DART through 2 weeks of treatment.

Headline: Adjuvant radiation following TORS for HPV+ oropharyngeal cancer to only 30-36 Gy delivered twice-daily over 10 days is very effective and much less toxic than the standard 60 Gy over 6 weeks.

The Study: Now that’s what we call de-escalation. It was all born from the promising results of a single arm phase 2 trial first reported a couple of years ago. The rapid phase 3 follow-up MC1675 enrolled patients with resected HPV+ oropharyngeal cancer (and < 10 years smoking history) with broad pathologic inclusion including extranodal extension (ENE) but not pT4 tumors. Important to remember is that all patients were treated within the Mayo Clinic system and underwent transoral robotic surgery (TORS) with negative margins (no tumor on ink) achieved after no more than on re-resection. 194 patients were randomized 1:2 to standard versus de-escalated adjuvant radiation (aka DART). Again, DART was 1.5 Gy (with 1.8 Gy simultaneous integrated boost to areas of resected ENE) x 20 twice daily fractions with concurrent low-dose docetaxel 15 mg/m2 on days 1 and 8. Now, this may seem like a pretty extreme change from the standard of 60 Gy +/- cisplatin, but the idea is: if you are going to meaningfully decrease toxicity, you have to stop before the steep part of the toxicity curve. The discussant did a deep dive in EQD2 calcs, and it comes out to about 36 Gy versus 50 Gy without ENE and 42 Gy versus 56 Gy with ECE. Also, only a primary tumor that is large or crosses midline bought elective contralateral neck radiation. The primary endpoint of G3+ toxicity at 3+ months after treatment completion was 7.1% with standard radiation and 1.6% with DART. What’s more, swallowing function, pain, and feeding tube use (27.4% versus 1.6%) were all significantly better with DART. Finally, all patients achieved superb disease outcomes with the important exception of pN2 patients with ENE who had clearly inferior progression-free survival with DART, driven by both higher rates of locoregional recurrence and distant mets. The question is how applicable such an approach is outside the Mayo Clinic.

TBL: With slam dunk improvements in toxicity and the obvious convenience factor, DART is now the standard of care at Mayo for post-TORS HPV+ oropharyngeal cancer without ECE or pN2 disease, but don’t take our word for it—take a listen to how Dr. Ma breaks it all down. | Ma, ASTRO 2021