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Have We Finally De-Escalated Conflicts? Treatment De-Escalation for HPV-Positive Oropharyngeal Cancer

November 18, 2021

This Saturday November 20th starting at 8AM CST to Sunday November 21st 2021 the Global Radiation Oncology Journal Club (#RadOnc #JC) will be discussing treatment de-escalation for head & neck cancer on Twitter.

We’ll be doing something a little different.

At #ASTRO21 last month, a phase 3 trial of head and neck cancer treatment de-escalation (MC1675 DART) struck chords with early results favoring less radiation treatment.  Although the final paper is pending, its phase 2 results have been out for a while.

We’ll review MC1273 in more detail then DART deeper into MC1675:

Ma, D.J., et al., Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus–Associated Oropharynx Squamous Cell Carcinoma. Journal of Clinical Oncology, 2019. 37(22): p. 1909-1918. 10.1200/JCO.19.00463

Thanks to the Journal of Clinical Oncology (JCO) for making it free to access here.

We’ll be kindly joined by lead author Dr. Daniel Ma (@DanielMaMD) and special guests.

We’ll also discuss related papers from the team including on its health economics1;  long-term results2 and early results of the phase 3 DART presented at #ASTRO21.3

For those newer to the de-escalation debate, a little background:

Rates of head & neck cancer are increasing worldwide while survival outcomes are improving. Especially for HPV+ tumors in oropharyngeal squamous cell cancer (OPSCC), survival and locoregional control is better than their HPV-negative counterparts. This has made HPV+ OPSCC a distinct target for new treatment regimens.

Standard treatment of OPSCC is either definitive radiation treatment combined with concurrent cisplatin over 7 weeks or surgery followed by 6 weeks of adjuvant radiation treatment.  Toxicity of both approaches is an issue – dry mouth, trouble swallowing, neuropathy, neck fibrosis, and osteoradionecrosis.

Together, this has suggested a wider therapeutic window of opportunity for treatment de-escalation to reduce the treatment toxicity without sacrificing cure rates for HPV+ OPSCC – through systemic, surgical, and/or radiation optimizations.

Systemics: NRG/RTOG 1016 compared cisplatin vs Cetuximab chemoradiation. It and others (De-Escalate & ARTSCAN 3) showed inferior results with the EGFR antibody.4 Multiple systemic induction trials have had positive signals, but only with phase 2 data (OPTIMA, Quarterback, & ECOG1308; with OPTIMA including reduced treatment volumes). Phase 3 randomized control trial (RCT) data including studies with immunotherapy are pending.

Surgery: the phase 2 RCT ORATOR2 compared primary dose-reduced chemoradiation against primary transoral surgery (TOS) and neck dissection. It stopped early due to surgical toxicity with results presented at #ASTRO21. 5 This was different than surgical toxicities in other trials.6

Radiation: Promising phase 2 data for de-escalated radiation dose (i.e. NRG HN002) has led to phase 3 trials that have not reported yet (i.e. HN005). Others are investigating proton treatment (MDACC).   

So far, the most promising de-escalation trials only provided phase II data, until recently. 

MC1273 was a phase II adjuvant study looking at ‘aggressive de-escalation’ with 30Gy (1.5Gy twice daily) over 2 weeks combined with docetaxel. Its results led to one of the first completed phase III de-escalation trials – MC1675 DART that compared it against standard 60Gy (2Gy once daily) over 6 weeks.  The results were recently presented at #ASTRO21. Shortly after, the adjuvant phase III ECOG-ACRIN (E3311) trial was also published. Both were positive.

So, can we finally apply de-escalated radiation treatment to head & neck cancer?

Join us for this #RadOnc #JC Twitter discussion:

Starting Saturday November 20th 2021 at 8AM CST until Sunday afternoon.

Guiding Topics will include:

T1. Background: Why is de-escalation important in head and neck cancer?  What are the most common de-escalation strategies?

T2. Methods: What methods did MC1273 use?  Was there a cost-analysis? How did this lead to the phase 3 DART study?

T3. Results/Discussion:
What were the results of MC1273?  What about DART?  How does this compare to other studies (i.e. E3311)? How do you treat HPV+ OPSCC in your practice and will these results change anything?

T4. #PatientsIncluded:  What is important for patients undergoing treatment for head & neck cancer?

T5. Conclusion/Next Steps:
What are the key takeaways from MC1273, DART, and de-escalation studies so far?  What more can be done to improve outcomes for head & neck cancer patients and your practice?


  • Guidelines on how to sign up & participate
  • Disclaimer for ways to keep #RadOnc #JC rewarding and professional. If you’re not ready, just lurk & tune in to the conversation.
  • Just don’t forget to include #RadOnc #JC tags in your tweets!

Suggestions? Leave a comment or tweet/DM us at @Rad_Nation.
And please join us this weekend!

Select References

1.         Waddle, M.R., et al., Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx. Int J Radiat Oncol Biol Phys, 2021. 110(2): p. 396-402.

2.         Ma, D.J., et al., Long-Term Results for MC1273, A Phase II Evaluation of De-Escalated Adjuvant Radiation Therapy for Human Papillomavirus Associated Oropharyngeal Squamous Cell Carcinoma (HPV+ OPSCC). International Journal of Radiation Oncology, Biology, Physics, 2021. 111(3): p. S61.

3.         Ma, D.J., MC1675, a Phase III Evaluation of De-Escalated Adjuvant Radiation Therapy (DART) vs. Standard Adjuvant Treatment for Human Papillomavirus Associated Oropharyngeal Squamous Cell Carcinoma. 2021 ASTRO Annual Meeting. Abstract LBA-1, 2021.

4.         Gillison, M.L., et al., Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. The Lancet, 2019. 393(10166): p. 40-50.

5.         Palma, D.A. and A.C. Nichols, A phase II randomized trial of treatment de-escalation for HPV associated oropharyngeal squamous cell carcinoma: radiotherapy vs. trans-oral surgery (ORATOR 2). Presented at: 2021 American Society for Radiation Oncology; October 24-27, 2021; Chicago IL. 2021. Abstract LBA-2.

6.         Ferris, R.L., et al., Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311). J Clin Oncol, 2021: p. Jco2101752.

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