Intraoperative Magnetic Resonance Imaging Assisted Endoscopic Endonasal Resection of Clival Chordomas

BackgroundCranial base chordomas are typically indolent and usually appear as encapsulated tumors. They slowly grow by infiltrating the bone, along with the lines of least resistance. Due to its relationship with important neurovascular structures, skull base chordoma surgery is challenging.ObjectiveThe usefulness of intraoperative magnetic resonance imaging (IO-MRI) in achieving the goal of surgery, is evaluated in this study.MethodsBetween March 2018 and March 2020, 42 patients were operated on for resection of skull base chordomas in our institution. All of them were operated on under IO-MRI. Patients were analyzed retrospectively for identifying common residue locations, complications and early post-operative outcomes.ResultsIn 22 patients (52,4%) gross total resection was achieved according to the final IO-MRI. In 20 patients (47,6%) complete tumor removal was not possible because of extension to the petrous bone (8 patients), pontocerebellar angle (6 patients), prepontine cistern (4 patients), temporobasal (1 patient), cervical axis (1 patient). In 13 patients, the surgery was continued after the first IO-MRI control was performed, which showed a resectable residual tumor. 7 of these patients achieved total resection according to the second IO-MRI, in the other 6 patients all efforts were made to ensure maximal resection of the tumor as much as possible without morbidity. Repeated IO-MRI helped achieve gross total resection in 7 patients (53.8%).ConclusionsOur study proves that the use of IO-MRI is a safe method that provides the opportunity to show the degree of resection in skull base chordomas and to evaluate the volume and location of the residual tumor intraoperatively. Hence IO-MRI can improve the life expectancy of patients because it provides an opportunity for both gross total resection and maximal safe resection in cases where total resection is not possible.

Proton therapy with a fixed beamline for skull-base chordomas and chondrosarcomas: outcomes and toxicity

Aim This study presents an analysis (efficacy and toxicity) of outcomes in patients with skull-base chordomas or chondrosarcomas treated with a fixed horizontal pencil proton beam. Background Chordomas (CAs) and chondrosarcomas (CSAs) are rare tumours that are usually located near the base of the skull and very close to the brain's most critical structures. Proton therapy (PT) is often considered the best radiation treatment for these diseases, but it is still a limited resource. Active scanning PT delivered via a fixed pencil beamline might be a promising option. Methods This is a single-centre experience describing the results of proton therapy for 31 patients with CA (n = 23) or CSA (n = 8) located near the base of the skull. Proton therapy was utilized by a fixed pencil beamline with a chair to position the patient between May 2016 and November 2020. Ten patients underwent resection (32.2%), 15 patients (48.4%) underwent R2 resection, and 6 patients had unresectable tumours (19.4%). In 4 cases, the tumours had been previously irradiated. The median PT dose was 70 GyRBE (relative biological efficacy, 1.1) [range, 60 to 74] with 2.0 GyRBE per fraction. The mean GTV volume was 25.6 cm3 [range, 4.2–115.6]. Patient demographics, pathology, treatment parameters, and toxicity were collected and analysed. Radiation-induced reactions were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. Results The median follow-up time was 21 months [range, 4 to 52]. The median overall survival (OS) was 40 months. The 1- and 2-year OS was 100%, and the 3-year OS was 66.3%. Four patients died due to non-cancer-related reasons, 1 patient died due to tumour progression, and 1 patient died due to treatment-related injuries. The 1-year local control (LC) rate was 100%, the 2-year LC rate was 93.7%, and the 3-year LC rate was 85.3%. Two patients with CSA exhibited progression in the neck lymph nodes and lungs. All patients tolerated PT well without any treatment interruptions. We observed 2 cases of ≥ grade 3 toxicity, with 1 case of grade 3 myelitis and 1 case of grade 5 brainstem injury. Conclusion Treatment with a fixed proton beam shows promising disease control and an acceptable toxicity rate, even the difficult-to-treat subpopulation of patients with skull-base chordomas or chondrosarcomas requiring dose escalation.

Endoscopic Endonasal Surgical Strategy for Skull Base Chordomas Based on Tumor Growth Directions: Surgical Outcomes of 167 Patients During 3 Years

BackgroundSkull base chordomas (SBCs) are rare malignant bone tumors with dismal long-term local control. Endoscopic endonasal surgeries (EESs) are increasingly adopted to resect SBCs recently. Gross total resection (GTR) favors good outcomes. However, the SBCs often invade the skull base extensively and hide behind vital neurovascular structures; the tumors were challenging to remove entirely. To improve the GTR, we established a surgical strategy for EES according to the tumor growth directions.MethodsA total of 112 patients with SBCs from 2018 to 2019 were classified into the derivation group. We retrospectively analyzed their radiologic images and operation videos to find the accurate tumor locations. By doing so, we confirmed the tumor growth directions and established a surgical strategy. Fifty-five patients who were operated on in 2020 were regarded as the validation group, and we performed their operations following the surgical strategy to verify its value.ResultsIn the derivation group, 78.6% of SBCs invade the dorsum sellae and posterior clinoid process region. 62.5% and 69.6% of tumors extend to the left and right posterior spaces of cavernous ICA, respectively. 59.8% and 61.6% of tumors extend to the left and right posterior spaces of paraclival and lacerum ICA (pc-la ICA), respectively. 30.4% and 28.6% of tumors extended along the left and right petroclival fissures that extend toward the jugular foramen, respectively. 30.4% of tumors involved the foramen magnum and craniocervical junction region. The GTR was achieved in 60.8% of patients with primary SBCs in the derivation group. Based on the tumors’ growth pattern, pituitary transposition and posterior clinoidectomy techniques were adopted to resect tumors that hid behind cavernous ICA. Paraclival ICA transposition was used when the tumor invaded the posterior spaces of pc-la ICA. Lacerum fibrocartilage resection and eustachian tube transposition may be warranted to resect the tumors that extended to the jugular foramen. GTR was achieved in 75.0% of patients with primary SBCs in the validation group.ConclusionBesides the midline clival region, the SBCs frequently grow into the eight spaces mentioned above. The surgical strategy based on the growth pattern contributes to increasing the GTR rate.

POSSIBILITIES OF PROTON THERAPY IN THE TREATMENT OF PEDIATRIC SKULL BASE CHORDOMAS: A CASE SERIES REPORT

Chordomas are rare malignant tumors that account for no more than 4% of primary bone tumors. The incidence of chordomas in children does not exceed 5%. Tumor removal is the primary method of treatment, however, due to the high frequency of non-radical surgery, most patients require an adjuvant course of radiotherapy. Photon radiation therapy in doses of 50–60 Gy does not provide the required antitumor effect. At the same time, the use of a proton beam allows delivering a dose of 72 Gy or more with low toxicity. The article presents 4 clinical case reports of base-skull chordoma in children describing their own experience with proton therapy. An analysis of radiation exposure plans was carried out, with an evaluation of the main qualitative indicators characterizing the high-dose coverage of tumours and the radiation load on healthy tissues. The case reports described confirm that the technique of proton irradiation with a pencil beam makes it possible to safely administer ultra-high doses of radiation in close proximity to healthy tissues, including in children. Further improvement of the irradiation planning technique is required, which will improve the target coverage with a high dose of ionizing radiation.

Chordomas and chondrosarcomas of the skull base: treatment and outcome analysis in a consecutive case series of 24 patients

Background We present our 9-year consecutive case series of skull base chordomas and chondrosarcomas from a UK tertiary referral centre, discussing treatments offered and outcomes. This was carried out to improve understanding around current treatment and to better inform the management of future patients. Methods Consecutive case series over a 9-year period (2007–2016). Retrospective data analysis from the electronic skull base multidisciplinary team database and the digital patient records at a UK tertiary referral centre Results Twenty-four patients were identified (11 chordomas, 13 chondrosarcomas, mean age 52). Nineteen had proton beam therapy (PBT) postoperatively; two had intensity-modulated radiotherapy; two had no further treatment. One patient was lost to follow-up. All chordomas were resected via a transnasal endoscopic approach. Of the 19 patients undergoing resection with PBT, 13 were disease free at latest follow-up, and six patients had local recurrence, of which two died (mean follow up 7.4 years). Of the three patients treated with surgery then IMRT/TomoTherapy, one died 4 years post-treatment, and the other two are alive after 4 and 5 years of follow-up respectively. Of the two patients treated with surgery alone, one was lost to follow-up, and the other is alive after more than 8 years. Chondrosarcoma 5-year survival was 91.6%, and chordoma 4-year survival was 75%. Conclusion Skull base chordomas and chondrosarcomas can be challenging to resect, and most cases require adjuvant therapy to achieve control. Where complete resection is not possible, it is critical to undertake sufficient resection to permit high-dose radiation.

Whole genome sequencing of skull-base chordoma reveals genomic alterations associated with recurrence and chordoma-specific survival

Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/2B locus are the most prevalent events. The combination of PBRM1 alterations and the chromosome 22q deletion, which involves another SWI/SNF gene (SMARCB1), shows strong associations with poor chordoma-specific survival (Hazard ratio [HR] = 10.55, 95% confidence interval [CI] = 2.81-39.64, p = 0.001) and recurrence-free survival (HR = 4.30, 95% CI = 2.34-7.91, p = 2.77 × 10−6). Despite the low mutation rate, extensive somatic copy number alterations frequently occur, most of which are clonal and showed highly concordant profiles between paired primary and recurrence/metastasis samples, indicating their importance in chordoma initiation. In this work, our findings provide important biological and clinical insights into skull-base chordoma.