Episode 160: Head and Neck Cancer Series, Pt. 3 – Discussion with ENT
Throughout this series, we have discussed how multidisciplinary the management of head and neck cancer is and the critical role that our surgical colleagues play in the management of this disease. This week, we welcome Dr. Michael Topf, Associate Professor for Associate Professor of Otolaryngology-Head and Neck Surgery at Vanderbilt University Medical Center to our show to share with us how he determines which patients are appropriate for surgery, what his approach is, and so much more. It’s rare that we get insights into the factors that our surgery colleagues think about when determining surgical candidacy and surgical approaches and so get ready for an incredibly informative conversation! Another high yield episode you do not to miss!
This episode is sponsored by Primum! To learn more, sign up for your free account, and to ask questions to Primum experts, click here!
Oral cavity
Our framing case: a 58-year-old man with a heavy smoking and alcohol history, diagnosed with a floor-of-mouth / ventral tongue squamous cell carcinoma, with imaging concern for cortical erosion of the mandible, clinically node-negative (a clinical T4N0).
A patient arrives in your ENT clinic with a tongue lesion or a neck mass — how do you approach that first visit and the initial workup?
Everything in head and neck is anatomic-subsite specific — the exam, the biopsy plan, and the reconstruction all follow from where the tumor is.
For a floor-of-mouth primary like this, there may be no node to FNA; the work is characterizing the primary and its local extension on exam and imaging.
With cortical erosion of the mandible, how do you decide between a marginal and a segmental mandibulectomy?
Even a little cortical erosion means you're into the marrow space — Dr. Topf's approach is a full-thickness segmental mandibulectomy, not a marginal one.
Marginal mandibulectomy is reserved for tumors abutting but not invading the cortex.
He's also thinking about posterior and ventral tongue extension, because that drives long-term function: a lesion along the anterior alveolar ridge is a very different functional outcome than one requiring a hemi/anterior glossectomy (articulation, communication, eating and drinking).
Reconstruction planning starts here too — assessing donor sites for free flaps (fibula from the leg, radial forearm, scapula) to "put the patient back together."
Help us picture margins in the oral cavity — what counts as adequate, and is there a role for intraoperative frozen section?
In 2026, a positive margin is generally invasive carcinoma at the ink; close is tumor up to 5 mm; clear is greater than 5 mm (the 5 mm cutoff is debated).
Pathology typically reports the closest margin by distance (e.g., "closest margin, anterior soft tissue, 4 mm").
Important caveat: HPV-positive oropharynx cancer uses a completely different margin definition — don't apply oral-cavity rules there.
A close margin is traditionally an indication for adjuvant radiation, though a 4 mm margin with no other adverse features is a tumor-board conversation; close margin plus perineural invasion or other adverse features pushes toward adjuvant RT.
The hard triggers for adding chemotherapy to adjuvant radiation — extranodal extension and/or positive margins — come from two landmark 1990s-era trials:RTOG 9501 (Cooper et al., NEJM 2004) andEORTC 22931 (Bernier et al., NEJM 2004), which together defineadjuvant platinum-based chemoradiation for high-risk pathology.
Our patient is clinically node-negative — who gets an elective neck dissection, and is there a role for sentinel lymph node biopsy like in breast cancer?
The practice-changing trial isD'Cruz et al. from Tata Memorial (NEJM 2015): elective neck dissection conferred an overall survival benefit versus watchful waiting. Note the important detail — that trial enrolled clinical T1–T2N0 oral cavity patients (not the T4N0 in our vignette).
For a midline T4N0 like our case, Dr. Topf does a bilateral elective neck dissection.
For a well-lateralized T1/T2N0 oral tongue cancer, depth of invasion guides the decision — the D'Cruz subset benefit appeared around 3 mm DOI, and Vanderbilt's internal data suggested improvement as early as 2 mm. His practice is to be aggressive about elective neck dissection in these patients.
He's a believer in sentinel lymph node biopsy but does it on trial —NRG-HN006 (NCT04333537), national PI Stephen Lai, a non-inferiority study of SLNB versus elective neck dissection, is open at Vanderbilt.
Perioperative immunotherapy is the big new development — which patient is the right one for neoadjuvant pembrolizumab?
The advance isperioperative pembrolizumab fromKEYNOTE-689 (Uppaluri et al., NEJM 2025) — the first practice-changing trial in head and neck surgery in a couple of decades. It showed an event-free survival benefit (not yet an OS benefit), with much of the improvement in distant metastases, and about 10% of patients had high-risk pathology needing adjuvant platinum-based therapy.
Context for why this matters: earlier swings — cetuximab substitution (De-ESCALaTE andRTOG 1016) and immunotherapy added to definitive chemoradiation — have largely not panned out, so a positive perioperative trial is a genuine shift.
Patient selection (Dr. Topf's practice): inclusion is roughly stage III–IVA, mainly HPV-negative disease — so oral cavity and larynx. He repeats biopsies to obtain a PD-L1 CPS ≥ 1, and observes more robust pathologic responses at higher CPS (perhaps >10, even >20). His first Vanderbilt case — a CPS-5, cT4N0 larynx cancer — had a complete pathologic response after two cycles of pembrolizumab.
Practical modifiers: overall performance status, the airway (a bulky supraglottic tumor may need a trach to get through neoadjuvant therapy — sometimes going straight to laryngectomy is safer), and the social situation. On exploratory subset analysis, T4 tumors appeared to benefit less, and T4 oral cavity cancers are the ones that can become unresectable during the neoadjuvant window — a real concern.
Complementary data point:NIVOPOSTOP / GORTEC 2018-01 (ASCO 2025) showedpostoperative nivolumab added to adjuvant cisplatin-radiation improves disease-free survival in high-risk resected disease — an adjuvant-only IO strategy alongside the perioperative pembrolizumab approach.
Oropharynx
Case: a p16-positive tonsil primary, small T stage, with limited ipsilateral nodal disease — the kind of patient who could go to chemoradiation or to surgery.
Traditional open oropharynx surgery was morbid. What is transoral robotic surgery (TORS), and which patients are best served by it?
Open approaches to the oropharynx carried significant morbidity, which is why the disease — even early-stage — was managed non-surgically with chemoradiation for decades.
For HPV-associated, low-volume disease, survival is equivalent between upfront surgery with pathology-directed adjuvant therapy and definitive radiation with or without chemotherapy — with a 2–3 year disease-free survival greater than 92%. These patients do very well, so the decision hinges on toxicity profile and shared decision-making (surgery is toxic; radiation and chemo are toxic).
Dr. Topf frames surgery honestly as "a bit of a dice roll" — you can't reliably predict nodal involvement or extranodal extension before you have the pathology.
The technology: the da Vinci robot was FDA-approved for oropharyngeal TORS (T1–T2) in 2009 (the Si system), and the single-port (SP) robot was approved in 2019, which most surgeons now use. The primary tumor is removed transorally; the lymph nodes are removed via an open neck dissection; and surgeons often perform transcervical ligation of external carotid artery branches during the neck dissection to reduce the risk of major post-operative bleeding.
If final pathology shows extranodal extension or positive margins, do you still add chemoradiation?
Yes — the same RTOG 9501 / EORTC 22931 logic applies.
But there's an important nuance: retrospective data suggest ENE may be a weaker adverse factor in HPV-positive disease, and fewer than ~10% of patients on those original trials would have had HPV-positive oropharynx cancer.
The phase 3PATHOS trial (NCT02215265) (largely UK) is testing whether platinum chemotherapy is actually needed for ENE in this population. Dr. Topf's hypothesis: HPV-positive ENE patients do worse, but adding platinum may not improve their outcomes — a chance to spare a third modality.
What features make you steer a patient away from upfront surgery toward definitive chemoradiation?
Tonsil: significant soft-palate extension (risk of velopharyngeal insufficiency), a fixed tumor (trouble getting an adequate deep margin on the superior constrictor), or a retropharyngeal internal carotid artery.
Base of tongue: not all T2–T3 tumors are equal — an exophytic tumor on a small stalk (even ~4 cm) may do well with surgery, whereas an endophytic tumor with significant anterior extension into the tongue base musculature is functionally problematic.
The overarching principle: avoid triple-modality therapy. Gross radiographic ENE or two or more clinically involved nodes will often steer him toward definitive chemoradiation, since those patients will likely need chemoradiation in the adjuvant setting anyway.
Larynx
We're taught that organ preservation is the priority, with total laryngectomy as salvage. Is that generally right?
At most US centers, yes — for early and non-T4 advanced larynx cancer, the goal is organ preservation.
The critical addition surgeons bring: understanding laryngeal function. If a patient already has a tracheostomy and feeding tube and is aspirating on formal speech-language pathology evaluation, chemoradiation has a high chance of cure but is unlikely to restore a non-functional larynx.
So a non-functional larynx — even at T3 — is a scenario where Dr. Topf leans toward upfront surgery ± perioperative pembrolizumab, followed by adjuvant therapy based on pathology. The speech-language pathologist is an essential member of the team here.
This complements the classic organ-preservation data (RTOG 91-11 and theVA Larynx trial) — no overall survival penalty for preservation because you can salvage with laryngectomy — but those trials don't capture the function and quality-of-life dimension that surgeons and SLPs weigh at the bedside.
Recurrence
What about an isolated recurrence in the neck after definitive chemoradiation — is there a role for surgery, or is this systemic-therapy territory?
In head and neck cancer, you often "only get to play the radiation card once," which makes salvage decisions hard. A resectable persistent or recurrent node generally prompts consideration of surgery.
Biology matters: an HPV-negative nodal recurrence or persistence is an ominous sign. For HPV-positive disease, the key question is how far out from treatment the patient is — much like rectal cancer, they may still be responding 3–6 months after finishing therapy.
Dr. Topf is deliberate about not rushing to a salvage neck dissection, given the morbidity of operating in a previously radiated neck.
A practical pearl: PET/CT at three months post-treatment is a poor test in HPV-positive patients (he cites a positive predictive value around 35%). He increasingly incorporates circulating tumor DNA (HPV ctDNA) for the indeterminate nodal-response patient — head and neck is a bit behind other solid tumors here, but adoption is growing.
And for an HPV-negative patient with a PET-positive node after treatment — how do you approach that?
Biology drives the timeline: HPV-positive nodes involute slowly, whereas HPV-negative nodes involute faster — so a persistently PET-avid node in HPV-negative disease is more actionable and gets addressed sooner rather than watched.
The options on the table are FNA of the node, surgical resection (salvage neck dissection), or close observation — the choice depends on the clinical picture and multidisciplinary input.
What makes operating in previously radiated tissue so challenging?
The extent of disease is harder to define in a radiated, distorted field.
Wound healing is impaired, making complications more likely.
The biology is different — this is persistent or recurrent disease, so a surgical salvage is often the patient's last chance at cure, which raises the stakes of every decision.
An active trial in this space is NEOPOLIS (NRG-HN016) — aphase II study of neoadjuvant chemotherapy versus chemo-immunotherapy versus standard of care before salvage surgery in recurrent/persistent, PD-L1–enriched head and neck squamous cell carcinoma.
Which specialists are critical to a robust head and neck multidisciplinary team — and what should centers without ready access to all of them keep in mind?
Surgical oncology, medical oncology, and radiation oncology — the three treating modalities.
Speech-language pathology (SLP) — essential for swallowing and voice, and (as in the larynx discussion) for defining laryngeal function.
Nutrition — these patients are at high risk for weight loss and treatment-related swallowing difficulty.
Social work — the social situation frequently shapes what treatment is feasible and safe.
Physical medicine and rehabilitation (PM&R) — to preserve and restore quality of life through and after treatment.
The through-line of the whole episode: this is a disease genuinely managed by the whole team, and access to these members is part of what defines high-quality head and neck cancer care.
Key take-aways
Head and neck surgery is subsite-specific — the exam, resection, margins, and reconstruction all follow from anatomy.
Oral cavity: cortical erosion → segmental mandibulectomy; margins are positive at ink / close ≤5 mm / clear >5 mm; ENE and/or positive margins drive adjuvant chemoradiation (RTOG 9501, EORTC 22931).
cN0 oral cavity → elective neck dissection improves survival (D'Cruz 2015; trial population was T1–T2N0); sentinel node is promising and being tested in NRG-HN006.
Perioperative pembrolizumab (KEYNOTE-689) is the first major advance in decades for resectable, largely HPV-negative disease — select for CPS ≥ 1, performance status, and airway; watch the T4s.
Oropharynx: TORS offers equivalent survival to chemoradiation in low-volume HPV+ disease with excellent outcomes; choice is about toxicity. Avoid triple-modality therapy; PATHOS may let us spare chemo for ENE in HPV+ disease.
Larynx: organ preservation is the default, but a non-functional larynx shifts the calculus toward upfront surgery — the SLP is essential.
Recurrence: don't rush salvage; PET at 3 months is unreliable in HPV+ disease (PPV ~35%); HPV ctDNA is entering practice. HPV-negative nodes involute faster, so a persistently positive node is addressed sooner (FNA vs. salvage resection vs. observation).
Salvage in radiated tissue is hard — indistinct disease extent, impaired wound healing, and it's often the last chance at cure (see NEOPOLIS / NRG-HN016).
A robust team spans surgical, medical, and radiation oncology plus SLP, nutrition, social work, and PM&R — access to these members is part of the definition of quality care.
References
https://pubmed.ncbi.nlm.nih.gov/15128893/ — Cooper JS, et al. (RTOG 9501) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937–1944.
https://pubmed.ncbi.nlm.nih.gov/15128894/ — Bernier J, et al. (EORTC 22931) Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945–1952.
https://pubmed.ncbi.nlm.nih.gov/26027881/ — D'Cruz AK, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med. 2015;373(6):521–529.
https://clinicaltrials.gov/study/NCT04333537 — NRG-HN006: Randomized phase II/III trial of sentinel lymph node biopsy versus elective neck dissection for early-stage oral cavity cancer (ongoing).
https://pubmed.ncbi.nlm.nih.gov/40532178/ — Uppaluri R, et al. (KEYNOTE-689) Neoadjuvant and adjuvant pembrolizumab in locally advanced head and neck cancer. N Engl J Med. 2025;393(1):37–50.
https://ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA2 — Bourhis J, et al. (NIVOPOSTOP / GORTEC 2018-01) Adjuvant nivolumab added to radio-chemotherapy in resected high-risk head and neck cancer. J Clin Oncol. 2025;43(suppl 17):LBA2.
https://pubmed.ncbi.nlm.nih.gov/30449623/ — Mehanna H, et al. (De-ESCALaTE HPV) Radiotherapy plus cisplatin or cetuximab in low-risk HPV-positive oropharyngeal cancer. Lancet. 2019;393(10166):51–60.
https://doi.org/10.1016/S0140-6736(18)32779-X — Gillison ML, et al. (NRG/RTOG 1016) Radiotherapy plus cetuximab or cisplatin in HPV-positive oropharyngeal cancer. Lancet. 2019;393(10166):40–50.
https://clinicaltrials.gov/study/NCT02215265 — PATHOS: Post-operative adjuvant treatment for HPV-positive tumours (ongoing phase 3 de-escalation trial).
https://pubmed.ncbi.nlm.nih.gov/14645636/ — Forastiere AA, et al. (RTOG 91-11) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349(22):2091–2098.
https://doi.org/10.1056/NEJM199106133242402 — Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in advanced laryngeal cancer. N Engl J Med. 1991;324(24):1685–1690.
Regimen references (HemOnc.org):Perioperative pembrolizumab ·Postoperative nivolumab + cisplatin + RT ·Adjuvant cisplatin + RT
About our guest:
Michael Topf, MD, MSCI is an Associate Professor of Otolaryngology-Head and Neck Surgery at Vanderbilt University Medical Center in Nashville, Tennessee. He completed his residency in ENT at Thomas Jefferson University Medical Center after which he went to FellowDoctor of Medicine - University of Rochester, 2014
Residency - Thomas Jefferson University Medical Center, 2019
Fellowship - Stanford University Medical Center, 2020
Master of Science in Clinical Investigation - Vanderbilt University, 2023
This episode is sponsored by Primum! To learn more, sign up for your free account, and to ask questions to Primum experts, click here!
The crew behind the magic:
Show outline: Vivek Patel
Production and hosts: Vivek Patel, Dan Hausrath, Ronak Mistry
Editing: Resonate Recordings
Shownotes: Assistance of Claude, reviewed and edited by Ronak Mistry
Graphics, social media management: Ronak Mistry
