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    Dental experts urge diabetics to be mouth cancer aware this November

    Wed, Nov 19, 2014


    Author: staff

    November is Mouth Cancer Action Month, and dental experts are urging diabetics to be mouth cancer aware. Mouth cancer has become more prevalent in the UK in the last decade and studies show that people who have diabetes have a higher risk of developing mouth cancer.

    In the UK, more than 3 million people have diabetes and research has suggested that diabetics are up to 50 per cent more likely to develop mouth cancer than non-diabetics. Researchers discovered that diabetics aged between 40 and 50 years old were most likely to be affected.

    Dr Nigel Carter OBE, chief executive of the British Dental Health Foundation, the charity responsible for Mouth Cancer Action Month, said that it is extremely important that people are aware of the causes and symptoms of mouth cancer. Mouth cancer takes more lives in the UK than cervical and testicular cancer combined, yet many are still unaware of the warning signs and risk factors. Last week was World Diabetes Day and dental experts were eager to stress the importance of being mouth cancer aware for diabetics.

    Dr Nigel Carter stated that the study was a “very significant piece of research” and hoped that it would help to save lives in the future. Diabetes has been linked to oral health issues, but this is the first study to identify a link between diabetes and an increased risk of oral cancer. Dr Carter also stressed the importance of regular dental checks for diabetic patients.

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    1 in 10 unaware of mouth cancer risk

    Wed, Nov 19, 2014


    Author: press release

    One in ten people in the UK are unaware of the risk posed by mouth cancer, according to research carried out by the British Dental Health Foundation.

    This month, the UK’s leading charity, the BDHF, is joining forces with dental practices all over the country and mouth cancer charities to raise awareness of mouth cancer, and encourage people to have a screening check. Mouth Cancer Action Month runs throughout November and the aim is to get more people talking about oral cancer and visiting their dentist for routine check-ups and screening tests.

    Although 10 per cent of the population is unaware of mouth cancer, surveys show that around half of us are most worried about this form of cancer. Within the last decade alone, the amount of cases has nearly doubled and experts anticipate that as many as 30,000 new cases could be diagnosed in the coming 10-15 years.

    In the UK last year, 18 cases were diagnosed each day and figures suggest that the disease is becoming more prevalent. The main risk factors are smoking and drinking alcohol. There has been an increase in the number of young people affected, and it is believed that this is due to the increased threat of HPV infection. HPV (human papilloma virus) is also linked to cervical cancer.

    This month, dental experts all over the country are urging patients to be mouth cancer aware and to keep an eye out for changes in the mouth, ulcers that take a long time to heal, difficulty swallowing and the appearance of red or white patches in the mouth.

    Clinics and surgeries are offering free screening this month and screening checks can be organized by simply contacting your local dental practice at any time of the year. Dentists also carry out routine checks during your normal check-up.

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    ctDNA ‘Liquid Biopsy’ could revolutionize cancer care

    Wed, Nov 19, 2014


    Author: Janis C. Kelly

    Bits of tumor cell somatic DNA shed into the circulation or released when cells die can now be detected and counted, thanks to advances in gene sequencing. This circulating tumor DNA (ctDNA) is derived from somatic mutations that occur in the tumor during an individual’s life, unlike hereditary mutations that are present in every cell in the body, so ctDNA is a specific cancer biomarker that can be detected, measured, and tracked.

    Monitoring ctDNA is expected to provide clinicians with faster, cheaper, less invasive ways to assess cancer patients’ clinical status and response to therapy. ctDNA assay for multiple genes via next-generation sequencing (NGS) might become a “liquid biopsy” alternative to invasive tissue biopsy, experts told Medscape Medical News.

    However, they also cautioned that rigorous testing of this concept is needed before the test can be used in practice, saying: “for now, we would counsel clinicians not to jump the gun on this.

    Faster, Cheaper, More Accurate Tumor Tests
    Paul B. Chapman, MD, a medical oncologist with the Melanoma and Sarcoma Service at Memorial Sloan Kettering Cancer Center in New York City and Chair of the Medical Advisory Panel at the Melanoma Research Alliance in Washington, DC, said that ctDNA assay is less invasive than biopsy, requires no radiation exposure, is relatively inexpensive, uses fresh DNA not exposed to preservatives, and allows near real-time monitoring of response to treatment.

    “The beauty of ctDNA monitoring is the speed,” Dr Chapman said. “If you are looking for a change in a tumor, based on CT scan, you are talking about not only killing billions of tumor cells but also waiting for the resulting cell debris to be cleared by the body before the change shows up on imaging. That can take weeks. But cell death happens in minutes to hours, so you would expect the change in ctDNA to be a quick effect, and it is.”

    Chetan Bettegowda, MD, Luis A. Diaz Jr, MD, and colleagues at Johns Hopkins Medical Institutions in Baltimore, Maryland, working in collaboration with 16 other institutions worldwide, recently reported that ctDNA levels differentiate early vs advanced tumors in a wide variety of cancers. In 640 patients, the researchers found that ctDNA was detectable in over 75% of advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers but was found in less than 50% of primary brain, renal, prostate, and thyroid cancers. In 206 additional patients with metastatic colorectal cancers, ctDNA for KRAS gene mutations had 87.2% sensitivity and 99.2% specificity. The researchers also found that 96% of patients who relapsed after epidermal growth factor receptor (EGFR) blockade had ctDNA indicating one or more mutations in genes in the mitogen-activated protein kinase pathway.

    Counting the methyl groups on ctDNA fragments might be even more precise. An assay for hypermethylation of one or more breast cancer genes was 95% accurate in detecting identifying patients with metastatic breast cancer.

    However, Ben Ho Park, MD, PhD, from John Hopkins Sidney Kimmel Comprehensive Cancer Center and the department of chemical and biomolecular engineering at Johns Hopkins University in Baltimore, urged some caution in interpreting these data.

    Dr Park told Medscape Oncology that key unanswered questions include: “Can we use ctDNA for identifying patients that have mutations that are susceptible to targeted therapies? Can we use ctDNA to follow response to therapies in metastatic disease that actually makes a positive difference for patient care? And can we use ctDNA as tumor biomarkers for assessing residual disease for early stage cancers, and to determine if we can tell patients that they are cured after surgery and do not need additional adjuvant therapies [including chemotherapy]?”

    Advances in Gene Sequencing Led to Clinically Useful ctDNA Tests
    A major factor in the surging interest in ctDNA has been the rapid drop in cost for analyzing genetic information. In a development that puts Moore’s Law to shame, costs for whole genome sequencing dropped from $1 billion for the first complete genome sequenced by the Human Genome Project to $350,000 per genome in 2008 and more recently to about $1,000 for a genome sequenced with Illumina’s commercially available HiSeq X Ten sequencing system.

    Cancer researchers have been challenged by the problems of how to discriminate ctDNA from normal cell-free DNA, to detect extremely low levels of ctDNA, and to count accurately the number of mutant ctDNA fragments in a blood sample. The sensitivity of polymerase chain reaction (PCR)-based digital approaches improved with the addition of NGS, in which DNA is fragmented into small segments that can be quickly sequenced in millions of parallel reactions known as “reads” and then reassembled so that the set of reads shows the entire DNA sequence.

    The half-life of ctDNA is about two hours, and changes in ctDNA levels can be apparent days to weeks before changes in imaging or in protein biomarkers. Because ctDNA is specific for the individual patient’s tumor, it is likely to avoid some of the false-positive problems associated with other cancer biomarkers.

    Detecting Cancer and Monitoring Cancer Stages Without Biopsy
    Most ctDNA strands contain between 180 and 200 base pairs, similar to the 180 base-pair multiples characteristic of apoptosis, and are thought to result mainly from passive release into the blood of ctDNA after cell death.

    The presence of ctDNA after resection (but before adjuvant chemotherapy) indicates residual disease. Absence of ctDNA might identify a patient subgroup at low risk for recurrence who could be spared the risk, expense, and discomfort of adjuvant therapy. In 2008, a team of Johns Hopkins researchers reported that mutation-specific probes for 18 subjects undergoing multimodality therapy for colorectal cancer and monitored for two to five years showed that “ctDNA measurements could be used to reliably monitor the tumor dynamics in subjects with cancer who were undergoing surgery or chemotherapy.”

    The authors suggested that ctDNA levels reflect the total systemic tumor burden because they decreased after complete resection and increased as new radiologically-apparent lesions developed. The researchers also pointed out that micrometastatic lesions (smaller than a few millimeters) contribute to tumor burden and to ctDNA levels although they are not detectable by imaging.

    “For a melanoma patient who is free of disease after surgery but at risk for recurrence, ctDNA could be a nice way to follow without having to do frequent CT scans,” Dr Chapman said. It is also expected to be useful in situations in which tissue biopsy is undesirable or cannot be done.

    However, an important unanswered question is how often these tests should be done. “We need to know how meaningful small changes in the ctDNA level are — sensitivity, specificity, and lead-time bias,” he said.

    Monitoring Tumor Burden, Response to Therapy, and Resistance
    “Another key advantage is that ctDNA could overcome the issue of tumor heterogeneity,” commented Dr Park. “Different sites of disease often have different mutational profiles. Since blood, and therefore ctDNA, acts as a ‘reservoir’ for all sites of disease, ctDNA is representative for all sites of metastases.”

    A research team from Dr Chapman’s lab led by Parisa Momtaz, MD, reported at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting that in melanoma patients with BRAF-v600E mutations, ctDNA correlated well with tumor burden measured by radiographic imaging.

    “The ASCO cohort of 11 patients was to convince ourselves that we could get the assay to work (proof-of-principle) and that it correlated with what was clinically going on,” Dr Chapman said. “We have now studied ctDNA in about 60 patients. We are focusing on patients treated with immunotherapy because radiographic evaluation of these responses are somewhat equivocal. We hope that ctDNA will add more clarity and tell us whether the immune system is attacking the tumor or not.”

    Also at ASCO, Nicholas C. Turner, MD, consultant medical oncologist at the Institute of Cancer Research, London, United Kingdom, and colleagues reported that in primary breast cancer tumor-specific ctDNA levels can predict early relapse.

    ctDNA might also provide early warning that the patient has developed treatment-resistant disease. Sarah B. Goldberg, MD, MPH, assistant professor of medicine at Yale University School of Medicine, New Haven, Connecticut, and colleagues reported that ctDNA could be used to detect both sensitizing and resistance EGFR mutations in patients with advanced lung cancer treated with EGFR tyrosine kinase inhibitors. The researchers suggested that using NGS to detect sensitizing and resistance mutations in plasma ctDNA might allow earlier identification of resistance in patients treated with targeted therapies.

    Similarly, a team of researchers from nine cancer centers in Italy found that KRAS mutations in ctDNA could be detected in over 35% of patients with non–small-cell lung cancer who became resistant to tyrosine kinase inhibitors.

    In discussing this research, Luis A. Diaz Jr, MD, from the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University School of Medicine in Baltimore, and Alberto Bardelli, PhD, from the Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino, Italy, wrote, “This understanding of the mechanisms of acquired resistance to targeted agents at the molecular level can be used to plan combinatorial treatments with drugs that will suppress the expansion of the clones that are responsible for most of the current failures of medical treatment. This knowledge could result in the early adoption of alternate therapies before clinical resistance is detected.”

    Dr Chapman said, “I have this fantasy that you might use this to screen chemotherapy drugs in a patient. You could give them one dose of drug, then measure their ctDNA response. If there is no tumor death, the ctDNA levels wouldn’t change.”

    ctDNA: From Bench to Bedside
    Currently, monitoring genetic changes in a tumor requires multiple biopsies. “In the future, it might just be a matter of drawing a tube of blood,” Dr Chapman said.

    However, Dr Park warned that there has yet been little to no validation of ctDNA testing and that published studies show considerable variability due partly to lack of quality control and uniform standards.

    “How the plasma is prepared makes a huge difference, which isn’t always appreciated. How the ctDNA is analyzed is also quite variable among studies, with some technologies being better suited for specific applications. So for now, we would counsel clinicians not to jump the gun on this. We have to be extremely thoughtful and careful when dealing with ctDNA and its applications,” Dr Park commented. He quoted another researcher (Dan Hayes, MD, from the University of Michigan), who says it best: “A bad test can be just as bad as a bad drug.”

    “Therefore I believe we need to apply the same rigorous standards of testing drugs to the development of ctDNA as a liquid biopsy,” Dr Park said.

    Dr Chapman disclosed anticipated research funding from Trovagene. Dr Park reported no relevant financial interests.

    Ann Transl Med. Published online January 2014. Abstract; Sci Transl Med. Published online February 2014. Abstract

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    Federal goal is set to increase the amount of boys and girls vaccinated against HPV by 2020

    Wed, Nov 12, 2014


    Source: www. (Wall Street
    Author: Caitlin McCabe

    Public-health officials are pushing for higher HPV vaccination rates amid growing evidence that cancers linked to the virus are afflicting more men.

    The National Cancer Institute announced recently it is pouring nearly $2.7 million into 18 U.S. cancer centers to boost HPV vaccinations among boys and girls. The cancer centers will work with local health clinics to set recommendations for vaccinating against the sexually transmitted infection, which in some cases can cause cancers in men and women later in life.

    HPV, or human papillomavirus, was considered a women’s-only issue, after researchers discovered a link between it and cervical cancer in the 1980s. 

    Now, as cervical-cancer rates are falling and oral-cancer rates in men steadily rise, “the burden of HPV cancer is shifting to men,” said Maura Gillison, a professor in the College of Medicine at Ohio State University Comprehensive Cancer Center.

    Vaccination rates remain stifled, despite the availability of two vaccines that experts say provide effective coverage against cancer. 

    The Department of Health and Human Services’ goal is to boost HPV-vaccination rates to 80% by 2020—which is far higher than the 38% of girls and 14% of boys who completed the three-dose HPV vaccine last year, according to data from the National Immunization Survey of teenagers.

    Pediatricians say boosting those rates can be difficult. Pediatricians may feel uneasy talking to parents of young children about sexually transmitted infections, health experts say, while parents may resist the vaccine because they believe their child isn’t at risk.

    “Discussing this vaccination is difficult because there’s an implication of sexual activity,” said Carrie Byington, a practicing pediatrician in Salt Lake City and chairwoman of the Committee on Infectious Diseases for the American Academy of Pediatrics. “It can make some pediatricians uncomfortable with the topic.”

    A study conducted in 2011 by the Moffitt Cancer Center in Tampa, Fla., found fewer than 15% of physicians always recommended the vaccine to boys, and no more than 55% always recommended it to girls. Susan Vadaparampil, a professor in the department of oncologic services at Moffitt who helped lead the study, said she thinks recommendation rates have risen today but there’s a long way to go.

    To ease difficult conversations, Dr. Vadaparampil said resources on the Centers for Disease Control and Prevention website suggests that pediatricians should emphasize the vaccine is ultimately a protection against cancer and explain why children should receive the shots at such a young age. 

    Experts recommend the vaccine at age 11 or 12, but it can be given to girls up to age 26 and boys up to age 21. It is important for children to receive all three doses of the vaccine before they become sexually active.

    “There’s science behind giving it at age 11—it’s not just about moral or family choices, or a child’s choice for sexual debut,” said Wendy Sue Swanson, a pediatrician and executive director of digital health at Seattle Children’s Hospital. “The immune response is better if you give it to an 11-year-old.”

    Administering the vaccine at a young age doesn’t encourage sexual activity, Dr. Swanson said, citing a concern some parents have. A 2012 study comparing girls who had been vaccinated at ages 11 and 12 to nonvaccinated girls showed the vaccine made no difference in sexual behavior for at least three years after receiving the doses.

    Not all cases of HPV are cancerous. Experts estimate nearly 79 million Americans are currently infected with one of the 100 different strains of HPV, which is passed via sex. 

    Typically, a body’s immune system fights off HPV naturally within two years of exposure. Complications, such as genital warts or cancer, arise when the virus lingers. 

    About 26,800 Americans are diagnosed with HPV-related cancers each year, about two-thirds of whom are women, according to 2010 data, the latest available, from the CDC.

    The largest HPV-related threat to men is throat cancer, which has grown sharply in the past decade, Dr. Gillison said. 

    Today, more than 90% of all oral cancers are HPV-related, according to trends Dr. Gillison has observed in clinical settings in developed countries. That is up from about 72% between 2000 and 2004 and 16% between 1984 and 1989, she said, referencing a study she conducted that analyzed throat tumors in the U.S.

    Most of that growth has been in men: Each year, about 7,200 American men are diagnosed with HPV-related oral cancer, versus 1,800 cases in women, according to 2010 CDC data. 

    Dr. Gillison said researchers estimate that around 2020, HPV-related oral cancers in men will eclipse cervical cancer, which afflicts some 12,000 new women each year, according to 2014 data from the American Cancer Society.

    It’s unclear why men are more at risk for oral cancer than women, though some researchers suggest a person’s number of sexual partners may be related. The rise is problematic, Dr. Gillison said, because no preventive screening against throat cancer exists. 

    “The problem with HPV-positive oral cancer is that premalignant lesions are not clinically detectable. They’re deep within the tonsils that are in the base of the tongue,” Dr. Gillison said. “By the time HPV-infection is detected, they usually already have Stage 3 or 4 cancer.”

    That is why doctors and experts are relying so heavily on vaccination as prevention.

    Two vaccines—Cervarix, manufactured by GlaxoSmithKline Inc., and Gardasil, manufactured by Merck & Co.—are currently available, though only Gardasil is usually recommended for boys.

    Cervarix offers protection against two strains of HPV; Gardasil against four. A third vaccination from Merck currently awaiting approval from the Food and Drug Administration would offer protection against an additional five strains of HPV—nine in total. Doctors expect approval within in the next several months.


    *This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

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    UK researchers improve comfort levels for cancer patients by 3D printing radiotherapy body molds

    Wed, Nov 12, 2014


    Author: Bridget Butler Millsaps

    Cancer patients undergoing brain or head and neck radiotherapy are required to be immobilized, which is certainly not always popular with those undergoing the procedure, who may already be suffering from anxiety. To make things worse, in order to be immobilized completely during the procedure, it is crucial that they are wearing a fitted mold to prevent motion. Having the mold made is a whole process in itself before the procedure can begin.


    In a recent study produced by the Journal of Radiotherapy in Practice, over half of the patients describe the process of having a mold made as ‘horrific.’ Many of them also described the process as ‘uncomfortable.’

    Topping that off with molded shells that quite often do not fit appropriately, the anxiety levels are heightened for patients — enough so that researchers centered their study around the creation of molded shells through 3D printing that could be created from data conveniently already existing in the form of a CT scan. The process would increase the comfort level for the patient and save a great deal of time in preparing a molding.

    Radiotherapy is a type of cancer treatment which uses high-energy rays to zap cancer cells. The procedure has to be precisely aimed directly at specific areas to have effect, and it’s not a procedure anyone wants immediately repeated; therefore, It’s important to have the head shell or molding during radiotherapy because the patient must lie still. The mold or shell holds the head and neck in the correct position, and is fixed to the radiotherapy treatment table.


    The shell is made in what is usually a 30-minute process, and there are a number of factors involved in the process which make it even more inconvenient, such as hairstyle, dental issues, facial hair, and more. The current method for using molds during radiotherapy in the UK is in using the Orfit mask, which is made through soft draping, in a process where soft plastic is draped over the head and shoulders of the patient and it is molded to their body. Another method for making mask3the mask or mold is completed through use of high-temperature thermoplastics which are molded onto a plaster of the patient’s face.

    In the study, the multiple researchers confronted the issue of patient discomfort and anxiety over the radiotherapy molds and evaluated whether it would be possible to 3D print them and if the time, expense, and product outcome would make it a feasible idea. Their focus was on 3D printing the front of a test shell, and measuring whether it would interfere with the dose being given to the patient in radiotherapy. The actual material used in 3D printing was of obvious concern as well.

    The researchers reconstructed the head and neck of a whole body scan at a slice thickness of 3.75 mm and processed Digital Communications in Medicine (DICOM) data from MRI or CT scans with data relating to items such as masking, segmenting, conversion of the data from black to white, conversion to a hollowed out positive head, creation of a negative shell, and then conversion to an .stl file format for 3D printing. Visijet clear and EOS PA 3200 were the materials used, and researchers point out that any materials used for 3D printing of the shells should be the same or of even better quality to reach the same standard or better.

    Using a Z-Corps 650 printer from 3D Systems, researchers 3D printed their shells and set out to measure how they would affect the dosage being sent through the radiotherapy. Their findings were quite positive. Using three different types of materials, they found that the dosimetric properties of the 3D printing were promising in that all materials produced a small decrease in the dose of radiotherapy of up to one percent. All of the materials also produced an increase in skin dose between 54 and 80 percent, which could be minimized in using thinner materials, or creating holes in the masks, as having it increased too much is obviously not a good idea.


    Z-Corps 650 printer

    While 3D printing of the shells proved to be a bit more expensive than the more conventional methods, the researchers point out that this can be reduced if multiple masks are created in the same build chamber. It’s also possible that multiple hospitals could coordinate to purchase 3D printers together, thus reducing upfront cost.

    The bottom line was that the items can be feasibly 3D printed without reducing the dose, saving patients the anxiety of having the molds created through direct contact with their bodies, and affordability should be not be an issue in the near future as prices have been coming down consistently.

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    Smoking associated with elevated risk of developing a second smoking-related cancer

    Wed, Nov 12, 2014


    Author: staff

    Results of a federally-funded pooled analysis of five prospective cohort studies indicate that cigarette smoking prior to the first diagnosis of lung (stage I), bladder, kidney or head and neck cancer increases risk of developing a second smoking-associated cancer. This is the largest study to date exploring risk of second cancers among current smokers.

    An analysis of five large, prospective cohort studies indicates that lung (stage I), bladder, kidney and head and neck cancer survivors who smoked 20 or more cigarettes a day prior to their cancer diagnoses have an up to five-fold higher risk of developing a second smoking-associated cancer compared to survivors of the same cancers who never smoked. The association between smoking and developing a second primary smoking-associated cancer was similar to the association between smoking and developing a first primary smoking-associated cancer (patients who smoked more than 20 cigarettes per day had a 5.41-fold higher risk of developing cancer than individuals who have never smoked). Notably, current smoking at any level increased the risk of overall mortality across all cancer disease sites. The study, published on November 10 in the Journal of Clinical Oncology, affirms the 2014 Surgeon General report’s conclusion that patients and survivors who smoke are at a higher risk of developing a second cancer.

    Clinicians term an individual’s initial diagnosis a first primary cancer. A second primary cancer is one diagnosed at some point after the first diagnosis. Second primary cancers are not metastases of the first cancer but instead are distinct, new malignancies. This study focused on patients with a history of cancer who developed a second primary cancer.

    “As survival improves for a number of smoking-related cancers, patients are living longer; however, smoking may increase the risk of developing a second smoking-related cancer among these survivors,” said lead study author Meredith S. Shiels, PhD, MHs, a research fellow with the National Cancer Institute’s Division of Cancer Epidemiology and Genetics. “Our study demonstrates that health care providers should emphasize the importance of smoking cessation to all their patients, including cancer survivors.”

    Tobacco use constitutes the largest preventable cause of death and disability in developed countries and is a rapidly growing health problem in developing nations. It is responsible for 30% of all cancer deaths and is associated with increased risk for at least 17 types of cancer , . However, few studies have explored the association between smoking and second cancer risk. According to the authors, this is the largest study of its kind.

    Researchers examined data from five prospective epidemiologic cohorts, which included 2,552 patients with stage I lung, 6,386 with bladder, 3,179 with kidney and 2,967 with head and neck cancer from the following studies:

    • National Institutes of Health-AARP Diet and Health Study
    • Agricultural Health Study
    • Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
    • Iowa Women’s Health Study
    • Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

    A total of 866 second primary smoking-associated cancers were diagnosed among the survivors. The association between smoking status prior to primary cancer diagnosis and second smoking-associated cancer risk was assessed. Across all four cancer types, survivors who smoked 20 or more cigarettes per day at prior to their first primary diagnoses were more likely to develop a second smoking-associated cancer when compared to those who never smoked. Specifically, the risk increases were as follows:

    • Stage I Lung Cancer: 3.3 times more likely to develop a second cancer
    • Bladder Cancer: 3.7 times more likely to develop a second cancer
    • Head and Neck Cancers: 4.5 times more likely to develop a second cancer
    • Kidney Cancer: 5.3 times more likely to develop a second cancer

    Current smokers who smoked fewer than 20 cigarettes per day and former smokers who had quit before their first cancer diagnosis also had an elevated risk of developing a second primary smoking-associated cancer compared to survivors who never smoked (although risks decreased with the number of years since smoking cessation).

    Dr. Shiels stated that further research should directly assess the association between smoking after a first cancer diagnosis and second cancer risk.

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    Cialis shown to benefit head and neck squamous cell cancer patients

    Wed, Nov 12, 2014


    Author: staff

    Researchers at the Sylvester Comprehensive Cancer Center, in collaboration with Johns Hopkins University, have found that Tadalafil, commonly known as Cialis, can be therapeutic for certain types of cancer. When used before surgery, Tadalafil can reduce certain cells that are detrimental to head and neck squamous cell carcinoma patients’ prognoses.

    In a study recently published in Clinical Cancer Research, a publication of the American Association for Cancer Research, Donald T. Weed, M.D., professor of otolaryngology and Head and Neck Site Disease Group leader at Sylvester, and Paolo Serafini, Ph.D., assistant professor of microbiology and immunology, determined that moderate doses of Tadalafil given before surgery in patients with squamous cell cancers of the mouth and throat resulted in significant and potentially beneficial changes in the patients’ immune response to their cancer. The results suggest that the use of Tadalafil to modulate the body’s immune system could be a new therapeutic strategy for these cancers.

    Head and neck squamous cell carcinoma is a deadly disease with a high rate of recurrence, despite advances in treatment. This is partly attributed to the fact that these cancers can suppress the body’s immune response to the abnormal tumor cells, allowing the cells to defend themselves against immune system attack. Two important components of this defense against immune attack are myeloid derived suppressor cells (MDSCs) and regulatory T cells (Treg).

    MDSCs, named by Nature as one of the most important discoveries of the last decade, were originally identified at the University of Miami by Diana Lopez, Ph.D., professor of microbiology and immunology. They were then rediscovered and more fully characterized by Serafini and Vincenzo Bronte, M.D., at the University of Padova.

    The presence of MDSCs and Treg at the tumor site or in the patient’s blood can negatively affect patient outcomes by quelling the immune response to the cancer. Preclinical studies showed that Phosphodiesterase-5 inhibitors, such as Tadalafil, could suppress MDSCs and Treg by modifying the tumor environment.

    In a double-blind, placebo-controlled clinical trial, Weed and Serafini for the first time found that these preclinical findings hold true in humans. In addition, they discovered that Tadalafil increases CD8+T cells that boost immunity against squamous cells, resulting in minimized tumor growth.

    “Specifically, a short course of daily Tadalafil treatment prior to surgery is sufficient to significantly reduce MDSCs and Treg systemically and at the tumor site,” said Weed. “It increases the percentage of tumor specific CD8+T cells in circulation and also promotes the activation of CD8+T cells at the tumor site.”

    “What we are trying to do is prime the immune response,” said Serafini.

    “The big picture message is that Tadalafil has an immune effect that is potentially therapeutic,” added Weed. “The whole idea is that throat cancers protect themselves from immune attack by recruiting MDSCs and Treg. Interventions like Tadalafil, which interrupt pathways for recruiting MDSCs and Treg, can restore the body’s immune response and enable a more efficient killing of the tumor.”

    While both Weed and Serafini emphasize that the results of their trial do not support the use of Tadalafil alone as an option for cancer therapy, the researchers do hope that when combined with other immunotherapeutic strategies, the drug could reduce the tumor’s ability to defend itself against the immune system. To assess the viability of this theory, Weed and Serafini are now investigating whether Tadalafil can be combined with a tumor vaccine to cause an even more potent immune response and to reduce recurrence rates in patients with these cancers.

    The two researchers are preparing to open a clinical trial and are collaborating with renowned cancer immunologist Olivera “Olja” Finn, Ph.D., at the University of Pittsburgh. Finn is the developer of the anti-MUC1 cancer vaccine, which is designed to prime the body’s immune response against an antigen (MUC1) commonly found on the surface of squamous cell carcinomas of the head and neck and other cancers. This trial will only be open at Sylvester, and it will enroll patients suffering from Stage 3 or 4 recurrence of squamous cell carcinoma of the head and neck who are undergoing surgery as treatment.

    Patients will receive a short course of Tadalafil and the anti-MUC1 vaccine prior to surgery, then four courses after surgery. The goal is to demonstrate that this therapeutic strategy can effectively prime the body’s immune response against these cancers and hopefully reduce recurrence rates among patients. An added benefit is to promote a condition by which the body would recognize the cancer cells as foreign should they ever recur, even years after initial treatment, and the immune system would destroy them well before they could develop into a clinically significant tumor growth.

    Source: Miller School Departments, Centers and Institutes

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    Immune-related gene may predispose to HPV-related cancer

    Thu, Oct 23, 2014


    Author: Julia Parsons

    An international coalition of cancer specialists led by a researcher now at Baylor College of Medicine has identified an immune related gene called transforming growth factor beta receptor 1 (TGFBR1) that appears to play an important role in determining whether a person develops a cancer related to human papilloma virus (HPV). HPV is, in particular, associated with anal cancer and cancers of the cervix, and the head and neck.

    Their findings appear in the journal Cancer Research.

    Until recently, head and neck cancer has been found primarily in smokers, but there has been a rise in HPV-associated head and neck cancer in nonsmokers. The head and neck cancer most-associated with HPV is oropharyngeal cancer, involving the tonsils and base of the tongue.

    HPV is also one of the most common sexually transmitted diseases, with certain strains known to cause head and neck and/or cervical cancer.

    The National Cancer Institute predicts that HPV-positive oropharyngeal cancer will likely surpass cervical cancer as the most common HPV-associated cancer in the United States by 2020.

    “The real mystery is that in western countries, pretty much everyone is exposed to HPV but only a small number of people get HPV-related cancers,” said Dr. Andrew Sikora, vice-chair for research in the Department of Otolaryngology Head and Neck Surgery at Baylor. “We are trying to figure out what makes the people who actually get the cancer different from those who don’t, given that so many people are exposed.”

    Using data collected as part of a genome-wide association study of head and neck cancer performed by the INHANCE consortium, the researchers were able to associate alterations in a number of immune-related genes with oropharyngeal cancer. One of these genes, TGFBR1, was found to be deregulated in patients with both oropharyngeal and cervical cancer.

    “The fact that we were able to independently replicate our findings in two-different HPV-related cancers is exciting because it suggests that we have found something that is critical to the biology of how HPV causes cancer,” said Sikora, also co-director of the head and neck cancer program in the NCI-designated Dan L. Duncan Cancer Center Baylor.

    “We hope to learn more about this gene and how it affects cancer,” Sikora added. “In the future we hope to develop a tool to identify who is more susceptible to HPV-related cancers.”

    Sikora conducted the study while on faculty at the Icahn School of Medicine at Mount Sinai in New York prior to joining the Baylor faculty in July 2014. Co-author, Paolo Boffetta, director of the Institute for Translational Epidemiology at ISMMS was one of the investigators for the original INHANCE study.

    Others who took part in this study include:  Chaya Levovitz; John Finnigan; Sara Alshawish; Marshal R. Posner; Weija Zhang; Eric E. Schadt; Eric M. Genden and Paolo Bofetta; The Icahn School of Medicine at Mount Sinai in New York; Dan Chen and Emma Ivansson of Uppsala University, Uppsala, Sweden.

    *This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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    Mandibular reconstruction using plates prebent to fit rapid prototyping 3-dimensional printing models ameliorates contour deformity

    Thu, Oct 23, 2014


    Authors: Masaki Azuma, Toru Yanagawa, Naomi Ishibash Kanno, Fumihiko Uchida, Takaaki Ito, Kenji Yamagata, Shogo Hasegawa, Kaoru Sasaki, Koji Adachi, Katsuhiko Tabuchi, Mitsuru Sekido and Hiroki Bukawa

    Recently, medical rapid prototyping (MRP) models, fabricated with computer-aided design and computer-aided manufacture (CAD/CAM) techniques, have been applied to reconstructive surgery in the treatment of head and neck cancers. Here, we tested the use of preoperatively manufactured reconstruction plates, which were produced using MRP models.

    The clinical efficacy and esthetic outcome of using these products in mandibular reconstruction was evaluated.

    Methods: A series of 28 patients with malignant oral tumors underwent unilateral segmental resection of the mandible and simultaneous mandibular reconstruction. Twelve patients were treated with prebent reconstruction plates that were molded to MRP mandibular models designed with CAD/CAM techniques and fabricated on a combined powder bed and inkjet head three-dimensional printer.

    The remaining 16 patients were treated using conventional reconstruction methods. The surgical and esthetic outcomes of the two groups were compared by imaging analysis using post-operative panoramic tomography.

    Results: The mandibular symmetry in patients receiving the MRP-model-based prebent plates was significantly better than that in patients receiving conventional reconstructive surgery.

    Conclusions: Patients with head and neck cancer undergoing reconstructive surgery using a prebent reconstruction plate fabricated according to an MRP mandibular model showed improved mandibular contour compared to patients undergoing conventional mandibular reconstruction.

    Thus, use of this new technology for mandibular reconstruction results in an improved esthetic outcome with the potential for improved quality of life for patients.

    *This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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    Critical Outcome Technologies and MD Anderson Cancer Center to evaluate COTI-2 in treating head and neck cancers

    Thu, Oct 23, 2014


    Author: press release

    Critical Outcome Technologies Inc. (“COTI”), the bioinformatics and accelerated drug discovery company, announced today that it recently executed a material transfer agreement (“MTA”) with Dr. Jeffery Myers, MD, PhD, FACS of The University of Texas MD Anderson Cancer Center for the continued evaluation of COTI-2 in the potential treatment of patients with head and neck squamous cell cancer (“HNSCC”).

    There are approximately 500,000 new cases worldwide of HNSCC a year, making it the sixth leading cancer in terms of new cases. In the United States, HNSCC is considered to be a rare disease and therefore represents a second “Orphan Disease” opportunity for COTI-2.

    If HNSCC is caught at an early stage, current therapies, which include surgery and radiation followed by chemotherapy, can be effective. Unfortunately, HNSCC tumors with p53 mutations tend to be more difficult to treat with such mutations occurring in 30-70% of HNSCC tumors. These mutations are associated with poorer patient outcomes as traditional chemotherapy, using the current first line chemotherapy, cisplatin, is often ineffective. The overall five-year survival rate of patients with HNSCC is 40-50%.

    As a small molecule activator of misfolded mutant p53 protein, COTI-2 has demonstrated in preclinical studies its ability to restore p53 function and thus induce cancer cell death for many common p53 mutations. As previously announced, the Company is planning a Phase 1 study in gynecological cancers (ovarian, cervical and endometrial) at MD Anderson with Dr. Gordon Mills and his team and these studies in HNSCC with Dr. Myers will seek to extend the understanding of COTI-2′s ability to treat p53 mutations across multiple cancer types.

    Dr. Jeffrey Myers, leader of MD Anderson’s Multi-Disciplinary Head and Neck Cancer Research Program, has been studying the impact of p53 mutation, a common event in HNSCC, on tumor progression and response to therapy. His group has evaluated a number of single agent and combination treatments for p53 mutant tumors, and his preliminary findings with single agent COTI-2 in HNSCC in vitro tumor models show tremendous promise. In addition to seeing sensitivity of HNSCC cells to COTI-2, his group has found that this drug sensitivity is associated with activation of p21, an important mediator of p53′s response to cellular DNA damage. This response is consistent with the p53-dependent mechanism of action studied by Dr. Mills in ovarian cancer. Dr. Myers and his colleagues are planning more extensive studies of COTI-2 and its dependence on p53 re-activation for its effects in both in vitro and in vivo HNSCC tumor models.

    “We look forward to further exploring COTI-2′s impact on HNSCC tumors,” said Dr. Wayne Danter, President and CEO. “We continue to believe that COTI-2 represents a potential breakthrough treatment given the central importance of p53 gene mutations in many cancers, including HNSCC. This second indication would broaden the treatment opportunities for our lead oncology asset, which has already been granted the Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of ovarian cancer.”

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