What are your top takeaways in Head & Neck Cancers from ASTRO 2024?

Here are my impressions from 3 interesting presentations related to head and neck cancer:

1. S2-S3, Yom et al., Interim futility results of NRG-HN005 a randomized phase II/III non-inferiority trial for non-smoking p16+ oropharyngeal ca. The study tested non-inferiority regarding DFS of two de-escalated regimens vs the standard 70 Gy RT + cisplatin (arm 1). The de-escalated regimens were 60 Gy over 6 weeks plus cisplatin (arm 2) and 60 Gy over 5 weeks plus nivolumab (arm 3). Interim futility analyses after median f/u of 1.1 and 1,7 years, both showed higher HR for the de-escalated arms compared with the standard arm. Two-year DFS in Arm 1 was 98. DFS was statistically significantly lower for Arm 2 and almost statistically significantly lower in Arm 3. The conclusion was that taking into account the highly favorable outcome in Arm 1, non-inferiority of the de-escalated arms could not be established and a phase III study will not proceed.
   The importance of these data is the realization that de-escalation of therapy in p16+ good prognosis OPC should not be done outside of a well-designed clinical trial. The important next step in related clinical research is to identify pre or during therapy the minority of the patients who are likely to fail and who should be excluded from de-escalation. Many studies are currently looking at this issue and we need to wait for these studies to mature.
   
   
2. The group from Sun Yat-Sen University in South China (S8: Ma J et al, “Radiotherapy target volume delineation based on post-induction chemotherapy gross tumor volume vs pre-induction volume for locoregionally advanced NPC: Open-label, non-inferiority, randomized phase III trial”) presented a phase III study in patients with local-regional NPC undergoing induction chemotherapy comparing defining the GTV from pre-induction or from post-induction imaging. They found similar 3-year outcomes for both groups, while the group treated to the post-induction GTV enjoyed less toxicity and better QOL.
   Using the smaller, post-induction GTV, rather than the induction one, is generally not recommended in HNC. However, these results make clinical sense in EBV-related non-keratinizing endemic NPC which is highly responsive locally to chemo-RT. Importantly, it is advised to not use this method in non-endemic, EBV negative NPC, as Caucasian NPC patients demonstrate a high rate of LR failure after therapy (see Stenmark et al., PMID 24521676).
   
   
3. S121 (Lukens JN et al. Phase II study of radiation volume and dose de-intensification following TORS and neck dissection for p16+ OPC): For HPV+, T1-2 N+ undergoing TORS with negative margins and no PNI/LVI, omitting RT to the primary site (while treating neck nodes) resulted in this study in no local recurrences, suggested that the primary may be omitted from the RT targets in such cases. These data agree with other recently published data. It is esp. relevant in BOT cancers where adjuvant RT of the primary is expected to result in substantial toxicity.