New treatment approach preserves organs, improves survival in head and neck cancer patients

Bottom line: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors responded to neoadjuvant immunochemotherapy (ICT) and who underwent less extensive surgery had high disease-free survival and organ preservation rates.

Journal in which the study was published: Clinical Cancer Research, a journal of the American Association for Cancer Research.

Author: Kunyu Yang, MD, director of Union Hospital Cancer Center at Tongji Medical College and Huazhong University of Science and Technology in China and one of the study's senior authors.

Background: Head and neck cancers are malignancies that arise in the nasal cavity, sinuses, lips, mouth, salivary glands, throat, or larynx. The most common types begin in squamous cells in the oral cavity, pharynx, or larynx. More than 60% of patients with HNSCC are diagnosed at the locally advanced stage and are at high risk of recurrence and metastasis. Outcomes are particularly poor for patients with HPV-negative HNSCC.

"Traditionally patients with locally advanced HPV-negative HNSCC undergo either definitive chemoradiotherapy without surgery or radical surgery followed by radiotherapy," Yang said.

"Radical surgery-extensive surgery to remove the tumor and all surrounding tissues-for locally advanced HNSCC often results in organ dysfunction and facial disfigurement. Although chemoradiotherapy can preserve organs like larynx and pharynx, long-term follow up studies have shown it can cause severe toxicities such as dysphagia, feeding tube dependence, and voice loss," added Yang. "Thus, there remains a significant unmet need for improved treatment options, as these approaches continue to be associated with high recurrence rates and poor quality of life."

Previous research has shown that adding immunotherapy to the treatment regimen for HNSCC improves overall survival. An earlier study by Yang's group, also published in Clinical Cancer Research, demonstrated that administering ICT before surgery and radiotherapy significantly improved outcomes for patients with locally advanced HNSCC.

"Because patients responded so well to neoadjuvant ICT and displayed profound tumor shrinkage, we next wanted to ask if this strategy could allow for less extensive surgery while still maintaining disease control and positive functional outcomes," said Yang.

How the study was conducted: To test this, Yang and his team treated 52 patients with HPV-negative locally advanced resectable HNSCC with three cycles of ICT. During the neoadjuvant treatment, patients were monitored by imaging for tumor response. Patients who had ≥50% tumor regression following ICT underwent reduced-volume surgery-a procedure that removes the residual tumor but aims to minimally affect nearby structures and organs-while those who had <50% received standard-volume surgery. 

Results: Forty-seven patients completed three cycles of neoadjuvant therapy and proceeded to surgery, while five patients did not continue with the study protocol. Among these 47 patients, 42 (90%) had their tumor shrink by ≥50% and underwent reduced-volume surgery. Five patients (10%) had <50% tumor regression after ICT and received standard-volume surgery.

At two years, 90% of patients who received reduced-volume surgical treatment remained free of recurrence, metastasis, or death. Furthermore, laryngeal function was preserved in all 39 (100%) patients who presented with laryngeal or hypopharyngeal cancer and had reduced-volume surgery.

In contrast, patients who had <50% tumor regression and underwent standard-volume surgery had a two-year disease-free survival rate of only 20%. Complete loss of laryngeal function occurred in one of the three patients undergoing laryngeal or hypopharyngeal surgery.

The study also revealed that PD-L1 expression may serve as a potential predictive biomarker for response to ICT. Higher PD-L1 Combined Positive Score (CPS), a measure of PD-L1 expression, was positively correlated with improved pathological complete response (pCR) rates after neoadjuvant ICT. Sixty-five percent of patients with a high PD-L1 CPS (>20) had a pCR compared with 28% of those with CPS 1-19 and 14% of those with CPS <1.

Author's comments: "Our results are promising and provide strong rationale for further investigation," said Yang. "While they are not yet sufficient to change current standard of care, we show that ICT before surgery resulted in remarkable tumor reduction and patient outcomes even with reduced-volume surgery. This suggests that surgery may be individually tailored based on tumor response to neoadjuvant ICT. These findings also suggest that resistance to early treatment may be a strong prognostic marker and highlight the urgent need for alternative therapeutic strategies for nonresponding cancers."

Study limitations: The study limitations include its single-arm design and its relatively small sample size, which was predominantly comprised of laryngeal and hypopharyngeal cancers.