Skull Base Chordomas Research Articles

Craniovertebral junction chordomas: Case series and strategies to overcome the surgical challenge.

Introduction:Chordomas are rare and malignant primary bone tumors. Different strategies have been proposed for chordomas involving the craniovertebral junction (CVJ) compared to other locations. The impossibility to achieve en bloc excision, the impact on stability and the need for proper reconstruction make their surgical management challenging.Objective:The objective is to discuss surgical strategies in CVJ chordomas operated in a single-center during a 7 years' experience (2013-2019).Methods:Adult patients with CVJ chordoma were retrospectively analyzed. The clinical, radiological, pathological, and surgical data were discussed.Results:A total number of 8 patients was included (among a total number of 32 patients suffering from skull base chordoma). Seven patients underwent endoscopic endonasal approach (EEA), and posterior instrumentation was needed in three cases. Three explicative cases were reported: EEA for midline tumor involving lower clivus and upper cervical spine (case 1), EEA and complemental posterior approach for occurred occipitocervical instability (case 2), C2 chordoma which required aggressive bone removal and consequent implant positioning, focusing on surgical planning (timing and type of surgical stages, materials and customization of fixation system) (case 3).Conclusion:EEA could represent a safe route to avoid injuries to neurovascular structure in clival locations, while a combined approach could be considered when tumor spreads laterally. Tumor involvement or surgical procedures could give raise to CVJ instability with the need of complementary posterior instrumentation. Thus, a tailored preoperative planning should play a key role, especially when aggressive bone removal and implant positioning are needed.

A personalized management paradigm for skull base chordoma based on surgical outcome and a genetic panel consisting of 1p36 and 9p21(p16) deletions

A personalized management paradigm for skull base chordoma based on surgical outcome and a genetic panel consisting of 1p36 and 9p21(p16) deletions

An institutional review of clinical outcomes for skull base chordoma: an analysis of 268 cases over 19 years

An institutional review of clinical outcomes for skull base chordoma: an analysis of 268 cases over 19 years

Endovascular Approach to Ruptured Sphenopalatine Artery: A Case Report and Literature Review

Epistaxis is a rare complication following the endonasal approach of skull base surgery. Conservative methods like anterior and posterior nasal packing can be useful, but when these fail, a neuro-interventional technique can be used as a last-resort measure in cases of severe bleeding. The authors identify a 22-year-old female patient with recurrent epistaxis following resection of skull-base chordoma through an endonasal approach. An endovascular catheter digital subtraction angiogram identified the cause of epistaxis as a rupture of the left sphenopalatine artery branch of the left external carotid artery. A large dissecting aneurysm in the right intracerebral artery was also incidentally found. The unique co-occurrence of vascular problems was successfully managed by neuro-interventional techniques.

RARE-32. PEDIATRIC METASTATIC SKULL BASE CHORDOMA WITH TP53 MUTATION – A CASE REPORT AND REVIEW OF THE LITERATURE

Chordoma is an uncommon bone tumor arising from notochordal remnant, which accounts for 1–4% of all bone malignancies. It commonly occurs along the cranial-spinal axis, and skull base is one of most frequent sites, representing 35–49% of all chordoma cases. Surgical resection is widely accepted as the first choice of treatment. There are only limited number of reports about pediatric chordoma cases, and its biological behavior including genetic backgrounds were largely unknown. Here, we present a 5 year-old girl with a large aggressive skull base chordoma of 6 cm in maximum diameter, which eventually had multiple systemic metastasis. We initially tried chemotherapy based on the protocol for the osteosarcoma, but in vain. Because the tumor was highly vascularized on angiography, after embolization of the feeding arteries and bilateral internal maxillary arteries, endoscopic endonasal surgery was performed. The tumor was sufficiently removed, achieving effective mass reduction, and the residual tumors involving the lower cranial nerves and craniocervial junction were additionally treated with Gamma Knife radiosurgery. However, one month later, it showed systemic metastasis to bilateral cervical lymph nodes and lung. We tried chemotherapy with nivolmab and imatinib for this patient, whereas they showed the partial effect. The genetic analysis revealed somatic TP53 c.569C>T, (p.P190L) mutation in chordoma specimen. In the past literature, we found only one study of the adult chordoma cases, in which majority of the patients had somatic TP53 mutation (p.P72R). Further investigation with large number of the cases is essential to clarify the molecular biology of pediatric chordomas.

Long-term outcomes in the treatment of pediatric skull base chordomas in the endoscopic endonasal era.

Pediatric skull base chordoma is a rare entity that is traditionally considered to display aggressive behavior with an increased risk of recurrence. There is an absence of literature examining outcomes in the pediatric population in general and using the endoscopic endonasal approach (EEA). The authors retrospectively reviewed all patients with skull base chordomas presenting by the age of 18 years to the Children's Hospital of Pittsburgh or the University of Pittsburgh Medical Center from 2004 to 2019. Clinical outcomes, the number and location of recurrences, and progression-free survival time were determined. Twenty patients met the study criteria. The most common presenting complaints were diplopia (n = 7), headache (n = 6), and swallowing difficulty (n = 4). Three cases were incidentally discovered. Twelve patients underwent single-stage EEA alone, 2 patients had two-stage EEA, and 6 patients had combined EEA with open far-lateral or extreme-lateral approaches. Fourteen patients underwent gross-total resection (GTR), and 6 patients had near-total resection. Larger tumors were more likely to require staging or a combined approach (86% vs 7%) and were less likely to receive GTR (33% vs 86%) but had comparable recurrence and mortality rates. Five patients developed CSF leaks requiring reoperation, 2 patients developed a permanent abducens nerve palsy, 1 patient suffered an internal carotid artery injury, 1 patient developed an epidural hematoma, and 1 patient developed a subdural empyema. Four (20%) patients had recurrence during follow-up (mean radiographic follow-up 59 months and mean time to local recurrence 19 months). Two patients with recurrence underwent further resection, and 1 patient elected to stop treatment. Both patients who underwent repeat resection experienced a second recurrence, one of whom elected to stop treatment. Both patients who died had an elevated Ki-67 (p = 0.039), one of whom developed de-differentiated histology. A third patient died of progressive spinal metastases without local recurrence and is one of 2 patients who developed postoperative spinal metastases. Both patients whose tumors became de-differentiated progressed from tumors with an initial Ki-67 of 15 or greater (p = 0.035) and received prior radiotherapy to the bulk tumor (p = 0.03). The majority of pediatric skull base chordomas, when managed at a specialized center with a goal of GTR, may have a better outcome than traditionally believed. Elevated Ki-67 rates may predict poor outcome and progression to de-differentiation.

Dosimetric analysis of local failures in skull-base chordoma and chondrosarcoma following pencil beam scanning proton therapy

BackgroundDespite combined modality treatment involving surgery and radiotherapy, a relevant proportion of skull-base chordoma and chondrosarcoma patients develop a local recurrence (LR). This study aims to analyze patterns of recurrence and correlate LR with a detailed dosimetric analysis.Methods222 patients were treated with proton radiotherapy for chordoma (n = 151) and chondrosarcoma (n = 71) at the PSI between 1998 and 2012. All patients underwent surgery, followed by pencil-beam scanning proton therapy to a mean dose of 72.5 ± 2.2GyRBE. A retrospective patterns of recurrence analysis was performed: LR were contoured on follow-up MRI, registered with planning-imaging and the overlap with initial target structures (GTV, PTVhigh-dose, PTVlow-dose) was calculated. DVH parameters of planning structures and recurrences were calculated and correlated with LR using univariate and multivariate cox regression.ResultsAfter a median follow-up of 50 months, 35 (16%) LR were observed. Follow-up MRI imaging was available for 27 (77%) of these recurring patients. Only one (3.7%) recurrence was located completely outside the initial PTV (surgical pathway recurrence). The mean proportions of LR covered by the initial target structures were 48% (range 0–86%) for the GTV, 70% (range 0–100%) for PTVhigh and 83% (range 0–100%) for PTVlow. In the univariate analysis, the following DVH parameters were significantly associated with LR: GTV(V < 66GyRBE, p = 0.01), GTV(volume, p = 0.02), PTVhigh(max, p = 0.02), PTVhigh(V < 66GyRBE, p = 0.03), PTVhigh(V < 59GyRBE, p = 0.02), PTVhigh(volume, p = 0.01) and GTV(D95, p = 0.05). In the multivariate analysis, only histology (chordoma vs. chondrosarcoma, p = 0.01), PTVhigh(volume, p = 0.05) and GTV(V < 66GyRBE, p = 0.02) were independent prognostic factors for LR.ConclusionThis study identified DVH parameters, which are associated with the risk of local recurrence after proton therapy using pencil-beam scanning for patients with skull-base chordoma and chondrosarcoma.

PO-0883: Early outcomes in patients with skull base chordomas and chondrosarcomas treated with proton therapy

PO-0883: Early outcomes in patients with skull base chordomas and chondrosarcomas treated with proton therapy

Proton Radiation Therapy for Pediatric Chordomas of the Base of Skull

There are few data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population due to its rarity. We report outcomes for pediatric patients with BOS chordomas treated with proton radiotherapy (PRT). Between 1981 and 2019, pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (comboRT) at a single institution. The primary endpoints were overall survival (OS) and progression free survival (PFS). Univariable and multivariable analysis was used to identify prognostic factors for OS. Cox proportional hazards regression and Kaplan Meier estimates were used for survival analyses. 186 patients were identified [104 female (56%) and 82 male (44%]. Median age at diagnosis was 11 years (IQR 7-16, 1-21). 114 patients (61%) had chordomas located in the upper and/or middle clivus, 65 (35%) in the lower clivus and 7 (4%) in the cranio-cervical junction. The majority of the patients (n = 128, 68%) were diagnosed with conventional chordoma, 53 (28%) with a chondroid subtype and 7(4%) with poorly-differentiated chordoma. All patients underwent surgical resection (range, 1-8). 29 patients (16%) underwent gross total resection, 149 patients (80%) underwent STR while 8 patients (4%) had biopsy only. 2 patients (1%) were treated with pre- and post-op RT, while 184 patients (99%) received only post-op RT. 7 patients (4%) received radiation in a twice daily (BID) fashion. 13 patients (7%) received pre-RT chemotherapy. 54 patients (29%) developed progressive disease prior to RT. 37 patients (20%) were treated with PRT and 149 (80%) patients received comboRT. Median prescription dose was 77.4 Gy (RBE) (range, 59.3 – 83.3) delivered in 1.2 - 2.2 Gy (RBE) fractions (1.2 Gy for BID). The median maximum dose to the brainstem was 65.7 Gy (RBE) (range, 40.8 - 80). At a median follow-up of 7.3 years (range, 0.6 – 35.5) from the date of diagnosis 52 patients recurred (33 local, 13 distant and 6 iatrogenic). The median OS and PFS were 23.8 and 23.3 years, respectively. The 5- and 10-year OS rates were 83% and 78%, respectively. The 5- and 10-year PFS rates were 76% and 71%, respectively. On multivariate analysis, chondroid and cellular pathological subtype, the administration of chemotherapy prior to RT and the lower clivus location of the tumor were prognostic factors for OS and PFS. RT was well tolerated, with most acute side effects limited to moderate erythema and otitis media. Late toxicities included 4 cases of brainstem injury, and single case each of moyamoya disease, osteomyelitis, and esophageal stricture. 3 patients developed secondary radiation related malignancies. This is the largest cohort of pediatric skull base chordomas in the literature to date. High dose PRT following surgical resection is an effective treatment with a high rate of disease control and minimal late toxicity.

Vision Loss Following High-Dose Proton-Based Radiotherapy For Skull-Base Chordoma And Chondrosarcoma

Vision Loss Following High-Dose Proton-Based Radiotherapy For Skull-Base Chordoma And Chondrosarcoma

Mean platelet volume and platelet distribution width serve as prognostic biomarkers in skull base chordoma: a retrospective study

BackgroundIncreasing studies have demonstrated that activated platelets play an essential role in tumour progression. However, the level and prognostic role of platelet indices in chordoma patients remain unclear. The aim of the current study was to characterize the prognostic performance of platelet count (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) in skull base chordoma patients.Methods187 primary skull base chordoma patients between January 2008 and September 2014 were enrolled in this retrospective study. The optimal cut-off values were determined by X-tile software, and the correlations between PLT, MPV, PDW and clinicopathological features were further analysed. Kaplan-Meier curve and Cox regression analysis were used for survival analysis.ResultsThe values of preoperative PTL, MPV and PDW ranged from 104 to 501 × 109/L, 6.7 to 14.2 fl, and 7.8 to 26.2%, respectively. Elevated PLT was associated with larger tumour volume (p = 0.002). Kaplan-Meier survival analysis revealed that increased MPV and PDW were associated with shorter overall survival (p = 0.022 and 0.008, respectively). Importantly, multivariate Cox analysis demonstrated that elevated PDW was an independent unfavourable predictive factor for overall survival (hazard ratio (HR), 2.154, 95% confidence interval (CI), 1.258–3.688, p = 0.005).ConclusionsOur data show that elevated MPV and PDW are associated with poor outcomes in skull base chordoma and that PDW may be helpful to identify patients with high risk.

Vertebrobasilar Artery Encasement by Skull Base Chordomas: Surgical Outcome and Management Strategies.

Vascular encasement by skull base chordomas can increase surgical risk and hinder completeness of resection. However, the evidence behind this remains anecdotic. To give a better portrayal of chordomas encasing vertebrobasilar arteries mainly in regard of surgical vascular risk and its impact on extent of resection. A retrospective cohort study comparing skull base chordomas with encasement (≥180o encirclement) of the vertebrobasilar arteries to a control group of skull base chordomas with intradural extension. Data gathered involved pre- and postoperative volumetric analysis of the tumor, degree of encasement of involved vessel, occurrence of complication, and survival data including progression-free survival (PFS) and overall survival (OS). A total of 24 patients with vertebrobasilar encasement were included in the study and an equal number of control cases were randomly selected from the same time period, totalizing 48 patients. Lower clival tumors with condyle involvement were more likely to have encasement. Gross total resection (GTR) rate was significantly lower in the encasement group (13% vs 42%, P=.023). Rates of postoperative new neurological deficit, CFS leak and 30 d postoperative mortality were not statistically different between groups. There was no statistically significant difference in mean PFS (P=.608) and OS (P=.958). Skull base chordomas encasing vertebrobasilar arteries are highly challenging tumors. This study demonstrates that although safe resection is possible, GTR is hindered by the presence of encasement. We advocate letting the tumor's adherence to vessels lead the resection, leaving a small piece of tumor behind if adherent to the vessels.

Endoscopic endonasal resection and radiotherapy as treatment for skull base chordomas

Background The role of endonasal endoscopic surgery and radiotherapy in the treatment of skull base chordomas remains unclear.Objective We investigated the effect of endonasal endoscopic surgery and radiotherapy as treatment for skull base chordomas.Method We investigated 46 patients (2006–2018) treated at the Affiliated Eye Ear Nose and Throat Hospital, Fudan University. We documented demographics, clinical presentation, operative resection, complications, postoperative radiotherapy, follow-up time, and survival in all patients.Result Complete tumour resection was performed in 18 (39.1%), subtotal tumour resection in 16 (34.8%), and partial tumour resection in 12 (26.1%) patients. Most common clinical manifestations included nasal obstruction (41%), headaches (30%), and visual impairment (20%). The median duration of progression-free survival (PFS) and overall survival (OS) was 21.5 and 33.5 months, respectively. Primary vs. recurrent disease (p = .043), partial resection (PR) vs. subtotal resection (STR) (p = .006), STR vs. gross total resection (GTR) (p = .020), GTR vs. PR (p = .001), and complicated vs. uncomplicated status (p = .002) were significantly associated with PFS. Primary vs. recurrent disease (p = .002), PR vs. STR (p = .001), GTR vs. PR (p = .001), surgery alone vs. surgery concomitant with radiotherapy (p = .048), and complicated vs. uncomplicated status (p = .017) were significantly associated with OS.Conclusion Surgery is the primary treatment for chordoma; higher tumour resection rates are associated with higher OS and PFS. Surgeons should aim to resect as much tumour as is safely possible. Postoperative radiotherapy is useful adjuvant treatment to improve OS, and IMRT serves as an effective alternative to PBRT.The optimal radiotherapeutic technique is determined by cost, accessibility, availability of the modality, and tumour volume.

Prognostic Value of Cumulative Score Based on Preoperative Fibrinogen and Albumin Level in Skull Base Chordoma.

ObjectiveInflammation and malnutrition have been shown to be correlated with tumor progression and a poor prognosis in various cancers. However, the clinical implications of biomarkers of inflammation and malnutrition in chordoma have not been elucidated. We attempted to characterize the fibrinogen and albumin levels in skull base chordoma and investigate their correlations with clinicopathological data and survival.MethodsThe preoperative levels of fibrinogen and albumin were assessed in 183 primary skull base chordoma patients. The cutoff values were determined by X-tile software, and their correlations with patient prognosis were further explored using the Kaplan–Meier curve and Cox proportional hazards regression analysis. In addition, the predictive performances of these markers in survival were evaluated by receiver operating characteristic curves.ResultsThe values of fibrinogen and albumin in skull base chordoma patients ranged from 1.73 to 7.40 and 37.6 to 53.0 g/L, respectively. The optimal cutoff values for fibrinogen and albumin were 3.29 and 44.60 g/L, respectively. Fibrinogen and albumin were correlated with the patient age and tumor pathology types. Albumin, but not fibrinogen, was associated with the patients’ progression-free survival and overall survival. Importantly, the FA score, which combines fibrinogen and albumin, could independently predict both progression-free survival and overall survival, and enhanced the performance of fibrinogen or albumin in survival prediction in skull base chordoma.ConclusionOur data reveal the clinical prognostic role of albumin and suggest that the FA score may be a valuable prognostic grading system in skull base chordoma.

Proton and carbon ion therapy for skull base chordomas.

Proton and carbon ion therapy for skull base chordomas.

Skull base chordomas review of current treatment paradigms.

BackgroundChordomas are locally invasive neoplasms, arising from notochordal remnants and can appear anywhere along the axial skeleton. Local recurrences are common, and distant metastases may occur years after the initial presentation.MethodsLiterature review of current treatment strategies for chordomas of the skull base.ResultsSurgery is the mainstay of treatment and complete resection has paramount importance for prognosis.When complete resection is not achieved recurrent disease is common. The anatomical complexity of the skull base makes resection complex. Endonasal endoscopic approaches to the clivus has become increasingly favored in recent years although addressing reconstruction of the skull base to prevent CSF leak may be challenging.Evidence suggests that radiotherapy should not be considered as a primary single modality when trying to achieve cure of the disease. Nonetheless, immediate post-operative radiotherapy improves survival. Many strategies have been suggested to preserve sensitive vital structures in the skull base during treatment but as for survival there is no evidence of advantage when comparing adjuvant therapy with photon radiotherapy, gamma knife surgery, proton beam therapy, and carbon ion radiation therapy.There is no evidence to support cytotoxic chemotherapy in the treatment of chordomas but targeted therapies have started to show promise. Several optional molecular targets exist. Brachyury is overexpressed in 95% of chordomas but not in other mesenchymal neoplasms. However, its precise role in chordoma pathogenesis is currently unclear, and its cellular location in the nucleus makes it difficult to target. The inhibition of brachyury in chordoma cell lines induces growth arrest and apoptosis. This does not have clinical application to date. There are retrospective results with different molecular targeted therapies for advanced chordomas with some effectiveness.ConclusionDespite improvements made in the past 10 years in our knowledge of chordoma biology, available therapies still offer a limited benefit. There is an unmet need for new therapeutic options for patients with advanced disease. Therefore, patients with advanced disease should be encouraged to participate in clinical trials when and where available.

Long-term outcomes of skull base chordoma treated with high-dose carbon-ion radiotherapy.

BackgroundWe evaluated the long‐term efficacy and safety of carbon‐ion radiotherapy (C‐ion RT) for skull base chordoma, a rare neoplasm.MethodsThirty‐four patients with skull base chordoma who were treated with C‐ion RT were prospectively enrolled and analyzed retrospectively. C‐ion RT was delivered with 60.8 Gy (relative biological effectiveness [RBE]) in 16 fractions at four fractions per week.ResultsThe median follow‐up period was 108 months. The 5‐ and 9‐year local control rates were 76.9% and 69.2%, respectively. The 5‐ and 9‐year overall survival rates were 93.5% and 77.4%, respectively. Regarding grade 3 or more severe late reactions, one patient developed a grade 3 mucosal ulcer, two developed grade 4 ipsilateral optic nerve injuries, and one developed a grade 5 mucosal ulcer at 9 years and 3 months after C‐ion RT.ConclusionC‐ion RT with 60.8 Gy (RBE)/16 fractions is a promising treatment option for inoperable skull base chordoma.

Prognostic impact of the \u201cSekhar grading system for cranial Chordomas\u201d in patients treated with pencil beam scanning proton therapy: an institutional analysis

BackgroundSkull base chordomas are rare and heterogeneously behaving tumors. Though still classified as benign they can grow rapidly, are locally aggressive, and have the potential to metastasize. To adapt the treatment to the specific needs of patients at higher risk of recurrence, a pre-proton therapy prognostic grading system would be useful. The aim of this retrospective analysis is to assess prognostic factors and the “Sekhar Grading System for Cranial Chordomas” (SGSCC) by evaluating the larger cohort of patients treated at our institution as to determine its reproducibility and ultimately to ensure more risk adapted local treatments for these challenging tumors.MethodsWe analyzed 142 patients treated for skull base chordomas between 2004 and 2016. We focused the analysis on the 5 criteria proposed for the SGSCC (tumor size, number of anatomic regions and vessels involved, intradural invasion, as well as recurrence after prior treatment) and classified our patients according to their score (based on the above mentioned criteria) into three prognostic groups, low-risk, intermediate-risk and high-risk. The three groups were then analyzed in regards of local control, local recurrence-free survival and overall survival.ResultsThe median follow up was 52 months (range, 3–152). We observed 34 (24%) patients with a local recurrence, resulting in a local control of 75% at 5 years. Overall survival was 83% at 5 years, 12 (9%) patients had died due to local progression. When split into the three prognostic groups according to the SGSCC the observed local control was 90, 72 and 64% (p = 0.07) in the low-, intermediate- and high-risk group, respectively. A similar correlation was observed for local recurrence-free survival with 93, 89 and 66% (p = 0.05) and for overall survival with 89, 83 and 76% (p = 0.65) for the same prognostic groups.ConclusionsAfter splitting our patient cohort into the three SGSCC risk groups, we found a trend towards better outcome for those patients with lower as opposed to higher scores. These results suggest that this prognostic grading system published by Sekhar et al. could be integrated in the management decision-tree for patients with skull base chordoma.

MRI Signal Intensity and Electron Ultrastructure Classification Predict the Long-Term Outcome of Skull Base Chordomas.

MR imaging is a useful and widely used evaluation for chordomas. Prior studies have classified chordomas into cell-dense type and matrix-rich type according to the ultrastructural features. However, the relationship between the MR imaging signal intensity and ultrastructural classification is unknown. We hypothesized that MR imaging signal intensity may predict both tumor ultrastructural classification and prognosis. Seventy-nine patients with skull base chordomas who underwent 95 operations were included in this retrospective single-center series. Preoperative tumor-to-pons MR imaging signal intensity ratios were calculated and designated as ratio on T1 FLAIR sequence (RT1), ratio on T2 sequence (RT2), and ratio on enhanced T1 FLAIR sequence (REN), respectively. We assessed the relationships among signal intensity ratios, ultrastructural classification, and survival. Compared with the matrix-rich type group, the cell-dense type chordomas showed lower RT2 (cell-dense type: 1.90 ± 0.38; matrix-rich type: 2.61 ± 0.60 P < .001). The model of predicting cell-dense type based on RT2 had an area under the curve of 0.83 (95% CI, 0.75-0.92). In patients without radiation therapy, both progression-free survival (P = .003) and overall survival (P = .002) were longer in the matrix-rich type group than in the cell-dense type group. REN was a risk factor for progression-free survival (hazard ratio = 10.24; 95% CI, 1.73-60.79); RT2 was a protective factor for overall survival (hazard ratio = 0.33; 95% CI, 0.12-0.87); and REN was a risk factor for overall survival (hazard ratio = 4.76; 95% CI, 1.51-15.01). The difference in MR imaging signal intensity in chordomas can be explained by electron microscopic features. Both signal intensity ratios and electron microscopic features may be prognostic factors.

Outcomes, Prognostic Factors and Salvage Treatment for Recurrent Chordoma After Pencil Beam Scanning Proton Therapy at the Paul Scherrer Institute

AimsThe outcome of chordoma patients with local or distant failure after proton therapy is not well established. We assessed the disease-specific (DSS) and overall survival of patients recurring after proton therapy and evaluated the prognostic factors affecting DSS. Materials and methodsA retrospective analysis was carried out of 71 recurring skull base (n = 36) and extracranial (n = 35) chordoma patients who received adjuvant proton therapy at initial presentation (n = 42; 59%) or after post-surgical recurrence (n = 29; 41%). The median proton therapy dose delivered was 74 GyRBE (range 62–76). The mean age was 55 ± 14.2 years and the male/female ratio was about one. ResultsThe median time to first failure after proton therapy was 30.8 months (range 3–152). Most patients (n = 59; 83%) presented with locoregional failure only. There were only 12 (17%) distant failures, either with (n = 5) or without (n = 7) synchronous local failure. Eight patients (11%) received no salvage therapy for their treatment failure after proton therapy. Salvage treatments after proton therapy failure included surgery, systemic therapy and additional radiotherapy in 45 (63%), 20 (28%) and eight (11%) patients, respectively. Fifty-three patients (75%) died, most often from disease progression (47 of 53 patients; 89%). The median DSS and overall survival after failure was 3.9 (95% confidence interval 3.1–5.1) and 3.4 (95% confidence interval 2.5–4.4) years, respectively. On multivariate analysis, extracranial location and late failure (≥31 months after proton therapy) were independent favourable prognostic factors for DSS. ConclusionThe survival of chordoma patients after a treatment failure following proton therapy is poor, particularly for patients who relapse early or recur in the skull base. Although salvage treatment is administered to most patients with uncontrolled disease, they will ultimately die as a result of disease progression in most cases.