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New weapons in the fight against oropharyngeal cancer

The GW hospital makes use of the Da Vinci surgical platform, which combines laparoscopic technology with surgical robots.Credit: Intuitive Surgical Operations, Inc.

In July 2018, Sabrina Barnhart got a terrible shock. She was diagnosed with tonsil cancer and told she needed an aggressive course of chemotherapy and radiation, blasting her neck from ear to clavicle.

Chemotherapy combined with radiotherapy is the traditional treatment for oropharyngeal cancer. All cancer treatments can have side effects, but radiotherapy for this form of the disease often comes with especially unpleasant and long-lasting impacts, such as difficulty swallowing. Some patients even need to have a tracheostomy, in which a tube is inserted into the neck to aid breathing.

Sabrina’s research made her worry that such extreme radiation therapy could severely reduce her quality of life. Her ear, nose and throat doctor put her in touch with The George Washington University Hospital (GW Hospital), where experts at the GW Cancer Center are developing ways to treat her type of cancer without the need for radiotherapy. They have discovered that many patients can be given chemotherapy alone, to shrink the tumour until it’s small enough to be surgically removed.

“I was really scared, but I felt I was in safe hands,” says Sabrina. “This was literally about the rest of my life, so I asked a lot of questions. The GW Cancer Center team understood that, explaining everything along the way, making me feel super comfortable with my decision.”

The team at GW Cancer Center had worked out that cancers like Sabrina’s were different from apparently similar cancers, which allowed them to modify treatment accordingly. That’s part of a pioneering treatment approach that the researchers are developing at the research hospital.

Ditching convention

Historically, most head and neck cancers were the result of heavy smoking or drinking. But, in the past few decades, specialists have seen more and more cases of cancer caused by human papillomavirus (HPV), which can colonize and change the lymphoid tissue at the back of the throat, specifically the tonsils and the base of the tongue. The good news is that HPV-related cancers are usually very sensitive to treatment, including chemotherapy, radiotherapy and surgery.

At GW Cancer Center, the focus on chemotherapy makes that treatment less intense for patients with HPV-induced oropharyngeal cancer.

“We're trying to avoid giving all three because radiation can cause significant issues in terms of pain, swallowing, fibrosis, dry mouth and everything else that comes after cancer treatment in this particular area,” says Joseph Goodman, Otolaryngology Residency Program Director at the GW School of Medicine and Health Sciences. “With HPV, our experts look at how to de-escalate treatment.”

The team will only use radiation as a follow-up treatment for particularly aggressive tumours or if the cancer has spread into nearby lymph nodes.

Chance discovery

This novel approach was discovered by chance at GW about 15 years ago. It started with patients who had large treatable tumours but could not receive standard therapies for a variety of reasons. The GW Cancer Center could only offer chemotherapy as they waited for treatment plans to be set up. Team members noticed a trend: many patients’ tumours responded completely to chemotherapy alone. When the patients were eventually taken to surgery, in many cases no radiation was needed.

“We started asking ourselves, which sorts of patients would respond to this treatment,” says Arjun Joshi, Head and Neck Oncology Division Director at The George Washington University Hospital. “Back then, we weren’t testing for HPV, but more recently we’ve realised it’s likely those patients were HPV-positive. So, we have designed a formal clinical trial looking at exactly this question.”

GW Cancer Center, with other institutions, is now treating patients including Sabrina as part of a phase II trial to examine this radiotherapy-free protocol.

Other research supports the idea that radiation is often not needed in HPV-positive head and neck cancer. A prospective phase II study from 2020 showed disease-free survival rates of 96%, five years after treatment with chemotherapy followed by surgery and no radiation. 1

This built on an earlier observational study of 54 patients with HPV-positive oropharynx cancer receiving only chemotherapy followed by surgery at GW Hospital. Their tumour volumes reduced more than 90% following neoadjuvant chemotherapy.2 Shrinking a tumour to that extent helps a surgeon to completely remove all the cancerous material, causes less pain, and reduces swallowing problems and other dysfunctions.

Minimally invasive surgery

A surgeon operates the Da Vinci system from a console.Credit: Intuitive Surgical Operations, Inc.

GW hospital also uses other cutting-edge techniques to treat oropharyngeal cancers. These include the Da Vinci surgical platform, which combines laparoscopic technology with surgical robots.

Complete with robotic arms flexible enough to almost reach around corners, direct lighting and 3D visualization that provides levels of magnification impossible in non-robotic surgery, the Da Vinci system offers less invasive procedures. This allows surgeons to perform precise resections of tumours in the tonsils or base of tongue, without having to cut through the jaw or palate.

The procedure is also backed with good evidence. GW Cancer Center's study of swallowing function in 37 patients who had neoadjuvant chemotherapy and transoral robotic surgery to treat oropharynx cancer reported satisfactory swallowing outcomes two years after the operation.3

And a retrospective study of the National Cancer Database from 2010-2016, found patients with HPV-induced oropharyngeal squamous cell carcinoma (OPSCC) who had transoral robotic surgery had better overall survival rates than those who had conventional surgery.4

The advantage comes from how the surgeon accesses the tumour. “If you come from outside, you cut through the tube of the pharynx, and the patient ends up having a lot of swallowing difficulty,” says Goodman. “Going from the inside preserves function.”

Flexible robotic arms, direct lighting and 3D visualization allow surgeons to perform procedures less invasively.Credit: Intuitive Surgical Operations, Inc.

Three months after surgery, patients are checked to make sure the cancer is gone. Traditionally this is done by physical exam and endoscopy or with a PET scan. To streamline the process, the GW team uses a liquid biopsy test that analyses tumour-tissue-modified DNA in the blood to find any HPV-related cancer.

Patient-centred care

The GW Cancer Center team no longer treats HPV-positive and HPV-negative cancers with the same approach, and is examining the genetic underpinnings and immune microenvironment of the different cancers.

“In our pre-operative clinical trials, we’re tailoring the targeted therapy to the patient’s stage and HPV status, as HPV-positive and HPV-negative head and neck cancers are two different diseases,” says Julie Bauman, who joined the GW Cancer Center as director in 2022. “We’re learning about the mechanism of these drugs and, ultimately, how we can select patients who would benefit from them.”

The head and neck cancer team at GW Cancer Center excels at these studies, says Bauman. By accelerating the development of targeted therapies and immunotherapies for head and neck cancer in both HPV-positive and HPV-negative cases, the team is driving progress in this field, she adds.

“Just like the exceptional head and neck cancer team, my vision is to create multidisciplinary cancer services where sub-specialized disease teams communicate over each patient’s case to offer cutting-edge strategies, so that every aspect of a patient’s care is considered in advance,” she says. “A highly coordinated treatment plan could include ground-breaking surgical and radiation techniques, modern systemic therapies, and knowledge gained from extensive clinical trials.”

Bauman says she was keen to take up the directorship because she believes the GW team is uniquely positioned to address alarming disparities in cancer incidence and mortality in the US capital.

“I’m focused on building teams that truly encompass the whole patient experience,” she says. Bauman is growing patient support services including patient navigation, community outreach and engagement, as well as establishing a clinical research office. “I want to ensure that our clinical trials match the needs of our unique population and contribute to transforming cancer survival and survivorship for our community.”

Quality of life

For Sabrina Barnhart, the journey has not been easy. She started her first round of three chemo treatments in late September 2018, and underwent surgery in December of that year.

She has now been cancer-free for more than three and a half years. “I can't thank the GW Cancer Center team enough for what they have done for me and my family. I'm sure my life would look very different today if it weren't for their drive and foresight.”

Sabrina has advice for other people in a similar situation. “Be your own champion, ask hard questions, be willing to do the research. Make sure the treatment plan that is being recommended is truly the best option for you.”

Indeed, a survey published in 2022 showed that patients treated for HPV OPSCC with neoadjuvant chemotherapy and transoral robotic surgery had near-normal scores in most quality-of-life domains.5

These outcomes keep the GW team enthusiastic about the radiation-free protocol. “GW Hospital is one of the few research hospitals investigating treatment in this way,” says Goodman. “With well-designed clinical trials, we’re hoping that our method will be proven just as effective at treating the cancer but with less toxicity than standard approaches. It would be a big paradigm shift.”

For more information on this innovative cancer treatment visit GW Cancer Center


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