By Jennifer Jang, MHS, ASTRO Communications
David Sher, MD, MPH, FASTRO, University of Texas Southwestern Medical Center, opened his talk with the following question: Rethinking Elective Nodal Irradiation – Is Dogma our Friend or Foe? He subsequently provided a sweeping overview of updates on clinical trial data, examining a decreased elective radiation dose and volume for both HPV related and unrelated cancers.
Laying the groundwork for discussion, Dr. Sher defined the two basic targets in radiation oncology: gross disease (that which is seen on PET scans) and microscopic disease which is treated electively. And consequently, there are two basic elective targets around the primary tumor and neck volumes termed elective nodal irradiation, or ENI.
Acknowledging the range of specialists in the room, Dr. Sher reminded the audience of reasons everyone should care:
Dr. Sher emphasized that when de-escalation is the option under investigation, what is really being considered is minimizing the toxicity of H&N radiotherapy, in areas like swallowing, xerostomia and the impact on skin and soft tissue.
When rewinding to review the history of ENI doses, disentangling dose and volume is important. The common thought is that because an area in the neck is at higher risk of occult disease, then it needs a higher dose, when in fact, treating a nodal station is a function of probability. The dose rather is a function of radiosensitivity and volume.
Looking at ENI dose, Dr. Sher hearkened back to the ASTRO 1982 keynote address of Gilbert Fletcher, MD, a “titan of doses,” who stated that the basic concept for irradiation has to be for two parameters: 1) the density of infestation, that is, how much microscopic disease there is, and 2) a measure of hypoxia due to scar tissue and edema. The doses have not changed essentially for 50 years, and Dr. Sher cited multiple studies assessing classic ENI dosing, including RTOG 9003, all the way to the ARTSCAN trial.
Then came IMRT, where previously, H&N radiotherapy treated patients with sequential treatments, IMRT moved to a simultaneous integrated boost (SIB) approach. Dr. Sher cited multiple studies that showed how IMRT can contribute to a rapid ENI dose creep. The reality is that elective failures are rare, and microscopic volume matters. The pre-treatment size of the recurrent lymph node was strongly related to recurrence. In-field failures are the dominant pattern of recurrence. Solitary elective neck failures are rare, but when they happen, are salvageable and almost always come in pre-existing nodes. The field moved quickly to de-escalation in HPV-positive disease, with ENI ripe for de-escalation.
Dr. Sher shared several prospective trials, along with numerous retrospective studies, and gave a balanced overview of the case for de-escalation along with the accompanying criticism. The conclusions he derived are that both prospective and retrospective studies have demonstrated a low risk of elective nodal failure with de-escalation, and that dose reduction is often associated with an improved quality of life thanks to less severe side effects (such as less severe speech problems or better tolerance of treatment). A third RCT is pending but is anticipated to confirm that 40 Gy ENI should be considered a standard dose. De-escalation provides the space to modulate dose as needed, and Dr. Sher’s overall sentiment is that we can keep improving.
ENI volumes generally follow a very standard approach, and nodal spread is typically contiguous, especially in oropharynx and larynx cancer. Here, Dr. Sher reviewed prospective trials, followed by multiple studies where results recapitulated making the case for de-escalation. Given the burden on patients, Dr. Sher extrapolated his exploration to even bolder territory, posing the notion of omitting ENI entirely. After all, lung cancer and lymphoma have moved to involved node radiotherapy, what would happen if for head and neck cancers, only involved and “suspicious” nodes were treated?
The INRT-AIR Trial study was a phase II study of involved node RT. Nodes were identified by size, contrast-enhancement, PET-CT and AI. The AI model produced malignancy probability, and when greater than 50%, the node was considered positive. Although a small study, the implications for toxicity showed that this approach allowed for superior dosimetry, favorable swallowing and other patient-reported outcomes, to name a few. For oncology, the implications are that de-escalation could allow for more intensive treatment (both novel and standard systemic therapy) and immunotherapy.
After surveying additional studies, Dr. Sher derived multiple conclusions: “standard” ENI delivers substantial integral dose, with implications to key normal tissues; strategies that substantially reduce ENI dose have randomized data supporting them and that in fact, patients are being over-treated and quality of life can take less of a burden; and that volume reduction requires more research but holds further promise to the lowest possible ENI dose.
“A volume reduction approach is extremely exciting,” said Dr. Sher. “I am hopeful that a few more years of research will contribute to more creative ways of safely reducing dose to neck.”
He acknowledged that these findings were helped in large part by working with other physicians, physicists, and that ultimately, the patients are the ones bearing the risk, and upholding their quality of life is what drives the research.
Published February 21, 2026
