radiation therapy

Gold nanorods could improve radiation therapy of head and neck cancer

Source:National Cancer Institute

Radiation therapy is an important part of head and neck cancer therapy, but most head and neck tumors have a built-in mechanism that makes them resistant to radiation. As a result, oncologists have to deliver huge doses of X-rays to the patient, damaging surrounding tissues and producing significant side effects. To overcome this resistance, researchers at the State University of New York (SUNY) at Buffalo and the University of Southern California (USC) have developed a nanoparticle formulation that interferes with the resistance mechanism, and as a result, increases the efficacy of radiation therapy in a mouse model of head and neck cancer. Reporting its work in the journal Integrative Biology (“Gold nanorod–sphingosine kinase siRNA nanocomplexes: a novel therapeutic tool for potent radiosensitization of head and neck cancer”), a research team headed by Paras Prasad of SUNY Buffalo and Rizwan Masood of USC’s Keck School of Medicine describes how it used gold nanorods to deliver a small interfering RNA (siRNA) molecule to head and neck tumors. This siRNA molecule blocks the production of a protein known as sphingosine kinase 1 (SphK1). Previous work by the USC team had shown that this protein prevents radiation-damaged cells from undergoing apoptosis, the cell death program triggered in healthy cells when they age or experience major damage. RNA interference, which uses siRNAs to reduce the production of specific proteins, has shown promise for treating cancer and other diseases, but these molecules are readily degraded in the blood stream. To overcome this problem, the SUNY-Buffalo team, an early pioneer in the cancer nanotechnology field and an original member of the National Cancer Institute’s Alliance for Nanotechnology in Cancer, has developed biocompatible gold nanorods that can protect siRNAs from degradation and deliver them to tumors. Working together, the two groups created a gold nanorod-siRNA construct that targets SphK1. When injected directly into head and neck tumors growing in mice prior to radiation therapy, this formulation boosted the efficacy of radiation therapy by over 50 percent. Moreover, this boost in efficacy was seen using greatly reduced doses of radiation. Animals that were treated with the nanoparticle formulation showed no ill effects from the drug. The investigators are now developing a new formulation that could be used to sensitize tumors for which direct injection of drug is not feasible.

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

January, 2012|Oral Cancer News|

Third Head and Neck Indication for Erbitux

Source: The ASCO Post, January 1, 2012, Volume 3, Issue 1, Matthew Stenger

 

In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.Cetuximab (Erbitux) was recently approved by the FDA for use in combination with platinum-based therapy plus fluorouracil (5-FU) for the first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck.1-3 Cetuximab has prior indications in combination with radiation therapy in locally or regionally advanced squamous cell head and neck cancer and in recurrent or metastatic head and neck cancer that has progressed after platinum-based therapy. It also has indications in colorectal cancer.

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The most recent approval is based primarily on results of a study conducted outside the United States in 442 patients with metastatic or locally recurrent squamous cell carcinoma of the head and neck who were not suitable for curative treatment with surgery or radiation. The study used a European Union (EU)-approved cetuximab rather than the U.S.-approved cetuximab (Erbitux). Erbitux provides approximately 22% higher exposure than the EU-approved cetuximab; these pharmacokinetic data, together with the results of the study conducted in Europe and other data using Erbitux establish the safety and efficacy of Erbitux at the recommended dose.In this trial, the addition of cetuximab (n = 222) to platinum-based therapy plus 5-FU (n = 220) significantly increased median overall survival from 7.4 to 10.1 months, representing a 20% reduction in risk of death (HR = 0.80, P = .034), and significantly increased median progression-free survival from 3.3 to 5.5 months, representing a 43% reduction in risk of disease progression (HR = 0.57, P < .0001). Objective response rates were 35.6% in the cetuximab group and 19.5% in the chemotherapy-alone group (P = .0001).


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How It Works

Cetuximab is an IgG1 monoclonal antibody that inhibits ligand-binding to the epidermal growth factor receptor (EGFR) on both normal and tumor cells. Binding of cetuximab to EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased production of matrix metalloproteinase and vascular endothelial growth factor. In cells with activating KRAS mutation, however, the KRAS proteins are continuously active and are independent of EGFR regulation. Cetuximab also stimulates antibody-dependent cell-mediated cytotoxicity and enhances the activity of a number of chemotherapeutic agents, including cisplatin.

How It Is Given

For the new indication, the recommended dose is 400 mg/m2 as a 120-minute IV infusion, with a maximum rate of 10 mg/min, on the day that platinum-based therapy plus 5-FU is started. The infusion must be completed 1 hour prior to beginning platinum-based therapy plus 5-FU. The subsequent weekly dose is 250 mg/m2 over 60 minutes until disease progression or unacceptable toxicity.Patients should be premedicated with an H1 antagonist (eg, diphenhydramine, 50 mg) IV 30 to 60 minutes before the first dose of cetuximab; premedication for subsequent doses depends on clinical judgment and presence/severity of prior infusion reactions. The infusion rate should be reduced by 50% for grade 1 or 2 or nonserious grade 3 infusion reactions. Cetuximab should be immediately and permanently discontinued for severe infusion reactions.In cases of severe acneiform rash, administration should be delayed by 1 to 2 weeks, and cetuximab discontinued at the fourth occurrence. The weekly dose should be reduced to 200 mg/m2 after the second occurrence and 150 mg/m2 after the third.Cetuximab should be administered via infusion pump or syringe pump and through a low protein-binding 0.22-micrometer in-line filter.

Safety Profile

Cetuximab carries a boxed warning for infusion reactions and cardiopulmonary arrest. Serious infusion reactions occurred in approximately 3% of patients in clinical trials, with fatal outcome in less than 1 in 1,000 cases. In patients with squamous cell carcinoma of the head and neck receiving cetuximab, cardiopulmonary arrest or sudden death occurred in 2% of those receiving radiotherapy and in 3% of those receving platinum-based therapy plus 5-FU. Serum electrolytes, including magnesium, potassium, and calcium, must be carefully monitored during and after cetuximab administration.In the trial supporting the current indication, the most common adverse reactions (≥ 25%) in patients in the cetuximab group were nausea, anemia, vomiting, neutropenia, rash, asthenia, diarrhea, and anorexia; conjunctivitis occurred in 10%. Other adverse reactions, sometimes severe, caused by cetuximab included infusion reactions, hypomagnesemia, hypocalcemia, and hypokalemia. Death attributed to cardiovascular event or sudden death was reported in 3.2% of the patients in the cetuximab group and in 1.9% in the chemotherapy alone group.

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

January, 2012|Oral Cancer News|

Tongue and tonsil cancer patients surviving longer

Source: Dr.Biscuspid.com

The five-year survival rate for U.S. patients with cancer of the base of the tongue or tonsils doubled between 1980 and 2002, according to a new study in Cancer Causes & Control (January 2012, Vol. 23:1, pp. 153-164).

In addition, patients with human papillomavirus (HPV)-related cancers had greater survival rates than those with other oral cancers, and survival was greater for male patients than females regardless of age, according to the study authors, from the New York Eye and Ear Infirmary, the University of Utah School of Medicine, and the University of California, Los Angeles School of Public Health. However, patients with subsequent multiple cancers showed no overall survival improvement.

The incidence rates of tongue and tonsil cancers have increased significantly in recent decades in the U.S., particularly among younger patients, the researchers noted. At the same time, a number of studies have shown a strong association between HPV infection and tongue and tonsil cancers.

For this study, they used data from the Surveillance, Epidemiology, and End Results (SEER) 1973-2006 registry system to examine changes in survival rates among patients with base of tongue, tonsil, and other tongue cancers in recent decades. The study included 10,704 patients with squamous tongue or tonsil cancer who were at least 20 years old.

The researchers separated the patients into those with one primary cancer and those with subsequent multiple cancers, then compared trends using three nonoverlapped periods: 1980-1982, 1990-1992, and 2000-2002. The first group included those with only one primary base of tongue, tonsil, or other tongue cancer, while the other consisted of those with subsequent primary cancers after an initial diagnosis of base of tongue, tonsil, or other tongue cancer.

Some 9,187 patients had one primary base of tongue, tonsil, or other tongue cancer, including 2,619 who were diagnosed with base of tongue cancer, 3,225 with tonsil cancer, and 3,343 with cancer in other sites of the tongue. Another 1,517 had subsequent multiple cancers, including 450 who were previously diagnosed with base of tongue cancer, 514 with tonsil cancer, and 553 with other tongue cancer.

Overall survival rates

After analyzing the data, the researchers found that the five-year overall survival rates for base of tongue cancer rose from 24.7% in the 1980s to 50.5% by 2002 (p < 0.001). For patients with tonsil cancer, the survival rate increased from 28.2% to 60.0% (p < 0.001). Patients with other tongue cancers experienced survival rate increases from 36.3% to 52.4% (p < 0.001) in the same 20-year period.

Compared with patients with one primary cancer, however, survival rates for patients with multiple tumors in the base of tongue, tonsil, or other tongue sites dropped significantly, the study authors noted.

Most notably, the five-year cancer-specific survival rates went up by 222.4% (17.4% in 1980 versus 56.1% in 2002) for the base of tongue cancer, 292.3% (16.8% in 1980 versus 65.9% in 2002) for tonsil cancer, and 95% (29.9% in 1980 versus 58.3% in 2002) for other tongue cancers.

Younger patients had much better survival rates, and young men’s survival doubled during the 20-year period, the researchers found. Five-year overall survival rates among female patients ages 20 to 59 years old increased by 71.3% (p < 0.001) and 27% (p = 0.03) for women age 60 and older. In contrast, survival rates increased by 152.1% (p < 0.001) for males ages 20 to 59 and 101.0% (p < 0.001) for men age 60 and older, they noted.

Screening and early treatment key

Survival was similar between patients who received surgery alone or those who had radiation therapy, the study authors found.

“A possibility for the improved survival trends is the effects of early oral screening and early diagnosis and early treatment of oral cancer,” they wrote.

They also speculated that cancers of the tongue and tonsil may be diagnosed more easily and earlier during oral screening, thus increasing survival.

Patients with regional stage tumors also showed improved survival, the researchers found.

The strong association between HPV infection and base of tongue and tonsil cancers probably played a part in the improved survival of both cancers, they noted. This could be related to the nature of the epithelium of the base of the tongue and the tonsil since HPV infection is close to lymphoid tissue, they wrote.

“Survival has significantly improved from the 1980s to the 2000s among patients with base of tongue or tonsil cancer, as well as among patients with other tongue cancer,” the researchers concluded. “Because of the reported strong association of HPV infection with base of tongue and tonsil cancers in incidence and in prognosis, we suspect that the time-dependent improvement may be related with increased HPV infection among patients.”

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

 

January, 2012|Oral Cancer News|

Quality-of-Life Outcomes in Transoral Robotic Surgery

Source: SAGE Journals Online

Abstract

Objective. To report long-term, health-related quality-of-life (HRQOL) outcomes in patients treated with transoral robotic surgery (TORS).

Study Design. Prospective, longitudinal, clinical study on functional and HRQOL outcomes in TORS.

Setting. University tertiary care facility.

Subjects and Methods. Patients who underwent TORS were asked to complete a Head and Neck Cancer Inventory before treatment and at 3 weeks and 3, 6, and 12 months postoperatively. Demographic, clinicopathological, and follow-up data were collected.

Results. Sixty-four patients who underwent TORS were enrolled. A total of 113 TORS procedures were performed. The mean follow-up time was 16.3 ± 7.49 months. The HRQOL was assessed at 3 weeks and at 3, 6, and 12 months, with a response rate of 78%, 44%, 41%, and 28%, respectively. TORS was performed most frequently for squamous cell carcinoma (88%). There was a decrease from baseline in the speech, eating, aesthetic, social, and overall QOL domains immediately after treatment. At the 1-year follow-up, the HRQOL scores in the aesthetic, social, and overall QOL domains were in the high domain. Patients with malignant lesions had significantly lower postoperative HRQOL scores in the speech, eating, social, and overall QOL domains (P < .05). Patients who underwent adjuvant radiation therapy or chemotherapy and radiation therapy had lower postoperative scores in the eating, social, and overall QOL domains (P < .05).

Conclusion. The preliminary data show that patients who undergo TORS for malignancies and receive adjuvant therapy tend to have lower HRQOL outcomes. TORS is a promising, minimally invasive, endoscopic alternative surgical treatment of laryngopharyngeal tumors.

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

December, 2011|Oral Cancer News|

Lymphedema Common After Head and Neck Cancer

Source: Elsevier Global Medical News

 

SAN FRANCISCO (EGMN) – Lymphedema is highly common and a source of considerable morbidity among patients who undergo treatment for head and neck cancer, finds a cross-sectional study among 103 survivors.

Fully three-fourths had developed some degree of lymphedema, according to results presented at the annual Oncology Congress presented by Reed Medical Education. The more severe it was, the more likely patients were to have symptoms, functional impairments, and poorer quality of life.

Disease and treatment-related factors such as high radiation dose and combined surgery and radiation therapy were risk factors for the development of lymphedema.

“This is the first study that we are aware of in the United States of this depth to systematically examine lymphedema” in this population, noted lead investigator Jie Deng, Ph.D., R.N., O.C.N., a postdoctoral fellow at the Vanderbilt University, Nashville, Tenn.

“Health care professionals should be aware that lymphedema is a frequent late effect in the head and neck cancer population,” she advised. “We need to educate patients about the risk of lymphedema prior to treatment, during treatment, and posttreatment, and we need to conduct external and internal examinations to evaluate related signs and symptoms at each clinic visit.”

Patients found to have any signs or symptoms should be referred for lymphedema assessment. Furthermore, “it’s very important we have very detailed documentation so we can follow up on patients’ treatment effect and also identify potential issues in this population,” Dr. Deng stressed. “An interdisciplinary approach is needed to best manage lymphedema.”

She and her colleagues are now evaluating interventions to treat head and neck lymphedema. Manual lymphatic drainage is one possibility. Elevating the head of the bed at night is another, as anecdotal comments suggest that symptoms worsen in the recumbent position.

“Patients will mention in the morning they feel more tightness, more fluid accumulated in the submental area; around noontime or afternoon, they feel it has drained by itself,” she explained.

There are more than half a million survivors of head and neck cancer in the United States, according to Dr. Deng. As a result of their disease and its treatment, these patients can develop both external lymphedema, causing symptoms such as facial puffiness, and internal lymphedema, causing issues such as epiglottal swelling.

The investigators studied adult patients treated for head and neck cancer at the Vanderbilt-Ingram Cancer Center who were at least 3 months out from the end of their treatment and had no evidence of cancer. External lymphedema was assessed with a clinical exam, using the Foldi scale. Internal lymphedema was assessed with an endoscopic exam, using the Patterson scale for edema of the larynx and pharynx.

The patients were 60 years old, on average. The majority were male (69%) and white (89%). In terms of health behaviors, 66% had a history of smoking and 38% had a history of alcohol use.

In all, 81% of the patients had had locally advanced cancer, and 90% had received at least two treatment modalities. The median time since end of treatment was 20 months.

Study results, reported at the meeting and also recently published, showed that 75% of the patients overall had lymphedema of the head and neck; of those with lymphedema (61 out of 81), 10% had only the external kind, 39% had only the internal kind, and 51% had both (J. Pain Symptom Manage. 2011 July 29 [doi:10.1016/j.jpainsymman.2011.03.019]).

The type and severity of lymphedema were associated with both physical and psychological symptoms, Dr. Deng reported.

As the severity of lymphedema increased, patients were significantly more likely to report difficulty swallowing, issues with mucus or dry mouth, nutritional problems, pain, and voice problems (P = .001 to P = .047, depending on the type of lymphedema and the specific symptom).

Additionally, increasing severity was associated with poorer body image (P = .028 to P = .049). “However, there was no statistically significant relationship between lymphedema and anxiety and depressive symptoms,” she noted.

Lymphedema severity was also associated with hearing deficits, limitation of neck range of motion, and impaired quality of life (P = .004 to P = .045).

Analyses identified certain disease and treatment-related factors to be risk factors for the development of lymphedema, according to Dr. Deng.

Namely, patients were more likely to develop lymphedema if they had pharyngeal tumors; were a shorter time out from the end of treatment; received a high total dose of radiation, mirroring what has been seen in breast cancer; received a greater number of treatment modalities, a marker of treatment intensity; or had combined surgery and radiation therapy – specifically, either surgery plus postoperative radiation, or salvage surgery within the irradiated field – as compared with surgery alone.

The higher risk with shorter time since surgery hints that the lymphatics in the area may undergo regeneration over time, she speculated. “This was identified in the murine tail [model of lymphedema]; however, we didn’t know whether or not this phenomenon or similar exists in the head and neck cancer population.”

None of the demographic factors or health behaviors assessed were found to be risk factors for the development of lymphedema. But the lack of association between smoking and alcohol consumption and lymphedema may have been related to the fact that patients were asked whether they smoked or drank but not the intensity, or to the cross-sectional nature of the study, Dr. Deng noted. “In the future, longitudinal study is needed to examine whether or not these are risk factors,” she said.

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

December, 2011|Oral Cancer News|

FDA Approves Cetuximab for Late-Stage Head and Neck Cancer

Source: The Oncology Report

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for “recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU,” according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for “locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy,” and for “recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

“Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. “Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible,” he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study “and other clinical trial data establish the efficacy of Erbitux at the recommended dose,” according to the revised prescribing information posted on the FDA Web site.

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

November, 2011|Oral Cancer News|

What accounts for racial differences in head/neck cancer?

Source: www.drbicuspid.com
Author: DrBicuspid Staff

Why are African-Americans more likely than Caucasians not only to be diagnosed with head and neck cancer, but also to die from the disease? While the answer isn’t a simple one, differences in lifestyle, access to care, and tumor genetics may be partly to blame, according to a new study from Henry Ford Hospital.

The study, which was presented September 14 at the American Academy of Otolaryngology – Head and Neck Surgery Foundation’s annual meeting in San Francisco, also found that African-Americans are more likely to be past or current smokers, one of the primary risk factors for head and neck cancer.

“We’re really trying to understand why African-Americans with head and neck squamous cell carcinoma do so poorly,” said lead author Maria Worsham, PhD, director of research in the department of Otolaryngology – Head and Neck Surgery at Henry Ford, in a news release. “Using a comprehensive set of risk factors that are known to have some bearing on the disease, we’re able to gain a better understanding of what contributes to racial differences and work to help improve patient care.”

This year alone, it’s estimated that 52,140 new cases of head and neck cancer will be diagnosed, and roughly 11,460 will die in 2011 from oral cavity and pharyngeal and laryngeal cancers, she and her team members noted.

African-Americans are more likely to be diagnosed with late-stage head and neck squamous cell carcinoma (HNSCC) and have a worse five-year survival rate than Caucasians. It’s unknown whether significant biological rather than socioeconomic differences account for some of the disparities in outcomes.

To get at the root of these differences, Worsham and her team used a large Detroit multiethnic group of 673 patients with HNSCC. Most notably, 42% of the study group was African-American.

The researchers took a broad approach to the study, examining many of the intertwined variables influencing health and disease to look for differences among African-Americans and Caucasians. In all, the study focused on 136 risk factors, including demographics (age, race, gender), smoking and alcohol use, access to care, and type of cancer treatment (radiation and/or surgery). Tumor characteristics, including stage, biology, and genetics, also were examined.

Among the study findings:

  • While 88% of African-Americans in the study had medical insurance, the majority had Medicare or Medicaid instead of private health insurance.
  • African-Americans also were more likely to be unmarried or living alone, both of which previous studies suggest have a negative impact on quality of life and survival.
  • In terms of cancer treatment, African-Americans in this study were more than two times more likely than Caucasians to receive radiation therapy. The study showed fewer African-Americans (43%) opted for surgery than Caucasians (49%).
  • African-American tumors were six to seven times more likely to present with lymphocytic response.
  • Compared to Caucasian tumors, African-American tumors were almost two times more likely to have loss of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and gain of the small inducible cytokine A3 (SCYA3) gene. CDKN2A is important to cell cycle regulation, and the SCYA3 gene product has dual roles of tumor lymph node metastasis and local host defense against tumors in HNSCC.
September, 2011|Oral Cancer News|

Michael Douglas Continues to Put Oral Cancer in the Spotlight

Source: Dr.Biscupid.com

Actor Michael Douglas’ recent revelation that he had stage IV oropharyngeal cancer has highlighted the growing incidence of oral cancer, and experts say dentists can help stem the alarming increase of the disease by checking for it during routine examinations.

The actor’s cancer included a walnut-sized tumor at the base of his tongue,  requiring radiation therapy, chemotherapy, and surgery. Douglas says his doctors told him he had an 80% survival rate if it hadn’t spread to his lymph nodes.

While tobacco was the prime cause of oral cancer in the past, recent studies have attributed the steady increase of the disease to the human papillomavirus (HPV16). There are approximately 130 versions of HPV but only nine cause cancers, and the HPV16 version causes almost half of the oral cancers in the U.S., said Brian Hill, executive director of the Oral Cancer Foundation.

“Tobacco is no longer the only bad guy,” he told DrBicuspid.com. “HPV16 is increasing in incidence as the causative etiology, and if it continues on this trend line, it will replace tobacco as the primary cause of oral cancers.”

Dentists can play a key role in catching the disease in its early stages if they check for it during examinations, Hill pointed out. “But many dentists think it’s such a rare disease that they don’t bother to screen for it,” he said. “Most Americans have never even heard of oral cancer, but it’s not as rare or uncommon as people would like to think it is. This is why an opportunistic screening by the dental community is so important.”

Hill, a nonsmoker, got the same diagnosis as Douglas in 1998 and underwent radiation therapy, chemotherapy, and surgery. Since Hill’s oral cancer had metastasized to both sides of his neck by the time it was discovered, surgeons removed the right side of his neck to remove the lymph nodes there. He has been cancer-free for 10 years and said there are a lot of stage IV survivors out there.

“I’m on this side of the grass and that’s all that’s important,” he said, adding with a laugh, “I’m not pretty, but I’m still here.”

Changing demographics

In the last decade, the demographics of oral cancer have changed dramatically, according to Hill and other experts, pointing to the sexual revolution and accompanying increase in the prevalence of oral sex. Today almost half of those diagnosed with the disease are younger than 50 years old — with some as young as 20, according to Hill — and they are usually nonsmokers. According to the American Cancer Society, oral cancer occurs almost as frequently as leukemia and claims more lives than melanoma or cervical cancer. The incidence in oral cancer patients younger than age 40 has increased nearly fivefold, with many patients with no known risk factors, according to the ADA.

“Social and sexual behaviors have changed,” Hill said. “Oral sex is more common. The virus is spreading, especially among young people because sexual contact is more common, and this virus is not only ubiquitous in our society, but the mechanism of transfer is very simple.”

Until 2000, scientists were unsure if HPV caused oral cancer, Hill said, but definitive research in 2000 revealed it as a distinct etiology for the disease, and more recent studies have supported this finding.

The disease is dangerous because often there are no symptoms in the early stages that a person might notice. “It’s a very insidious disease,” Hill explained. He recalled that it was not until a lymph node became swollen that Hill realized something was wrong. Even then, it was not painful, he said.

But an alert dentist will notice subtle signs and symptoms in a simple three to five minute visual and tactile exam, Hill noted. “There will be things he’ll pick up on, and that’s why we’re urging that the dental community to become more involved in oral cancer screening,” he said.

Approximately 37,000 new cases of oral cancer are diagnosed each year in the U.S., according to OCF, and some 43% of those people will die of the disease. Only 57% of all diagnosed oral cancer patients (considering all stages at time of discovery) will be alive five years after their diagnosis, Hill said. Approximately 100 people in the U.S. will be diagnosed with oral cancer every day, he added, and one person will die every hour from it.

And when celebrities get oral cancer, it helps bring about much needed public awareness about the disease, said Hill, noting that, in addition to Michael Douglas, such luminaries as Sigmund Freud, Babe Ruth, Beatle George Harrison, and Ulysses S. Grant have been among its victims.

“When somebody famous gets the disease, it finally gets the world’s attention,” he noted.

Oral cancer screening tips

According to the Oral Cancer Foundation, an oral cancer screening includes a systematic visual examination of all the soft tissues of the mouth, including manual extension of the tongue to examine its base, a bimanual palpation of the floor of the mouth, and a digital examination of the borders of the tongue, and a tactile examination of the lymph nodes surrounding the oral cavity and in the neck.

“Any sore, discoloration, induration, prominent tissue, irritation, or hoarseness that does not resolve within a two-week period on its own, with or without treatment, should be considered suspect and worthy of further examination or referral,” the foundation’s website states.

The website also offers a more complete oral cancer screening protocol and a photo gallery showing various forms oral cancer can take. It can be accessed at www.oralcancer.org

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

Targeting Cancer Treatment

Source: Medical News Today

Cancer treatment is depending more and more today on specific factors of a patient’s tumor, including gene mutations, or proteins that are commonly typical of certain cancer cells, rather than focusing on where in the body the cancer started. Before, treatment was based on finding where in the body the cancer originated, such as the breast or lung.

Targeted therapy is all about the cancer’s genes, tissue environment that contributes the tumor’s growth and survival, and its proteins. Nowadays, cancer therapy is designed to interfere with a signal that tells the cancer cells not to die or tells it to divide, while before, chemotherapies had the goal of interfering with cancer cells as division was already underway, when the cells were dividing into new ones.

The human body is made of various types of cells, including skin cells, brain cells, or blood cells. Each one has a specific function.

Cancer occurs when healthy cells change and start growing out of control; they eventually form a tumor – a mass. A benign tumor is noncancerous, whereas a malignant one is cancerous, it can spread to other parts of the body.
Cancer cells either divide too quickly or do not die when they should do
Specific genetic mutations within a cell change the way it behaves.

When the genes that control cell division mutate (change), they can multiply too quickly; the cell has become cancerous.
Cells are genetically programmed to die, when the specific genes that tell the cell to die mutate, and the cell does not die, it has become a cancerous cell.

Put simply, cancerous cells either divide too rapidly or do not die when they should, in both cases because their genes have changed.

Researchers study cancer cells and how they respond to their environment; by doing this they are finding that particular gene mutations are linked to the development of certain cancers. They are then able to develop medications that modify the alterations that had occurred in the cancer cell to stop the erroneous instructions of either dividing too fast or not dying – the effect can be to destroy the tumor, or at least to slow down its progression.

One example is a type of breast cancer that has too much HER2 (human epidermal growth factor receptor 2), a type of protein. The drug Herceptin (trastuzumab) blocks HER2. 25% of breast cancers are of this type. Herceptin only works for this specific type of breast cancer.

A tumor is part of a network of blood vessels, lymph and tissues. Without this network the tumor would not exist. Cancer spreads when a bit breaks off from the tumor and travels through the bloodstream or lymph system. Blood vessels nearby help feed the growing tumor.

Targeting the new blood vessel growth around a tumor is an effective way of treating some cancers. The process of growing new blood cells is known as angiogenesis. Bevacizumab (Avastin), sunitinib (Sutent), sorafenib (Nexavar), lenalidomide (Revlimid), and thalidomide (Thalomid) are drugs that interfere with angiogenesis – they stop blood vessels being formed and growing around the tumor.

Targeted therapies can be classified as:

Monoclonal antibodies – these are designed to block a specific target on the outside of cancer cells. A bit like trying to prevent electricity from flowing by placing a plastic plug into an electrical socket. As they are generally made up of large compounds which the body cannot absorb very well, they are administered intravenously. Examples include pertuzumab (Omnitarg), alemtuzumab (Campath-1H), panitumumab (Vectibix), bevacizumab, cetuximab (Erbitux), rituximab (Rituxan), and trastuzumab.
Oral small molecules – the patient swallows a pill, as the molecules are much smaller than those in monoclonal antibodies the body can absorb them well. This type of medication usually interferes with cancer processes within the cancer cell, inside it. Examples include nilotinib (Tasigna), lapatinib (Tykerb), imatinib (Gleevec), sorafenib, dasatinib (Sprycel), erlotinib (Tarceva), gefitinib (Iressa), sunitinib, and temsirolimus (Torisel).
Proteasome inhibitors – these are specialized proteins that interfere with enzymes (proteasomes) that break down other proteins within the cell when they are no longer needed. Bortezomib (Velcade), an injection that is used for treating multiple myeloma is an example.

Not all tumors have the same targets, though, recent studies have shown. A targeted treatment might not work for each patient. As these treatments may have side effects, and can be very costly, doctors have to try hard to match each patient to the most effective treatment whenever possible.

Sometimes targeting a medication to a tumor is not as simple as it sounds. What was targeted might turn out to be of no importance, or what worked before has no effect after a while – the cancer becomes resistant to the treatment. Targeted therapies may have serious side effects. Angiogenesis inhibitors are frequently linked to hypertension (high blood pressure).

Scientists and oncologists see targeted treatments as a major breakthrough in medicine. However, except in very few cases, these medications are not used on their own. Patients usually also undergo a combination of chemotherapy, radiation therapy, hormonal therapy or surgery.

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

Oral Cancer…what does sex have to do with it?

Source: DentistryIQ.com

The answer is … plenty! This issue will focus on oral cancer awareness. While there are many topics we can delve into regarding this dreadful disease, we will focus on a few topics.

We will share two personal and very poignant stories. Kim Anzalotti, Bill Wislon, and Eva Grayzel impart information that will move you and make you think about your daily in-office procedures. JoAnn Gurenlian, RDH, PhD, will share insights on the human papillomavirus, or HPV, a sexually transmitted virus, and its relationship to oral cancer. And last, but certainly not least, Jamie O’Day, Treatment Facilities Coordinator, The Oral Cancer Foundation Inc., The Bruce Paltrow Oral Cancer Fund, will share her insight on oral cancer screening and the need for a thorough examination.

One personal story is shared by Eva Grazel, an international motivational speaker, author, performer, and cancer survivor. I had the pleasure of meeting Eva a number of years ago. In 1998 at age 33, Eva, a non-smoker, saw a number of dentists and physicians for over two years for an “ulcer” on her tongue that became larger and more painful, without any resolution. She was finally diagnosed with advanced oral cancer, Stage IV squamous cell carcinoma, on the lateral border of her tongue.

After the many missed opportunities for diagnosis, Eva was given a 15% chance of survival. While her late stage diagnosis is not uncommon, her recovery was unique, as she beat the odds. After diagnosis, Eva underwent a partial tongue reconstruction, a modified radical neck dissection, and a maximum dose of radiation therapy. The good news is that Eva is very much alive today, and helps to motivate professionals and patients about oral cancer examinations and risk factors. She also authored the Talk4Hope book series, written to inspire children and parents who have a family member with cancer.This Family Book Series helps families cope with their feelings about cancer, enlightens parents on how to communicate with their children, and creates special moments to cherish. Read Eva’s contribution in this eVillage FOCUS issue.

For the 12th year in a row, April was the official oral cancer awareness month in the U.S. Oral cancer awareness means raising public awareness through group collaboration to ensure that oral cancers get the national media attention necessary to highlight risk factors and oral cancer screening. Free oral cancer screenings were held throughout the country. But it does not have to be a special month to conduct oral cancer screenings in the community. There are a variety of forms for editable press releases for events. Conduct your community activity when it is convenient for you.

Rates of oral cancer are on the rise among men, and researchers say the cause is not the use of tobacco and alcohol, risk factors we have been aware of for years. The number of smokers in the U.S. has steadily declined in the past 50 years, according to the CDC, yet the rate of oral cancer has remained relatively steady, and has recently been on the increase. The culprit is the human papillomavirus, or HPV, the sexually transmitted virus responsible for the majority of cases of cervical cancer in women. Approximately 65 percent of oral cancer tumors were linked to HPV in 2007, according to the National Cancer Institute.

The profile of these new cases of oral cancer is non-smokers who are predominantly white, upper middle class, college-educated men. HPV-16, the strain of the virus that causes cervical cancer in women, has become the leading cause of oral cancer in non-smoking men. Oral HPV infection was strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use in this case-controlled study. An even greater than-additive risk has been reported, although inconsistently, for patients exposed to both HPV and tobacco and those exposed to both HPV and alcohol.

A University of North Carolina (UNC) study found the incidence of oral tongue cancer increasing in young, white females, even though overall, incidence of oral cavity squamous cell carcinoma (OCSCC) was decreasing for all ages. The increasing incidence was most dramatic for white females ages 18 to 44. They had a percentage change of 111 percent.

Interestingly, the incidence decreased for African American and other racial groups. They analyzed incidence and survival data from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1975 to 2007 for OCSCC and oral tongue squamous cell carcinoma (OTSCC).

 

There is an enormous effort to vaccinate girls and women between the ages of 11 and 26 against HPV, and according to experts, should have included boys and men from the beginning. Gardasil (Merck), one of the two major vaccines used to prevent HPV infection, wasn’t approved for use in males in the United States until 2009, three years after it was approved for women. Men have a greater chance of contracting the HPV virus from oral sex than women do from the same behavior, though researchers are not clear on the reason for this phenomenon. For CDC information on HPV vaccines, visit their website.

 

The other vaccine is Cervarix (GlaxoSmithKline). According to the CDC, both vaccines are very safe, and are made with very small parts of the human papillomavirus (HPV) that cannot cause infection. As with any pharmaceuticals, there can be side effects. For a recently updated Q & A page on these vaccines, visit the CDC website.

In girls and young women ages 9 to 26, Gardasil® helps protect against two types of HPV that cause about 75% of cervical cancer cases, and two more types that cause 90% of genital warts cases. In boys and young men ages 9 to 26, Gardasil helps protect against 90% of genital warts cases. Gardasil also helps protect girls and young women ages 9 to 26 against 70% of vaginal cancer cases and up to 50% of vulvar cancer cases.

While the vaccines available are not approved for prevention of oral cancer, the impact the vaccines may have on oral cancer should be considered. The Oral Cancer Foundation believes that elimination of a causative agent (HPV16), by preventing infection from it by use of a vaccine, will subsequently prevent any disease that agent may have produced in the protected individual. This is simple scientific extrapolation, and a view shared by many in the science community. Makes sense to me!

Oral cancer has a low survival rate because it is generally not discovered until it has spread to other areas, according to the CDC. Only half of people who’ve been diagnosed with oral cancer will live longer than five years. Prevention is the name of the game. Do not use tobacco products, use alcohol in moderation, limit the number of sexual partners and use protection, and screen (or be screened) annually for oral cancer. Anyone old enough to have engaged in sexual behaviors which are capable of transferring the HPV needs to be screened annually for oral cancer. There are many cancer screening protocols available. Education, prevention, screening and early intervention can save lives.