Radiation Therapy Oncology Group

Study suggests that experience counts when it comes to head and neck cancer treatments

Source: medicalxpress.com
Author: staff
 

When it comes to specialized cancer surgery, it’s generally true that the more experienced the surgeon, the better the outcome. The same might hold true for radiation therapy used to treat head and neck cancer, according to a new study led by researchers Evan Wuthrick, MD, assistant professor of radiation oncology at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), and Maura Gillison, MD, PhD, professor of internal medicine and epidemiology at the OSUCCC – James.

Published in the Journal of Clinical Oncology with an accompanying editorial, the study compared survival and other outcomes in 470 patients treated with radiation therapy at 101 treatment centers through a clinical trial held from 2002 to 2005. The trial was sponsored by the National Cancer Institute and organized by the Radiation Therapy Oncology Group (RTOG).

The findings indicated that patients treated at the less-experienced centers were more likely to have cancer recurrence (62 percent versus 42 percent at five years) and had poorer overall survival compared with those at the highly-experienced centers (51 percent versus 69 percent five-year survival, respectively).

“Our findings suggest that institutional experience strongly influences outcomes in patients treated with radiation therapy for head and neck cancer,” says Wuthrick, the paper’s first author. “They indicate that patients do better when treated at centers where more of these procedures are performed versus centers that do fewer.”

Radiation therapy for head and neck cancer requires complex treatment planning that can vary considerably between institutions and physicians. In addition, significant short-term and long-term side effects can occur that require management by a carefully coordinated multidisciplinary care team. National Comprehensive Cancer Network guidelines recommend that head and neck cancer patients receive treatment at experienced centers, but whether provider experience affects outcomes was previously unknown.

Wuthrick, Gillison and their colleagues used participation in previous RTOG head and neck cancer clinical trials as a surrogate for experience. They identified 88 low-accruing centers that enrolled an average of four patients yearly to the trials, and 13 high-accruing centers that enrolled an average of 65 patients annually. Next, the researchers compared outcomes based on whether patients were treated at the high-accruing (more experienced) or low-accruing (less experienced) centers.

The study’s key findings include:

  • Five-year local recurrence rates were higher among patients treated at less experienced centers versus more experienced centers (36 percent and 21 percent, respectively);
  • The radiation therapy plan was more likely to deviate from protocol at less experienced centers (18 percent versus 6 percent);
  • Treatment at low-accruing centers was associated with a 91-percent increased risk of death and an 89-percent increase in progression or death when compared with high-accruing centers.

Institutional elements not assessed by the study that can also influence outcomes included use of a tumor board, the number of colleagues and their years of practice, and ancillary services such as speech and swallowing therapy, dietetic and nutritional support, and specialized nursing.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
December, 2014|OCF In The 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|

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|

Prognostic Significance of HPV Status in Oropharyngeal Cancer

OncologySTAT Editorial Team

Dr. Maura Gillison is Professor of Medicine, Epidemiology, and Otolaryngology at Ohio State University in Columbus.

OncologySTAT: The results of the Radiation Therapy Oncology Group (RTOG) 0129 trial showed that the human papillomavirus (HPV) is an independent prognostic factor in oropharyngeal cancer. Could you tell us about the rationale for this study?

Dr. Gillison: Over the last 10 years, our research has shown that cancers of the oropharynx are actually 2 completely different diseases that can look quite similar. One subset is caused HPV infection, and the other is more closely associated with long-term use of alcohol and tobacco.

Initial studies suggested that the presence of HPV in a patient’s tumor had prognostic significance, but study limitations made that conclusion dubious. We set out to determine whether or not HPV was indeed an independent prognostic factor in head and neck cancer. To show whether there was a direct relationship between HPV infection and head and neck cancer, we needed to prospectively study a uniformly treated and uniformly staged patient population. Thus, we used the study population from the trial conducted by the RTOG. We divided the patients into 2 groups—those whose tumors were caused by HPV and those whose tumors were not—and we compared survival outcomes for the 2 groups.

The results showed that HPV status was the single most important predictor of patient outcome, even more so than disease stage and other well-known prognostic factors such as performance status and presence of anemia. In fact, after accounting for 6 other nonprognostic factors, patients with HPV-positive cancer had less than half the risk of dying from their cancer as did patients whose cancer was HPV negative. At 5 years, that translated into a 30% absolute difference in survival.

On the basis of these results, we can state definitively that HPV is a strong and independent prognostic factor for oropharynx cancers. Currently, tumor HPV status is determined for all patients with head and neck cancer prior to enrollment into a clinical trial. I believe that HPV-positive oropharynx cancer is a completely different disease from traditional head and neck cancer, to the extent that we need to design separate clinical trials that are specific for the HPV-positive patient, as distinct from the HPV-negative patients.

Unfortunately, we have not made true progress over the last 15 to 20 years in therapy for patients with head and neck cancer. The major advances have been in our understanding of the underlying etiology of the disease and its inherent biologic responsiveness. Patients with HPV-negative head and neck cancer, in particular, are still doing extraordinarily poorly. Even with the use of intense, concurrent chemoradiation, as was done in the RTOG trial, 5-year survival is only about 30%.

OncologySTAT: Now that we can stratify patients by HPV status, it will be possible to separate out people who have head and neck cancer related to tobacco use and conduct separate trials on those patients, or investigate different therapies for them.

Dr. Gillison: Exactly. Our data indicate that patients with HPV-positive tumors do extraordinarily well. Some still do die of their cancer, but about 80% are alive and doing well 5 years later. Many of these patients are quite young; it’s not unusual to see patients in their 30s or 40s. If they’re expected to survive their cancer, then they will have to deal with the consequences of the therapy for 30, 40, or 50 years.

OncologySTAT: Are they surviving longer?

Dr. Gillison: They are surviving longer. Now we need to focus on improving their outcomes. The more aggressive approaches being used in head and neck cancer, such as combination therapy with multiple agents, together with standard chemotherapy, biologics, and radiation therapy, all should be studied in HPV-negative patients. The increased toxicity of combined therapies may be warranted in terms of the risk-benefit analysis because these patients have such poor survival. At present, it would be inappropriate to use such therapies for the HPV-positive group.

OncologySTAT: Will you be following the HPV-positive patients over the long term? Patients with head and neck cancer are at risk for second cancers later on.

Dr. Gillison: We analyzed second cancers in our trial and found that they were significantly less likely to occur in HPV-positive patients than in HPV-negative patients. The difference was largely explained by a difference in rates of smoking in the 2 groups of patients. The rate of second cancers is approximately 20% among HPV-negative patients, whereas it’s about 5% in the HPV-positive group.

OncologySTAT: Are there any follow-up studies planned or underway right now?

Dr. Gillison: The National Cancer Institute (NCI) steering committee has adopted my recommendation to design separate clinical trials for HPV-positive and HPV-negative patients. We also hope to conduct clinical trials with the European Organisation for Research and Treatment of Cancer (EORTC) and the French Head and Neck Oncology and Radiotherapy Group. This work will focus on how best to treat patients with HPV-positive head and neck cancer. We don’t know the best treatment strategy, because HPV-positive cancer wasn’t recognized until recently as a unique disease entity.

In the United States, incidence rates of HPV-positive cancer are rising dramatically. NCI data for 2000 put the incidence at 10% per year, but this rate is expected to double in the current decade. Thus, in the future, the alcohol- and tobacco-related cancers are going to be the rare cancers.

We need to figure out as rapidly as possible the standard of care for this cancer. Together with RTOG and the Eastern Cooperative Oncology Group (ECOG), we are in the process of designing a large, randomized phase II study specific to HPV-positive patients. We estimate enrolling 800 to 1,000 patients. Endpoints will include quality of life and toxicity outcomes. Because HPV-positive patients respond so well to therapy, the question now is whether we can reduce the use of intense therapy and thereby decrease the long-term consequences of the therapy. Some therapies used during the last 15 years for head and neck cancer have yielded only a 5% to 8% absolute benefit in 5-year survival, but they have contributed to a 500% increase in morbidity over the long term. Many patients end up not being able to swallow food and are therefore dependent on gastrostomy tubes, which has significant social and quality-of-life implications.

So the goal of that trial is to compare standard-of-care therapy, as it was developed in RTOG 0129, with 2 other treatment algorithms involving reduced-intensity therapy. Hopefully, we will find that reduced-intensity therapy does not compromise survival. We hope we can get answers sooner rather than later.

OncologySTAT: Do you think vaccination is going to have a role in reducing the incidence of HPV-related head and neck cancers over time?

Dr. Gillison: I certainly hope so. Half of my research program involves work on oral HPV infection, looking at its prevalence in the US population, predictors, and the natural history. Soon we will be starting a clinical trial that evaluates whether the currently approved HPV vaccines can more effectively prevent oral HPV infections. We hope to have answers in 5 years.

HPV vaccines are extraordinarily effective (nearly 100%) in preventing cervical dysplasia and cancer among women. Both the Food and Drug Administration and the Centers for Disease Control and Prevention report virtually no evidence of any severe toxicities or negative outcomes from the vaccine. However, only 1 out of 4 parents in the United States have made the decision to have their daughters vaccinated.

OncologySTAT: Pediatricians appear to be proponents of vaccination against HPV.

Dr. Gillison: Yes. I understand that there are social implications to the vaccine, as well as cost-benefit considerations, because the vaccine is expensive. However, my patients look at it this way: If they had the option, in retrospect, of getting 3 vaccines in their teens instead of having to deal with the consequences of a cancer diagnosis for themselves and their families later on, they say it would have been an easy decision.

For HPV-related cancers, we’ve found the Achilles heel, in that HPV is necessary for these cancers, causing about 20,000 cases in the United States every year. The vaccine appears to be fairly effective at every site where it’s been tested. My concern is that, if we can’t make the appropriate decisions on a policy level that could eliminate a cancer for which we’ve identified a single cause, what will we do for all these other cancers, the genetics of which are much more complex? Cancers such as colon cancer and breast cancer are tremendously heterogeneous in terms of genetic predisposition. There’s probably not going to be an Achilles heel for those cancers. In my opinion, potentially 20,000 US families are affected each year by a cancer for which the HPV vaccine holds promise. Worldwide, that’s more than a million cases.

OncologySTAT: What are the implications of your results for community-based oncologists?

Dr. Gillison: The patient population that gets HPV-related head and neck cancer is highly educated; they tend to be of high socioeconomic status. This is a different population than head and neck cancer patients in the past, who, because of their protracted alcohol and tobacco abuse, maybe didn’t advance as well in society as these patients, who tend not to smoke and drink. Patients we see tend to be Internet savvy, and when they read about the profound prognostic significance of the HPV test, they demand it.

If you knew that you had been diagnosed with a cancer for which there was a test that could determine whether you had an 85% chance of 5-year survival as opposed to a 30% chance, you’d probably demand it, too, because you’d want to make plans for your life. Community oncologists should be aware of these data, because any patient with an oropharynx cancer who does not have traditional risk factors probably has an HPV-related cancer.

Unfortunately, a lot of medical oncologists in the community are still unaware of the relationship between HPV and oropharynx cancer. They need to be made aware of the relationship so that they can counsel their patients appropriately. Many patients are completely stumped as to why they’ve gotten this cancer. Community oncologists need to know that HPV testing is available in at least 2 institutions, Johns Hopkins and Ohio State University.

All clinical trials conducted by ECOG and RTOG will now require determination of HPV status for eligibility. Oncologists in the community who refer patients for clinical trials need to be aware of this and know how to counsel their patients when the results come back. There is still a social stigma to having a cancer caused by a sexually transmitted infection, and community oncologists need to be sensitive to that. In my clinical practice, I’ve seen marriages dissolve over the blame game, and relationships strained because of guilt feelings in one partner or the other. Community oncologists need to educate themselves about HPV so that they can handle this difficult counseling.

OncologySTAT: That’s an interesting aspect that we don’t often think about in terms of participation in a clinical trial.

Dr. Gillison: Telling someone that they have a cancer caused by a sexually transmitted infection can have social implications. In my opinion, there should be no stigma associated with it. As an HPV biologist, I recognize that 80% of individuals will have an HPV infection at some point in their life. That may even be an underestimation, as it is based solely on data for cervical cancer. Anal HPV infection and oral HPV infection didn’t factor into those previous estimates.

I see HPV infection as a consequence of being human. Nearly all people who get an HPV infection can handle it immunologically, without developing any health consequences. We don’t know what’s different about the 0.01% of people who develop cancer from the virus and those who don’t. I try to educate people about the high prevalence of HPV infection. Education can help remove the social stigma.

A lot of my patients feel relieved when I tell them how common the infection is. There’s also a perception that HPV infection is an indication of promiscuity, which is not correct. A study done at the University of Washington followed college-aged women from their freshman year forward to assess the incidence of HPV infection. The analysis was restricted to women who were virgins at entry into the study. The women were followed only through their first sexual partner, after which they were censored. By the end of 1 year, 25% of the women had contracted an HPV infection. By the end of 2 years, the incidence had risen to one-third. Men are remarkable reservoirs for HPV infection. An estimated 63% of men in the United States have a genital HPV infection.

So it’s best to think of HPV infection as a consequence of being human and having evolved with the virus for a long time. With this viewpoint, people won’t attach such a stigma to it.

OncologySTAT: It will also be important to determine which patients can have good outcomes despite receiving less aggressive therapy. This could spare them some of the speech and eating problems that result from head and neck cancer.

Dr. Gillison: As the principal investigator on the planned RTOG study, I know some of the comparisons we will be looking at. Less intensive radiation is one option for less aggressive therapy. Most of the complications from therapy are related to patients’ receiving chemotherapy and radiation at the same time; an alternative approach might be to administer these treatments sequentially. Or, if given together, they could be given at lower doses. These are some of the different options being considered for this study.

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

April, 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|

New Therapies and Prognostic Techniques Highlighted in Head and Neck Cancer

The Asco Post

D. Neil Hayes, MD, MPH, of the University of North Carolina at Chapel Hill, described efforts to position the epidermal growth factor receptor (EGFR) inhibitor cetuximab (Erbitux) in head and neck cancer treatment.

Surprisingly negative results came from the phase III Radiation Therapy Oncology Group (RTOG) 0522 trial (N = 940), which showed no benefit to adding cetuximab to the radiation/cisplatin platform for front-line therapy of advanced head and neck squamous cell carcinoma.1 At 2 years, progression-free survival was approximately 64% in both arms; overall survival was 79.7% with chemoradiation (P = .68) and 82.6% with the addition of cetuximab (P = .17). Rates of locoregional relapse and distant metastases were also similar.

Cetuximab increased grade 3/4 mucositis (43% vs 33%;P < .004), in-field skin toxicity (25% vs 15%;P < .001), and out-of-field skin reactions (19% vs 1%;P < .001), but toxicity beyond 90 days was similar between the arms.

Table 1: After the RTOG 0522 Trial: Where Do We Go from Here?

“RTOG 0522 was the study of the year in head and neck cancer. Unfortunately, it was flat-out negative,” Dr. Hayes noted.

No differential effect emerged by p16 (HPV status). “While 70% of patients had oropharynx tumors (suggesting HPV positivity), tissue collection was lacking in half the patients. Our ability to make inferences with this amount of missing data is very limited,” Dr. Hayes said.

Even as a negative study, RTOG 0522 is practice-changing. “Many physicians have been treating with this regimen, assuming this study would be positive,” he said. “But we now have no data to support this.”

Cetuximab Equivalent to Cisplatin after Induction

The phase II TREMPLIN study (N = 153) evaluated sequential chemoradiotherapy in previously untreated, operable squamous cell carcinoma of the larynx/hypopharynx.2 Patients received induction chemotherapy with docetaxel, cisplatin, and fluorouracil; nonresponders underwent laryngectomy, whereas those with more than a 50% response were randomly assigned to radiotherapy plus either cisplatin or cetuximab.

All endpoints were similar between the arms. Larynx preservation rates at 3 months were 95% with cisplatin and 93% with cetuximab (P = .63). Preservation of larynxfunctionat 18 months (or at death) was seen in 87% and 82%, respectively (P= .68). Overall survival was 92% and 89%, respectively (P = .44), and laryngoesophageal dysfunction-free survival was 79% vs 71% (P = .30). Acute toxicities compromising treatment and late toxicities were more common with cisplatin.

Dr. Hayes concluded, “The take-home message is that these two regimens are equivalent, and that cetuximab plus radiotherapy may be reasonable after induction.”

Laser Treatment Effective for Mucositis

In a phase III randomized trial of 94 patients, upfront use of low-level laser therapy helped prevent oral mucositis associated with chemoradiation.3 Grade 3/4 mucositis was observed in < 7% of the laser therapy group, compared with almost 50% of controls (who received “placebo” laser applications from the same machine but without light), for an 84% reduction (P < .001). Patients receiving active laser therapy also had less pain, narcotic use, and gastrostomia and better quality of life.

“Mucositis, especially grade 3 and 4, may limit treatment and compromise outcomes. While we need confirmatory data, the study shows we can intervene to improve mucositis.”

Future Directions

Key Head and Neck Cancer Findings Presented at Best of ASCO®

An international group developed a 30-gene expression profile that predicted clinical outcomes in primary laryngeal carcinoma.4 Median disease-free survival was 34 months in high-risk patients vs 80 months in low-risk patients (P = .01). Recurrences were four times greater among those in the high-risk group (P = .017).

“This elegant study suggests subgroups of patients can be distinguished according to who will do well and who will do worse. For clinical usefulness, the issue is whether the difference between high- and low-risk groups will be sufficient to change therapy,” Dr. Hayes commented.

Finally, the novel vascular disrupting agent fosbretabulin (CA4P), combined with carboplatin and paclitaxel, tripled survival in the randomized phase II/III FACT trial (N = 80), from 9% at 1 year with chemotherapy alone to 26% (P = .065).5

“There is enthusiasm and excitement over this novel therapy for anaplastic thyroid cancer,” Dr. Hayes commented, urging oncologists to have patients enroll in the upcoming phase III trial.

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


October, 2011|Oral Cancer News|

ASCO: HPV Infection Linked to Better Outcome in Oropharyngeal Cancer

Source: MedpageToday.com 
Author: Michael Smith

TORONTO, May 14 — Patients with oropharyngeal cancer had a 50% lower five-year mortality risk when they also had human papillomavirus (HPV) infection, according to data from a randomized clinical trial.

HPV-positive patients had a two-year overall survival of 88% compared with 66% for HPV-negative patients (P<0.001), said Maura Gillison, M.D., of Ohio State University in Columbus.

The difference between groups increased with follow-up. HPV infection also was associated with a reduced risk of locoregional recurrence and second cancers, Dr. Gillison reported at a press briefing in advance of the American Society of Clinical Oncology annual meeting.

Cancer of the oropharynx arises from two principal causes: chronic use of tobacco and alcohol or HPV infection. Previous studies had suggested that HPV status of a patient’s tumor might have prognostic implications.

“HPV-positive patients have important associations with other favorable prognostic factors,” said Dr. Gillison. “They tend to be younger; they have smaller tumors; they present with better performance status. Therefore, improvement in survival for this patient population may be explained by these factors and not by HPV.”

To explore the role of HPV status in survival of oropharyngeal cancer, Dr. Gillison and colleagues reviewed data from a randomized clinical trial conducted by the Radiation Therapy Oncology Group.

Its principal objective was to compare standard chemotherapy with an investigational regimen.

The trial involved 721 patients. Of those, 60% had cancer of the oropharynx and 64% were HPV positive.

The two-year results demonstrated a clear survival advantage associated with HPV infection. Follow-up to five years revealed an overall survival of >75% in HPV-positive patients versus <50% in HPV-negative patients.

The difference remained largely unchanged in an analysis that accounted for other factors, including treatment assignment.

“HPV-positive patients had less than half the risk of dying from their cancer at five years than HPV-negative patients, after considering the effects of other important factors,” said Dr. Gillison.

“HPV-positive patients similarly had about half the risk of tumor progression or death, due in part to lower recurrence rates in the radiation field but not lower distant metastases.”

As a result of the findings, RTOG and the Eastern Cooperative Oncology Group will begin to stratify all clinical trials by HPV status and possibly design trials specifically for HPV-positive or negative patients, she added.

Dr. Gillison reported no competing interests.

 

Primary source: American Society of Clinical Oncology
Source reference:
Gillison ML, et al “Human papillomavirus and survival of patients with oropharynx cancer”ASCO 2009.
May, 2009|Oral Cancer News|