Optimizing radiotherapy strategies for skull base chordoma: a comprehensive meta-analysis and systematic review of treatment modalities and outcomes.

OBJECTIVE: In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC. METHODS: Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05. RESULTS: A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively. CONCLUSIONS: The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

The prognostic significance of different degrees of resection of skull base chordoma.

BACKGROUND: Complete resection combined with postoperative radiotherapy is ideal for skull base chordomas. The recent literature suggests that the degree of surgical resection is the most important prognostic factor. METHODS: We retrospectively analyzed the clinical data of 16 patients with initial chordoma treated at our center between August 2015 and December 2021 and conducted a retrospective study on the prognosis of surgical treatment of skull base chordoma between 2013 and 2022. RESULTS: According to the Kaplan-Meier method, there was a significant difference in PFS between patients aged > 50 years and < 50 years, and no significant difference was observed in PFS for tumor involvement of the internal carotid artery, dura, or superior or inferior clivus. However, there was still a correlation with prognosis. As observed in the included literature, the 5-year overall survival rate was significantly higher in patients undergoing total skull base chordoma resection than in those undergoing subtotal resection (STR), which in turn was significantly higher than in those undergoing partial resection (PR). Patients undergoing subtotal resection had significantly better 5-year PFS rates than those undergoing PR. CONCLUSION: Our study shows that gross total resection and STR have better survival in patients with skull base chordomas compared to PR.

[Stereotactic brain radiosurgery in the treatment of skull base tumors.] / Radiocirugía cerebral estereotáctica en el tratamiento de tumores de base de cráneo.

Stereotactic radiosurgery has shown effectiveness in the multimodal treatment of skull base tumors, however it is suggested that in radiobiologically sensitive areas (eg. optic nerves and brainstem) the radiation dose should be reduced due to radiotoxic effects. To avoid the consequent therapeutic ineffectiveness, a recently implemented alternative is multisession radiosurgery (RCH). We retrospectively analyzed a series of patients with skull base tumors, in order to evaluate the treatment with RCH through tumor control in the post-treatment images. Age, sex, tumor histology, tumor volume, radiation protocol, pre-treatment Karnofsky performance status (KPS) previous neurosurgery and radiant treatment were also evaluated. Eighty-four patients were treated between January 2009 and January 2017. The median age was 51.5 years; females: 53.6%. There was a 92.7% non-progression after treatment, with a median follow-up time of 36 months. Treated tumors were mainly pituitary adenomas, acoustic schwannomas, and skull base meningiomas. Most of the patients received a 5-day fractionated treatment scheme, with a total dose of 25 Gy. No clinically manifest late radiotoxicity was observed. In the multivariate analysis, a high pre-treatment KPS was significantly associated with tumor non-progression. In our series, the high incidence of tumor non-progression would indicate that treatment with RCH could be a therapeutic option in some cases of skull-base tumors, mainly recurrences or tumor residuals of pituitary adenomas, neurinomas and meningiomas.

La radiocirugía estereotáctica ha demostrado efectividad en el tratamiento multimodal de los tumores de base de cráneo, de todas maneras se sugiere que en áreas radiobiológicamente sensibles (ej. nervios ópticos y tronco cerebral) la dosis radiante debería reducirse por los efectos radiotóxicos. Para evitar la ineficacia terapéutica, una alternativa recientemente implementada es la radiocirugía multisesión (RCH). Se analizó en forma retrospectiva una serie de tumores de base de cráneo, con el fin de evaluar el tratamiento con RCH a través del control tumoral en las imágenes post-tratamiento. Se evaluó también edad, sexo, histología tumoral, volumen tumoral, protocolo radiante, Karnofsky performance status (KPS) pre-tratamiento y neurocirugía y tratamiento radiante previos. Fueron tratados 84 pacientes entre enero 2009 y enero 2017. La mediana de edad fue 51.5 años; sexo femenino: 53.6%. Hubo un 92.7% de no-progresión luego del tratamiento, con una mediana de tiempo de seguimiento de 36 meses. Los tumores tratados fueron principalmente adenomas hipofisarios, neurinomas del acústico, y meningiomas de base de cráneo. La mayoría de los pacientes recibió un esquema de tratamiento fraccionado de 5 días, con una dosis total de 25 Gy. No se observó radiotoxicidad tardía clínicamente manifiesta. En el análisis multivariado, un KPS alto pre-tratamiento fue significativamente asociado a la no-progresión tumoral. En esta serie, la alta incidencia de no-progresión tumoral indicaría que el tratamiento con RCH podría ser una opción terapéutica en algunos casos de tumores de base de cráneo, principalmente recurrencias o remanencias tumorales de adenomas hipofisarios, neurinomas y meningiomas.

Radiocirugía cerebral estereotáctica en el tratamiento de tumores de base de cráneo / Stereotactic brain radiosurgery in the treatment of skull base tumors

La radiocirugía estereotáctica ha demostrado efectividad en el tratamiento multimodal de los tumores de base de cráneo, de todas maneras se sugiere que en áreas radiobioló;gicamente sensibles (ej. nervios ó;pticos y tronco cerebral) la dosis radiante debería reducirse por los efectos radiotó;xicos. Para evitar la ineficacia terapó;©utica, una alternativa recientemente implementada es la radiocirugía multisesió;n (RCH). Se analizó; en forma retrospectiva una serie de tumores de base de cráneo, con el fin de evaluar el tratamiento con RCH a travó;©s del control tumoral en las imágenes post-tratamiento. Se evaluó; tambín edad, sexo, histología tumoral, volumen tumoral, protocolo radiante, Karnofsky performance status (KPS) pre-tratamiento y neurocirugía y tratamiento radiante previos. Fueron tratados 84 pacientes entre enero 2009 y enero 2017. La mediana de edad fue 51.5 aó;±os; sexo femenino: 53.6%. Hubo un 92.7% de no-progresió;n luego del tratamiento, con una mediana de tiempo de seguimiento de 36 meses. Los tumores tratados fueron principalmente adenomas hipofisarios, neurinomas del acó;ºstico, y meningiomas de base de cráneo. La mayoría de los pacientes recibió; un esquema de tratamiento fraccionado de 5 días, con una dosis total de 25 Gy. No se observó; radiotoxicidad tardía clínicamente manifiesta. En el análisis multivariado, un KPS alto pre-tratamiento fue significativamente asociado a la no-progresió;n tumoral. En esta serie, la alta incidencia de no-progresió;n tumoral indicaría que el tratamiento con RCH podría ser una opció;n terapó;©utica en algunos casos de tumores de base de cráneo, principalmente recurrencias o remanencias tumorales de adenomas hipofisarios, neurinomas y meningiomas.

Stereotactic radiosurgery has shown effectiveness in the multimodal treatment of skull base tumors, however it is suggested that in radiobiologically sensitive areas (eg. optic nerves and brainstem) the radiation dose should be reduced due to radiotoxic effects. To avoid the consequent therapeutic ineffectiveness, a recently implemented alternative is multisession radiosurgery (RCH). We retrospectively analyzed a series of patients with skull base tumors, in order to evaluate the treatment with RCH through tumor control in the post-treatment images. Age, sex, tumor histology, tumor volume, radiation protocol, pre-treatment Karnofsky performance status (KPS) previous neurosurgery and radiant treatment were also evaluated. Eighty-four patients were treated between January 2009 and January 2017. The median age was 51.5 years; females: 53.6%. There was a 92.7% non-progression after treatment, with a median follow-up time of 36 months. Treated tumors were mainly pituitary adenomas, acoustic schwannomas, and skull base meningiomas. Most of the patients received a 5-day fractionated treatment scheme, with a total dose of 25 Gy. No clinically manifest late radiotoxicity was observed. In the multivariate analysis, a high pre-treatment KPS was significantly associated with tumor non-progression. In our series, the high incidence of tumor non-progression would indicate that treatment with RCH could be a therapeutic option in some cases of skull-base tumors, mainly recurrences or tumor residuals of pituitary adenomas, neurinomas and meningiomas.

The use of proton therapy in the treatment of head and neck cancers.

External beam radiation therapy is a commonly utilized treatment modality in the management of head and neck cancer. Given the close proximity of disease to critical normal tissues and structures, the delivery of external beam radiation therapy can result in severe acute and late toxicities, even when delivered with advanced photon-based techniques, such as intensity-modulated radiation therapy. The unique physical characteristics of protons make it a promising option in the treatment of advanced head and neck cancer, with the potential to improve sparing of normal tissues and/or safely escalate radiation doses. Clinical implementation will require the continued development of advanced techniques such as intensity-modulated proton therapy, using pencil beam scanning, as well as rigorous methods of quality assurance and adaptive techniques to accurately adjust to changes in anatomy due to disease response. Ultimately, the widespread adaptation and implementation of proton therapy for head and neck cancer will require direct, prospective comparisons to standard techniques such as intensity-modulated radiation therapy, with a focus on measures such as toxicity, disease control, and quality of life.

Natural history and surgical treatment of chordoma: a retrospective cohort study / História natural e tratamento cirúrgico de cordoma: um estudo retrospectivo de coorte

CONTEXT AND OBJECTIVE: Chordoma is a rare tumor with a high risk of locoregional recurrences. The aim of this study was analyze the long-term results from treating this pathological condition. DESIGN AND SETTING: Cohort study in a single hospital in São Paulo, Brazil. METHODS: This was a retrospective cohort study on 42 patients with chordoma who were treated at Hospital A. C. Camargo between 1980 and 2006. The hospital records were reviewed and a descriptive analysis was performed on the clinical-pathological variables. Survival curves were estimated using the Kaplan-Meier method and these were compared using the log-rank test. RESULTS: Nineteen patients were men and 23 were women. Twenty-five tumors (59.5%) were located in the sacrum, eleven (26.2%) in the skull base and six (14.3%) in the mobile spine. Surgery was performed on 28 patients (66.7%). The resection was considered to have negative margins in 14 cases and positive margins in 14 cases. The five-year overall survival (OS) was 45.4%. For surgical patients, the five-year OS was 64.3% (82.2% for negative margins and 51.9% for positive margins). In the inoperable group, OS was 37.7% at 24 months and 0% at five years. CONCLUSION: Complete resection is related to local control and definitively has a positive impact on long-term survival. .

CONTEXTO E OBJETIVO: Cordoma é um tumor raro e com alto risco de recidiva locorregional. O objetivo deste estudo foi analisar os resultados a longo prazo do tratamento dessa doença. TIPO DE ESTUDO E LOCAL: Estudo de coorte realizado em um único hospital em São Paulo, Brasil. MÉTODOS: Estudo de coorte retrospectivo com 42 pacientes com cordoma tratados de 1980 e 2006 no Hospital A. C. Camargo. Os prontuários foram revistos e foi realizada a análise descritiva das variáveis clínicas e patológicas. As curvas de sobrevida foram estimadas pelo método de Kaplan-Meier e a comparação entre elas, pelo teste de log-rank. RESULTADOS: Dezenove pacientes eram homens e 23, mulheres. Vinte e cinco tumores (59,5%) estavam localizados no sacro, 11 (26,2%) na base do crânio e 6 (14,3%), na coluna móvel. A cirurgia foi realizada em 28 pacientes (66,7%). A ressecção foi considerada como tendo margens negativas em 14 casos e margens comprometidas em 14 pacientes. A sobrevida global (SG) em 5 anos foi de 45,4%. Para os pacientes cirúrgicos, a SG em 5 anos foi de 64,3% (82,2% para as margens negativas e 51,9% de margens positivas). No grupo inoperável, a SG em 24 meses foi de 37,7% e 0% em 5 anos. CONCLUSÃO: A ressecção completa está relacionada com o controle local e, definitivamente, tem impacto positivo na sobrevida a longo prazo. .

Natural history and surgical treatment of chordoma: a retrospective cohort study.

CONTEXT AND OBJECTIVE: Chordoma is a rare tumor with a high risk of locoregional recurrences. The aim of this study was analyze the long-term results from treating this pathological condition. DESIGN AND SETTING: Cohort study in a single hospital in São Paulo, Brazil. METHODS: This was a retrospective cohort study on 42 patients with chordoma who were treated at Hospital A. C. Camargo between 1980 and 2006. The hospital records were reviewed and a descriptive analysis was performed on the clinical-pathological variables. Survival curves were estimated using the Kaplan-Meier method and these were compared using the log-rank test. RESULTS: Nineteen patients were men and 23 were women. Twenty-five tumors (59.5%) were located in the sacrum, eleven (26.2%) in the skull base and six (14.3%) in the mobile spine. Surgery was performed on 28 patients (66.7%). The resection was considered to have negative margins in 14 cases and positive margins in 14 cases. The five-year overall survival (OS) was 45.4%. For surgical patients, the five-year OS was 64.3% (82.2% for negative margins and 51.9% for positive margins). In the inoperable group, OS was 37.7% at 24 months and 0% at five years. CONCLUSION: Complete resection is related to local control and definitively has a positive impact on long-term survival.

Occipital condyle syndrome secondary to bone metastases from rectal cancer.

Skull-base metastases are very unfrequent. Occipital condyle syndrome (OCS) is usually underdiagnosed. Until now few cases have been reported in the literature. We present a 71-year-old woman with metastatic rectum adenocarcinoma, with right occipital headache and ipsilateral hypoglossal palsy, diagnosed by computed tomography and magnetic resonance imaging of OCS due to a skull-base metastasis and treated with radiation therapy.

Anterolateral and lateral skull-base approaches for treatment of neoplastic diseases.

PURPOSE: Neoplasms affecting the anterolateral and lateral skull base have different sites of origin and histology, and its resection is technically difficult. The purpose of this study was to describe the surgical outcome and overall and disease-free survival of patients who had anterolateral and lateral skull base procedures for treatment of neoplasms with and without adjuvant therapy. MATERIALS AND METHODS: A retrospective study was performed on 26 patients who underwent anterolateral or lateral skull-base procedures through subcranial approaches such as maxillectomy with ethmoidectomy, osteoplastic maxillotomy, transmandibular, infratemporal, and transtemporal/infratemporal techniques for treatment of neoplastic diseases. Twenty-one cases were malignancies, with no evidence of metastasis. These approaches were combined frequently with a transbasal, pterional, subtemporal, or temporo-occipital craniotomy. Survival and disease-free intervals were evaluated with the Kaplan-Meier product limit method. RESULTS: Nine cases were maxillary antrum malignancies with extension to the middle fossa and/or infratemporal fossa, 7 with nasopharyngeal neoplasms, 3 malignant lesions in the infratemporal fossa, and 3 with auditory canal carcinomas. The rest had miscellaneous diagnosis. Major morbidity occurred in 15% of cases. Perioperative mortality was 0. From 21 cases with malignancies, 4 had recurrences and the overall survival was 78% at 36 months of follow-up. CONCLUSION: Anterolateral and lateral skull-base surgery is done with low morbidity and no operative mortality. The oncologic results are better than those reported in the literature probably because of a stringent selection of cases, although a longer follow-up period is required.

Chordomas of the skull base: follow-up review and prognostic factors.

OBJECT: Chordomas are rare tumors that arise from the remnants of the notochord. Because of their deep location, local infiltrative nature, and involvement of surrounding bone, treatment of chordoma is a challenge. The authors analyze the data and prognostic factors obtained during the follow-up period (range 1-150 months, median 38 months) in 53 patients with craniocervical junction chordoma and 10 patients with chondrosarcoma. METHODS: Several surgical approaches were used, and some tumor excisions required staged procedures. Survival was calculated according the Kaplan-Meier method. Statistical analysis was performed using the Fisher exact and Kruskal-Wallis tests. Radical/subtotal resection was achieved in 77.8% of the patients. The mortality rate during the follow-up period was 14.3%. In patients harboring chondrosarcoma better 5-year recurrence-free survival (RFS) rates were demonstrated than in those with chordoma (100% and 50.7%, respectively). Histological patterns (typical or chondroid chordoma) and patient age at onset of symptoms had no effect on the RFS rates. Radical/subtotal resections were associated with better RFS rates than partial resection. Adjuvant proton-beam radiotherapy was shown to increase the RFS rates compared with conventional radiotherapy (90.9% and 19.4%, respectively at 4 years posttreatment). Karyotypically abnormal tumors were associated with worst RFS rates as compared with karyotypically normal lesions (44.5% and 90.3%, respectively at 3 years). Cases of cranial nerve palsy, followed by CSF leakages were the most frequent postoperative complication. Permanent postoperative neurological deficit was observed in 28.6% of the patients. CONCLUSIONS: A better prognosis was observed in patients with chondrosarcoma compared with those harboring chordoma. Histological pattern and the patient's age at symptom onset were not factors that influenced prognosis in cases of chordoma. Extensive resection and possibly adjuvant proton-beam radiotherapy provided better prognosis for these patients.

Chordomas of the craniocervical junction: follow-up review and prognostic factors.

OBJECT: Chordomas are rare tumors that arise from the remnants of the notochord. Because of their deep location, local infiltrative nature, and involvement of surrounding bone, treatment of chordomas is a challenge. In this study the authors analyze the data and prognostic factors obtained during the follow-up period (range 1-150 months, median 38 months) in 53 patients with craniocervical junction chordomas and 10 patients with chondrosarcomas. METHODS: Several surgical approaches were used, and some tumor excisions required staged procedures. Survival was calculated according the Kaplan-Meier method. Statistical analysis was performed using Fisher exact, log rank and Kruskal-Wallis tests. Radical/subtotal resection was achieved in 77.8% of the patients. The mortality rate during the follow-up period was 14.3%. In patients harboring chondrosarcoma better 5-year recurrence-free survival (RFS) rates were demonstrated than in those with chordoma (100% and 50.7%. respectively). Histological patterns (typical or chondroid chordomas) and patient age at onset of symptoms had no effect on the RFS rates. Radical/subtotal resections were associated with better RFS rates than partial resection. Adjuvant proton-beam therapy was shown to increase the RFS rates compared with conventional radiotherapy (90.9% and 19.4%, respectively, at 4 years posttreatment). Karyotypically abnormal tumors were associated with the worst RFS rates compared with karyotypically normal lesions (44.5% and 90.3%, respectively, at 3 years). Cases of cranial nerve palsy followed by those with cerebrospinal fluid leakages were the most frequent postoperative complications. Permanent postoperative neurological deficit was observed in 28.6% of the patients. CONCLUSIONS: A better prognosis was observed in patients with chondrosarcoma compared with those harboring chordoma. Histological pattern and patient age at symptom onset were not factors that influenced prognosis in cases of chordoma. Extensive resection and possibly adjuvant proton-beam therapy provided better prognoses for these patients.

Hemangioblastoma of the posterior fossa. The role of multimodality treatment.

The authors made a review of a series of patients with hemangioblastomas of the posterior fossa treated between 1973 and 1993. A total of 32 patients were analyzed with 24 patients receiving resection, 8 patients receiving radiosurgery and 2 patients receiving conventional radiotherapy. The mortality in the patients with a resection was considered acceptable with 2 deaths (8%) and with a morbidity of 3 patients (12.5%). A review of the literature suggests that conventional radiotherapy with high doses (45-60 Gy) may have a role in the post-operative control of hemangioblastomas and in some cases could be employed even before the resection in order to facilitate the surgery. The radiosurgical treatment is regarded like adjuvant. Poor results were obtained with radiosurgery in large tumors where low doses (less than 20 Gy) were used. Because of the rarity and complexity of these tumors, mainly when associated with von Hippel-Lindau disease, a multicenter study could be useful with the assessment of the optimal utilization and combination of these treatment modalities.

Skull base chordomas

Chordomas are difficult and challenger tumors to treat. Despite of its pathological appearance that demonstrates an slow-growing behavior, their location and patterns of spread through the base of the skull make these tumors one of the most difficult diseases to treat at the base of the skull. The inadequate response to the conventional radiation therapy and the high incidence of recurrence, in cases treated with classical neurosurgical approaches, make mandatory a radical removal of the tumor mass and the surrounding pathological bone which can only be achieved with the use of skull base approaches associated with an extensive drilling of the bony tumor. In order to reach the goal of the surgical treatment of the skull base chordomas, the mastery of the skull base anatomy and the management of the drill are crucial points to obtain a successful results. In this report, we express our philosophy to treat these tumors which is based on the radical removal associated to a postoperative proton beam therapy. The main characteristic of the skull base chordomas is to spread through the base of the skull, which dictates the surgical approach that should be employed for each patient. In this article we will address the management of the skull base chordomas, with special emphasis to the role of the surgical and radiation treatment. The pathologic diagnosis and the radiological findings of chordomas of the skull base also will be discussed.