Lower radiation doses feasible for HPV-positive head and neck cancers

Tanguy Seiwert

Patients with HPV-related head and neck cancers safely and effectively received lower radiation doses after initially responding to chemotherapy, according to results from the OPTIMA trial scheduled for presentation at the Multidisciplinary Head and Neck Cancers Symposium.

Researchers also observed this association among patients with advanced nodal disease.

“HPV-positive head and neck cancers are increasing rapidly in incidence. What is particularly important about these types of cancers is [although] they are starting to be more and more common, they actually have a favorable prognosis and good outcomes with curative therapy radiation, but also chemotherapy,” Tanguy Seiwert, MD, assistant professor of medicine at University of Chicago Medicine, said during a press conference. “Given these improved outcomes, but also the fact that they occur in younger patients, long-term side effects are of particular concern. We have started to apply a de-escalation approach to this type of cancer, giving less treatment and trying to avoid toxicities.”

Seiwert and colleagues studied 62 patients with HPV-positive head and neck cancers, including those with advanced nodal disease.

Researchers stratified patients as low risk ( T3, N2B, 10 pack-year smoking history; 45%) or high risk (T4 or N2C or > 10 pack-years; 55%). Patients then underwent three cycles of induction chemotherapy with carboplatin and nab-paclitaxel to determine treatment response.

Researchers defined favorable response to induction chemotherapy as 50% or greater reduction in tumor size for high-risk patients and 30% or greater reduction for low-risk patients.

Treatment groups included:

Low-risk patients with favorable response received low-dose 50 Gy radiation (RT50 arm);
Low-risk patients with moderate response (30%-50%) received low-dose 45 Gy chemoradiation (CRT45 arm);
Low-risk patients with little to no response (< 30%) received standard 75 Gy chemoradiation (CRT75 arm);
High-risk patients with favorable response received low-dose 45 Gy chemoradiation (CRT45 arm); and
High-risk patients with favorable response received standard 75 Gy chemoradiation (CRT75 arm).

Median follow-up was 22.3 months (range, 9-39).

Two-year PFS rates reached 93.5% among high-risk patients and 100% for low-risk patients.

OS at 2 years was 100% among low-risk patients and 97% for high-risk patients.

De-escalated therapy significantly improved side effects compared with standard treatment:

Grade 3 or higher mucositis occurred among 16% of those in the RT50 arm, compared with 46% in the CRT45 arm and 60% of in the CRT75 arm (P = .033);
No patients in the RT50 arm experienced grade 3 or higher dermatitis compared with 21% of those in the CRT45 arm and 30% in the CRT75 arm (P = .056); and
No patients in the RT50 arm experienced long-term dependency on a feeding tube compared with 3.5% of those in the CRT45 arm and 9% in the CRT75 arm (P < .0001).

“The OPTIMA trial showed a de-escalation approach is not just feasible, but it’s also efficacious,” Seiwert said. “The majority of patients did receive de-escalation treatment, and we were able to further reduce the dose of radiation than other trials have recorded before to 50 Gy for radiation and 45 Gy for chemoradiation. Importantly, this trial did include high-risk nodal stages in these tumors and this did not affect our ability to de-escalate.

“There are a number of de-escalation approaches and they all seem to work well. At this point large centers should use a de-escalation approach and we could start to say a de-escalation approach is the new standard of care,” he added.

Seiwert specifically praised the OPTIMA trial’s approach to de-escalation because it accounted for stratifying patients. – by Cassie Homer

Reference:

Seiwert T, et al. Abstract 5. Presented at Multidisciplinary Head and Neck Cancers Symposium; Feb. 15-17, 2018; Scottsdale, Ariz.

Disclosures: Seiwert reports honoraria from Celgene. The other authors report no relevant financial disclosures.