radiotherapy

‘Dentist should have spotted my cancer’

Source: menmedia.co.uk
Author: staff

An NHS dentist who advised a patient to treat what turned out to be a life-threatening oral cancer with mouthwash is being sued for tens of thousands of pounds in damages.

Paula Drabble, 58, went to Pinfold Dental Practice, in Hattersley, Hyde, in June 2008 with concerns about a white lesion on her gum.

She was told by her dentist, Ian Hughes, it was nothing serious, a court heard.

Mrs Drabble of Mottram Moor, Mottram, Hyde, had five further appointments with Mr Hughes and was advised to ‘manage’ her complaint with mouthwash. She was eventually referred to hospital in April 2009, and ‘seriously invasive cancer’ diagnosed.

She had surgery, including removal of affected bone, followed by radiotherapy and chemotherapy.

She has now made a good recovery and has begun a High Court fight for damages, claiming Mr Hughes was negligent to have not spotted the cancer and referred her to hospital earlier. Timothy Briden, for Mrs Drabble, told the court his client had developed the patch on her gum some years earlier. The lesion was found to be benign by medics at the University Dental Hospital in Manchester and she was discharged in 2004 with a letter being sent to Mr Hughes, warning him to ‘re-refer if you notice or indeed Mrs Drabble notices any changes’.

Marcus Dignum, for Mr Hughes, denied that his client was at fault in failing to spot the cancer. He said: “Plainly the court will have every sympathy with Mrs Drabble in respect of her ordeal, as does Mr Hughes, but the allegations made against him are extremely serious from both a personal and professional standpoint. They are vigorously denied.

“In June 2008 the presence of the cancer would not have been detectable with the human eye, as its presence would have been at a cellular level only.”

January, 2013|Oral Cancer News|

Neoadjuvant chemo does not improve oral cancer survival rates

Source: www.drbicuspid.com
Author: DrBicuspid Staff

Patients with advanced resectable oral squamous cell carcinoma (OSCC) who undergo surgery do not benefit from improved survival after induction with docetaxel, cisplatin, and fluorouracil (TPF), according to a new study (Journal of Clinical Oncology, November 5, 2012). Study author Zhi-yuan Zhang, MD, PhD, from Shanghai Jiao Tong University School of Medicine, and colleagues assessed 256 patients with resectable locally advanced OSCC.

A total of 222 patients completed the full treatment protocol. They received two cycles of TPF induction chemotherapy (75 mg/m2 of docetaxel on day 1, 75 mg/m2 of cisplatin on day 1, and 750 mg/m2 of fluorouracil on days 1 to 5) followed by radical surgery and postoperative radiotherapy versus upfront radical surgery and postoperative radiotherapy.

The primary end point was overall survival. Secondary end points included local control and safety.

After a median follow-up of 30 months, there was no significant difference in overall survival or disease-free survival between patients treated with or without TPF induction, the study authors noted. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response had superior overall survival and locoregional and distant control.

“Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with upfront surgery in patients with resectable stage III or IVA OSCC,” the authors concluded.

The lack of survival benefit indicates that TPF induction chemotherapy without selection could not benefit OSCC patients in general, Dr. Zhang told Reuters Health in a news story.

“On the other hand, superior outcomes are seen in responders, as assessed both by clinical and pathologic responses,” he said. “Therefore, induction chemotherapy is likely to be effective for biologically distinct subgroups, and biomarker development might lead to identification of patients whose tumors are likely to respond to a particular treatment.”

November, 2012|Oral Cancer News|

DNA alone inadequate to identify HPV-related cancers

Source: www.oncologypractice.com
Author: Mary Ann Moon

Testing for the presence of human papillomavirus DNA alone, especially using polymerase chain reaction methods, is not adequate to identify which head and neck squamous cell carcinomas are caused by the virus, according to two studies published online Sept. 18 in Cancer Research.

Identifying HPV-driven malignancies is important because they respond better to treatment and have better outcomes than those unrelated to HPV infection. Indeed, treatment of head and neck squamous cell carcinoma (HNSCC) may soon be guided by the tumor’s HPV status, since trials are now underway to determine whether de-escalation of chemo- and radiotherapy is safe and effective in such patients.

At present, however, the biomarkers that are best suited to making this identification are unclear.

Case Series Assesses Biomarkers
In the first study, researchers assessed the usefulness of four biomarkers in determining which HNSCCs in a case series were driven by HPV. They began by examining fresh-frozen tumor biopsy samples from 199 German adults diagnosed as having oropharyngeal squamous cell cancer between 1990 and 2008.

The four biomarkers were HPV-16 viral load, viral oncogene RNA (E6 and E7), p16INK4a, and RNA patterns similar to those characteristic of cervical carcinomas (CxCa RNA), said Dr. Dana Holzinger of the German Cancer Research Center at Heidelberg (Germany) University and her associates.

The simple presence of HPV DNA in a tumor sample was found to be a poor indicator of prognosis, likely because it often signaled past HPV infections or recent oral exposure, rather than active HPV infection that progressed to malignancy, the investigators said (Cancer Res. 2012 Sept. 18).

Instead, “we showed that high viral load and a cancer-specific pattern of viral gene expression are most suited to identify patients with HPV-driven tumors among patients with oropharyngeal cancer. Viral expression pattern is a completely new marker in this field, and viral load has hardly been analyzed before,” Dr. Holzinger said in a press statement accompanying the publication of these findings.

“Once standardized assays for these markers, applicable in routine clinical laboratories, are established, they will allow precise identification” of cancers that are or are not HPV-driven, which will in turn influence prognosis and treatment, she added.

Results Back Combination Approach
In the second study, Dr. Caihua Liang of Brown University, Providence, R.I., and her associates examined 488 HNSCC samples as well as serum samples collected in a population-based study in the Boston area during 1999-2003.

As in the first study, these investigators found that the mere presence of HPV-16 DNA in these tumors, particularly when detected by PCR analysis, did not accurately predict overall survival or progression-free survival.

Instead, “our study strongly suggests that the combination of detection of HPV-16 DNA in HNSCC tumors [plus] p16 immunostaining with E6/E7 antibodies represents the most clinically valuable surrogate marker for the identification of patients . . . who have a better prognosis,” they said (Cancer Res. 2012 Sept. 28).

“Assessment of HPV DNA using polymerase chain reaction methods as a biomarker in individual head and neck cancers is a poor predictor of outcome, and is also poorly associated with antibody response indicative of exposure and/or infection by HPV,” senior author Dr. Karl T. Kelsey added in the press statement.

“We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments,” said Dr. Kelsey, a professor in the department of epidemiology and the department of pathology and laboratory medicine at Brown University.

Dr. Holzinger’s study was funded in part by the European Commission, BMBG/HGAF-Canceropole Grand-Est, and the German Research Foundation. Her associates reported ties to Qiagen and Roche. Dr. Liang’s study was supported by the National Institutes of Health and the Flight Attendant Medical Research Institute, and one associate reported ties to Bristol-Myers Squibb.

September, 2012|Oral Cancer News|

Study will evaluate Panitumumab regimen in advanced SCCHN

Source: http://www.onclive.com/
Author: staff

Canadian researchers are investigating standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN).

The NCIC Clinical Trials Group has completed accrual for the randomized phase III study, which has a planned sample size of 320 patients with SCC of the oral cavity, oropharynx, larynx, or hypopharynx. The trial was launched in December 2008, and the Data Safety and Monitoring Committee recommended continuing the trial in October 2011.

Patients assigned to arm I will undergo standard fractionation radiotherapy once daily, five days a week, for seven weeks; they will also receive cisplatin intravenously over one hour on days 1, 22, and 43 of radiotherapy.

Participants assigned to arm II will undergo accelerated fractionation radiotherapy once or twice daily, five days a week, for six weeks; they will also receive panitumumab intravenously over 30-90 minutes one week prior to and on days 15 and 36 of radiotherapy.

The primary endpoint is progression-free survival (PFS), while secondary endpoints include overall survival, local and regional PFS, distant metastases, adverse events, swallowing-related quality of life, functional swallowing outcomes, and economic assessments.

The FDA has approved panitumumab under the brand name Vectibix for the treatment of patients with metastatic colorectal carcinoma with disease progression on or following chemotherapy regimens containing fluoropyrimidine, oxaliplatin, and irinotecan. Panitumumab is a human IgG2 kappa monoclonal antibody that binds specifically to human epidermal growth factor receptor (EGFR).

Amgen, which markets Vectibix, has joined the Canadian Cancer Research Society Institute in supporting the trial (NCT00820248).

Source:
Waldron JN, Parulekar W, O’Sullivan B, et al. A phase III study of standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy (RT) with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) (NCIC Clinical Trials Group HN.6). J Clin Oncol. 2012;30(suppl; abstr TPS5600)

September, 2012|Oral Cancer News|

The Impact of Timing of EGFR and IGF-1R Inhibition for Sensitizing Head and Neck Cancer to Radiation

Source: AntiCancer Research

Abstract

Background: Targeting the epidermal growth factor receptor (EGFR) improved radiotherapy outcome by 10-15% in head and neck tumors (HNSCC). We tested the therapeutic benefits of co-targeting EGFR and insulin-like growth factor-1 receptor (IGF-1R) to further enhance tumor response to radiation. Materials and Methods: Mice bearing FaDu tumor xenografts were treated with ganitumab (previously known as AMG479, an anti-IGF-1R antibody), panitumumab (an anti-EGFR antibody), or both in combination with fractionated doses of radiation. Tumor growth delay and tumor cure/recurrence served as end-points. Results: The best tumor growth delay was achieved when ganitumab and panitumumab were given concurrently with radiation. Tumor cure/recurrence studies showed that combining ganitumab, panitumumab and radiation resulted in significantly higher radiocurability rates than use of either of the agents given with radiation. Conclusion: These findings provide the rationale for clinical testing of the combination of ganitumab and panitumumab for the treatment of HNSCC.

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

July, 2012|Oral Cancer News|

Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer

Source: Journal of Clinical Oncology

Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown.

Patients and Methods Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models.

Results Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026).

Conclusion Risk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment.

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

June, 2012|Oral Cancer News|

The UK’s first robotic mouth cancer operation

Source: www.privatehealth.co.uk
Author: staff

Pioneering surgery which allows doctors to remove cancer in the mouth using a minimally invasive technique is now available at the Wellington Hospital.

Traditionally, the only way to remove Squamous Cell Carcinoma – cancer of the oropharynx which encompasses the tonsils and base of the tongue – has been to split the jaw, take out the cancer and repair the neck with tissue from the forearm.

This 10-hour procedure requires two surgical teams and often has complications. Patients are in hospital for at least three weeks and need months of rehabilitation to help them swallow and speak again.

Because the treatment is so invasive, many doctors try to avoid it using chemotherapy and radiotherapy instead. However, surgery is often the best chance of a cure.

The new one-hour technique called Transoral Robotic Surgery allows the cancer to be removed without splitting the jaw or taking tissue from other parts of the body. Instead, the tonsils are accessed through the mouth using a specially designed robotic machine.

Developed in the US in 2009 and now approved by the American Food and Drug Administration and licensed for use in the UK, it uses the Da Vinci robot to access this difficult to reach area.

It gives the surgeon greater precision, dexterity and accuracy while carrying out the procedure and the patient has no stitches. Infection rates are reduced which speeds up recovery rates, patients are in hospital for just a week and are able to swallow normally soon afterwards and require no long-term feeding tubes.

Neil Tolley, a Consultant Head and Neck Surgeon at the Wellington Hospital, who is now carrying out the new technique, says: “The mouth is a small place. The da Vinci robot allows access to anatomical sites and permits surgery to be performed which would otherwise be technically very difficult or impossible to perform conventionally.

“On the patients treated so far, the swallowing outcomes have been excellent with no need for a gastrostomy tube to feed them, yet the same cure rates have been achieved.”

Keith Hern – Battling throat cancer, chemotherapy, radiotherapy and NLP

Source: www.youtube.com

Keith Hern was diagnosed with throat cancer and his story is captured in the book Bangers and Mash. In this video Keith talks frankly and honestly about the moment that changed his life forever – when he found he had cancer.

Actor’s Diagnosis Puts Spotlight on Oral Cancer

Source: DrBicuspid.com

May 9, 2012 — Actor Michael Douglas’ recent revelation that he has 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 includes a walnut-sized tumor at the base of his tongue, and he will require radiation therapy, chemotherapy, and surgery. Douglas says his doctors told him he has an 80% survival rate if it hasn’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 (HPV). 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

Oral cancer screening tipsAccording 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 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.

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 36,000 new cases of oral cancer are diagnosed each year in the U.S., according to the ADA, and some 25% of those people will die of the disease. Only 57% of all diagnosed oral cancer patients 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 and Ulysses S. Grant have been among its victims.

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

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

May, 2012|Oral Cancer News|

Radiotherapy May Be Enough for HPV-Positive Throat Cancer

Source: Medscape Today

May 11, 2012 (Barcelona, Spain) — Radiotherapy alone might be just as effective as more toxic regimens in the treatment of light smokers or nonsmokers with human papillomavirus (HPV)-positive advanced oropharyngeal carcinomas, according to research presented here at ESTRO 31: European Society for Radiotherapy and Oncology 2012 Annual Conference.

“Moderately accelerated radiotherapy as a single modality may be a safe and presumably morbidity-sparing treatment strategy for these patients,” said Pernille Lassen, MD, a resident in medical and radiation oncology at Aarhus University Hospital in Denmark.

“What we are suggesting — knowing that it’s not randomized and knowing that it’s not a very large series — is that perhaps we don’t need to treat these patients with chemotherapy and all the other things that we do,” she told Medscape Medical News. We’re “not recommending one treatment over another; this is a contribution to the ongoing debate. But [we’re] showing that we really cure a lot of patients with radiotherapy alone in this select group of nonsmokers or light smokers and HPV positivity.”

The researchers examined 181 patients from the Danish Head and Neck Cancer Group (DAHANCA) database who had advanced oropharyngeal cancer that had metastasized to the lymph nodes or beyond (stage III and IV).

Cumulative smoking history was categorized as greater than or less than 10 pack-years (1 pack-year is equivalent to 20 cigarettes per day for 1 year), and pretreatment tumor immunohistochemistry was assessed on the basis of HPV-associated p16 expression (positive or negative).

“p16 expression is a striking feature of these tumors, and this immunohistochemical marker is now considered a reliable marker of infection with HPV in these tumors,” said Dr. Lassen.

Radiotherapy was delivered in a moderately accelerated fractionated dose (66 to 68 Gy in 33 to 34 fractions at 6 fractions per week) with concomitant nimorazole.

The researchers found that 57% of the tumors were p16-positive, in line with current observations of an “epidemic rise” in such tumors, she said.

Although “classical tobacco-induced carcinomas of the larynx are actually declining,” there has been a “striking” 12-fold rise in the overall incidence or oropharyngeal cancers in the past 30 years — “and much is pointing to the fact that HPV is the predominant cause of this epidemic rise,” she said.

The researchers found that p16 positivity correlated with significantly better locoregional tumor control than p16 negativity (81% vs 48%), with 5-year disease-specific survival (90% vs 56%), and with overall survival (77% vs 38%).

Combining these data with smoking history, light (less than 10 pack-years) or nonsmokers who were also HPV-positive “had significant benefit in terms of all 3 outcomes” on univariate analysis, but this disappeared in the multivariate calculation.

“In this small study, this means that the effect of being p16-positive is so strong that when you put that in the multivariate analysis with smoking, smoking is no longer of significance,” Dr. Lassen said in the interview. “But we know from other studies that smoking is of independent prognostic significance.”

Patients with HPV-negative tumors fared poorly, regardless of their smoking status, she said.

These findings add to the growing body of evidence that HPV-associated p16 status “has a significant influence on outcome after radiotherapy in advanced oropharyngeal carcinomas,” she said.

Additionally, “higher rates of tumor control and survival are achievable in patients with HPV-positive tumors and a smoking history of less that 10 pack-years — even when we treat these patients without chemotherapy.”

“These tumors respond extremely well to therapy,” she explained. “When you have a survival probability of 95% at 5 years, it’s really, really, hard to determine which treatment will be most optimal. I think we will have a spectrum of equally efficient treatment strategies and it will end up that the institution a patient is in and the expertise there will determine the treatment they get.”

Asked to comment, Vincenzo Valentini, MD, president of ESTRO and a radiation oncologist at Policlinico Universitario “A. Gemelli” in Rome, Italy, said the findings should be interpreted with caution.

“At this moment, we still do not have definitive data telling us that for these very good responders, we can deescalate treatment,” he told Medscape Medical News. “We can say they have a much better prognosis, but we still cannot say in a definitive way that we can reduce treatment. We have to test it; there is a nice group of studies going on to test this hypothesis.”

He emphasized that although HPV status is of proven prognostic significance, it should not overshadow the importance of smoking status. “The evidence [from this study] is a little in conflict with other larger studies. [HPV status and smoking] are really relevant, and we still need final validation of whether they are really independent or whether one is more significant than the other. But in our clinical evaluation, we see that smoking has a very negative impact on prognosis and also tolerability of treatments.”

Prevention is a key message that should be spread about smoking, “when we see that 10 pack-years could change the possibility of cure,” he said. “We have a lot of people who start to smoke very early, at 15 or 16, and when they are 25, they have already put themselves on the dark side of the moon. The damage of 1 cigarette is permanent — it is not something you can dilute just because it happened 25 years ago.”

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

May, 2012|Oral Cancer News|