Positron-emission tomography (PET) scans obtained before and midway through treatment can be used to de-escalate therapy for oropharyngeal cancer, potentially leading to fewer short-term side effects, according to data presented by Allen et al at the 2022 Multidisciplinary Head and Neck Cancers Symposium (Abstract 1). Interim acute toxicity analysis of the phase II study showed that by using the midtreatment imaging marker, approximately half of patients with early-stage p16-positive oropharyngeal cancer could undergo de-escalation 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 approximately 25% dose reduction to structures known to critically govern head to neck toxicity. The study authors also reported a significant decrease in several objective measures of toxicity.
“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 fluorodeoxyglucose (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.”
As Dr. Allen reported, pre- and midtreatment PET imaging using FDG to detect responses to chemoradiation has been shown to be prognostic of treatment response in patients with HPV-driven oropharynx cancer. While 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, while 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 were de-escalated 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 and 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 median pack-year use of 15 and 20 years, respectively.
“Half of the patients met de-escalation criteria and received the lower radiation dose, resulting in approximately 25% less radiation exposure to the sensitive structures in the head and neck known to be associated with side effects during treatment,” said Dr. Allen.
Importantly, this de-escalation resulted in significantly less acute toxicity. At 1 month after treatment, the standard treatment group lost a median 11% of their body weight compared to just 6% body weight 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).
“Although the trial remains ongoing, the results that we have today appear promising with our de-escalated cohort,” Dr. Allen concluded.
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