Positron-emission tomography (PET) scans obtained before and midway through treatment may be used to de-escalate therapy for patients with oropharyngeal cancer, leading to fewer side effects, according to data presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium.1 An interim acute toxicity analysis of the phase II study showed that by using the midtreatment imaging marker, approximately half of patients with early-stage human papillomavirus (HPV)-associated oropharyngeal cancer could be de-escalated to a total dose of 54 Gy in 27 fractions, rather than the standard dose of 70 Gy in 35 fractions.
This de-escalation strategy resulted in an approximately 25% dose reduction to structures known to critically govern head to neck toxicity. Authors of the study also reported a significant decrease in several objective measures of toxicity.
Steven Allen, MD,PhD
“Advanced imaging helps physicians personalize therapy based on patients’ individual tumor characteristics and response to treatment,” said lead author Steven Allen, MD,PhD, a radiation oncology resident at the University of Michigan. “By incorporating FDG-PET scans before and midway through treatment, we were able to adjust the radiation dose for about half of our patients and reduce their short-term side effects while still focusing on tumor control.”
Background and Study Details
As Dr. Allen reported, pre- and midtreatment PET imaging using fluorodeoxyglucose (FDG) to detect responses to chemoradiation has been shown to be prognostic of treatment response in patients with HPV-driven oropharyngeal cancer. Although FDG is the most used radiotracer in clinical PET imaging, said Dr. Allen, this phase II trial is the first to report its use as a midtreatment imaging marker to guide de-escalation for oropharyngeal cancer.
Patients with stage I to II p16-positive oropharyngeal cancer with FDG-avid disease were included in the study. Those with matted lymph nodes or a history of head and neck surgery were excluded.
Patients underwent FDG-PET scans to determine their metabolic tumor volume before and midway through treatment. Those who had tumors with lower metabolic activity before treatment and more than 50% reduction in metabolic tumor volume after 2 weeks of treatment underwent de-escalation from the standard total dose of 70 Gy in 35 fractions to a total dose of 54 Gy in 27 fractions. All patients received concurrent weekly carboplatin/paclitaxel.
This interim analysis reported findings for the first 59 patients accrued to the trial.
Although this was a nonrandomized study, Dr. Allen reported that baseline characteristics showed that both standard and de-escalated cohorts had similar patient demographics and pathology. Notably, just under half of patients in the trial were former smokers with a median pack-year use of 15 and 20 years, respectively.
“Half of the patients met de-escalation criteria and received the lower radiation dose. This resulted in approximately 25% less radiation exposure to the sensitive structures in the head and neck known to be associated with side effects during treatment,” explained Dr. Allen.
Of note, de-escalation of therapy resulted in significantly less acute toxicity. At 1 month after treatment, the standard treatment group lost a median 11% of their body weight compared with 6% in the de-escalated cohort (P < .001). Patients in the de-escalated group were also less likely to need a feeding tube (1 vs 7 patients; P = .037) and had improved swallowing function on a video swallow study administered after treatment (P = .036).
Michelle L. Mierzwa, MD
“We anticipated long-term improvements in side effects, but the short-term improvements were better than expected,” senior author and principal investigator Michelle L. Mierzwa, MD, Associate Chair of Clinical Research and Co-Chair of Head and Neck Clinical Trials at the University of Michigan, noted in a press release. “Experiencing fewer short-term side effects potentially allows patients to get back to their normal activities more quickly.”
In addition to these acute measures of toxicity, investigators collected a panel of patient-reported survey outcomes. Not surprisingly, said Dr. Allen, all patients in both cohorts reported being significantly worse than baseline 1 month after treatment. Although the de-escalated cohort numerically scored better on the quality-of-life surveys, however, the differences between the two cohorts were not statistically significant.
“Although the trial remains ongoing, the results appear promising with our de-escalated cohort,” Dr. Allen concluded.
DISCLOSURE: Dr. Allen and Dr. Mierzwa reported no conflicts of interest.
1. Allen SG, Rosen BS, Cao Y, et al: Early toxicity and patient reported outcomes from a phase 2 trial of FDG-PET response-based de-escalated definitive radiotherapy for p16+ oropharynx cancer. 2022 Multidisciplinary Head and Neck Cancers Symposium. Abstract 1. Presented February 24, 2022.
In an interview with The ASCO Post, Quynh-Thu Le, MD, FACR, FASTRO, Professor and Chair of Radiation Oncology at Stanford Cancer Center, called this phase II de-escalation trial an “intriguing study” that heads in the right direction for treatment de-escalation. However, Dr. Le noted, the...