Episode 162: Head and Neck Cancer Series, Pt. 4 – Discussion with Radiation Oncology
This week the Head and Neck series turns to radiation oncology, with guest Dr. David Palma, a Professor and Radiation Oncologist at the Verspeeten Family Cancer Centre and professor at the Schulich School of Medicine and Dentistry, Western University (London, Ontario). A clinician-scientist who splits his time between clinical-trials research and treating head and neck and lung cancers, David walks us through how radiation actually works and gets planned, the de-escalation question, PET after treatment, larynx preservation, re-irradiation, oligometastatic disease, and the proton-versus-photon debate - all with some of the best analogies we've had on the show.
This episode is sponsored by Primum! To learn more, sign up for your free account, and to ask questions to Primum experts, click here!
Our framing case: a 58-year-old with locally advanced, p16-positive oropharyngeal squamous cell carcinoma, referred for definitive concurrent chemoradiation.
When a new head and neck patient is referred to you, what should already be in place (imaging, dental, blood work) so you can start planning?
David's center runs an integrated intake clinic where a radiation oncologist and a surgeon see new consults together (about 10 a morning), examine the patient, and build the plan as a group..
To be seen, a patient needs pathology and basic imaging (a CT neck or MR neck). Everything else, namely PET, blood work, dentistry, audiology, speech-language pathology, dietitian, gets ordered from there when the patient is heading down the radiation route.
The supportive services can make the difference between life and death. His example: a free home-hydration program where a nurse gives a liter of IV fluid at home each night when patients are struggling, which likely prevents feeding tubes and admissions.
Practical message for referrers: mostly you just need the CT and the pathology (and ENT is often getting the pathology anyway); don't over-worry about ordering the rest.
How do you counsel a patient about radiation? What is that simulation mask?
His framing analogy: radiation is like 300 weak flashlights pointed from different angles, each harmless alone, but where they converge on the tumor it gets "really, really bright." The side effects are "a sunburn, inside and out."
Immobilization: a warmed plastic mesh mask is molded to the face and bolted to the table, hardening over 10–15 minutes, so the patient can't move during treatment.
On the planning CT (done over about a week), the physician contours the tumor, the elective nodal levels to treat at lower dose, and the organs at risk to avoid (parotids, submandibular glands, pharyngeal constrictors, eyes, lenses, optic nerves, brain, brainstem). Much of the organ-at-risk contouring is now done by AI auto-contouring, and a dosimetrist then designs the plan over a couple of days.
Day to day: ~20–30 minutes in the department, mask on, an invisible beam you don't feel, then home, followed by weekly visits to manage mucositis, dermatitis, and xerostomia.
What exactly is IMRT, and does the data show it improves outcomes?
IMRT (intensity-modulated radiation therapy) is a more sophisticated flashlight.
Imagine one flashlight beam divided into a hundred-by-hundred grid of tiny lights you can switch on individually and rotate around the patient, so you can sculpt the dose point by point.
When David trained in the early 2000s, radiation was "a beam from each side" that blasted through the parotids, oral cavity, and salivary glands. IMRT is far more conformal, sparing the parotids and submandibular glands.
The payoff is real: in randomized trials, IMRT reduces toxicity. Feeding-tube rates that used to be near-universal for concurrent chemoradiation are now around 25% at his center, admission rates ~5%, with treatment-related mortality down as well.
What are the basics of dose and fractionation? Where does altered fractionation fit?
The analogy: fractionation is like putting weed-killer on a dandelion - dump it all at once and you kill the dandelion but poison the whole lawn (and yourself); spread it too thin over a year and the weed regrows between doses. Radiation aims for the sweet spot that hits the tumor while letting normal cells recover between fractions. This is complicated in head and neck cancer because the tumor grows fast and can repopulate if treatment drags on.
The standard for most head and neck cancers is 70 Gy in 35 fractions: five fractions a week over seven weeks. Doses can vary by a few percent with similar efficacy (like 900 vs 1100 mg of an antibiotic).
On altered fractionation, the MARCH meta-analysis (Lacas et al., Lancet Oncol 2017) showed it improves locoregional control with a modest survival benefit, with hyperfractionation (twice-daily) the most effective. In the 2000s, twice-daily and six-fractions-a-week looked similar so most centers adopted the easier six-per-week; with mature data, twice-daily is better for tumor control/survival, but it's onerous (patients waiting 6–8 hours between treatments), so many centers don't use it.
The bigger point: concurrent chemotherapy largely obviates the need for altered fractionation. One strategy is to shorten radiation to six weeks and drop from three cycles to two cycles of high-dose cisplatin. On the cisplatin schedule itself, David favors weekly cisplatin (40 mg/m²) — non-inferior to q3-weekly 100 mg/m² in the Japanese JCOG 1008 trial in the post-op setting — and predicts weekly 40 will eventually win in the definitive setting too (a small dose "on board the whole time" as a radiosensitizer).
HPV-positive patients do so well so can we de-escalate, with less or shorter radiation?
This is "the hottest topic in head and neck cancer." David flags a candid possible bias: these patients are often younger and higher-SES, and the field may over-focus on the patients "most like us."
Why it matters: HPV-associated oropharyngeal cancer is highly curable (especially in non-smokers), and these young survivors face decades of life during which treatment effects on the face, voice, breathing, eating, and social life dominate. He notes quality-of-life scales miss the small things (the "double swallow," whether you can eat at a restaurant).
The trade-off is genuinely hard to counsel: would you accept, say, 70 Gy with a 95% cure rate versus 60 Gy with a 90% cure rate and better swallowing? Most patients (and clinicians) find that a very difficult number to weigh.
The definitive de-escalation attempt is NRG-HN005 (NCT03952585): a three-arm trial of 70 Gy + cisplatin (control) versus 60 Gy + cisplatin versus 60 Gy + nivolumab. It was stopped at futility: the control arm reached a remarkable 2-year PFS of ~98%, and dropping to 60 Gy cost roughly 8 points of PFS (down to ~88–90%), even though overall survival looked similar and swallowing outcomes aren't yet reported. So most centers are not de-escalating outside a trial, and 70 Gy remains standard.
The provocative frontier: biologically-selected de-escalation to as low as 30 Gy for non-hypoxic tumors (see the F-MISO discussion below). David is hopeful that in ~5 years de-escalation will be guided by PET, by lower dose, or both.
How do you use the post-treatment PET/CT, and how does p16 status change your thinking?
A provocative reframe: in HPV-positive disease, a "test" that just says "no recurrence" every time has a ~90% negative predictive value, because ~90% are cured (his Homer-Simpson-bird analogy). The problem is that positive PETs are usually wrong, i.e., the positive predictive value is poor.
Why that matters: a false-positive PET can send someone to a neck dissection in a radiated neck, with real morbidity (chronic pain, shoulder dysfunction). So PET-positivity must be acted on cautiously.
His center's approach: a plain CT at 3 months first (tumors need time to regress). If all nodes are < 1 cm short-axis, no further imaging; if > 1 cm, get a PET. Positive PETs get an FNA first, and in HPV-positive patients with any uncertainty they favor close observation over neck dissection (primary/residual failure risk is ~5% or less). Of ~500 multidisciplinary consults a year, only about five go on to a post-chemoradiation neck dissection.
On the horizon: F-MISO (¹⁸F-fluoromisonidazole) PET images tumor hypoxia. Groundbreaking work from Nancy Lee's team at Memorial Sloan Kettering (with Jillian Tsai), the 30 ROC approach (NCT03323463), suggests patients with no hypoxia before/during treatment can be cured with just 30 Gy plus chemo. Now moving toward phase 3 and FDA consideration; not yet widely available, but potentially a game-changer for de-escalation.
Which larynx patient goes to chemoradiation versus surgery?
Start with what the larynx does: talk, breathe (pass air), and protect the airway during swallowing. If a patient is failing those functions, the larynx may not be preservable.
For borderline patients, the downstream matters: good lungs can tolerate some aspiration (lean toward preservation); poor lungs argue against it. The integrated clinic with the surgeon helps give balanced, non-competitive advice (radonc and surgeon are "adjacent, but not doing the same thing").
Rules of thumb: a T4 laryngeal cancer through the cartilage classically goes to laryngectomy, though a small T4 with a good functioning voice box might still attempt preservation; a T2–T3 with poor function may not be preservable. And in patients over ~70, some RCTs show no benefit from chemotherapy, which changes whether a true preservation option even exists. This complements the surgical episode's discussion of RTOG 91-11.
If laryngectomy is needed, SLPs demystify it early: patients can phonate with an electrolarynx, a tracheoesophageal puncture (TEP), or esophageal (burping) speech. The overarching principle again: fewer modalities are better. Avoid triple-modality therapy, which usually adds toxicity without improving cure.
Is there a role for re-irradiation at recurrence, and how do you think about timing?
Yes, but exhaust other options firstL surgery if possible, sometimes immunotherapy to buy time because you often "only get to play the radiation card once."
A six-month interval is roughly the minimum, and the shorter the interval, the worse both tumor control and toxicity.
Technically, they treat smaller volumes (target plus a setup margin, not the big elective fields), sometimes use a twice-daily schedule to reduce late effects, and in selected cases use SBRT (stereotactic body radiotherapy) over about a week, offered carefully when there's no other option.
For patients who have oligometastatic disease, should these head and neck patients be radiated?
The concept is old (the term "oligometastatic" was coined by Hellman and Weichselbaum ~30 years ago; a 1960s monograph already noted "the chance of cure exists, but it's small").
David's SABR-COMET trial (Palma et al., Lancet 2019), a randomized phase 2 across tumor types, found that ablating oligometastases improved survival, though most patients still eventually recurred. Head-and-neck-specific oligometastatic trials have struggled: an ECOG head and neck RCT and an esophagus trial both closed for poor accrual (open-label radiation trials with no placebo are hard to accrue).
Practical stance: for low-risk ablation (e.g., two lung mets with a well-controlled primary), it's probably worthwhile; if the treatment is risky or the disease is pacing quickly, maybe not. A corollary: aggressively treating the primary in metastatic disease helps in nasopharynx (full-dose chemoradiation improves survival even with mets) and some other sites like lung.
Protons versus photons: Worth it, or overhyped?
His honest take: "for all the hype, it probably doesn't matter too much." Photons are x-rays/gamma rays that pass through the body; protons are like a bowling ball that stops at the tumor — appealing, except there's uncertainty about exactly where it stops, and anatomy changes like weight loss can push the stopping point to the wrong place.
Two head and neck RCTs now conflict: the MD Anderson trial (Frank et al., Lancet 2025) found IMPT non-inferior for PFS with an OS benefit and less high-grade toxicity, while the UK TORPEdO trial (Lancet 2026) was negative — similar QoL, feeding-tube dependence, local control, and OS. One hypothesis for the difference: the US trial re-planned protons quickly as patients lost weight, whereas the UK trial re-planned less often (proton plans "get hot" with weight loss).
The other axis is cost and values — protons are expensive, and how you weigh a modest quality-of-life gain against a patient "mortgaging their house" differs by country and health system. His bottom line: if the price is similar, go with protons at an experienced high-volume center; if it means a generational financial hit, be very thoughtful. Outside head and neck, protons haven't been a home run (a large prostate trial showed no difference).
Key take-aways
Multidisciplinary, integrated care (radonc + surgeon seeing patients together) and supportive services — dental, SLP, dietitian, hydration — are central, not peripheral.
Standard definitive dose is 70 Gy in 35 fractions; IMRT reduces toxicity (parotid sparing, fewer feeding tubes) in RCTs.
Altered fractionation (MARCH) helps modestly, but concurrent chemo largely replaces the need for it; weekly cisplatin 40 mg/m² is favored and may become the definitive-setting standard (JCOG 1008).
De-escalation isn't ready for routine use: NRG-HN005 stopped at futility with a ~98% control-arm PFS; 70 Gy remains standard. Hypoxia-guided 30 Gy (F-MISO / 30 ROC) is the exciting frontier.
Post-treatment PET in HPV+ disease has a poor positive predictive value — CT at 3 months, PET only for nodes > 1 cm, FNA before acting, and favor observation over reflexive neck dissection.
Larynx: preserve if the larynx is functional; the SLP is essential; avoid triple-modality therapy.
Re-irradiation: exhaust other options, ≥ 6-month interval, smaller volumes, selective SBRT.
Oligometastatic disease (SABR-COMET): benefits selected patients; treating the primary aggressively helps in nasopharynx and some other sites.
Protons vs photons: conflicting RCTs (MD Anderson positive, TORPEdO negative); reasonable if similarly priced at an experienced center — patients aren't getting substandard care with photons.
References
https://pubmed.ncbi.nlm.nih.gov/28757375/ — Lacas B, et al. (MARCH) Role of radiotherapy fractionation in head and neck cancers: an updated meta-analysis. Lancet Oncol. 2017;18(9):1221–1237.
https://ascopubs.org/doi/10.1200/JCO.21.01293 — Kiyota N, et al. (JCOG 1008) Weekly cisplatin plus radiation for postoperative head and neck cancer. J Clin Oncol. 2022;40(18):1980–1990.
https://clinicaltrials.gov/study/NCT03952585 — NRG-HN005: De-intensified radiation with cisplatin or nivolumab in early-stage, HPV-positive, non-smoking-associated oropharyngeal cancer (phase II/III; halted at futility, reported ASTRO 2024).
https://clinicaltrials.gov/study/NCT03323463 — "30 ROC": Major de-escalation to 30 Gy for select HPV-associated oropharyngeal carcinoma, guided by ¹⁸F-FMISO PET hypoxia imaging (Lee et al., Memorial Sloan Kettering).
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://pubmed.ncbi.nlm.nih.gov/30982687/ — Palma DA, et al. (SABR-COMET) Stereotactic ablative radiotherapy versus standard of care palliative treatment in oligometastatic cancers: a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051–2058.
https://doi.org/10.1016/S0140-6736(25)01962-2 — Frank SJ, et al. Proton versus photon radiotherapy for oropharyngeal cancer in the USA: a multicentre, randomised, non-inferiority phase 3 trial. Lancet. 2025.
https://doi.org/10.1016/S0140-6736(26)00314-4 — (TORPEdO) Proton beam therapy for oropharyngeal cancer: a phase 3, randomised controlled trial. Lancet. 2026.
Regimen reference (HemOnc.org): Concurrent cisplatin + RT (definitive 70 Gy with cisplatin; includes weekly 40 mg/m² and q3-weekly 100 mg/m² variants).
About our guest:
David Palma, MD, MSc, PhD is a Professor and Radiation Oncologist at Verspeeten Family Cancer Centre and professor at the Schulich School of Medicine and Dentistry, Western University. He specializes in the treatment of thoracic cancers, head and neck cancers, and oligometastatic disease.
BSc: Queen’s University (Canada)
MD: University of Western Ontario (Canada)
MSc: Master’s Degree in Epidemiology from the Harvard School of Public Health
PhD: from the VU University Medical Center (Netherlands)
Residency: University of British Columbia
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: Ronak Mistry
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
