It has long been said that when it comes to cancer, “the treatment is worse than the disease.” At WashU Medicine, a multidisciplinary team of head and neck surgeons, radiation oncologists and medical oncologists is trying to change that.
Treatment of head and neck cancers like squamous cell carcinomas, typically utilizes a multidisciplinary approach that includes surgery, radiation and chemotherapy. Unfortunately, the treatments themselves are associated with toxicities that result in physical disfigurement, difficulty with swallowing and speaking, and loss of taste and hearing.
The greater cure rates and increased prevalence of human papilloma virus (HPV)-positive tumors has increased interest in reducing treatment toxicity through a strategic de-escalation of therapeutic interventions. These strategies may include any combination of the reduction or elimination of chemotherapy; reduction of radiation dosage; and utilization of less-invasive surgical approaches.
Not all approaches to de-escalation have yielded positive results, and these failures emphasize the importance of patient selection and study design.
Surgery Followed by Risk-Directed Post-Operative Adjuvant Therapy for HPV-Related Oropharynx Squamous Cell Carcinoma: “The Minimalist Trial (MINT)”
The multidisciplinary effort to test the efficacy of de-escalation treatment is a Phase 2 clinical trial run by medical oncologist Doug Adkins, MD. Ongoing since 2018, the WashU Minimalist Trial or MINT has tested three variations of combined reductions in radiation and cisplatin chemotherapy following surgery for HPV-positive oropharyngeal squamous cell carcinoma. Outcomes measured included weight loss, recurrence rate, progression-free survival and overall survival as well as assessment by a number of Quality of Life indices.
Results revealed a significant reduction in weight loss in patients on the de-escalated treatment regimen, compared to historical control patients. Importantly, there was also no change in progression-free survival or the time between study enrollment and progression of the cancer, suggesting de-escalated treatment is no less effective at controlling the cancer.
“As we learn more about the biology of HPV+ head and neck cancers, it is clear that we have probably been over-treating these patients for decades,” said Division Chief of Head and Neck Surgery Sid Puram, MD, PhD. “However, it is critical to be judicious as we slowly pare down treatment and de-escalate to make sure that we do not overshoot, resulting in reduced cancer control. There must be a sweet spot and we have to slowly march towards that through well designed, well considered clinical studies such as MINT.”
WashU Med ENT resident Theresa Tharakan, MD, MSCI, and head and neck surgeon Ryan Jackson, MD, studied the swallowing outcomes in these patients. Their results suggest patient-reported swallowing function is improved with de-escalation treatment, at least in the early treatment period.
One of the most positive changes observed with de-escalation was the reduction of ototoxicity or cisplatin-induced hearing loss. Using normal doses of cisplatin, many patients experience some permanent hearing loss. WashU Med ENT resident David Lee, MD, MSCI, followed one MINT cohort of 29 patients and compared the occurrence of hearing loss to a group of 27 historical control patients. Only 5% (3 of 58 ears) of patients in the MINT trial suffered hearing loss, compared to 46% of historical patients receiving standard cisplatin therapy.
According to Puram, additional patient-reported outcomes will be a focus of the next phase of study. The team hopes to open the next iteration of this study MINT2 in the upcoming year, which will further de-escalate treatment given the favorable results of the first study.
For more information, please visit the Head and Neck Tumor Center at Siteman Cancer Center.