Expert Point of View: Paul Harari, MD


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Paul Harari, MD

Paul Harari, MD

COMMENTING ON THIS STUDY, ASTRO President Paul Harari, MD, was enthusiastic about the results. Dr. Harari is the Jack Fowler Professor and Chairman of the Department of Human Oncology at the University of Wisconsin School of Medicine and Public Health and Associate Director of the University of Wisconsin Carbone Cancer Center in Madison. 

“These results are exciting. Human papillomavirus (HPV)-associated head and neck cancer has a distinct molecular profile and clinical course compared with other head and neck cancers, and warrants a different treatment approach,” Dr. Harari explained. 

“Historically, it has been common to stack new therapies on top of one another in an attempt to increase cure rates, particularly for low cure-rate cancers. However, it can be quite challenging to de-intensify therapy for cancer patients who already have high cure rates. This requires careful and systematic clinical trials validation to ensure that we don’t prematurely de-intensify treatment to the point where patient survival is compromised. Most patients will choose cure over toxicity in this type of high cure-rate setting,” Dr. Harari added. 

“The last thing we want to do is reduce the cure rate. But radiation and chemotherapy for head and neck cancer produce notable toxicities. It would be a powerful advance if we could safely de-escalate the therapy,” he continued. 

A Bold Step 

“THE APPROACH used by Dr. Ma and colleagues was a bold step,” continued Dr. Harari. “We have seen increasing evidence of greater radiation sensitivity and high response rates in HPV-positive head and neck cancer patients. Many investigators are performing dose de-escalation studies where radiation and/or chemotherapy is reduced. This study is a strong example of radiation dose reduction. This approach may be effective. It may maintain the cure rate and reduce side effects. It is no surprise that this strategy profoundly diminishes the toxicity associated with radiation. The compelling question is can we maintain the cure rate?” 

“This phase II trial opens the window for a phase III trial. The strategy of de-escalation appears safe and the preliminary results are encouraging. We wait for the results of DART-HPV with high interest and anticipation,” he said. 

“A positive randomized phase III trial would be necessary to truly change practice. These are high cure-rate cancer patients, and although we would love to lessen their toxicity profile, we don’t want to inadvertently sacrifice overall cure rates,” Dr. Harari stated. ■

DISCLOSURE: Dr. Harari reported no conflicts of interest. 


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