radiotherapy

Photographer inspires others with throat cancer survival

Source: www.getsurrey.co.uk
Author: Rebecca Younger

When Thames Ditton photographer, Keith Hern, was diagnosed with throat cancer five years ago, he dealt with it the only way he knew how – by taking pictures.

Through an incredibly honest and stark photographic portrayal of his treatment, Keith captured everything from the first bout of chemotherapy at the Royal Marsden Hospital in London to the making of his radiotherapy mask and the eight-inch scar left on his neck after an operation to remove dead cancer cells. The candid imagery appears in Keith’s book, Bangers & Mash, which he started writing shortly after he was first diagnosed in 2007.

“I’d started writing a couple of days after diagnosis as the only way I could maintain some semblance of mental control, it would later become therapeutic,” he recounted. “My treatment consisted of five days of 24×7 chemotherapy, 11 days off, five days of chemotherapy again, 11 days off, then radiotherapy for six weeks daily with two top-up chemo sessions in weeks one and five.

“Radiotherapy side effects kicked in at the end of week one – I could no longer eat, then lost my taste, then I couldn’t sleep (my mouth was so dry I was sipping water 24×7), I lost two-and-a-half stone in the six weeks.”

Keith worked with a Neurolinguistic Programming (NLP) coach to stay positive and it was while talking to her about writing a book of his experiences that the idea for a photo diary came about.

“She laughed at the idea and said, why didn’t I do what I was good at and photograph the treatment. It really started there,” he said.

Bangers & Mash, so titled because that was the first proper meal Keith ate after coming through the disease (treatment meant eating solids was painful and food in general tasteless), was published in November 2009. The book not only recorded Keith’s experiences at the Royal Marsden but also his fundraising expeditions to raise cash for hospital including a trek in Iceland, which raised around £7,000.

“That was a real achievement for me. When I first saw the leaflet for the trek at the hospital in 2007, I was at my lowest ebb. I signed up not knowing if I would be alive a year later to actually take part,” the 54-year-old said.

Quite ironically, just two weeks after Keith saw his incredible story of survival in print, he was told the cancer had returned, this time in his chest.

“I was given a 10% to 40% chance of survival. The tumour was too inaccessible and close to key organs to operate so I had to have three sets of five-day chemotherapy sessions, followed by four weeks of daily radiotherapy,” he explained. “That’s a pretty sobering fact to be told, but having survived before I was determined to do so again.

“A lot of it is in the mind. I know three people who were given three months to live – for one of them that was 25 years ago and they are still here.”

In May 2010, Keith was once again pronounced clear of the cancer and it was around this time that publicity surrounding his book began to grow, partly due to Hollywood actor Michael Douglas’ high profile diagnosis later that year.

“I was then interviewed on radio, in the Daily Mail, and then on ITV’s This Morning, from which a number of people got in touch including one young lady recently diagnosed and in the same mental state as I was at the start,” he said. “She found Bangers & Mash really helpful and gave a great testimonial.”

Keith has started a follow-up book and regularly gives motivational talks to businesses, schools and groups across Surrey. He is also planning another fundraising expedition to Nepal in November to raise more money for the Marsden.

“I’d like to think my story not only helps those living with throat cancer but also their relatives and even those, who have had no experience of the disease,” Keith said. “Talking about it and being completely open about the whole experience, warts and all, raises awareness and that can only be a good thing.”

Wider Surgical Margins Better for Early Tongue Cancer

Source: Dr.Biscuspid.com

Wider surgical margins for early tongue tumors may reduce local recurrence and improve survival for most early-stage (T1 or T2) oral tongue squamous cell carcinoma (SCC) tumors, according to a new study in the Journal of Laryngology & Otology.

Oral tongue SCC is usually treated with initial surgical resection with or without post-operative chemo- and radiotherapy. Regional recurrences occur in approximately one in four patients with T1 or T2 oral tongue SCC, justifying aggressive treatment, according to the study authors from the University of Melbourne (JLO, March 2012, Vol. 126:3, pp. 289-294).

“We feel that wider surgical margins may be justified, being the only prognostic factor that surgeons have the ability to improve.”

Among the most important histological factors that impact the prognosis for early oral cancer are lymph node metastases, extracapsular extension, and close or involved surgical margins, they noted.

“Although other factors have an impact on adjuvant treatment, surgical margins is the only factor that may be improved by the surgeon,” they wrote.

Traditionally, a 1-cm margin is taken in all planes around a macroscopic or palpable oral tongue SCC, the study authors noted. Pathologists and clinicians have agreed to define involved margins as less than 1 mm and close margins as 5 mm or less, while margins greater than 5 mm are designated as clear.

However, mucosal margins shrink by approximately 30% to 50% with formalin fixation and slide preparation. This results in a final pathological margin of approximately 5 mm where the surgeon measured 1 cm, leaving little room for error.

Statistically significant findings

For this study, the research team set out to determine the site of closest margins for previously untreated early oral SCC cases from 2000 to 2009 at Royal Melbourne Hospital. The median age at diagnosis was 63.

Through a retrospective chart review, the researchers identified 68 T1 tumors and 13 T2 tumors, with a median follow up of 38 months. Sites of close and involved margins were reviewed histologically.

Slides were categorized as clear if the margin was more than 5 mm (n = 24), close if the margin was 1.1 to 5 mm (n = 44), and involved if the margin was less than 1 mm (n = 10).

The site of close and involved margins was classified according to its quadrant, i.e. medial, lateral, anterior or posterior. Close and involved margins were also designated as deep (more than 3 mm from the cut mucosal edge) or mucosal (less than 3 mm from the mucosal edge or on the actual mucosa).

Other prognostic variables included depth of invasion, tumor differentiation, maximum diameter, lymphovascular invasion, perineural invasion, pathological cervical nodes, and extracapsular extension.

The researchers found clear margins in 24 patients (30.8%), close margins in 44 patients (56.4%), and involved margins in 10 patients (12.8%). There was a non-significant trend toward deeper tumors having more involved margins (p = 0.18). Clear or close margins were just as likely to be achieved in T1 cases (90%) as in T2 cases (82%) and node-negative (100%) and node-positive cases (82%).

Perineural or lymphovascular invasion was seen equally in cases with involved margins (20%) and cases with clear or close margins (21%).

Patients with deeper tumors were more likely to undergo neck dissection for the N0 neck than patients with thin tumors (p = 0.02). Four patients (22%) with a tumor depth of 2.1 to 4 mm had a prophylactic neck dissection, as did 15 patients (58%) with a tumor depth of 4.1 to 7 mm.

A majority of the tumors had the closest margin at or near the mucosal edge (59%) rather than on the deep surface (41%, p = 0.22), the study found.

1-cm margins ‘inadequate’

Local recurrence occurred in 22 patients (28%) at a median of 12 months. Five of the 10 patients (50%) with involved margins developed local recurrence, the study found. Nine (21%) of the 43 patients with close margins had local recurrence, compared with eight (33%) of the 24 patients with clear margins (p = 0.10).

The study found that involved surgical margins had a trend to worse local recurrence (p = 0.10) and significantly worse survival (p = 0.002). Over the last 10 years at the hospital, 14% of patients had involved margins and 55% had close margins, the researchers noted.

“Consequently, we feel that wider surgical margins may be justified, being the only prognostic factor that surgeons have the ability to improve,” the researchers wrote.

Histological clear margins may be one of the few prognostic factors on which good surgery can have an impact, they added. Wider margins, however, may have an impact on functional outcomes and significantly affect quality of life.

“This study’s findings support the hypothesis that wider surgical margins may be appropriate for most T1and T2 oral tongue SCC tumors, with the aim of reducing local recurrence and thereby improving survival,” the study authors concluded. “The historically accepted 1-cm margin around macroscopic and palpable oral tumors seems to provide inadequate pathological results.”

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

March, 2012|Oral Cancer News|

Epidermal Growth Factor Receptor and the Changing Face of Oropharyngeal Cancer

Source: Journal of Clinical Oncology

To the Editor:

In their article, Chaturvedi et al1 document the rise in human papillomavirus (HPV) –associated cancers as a proportion of squamous cell carcinomas of the oropharynx over the last 25 years. The contemporary figures are mirrored by two recent British studies2,3 demonstrating that the majority of oropharyngeal cancers are now HPV related.

In the accompanying editorial,4 Mroz et al rightly highlight the importance of evaluating HPV vaccination for both men and women in the light of these data and lament the lack of significant improvement in the outcomes for non–HPV-associated head and neck cancers. However, they also suggest that the benefit of targeting epidermal growth factor receptor (EGFR) through concurrent cetuximab may be confined to HPV-associated tumors. Although EGFR expression per se does not correlate closely with response to cetuximab, there is increasing evidence of an inverse correlation between p16INK4A expression (as a marker of HPV association) and EGFR expression shown by immunohistochemistry.5,6 Though suppressed by viral oncogenes, HPV-associated tumors retain wild-type P53,7 and patients with this tumor type have demonstrated excellent survival with existing protocols such as concurrent chemoradiotherapy or surgery with postoperative radiotherapy. Conversely, non-HPV tumors, harboring a range of mutations,8 may respond less well to DNA-damaging agents, but patients with these tumors might benefit from the addition of concurrent EGFR blockade to radiotherapy. Data from the recent SPECTRUM (Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer) study of adding another EGFR-targeting monoclonal antibody, panitumumab,9 suggest that in the metastatic setting at least, only patients with HPV-negative tumors benefit from a combination of palliative chemotherapy and an anti-EGFR strategy. If confirmed in sample sets containing non-HPV tumors treated with EGFR-targeting agents in combination with radiotherapy, this could open the door to the improvements urgently needed in HPV-negative oropharyngeal cancers, where an older demographic and greater burden of comorbidities make the uncomplicated and complete delivery of concurrent chemoradiotherapy challenging.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

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

March, 2012|Oral Cancer News|

Radiotherapy technique significantly reduces irradiation of healthy tissue

Source: www.sciencecodex.com/
Author: staff

Researchers at the University of Granada and the university hospital Virgen de las Nieves in Granada have developed a new radiotherapy technique that is much less toxic than that traditionally used and only targets cancerous tissue. This new protocol provides a less invasive but equally efficient cancer postoperative treatment for cases of cancer of the oral cavity and pharynx.

The study -conducted between 2005 and 2008- included 80 patients diagnosed with epidermoid cancer of the oral cavity and pharynx, who had undergone lymph node removal. The affected nodes were located by the surgeon during the intervention and classified into different risk levels. Classification allowed physicians to target the areas at a higher risk of recurrence. This way, neck areas at a lower risk of containing residual cancer cells were not irradiated. Researchers achieved both to minimize the side effects of radiotherapy, and to reduce treatment discontinuation, thus achieving the therapy to be more effective.

A Highly Toxic Treatment
Over 70% of oral and pharynx cancer treated with surgery require supplementary treatment with radiotherapy occasionally associated to chemotherapy, because of the high risk for recurrence and spread through the lymph nodes. Radiotherapy and chemotherapy are highly toxic, mainly due to the ulceration of the mucous membranes lining the oral cavity; toxicity leads may patients to stop the treatment, which significantly reduces the chances of cure.

By using the risk map obtained with the collaboration of the surgeon and the pathologist, an individualized treatment was designed and adapted to the specific risk level of recurrence in each neck area. The volume of tissue irradiated was significantly smaller than that usually irradiated with traditional techniques.

This trial was led by the radiation oncologist at the university hospital Virgen de las Nieves, Miguel Martínez Carrillo, and conducted in collaboration with the Services of Radiation Oncology, Medical Physics, Maxillofacial Surgery and Pathology of the university hospital Virgen de las Nieves, and the University of Granada Department of Radiology and Physical Medicine

After a three-year follow up, using this new technique, scientists achieved to reduce the volume of irradiated tissue in 44% of patients. By this new technique, irradiation of an average volume of 118 cc of tissue was avoided. A total of 95% of patients completed radiotherapy and presented significantly lower toxicity than patients treated with the traditional technique. Recurrence rates did not increase.

This study was coordinated by University of Granada professors Rosario del Moral Ávila and José Mariano Ruiz de Almodóvar Rivera. The results of this study will be published in the next issue of the journal Radiation Oncology.

Source: University of Granada

February, 2012|Oral Cancer News|

Adaptive radiotherapy may benefit patients with head and neck cancer

Source: News-Medical.net

Researchers led by a senior investigator at Hofstra-North Shore LIJ School of Medicine and The Feinstein Institute for Medical Research have released initial findings from a first-of-a-kind clinical trial in adaptive radiotherapy (ART) for head and neck cancer. The trial, sponsored by the National Cancer Institute, provides evidence that ART may benefit patients with less technical difficulty than previously believed. The findings of this trial were released online in advance of publication in the International Journal of Radiation Oncology Biology Physics.

Physicians commonly use radiotherapy to treat squamous cell carcinoma of the oropharynx (back of throat). Current standard-of-care treatment is called intensity-modulated radiotherapy, or IMRT. IMRT allows physicians to “sculpt” radiation to fit the anatomy of individual patients. Although appealing, this technique has a crucial Achilles’ heel – it is based entirely on a CT or MRI scan taken before actual treatment begins. Since a typical course of radiation treatment for oropharynx cancer lasts 6-7 weeks, standard IMRT cannot compensate for common changes that take place in a patient’s body during this time, such as weight loss, shrinkage of tumor, or gradual movement of normal tissues. Recent work suggests that the inability of standard IMRT to keep up with these changes may lead to unanticipated toxicity, or potentially worse, missing of tumor.

For this new trial, which was conducted at the University of Texas M.D. Anderson Cancer Center, investigators started patients on standard IMRT. They then took CT scans while patients were lying in the radiation treatment room each day so they could monitor changes in tumor and normal tissues during the entire course of treatment. Through computerized techniques, the investigators “adapted” (thus the name “adaptive radiotherapy“) treatment if they noticed significant tumor or body changes that could affect quality of treatment. Most strikingly, the group found that most patients required only one, or at most two adaptions of IMRT to maintain treatment quality.

“This is the first prospective clinical trial of its kind to gauge how “refitting” of IMRT to a patient’s body actually impacts care for a patient who has head and neck cancer,” noted David Schwartz, MD, vice-chair of radiation medicine at the North Shore-LIJ Health System, associate professor at the Hofstra North Shore-LIJ School of Medicine, and a senior investigator at The Feinstein Institute for Medical Research. “What most encouraged us was that ART appears effective with only 1 or 2 additional replans. This means that ART does not have to be overly burdensome or expensive to make a difference. This is something that is feasible, and could eventually make a real-world difference in many clinics.”

“ART keeps radiation treatment tightly fitted to a patient’s body, almost as if it were being shrink-wrapped,” Schwartz added. “It is as individualized as our current treatment can realistically be.”

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

February, 2012|Oral Cancer News|

Cisplatin Aids Survival of High-Risk Head and Neck Cancer

Source: Oncology Report

Adding chemotherapy to radiotherapy improved 10-year survival of resectable head and neck carcinomas among high-risk patients who had microscopically involved resection margins and/or extracapsular spread of disease – but not in high-risk patients who only had tumor in multiple lymph nodes.

The findings come from a long-term update and unplanned subset analysis of 410 evaluable patients from the RTOG (Radiation Therapy Oncology Group) 9501 phase III study, which previously showed no overall survival advantage from the addition of cisplatin chemotherapy to radiation.

The new data are “good news,” according to lead author Dr. Jay Cooper, director of Maimonides Cancer Center in Brooklyn, N.Y.

“We now can eradicate some advanced head and neck tumors that we couldn’t before by adding chemotherapy to radiation therapy. At the same time, we can spare other patients who would not do better with the addition of chemotherapy from its side effects,” he said at a head and neck cancer symposium sponsored by the American Society for Radiation Therapy.

The RTOG 9501 study randomized 459 patients with high-risk, resected head and neck cancers to receive either radiation therapy of 60 Gy in 6 weeks (RT), or identical radiotherapy plus cisplatin at 100 mg/m2 IV on days 1, 22, and 43 (RT+CT).

When reported at a median follow-up of 45.9 months, the locoregional control rate was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for locoregional recurrence, 0.61); disease-free survival was significantly longer with combined therapy (HR for disease or death, 0.78), but overall survival was not (HR for death, 0.84). Moreover, four patients who received combination therapy died as a result of treatment (N. Engl. J. Med. 2004;350:1937-44).

In the current updated analysis conducted 10 years post treatment, none of the primary outcomes differed significantly between the two groups. The evaluable population comprised 208 patients who received RT and 202 given RT+CT. For patients treated by RT vs. RT+CT, the rates were, respectively, 28.8% vs. 22.3% (P = .10) for locoregional failure, 19.1% vs. 20.1% (P = .25) for disease-free survival, and 27.0% vs. 29.1% (P = .31) for overall survival.

In a subset analysis that had not been performed previously, however, statistically significant differences appeared within the 242 patients who had microscopically involved resection margins and/or extracapsular spread of disease. In this group, 115 patients received RT and 127 were given RT+CT. Locoregional failure occurred in 33.1% of the CT group vs. 21.0% of those treated with RT+CT (P = .02). The disease-free survival rate was 12.3% vs. 18.4% (P = .05), and the overall survival rate was 19.6% vs. 27.1% (P = .07), with both end points favoring RT+CT.

That left 168 patients who did not have involved margins or extracapsular extension and were included in the trial solely because they had multiple involved nodes. In this group, 93 received RT and 75 RT+CT, with no significant difference in long-term outcomes.

There was a trend in improved cause-specific survival with RT+CT for patients whose death resulted from head and neck cancer, but more deaths not due to the study cancer were observed in patients treated with concurrent cisplatin. This is a hypothesis-generating finding that needs to be investigated in future trials, Dr. Cooper noted.

In an interview, he explained that the rationale for looking specifically at the patients with microscopically involved resection margins and/or extracapsular spread came from a previous analysis of the raw data from the RTOG trial combined with those of a concurrently published study conducted by the EORTC (European Organisation for Research and Treatment of Cancer).

Although the design of the EORTC 22931 study was similar, the outcome was different. Of a total 167 patients who had been randomized to RT or RT+CT, the rate of progression-free survival at a median follow-up of 60 months was significantly higher in the combined-therapy group than in the group given radiotherapy alone (P = .04) (N. Engl. J. Med. 2004;350:1945-52).

When the data from RTOG and EORTC were combined, it became clear that the main reason for the difference in outcome was in the different entry criteria for the two trials, and that extracapsular extension (ECE) and/or microscopically involved surgical margins were the only risk factors for which the impact of adjuvant chemotherapy-enhanced radiation therapy was significant in both trials (Head Neck 2005;27:843-50).

“What we learned from that analysis is that the patients who got on one of the trials but wouldn’t have qualified for the other trial were not getting much benefit from the study regimen, whereas those who qualified for either study – due to having involved margins and/or extracapsular extension – did better with chemotherapy on all three measures.

“These results were highly significant. But more importantly, the data suggested a subgroup where the big bang for the buck was,” Dr. Cooper said in the interview.

The findings don’t mean that the patients who did not benefit are not “high risk,” Dr. Cooper said. “Would they benefit from other chemotherapy? We don’t know. Would they benefit from different drugs or different regimens? Maybe. But we can now fairly comfortably say that in both the short and long run, if patients are high risk only because of involved lymph nodes, don’t treat them with this combination, and spare them the toxicity.”

Dr. Cooper stated that he has no disclosures, as did nine coauthors. One additional coauthor is an employee of Lilly USA.

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

February, 2012|Oral Cancer News|

Cisplatin aids survival of high-risk head and neck cancer

Source: www.oncologyreport.com
Author: Miriam E. Tucker

Adding chemotherapy to radiotherapy improved 10-year survival of resectable head and neck carcinomas among high-risk patients who had microscopically involved resection margins and/or extracapsular spread of disease – but not in high-risk patients who only had tumor in multiple lymph nodes.

The findings come from a long-term update and unplanned subset analysis of 410 evaluable patients from the RTOG (Radiation Therapy Oncology Group) 9501 phase III study, which previously showed no overall survival advantage from the addition of cisplatin chemotherapy to radiation.

The new data are “good news,” according to lead author Dr. Jay Cooper, director of Maimonides Cancer Center in Brooklyn, N.Y.

“We now can eradicate some advanced head and neck tumors that we couldn’t before by adding chemotherapy to radiation therapy. At the same time, we can spare other patients who would not do better with the addition of chemotherapy from its side effects,” he said at a head and neck cancer symposium sponsored by the American Society for Radiation Therapy.

The RTOG 9501 study randomized 459 patients with high-risk, resected head and neck cancers to receive either radiation therapy of 60 Gy in 6 weeks (RT), or identical radiotherapy plus cisplatin at 100 mg/m2 IV on days 1, 22, and 43 (RT+CT).

When reported at a median follow-up of 45.9 months, the locoregional control rate was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for locoregional recurrence, 0.61); disease-free survival was significantly longer with combined therapy (HR for disease or death, 0.78), but overall survival was not (HR for death, 0.84). Moreover, four patients who received combination therapy died as a result of treatment (N. Engl. J. Med. 2004;350:1937-44).

In the current updated analysis conducted 10 years post treatment, none of the primary outcomes differed significantly between the two groups. The evaluable population comprised 208 patients who received RT and 202 given RT+CT. For patients treated by RT vs. RT+CT, the rates were, respectively, 28.8% vs. 22.3% (P = .10) for locoregional failure, 19.1% vs. 20.1% (P = .25) for disease-free survival, and 27.0% vs. 29.1% (P = .31) for overall survival.

In a subset analysis that had not been performed previously, however, statistically significant differences appeared within the 242 patients who had microscopically involved resection margins and/or extracapsular spread of disease. In this group, 115 patients received RT and 127 were given RT+CT. Locoregional failure occurred in 33.1% of the CT group vs. 21.0% of those treated with RT+CT (P = .02). The disease-free survival rate was 12.3% vs. 18.4% (P = .05), and the overall survival rate was 19.6% vs. 27.1% (P = .07), with both end points favoring RT+CT.

That left 168 patients who did not have involved margins or extracapsular extension and were included in the trial solely because they had multiple involved nodes. In this group, 93 received RT and 75 RT+CT, with no significant difference in long-term outcomes.

There was a trend in improved cause-specific survival with RT+CT for patients whose death resulted from head and neck cancer, but more deaths not due to the study cancer were observed in patients treated with concurrent cisplatin. This is a hypothesis-generating finding that needs to be investigated in future trials, Dr. Cooper noted.

In an interview, he explained that the rationale for looking specifically at the patients with microscopically involved resection margins and/or extracapsular spread came from a previous analysis of the raw data from the RTOG trial combined with those of a concurrently published study conducted by the EORTC (European Organisation for Research and Treatment of Cancer).

Although the design of the EORTC 22931 study was similar, the outcome was different. Of a total 167 patients who had been randomized to RT or RT+CT, the rate of progression-free survival at a median follow-up of 60 months was significantly higher in the combined-therapy group than in the group given radiotherapy alone (P = .04) (N. Engl. J. Med. 2004;350:1945-52).

When the data from RTOG and EORTC were combined, it became clear that the main reason for the difference in outcome was in the different entry criteria for the two trials, and that extracapsular extension (ECE) and/or microscopically involved surgical margins were the only risk factors for which the impact of adjuvant chemotherapy-enhanced radiation therapy was significant in both trials (Head Neck 2005;27:843-50).

“What we learned from that analysis is that the patients who got on one of the trials but wouldn’t have qualified for the other trial were not getting much benefit from the study regimen, whereas those who qualified for either study – due to having involved margins and/or extracapsular extension – did better with chemotherapy on all three measures.

“These results were highly significant. But more importantly, the data suggested a subgroup where the big bang for the buck was,” Dr. Cooper said in the interview.

The findings don’t mean that the patients who did not benefit are not “high risk,” Dr. Cooper said. “Would they benefit from other chemotherapy? We don’t know. Would they benefit from different drugs or different regimens? Maybe. But we can now fairly comfortably say that in both the short and long run, if patients are high risk only because of involved lymph nodes, don’t treat them with this combination, and spare them the toxicity.”

Dr. Cooper stated that he has no disclosures, as did nine coauthors. One additional coauthor is an employee of Lilly USA.

February, 2012|Oral Cancer News|

Implications of the Oropharyngeal Cancer Epidemic

Source: Journal of Clinical Oncology

Chaturvedi et al,1 analyzing specimens back to 1984, validate the long-held hypothesis that infection with human papillomavirus (HPV) has increased oropharyngeal squamous cell carcinoma (OPSCC) incidence in the US. They find the incidence of OPSCC in men—who have higher risks of both HPV-positive and HPV-negative OPSCC than women—similar to that of cervical cancer in women. From 1988 to 2004, incidence of HPV-negative OPSCC decreased in parallel with smoking whereas incidence of HPV-positive OPSCC increased at about 7.5% per year, so the percentage of OPSCC that was HPV-positive went from less than 20% to more than 70%.

HPV-positive and HPV-negative OPSCC are etiologically and clinically distinct,2,3 with HPV-positive disease having better outcome.46 In the current study,1 the hazard ratio of 0.3 for HPV-positive/HPV-negative in survival analysis essentially balances the difference in prevalence so each form of OPSCC now accounts for a similar number of deaths. Notably, the authors found that outcomes for HPV-positive OPSCC have improved over time, whereas outcomes for HPV-negative OPSCC are as dismal as they were 25 years ago. The authors argue convincingly that vaccination to prevent oral HPV infections should be evaluated and that better treatments for both types of OPSCC should be developed.

We are unlikely to get a better picture of the recent history of OPSCC in the United States. This study used all available OPSCC specimens from the three Surveillance, Epidemiology, and End Results (SEER) registries that participate in the Residual Tissue Repositories Program, analyzed them in several ways, adjusted for loss of detectability over time, corrected for demographic differences between the analyzed cases and all registry cases, and extrapolated the results from these three registries to the US population so far as possible (given that nearly half of specimens came from the small island state of Hawaii and none came from states east of the Mississippi River). The authors’ predictions—that the number of specifically HPV-positive OPSCC will surpass cervical cancers by 2020 and that OPSCC will be a majority of all head and neck cancers by 2030—are acknowledged as being on less solid ground. We do not know where we are in the course of the epidemic of oral HPV leading to OPSCC, whether currently increasing incidence of HPV-positive OPSCC will continue as projected, level off, accelerate, or eventually diminish (eg, with HPV vaccination). In any event, during the next decade, we can expect some 10,000 to 15,000 patients with OPSCC per year in the United States, with the great majority having HPV-positive OPSCC.

These findings have three important implications for clinical practice. First, with cancers related to HPV now affecting both men and women and with present vaccines only effective before infection is established,7 primary care providers should inform parents of boys (not only girls) about risks of HPV-associated tumors and the likely reduction in risk provided by vaccination. The HPV quadrivalent (types 6, 11, 16, 18) vaccine is approved by the US Food and Drug Administration for patients through age 26 years for prevention of genital warts and anal cancer,8 although the Centers for Disease Control and Prevention do not yet recommend HPV vaccination of males,9 and the efficacy of vaccination for reducing oral HPV infection or OPSCC, although expected,1,10 is not yet documented. Direct tests of this efficacy are needed, given that prevention through vaccination will almost certainly be the ultimate solution to HPV-positive OPSCC. As Chaturvedi et al recommend,1 prior cost-benefit analyses of vaccinating males, which underlie Centers for Disease Control and Prevention recommendations, must be reconsidered in light of the growing incidence of male HPV-positive OPSCC demonstrated in the current report. Second, with significant risk factors for both HPV-positive and HPV-negative OPSCC well-known,11 patients should be encouraged to minimize behaviors that put them at risk for either form of OPSCC. Third, oncologists should routinely test all patients with OPSCC for HPV status, if for no other reason than to refine prognosis. Nodal involvement in HPV-positive OPSCC typically leads to a high TNM stage that does not represent disease risk relative to other head and neck cancers.12,13 Chaturvedi et al1 found that several analytic methods provided similar results for identifying HPV-positive tumors, including the readily available surrogate marker of high immunohistochemical p16 protein expression.14 Such testing is already part of OPSCC clinical study design15 with the hope that the HPV-positive/HPV-negative distinction (in practice, perhaps the closely associated p16-positive/p16-negative distinction) may soon assist in selecting treatments.

The major difference in outcome between HPV-positive and HPV-negative OPSCC, in particular the lack of change of outcome of HPV-negative OPSCC over two decades, requires serious re-evaluation of prior work on head and neck squamous cell carcinoma (HNSCC). Patients who have HPV-positive OPSCC tend to have different associated health-endangering behaviors than those who have HPV-negative OPSCC11 and are probably less likely to show field cancerization.16 Their tumors, arising from the epithelium of lymphoid tissue17 and with viral proteins instead of a long history of somatic mutations disrupting tumor suppressor mechanisms18 may respond differently to genotoxic therapy19 and have different tendencies for extracapsular spread, perineural invasion, and metastasis. Many clinical studies on HNSCC in the past two decades were done in the context of an increasing prevalence of HPV-positive OPSCC within a mix of HNSCC subsites. Interpretation of these studies might have been misled by what we now know to have been the substantially different tumor biology of undetermined numbers of patients with HPV-positive OPSCC. For example, it may be that the benefit of adding cetuximab to radiotherapy in HNSCC20 is restricted to HPV-positive OPSCC21 and that racial disparity in treatment outcomes after chemoradiotherapy for HNSCC represents racial differences in the prevalence of better-outcome HPV-positive OPSCC.22 Such re-evaluation of other HNSCC studies in light of the increasing prevalence of HPV-positive OPSCC over these decades may be important for better understanding and treatment of both HPV-positive OPSCC and other HNSCC.

The challenge for future research on therapy differs between these two forms of OPSCC. For HPV-negative OPSCC, this study shows that decades of trials have yet to improve outcome; development and adoption of more effective treatments are still required. For HPV-positive OPSCC, the combination of increasing incidence, young age at presentation, and substantial long-term survival2 presents an urgent need for lower-intensity therapy that maintains control of disease while avoiding the significant short- and long-term morbidity of current therapy.12,21,23 Within both HPV-positive and HPV-negative OPSCC, additional biomarker-based delineations of tumor subtypes24,25 may contribute to development of better individualized therapy.

Unfortunately, the nature of current clinical trials may not provide useful treatment comparisons in a reasonable time frame. Of 100 patients with OPSCC as might be seen per year in an academic referral center, about 70 patients will have HPV-positive disease versus 30 patients with HPV-negative disease, and about 15 recurrence-related deaths are expected in each group at 2 to 3 years. With these numbers of events, distinguishing treatment outcomes in a clinical trial on either HPV-positive or HPV-negative OPSCC requires hundreds of patients per treatment group, particularly if there is additional stratification of patients by additional biomarkers. For example, the recently activated RTOG-1016 trial design for comparing cetuximab versus cisplatin in combination with radiation therapy for p16-positive OPSCC15 anticipates enrollment of more than 700 patients. Yet expected rates of patient accrual combined with necessary follow-up time may mean no definitive results for 7 years. In principle, results could be obtained more quickly if more of the 10,000 patients with OPSCC in the United States each year were involved in trials, but that would require a major increase in the number of participating institutions, substantial success at obtaining patient consent, and an unprecedented level of cooperation and coordination in study design, execution, and analysis. It is noteworthy that this trial was developed and approved within the new National Cancer Institute framework for extramural trials26 in response to the Institute of Medicine report.27 Without additional funding and a mechanism in place to effect broader participation beyond cooperative group head and neck committee members, however, a substantive increase in accrual rate may be slow in coming.

The current study1 illustrates how difficult such interinstitutional cooperation can be. During the two decades examined, there were approximately 200,000 patients with OPSCC nationwide. With the limits of the SEER network, only three SEER Residual Tissue Repositories Program registries and fewer than 5% of patients in those three registries having available specimens, this reconstruction of the history of OPSCC in the United States is based on only 271 patients. We need much more complete representation of patients with OPSCC in future studies and trials.

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

November, 2011|Oral Cancer News|

EU grants orphan drug status to BioAlliance Pharma’s clonidine Lauriad

Source: www.pharmabiz.com
Author: staff

European Commission has granted orphan drug designation to BioAlliance Pharma SA’s clonidine Lauriad for prevention of radiotherapy-induced oral mucositis in patients with head and neck cancer.

Oral mucositis is a very frequent inflammation of the oral mucosa in head and neck cancer patients treated with radio- and chemotherapy (98,000 new patients estimated per year in Europe). Severe oral mucositis occurs in 60% of these patients and may induce intense oral pain and eating disability requiring artificial nutritional support. In 20 to 30% of cases, patients have to be hospitalized and the disease may result in a modification or a stop of the radiotherapy treatment in more than 10% of them. Radiotherapy-induced oral mucositis has currently no preventive cure.

In Europe, the orphan designation is granted for medicinal products in diseases affecting less than 5/10,000 patients. This status permits to benefit from incentives related to the clinical development, thus enabling a faster registration, and an extra protection with a 10- year commercial exclusivity after market authorization.

“The European designation for clonidine Lauriad as an orphan drug is key in shortening its development timeline, optimizing costs and reinforcing its future market access. Clonidine Lauriad, currently in Phase II clinical trial, is the second product from our “Orphan Oncology Products” portfolio to be granted orphan status in Europe. The portfolio comprises assets with high commercial potential and will leverage our future growth”, stated COO, Judith Greciet.

Dedicated to cancer and supportive care treatment with a focus on resistance targeting and orphan products –– BioAlliance conceives and develops innovative products, for specialty markets especially in the hospital setting and for orphan or rare diseases.

November, 2011|Oral Cancer News|

GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy

Source: http://7thspace.com
Author: Chien-Yu Lin et al.

Oral cavity cancers (ORC) are the most common cancers, and standard treatment is radical surgery with postoperative radiotherapy. However, locoregional failure remains a major problem, indicating radioresistance an important issue.
Our previous work has shown that GP96 contributed to radioresistance in nasopharyngeal and oral cancer cell lines. In this study, we determined clinical significance of GP96 in ORC by evaluation of GP96 expression and its association with disease prognosis in patients receiving radiotherapy

Methods:
Total of 79 ORC patients (77 males, median age: 48 years old) receiving radical surgery and postoperative radiotherapy between Oct 1999 and Dec 2004 were enrolled.

Patients in pathological stages II, III and IV were 16.5%, 16.5% and 67%, respectively. For each patient, a pair of carcinoma tissue and grossly adjacent normal mucosa was obtained.

GP96-expression was examined by western blot analysis, and the association with clinicopathological status was determined.

Results:
Three-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) rates were 69%, 79%, 63% and 57%, respectively. We found that 55 patients (70%) displayed GP96-overexpression in the tumor tissue, which correlated with a higher pN stage (p=0.020) and tumor depth (>10 mm) (p=0.045).

Nodal extracapsular spreading (ECS) and GP96-overexpression predicted adverse LRC (p=0.049 and p=0.008). When stratified by nodal ECS, the adverse impact of GP96 remained significant in three-year LRC (p=0.004).

In multivariate analysis, GP96-overexpression was also an independent predictor of LRC, DSS and OS (p=0.018, p=0.011 and p=0.012).

Conclusion:
GP96 may play roles in radioresistance which attributes to tumor invasiveness in oral cancer patients receiving radiotherapy. GP96 may serve as a novel prognostic marker of radiotherapy.

However, further independent studies are required to validate our findings in a larger series.

Authors: Chien-Yu Lin, Ting-Yang Lin, Hung-Ming Wang, Shiang-Fu Huang, Kang-Hsing Fan, Chun-Ta Liao, I-How Chen, Li-Yu Lee, Yan-Liang Li, Yin-Ju Chen, Ann-Joy Cheng, Joseph Chang

Source: Radiation Oncology 2011, 6:136

October, 2011|Oral Cancer News|