Saturday, December 24, 2011
Friday, December 23, 2011
CureToday.com: Winter 2011 Article - "Patients on Angiogenesis Inhibitors Should Be Monitored for Heart Issues"
Patients on Angiogenesis Inhibitors (Including Sutent - jhh) Should Be Monitored for Heart Issues
PUBLISHED DECEMBER 21, 2011
Wednesday, December 21, 2011
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.
Friday, December 16, 2011
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!
Wednesday, November 23, 2011
BRAF addiction of thyroid cancers makes them therapeutically vulnerablePapillary 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.
James A. Fagin
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Phone: 646-888-2136; Fax: 646-422-0890; E-mail: firstname.lastname@example.org.
Tuesday, November 22, 2011
Overcoming Thyroid Cancer Resistance
BRAF mutations may restore RAI efficacy in papillary carcinomas
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.
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 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.
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.
Friday, November 18, 2011
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)
Thursday, November 17, 2011
Mortality Greatest With Recurrence of Papillary Type Thyroid Cancer
Friday, October 28, 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 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
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)
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
Tuesday, October 25, 2011
(Reuters) -'s drug to treat a rare form of met 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( ).
"With the positive data, we expect cabozantinib's filing to be completed in first quarter of 2012, with potential approval in the third quarter,"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'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 forand 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)
Friday, October 14, 2011
Thursday, October 6, 2011
For some people, cancer is a one-time event. They go through treatment and recovery, and the disease does not return. For others, cancer may not ever fully disappear. Their cancer may respond to treatment and then come back, or treatment may simply keep it from growing and spreading. For people living with cancer, it's important to understand what it means when cancer doesn't go away – and how remission and recurrence may be part of your cancer journey.
|Facing the same cancer more than once can be a frustrating and exhausting experience. Learn how you can better cope with the effects of recurring cancer here.|
When a cancer comes back after treatment, it is known as cancer recurrence. The cancer sometimes returns at the same spot (known as local recurrence) or it may show up in parts of the body that were not previously affected. Some types of cancers, such as ovarian cancer, are more likely to return than others. People with recurring cancer may need multiple rounds of treatment or they may need to change the type of treatment they receive.
Remember that even when a cure is not possible, treatment may help keep cancer at bay. If you have cancer that does not go away, talk to your doctor about what options may be right for you.