Accelerating Progress in the Treatment of Head and Neck Disease
Dr. Andrew B. Tassler, Dr. Victoria E. Banuchi, and Dr. David I. Kutler
Andrew B. Tassler, MD, David I. Kutler, MD, and Victoria E. Banuchi, MD, are among the many otolaryngologists in the Department of Otolaryngology – Head and Neck Surgery at NewYork-Presbyterian/Weill Cornell Medical Center who continue to advance treatment for conditions of the head and neck. Their specialized expertise ranges from robotic surgery for oropharyngeal cancer, a new intraoperative procedure for mapping sentinel lymph nodes, and a novel endoscopic procedure for treating thyroid disease, to research initiatives that seek to minimize the amount of surgery needed to treat head and neck disease, while still achieving optimal outcomes.
Robotic Surgery Targets Oropharyngeal Cancer
Oropharyngeal cancer represents a growing proportion of head and neck malignancies, largely associated with the increase in infection of the oropharynx by oncogenic strains of human papillomavirus (HPV). “These are tumors for which the prognosis is overall better than those related to environmental toxins like tobacco and alcohol,” says Dr. Andrew Tassler. “HPV-related tumors are driven by chronic viral infection and, fortunately, these patients do really well with treatment. However, the patient population that develops HPV-related cancers is generally younger, healthier, and will have a longer time to live with the side effects of the treatment, however rendered, for the disease. When you're dealing with a disease that has a better prognosis in younger, healthier patients, those factors push you to try and find a therapy that will achieve the same results without as much toxicity.”
In the setting of HPV-related oropharyngeal squamous cell cancer, Dr. Tassler believes transoral robotic surgery is an excellent option for the right patient. “Unless tumors are very small and easy to remove through the mouth, the traditional method to gain access would be externally through the patient’s neck or sometimes by opening the lower jaw. These are morbid surgeries and because of this, tumors in that area traditionally have been treated non-surgically, particularly since earlier studies did not demonstrate any advantage to surgery over radiation, which has its own long-term effects. Our focus is on providing treatments that accomplish the goal of cure, but also maintain the individual’s function as close to normal as possible.”
“The da Vinci robots allow us to work straight through the mouth, giving us excellent visualization and the ability to articulate the robot’s arms at extreme angles that we cannot achieve manually,” continues Dr. Tassler. “We can view and work on tissues that otherwise would have needed larger, open surgical approaches to accomplish. We often work as a two-surgeon team for robotic cases. More than one set of expert hands and eyes on each of these cases helps with both the planning and the execution of the procedures and gives us excellent results.”
Transoral robotic surgery offers direct access and precise control for oncologic resection.
Dr. Tassler notes that potential factors that would preclude a patient from undergoing transoral robotic surgery are tumor size and extent of spread. With this in mind, he is partnering with Weill Cornell radiation oncologist Nicholas Sanfilippo, MD, to develop a feasibility study in which immunotherapy and radiation therapy would precede the transoral surgery. “Patients will undergo a short course of immunotherapy and a few sessions of focused radiation therapy directed at the tumor with the hope of initiating an immune response to the cancer. The goal is to try to minimize the surgery and need for any additional treatment following surgery with this new protocol, but still achieve the same result oncologically. We would then operate on the patient in similar fashion. We will be looking to see what, if anything, was the effect on the tumor in the throat from that very brief therapy we gave. And, almost more importantly, because most of these patients present with lymph node involvement in their neck, does the initial experimental portion of treatment have an effect on the lymph nodes? If so, this would lead us to believe that we have been able to induce this immune response to the tumor throughout the body.”
The Weill Cornell researchers plan to evaluate this approach in 5 to 10 patients in the coming months. “It’s exciting to envision a new and different paradigm of treatment for these patients,” says Dr. Tassler. “This protocol integrates all the newer therapies emerging in this field, while allowing us to safely assess whether this type of a therapy would work. I am optimistic that patients will do as well, if not better, than those who receive the standard treatment.”
Sentinel Node Mapping Using Fluorescent Nanoparticles
A new intraoperative procedure for mapping sentinel lymph nodes during head and neck cancer surgery is the focus of a pilot study underway by researchers at Weill Cornell Medicine in collaboration with Memorial Sloan-Kettering Cancer Center and NewYork-Presbyterian Hospital. “It is very important from both a prognostic and a treatment standpoint to know which lymph nodes need to be treated,” says Dr. David Kutler, who serves as the primary investigator of the study. “While the use of technetium-99m sulfur colloid in sentinel node mapping is well established, there are radiation safety protocols and other limitations to its use.”
To address those limitations, the researchers investigated a different type of sentinel node mapping involving targeted silica nanoparticles – known as cRGDY-PEGCy5.5-C dye-labeled particles (dots) – in some 60 patients with melanoma and oral cavity squamous cell carcinoma. The fluorescent nanoparticles are injected intraoperatively and taken up by the lymphatics in about 30 minutes.
“These nanoparticles achieve the same objective as radioactive tracers except they don’t use radioactivity – they’re fluorescent – so we don’t need to take the precautions typically associated with radioactive tracers,” notes Dr. Kutler. “The nanoparticles are also potentially more sensitive in finding the lymph nodes. They provide a lighted road map, and in real time we can identify the sentinel nodes – the ones most likely to have cancer in them.”
Mapping sentinel lymph nodes with fluorescent nanoparticles is a new approach under evaluation in head and neck cancer surgery at Weill Cornell.
In phase 2 of the clinical trial, patients were injected with technetium-99m sulfur colloid prior to surgery as part of their standard of care. The images were acquired about two hours later using a gamma probe. Additionally, each patient received a locally administered injection of fluorescent cRGDY-PEG-Cy5.5-C dots in four quadrants around the primary lesion to assess for metastatic disease. Imaging of this agent using a hand-held camera system and video monitoring continued throughout the procedure. After completion of the neck dissection, nodal specimens were examined ex vivo for a fluorescence signal. The fluorescent and non-fluorescent nodes were compared to the true positive and false positive rates for cancer detection.
“This approach to sentinel lymph node mapping has been approved for melanoma and a few other cancers, but not for head and neck cancers due to the novelty of using targeted silica nanoparticles for oral cavity cancers,” says Dr. Kutler. “This is a completely new application of fluorescent nanoparticles.” Results of this research will be published shortly.
A Role for Genetics
Dr. Kutler’s research also focuses on genetic causes of head and neck cancer, chromosomal instability and its relationship to cancer development, and adenoviral gene therapy for the treatment of squamous cell carcinoma. “We’ve been looking at different stages of tumors, from dysplasia to carcinoma in situ, using RNA profiling,” says Dr. Kutler.
In an article published in the August 4, 2020, edition of Head & Neck, Dr. Kutler, along with colleagues at Columbia University Irving Medical Center, report on a microRNA-based risk scoring system to identify early-stage oral squamous cell carcinoma patients at high risk for cancer-specific mortality. The study sought to identify a clinical modality that would fill the current gap of stratifying patents at high risk for mortality from their cancer other than by conventional TNM staging, with the overall goal of improving decision-making about treatment and lengthening survival of patients.
The study looked at 306 patients from NewYork-Presbyterian Hospital who had early stage oral squamous cell carcinoma, had undergone surgery, and had a minimum of five-year clinical outcomes. The authors concluded that the scoring system using the miRNA-based 5-plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients with an early-stage oral squamous cell cancer.
Yoon AJ, Wang S, Kutler DI, Carvajal RD, Philipone E, Wang T, Peters SM, LaRoche D, Hernandez BY, McDowell BD, Stewart CR, Momen-Heravi F, Santella RM. MicroRNA-based risk scoring system to identify early-stage oral squamous cell carcinoma patients at high-risk for cancer-specific mortality. Head & Neck. 2020 Aug;42(8):1699-1712. https://onlinelibrary.wiley.com/doi/full/10.1002/hed.26089
Scarless Thyroid and Parathyroid Surgery
Since 2016, when the transoral endoscopic thyroidectomy via vestibular approach (TOETVA) was first described around the world, Dr. Victoria Banuchi, along with a hand full of colleagues around the country specializing in thyroid and parathyroid surgery, has been refining methods to apply this technique here in the United States.
“For over 20 years, we have been attempting as a specialty to pursue remote access approaches for thyroidectomy to avoid unsightly scars,” says Dr. Banuchi. “We’ve tried robotic approaches through the axilla, through the nipple, and through a facelift approach. Nothing has really gained momentum like the transoral endoscopic thyroidectomy vestibular approach. With this procedure, we enter the lower lip through three incisions – one to put a camera in and two on the sides to place our dissecting instruments. CO2 insufflation is used to preserve our working space and access the central neck to remove the thyroid, perform parathyroid surgery, and remove central compartment lymph nodes. The route is a shorter course than the transaxillary, nipple, or facelift approaches…more of a straight shot so there’s minimal soft tissue trauma to reach it.”
Dr. Banuchi became the third head and neck surgeon in the country to perform this operation and today is among only a handful of surgeons in the U.S. using this approach. “There are over 3,000 cases published worldwide and, with at least three courses offered in the United States yearly, more and more surgeons are being trained to use it,” says Dr. Banuchi, who also teaches the procedure.
Endoscopic view during TOETVA: (A) Division of thyroid isthmus (B) Dissection of the recurrent laryngeal nerve
TOETVA also appeals to patients as entering through a natural orifice allows for the cosmetic advantage of no visible scar. Dr. Banuchi believes the procedure does not only give a cosmetic advantage but also actually enhances patient privacy. “Patients prefer this approach partly because of the issue of privacy,” she says. “It enables them to manage their thyroid cancer or thyroid disease privately. They don’t have to worry about explaining a visible scar to others.”
Dr. Banuchi notes that the procedure will continue to evolve, and robotics will likely play a significant role in extending its applications. “The single-port system, for example, is extremely promising. Once the robotics advance to the point where we can have a single port placed in that central incision that goes directly to the neck, we will be able to perform this procedure better, faster, and even more precisely than we do now.”