Responsive design.

Top Line: Hypopharyngeal cancer is bad.

The Study: While definitive chemoradiation has become a mainstay for most locally-advanced head and neck cancers, its use for unselected hypopharyngeal primaries leads to high rates of salvage surgery, which in turn have very meh oncologic outcomes with serious wound complications being the norm. A commonly talked about alternative approach is the use of induction chemo, relying on the correlation between chemosensitivity and radiosensitivity to extrapolate which good responders should move forward with definitive radiation. The problem is, even with this approach, survival with a functioning larynx caps out at about 25%. This Chinese group asks a good follow-up question: wouldn’t response to radiation be a better indicator of radiosensitivity? Here is a look back at 423 patients with stage III-IV hypopharyngeal squamous cell carcinoma (SCC) who received either upfront surgery (n=144), upfront definitive chemoradiation (n=67), or a radiation response-adapted approach (n=212). This latter approach involved initiating chemoradiation with a pre-planned re-staging scan at 50Gy. If tumor response was ≥80%, the patient proceeded to a total of 70 Gy (n=166). Otherwise, radiation ceased and surgery was planned 4-6 weeks later (n=46). First up, definitive chemoradiation had a 5 year overall survival rate of 28% compared to 54% with upfront surgery and 53% with adaptive therapy. Second up, adaptive therapy achieved a significantly higher rate of surviving with a functioning larynx at 5 years with a rate of 41% compared to 34% with upfront surgery. To drive home this distinction, it’s important to note the proportion of patients deemed to need a total laryngectomy upfront was nearly double in the response-adapted group (88%) compared to surgery (45%)—remember, treatment wasn’t randomized. Finally, surgery after 50 Gy appeared not so terrible with a wound complication rate of 34% compared to 23% with upfront surgery. This all leaves us with a couple of things to ponder. The survival discrepancy between treatment strategies points to appropriate timing of surgery for nonresponders—either upfront and/or planned early versus upon apparent progression—as key. Second, trying radiation first with a low threshold for proceeding to surgery affords folks who would otherwise require a total laryngectomy a safe and meaningful chance of achieving organ preservation.

TBL: This retrospective study suggests a radiation response-adaptive therapy strategy for locally-advanced hypopharyngeal cancer may improve the chance for a long-term functioning larynx without compromising survival. | Luo, JAMA Netw Open 2022