Mid-treatment imaging guides radiation de-escalation in oropharynx cancer
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Mid-treatment imaging helped guide de-escalation of radiation for certain patients with oropharynx cancer, according to phase 2 study results presented at Multidisciplinary Head and Neck Cancers Symposium.
Fluorodeoxyglucose (FDG)-PET scans performed prior to and during therapy identified which patients with stage I or stage II p16-positive disease could receive lower doses of radiation in the second half of their treatment course without compromising efficacy, results showed.
De-escalated therapy appeared associated with fewer short-term adverse effects.
“While we are careful to slowly decrease radiation therapy dose and not expose patients to unnecessary risk for treatment failure, an imaging marker-based strategy for deintensified definitive chemoradiation may allow nonsurgical de-escalation strategies that improve toxicity,” researcher Michelle L. Mierzwa, MD, associate chair of clinical research and co-chair of head and neck clinical trials at University of Michigan, told Healio.
“Improvements in acute toxicity allow patients to more quickly resume their typical activities,” Mierzwa added. “We also frequently see that acute toxicities predict late toxicities, and we hypothesize that we will see long-term improvements in side effects for patients who can be de-escalated — especially dysphagia and xerostomia. For example, we saw that the patients who were able to [receive the lower radiation dose] had no change from baseline on swallow studies 3 months after radiation therapy, potentially suggesting normal long-term swallow function.”
Mierzwa and colleagues conducted a multi-institution prospective study to assess the potential of FDG-PET response criteria to identify which patients with stage I or stage II p16-positive disease could be eligible for de-escalated therapy.
The analysis included 59 patients (median age, 60 years; range, 52-69; 93% male) with FDG-avid disease and any smoking history. Researchers excluded patients with any prior surgery or head/neck radiotherapy, matted lymph nodes or contraindication to FDG-PET.
Slightly less than half (46%) of study participants were former smokers, with median pack-year history of 20 years (range, 6-35).
All patients underwent pretreatment PET imaging and began a definitive course of standard radiation therapy planned to 70 Gy in 35 fractions, with concurrent chemotherapy consisting of carboplatin/paclitaxel.
Patients underwent repeat FDG-PET after 2 weeks of definitive treatment. Those whose tumors demonstrated lower metabolic activity prior to treatment and at least 50% reduction in metabolic tumor volume after 2 weeks of treatment received de-escalated treatment (54 Gy in 27 fractions).
“There was no replan of the radiation treatment or change in the volume. Patient treatment was stopped at 27 fractions instead of 35,” researcher Steven Allen, MD, PhD, radiation oncology resident at University of Michigan, said during a presentation.
Noninferior local regional control compared with a historical cohort served as the study’s primary outcome.
At Multidisciplinary Head and Neck Cancers Symposium, Allen presented results of an interim acute toxicity analysis.
Twenty-eight patients (47.4%) met de-escalation criteria and received the lower radiation dose, leading to 20% to 30% reductions in radiation exposure to critical structures known to govern head and neck toxicity. These included the head and neck, including the larynx, constrictors, oral cavity and salivary glands.
The de-escalated and standard dose groups appeared similar with regard to patient demographics and pathology, as well as primary tumor and lymph node size, Allen said. Initial 70 Gy treatment plans also appeared nearly identical between groups.
“We were expecting improvements in late toxicity, but [we] were able to see significant improvements in acute toxicity for the de-escalated cohort,” Mierzwa said.
Patients who received de-escalated therapy lost less weight as a percentage of baseline (median, 6% vs. 11%; P < .001) and exhibited improved video fluoroscopic swallowing function (P = .036).
“Strikingly, 3 months after de-escalated treatment, the median change in [Penetration Aspiration Scale] score was 0 for the de-escalated group,” Allen said.
University of Michigan’s institutional practice recommends temporary feeding tubes for patients with 10% weight loss from baseline. Following this threshold, one patient (3.5%) in the de-escalation group required feeding tube placement during treatment, compared with seven (22.5%) in the standard group (P = .037).
Researchers also assessed patient-reported outcomes with the Xerostomia questionnaire, University of Washington Quality of Life questionnaire, the Functional Assessment of Cancer Therapy-Head and Neck Scale and the Patient Reported Outcomes-Common Terminology Criteria for Adverse Events instrument.
“Not surprisingly, at 1 month after treatment, all patients in both cohorts reported being significantly worse than baseline and clinically meaningfully so,” Allen said. “But when looking at the differences between the two cohorts, while the de-escalated cohorts numerically scored better on the quality-of-life surveys, these results were not statistically significant in our sample.”
Investigators will complete accrual to this study and are planning a follow-up study, Mierzwa said.
“Our long-term goal is to establish biomarker-driven, definitive chemoradiation de-escalation strategies for HPV-related oropharynx cancer that are based on broadly available imaging and lab tests [that] may be translated into multiple practices in the future,” Mierzwa told Healio.
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Allen SG, et al. Abstract 1. Presented at: Multidisciplinary Head and Neck Cancers Symposium; Feb. 24-26, 2022; Phoenix.
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