Low-Dose Radiation Okay in Some HPV-positive Head and Neck Cancers

Kate Johnson

May 30, 2014

CHICAGO — Human papillomavirus (HPV)-positive oropharyngeal cancer patients who demonstrate sensitivity to induction chemotherapy can safely forgo standard radiation therapy in favor of a lower, less-toxic dose, according to the phase 2 ECOG 1308 study.

Dr. Anthony Cmelak

This "chemoselection" strategy can guide radiotherapy treatment decisions to allow fewer acute and late toxicities," said researcher Anthony Cmelak, MD, professor of radiation oncology at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

"The lower dose allows patients to avoid long-term dysphagia, fibrosis, xerostomia, dental problems, strictures, and long-term percutaneous endoscopic gastrostomy tubes," he told Medscape Medical News. "The risks of these types of complications escalate rapidly after 54 Gy of intensity-modulated radiation therapy (IMRT), and become the most commonly seen long-term problems in patients treated to the standard dose of 70 Gy."

The study, presented here at the 2014 Annual Meeting of the American Society of Clinical Oncology® (ASCO), involved 90 patients with stage III/IV HPV-positive oropharyngeal squamous carcinoma who received induction chemotherapy with paclitaxel, cisplatin, and cetuximab.

The 62 patients who had a complete clinical response to chemotherapy, meaning no signs of cancer on endoscopic exam, were selected to receive 54 Gy of IMRT; the other 28 patients received the standard dose of 70 Gy.

At 2 years, overall survival was better in the low-dose group than in the standard-dose group (93% and 87%), as was progression-free survival (80% and 65%). For minimal smokers (less than 10 pack-years) who had early-stage disease, overall and progression-free survival were both 96%.

Patients who received a low dose but appeared not to do as well were those with bulky tumors, those with clinical T4a disease, and those with contralateral lymph node involvement, he noted.

Despite the favorable results with the lower radiation dose, it would be premature to translate this into clinical practice, said Dr. Cmelak.

There has been a lot of discussion among head and neck cancer specialists about reducing the aggressiveness of treatment for patients with HPV-positive disease, who have a better prognosis than HPV-negative patients. However, clinicians are also concerned that this might result in undertreatment.

"I don't recommend using lower doses of radiation for these patients off-study," he added.

Ultimately, it will take a large randomized trial comparing standard approaches with a deintensified regimen in up-front responders "to safely ensure that we're not going to be jeopardizing patient survival to minimize toxicity," he explained.

These results represent "great progress," said Gregory Masters, MD, director of medical oncology at the Helen F. Graham Cancer Center in Newark, Delaware, and ASCO's expert on head and neck cancers.

"Most of what we've been doing in oncology is escalating doses and treatment. That's not necessarily always the right answer," Dr. Masters explained. "This is a step in the right direction, but I don't think anyone would say we're at the point where we know exactly how to modify the doses for HPV-positive cancer."

"It is laudable to see a trial addressing a means of separating a disease into 2 populations," said Brian O'Sullivan, MD, from the Department of Radiation Oncology at the University of Toronto.

He is an expert in head and neck cancer and has studied the nuances of deintensifying therapy in HPV-positive oropharyngeal cancer, as reported by Medscape Medical News.

The ECOG 1308 study "was designed in the era before there was the same appreciation for the stratification of risk in this disease," said Dr. O'Sullivan. More recent trials take into account the risk for distant metastasis — "which has emerged as one of the leading causes of death in this patient population" — to allow an even more precise stratification of risk in HPV-positive disease.

In the future, "trials should probably be designed with this in mind, potentially using the strategy illustrated by ECOG 1308, which employs an induction systemic approach emphasizing agents capable of addressing distant metastases and potentially using a less intense local treatment approach in those who respond," Dr. O'Sullivan explained.

The lesson from this study is that "we need to select patients better for dose de-escalation," said study discussant Quynh-Thu Le, MD, professor of radiation oncology and otolaryngology–head and neck surgery at Stanford University Medical Center in California.

"It's an exciting era of de-escalation and deintensified treatment, but we need to figure out the best strategy to try to decrease treatment and minimize toxicity while maintaining the same outcome. One thing we learned from the work by Dr. O'Sullivan's team is maybe there are subgroups that we can de-escalate; these are patients with T1, T2 tumors, nonsmokers, and N0 to N2d disease. These patients do very well."

The study was funded by the National Institutes of Health. Anthony Cmelak reports financial relationships with Bristol-Myers Squibb. Dr. O'Sullivan and Dr. Masters have disclosed no relevant financial relationships. Dr. Le reports a financial relationship with Amgen.

2014 Annual Meeting of the American Society of Clinical Oncology (ASCO): Abstract LBA6006. Presented May 30, 2014.


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