Combination Therapy Before Surgery Drives Stronger Tumor Reduction in Head and Neck Cancer

Patients with head and neck cancer who are scheduled for surgery often face a waiting period with limited treatment, creating an opportunity to reduce viable tumor burden before the operation. Clinicians have explored immunotherapy in this neoadjuvant window, with debate over whether adding chemotherapy confers additional benefit. Establishing the most effective preoperative regimen could improve the pathologic response observed at surgery. A new study shows that chemotherapy plus immunotherapy given before surgery led to substantially greater tumor reduction than immunotherapy alone.

The Mount Sinai Health System evaluated a neoadjuvant chemo-immunotherapy approach—chemotherapy administered with immunotherapy prior to surgery—against immunotherapy alone in adults with head and neck cancer. The strategy targets tumor burden in the presurgical window to reduce the amount of living cancer present at resection. Investigators compared outcomes at the time of operation between the two preoperative regimens.

In this program, patients received active treatment while awaiting surgery rather than the traditional wait of up to six weeks without therapy. Most patients underwent two cycles of their assigned regimen before the operation. After surgery, pathologists assessed the resected tumors to determine how much viable cancer remained.

Researchers reviewed the records of 86 adults treated within the Mount Sinai Health System between July 2024 and March 2026. Fifty-eight patients received chemotherapy plus immunotherapy, and 28 received immunotherapy alone. The analysis used real-world data collected over a two-year period.

Pathologic assessment showed markedly stronger responses with the combined approach. Roughly two-thirds of patients who received chemotherapy plus immunotherapy had either no residual cancer or only a very small amount present at surgery, whereas the same effect was observed in only one of the 28 patients given immunotherapy alone. These findings indicate a significantly greater preoperative tumor reduction with the dual regimen.

The work is described as the first real-world comparison of immunotherapy alone versus chemo-immunotherapy before surgery for head and neck cancer. The study was published in JAMA Otolaryngology–Head & Neck Surgery. The project was conducted through the Icahn School of Medicine at Mount Sinai and the broader Mount Sinai Health System.

According to the investigators, these results support evaluating preoperative chemo-immunotherapy in larger clinical trials and may help physicians tailor treatment intensity by identifying patients who need more aggressive therapy and those who could avoid unnecessary treatments. Next steps include determining whether stronger preoperative responses translate into improved long-term survival and lower recurrence, which has been shown in other solid tumors but has not yet been examined in head and neck cancer. For patients, the authors note that administering chemotherapy with immunotherapy before surgery can likely destroy more of the tumor than immunotherapy alone.

“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. 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,” said Scott Roof, MD, MS, Associate Professor of Otolaryngology-Head and Neck Surgery (Oncologic and Reconstructive Surgery), Icahn School of Medicine at Mount Sinai.

Related Links
Icahn School of Medicine at Mount Sinai