HNSCC 6 wks->2(!)wks

[scarbrtj]

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Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus–Associated Oropharynx Squamous Cell Carcinoma

Ironic. Not long ago "aggressive" meant more, or additive, treatment. Now it means less treatment?
When a word begins to mean almost anything... it loses its meaning.
✔Easier
✔Less toxicity
✔Less cost
B.I.D. making the overall fraction number decrease "just" about 33%, yet still an improvement overall.
Who woulda thunk ~30 Gy could give ~90-95% LRC in HNSCC. Gilbert Fletcher had it (sort of) wrong. (Although it's known 30Gy chemoRT occasionally cures gross HPV-assoc dz.)

Of interest, and if you believe in radiobiological math, this suggests 1) HPV+ HNSCC is very radiosensitive, and 2) HPV+ HNSCC can be cured with 39 (low end)-42 (high end) Gy over 13-14 days. (See below.)

 

[evilbooyaa]

De-escalation looks great in a well-selected phase II population until they run it against the gold standard in a phase III and it completely falls on its face (see RTOG 1016).

With the results of 1016 out showing that MILD de-escalation is not safe, there is a zero percent chance that I am putting my patients at risk (specifically in H&N de-escalation) off-protocol without multi-institutional phase III data. The authors conclusion is sound in this regard and I look forward to their phase III trial.

Their inclusion criteria is extremely strict and is an extremely low-risk patient population to begin with. How many of these patients didn't need any adjuvant treatment? The TORS data argues that # of LNs requiring adjuvant RT is at a cut-off of 3 - 5. Is LVSI or PNI on its own an indication for adjuvant RT, let alone BID fractionated CRT?

 

[thecarbonionangle]

Dont feel good at all about “descalation” after 1016. Nrg002 will be interesting to watch as well, hopefully out soon.

At the end of day, i fear we may get too cute and mess up cure rates on very curable CANCER.

 

[TDDro]

Dont feel good at all about “descalation” after 1016. Nrg002 will be interesting to watch as well, hopefully out soon.

At the end of day, i fear we may get too cute and mess up cure rates on very curable CANCER.

I dunno if I'll ever understand the thinking behind 1016. There is HPV-driven and non-HPV driven HNSCC. The non-HPV-driven variety has increased EGFR, the HPV-driven does NOT. So why start a trial where you take away an active drug (cis) in the HPV-driven group and replace it with a drug there is no indication should work (Cetux)?

At the end of the day it was just an expensive way to see if you can do RT alone for HPV-OPSCC.

 

[deleted941485]

In the back of my head its more about pushing out the RT to inevitably make way for the new immunotherapy drug/indication. they are already running trials with GEJ tumors with immuno versus conv chemo. Won't be long before we see a trial with CRT vs IT (non inferiority of course) for these selct low risk HNC tumors who may not need RT, or CRT, or anything adjuvant for that matter.

 

[gmsquid]

Look at the paper. 60% of patients in their favorable cohort (non ECE) had old N0, N1 or N2a disease. Single node positive disease is a group we already consider observation for. How much does PNI or LVI add to these patients? The risk of LRR in this group is presumably low as it is. That left just over a dozen patients with N2b or N2c disease in that cohort, patients we have a stronger indication to treat. Not enough numbers to say anything substantial.

There unfavorable cohort had substantial LRR for p16 positive disease managed with trimodality therapy.

I think RT deescalation is probably fair at some point in p16 positive disease if the trials support it. Waiting for ECOG E3311 to prove it before I drop to 50 Gy after surgery, let alone 30.

Further, look back at the old Ang study (IJROBP 2001). Patients with 1 risk factor receiving 57.6 Gy had 90+% LRC. They were all likely p16 negative. Not surprising to see such high rates of LRC for p16+ disease with trimodality therapy.