Researchers have found that chemotherapy prior to surgery may reduce the amount of normal tissue that needs to be removed in patients with advanced nasal and paranasal sinus squamous cell carcinoma, according to recent findings presented by Saba et al at the European Society for Medical Oncology (ESMO) Congress 2024 (Abstract 850MO).
Background
Nasal and paranasal sinus squamous cell carcinoma is a rare disease that affects about 2,000 patients—especially those aged 55 and older—in the United States each year, according to the American Cancer Society. At presentation, patients typically have tumors in or near the orbit, the base of the skull bone, or both. The nasal cavity and paranasal sinus are close to many vital nerves, blood vessels, and other structures, making surgical planning and surgery itself challenging. Thus, patients may have to live with the debilitating effects of surgery and radiation for the rest of their lives. Patients enrolled in this trial had signs that surgery would result in loss of the eye, the base of the skull bone, or both.
Small single-institution trials investigating receipt of chemotherapy prior to surgery have yielded questionable results on the improvement of organ preservation. Based on these suggestive data, some oncologists and surgeons recommend chemotherapy followed by surgery in their patients. However, widespread adoption has been hampered by the lack of a randomized multicenter trial showing its advantages over primary surgery in terms of organ preservation.
Study Methods and Results
In the prospective multicenter EA3163 clinical trial (ClinicalTrials.gov identifier NCT03493425), the researchers recruited 29 patients with stage T3, T4a, and T4b nasal and paranasal sinus squamous cell carcinoma between March 2018 and August 2023 at multiple clinical sites in the United States. Enrollment closed in November 2023 after slow accrual. The results were reported for 23 evaluable patients.
The patients were randomly assigned to receive either three cycles of chemotherapy followed by surgery and radiation therapy (66 Gy) or surgery alone followed by radiation therapy (60 Gy). Although chemotherapy consisted of docetaxel at 75 mg/m2 and cisplatin at 75 mg/m2, the patients in the experimental arm could receive carboplatin at 40 mg/m2 instead of cisplatin if the treating physician deemed it necessary. These doses were considered acceptable by National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology.
“Because this disease is so rare, it was a bold move and significant undertaking to conduct this trial. Unlike the previously reported information on the role of chemotherapy in organ preservation, this study enrolled patients who were deemed to clearly need organ resection, and we tracked this information carefully, which allowed us to have a more objective examination as to the role of chemotherapy in organ preservation and be able to prove or disprove this approach,” detailed lead study author Nabil F. Saba, MD, FACP, Professor, Vice Chair, the Lynne and Howard Halpern Chair in Head and Neck Cancer Research, and Director of the Head and Neck Oncology Program at the Winship Cancer Institute at the Emory University School of Medicine as well as a member of the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network (ECOG-ACRIN) Cancer Research Group Head and Neck Cancer Committee. “The EA3163 trial, therefore, provided the reliable platform to objectively compare the two approaches,” he added.
The researchers discovered that the patients who received chemotherapy prior to surgery had a 50% chance of structure preservation. In contrast, those who had surgery had a 15% chance of preserving both the eye and the base of the skull bone.
Conclusions
“These results support chemotherapy before surgery as an effective intervention to improve the preservation of vital organs, bone, and tissue in patients with nasal and paranasal sinus squamous cell carcinoma,” highlighted Dr. Saba. “Despite being unable to complete the planned accrual and reach a definitive answer, the study results are striking and support the use of neoadjuvant chemotherapy as an intervention that could improve the chance of organ preservation for these patients. We are happy to see that structural preservation, in every possible way we examined it, favors neoadjuvant chemotherapy,” he emphasized.
The researchers hope their findings can help improve the 5-year survival rate for nasal and paranasal sinus squamous cell carcinoma, which is currently below 50%. The study participants will continue to be monitored for 2-year overall survival.
“We believe future trials will need to test whether modifying the choice of chemotherapy or adding immunotherapy could improve the chance of organ preservation,” concluded senior study author Barbara A. Burtness, MD, the Anthony N. Brady Professor of Medicine and Chief Translational Research Officer at Yale Cancer Center, Chair of the ECOG-ACRIN Head and Neck Committee, and Chair of the ECOG-ACRIN Task Force on Advancement for Women.
Disclosure: The research in this study was sponsored by the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit cslide.ctimeetingtech.com.
