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CHICAGO -- De-escalated adjuvant radiation therapy (DART) demonstrated less toxicity and led to similar oncologic outcomes for some patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, a found.

For the study's primary endpoint, the DART group (30-36 Gy plus docetaxel) saw numerically lower grade 3 or greater radiation-related adverse events (AEs) at 3 months versus those receiving standard of care (SOC; 60 Gy with or without cisplatin), at 1.6% versus 7.1%, respectively (P=0.058), reported Daniel Ma, MD, of the Mayo Clinic Alix School of Medicine in Rochester, Minnesota.

But only 1.6% of patients randomized to DART required a feeding tube compared with 27.4% of those who received SOC (P<0.0001), he said in a presentation here at the American Society for Radiation Oncology (ASTRO).

In addition, swallowing function change from baseline to 1 month was superior in the DART arm versus the SOC arm (median modified barium swallow impairment score -0.3 vs -2.6, P=0.0155). DART also offered significant improvement in the pain score (-8.6 vs 2.5), and quality-of-life (QoL) measures.

However, DART may not be appropriate for patients with extranodal extension (ENE), Ma stated, based on the inferior progression-free survival (PFS) in this higher-risk group.

Overall, the PFS rates at 2 years were 86.5% in the DART arm compared with 95.1% for the SOC arm, and rates were similar for intermediate-risk patients (no ENE), at 97.6% and 93.3%, respectively. But for those with ENE-positive disease, the 2-year PFS rate was 78.9% in the DART arm versus 96.2% in the SOC arm.

"When you break it down by nodal staging, in the ENE-positive cohort there was one outlier that contributed the majority of events in progression-free survival and that was DART patients who were pN2," Ma pointed out. In this group, the 2-year PFS rate was only 42.9% with DART, as compared to 100% with SOC.

"Caution is advised for de-escalating ENE-positive patients, particularly those with pN2 disease," Ma said.

The rationale for the study was the substantial toxicity associated with SOC treatment for HPV-positive oropharyngeal cancers, he explained.

"Although the cure rates for HPV-associated oropharyngeal squamous cell carcinoma are high, standard treatment can have serious and life-altering effects," he noted. "In addition to the physical side effects, treatment side-effect duration can have significant impact on patient's mental and financial well-being."

Ma noted that more than half of all head and neck cancer patients will have some form of depressive symptoms. And, on average, patients require 14 weeks after completion of treatment before they can resume work.

"Transoral robotic surgery [TORS], followed by low-dose hypofractionated radiation therapy, with concurrent chemotherapy, may be feasible in a select group of patients with intermediate-risk HPV-positive oropharyngeal cancers," commented ASTRO discussant Farzan Siddiqui, MD, PhD, of Henry Ford Hospital/Wayne State University in Detroit. "De-intensification should not be done in patients with pathologic ENE and/or N2 disease."

Siddiqui questioned the generalizability of the results. For example, he noted TORS surgeries are performed in highly specialized high-volume centers, while a high level of expertise is needed to assess margins and ENE status. In addition, he pointed out that twice daily hypofractionated RT "may be logistically challenging."

He also stressed the importance of against high-risk HPV. "In my mind, the best form of de-intensification or de-escalation will be the prevention of these cancers," he said.

The current trial included 194 patients (median age 59.4; 89% male), with 59% having ENE-positive disease. All underwent TORS and neck dissection for a margin-negative resection.

Patients were randomized 2:1 to either DART or SOC. For the DART arm, patients received docetaxel 15 mg/m² on days 1 and 8; those with intermediate-risk disease received 30 Gy/1.5 Gy twice daily, while those with ENE received 36 Gy/1.8 Gy twice daily.

The median 2-year OS in the SOC arm was 97.0% versus 96.1% in the DART arm. OS rates for ENE-negative patients were 90.9% in the SOC arm and 100% in the DART arm. Conversely, the OS rates for ENE-positive patients were 100% in the SOC cohort and 93.4% in the DART cohort.

In addition, local regional recurrence-free survival (RFS) at 2 years for the total population was 97.9% with SOC versus 95.5% with DART. For those without ENE, these rates were 93% and 100%, respectively. In the ENE-positive cohort, RFS at 2 years was 100% with SOC versus 92.2% with DART.

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