwig-Maximilians-University, Munich, Germany, are exploring a novel therapeutic approach intended to modify the genetic make-up of radioiodine-refractory forms of thyroid cancer to make them more susceptible to the anti-cancer effects of radioiodine therapy. Using a non-viral genedelivery system based on nanoparticle vectors, the researchers are able to introduce the gene for the sodium iodide symporter (NIS) into radioiodine-refractory tumor cells, enhancing their uptake of therapeutic radioiodine.
The vectors contain the NIS gene, a protective polymer, and a synthetic peptide that targets the particle to an epidermal growth factor receptor (EGFR) present at varying levels on the surface of thyroid tumor cells. The researchers mixed the thyroid tumor cells with the nanoparticles. In a parallel experiment, the researchers created a similar nanoparticle complex that lacked the EGFR-specific targeting peptide.
According to data presented today at the 81st Annual Meeting of the American Thyroid Association, tumor cell lines containing higher levels of EGFR incorporated more of the nanoparticle complexes. The tumor cell lines that exhibited the most efficient nanoparticle transduction had a 7-10 fold increase in iodide uptake when the nanoparticles contained the EGFR targeting peptide compared to experiments using the complexes lacking the EGFR targeting peptide.
Preliminary tests of this therapeutic approach in mice indicate that a tumor-selective gene delivery strategy can enhance radioiodine uptake by refractory DTC and ATC tumors.
Source: American Thyroid Association

Advanced papillary thyroid cancer patients with BRAFV600E gene mutation at higher risk

2011-10-28T08:41:00.001-05:00

Individuals with advanced papillary thyroid cancer (PTC) that are associated with the BRAFV600E gene mutation have a higher risk of recurrent disease and progression to more advanced, poorly differentiated thyroid cancer, according to data presented today at the 81st Annual Meeting of the American Thyroid Association (ATA). An understanding of the biological processes that underlie this progression could lead to the development of more effective therapies.
One approach to studying the role of BRAFV600E in PTC initiation and progression is to create mice in which the gene mutation (BRAFV600E) has been introduced and activated in the thyroid. These transgenic mice develop advanced PTCs that closely resemble human poorly differentiated PTCs. Mabel Ryder, MD, and colleagues from Memorial Sloan-Kettering Cancer Center and the Sloan-Kettering Institute (New York, NY) used BRAFV600E transgenic mice to study the effects of tumor-associatedmacrophages (TAMs), a type of white blood cell, on PTC initiation and progression. In cancers, TAMs are versatile and can either support or inhibit cancer progression. In PTCs, BRAF activation in the thyroid is accompanied by increased levels of colony stimulating factor 1, which stimulates the recruitment of TAMs to the thyroid. Once in the thyroid, TAMs accumulate alongside cancer-associated myofibroblasts (CAMs) to form a dense layer within and around the thyroid. The researchers used genetic techniques to kill the TAMs in PTCs. The result was a significant reduction in PTC size, total tumor cell volume and a more well-differentiated, less advanced PTC. The authors also demonstrated a functional link between TAMs, the recruitment of CAMs and PTC initiation. The researchers observed that when TAMs are depleted during PTC initiation, the density of CAMs is significantly diminished along with an impairment of PTC initiation.
"Many of the new treatments for thyroid cancer, such as kinase inhibitors, aim to block the activity of oncoproteins present within tumor cells. Our data suggests that immune cells in the tumor microenvironment play an important role in the biology of these cancers. This may be clinically relevant since there are new agents in development that can target TAMs, and we believe these should be explored, particularly in patients with advanced forms of the disease," said Dr. Ryder.
Based on these findings, the researchers concluded that TAMs have an important role in the initiation and progression of PTC and may represent a potent therapeutic target for combating advanced thyroid cancers that do not respond to conventional therapies.
Source American Thyroid Association (ATA)

New rapid method for detection of BRAF V600E gene in thyroid tissue

2011-10-28T08:39:00.000-05:00

During surgical removal of thyroid tissue suspicious for cancer, fast, reliable, and cost-effective techniques are needed to analyze the resected tissue for biomarkers—including BRAF V600E, is a molecular biomarker for papillary thyroid cancer (PTC)—that can confirm the presence and type of cancer cells. Researchers have developed a new, rapid method for direct detection of the BRAF V600E gene in thyroid tissue without the need to purify DNA from tumor cells—high resolution melting analysis (HRM).
In HRM analysis, a sample of the resected thyroid tissue is homogenized and the DNA-containing portion is collected and washed. Polymerase chain reaction (PCR), a targeted gene detection technique, is then used to identify the presence of the BRAF V600E gene in the tissue sample. This is achieved without having to purify or sequence the DNA.
Jun Hee Park and G. Park from Chosun University Hospital, Republic of Korea, have demonstrated that HRM is at least as effective as alternative methods that rely on purified DNA for intra-operative detection of the BRAF V600E biomarker, according to data presented today at the 81st Annual Meeting of the American Thyroid Association (ATA). Using HRM to analyze cancerous tissue from 96 patients, Park and Park obtained a positive result for BRAF V600E in 58 of 96 samples (60.4%). The same 96 samples were subjected to two other testing methods that both required DNA purification—DNAsequencing and restriction fragment length polymorphism (RFLP) analysis. These analytical methods yielded a positive BRAF V600E result in 46.8% and 61.5% of samples, respectively. In comparison to these two techniques, direct HRM produced comparable results, was economical, and was suitable for intra-operative use with results available within 50 minutes.
Source: American Thyroid Association

Exelixis' thyroid cancer drug may get early approval - Yahoo! News

2011-10-25T09:18:00.000-05:00

(Reuters) - Exelixis Inc's drug to treat a rare form of thyroid cancermet the main goal of a late-stage study, prompting the company to look to an accelerated approval process that could bring the drug to market within a year.

Shares of San Francisco-based Exelixis were up 18 percent at $7.09 in heavy trading on Monday on Nasdaq. They had touched a high of $7.53 earlier in the day.

Exelixis said based on the study it was requesting permission to begin a rolling submission of data toward the marketing application of the drug cabozantinib in advanced medullary thyroid cancer(MTC).

"With the positive data, we expect cabozantinib's filing to be completed in first quarter of 2012, with potential approval in the third quarter," Lazard Capital Markets analysts said in a note.

The drug significantly improved median progression-free survival (PFS) in patients suffering from MTC to 11.2 months versus 4 months for those on placebo in a trial called EXAM.

While that was lower than the numbers returned by AstraZeneca Plc's competing Caprelsa, Jefferies analysts said the drugs appeared comparable given that the EXAM trial appears to have enrolled more severe patients.

About 44,600 new thyroid cancer cases were diagnosed in the United States during 2010, and about 1,690 people died from the disease, according to the National Cancer Institute.

Cabozantinib, which is also being tested for metastatic ovarian cancer and castration-resistant prostate cancer (CRPC), is an oral drug designed to limit blood supply to tumors and block two segments of a pathway used by cancer cells to grow and spread.

In June, Exelixis reported data from a clinical trial showing cabozantinib led to significant tumor shrinkage in several different types of solid tumors, including 24 percent of patients with metastatic ovarian cancer, but also caused the deaths of six patients.

The EXAM trial is being conducted under a special protocol assessment (SPA) agreement, which guarantees that the design and analysis of the trial are adequate to support a marketing application submission to the U.S. Food and Drug Administration.

(Reporting by Esha Dey and Kavyanjali Kaushik in Bangalore; Editing by Roshni Menon and Supriya Kurane)

Many cancer survivors struggle with PTSD symptoms - Yahoo! News

2011-10-14T10:16:00.001-05:00

NEW YORK (Reuters Health) - A cancer diagnosis can leave lasting psychological scars akin to those inflicted by war, according to a new survey.

More than decade after being told they had the disease, nearly four out of 10 cancer survivors said they were still plagued by symptoms of post-traumatic stress disorder, or PTSD.

Those symptoms include being extra jumpy, having disturbing thoughts about the cancer and its treatment, or feeling emotionally numb toward friends and family.

One in 10 patients also said they avoided thinking about their cancer and one in 20 said they steered clear of situations or activities that reminded them of the disease.

That could amount to a medical problem, in addition to the psychological toll, said lead researcher Sophia Smith from the Duke Cancer Institute in Durham, North Carolina.

"You worry if the patient is avoiding medical care, you worry they might not be getting follow-ups," she told Reuters Health. "We don't have data to support that, but we worry about it."

The survey is based on 566 patients with non-Hodgkin's lymphoma, a relatively common kind of cancer that strikes about 66,000 Americans every year.

Smith's team had surveyed these patients for PTSD symptoms once before, estimating that about one in 12 had full-blown PTSD. The diagnosis involved a trio of symptoms, including avoidance, arousal and flashbacks.

Many more had one or more PTSD symptoms, however. And the new survey, published in the Journal of Clinical Oncology, shows they often persist.

Overall, half of the patients had no PTSD symptoms 13 years after their diagnosis. The problems had disappeared in 12 percent, but had remained or worsened in 37 percent.

"This study found that people seemed to have worse PTSD later on," said Bonnie L. Green, a trauma expert who pioneered the study of PTSD in breast cancer survivors, but was not linked to the new work.

"It's just very stressful for people to be told that they have cancer," Green, of Georgetown University in Washington, D.C., told Reuters Health. "You can't just assume that they feel bad now, but it will go away."

She stressed that it's only a minority of patients who develop full-blown PTSD, but added that depression is common after a cancer diagnosis.

The new survey shows that low-income people are extra vulnerable to the psychological impact of living with cancer.

"I am particularly concerned about the patients who are poor or have less resources," said Smith.

She said doctors have to be better at recognizing distress in patients and improving patients' experience when they get the diagnosis.

"Each time they come in you are asking not only if they're having pain, but also if they are having stress," Smith said. "There are wonderful therapies out there."

Those treatments include trauma counseling and talk therapy, which have been proved effective in several studies. Smith recommended the website http://www.ptsd.va.gov/ for people interested in more information about PTSD.

SOURCE: http://bit.ly/n1pJMg Journal of Clinical Oncology, online October 11, 2011.

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How do people cope emotionally if the cancer recurs?

2011-10-06T11:58:00.000-05:00

How do people cope emotionally if the cancer recurs?