Due to the rarity and surgical complexity of sinonasal poorly differentiated squamous cell carcinoma (PDSCC), treatment regimens are often extrapolated from those of more common cancers of the oral cavity and other areas of the head and neck. However, with such limited data, optimal treatment protocols remain controversial, particularly with regard to the role of chemotherapy and the definitive sequence of therapy for this cancer.

To help address this debate, Ralph Abi Hachem, MD, MSc, a Duke otolaryngologist and head and neck surgeon, and other researchers queried the National Cancer Database to analyze patient demographics, tumor characteristics, and treatment factors and their influence on overall survival for sinonasal PDSCC with that of cancers at other sites in the head and neck. Duke otolaryngologists David W. Jang, MD, and Bradley Goldstein, MD, PhD, also contributed to this study.

Abi Hachem explains that the sequence of therapy and the role of chemotherapy in treating advanced-stage PDSCC is controversial, regardless of whether surgical resection or radiation is also used. Because sinonasal cancers are surgically challenging, Abi Hachem adds, treatment for these patients must be very nuanced.

“Sinonasal cancers are so close to the eye and brain, so they are difficult to resect and still get a good cuff of normal tissue around them,” he says. “One patient might opt for removing the eye to get rid of the cancer, but another patient might care more about preserving their eye and quality of life, so it’s also challenging to balance the patients’ functional and cosmetic wishes.”

Abi Hachem’s research on treatment protocols, published in The Laryngoscope in September 2020, found that sinonasal malignancies—which represent 3% to 5% of all cancers in the head and neck—should be treated with the same principles as other cancers within the head and neck, with special indications for chemotherapy.

“This study shows that surgical resection followed by adjuvant radiation provides the best treatment outcomes and improved overall survival for patients with poorly differentiated SCC,” says Abi Hachem, senior author of the study, “but it also shows that adjuvant chemotherapy should be reserved only for a very specific subset of cases with positive margins.”

Of the 1,074 patients identified in a 10-year period, the most common treatment regimen was radiation therapy only (25.2%) followed by surgery with adjuvant radiation therapy (24.2%). A total of 626 underwent surgical resection as part of their treatment regimen, and negative margins were achieved in nearly 63% of those cases. Chemotherapy within the treatment regimen did not confer an overall survival benefit, the study notes, except in patients with positive margins following surgical resection.

“Induction or neoadjuvant chemotherapy should be reserved for unresectable cases or when organ preservation such as the eye is a priority,” Abi Hachem notes. A review of the benefits of these therapeutic approaches to sinonasal malignancies was published in a 2018 issue of The International Forum of Allergy and Rhinology by Abi Hachem, Jang, and others.

For any of these treatments, Abi Hachem emphasizes the value of referring patients to a high-volume center like Duke. In a retrospective study published in June 2020 in Otolaryngology – Head and Neck Surgery, Abi Hachem, Jang, and others showed that treatment at a high-volume facility conferred a significantly greater overall survival benefit for sinonasal squamous cell carcinoma than treatment at a low- or medium-volume facility.

Abi Hachem says that a prospective, multicenter, randomized controlled trial is necessary to further confirm the findings on optimal treatment protocols, but it’s difficult to get a significant number of patients to do a statistically significant study.

“Patients with poorly differentiated SCC were not initially included in big trials on other head and neck subsites because the disease is so rare in the sinonasal cavity and because there are so many controversies about how to treat them,” he says. “Our most recent work sheds light on the treatment controversy and confirms that cancers of the nose and sinuses should be treated the same as cancers elsewhere in the head and neck.”