Management of pediatric clival chordoma with extension to the craniocervical junction and occipito-cervical fusion: illustrative case

BACKGROUND Chordomas are rare malignant neoplasms that develop from the primitive notochord with < 5% of the tumors occurring in pediatric patients younger than the age of 20. Of these pediatric chordomas, those affecting the craniocervical junction (C1–C2) are even more rare; therefore, parameters for surgical management of these pediatric tumors are not well characterized. OBSERVATIONS In this case, a 3-year-old male was found to have a clival chordoma on imaging with extension to the craniocervical junction resulting in spinal cord compression. Endoscopic-assisted transoral transclival approach for clival tumor resection was performed first. As a second stage, the patient underwent a left-sided far lateral craniotomy and cervical laminectomy for resection of the skull base chordoma and instrumented fusion of the occiput to C3. He made excellent improvements in strength and dexterity during rehab and was discharged after 3 weeks. LESSONS In pediatric patients with chordoma with extension to the craniocervical junction and spinal cord compression, decompression with additional occipito-cervical fusion appears to offer a good clinical outcome. Fusion performed as a separate surgery before or at the same time as the initial tumor resection surgery may lead to better outcomes.

An experience in treatment of neurologically silent clival chordoma mimicking a nasopharyngeal tumor

Cranial chordoma is a rare neoplasm that is challenging to both diagnose and manage. We present our experience in treating a case of clival chordoma mimicking a nasopharyngeal mass without any signs of cranial deficits or intracranial insult. Management was comprised of endoscopic transnasal debulking surgery followed by radiotherapy. However, we failed to achieve an oncologic outcome due to the development of lethal central nervous system and respiratory infections 1 month after the surgery.

Drug combination screening as a translational approach toward an improved drug therapy for chordoma

Purpose Drug screening programmes have revealed epidermal growth factor receptor inhibitors (EGFRis) as promising therapeutics for chordoma, an orphan malignant bone tumour, in the absence of a known genetic driver. Concurrently, the irreversible EGFRi afatinib (Giotrif®) is being evaluated in a multicentric Phase II trial. As tyrosine kinase inhibitor (TKI) monotherapies are invariably followed by resistance, we aimed to evaluate potential therapeutic combinations with EGFRis. Methods We screened 133 clinically approved anticancer drugs as single agents and in combination with two EGFRis (afatinib and erlotinib) in the clival chordoma cell line UM-Chor1. Synergistic combinations were analysed in a 7 × 7 matrix format. The most promising combination was further explored in clival (UM-Chor1, MUG-CC1) and sacral (MUG-Chor1, U-CH1) chordoma cell lines. Secretomes were analysed for receptor tyrosine kinase ligands (EGF, TGF-α, FGF-2 and VEGF-A) upon drug treatment. Results Drugs that were active as single agents (n = 45) included TKIs, HDAC and proteasome inhibitors, and cytostatic drugs. Six combinations were analysed in a matrix format: n = 4 resulted in a significantly increased cell killing (crizotinib, dabrafenib, panobinostat and doxorubicin), and n = 2 exhibited no or negligible effects (regorafenib, venetoclax). Clival chordoma cell lines were more responsive to combined EGFR-MET inhibition. EGFR-MET cross-talk (e.g. via TGF-α secretion) likely accounts for the synergistic effects of EGFR-MET inhibition. Conclusion Our screen revealed promising combinations with EGFRis, such as the ALK/MET-inhibitor crizotinib, the HDAC-inhibitor panobinostat or the topoisomerase-II-inhibitor doxorubicin, which are part of standard chemotherapy regimens for various bone and soft-tissue sarcomas.

RARE-09. POORLY DIFFERENTIATED CLIVAL CHORDOMA IN EXTREME YOUNG AGE; CASE ILLUSTRATION AND REVIEW OF LITERATURE

Chordomas are rare tumors believed to be originated from notochordal remnants. Of all intracranial neoplasms, the incidence of cranial chordomas is less than 1%1. The youngest patient with an intracranial chordoma reported in the literature was a newborn in the first few days after birth9. Intracranial chondroma are more predominant in males compared to females1. The clinical features of intracranial chondroma in the pediatric age group commonly include increased Intracranial pressure, lower cranial nerves palsy, and torticollis2. There is no optimum treatment, however, surgical resection of the tumor followed by radiation therapy reported successful outcome3. This is a case of a poorly differentiated clival chordoma of a 23-month old boy. The clinical features, pathological, radiological findings, and surgical technique are discussed with an elaboration of the current review of the literature of clival chordoma in the extreme young age group. To the best of our knowledge, this is the youngest age of clivus chordoma reported in Saudi Arabia.

Spontaneous Regression of a Clival Chordoma: An Unusual Case Report

Introduction Chordoma is a malignant and aggressive tumor originating from remnants of the primitive notochord and usually involving the axial skeleton. Spontaneous regression of clival chordomas was described recently. We present the third case report of spontaneous regression of a clival chordoma and discuss similarities of cases and implications for clinical practice. Case Description We present the case of a previously healthy 21-year-old Caucasian woman who presented with progressive holocranial headache for 3 months, which encouraged image investigation. Magnetic resonance imaging (MRI) revealed an osteolytic clival lesion hyperintense in T2 and hypointense in T1 images. After 2 months of initial evaluation and surgical proposal, she repeated MRI to allow use for intraoperative neuronavigation. Surprisingly, there was tumor regression. Discussion The present reported case is somehow different from previous ones and does not share an underlying inflammatory/immunological recognizable fact, being interpreted by us as a spontaneous partial regression of the tumor. We highlight the need for continuous investigation of chordoma regression to uncover the underlying mechanisms.