Nabil F. Saba, MD
A recently launched clinical trial aims to improve outcomes and quality of life for patients with nasal and paranasal squamous cell carcinoma (NPNSCC), a rare type of head and neck cancer that is challenging to treat and carries significant morbidity.
The current preferred treatment for patients with advanced NPNSCC is surgical resection, followed by radiation and chemotherapy, depending on the surgical outcome.1
Because of the critical location of these tumors, patients who undergo surgery suffer from loss of the orbit or risk damage to the base of the skull.
The phase II study, which began recruiting patients in April 2018, seeks to evaluate the impact of administering chemotherapy before surgery and radiation (NCT03493425). Investigators hope the approach prevents disfiguring surgeries and improves overall survival (OS), thus establishing a course of treatment that will improve the quality of life for this patient population (Figure 1
“This cancer is very taxing on the patient because it develops in critical areas,” principal investigator Nabil F. Saba, MD, said in an interview with OncologyLive®
. “For patients who undergo orbital resection, it is a lifelong disfiguring treatment that also affects their quality of life, given that they are losing a major organ—their eye.
“Other possible adverse effects include facial disfigurement if they get a big surgical resection, or patients may experience complications including cerebral spinal fluid leaks if they have a base-of-skull resection,” said Saba, director of the Head and Neck Medical Oncology Program at Winship Cancer Institute of Emory University in Atlanta, Georgia.
Overall, an estimated 3% to 5% of patients with head and neck cancers have primary tumors of the sinonasal tract, accounting for approximately 2000 people a year in the United States.2,3
There are several histological subtypes of NPNSCC, with the most common being squamous cell carcinoma. The study will focus on patients with a diagnosis of stage T3 or T4a advanced NPNSCC (Figure 2
). These categories include tumors that have invaded the bone of the posterior wall of the maxillary sinus, the ethmoid sinuses, or the anterior orbital contents, according to the American Joint Committee on Cancer staging system.4
To participate in the trial, patients must be candidates for surgical resection.
Patients will be randomized into 2 arms. Arm A will provide standard-of-care surgery followed by postoperative image-guided intensity-modulated radiation therapy (IMRT) at 5 fractions per week for 30 fractions, beginning 4 to 6 weeks after surgery. Those with positive margins or positive extracapsular spread (ESC) in the lymph nodes will receive 66 Gy with weekly cisplatin or carboplatin.
Participants in the experimental arm B will receive an intensification of docetaxel plus cisplatin, or docetaxel plus carboplatin for patients who are cisplatin ineligible, for up to three, 21-day cycles. Patients will undergo standard- of-care surgery within 6 weeks of their last dose of chemotherapy, followed by IMRT at 5 fractions per week for 30 fractions. Additional cisplatin or carboplatin also will be administered to those with positive margins or ESC.
The primary outcome of the study is structure preservation rate defined as both skull base and orbit being preserved; the secondary outcome is OS. Additionally, administering chemotherapy prior to surgery may shrink the tumor and reduce the amount of normal tissue that needs to be removed and treated with radiation, Saba said.
Following the completion of treatment, patients will commit to follow-up appointments for 5 years. Because most treatment failures for NPNSCC occur within the first 2 years following therapy, patients should adhere to a meticulous follow-up schedule. Follow-up monitoring should take place every 3 months for 2 years and then every 6 months for years 2 to 5 after the study.5
Because of the rarity of this disease, there is a lack of uniformity, with no clear guidelines for treating these patients, Saba said. The results of this trial will also, hopefully, answer an important clinical question for changing the standard of care, he noted.