How can my dad manage squamous cell carcinoma at age 48?

Question

Hello doctor,

My dad is 48 and has squamous cell carcinoma that started in his right cheek about six years ago. He had surgery back then, along with chemotherapy and radiation, and was cancer-free for a while, then it showed up in his chest, and he had surgery there, too. His PD-L1 was high, so they put him on Pembrolizumab (Keytruda).

Then a PET scan found something in his right collarbone that came back as cancer on biopsy. His local team did surgery on the collarbone and radiation, but now a new PET shows something at his sternum with an SUV of 14.3.

They added Paclitaxel (Taxol) and Carboplatin (Paraplatin) to the Pembrolizumab, and he has had two cycles. He is having a rough time tolerating it. We are looking for a second opinion on where things stand and what comes next.

Please advise.

Thank you.

Answer 1

Hello,

Welcome back to icliniq.com.

I understand your concern.

I saw him about five years ago, and I have reviewed everything since. He had T3N0 (tumor- node) squamous cell carcinoma of the right buccal mucosa, surgery, then weekly Cisplatin (Platinol) with postop radiation. He was NED (no evidence of disease), then chest disease showed up, got biopsied as squamous cell, and was surgically resected as T1N1.

Whether that was metastatic head and neck cancer or a new lung primary was never fully resolved. The local team leaned toward metastasis given the short disease-free interval and the pleural-based location, and I would still read it that way. PD-L1 (programmed death-ligand 1) was high, Pembrolizumab was started, and he looked NED clinically for a stretch.

The clavicle biopsy came back positive for squamous cell carcinoma; there was now measurable disease, and treatment was clearly indicated. His team went with surgical resection of the clavicle and radiation to the bed. Now the PET (positron emission tomography) shows a hypermetabolic destructive lesion at the right lateral manubrium, SUV (standardized uptake value) 14.3.

There is also a sub-centimetre right lower lobe nodule that is PET-negative. The liquid biopsy showed RAD54L, CDKN2A/B, NOTCH1, and TP53 mutations, but no elevated tumour fraction was detected, and these differ from the earlier tissue sequencing. That blood-tissue discordance has been reported, and some of it is likely assay-related. Nothing in the current sequencing points to a more targetable mutation.

Adding Paclitaxel (Taxol) and Carboplatin (Paraplatin) to the Pembrolizumab was a defensible call. I would not write off single-agent Pembrolizumab as having failed; the course was short, and pseudoprogression is possible, but the imaging shows persistent disease, and the timeline is aggressive. He is about a month into the combination.

I would keep going another one to two months and rescan. If he is stable or responding, continue the combination. If he progresses off protocol, a Cetuximab (Erbitux)-based regimen is where I would look, and clinical trials should be in that conversation too.

On tolerance, if he keeps responding but is struggling with the every-three-week schedule, switching Paclitaxel and Carboplatin to weekly dosing could make it more manageable. The target would be six cycles of chemotherapy with the checkpoint inhibitor, though progression or toxicity could shift that.

If he is still responding at that point, transitioning to maintenance Pembrolizumab alone is a reasonable next move. If he progresses, I would push for a tissue biopsy with repeat NGS (next-generation sequencing) at that point, particularly given the blood-tissue discordance we are already seeing.

It would also be useful to compare the NGS from the original oral cavity tumor to the lung specimen, which could settle whether this is all metastatic head and neck cancer, which matters for clinical trial eligibility down the road.

I hope this helps you understand the situation better.

Thank you.