Bottom line: Patients with head and neck cancer who received chemotherapy in addition to immunotherapy before surgery had a significantly reduced tumor size at the time of operation than patients who received immunotherapy alone.

Why this study is unique: To our knowledge, this is the first study using real-world data to compare immunotherapy alone to combined immunotherapy with chemotherapy before surgery for head and neck cancer patients. While some experts have questioned whether adding chemotherapy improves the effects of immunotherapy, this study found that the combination led to a much greater reduction in tumor size and viability by the time of surgery.

Why this study is important: Earlier work from our researchers suggested that this combined approach can be administered safely in appropriately selected patients. This study further shows that not only is this approach safe, but it produces a stronger preoperative response to their cancer.

How the research was conducted: The study analyzed care provided to patients at the Mount Sinai Health System over a two-year period. Researchers reviewed the records of 86 adults with head and neck cancer who were treated before surgery between July 2024 and March 2026. Of those patients, 58 received immunotherapy plus chemotherapy, and 28 received immunotherapy alone. Most patients received two rounds of their predetermined treatment before undergoing surgery.

Results: After surgery, pathologists examined patients' removed tumors to see how much living cancer remained. Of the patients who received both chemotherapy and immunotherapy, roughly two-thirds had either no cancer or a very small amount of cancer left at the time of surgery, while only one of the 28 patients who received immunotherapy alone experienced the same effect.

What this study means for patients: Administering chemotherapy plus immunotherapy before surgery can likely destroy more of the tumor than immunotherapy alone for patients with head and neck cancer.

Traditionally, patients who require surgery meet with their surgeon before waiting up to six weeks for their operation without receiving any cancer treatment during that time. In this study, patients received two cycles of immunotherapy alone, or chemotherapy plus immunotherapy, in their presurgery window, giving them beneficial, active cancer therapies while waiting for their operation.

What this study means for doctors: These findings support further analysis of chemotherapy plus immunotherapy before surgery in clinical trials with larger sample sizes, with an ultimate goal of developing more effective cancer-killing therapies before surgery. This will allow physicians to further individualize head and neck cancer treatment by determining which patients need more aggressive therapy and which may be able to avoid unnecessary treatments altogether.

What the next steps are for this work: We now need to determine whether these more effective preoperative responses lead to better long-term survival rates as well as lower recurrence rates. This has been shown in other solid tumors such as in lung, colorectal, or breast cancer, but has yet to be analyzed in head and neck cancer.

Quotes: "In this study, we found that giving a combination of chemotherapy with immunotherapy before surgery led to much greater destruction of the tumor than immunotherapy alone," Dr. Roof says. "Our work is far from complete, and additional testing in larger sample sizes is required, but these findings are an important first step in providing a more personalized approach to head and neck cancer treatment."

Source:

Journal reference:

Gomez, E. A., et al. (2026) Pathologic Response After Neoadjuvant Chemoimmunotherapy in Head and Neck Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surgery. DOI: 10.1001/jamaoto.2026.225. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2852910