radiotherapy

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|

Stem cell sparing radiotherapy for head and neck cancer may avoid salivary gland damage

Source: European Society for Radiotherapy and Oncology (ESTRO)

Barcelona, Spain: Researchers believe they may have found a way to avoid damaging salivary glands during radiotherapy treatment for head and neck cancer – a discovery that could improve the quality of life of 500,000 patients a year worldwide with the disease.

Presenting their findings to the 31st conference of the European Society for Radiotherapy and Oncology (ESTRO31) [1], the researchers said that they had discovered that the stem cells essential for regenerating the parotid gland (the largest pair of salivary glands) were located mainly in its major ducts, and that these could easily be avoided during radiotherapy or given a minimal radiation dose. “This would significantly reduce complications arising from radiotherapy for head and neck cancer,” said Dr Peter van Luijk, a research associate at the University Medical Center Groningen, The Netherlands.

Around 40% of patients treated for head and neck cancer suffer from the distressing side-effects of dry mouth syndrome – a condition that can occur when the parotid gland stops working properly after radiation damage. This causes problems with eating, sleeping, speech, tooth loss and oral hygiene, leading to diminished quality of life, social isolation and difficulty in continuing work. Attempts to treat dry mouth syndrome and its consequences can cost hundreds or even thousands of Euros per patient per year and are mostly insufficient.

Dr van Luijk said: “Parotid gland dysfunction after radiotherapy for head and neck cancer was, and still is, a major clinical problem. During radiotherapy, attempts to minimise the risk of this complication have been aimed at reducing the average dose to the salivary gland, on the assumption that it would not make a difference where in the gland the radiation dose was reduced. However, this does not seem logical according to the anatomy of the salivary gland and, in previous work, we discovered that reductions in the radiotherapy dose to some parts of the gland allowed the parotid gland to regenerate, whereas a dose to other parts did not. Therefore, we decided to investigate the reason for these regional differences. We hypothesised that our observations could be explained by a non-uniform distribution of stem cells necessary for the long-term maintenance of organ function and affected by irradiation.”

Dr. Van Luijk and his colleagues investigated the location of stem cells and the effects of radiotherapy to particular regions of the gland first in mouse and rat models, and then in parotid and salivary gland tissue taken from patients (after informed consent) undergoing a neck dissection for head and neck cancer.

They found that in mouse, rat and human tissue, the stem cells were predominately located in the major ducts of the parotid gland. “We have found in previous work that these stem cells are capable of regenerating a parotid gland when they have been transplanted after irradiation,” said Dr van Luijk.

Dissection of the rat parotid gland and culturing of the different parts of the gland in Petri dishes showed that a greater concentration of stem cells capable of regenerating the gland were located in the centre, where the largest ducts are located. The researchers then directed high-precision irradiation at this centre part in living rats and found that it resulted in excessive reduction of saliva production, in contrast to the minimal effects observed after irradiating other parts of the gland.

Dr van Luijk explained: “The position of the stem cells in rats corresponds to the cranio-ventral extension of the gland in humans, where the excretory duct leaves the gland on the ventral, or outward-facing side. So even though the glands have different shapes in rats and humans, the stem cells are in the exact same anatomical structure.”

The researchers then tested their hypothesis by creating a mathematical model based on the treatment of 36 patients, which enabled them to estimate the expected parotid gland function depending on the dose to the stem cells.

“Excitingly, dose to the cranio-ventral extension of the gland containing the major ducts was most predictive of damage to saliva production. In addition, we found that it was possible to reduce the dose by approximately 50% to this part of the gland, without increasing the average dose to the whole gland or the dose to other critical structures in the head and neck region, and without compromising adequate target coverage,” said Dr Van Luijk. “Using the mathematical model, we estimated that with such dose reduction none of the patients would have developed parotid gland dysfunction. This is, however, a hypothesis that needs to be tested prospectively in a randomised clinical trial by comparing parotid gland function in a group of patients treated with current standard to a group in which, additionally, the dose to the stem cells is minimised using our proposed stem cell sparing technique. This technique should only be implemented in radiotherapy clinics when such a trial proves there is a benefit as predicted by our research.”

He continued: “Our findings can be seen as a proof-of-principle that elucidation of biological mechanisms in complications may lead to the identification of critical sub-structures of organs, possibly leading to new opportunities to reduce harm to normal tissue. Though we only show this for the parotid gland, such approach may apply to other organs as well.”

The researchers say that it is easy to spare the parotid gland during radiotherapy. “The stem cell region is on the side of the gland that is normally furthest away from the target area containing the tumour cells. Since only this area needs a high radiation dose, this distance makes avoiding the stem cell area easier than avoiding other parts of the gland,” said Dr van Luijk.

“Based on our results we hypothesise that sparing the parotid gland stem cell region, costing around €100 in extra man-hours, may effectively prevent salivary gland dysfunction. This will allow patients to more readily lead their normal lives without having to rely upon medical care and welfare. Maybe even more importantly, cancer patients will remain productive members of society, realising a cost reduction far beyond the cost of medication. Finally, it will improve quality of life of 500,000 patients treated with radiotherapy for head and neck cancer worldwide every year,” he concluded.

Professor Bradly G. Wouters (PhD), a radiobiologist at the Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada, and chair of the conference radiobiology track, commented: “This is an exciting clinical study that has identified a critical region of the salivary gland that contains stem cells that can regenerate the gland and preserve function in patients with head and neck cancer. Using advanced radiation techniques the investigators show it is possible to spare this region and thus deliver higher therapeutic doses without causing more toxicity to patients.”

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

Abstract

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.

May, 2012|Oral Cancer News|

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|