CANCER THERAPY & PALLIATIVE CARE NEWS
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(This is a sticky post, please find current news items below) By The Society of Cancer Management in General |
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This feed features recent developments in cancer management and general news associated with our objectives. Views in these articles do not necessarily represent those of the Cancer Management Society.
Please contact us if you would like to contribute a news item. We are keen to publish more items from UK-based research and findings that relate to microbial infections during therapy.
Racial disparities in success of prostate cancer surgery
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Wednesday, 16 May 12 - 11:06 PM (GMT) By The Society of Cancer Management in Presentation |
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Black prostate cancer patients may not be getting the same quality of care as white patients, according to a first-of-its-kind study by researchers at Henry Ford Hospital who found racial disparities in the results of surgery to remove diseased prostates. While it is possible that anatomical differences or tumor characteristics may explain why the results of radical prostatectomy are not as good for African Americans as for white patients undergoing the same procedure, the study concluded that "surgeons, administrators and policymakers need to implement measures to address these disparities."
The new research findings, based on population samples from throughout the U.S., will be presented this week at the American Urological Association's Annual Meeting in Atlanta.
Quoc-Dien Trinh, M.D., a Fellow at Henry Ford Hospital's Vattikuti Urology Institute and lead author of the study, says that while no one before has reported racial disparities in the results of cancer surgery, earlier studies have found similar differences in other areas of medical treatment and care.
"Again, research raises a serious issue in the difference between Caucasian and African American patients, and we're trying to understand why it is happening," Dr. Trinh says.
"Is it a biological issue? African American patients might present with worse disease, therefore surgery and treatment are more difficult. For some cancers, like pancreatic, if you have worse disease, the surgery is harder. But that's doubtful with prostate cancer. It shouldn't be the case."
Dr. Trinh also notes that it is possible that African American patients have an anatomical difference – the form of their pelvis – that makes their surgeries harder, and there are studies to support that. "It's not controversial, just related to bone structure. And it might, big question mark, might make surgery harder," he says.
"But if it's not anatomy or a disease aggressiveness issue then why do Caucasians have a better outcome than African American patients? While this study does not go into those specific issues, it raises the question."
Using the most recent available data from the Nationwide Inpatient Sample (NIS), Dr. Trinh and his fellow researchers identified 7,408 African American and 51,319 white prostate cancer patients who underwent radical prostatectomy (RP) between 2001 and 2007. In RP, the entire cancerous prostate and some surrounding tissue are surgically removed.
They then compared the surgery's immediate and short-term outcome, according to race, in five areas: rates of blood transfusions, complications during and after surgery, prolonged hospital stay, and in-hospital death. They found that compared to their white counterparts, African American patients had:
- Significantly higher rates of blood transfusions, 9 percent compared to 6 percent
- More complications during surgery, 1.7 percent compared to 1.3 percent
- Higher rates of overall complications after surgery, 13 percent vs. 10.3 percent
- Longer hospital stays (more than the median 3 days), 28.7 percent vs. 20.9 percent
- No differences for in-hospital mortality rates
Trinh says because of limitations on available data, there is no way to know exactly why these disparities exist yet. "Is it physician and patient interaction, types of insurance, how these patients are perceived? It's hard to know," he says.
"I'd say that it's a little bit of everything – worse disease, presentation, anatomy that makes surgery harder. But it's also a question of quality of care for ethnic minorities, especially in the American health care system. And that needs to be raised."
American Urological Association's Annual Meeting in Atlanta.
Vaccine combination therapy shows survival benefit in breast cancer
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Wednesday, 16 May 12 - 10:50 PM (GMT) By The Society of Cancer Management in Research |
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A vaccine that targets cancer cells in combination with the drug letrozole, a standard hormonal therapy against breast cancer, significantly increased survival when tested in mice, a team of UC Davis investigators has found. The findings will be published in the journal Clinical Cancer Research.
"We found that the vaccine and the hormonal drug letrozole were more effective when given together," said Michael DeGregorio, UC Davis professor of hematology and oncology and principal investigator of the study. "This adds critical evidence that immunotherapy with vaccines, which has traditionally been used to prevent infectious diseases, is also a promising new approach to combating cancer."
The vaccine, known as L-BLP25 (Stimuvax™), specifically targets Mucin1 glycoprotein (MUC1), an antigen that is expressed in an altered form on cancer cells. When introduced into the body, the vaccine generates an immune response by T-lymphocytes, which then recognize and destroy the tumor cells. Mice in the study were injected weekly with the vaccine -- or a placebo -- for eight weeks.
In addition to the vaccine or placebo, some mice were treated with either letrozole or tamoxifen, commonly used hormonal therapies against breast cancer. Both drugs work by blocking the effects of estrogen, which can slow or stop the growth of some types of breast cancer cells that need the hormone to grow. Although the drugs have similar actions, the benefits of the vaccine were greatest in the mice treated with letrozole; in contrast, vaccinated mice given tamoxifen actually fared worse than those given either the vaccine or tamoxifen alone.
"Hormonal drugs affect the immune system in different ways, and apparently the actions of tamoxifen prevent the vaccine from working effectively," said DeGregorio. "This highlights the importance of rigorous testing of different combinations of therapies before using them in patients."
Breast cancer is the second-leading cause of cancer death in women in the United States, following lung cancer. Most cases of breast cancer are "estrogen-dependent" and respond to hormonal therapy. For tumors that are independent of hormonal influence, treatment options are limited and would especially benefit from a new treatment strategy such as a vaccine.
The vaccine was found to work best when the tumor burden -- the amount of cancer present -- was low, indicating that the vaccine may one day be best used as a preventative measure for women at high risk of developing breast cancer or for treatment of early disease.
Vaccine therapy is a promising new cancer-fighting strategy; the first therapeutic vaccine for prostate cancer was approved by the U.S. Food and Drug Administration in 2010. Trials with L-BLP25 vaccine are currently under way for lung and pancreatic cancers, whose cells also express altered MUC1, the same tumor-associated antigen found on breast cancer cells. The current study is the first known to the authors to demonstrate that a hormonal therapy combined with a vaccine provides additive antitumor activity and survival benefit.
"This was a true alliance between academics and industry," added DeGregorio, who noted that trials such as this one are especially expensive because of the number of mice needed and the length of time -- about three and a half years -- required to establish their findings. The study had support from the pharmaceutical company, Merck KGaA Darmstadt Germany.
DeGregorio's group will further test the vaccine with other conventional therapies and determine optimal dosing. Clinical trials in patients with breast cancer are in the planning stages.
Mehta et al., (2012). L-BLP25 vaccine plus letrozole induces a TH1 immune response and has additive antitumor activity in MUC-1 expressing mammary tumors in mice. Clin Cancer Res., EPub Ahead of Print [Abstract]
Tumor size influences chemotherapy's effect on overall survival
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Wednesday, 16 May 12 - 10:33 PM (GMT) By The Society of Cancer Management in Research |
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Recent research released in June's Journal of Thoracic Oncology indicates there might be a positive correlation between tumor size and adjuvant platinum based chemotherapy in surgically resected patients with node negative non-small cell lung cancer. The study, published in the June 2012 issue of the International Association for the Study of Lung Cancer's (IASLC) Journal of Thoracic Oncology, analyzed the effect of tumor size and KRAS mutations on survival benefit from adjuvant platinum based chemotherapy in patients with node negative non-small cell lung cancer.
The purpose of the retrospective study was to apply the most current, 7th edition, TNM staging system, to a retrospective cohort of surgically resected, node negative, non-small cell lung cancer patients who were treated with adjuvant platinum based chemotherapy. Previous clinical trials confirmed a survival benefit for adjuvant platinum based chemotherapy for patients with stage II-IIIa non-small cell lung cancer. In addition, the authors explored the interaction between tumor size and KRAS mutations in predicting a benefit from the chemotherapy.
After analyzing data from 461 patients that were part of two previous adjuvant trials, JBR.10 and CALBG 9633, the authors found a positive correlation between the size of the tumor and efficacy of chemotherapy with respect to disease free survival. There was no clear demarcation of what T size threshold correlated with benefit of chemotherapy. KRAS mutation was detected in 27 percent of the specimens, correlated with a worse prognosis but not with the size of the tumor.
"Thus, our study reinforces the pressing need for improved understanding of the impact of the new T-size descriptors on adjuvant chemotherapy effect," the authors say. "This is particularly valid when we consider that up to 77 percent of surveyed lung cancer physicians would alter patient management in response to a change in stage designation."
Cuffe et al., (2012). A pooled exploratory analysis of the effect of tumor size and KRAS mutations on survival benefit from adjuvant platinum-based chemotherapy in node-negative non–small cell lung cancer. J.Thorac. Oncol., 7, 963-972 [Abstract]
Reforming disability assessment centres
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Monday, 14 May 12 - 01:08 PM (GMT) By The Society of Cancer Management in General |
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It seems that Ian Duncan-Smith has chosen the most unproductive way of dealing with disability claims. Forcing disabled people and those with chronic illnesses to attend fascist-style assessment centres does nothing to improve the public perception of his government. There is a better way of dealing with this problem. As there are now ATOS assessment centres scattered around the country why not utilize these resources in a more productive way. At present the system is throwing money down the drain in a cycle of assessments and appeals. These centres could instead offer helpful advice and support to disabled people in order that they can return to work. They could also be a place where potential employers could advertise job vacancies or opportunities specifically for disabled workers.
Most tax payers would probably not object to spending public money in this way. This government seems to favour a very lazy but confrontational approach of not assisting the disabled and chronically ill by implying they are feigning their illnesses. The UK has one of the worse records for Cancer survival in developed countries. It is time to turn this around by using resources in the UK more effectively.
Salivary gland damage avoided by sparing stem cells in radiotherapy for head and neck cancer
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Thursday, 10 May 12 - 11:17 PM (GMT) By The Society of Cancer Management in Presentation |
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Researchers believe they may have found a way to avoid damaging salivary glands during radiotherapy treatment for head and neck cancer – a discovery that could improve the quality of life of 500,000 patients a year worldwide with the disease.
Presenting their findings to the 31st conference of the European Society for Radiotherapy and Oncology (ESTRO31), the researchers said that they had discovered that the stem cells essential for regenerating the parotid gland (the largest pair of salivary glands) were located mainly in its major ducts, and that these could easily be avoided during radiotherapy or given a minimal radiation dose. "This would significantly reduce complications arising from radiotherapy for head and neck cancer," said Dr Peter van Luijk, a research associate at the University Medical Center Groningen, The Netherlands.
Around 40% of patients treated for head and neck cancer suffer from the distressing side-effects of dry mouth syndrome – a condition that can occur when the parotid gland stops working properly after radiation damage. This causes problems with eating, sleeping, speech, tooth loss and oral hygiene, leading to diminished quality of life, social isolation and difficulty in continuing work. Attempts to treat dry mouth syndrome and its consequences can cost hundreds or even thousands of Euros per patient per year and are mostly insufficient.
Dr van Luijk said: "Parotid gland dysfunction after radiotherapy for head and neck cancer was, and still is, a major clinical problem. During radiotherapy, attempts to minimise the risk of this complication have been aimed at reducing the average dose to the salivary gland, on the assumption that it would not make a difference where in the gland the radiation dose was reduced. However, this does not seem logical according to the anatomy of the salivary gland and, in previous work, we discovered that reductions in the radiotherapy dose to some parts of the gland allowed the parotid gland to regenerate, whereas a dose to other parts did not. Therefore, we decided to investigate the reason for these regional differences. We hypothesised that our observations could be explained by a non-uniform distribution of stem cells necessary for the long-term maintenance of organ function and affected by irradiation."
Dr van Luijk and his colleagues investigated the location of stem cells and the effects of radiotherapy to particular regions of the gland first in mouse and rat models, and then in parotid and salivary gland tissue taken from patients (after informed consent) undergoing a neck dissection for head and neck cancer.
They found that in mouse, rat and human tissue, the stem cells were predominately located in the major ducts of the parotid gland. "We have found in previous work that these stem cells are capable of regenerating a parotid gland when they have been transplanted after irradiation," said Dr van Luijk.
Dissection of the rat parotid gland and culturing of the different parts of the gland in Petri dishes showed that a greater concentration of stem cells capable of regenerating the gland were located in the centre, where the largest ducts are located. The researchers then directed high-precision irradiation at this centre part in living rats and found that it resulted in excessive reduction of saliva production, in contrast to the minimal effects observed after irradiating other parts of the gland.
Dr van Luijk explained: "The position of the stem cells in rats corresponds to the cranio-ventral extension of the gland in humans, where the excretory duct leaves the gland on the ventral, or outward-facing side. So even though the glands have different shapes in rats and humans, the stem cells are in the exact same anatomical structure."
The researchers then tested their hypothesis by creating a mathematical model based on the treatment of 36 patients, which enabled them to estimate the expected parotid gland function depending on the dose to the stem cells.
"Excitingly, dose to the cranio-ventral extension of the gland containing the major ducts was most predictive of damage to saliva production. In addition, we found that it was possible to reduce the dose by approximately 50% to this part of the gland, without increasing the average dose to the whole gland or the dose to other critical structures in the head and neck region, and without compromising adequate target coverage," said Dr Van Luijk. "Using the mathematical model, we estimated that with such dose reduction none of the patients would have developed parotid gland dysfunction. This is, however, a hypothesis that needs to be tested prospectively in a randomised clinical trial by comparing parotid gland function in a group of patients treated with current standard to a group in which, additionally, the dose to the stem cells is minimised using our proposed stem cell sparing technique. This technique should only be implemented in radiotherapy clinics when such a trial proves there is a benefit as predicted by our research."
He continued: "Our findings can be seen as a proof-of-principle that elucidation of biological mechanisms in complications may lead to the identification of critical sub-structures of organs, possibly leading to new opportunities to reduce harm to normal tissue. Though we only show this for the parotid gland, such approach may apply to other organs as well."
The researchers say that it is easy to spare the parotid gland during radiotherapy. "The stem cell region is on the side of the gland that is normally furthest away from the target area containing the tumour cells. Since only this area needs a high radiation dose, this distance makes avoiding the stem cell area easier than avoiding other parts of the gland," said Dr van Luijk.
"Based on our results we hypothesise that sparing the parotid gland stem cell region, costing around €100 in extra man-hours, may effectively prevent salivary gland dysfunction. This will allow patients to more readily lead their normal lives without having to rely upon medical care and welfare. Maybe even more importantly, cancer patients will remain productive members of society, realising a cost reduction far beyond the cost of medication. Finally, it will improve quality of life of 500,000 patients treated with radiotherapy for head and neck cancer worldwide every year," he concluded.
Professor Bradly G. Wouters (PhD), a radiobiologist at the Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada, and chair of the conference radiobiology track, commented: "This is an exciting clinical study that has identified a critical region of the salivary gland that contains stem cells that can regenerate the gland and preserve function in patients with head and neck cancer. Using advanced radiation techniques the investigators show it is possible to spare this region and thus deliver higher therapeutic doses without causing more toxicity to patients."
31st conference of the European Society for Radiotherapy and Oncology (ESTRO31), Barcelona
Gene-modified stem cell transplant protects against chemotherapy toxicity
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Thursday, 10 May 12 - 11:00 PM (GMT) By The Society of Cancer Management in Research |
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Study is first to show feasibility and efficacy of a new use for autologous stem cell transplant
For the first time, scientists at Fred Hutchinson Cancer Research Center have transplanted brain cancer patients' own gene-modified blood stem cells in order to protect their bone marrow against the toxic side effects of chemotherapy. Initial results of the ongoing, small clinical trial of three patients with glioblastoma showed that two patients survived longer than predicted if they had not been given the transplants, and a third patient remains alive with no disease progression almost three years after treatment.
"We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells," said Hans-Peter Kiem, M.D., senior and corresponding author of the study published in the May 9 issue of Science Translational Medicine.
Kiem, a member of the Clinical Research Division at the Hutchinson Center, said that a major barrier to effective use of chemotherapy to treat cancers like glioblastoma has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow. This results in decreased blood cell counts, increased susceptibility to infections and other side effects. Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment. In the current study, Kiem and colleagues focused on patients with glioblastoma, an invariably fatal cancer. Many of these patients have a gene called MGMT (O6-methylguanine-DNA-methyltransferase) that is turned on because the promoter for this gene is unmethylated. MGMT is a DNA repair enzyme that counteracts the toxic effect of some chemotherapy agents like temozolomide. Patients with such an unmethylated promoter status have a particularly poor prognosis.
A drug called benzylguanine can block the MGMT gene and make tumor cells sensitive to chemotherapy again, but when given with chemotherapy, the toxic effects of this combination are too much for bone marrow cells, which results in marrow suppression. By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. "P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine," Kiem said.
"This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded," said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiem's lab.
The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.
"Glioblastoma remains one of the most devastating cancers with a median survival of only 12 to 15 months for patients with unmethylated MGMT," said Maciej Mrugala, M.D., the lead neuro oncologist for this study.
As many as 50 percent to 60 percent of glioblastoma patients harbor such chemotherapy-resistant tumors, which makes gene-modified stem cell transplant therapy applicable to a large number of these patients. In addition, there are also other brain tumors such as neuroblastoma or other solid tumors with MGMT-mediated chemo resistance that might benefit from this approach. The researchers also found that chemotherapy increased the number of gene-modified blood and bone marrow cells in these patients. Kiem said this finding will have implications for other stem cell gene therapy applications where defective bone marrow stem cells can be corrected by gene therapy but their numbers need to be increased to produce a therapeutic benefit, or for patients with HIV/AIDS to increase the number of HIV-resistant stem and T cells.
Adair et al., (2012). Extended survival of glioblastoma patients after chemoprotective HSC gene therapy. Sci. Transl. Med., 4, 133ra57 [Abstract]
Racial and economic disparities in ovarian cancer survival
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Thursday, 10 May 12 - 10:45 PM (GMT) By The Society of Cancer Management in Presentation |
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White and affluent women did better than African American and poor women
Poor women and African Americans with ovarian cancer are less likely to receive the highest standards of care, leading to worse outcomes than among white and affluent patients, according to a study of 50,000 women presented by UC Irvine's Dr. Robert Bristow at the Society of Gynecologic Oncology's annual meeting.
"Not all women are benefiting equally from improvements in ovarian cancer care," said Bristow, UC Irvine's director of gynecologic oncology services. "The reasons behind these disparities are not entirely clear, which is why we need additional research."
The study's goal was to examine differences related to race and socioeconomic status among women being treated for epithelial ovarian carcinomas – cancer that forms on the surface of an ovary. It also aimed to determine whether their care adhered to National Comprehensive Cancer Network treatment guidelines.
Bristow and colleagues found that five-year survival rates varied significantly. (Improvement in ovarian cancer care is measured in length of survival after diagnosis rather than a "cure" rate.) Among those whose care met NCCN standards, the rate for white women was 41.4 percent, compared with 33.3 percent for African American women. Among those whose care did not meet NCCN standards, the rate for white women was 37.8 percent, compared with 22.5 percent for African American women.
Bristow said that women on Medicaid or those with no insurance had a 30 percent increased risk of death. Poor women – defined as having an annual household income of less than $35,000 – had worse survival rates regardless of race. He said it's likely that the effects of race and socioeconomic status are cumulative and that some combination of other medical conditions, poverty, culture and social injustice accounts for the majority of observed disparities.Ovarian cancer is the deadliest gynecologic cancer, accounting for more than 15,000 deaths a year, according to the National Cancer Institute.
"Under the best circumstances, treating ovarian cancer is challenging, because there's no screening tool available to detect the disease in its early stages," Bristow said.
Only 20 to 30 percent of ovarian cancers are diagnosed while still confined to the primary site; the remainder are identified in advanced stages after spreading to areas such as the liver, the lungs and nearby lymph nodes.
Society of Gynecologic Oncology's 43rd annual meeting, Austin
Physical activity linked to reduced cancer mortality
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Thursday, 10 May 12 - 10:25 PM (GMT) By The Society of Cancer Management in Research |
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Physical activity is associated with reduced breast and colon cancer mortality, but there is insufficient evidence on the association for other cancer types, according to a study published May 8 in the Journal of the National Cancer Institute.
Improvements in cancer treatment and screening have allowed cancer survivors to live longer and as a result, cancer survivors frequently look at information about how lifestyle factors like exercise can affect their prognosis. Multiple observational studies and randomized control trials (RCTs) have looked at the effects that physical activity can have on cancer survivors.
To examine the association between physical activity and cancer survival, Rachel Ballard-Barbash, M.D., of the Applied Research Program in the Division of Cancer Control and Population Sciences at the National Cancer Institute and colleagues reviewed 45 articles reporting both observational studies and randomized controlled trials (RCTs) that looked at the relationship between physical activity and mortality and/or cancer biomarkers among cancer survivors. The studies were published between January 1950 and August 2011. The researchers found that the RCTs with biomarker endpoints suggest that exercise may provide benefits to survivors' insulin levels, reduce inflammation, and, possibly, improve immunity. The strongest evidence is for breast cancer survivors: most studies showed a statistically significant reduced risk of breast cancer and all-cause mortality associated with exercise. The next strongest evidence was for colorectal cancer survivors.
The authors point out that because of the diversity of the studies, it would be impossible to extrapolate specific recommendations on type and timing of physical activity. However, they can attest to the overall safety, physical and mental benefits of exercise for cancer survivors. They add that future RCTs should look at different types of exercise, as well as how obesity, weight loss, and cancer treatments may influence the effects of exercise on biomarkers. Also, how exercise may influence comorbidities in cancer survivors should be studied, they write.
In an accompanying editorial, Edward L. Giovannucci, M.D., ScD, of the Department of Nutrition at the Harvard School of Public Health, writes that physical activity may extend the life-span of the cancer survivor, as well as their quality of life. "Even though direct effects of physical activity on cancer are not definitely proven, given that physical activity is generally safe, improves quality of life for cancer patients, and has numerous other health benefits, adequate physical activity should be a standard part of cancer care," he writes.
Immune-response genes affecting breast tumor eradication
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Friday, 04 May 12 - 10:02 PM (GMT) By The Society of Cancer Management in Presentation |
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Presentations at the 4th IMPAKT Breast Cancer Conference
Breast cancer patients whose tumors express high levels of genes related to immune response are more likely to have their tumor completely eradicated by pre-operative chemotherapy compared to patients with low expression of these genes, Belgian researchers report at the 4th IMPAKT Breast Cancer Conference in Brussels, Belgium.
Their research has identified a group of patients who might be good candidates for treatments with new immune-targeting therapies.
Dr Michail Ignatiadis from Institut Jules Bordet, Brussels, and colleagues analyzed gene expression data from eight studies in which patients had been treated with anthracyclines, with or without taxane chemotherapy, prior to surgery.
"We undertook this pooled analysis to explore whether patients with different breast cancer subtypes respond differently to commonly used pre-operative chemotherapy, based on differences related to the cells of the tumor itself or to the non-tumor cells surrounding the tumor," Dr Ignatiadis explains.
To that end, the researchers analyzed the expression of distinct groups of genes, which they refer to as gene modules, that had been shown by other investigators to be associated with either important oncogenic pathways responsible for tumor cell proliferation or with the way the host immune system reacts to the tumor.
Patients whose tumors expressed high levels of gene modules related to immune system functions were more likely to have their tumor eradicated by the chemotherapy, they found.
"Patients with breast tumors that have high expression of genes related to immune response are more likely to present complete eradication of their tumor after the administration of commonly used pre-operative chemotherapy compared to patients with low expression of these genes. This was mainly observed in the so-called HER2-positive and less so in the ER-negative/HER2-negative and ER-positive/HER2-negative subtypes," said Dr Ignatiadis.
"The role of agents that modulate immune response in breast cancer should be studied, and in these trials patients should be optimally stratified based on their immune response," the researcher added. "Moreover, future studies should investigate whether the efficacy of anti-HER2 agents in HER2-positive early breast cancer patients is also associated with tumor immune response."
Commenting on this study, which he was not involved in, Dr Angelo Di Leo from the Hospital of Prato, Italy, former IMPAKT Chair, noted: "This study highlights the importance of the immune response of the patient as a major factor that can substantially impact treatment efficacy. It is quite clear that response to a given anti-cancer treatment may vary from one patient to another based also on the ability of the patient's immune system to aggress the tumor. This and other recently published studies pave the way to the development of a new generation of cancer drugs that can stimulate the immune response of the patient and make it more efficient in aggressing the tumor."
4th IMPAKT Breast Cancer Conference in Brussels, Belgium
Beehive extract shows potential as prostate cancer treatment
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Friday, 04 May 12 - 09:46 PM (GMT) By The Society of Cancer Management in General |
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Proteomics reveals how ancient remedy slows prostate tumor cell proliferation
An over-the-counter natural remedy derived from honeybee hives arrests the growth of prostate cancer cells and tumors in mice, according to a new paper from researchers at the University of Chicago Medicine.
Caffeic acid phenethyl ester, or CAPE, is a compound isolated from honeybee hive propolis, the resin used by bees to patch up holes in hives. Propolis has been used for centuries as a natural remedy for conditions ranging from sore throats and allergies to burns and cancer. But the compound has not gained acceptance in the clinic due to scientific questions about its effect on cells. In a paper published in Cancer Prevention Research, researchers combined traditional cancer research methods with cutting-edge proteomics to find that CAPE arrests early-stage prostate cancer by shutting down the tumor cells' system for detecting sources of nutrition.
"If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace," said Richard B. Jones, PhD, assistant professor in the Ben May Department for Cancer Research and Institute for Genomics and Systems Biology and senior author of the study. "So it doesn't kill the cancer, but it basically will indefinitely stop prostate cancer proliferation."
Natural remedies isolated from plant and animal products are often marketed as cure-alls for a variety of maladies, usually based on vague antioxidant and anti-inflammatory claims. While substances such as ginseng or green tea have been occasionally tested in laboratories for their medicinal properties, scientific evidence is commonly lacking on the full biological effects of these over-the-counter compounds.
"It's only recently that people have examined the mechanism by which some of these herbal remedies work," Jones said. "Our knowledge about what these things are actually doing is a bit of a disconnected hodge-podge of tests and labs and conditions. In the end, you're left with a broad, disconnected story about what exactly these things are doing and whether or not they would be useful for treating disease."
To study the purported anti-cancer properties of CAPE, first author Chih-Pin Chuu (now at the National Health Research Institutes in Taiwan) tested the compound on a series of cancer cell lines. Even at the low concentrations expected after oral administration, CAPE successfully slowed the proliferation of cultured cells isolated from human prostate tumors.
CAPE was also effective at slowing the growth of human prostate tumors grafted into mice. Six weeks of treatment with the compound decreased tumor volume growth rate by half, but when CAPE treatment was stopped, tumor growth resumed its prior rate. The results suggested that CAPE stopped cell division rather than killing cancerous cells.
To determine the cellular changes that mediated this effect, the researchers then used an innovative proteomics technique invented by Jones and colleagues called the "micro-western array." Western blots are a common laboratory tool used to measure the changes in protein levels and activity under different conditions. But whereas only one or a few proteins at a time can be monitored with Western blots, micro-western arrays allow researchers to survey hundreds of proteins at once from many samples.
Chuu, Jones and their colleagues ran micro-western arrays to assess the impact of CAPE treatment on the proteins of cellular pathways involved in cell growth – experiments that would have been prohibitively expensive without the new technique.
"What this allowed us to do is screen about a hundred different proteins across a broad spectrum of signaling pathways that are associated with all sorts of different outcomes. You can pick up all the pathways that are affected and get a global landscape view, and that's never been possible before," Jones said. "It would have taken hundreds of Westerns, hundreds of technicians, and a very large amount of money for antibodies."
The micro-western array results allowed researchers to quickly build a new model of CAPE's cellular effects, significantly expanding on previous work that studied the compound's mechanisms. Treatment with CAPE at the concentrations that arrested cancer cell growth suppressed the activity of proteins in the p70S6 kinase and Akt pathways, which are important sensors of sufficient nutrition that can trigger cell proliferation.
"It appears that CAPE basically stops the ability of prostate cancer cells to sense that there's nutrition available," Jones said. "They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition."
The ability of CAPE to freeze cancer cell proliferation could make it a promising co-treatment alongside chemotherapies intended to kill tumor cells. Jones cautioned that clinical trials would be necessary before CAPE could be proven effective and safe for this purpose in humans. But the CAPE experiments offer a precedent to unlock the biological mechanisms of other natural remedies as well, perhaps allowing these compounds to cross over to the clinic.
"A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy," Jones said. "Now we'll actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds."
Chuu et al., (2012). Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer cells through inhibition of p70S6K and Akt signalling network. Cancer Prev. Res., 5, 788–797 [Abstract]
Poorer quality of life for gay men and minorities after prostate cancer treatment
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Monday, 30 April 12 - 10:43 PM (GMT) By The Society of Cancer Management in Review |
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To improve the quality of life in gay men and minorities treated for prostate cancer, a greater awareness of ethnic and sexual preference-related factors is needed to help men choose a more-suitable treatment plan, researchers from Thomas Jefferson University Hospital conclude in a literature review published May 1 in Nature Reviews Urology.
Some of the factors to consider, for example, include increased risk of urinary and bowel function decline in African Americans regardless of treatment received and differing sexual expectations and social support in gay men.
"Different communities of men view the effects of prostate cancer treatments very differently," said co-author Edouard J. Trabulsi, M.D., of the Department of Urology and Kimmel Cancer Center at Thomas Jefferson University Hospital, noting the poorer quality of life among certain subpopulations.
"It's in the patient's best interest for caregivers to acknowledge perceptions and expectations during the treatment decision process," he said. "They should take specific demographics, socioeconomic status, and sexual preference into consideration, and tailor an approach based on a patient's specific concerns about the implications of various treatments."
Today, many of these confounding factors are poorly documented and poorly addressed by medical practitioners when discussing treatment, be it radical prostatectomy, radiation or androgen deprivation therapy. There is also scant research about prostate-cancer-related quality of life effects in men who have sex with men (MSM).
In this literature review, the authors use several studies to illustrate differences in treatment outcomes, sexual function and coping mechanisms among subpopulations, including African Americans, Latin Americans, Asians and MSM. According to the analysis, African Americans, who have higher prostate cancer incidence and mortality rates than whites, are less likely to initiate and complete treatment and less likely to trust a physician. They are also at an increased risk of urinary, bowel and general physical function decline, regardless of treatment. Treatment preferences and sexual outcomes also differ. According to the review, in a study of 665 military men who had the same access to care, white men were three times more likely to choose a radical prostatectomy as their treatment options for low and intermediate risk prostate cancer, whereas African Americans tended to prefer non-surgical treatments, such as external beam radiation therapy.
A multicenter longitudinal cohort study set up to monitor urinary and sexual function in over 1,200 men who underwent radical prostatectomy for clinically localized prostate cancer showed that African Americans were more likely to retain sexual function. As with African Americans, Latin American men who underwent radiation therapy or a radical prostatectomy demonstrated greater levels of severe sleep dysfunction than whites. They were also are less likely to enter hospice.
MSM with prostate cancer have additional social and sexual challenges often overlooked. MSM are typically diagnosed later in life and may be reluctant to divulge their sexual preference to their caregiver. This may preclude them from discussing their quality of life expectations and sexual practices. One reason for poorer quality of life may also be attributed to a lack of social support group, the researchers discovered in their analysis. As MSM men are less likely to have long-term partners, they might not have the same level of support at home and might look for support in other places.However, the number of support groups specifically tailored for MSM with prostate cancer is limited.
"In the United States, MSM-specific support groups are available in just six cities. MSM living outside these cities might rely more on Internet-based support groups and are at increased risk of becoming socially isolated," the authors write.
MSM are also less likely to invite their partners into the examiner room when discussing treatment options and related adverse effects. Study findings also suggest that treatment with androgen deprivation therapy for prostate cancer could have a greater negative impact on quality of life for gay men compared to heterosexual men.
"There are potential barriers for accurately assessing and measuring quality of life in MSM. Here, we focus attention on these poorly studied aspects to help overcome such concerns," said Dr. Trabulsi, who is also the Director of the Multidisciplinary Genitourinary Cancer Center at Jefferson's Kimmel Cancer Center. "It's everything from discussion about sexual preference to toxicity-related effects to their ability to maintain a relationship with a partner."
Kleinmann et al., (2012). The effect of ethnicity and sexual preference on prostate-cancer-related quality of life. Nat. Rev. Urol., EPub Ahead of Print [Abstract]
High Risk of heart problems in childhood cancer survivors
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Monday, 30 April 12 - 10:21 PM (GMT) By The Society of Cancer Management in Research |
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Early successes in the treatment of childhood cancer mean that some individuals are now surviving 40 to 50 years after diagnosis, and late adverse effects of therapy can be quantified. Cardiac dysfunction is one of the most troubling cancer treatment–related late effects and is most often associated with the use of anthracycline chemotherapy and cardiac irradiation.
Dutch investigators describe the incidence of cardiac events in a population of 5-year survivors of childhood cancer (N = 1,362) who were treated at a single institution between 1966 and 1996.The authors report 50 cardiac events, including 27 cases of cardiac failure in 42 survivors that occurred at a median attained age of 27.1 years. Similar to other studies, this article demonstrates an increasing risk of experiencing an adverse cardiac event with increasing exposure to anthracyclines and cardiac irradiation.
The authors of the study have verified the cardiac events, and follow-up of survivors is almost complete; these are important factors in reliably estimating the frequency of events. A previous investigation from the Childhood Cancer Survivor Study reported a somewhat higher incidence of cardiac events than that observed in the current study (4.1% at 30 years in the Childhood Cancer Survivor Study compared with 2.7% in the Dutch study) in a large cohort of 5-year-plus survivors of cancer. This difference was perhaps a result of a selection bias that is commonly seen in nonpopulation-based studies in which survivors with problems are more likely to participate. The potential adverse impact of cardiac toxicity on long-term survival is supported by the Dutch report of poor outcomes for the survivors with cardiac events; only four survivors recovered fully. Among children who were treated with both anthracyclines and cardiac irradiation, one in eight had severe heart disease 30 years later.
Survivors of treatment for childhood cancer who were treated in the 1970s are now entering their sixth and seventh decades of life, and we can expect additional morbidities from the untargeted therapies used during that time. As targeted therapies and small molecules with specific and not generally cytotoxic modes of action emerge, we can hope for a reduction in late adverse effects 40 or 50 years from now. However, because the majority of children diagnosed with cancer in 2012 will achieve long-term survival with relatively modest refinements of the therapies used in the 1970s, continued focus on surveillance and management of late effects, and education of internists and insurers, remain at the heart of the matter.
Davies SM (2012). Getting to the Heart of the Matter. J. Clin. Oncol., 30, 1399-1400 [Article]
van der Pal et al., (2012). High risk of symptomatic cardiac events in childhood cancer survivors. J. Clin. Oncol., 30, 1429-1437 [Abstract]
Equal access to care helps close cancer survival gap
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Monday, 30 April 12 - 10:14 PM (GMT) By The Society of Cancer Management in Research |
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Researchers close survival gap for virtually all African-American and white children with cancer in a study that suggests equal access to care translates into an equal chance of a cure
A new analysis from St. Jude Children's Research Hospital adds to evidence that equal access to comprehensive treatment and supportive care typically translates into equally good outcomes for most young African-American and white cancer patients. Researchers found no significant difference in survival rates between African-American and white children treated at St. Jude for virtually all cancers during a 15-year period ending in 2007.
Racial disparities in cancer survival are widely recognized among African-American patients of any age. These patients are less likely than their white counterparts to become long-term cancer survivors. While this and previous studies have highlighted the success of St. Judes in closing the gap, investigators reported that the disparities persisted for many U.S. pediatric cancer patients. The work appears in the April 30 online edition of the Journal of Clinical Oncology.
The study spans an era of significant advances in the treatment of several childhood cancers that by 2007 had helped to push the nation's overall five-year pediatric cancer survival rate past 80 percent. But results reported to the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) program from throughout the U.S. show that African-American patients did not share equally in those advances. SEER compiles data from 17 states and metropolitan cancer registries. Together those registries cover about 26 percent of the U.S. population.
Ching-Hon Pui, M.D., chair of the St. Jude Department of Oncology and the study's lead author, said the findings underscore the importance of giving patients equal access to comprehensive cancer treatment. While an individual's cancer risk may vary based on race or ethnicity, Pui said this study demonstrates that comprehensive risk-directed therapy and supportive care help patients enjoy excellent outcomes equally. "This study shows that with outstanding medical care and psychosocial support African-American patients should not necessarily fare worse than white patients," he said.
The study focused on survival rates for African-American and white children battling one of 19 cancers. Researchers analyzed the outcome for 4,128 St. Jude patients and for 23,885 pediatric patients in the SEER database. The SEER patients were treated at various U.S. medical centers.
The cancers were all diagnosed between either 1992 and 2000 or 2001 and 2007. During that 15-year period, about 19 percent of St. Jude patients self-identified as African-American and about 75 percent as white. About 10 percent of the SEER patients in this study were African-American and almost 58 percent were white.
The analysis of SEER results found African-American patients generally had significantly worse outcomes than white patients with the same cancer. The racial survival gap narrowed during the treatment eras included in this study for patients with acute lymphoblastic leukemia (ALL) and Hodgkin lymphoma, but widened for those battling acute myeloid leukemia (AML) and neuroblastoma, a tumor of the nervous system.
During the same period at St. Jude, African-American and white patients enjoyed similar survival gains, particularly those treated for ALL, AML and the eye tumor retinoblastoma. Overall, African-American and white St. Jude patients had similar odds of becoming long-term survivors. The possible exception was children with a few rare cancers and advanced disease when treatment began.
"These findings flow directly from Danny Thomas' strong view that to conquer childhood cancer, treatment must be equally available across all racial and ethnic groups, which has been the case at St. Jude since he opened the doors in 1962," said Dr. William E. Evans, St. Jude CEO and a study co-author.
The SEER and St. Jude patients differed in several important ways; including the strength of diagnostic testing for certain brain tumors. St. Jude patients were also more likely than the ones from SEER to be enrolled in clinical trials.
Pui noted that high-risk or advanced cancers were more common among St. Jude patients than among other children with cancer. St. Jude is a referral center with clinical trials that focus on difficult or advanced cancer.
St. Jude treats all qualified patients regardless of a family's ability to pay. The hospital does not routinely collect socioeconomic information about patients but a check of the insurance coverage of patients in this study found African- American children were more likely than white children to be uninsured or covered through government health plans. Researchers noted that insurance coverage can be a marker of socioeconomic status and also influence a patient's access to bone marrow transplants and other expensive therapies.
Pui et al., (2012). Treatment outcomes in black and white children with cancer: Results from the SEER database and St Jude Children's Research Hospital, 1992 through 2007. J. Clin. Oncol., EPub Ahead of Print [Abstract]
Post cancer-related fatigue in breast cancer patients
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Thursday, 26 April 12 - 04:34 PM (GMT) By The Society of Cancer Management in Research |
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Prolonged and disabling fatigue is a common side-effect of many cancer treatments, with large numbers of women reporting that cancer-related fatigue persists for many months after treatment ends. Some studies put the figure as high as 50 percent.
But a study of breast cancer survivors from a group of collaborating hospitals in Sydney together with staff of the UNSW's newly established Cancer Survivors' Centre have found fatigue in a high number of patients but have not been able to correlate this with cancer or its treatment. And while the study, published this month in Journal of Clinical Oncology, looked at breast cancer, the researchers believe their results could apply to survivors of other cancers.
The 5-year prospective study followed 218 women with early-stage breast cancer. The women were observed and questioned at three-monthly intervals for a year after treatment and again at five years. The researchers seemed to adopt a unique definition of 'fatigue'. This was used to rule out any 'background' fatigue. It is unclear what they determine to be 'background' fatigue. However it seems to include a number of things such as, transient fatigue states associated with unrelated infections, surgery and minor psychiatric disorders and chronic fatigue states attributable to other conditions.
The researchers say for people who do experience ongoing fatigue, attention can now be focussed on early identification and directing resources where they are most needed.The success of cancer treatments and the increasing number of cancer survivors makes finding better ways to manage survivorship essential. It seem the researchers believe lack of 'exercise' may be one key element. To that end, the UNSW Cancer Survivors' Centre, in conjunction with one of its partners the UNSW Lifestyle Clinic, has begun trials of a twelve-week 'intensive' program of exercise and cognitive behaviour therapy to help people with established cancer-related fatigue.
"Exercise is increasingly being identified as a medicine, potentially even with a dose response, and it may have a very important role as a therapy not only in cancer recovery but also in the treatment process itself," Professor Goldstein said.
Goldstein et al., (2012). Cancer-related fatigue in Women With breast Cancer: Outcomes of a 5-Year prospective cohort study. J. Clin. Oncol., EPub Ahead of Print [Abstract]
Bridging the gap in treatment for older women with breast cancer
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Thursday, 26 April 12 - 04:18 PM (GMT) By The Society of Cancer Management in General |
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Sheffield researchers are investigating ways to improve the treatment and survival rate of elderly patients diagnosed with breast cancer. The pioneering programme has been awarded almost £2million by the National Institute of Health Research (NIHR) to ensure older women are treated as effectively as younger women.
Professor Malcolm Reed and Lynda Wyld from the Department of Oncology at the University of Sheffield are leading the ground-breaking programme - working in close collaboration with Dr Karen Collins from the Centre for Health and Social Care Research at Sheffield Hallam University.
Every year, more than 13,000 women in the United Kingdom aged 70 years and over are diagnosed with breast cancer, resulting in almost 7,000 deaths per year.Whilst intensive research has resulted in significant improvements in the treatment and survival for younger women with breast cancer, this has not been the case for older women.There is extensive evidence that older women are not always treated as effectively as younger women with the omission of treatments such as surgery, chemotherapy and radiotherapy in many cases. This is based on misunderstandings of the impact of breast cancer on survival rates in older women, the complications and side-effects of treatment and the preferences and perceptions these patients have of the disease and its treatment.
Lynda Wyld , Senior Lecturer in Surgical Oncology said: "The program will allow us to establish the most effective treatment for breast cancer in older patients tailored to their individual tumour characteristics and overall health.
"This will enable patients and their doctors to select the best treatment avoiding the common problem of under treatment but also that of overtreatment with the associated risk of side effects and loss of independence."
The research programme, which also involves colleagues from the University of Sheffield's School of Health and Related Research (ScHARR) and Cardiff University, will collect detailed information on the treatment and outcomes of a large national cohort of women with the aim of designing simple-to-use decision aids to help clinicians and patients decide on the most appropriate treatment.
Professor Malcolm Reed, Head of Surgical Oncology at the University of Sheffield said: "The award of a major programme grant funding from NIHR provides us with a superb opportunity to continue our work to improve the care in this previously under resourced area.
"We are pleased that NIHR have recognised the strength of the proposal and the partners at both Universities in Sheffield and other universities and hospitals in the UK.
"The research programme will receive funding for five years with the aim of producing benefits for patients in the NHS."
Balancing trastuzumab's breast cancer survival benefits with heart risks
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Wednesday, 18 April 12 - 01:42 PM (GMT) By The Society of Cancer Management in Review |
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Adding trastuzumab (trade name Herceptin) to the treatment offered to women who have HER2-positive breast cancer, significantly increases the chance of life being prolonged, and reduces the chance of tumours reappearing once therapy stops. This is important, because about one-fifth of women who develop early breast cancer have HER2-positive tumours that, if untreated, are associated with a worse outlook than HER2-negative tumours. At the same time, however, women given trastuzumab have a higher risk of experiencing problems with their heart. These findings are the key conclusions of a systematic review published in The Cochrane Library.
Breast cancer is the most common diagnosed cancer in women. There are different types of breast cancer cells, but one feature is whether the tumour's cells produce excess quantities of a particular protein called the human epidermal growth factor receptor 2 (HER2). Cells which do are known as HER2-positive, while those with normal production are referred to as HER2-negative. Trastuzumab is a new-generation antibody based medicine that blocks the receptor and stops it triggering the excessive cell growth that causes tumours.
To provide clinicians and patients with accurate evidence of trastuzumab's harms and benefits, a team of researchers based in Milan and Modena, Italy, were keen to study available clinical trial data. They identified eight trials that involved 11,991 women with HER2-positive operable breast cancer who had been assigned randomly either to receive trastuzumab or not, in addition to other treatments. Women were followed by clinicians for several years (three on average).
The overall finding was that breast cancer mortality was reduced by one-third, but the risk of heart toxicity went up five times for women receiving trastuzumab compared with women receiving standard therapy alone.
If 1000 women were given standard therapy with no trastuzumab then after three years about 900 would survive, but if 1000 women were treated with standard chemotherapy and trastuzumab for one year, about 933 would survive.
"This means that for every 1000 women treated with trastuzumab, 33 more women will have their lives prolonged," says lead researcher Lorenzo Moja who works in the Department of Public Health at the University of Milan. In addition, about 95 more women will remain disease-free once therapy has stopped.
However, the study showed that the treatment isn't free of problems. About 26 in 1000 women taking trastuzumab experienced serious heart toxicity. This is 21 more than the chemotherapy alone group.
"These heart toxicities are often reversible if the treatment is stopped straight away," says Moja.
The researchers conclude that in women at higher risk of recurrence and with no signs of a weak heart, trastuzumab offers far more benefits than risks.
The balance of risks to benefits is less clear and must be carefully evaluated in women at lower risk of recurrence, for example if they only have a small tumour, or those who are at increased risk for cardiac complications. "The oncologist should share the decision with the patient, after careful consideration of the risks and benefits," says Roberto D'Amico, senior scientist at the Clinical Trial Unit of the Department of Oncology of the University of Modena.
Moja et al., (2012). Trastuzumab containing regimens for early breast cancer (Review). The Cochrane Library, Issue 4 [Download Article]
Brain cancer vaccine proves effective
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Wednesday, 18 April 12 - 01:30 PM (GMT) By The Society of Cancer Management in Presentation |
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Phase 2 clinical trial paves way for testing therapy that combines cancer vaccine with the drug Avastin
A new brain cancer vaccine tailored to individual patients by using material from their own tumors has proven effective in a multicenter phase 2 clinical trial at extending their lives by several months or longer. The patients suffered from recurrent glioblastoma multiforme—which kills thousands of Americans every year.
These results, to be announced at the American Association of Neurological Surgeons (AANS) meeting in Miami, compared the effectiveness of the vaccine for more than 40 patients treated at UCSF's Helen Diller Family Comprehensive Cancer Center, at the Seidman Cancer Center at University Hospitals Case Medical Center in Cleveland and at New York-Presbyterian Hospital/Columbia University Medical Center in New York City.
The trial found the vaccine could extend survival for the patients by several months when compared to 80 other patients who were treated at the same hospitals and received standard therapy—47 weeks compared to 32 weeks. Several of the patients who received the cancer vaccine have survived for more than a year.
"These results are provocative," said UCSF neurosurgeon Andrew Parsa, MD, PhD, who led the research. "They suggest that doctors may be able to extend survival even longer by combining the vaccine with other drugs that enhance this immune response."
The next step, he said, will be a more extensive, randomized clinical trial to look at the effectiveness of the vaccine combined with the drug Avastin, a standard therapy for this type of cancer, compared to the effectiveness of Avastin alone. Those trials, to be run by the National Cancer Institute, will begin enrolling patients later this year.
CLINICAL TRIAL PARTLY FUNDED BY PATIENT GROUPS
The UCSF Department of Neurological Surgery is ranked by U.S. News & World Report as one of the top departments in the world. Its doctors perform more than 1,100 neurosurgeries a year to remove brain tumors, and in the last 30 years, this work has helped to build one of the most extensive brain tumor repositories in the United States, with tissue samples collected from thousands of people with cancer.
Part of the funding for the Phase 2 trial came though a $1.5 million-a-year grant to UCSF from the National Cancer Institute—called Brain Tumor SPORE (Specialized Program of Research Excellence). Now in its 10th year, the grant aims to translate basic laboratory and clinical discoveries into optimal ways of delivering treatment and monitoring a patient's progress.
The Phase 2 trial also was partially paid for with funds provided by the patient advocacy groups American Brain Tumor Association, Accelerate Brain Cancer Cure and the National Brain Tumor Society—groups that Parsa credits with spearheading the effort.
"It never would have happened without them," Parsa said. "Patient advocacy groups are an important component of how we inform patients about this disease. These groups are also increasingly critical to funding translational research, which bridges the gap between the laboratory and the clinic."
Parsa has not received any personal financial support, consulting fees, or travel expense reimbursement for this work from Agenus, Inc., the biotech company that makes the new vaccine. Neither Parsa nor UCSF have any financial interest in the company.
GLIOBLASTOMA AND CANCER VACCINES
Some 17,000 Americans are diagnosed with glioblastoma every year, and only 2 percent of them survive longer than five years – even with treatment. The cancer always recurs, he added, and it is only a matter of when.
Glioblastoma treatment generally begins with a surgical resection, in which neurosurgeons remove the cancerous tissue from the brain. The surgery usually is followed by radiation therapy and then chemotherapy to kill any remaining cancer cells. Many people undergo treatment only to have the cancer return a few months later, at which point doctors may operate again, followed by more chemotherapy.
Cancer vaccines are a relatively new approach that has appeared in the last decade. In 2010, the U.S. Food and Drug Administration approved the first therapeutic cancer vaccine for prostate cancer, and several more cancer vaccines are in clinical trial. The basic concept is similar to a vaccine for a disease like measles or mumps: an injection in the arm induces an immune response that helps the body fight the particular pathogen – or in this case, the cancer. An effective immune response would then shrink tumors and extend lives.
In the past, vaccines did not seem to work because they did not produce effective immune responses: either they did not kill all of the tumor cells or they worked on some patients but not on others. Work on the new vaccine began after several brain cancer advocacy groups pooled their resources several years ago and approached doctors at leading cancer centers, requesting proposals for new ways to fight recurrent glioblastoma. Parsa and his colleagues proposed a new type of cancer vaccine based on tiny molecular bundles called heat shock proteins.
These molecules are recovered from tumors surgically removed from patients in the trial. Agenus, Inc., prepares a vaccine specific for each patient and ships the vaccine back to the doctors who then inject it into the patient's arm several times over the course of the year.
American Association of Neurological Surgeons (AANS) annual meeting in Miami
Evaluating adverse effects in different radiation therapies for prostate cancer
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Wednesday, 18 April 12 - 01:16 PM (GMT) By The Society of Cancer Management in Research |
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In an analysis of three different types of radiation therapy used to treat localized prostate cancer, compared with conformal radiation therapy, intensity-modulated radiation therapy (IMRT) was associated with fewer diagnoses of gastrointestinal adverse effects, hip fractures, and receipt of additional cancer treatments but more erectile dysfunction, while proton therapy was associated with more gastrointestinal adverse effects than IMRT, according to a study in the April 18 issue of JAMA, a theme issue on comparative effectiveness research.
"Prostate cancer is the most common malignancy in men, with more than 200,000 diagnoses and 30,000 deaths per year. Recent advances in technology have led to costlier treatments such as minimally invasive radical prostatectomy, intensity-modulated radiation therapy, and proton therapy. The adoption of these technologies resulted in a $350 million increase in health care expenditures in 2005 alone," according to background information in the article. Various organizations have called for comparative effectiveness research of localized prostate cancer treatments. "The clinical benefit from these newer treatments is unproven, and comparative effectiveness research examining different radiation techniques is lacking," the authors write.
Dr. Chen and colleagues conducted a study to examine the comparative adverse effects and disease control outcomes after different radiation techniques in a recent cohort of prostate cancer patients. Specifically, the researchers compared IMRT, which has been rapidly adopted and is currently the most commonly used technique, with the older conformal radiation therapy; and compared proton therapy, the use of which also has increased, with IMRT. The population-based study used Surveillance, Epidemiology, and End Results-Medicare-linked data from 2000 through 2009 for patients with localized prostate cancer. The primary outcomes measured were rates of gastrointestinal adverse effects (such as rectal bleeding or diarrhea) and urinary adverse effects, erectile dysfunction, hip fractures, and receipt of additional cancer therapy – as an indicator for disease recurrence.
The use of IMRT vs. conformal radiation therapy increased from 0.15 percent in 2000 to 95.9 percent in 2008. In the propensity-score adjusted analysis (n = 12,976), the researchers found that men treated with IMRT were less likely to receive a diagnosis of gastrointestinal adverse effects and hip fracture but more likely to receive a diagnosis of erectile dysfunction. Also, IMRT patients were nearly 20 percent less likely to receive additional cancer therapy.
In a propensity score-matched comparison between IMRT and proton therapy (n = 1,368), IMRT patients had a 34 percent lower risk of gastrointestinal adverse effects. There were no significant differences in rates of other adverse effects or additional therapies between IMRT and proton therapy.
"Proton therapy is a high-profile, high-cost prostate cancer treatment. Since 2007, multiple proton facilities have been built, and direct-to-consumer advertising is likely to lead to a substantial increase in use," the authors write. "Overall, our results do not clearly demonstrate a clinical benefit to support the recent increase in proton therapy use for prostate cancer."
The researchers add that the findings that patients receiving IMRT were less likely than those receiving conformal radiation therapy to undergo additional cancer treatments is consistent with the use of IMRT to deliver dose-escalated treatment, resulting in improved cancer control, as demonstrated by randomized trials. "Taken together, these results suggest that IMRT facilitated radiation dose escalation without compromising acceptable long-term morbidity."
"Comparative effectiveness research in localized prostate cancer treatments is needed because of the large number of men with this disease and the continued trend of a rapid increase in use of newer and costlier treatments with unproven clinical benefit," the authors write.
Sheets et al., (2012). Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. JAMA, 307, 1611-1620 [Abstract]
New radiation therapy reduces treatment of gynecologic cancers from 5 weeks to 3 days
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Wednesday, 18 April 12 - 01:03 PM (GMT) By The Society of Cancer Management in Research |
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About 71,500 women in the United States are diagnosed with a gynecologic cancer every year, according to the Centers for Disease Control. Researchers from University Hospitals Case Medical Center have developed a more effective way to treat gynecologic cancers, shortening radiation treatment time from five weeks to three days. The method will be published in the Journal of Visualized Experiments (JoVE) on April 17.
The new method, stereotactic body radiotherapy (SBRT) has been used on other types of cancer, but Case Medical Center is the first treatment facility to apply it to gynecologic cancers. Dr. Charles Kunos, who co-authored the article, said the radiation therapy machine "looks like a robot you would make cars with, and targets specific cancer cells."
Unlike traditional radiation therapy, SBRT uses focused radiation beams and targets well-defined tumors. In order to focus in on the region, the tumors need to be imaged and marked (using fiduciary markers) in advance. During treatment with the Cyberknife system from Accuray, patients need to be immobilized, and even the movement from the patient's breathing needs to be taken into account.
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131 beams were used to treat on a pelvic relapse of a chemorefractory ovarian cancer target over 42 minutes |
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The highly specific nature of the procedure not only shortens treatment time, it limits the effect of the radiation on healthy tissues.
"SBRT holds great promise for treating persistent or recurrent gynecologic cancers," said JoVEScience Editor, Dr. Nandita Singh. "SBRT can deliver radiation with high precision and is particularly effective in delivering reduced radiation to cancer targets that are refractory to chemotherapy and conventional radiation."
Dr. Kunos said he chose to publish the method in JoVE, the only peer reviewed, PubMed-indexed academic journal to publish all of its content in both text and video format, because he felt it was critical that he and his team have a high-quality video of the protocol for people to see when he and his team launch a nationwide clinical trial.
Kunos et al., (2012). Stereotactic radiosurgery for gynecologic cancer. J. Vis. Exp., 62, e3793 [Article & Video]
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