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Study on Rare Skull Base Chordomas Provides New Insights for Clinical Practice and Surgical Management

April 15, 2021

A team of researchers from the UPMC Center for Cranial Base Surgery, led by senior author Georgios A. Zenonos, MD, associate director of the UPMC Center for Cranial Base Surgery, presented findings from their new study on skull base chordoma management at the 2021 North American Skull Base Society (NASBS) annual meeting.

The team’s research provides the first clear evidence and guidance for treatment approaches to skull base chordomas based on an individual patient’s tumor, genetic and molecular characteristics, and risk category. For some patients, high-intensity radiotherapy after gross total resection (GTR) may be avoided, thus sparing them the typical morbidities associated with this aspect of treatment.

The study constitutes a major step forward in the individualized treatment of these rare and difficult-to-treat tumors.

For its clinical importance and the underlying science, the research team was awarded the Best Basic Science Abstract award at NASBS 2021 for their study.

“Our study provides a new basis to achieve a much more nuanced approach to managing skull base chordomas than has existed in the past,” says Dr. Zenonos. "Stratifying tumors and their risk probability using genetic and clinical data can guide clinicians in a more evidence-based manner, thus allowing for a higher degree of personalized care."

Study Overview

Skull base chordomas are exceedingly rare, difficult to treat, have high recurrence rates, and carry with them the potential for substantial morbidities associated with surgical resection and subsequent radiotherapy.

Although surgical techniques and radiation practices have improved, the standard of care for skull base chordoma has changed little in recent decades: surgical resection to the degree possible based on tumor characteristics and location, followed by radiotherapy, has been the norm for all cases. This treatment paradigm is likely to change because of the research from Dr. Zenonos and colleagues. This, together with the establishment of the Endoscopic Endonasal Approach (EEA), largely developed at UPMC, will help create the new standard of care for these rare tumors.

The team’s research analyzed a total of 152 cases of skull base chordoma treated at the UPMC Center for Cranial Base Surgery from January 2007 to June 2020. The cases represent a broad spectrum of patient characteristics and ages: chordomas, in general, can occur in both pediatric and adult patients.

The researchers delved into the genetic similarities and differences of tumors, the prior treatments and outcomes of cases, and the clinical behaviors of the malignancies.

“With this study, we have shown that for tumors of intermediate or lower genetic risk, radiotherapy can be withheld in a number of scenarios. The genetic panel and the data we presented allow us to personalize care according to each patient's tumor's genetic findings. This is the first time such data are available with clear guidelines,” says Paul A. Gardner, MD, neurosurgical director of the UPMC Center for Cranial Base Surgery

Key Findings

The study cohort was stratified into three risk categories – low, intermediate, and high. These categories consider the genetic profile of the tumor and the degree of chromosomal deletions present in the 1p36 and 9p21 regions. The stratified risk profiles also take into account the ability for surgical removal to achieve gross total reduction of the tumor burden.

For the groups with the best and intermediate prognoses, the data uncovered by Dr. Zenonos and colleagues support withholding adjuvant radiotherapy if and only if GTR is achievable with no detrimental effects on outcomes and progression-free survival. In the best prognosis group with the lowest risk, the analysis was insufficient for a recommendation on adjuvant radiotherapy in the absence of GTR, given that almost all of these tumors had a complete resection. However, when GTR is not possible for the intermediate prognosis group, the study's data support the use of adjuvant radiation for more robust tumor reduction. For the tumor group with the worst prognosis, adjuvant radiotherapy is recommended regardless of the ability to achieve a GTR to improve outcomes potentials.

As Dr. Zenonos and colleagues' point out in the study, one particular finding with respect to the lowest risk group was compelling in that the tumors found in the group appear to be of a much less aggressive or virulent nature, are typically asymptomatic upon discovery and seen in younger age patients. The full implications of this potential tumor phenotype group are not fully understood and will require further study.

Implications for Clinical Practice and Future Studies

This new study by Drs. Zenonos, Gardner, and colleagues' affords the neurosurgical community with a robust yet relatively simple approach to clival chordoma stratification and management principles. It also has the potential to spare many patients the often profound and debilitating morbidities associated with skull base radiotherapy.

“With this initial data, we look forward to larger, multicenter trials and studies to further validate the data from our analysis and uncover new findings that may further help to individualize the care of these patients,” says Dr. Zenonos.

Abstract Reference

Abdallah HM, Gersey ZC, Muthiah N, McDowell MM, Costacou T, Snyderman CH, Wang EW, Gardner PA, Zenonos GA. An Integrated Management Paradigm for Skull Base Chordoma Based on Clinical and Molecular Characteristics. J Neurol Surg B Skull Base. 2021; 82(S 02): S65-S270.
DOI: 10.1055/s-0041-1725263.

Further Reading

Further details from the study will be available in a soon to be published paper in the Journal of Neurological Surgery – Part B Skull Base under the following citation:

Abdallah HM, Gersey ZC, Muthiah N, McDowell MM, Costacou T, Snyderman CH, Wang EW, Gardner PA, Zenonos GA. An Integrated Management Paradigm for Skull Base Chordoma Based on Clinical and Molecular Characteristics. J Neurol Surg B Skull Base. 2021; In Peer Review.