Kate Johnson

May 11, 2012

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."

Dr. Lassen and Dr. Valentini have disclosed no relevant financial relationships.

ESTRO 31: European Society for Radiotherapy and Oncology 2012 Annual Conference: Abstract OC-0149. Presented May 10, 2012.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: