How to Ensure Surgical Head and Neck Clinical Trials Are Beneficial to Patients

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Randomized controlled trials can take a great deal of time, money, and effort. Hisham Mehanna, MD, chair of head and neck surgery at the Institute of Cancer and Genomic Sciences and director of the Institute of Head and Neck Studies and Education at the School of Cancer Sciences at the University of Birmingham in the U.K., wondered about their return on investment for patients with head and neck cancer and the healthcare systems that serve them.

In his Eugene N. Myers, MD International Lecture on Head and Neck Cancer, “What Have Head and Neck Clinical Trials Ever Done for Our Patients Anyway?” Dr. Mehanna covered the benefits and flaws in clinical trials in head and neck cancer over the past two decades.

He referenced the presidential address delivered by John Andrew Ridge, MD, PhD, at the 2010 American Head and Neck Society meeting, which spoke of medical oncologists and clinical radiologists having a history of participating in clinical trials, whereas surgical oncologists did not. In the decade preceding
2010, surgical oncologists had not conducted a single clinical trial, and Dr. Ridge asserted that surgeons were willing to change their practice without Level 1 evidence. “Dr. Ridge believed surgeons had been dismissed as an intellectual force, even by surgeons themselves,” Dr. Mehanna said.

In the aftermath of Dr. Ridge’s address, surgeons led four major head and neck trials between 2011 and 2019. “Things have changed,” Dr. Mehanna said. “I think this reflects the rise of the head and neck surgeon–scientist.”

The Last 10 Years

Here are the four major clinical trials in head and neck cancer led by surgeons over the past decade and their results:

1. Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer. Led by Anil D’Cruz, MD, in Mumbai and also known as the Tata Trial because it was run by the Tata Memorial Centre, this
   trial concluded that, among patients with early-stage oral squamous-cell cancer, elective neck dissection resulted in higher rates of overall and disease-free survival than therapeutic neck dissection (N Engl J Med. 2015;373:521–529).
2. PET-NECK. This multicenter randomized phase III non-inferiority trial compared a PET-CT–guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell head and neck cancer. Led by Dr. Mehanna, the trial concluded that PET-CT–guided active surveillance showed similar survival outcomes with planned neck dissection but resulted in considerably fewer planned neck dissections, fewer complications, and lower costs, supporting its use in routine practice (N Engl J Med. 2016;374:1444–1454).
3. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. Led by Bob Ferris, MD in Pittsburgh, this trial concluded that, among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-
   agent therapy (N Engl J Med. 2016;375:1856–1867).
4. De-ESCALaTE HPV. This open-label randomized controlled phase 3 trial looked at radiotherapy plus cisplatin or cetuximab in low-risk HPV-positive oropharyngeal cancer. Also led by Dr. Mehanna, this trial’s interpretation was that cetuximab, compared with the standard cisplatin regimen, showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumor control. It advised that cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin (Lancet. 2019;393:51–60).

Design Flaws

Dr. Mehanna said there are issues that come up regularly in surgical research that are important to consider carefully. Clinical trials are a good way of addressing these pitfalls. They include: