At Penn Medicine, researchers in the Department of Otorhinolaryngology-Head and Neck Surgery have established a sinonasal cancer tissue banking repository in an effort to better understand the genetic variability of these malignancies, and their identification with patient outcomes and patient quality of life.
Understanding the Genetics of Rare Cancers
Sinonasal malignancies (SNMs) are in a class of their own. So little is known about these cancers that to date no predominant risk factor has been established, nor has any racial, ethnic or geographic propensity identified. Moreover, the existing literature on SNM is composed primarily of retrospective studies based on heterogeneous patient cohorts of limited size. The neoplasms are rare (about 6 per million in the United States), and comprise over two dozen unique cancer types. For investigators, this combination of disease rarity, histopathological diversity, and treatment uncertainty makes difficult the rigorous, longitudinal assessment of SNM and limits understanding of the disease, its characteristics and treatment outcomes.
Dr. James Palmer suggests “we like to think of Sinonasal malignancies as ‘orphan diseases’ based on their rare nature and need for specialized care.”
To address this dearth of practical and clinical information, Penn Otorhinolaryngology – Head and Neck Surgery partnered with researchers at Stanford University and seven other leading medical centers nationwide several years ago to create the Cole-Reagins Registry for Sinonasal Cancer (CORSICA). An observational registry, CORSICA prospectively captures data on sinonasal malignancies from patients enrolled in the registry.
“Our first step is to get the data, and make sure the data is without inherent errors. By partnering with D3b, we are working with a group that has conquered these same challenges in a similar ‘orphan disease’ field in pediatric brain tumors,” Dr. Palmer explained.
At Penn Medicine, the registry is managed by clinicians Drs. James Palmer, MD, Nithin Adappa, MD, and Michael Kohanski, MD. The Penn team is collaborating with two highly regarded specialists at the Children’s Hospital of Philadelphia, Philip B. Storm, MD, Chair of Pediatric Neurosurgery and Dr Adam Resnick, MD, PHD, Director of Data Driven Discovery in Biomedicine (D3b).
The challenges to biobanking include faulty record maintenance, errors in tissue analysis, misinterpretation of data and impositions on data sharing which have prevented a biobank like this being created up to now have all been addressed in the design and coordination of the CORSICA registry.
Better Treatment with Personalized Insights
A vital element of CORSICA at Penn Medicine involves the establishment of the sinonasal cancer tissue bank through philanthropic support from Innovate accelerator for skull base tumor sequencing and analysis fueled the consortium was able to add a biobanking arm to the research. The bank is made up of biospecimens donated by patients from all of the registry’s various partner institutions, which (in addition to Stanford) include the University of California at Los Angeles; the University of Washington; the University of Pittsburgh; the University of Arizona; Oregon Health and Science University, Mayo Clinic, University of California at Irvine, and the University of Colorado.
The goals of the biospecimen bank, Dr. Adappa explains, are to establish genetic profiles for the various cancer types known to present in the sinonasal cavity. In addition to his association with CORSICA, Dr. Adappa is the Surgical Director of the Penn AERD Center.
“If we can identify the differences among these cancers, we may be able to establish clear guidelines for treatment to identify their differences and, possibly improve tumor outcomes,” said Dr. Adappa. “Our D3b partners will help lead us on this journey of discovery, not just with genomic (DNA) data, but also proteomic (protein) data that will lead us toward new treatments and eventually cures.”
For patients who have had surgery for SNMs, the biobank offers unique advantages, Dr. Adappa explains. “These cancers have a very high recurrence rate,” he says. “If we can identify the cancer the patient had at initial surgery from the biobanked tissue, we may be able to both better detect that cancer type should the cancer return, and administer personalized targeted therapies to treat it.”
The use of donated autologous tissue for the treatment of cancer includes blood cells, and was thus the foundation for the development of CAR-T therapy, at the Abramson Cancer Center for the treatment of chronic lymphocytic leukemia and non-Hodgkin lymphoma.
Moreover, once a treatment has been linked to a specific biomarker in the tissue bank, that treatment can be administered to patients whose tumors have the same genetic profile. For tumor types not treatable with current targeted therapies, the biobank will serve as a foundation for investigation, with the aim of developing new targeted therapies. Currently, an effort by the Comprehensive Cancer Center in Finland is achieving this end with biobanked cancer tissue gathered from hospitals throughout the country to identify patients for new targeted drug trials. [Duodecim 2017;133(6):592-8.]
At this time, CORSICA is the world’s only prospective sinus cancer consortium collecting tissue for genetic sequencing. Begin in 2021, genetic analysis will have the goal of aligning specific genes with clinical outcomes in order to stratify patients to the best treatment for specific mutations.
On the Face of It: Quality of Life for SNM Survivors
Beyond survival, the importance of quality of life (QOL) is increasingly recognized in the management of SNMs, yet knowledge in this area is also significantly limited. Surgical manipulation of the nasal tract and skull base is associated with notable morbidity given the proximity of critical structures, with radiation and chemotherapy also adversely impacting QOL.5 Sinonasal QOL declines following surgical resection and partially recovers over the following 6-12 months.5 However, the impact that specific surgical approaches (endoscopic, open, or combined) or adjuvant therapies have on QOL is challenging to assess due to heterogeneity in treatment pathways and small patient cohorts. A deeper understanding of the expected QOL impact from specific treatment components would fill a crucial knowledge gap.
Conclusion
The tissue biobank at Penn Otorhinolaryngology – Head and Neck Surgery is the first step to better understanding sinonasal cancers, and subsequently being able to better treat, these complex malignancies.
“We know that these cancers are best treated at centers that have a high volume of surgery,” Dr Adappa says. “But so far, even the best standard treatments—chemotherapy, surgery and radiation—haven’t resulted in the improvement in outcomes we’d like to see, and diagnosis remains a challenge.” The hope, Dr. Adappa concludes, is that the CORSICA registry, and its concomitant accumulation of critical data and tissue, will bring Penn Medicine to the vanguard for the treatment of these rare, complex cancers.
“Our goal is universal cure of these orphan diseases,” says Dr. Palmer. “The only way to reach that goal is to continue advancing surgery and pairing it with subsequent targeted, personalized treatments with the next generation of chemotherapeutics and immunomodulators.”