Chordoma and Chondrosarcoma of the Skull Base and Spine: Small Post-operative Tumour Volume may still be Curable after High Dose Photon Radiotherapy

Abstract Background Meningiomas are the most common primary intracranial tumors in adults. The relationship between meningiomas and exogenous sex hormones such as cyproterone acetate (CPA) is well documented, yet the underlying mechanisms remain unknown. Defining the histomolecular status of meningiomas developed on CPA would help us to better understand the oncogenesis of these tumors. Methods We identified 30 patients operated for a meningioma after long-term high-dose CPA therapy and with a history of CPA discontinuation before establishing the indication for surgical intervention. We used array-comparative genomic hybridization (to characterize copy number changes in those 30 meningiomas and subsequently performed next-generation sequencing with the National Institute of Cancer (INCa) solid tumor panel, which is a targeted panel of clinically actionable genes. We also examined grade, type, and clinical features. Results We identified AKT1 mutations or PIK3CA mutations in 33.3% of CPA meningiomas. AKT1 and PIK3CA mutations were mutually exclusive. Enrichment in oncogenic PIK3CA mutations in the CPA cohort was detected. CPA meningiomas showed chromosomal stability and were located mainly in the skull base. Ninety percent of CPA meningiomas were low-grade meningiomas and 63.4% were meningotheliomas. Half of our CPA cohort had microcystic components. Conclusion Our study shows that low-grade meningothelial meningiomas of the skull base are predominant in CPA meningiomas. We identified PIK3CA/AKT1 pathway as a hypothetical actor in onco-pharmacological interaction between meningiomas and CPA. This signaling pathway could be an interesting target for precision medicine trials in meningioma patients who have been subjected to CPA. Our results could invite the scientific community to review the current classification of meningiomas and to evolve toward more specific histomolecular classification.

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Investigation of Newly Prepared Biodegradable 32P-chromic Phosphate-polylactide-co-glycolide Seeds and Their Therapeutic Response Evaluation for Glioma Brachytherapy

Contrast Media & Molecular Imaging ◽

10.1155/2018/2630480 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Guoqiang Shao ◽

Yuebing Wang ◽

Xianzhong Liu ◽

Meili Zhao ◽

Jinhua Song ◽

...

Keyword(s):

Therapeutic Effect ◽

Tumour Volume ◽

High Dose Rate ◽

High Dose ◽

Therapeutic Area ◽

Response Evaluation ◽

Early Evaluation ◽

Biodistribution Studies

32P high-dose rate brachytherapy allows high-dose radiation delivery to target lesions with less damage to adjacent tissues. The early evaluation of its therapeutic effect on tumours is vital for the optimization of treatment regimes. The most commonly used 32P-CP colloid tends to leak with blind therapeutic area after intratumour injection. We prepared 32P-chromic phosphate-polylactide-co-glycolide (32P-CP-PLGA) seeds with biodegradable PLGA as a framework and investigated their characteristics in vitro and in vivo. We also evaluated the therapeutic effect of 32P-CP-PLGA brachytherapy for glioma with the integrin αvβ3-targeted radiotracer 68Ga-3PRGD2. 32P-CP-PLGA seeds (seed group, SG, 185 MBq) and 32P-CP colloid (colloid group, CG, 18.5 MBq) were implanted or injected into human glioma xenografts in nude mice. Scanning electron microscopy (SEM) of the seeds, micro-SPECT imaging, and biodistribution studies were performed at different time points. The tumour volume was measured using a caliper, and 68Ga-3PRGD2 micro-PET-CT imaging was performed to evaluate the therapeutic effect after 32P intratumour administration. The delayed release of 32P-CP was observed with biodegradation of vehicle PLGA. Intratumoural effective half-life of 32P-CP in the SG (13.3±0.3) d was longer than that in the CG (10.4±0.3) d (P<0.05), with liver appearance in the CG on SPECT. A radioactivity gradient developed inside the tumour in the SG, as confirmed by micro-SPECT and SEM. Tumour uptake of 68Ga-3PRGD2 displayed a significant increase on day 0.5 in the SG and decreased earlier (on day 2) than the volume reduction (on day 8). Thus, 32P-CP-PLGA seeds, controlling the release of entrapped 32P-CP particles, are promising for glioma brachytherapy, and 68Ga-3PRGD2 imaging shows potential for early response evaluation of 32P-CP-PLGA seeds brachytherapy.

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High-dose Radiotherapy in the Management of Chordoma and Chondrosarcoma of the Skull Base and Cervical Spine: Part 1 — Clinical Outcomes

Clinical Oncology ◽

10.1016/j.clon.2007.04.004 ◽

2007 ◽

Vol 19 (7) ◽

pp. 509-516 ◽

Cited By ~ 40

Author(s):

K.L. Foweraker ◽

K.E. Burton ◽

S.E. Maynard ◽

R. Jena ◽

S.J. Jefferies ◽

...

Keyword(s):

Cervical Spine ◽

Skull Base ◽

Clinical Outcomes ◽

High Dose

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Clival chordoma presenting as a parapharyngeal mass: a diagnostic challenge

International Journal of Otorhinolaryngology and Head and Neck Surgery ◽

10.18203/issn.2454-5929.ijohns20192741 ◽

2019 ◽

Vol 5 (4) ◽

pp. 1112

Author(s):

Prita Pradhan ◽

Rudra Narayan Biswal ◽

Khageswar Rout ◽

Ranjita Panigrahi ◽

Pranati Misra ◽

...

Keyword(s):

Skull Base ◽

Parapharyngeal Space ◽

High Dose ◽

Diagnostic Challenge ◽

Clival Chordoma ◽

Base Of Skull ◽

Neoplastic Process ◽

Base Of The Skull ◽

Skull Tumour ◽

Uncommon Tumour

<p class="abstract">Though the parapharyngeal space is sites of primary involvement by neoplastic process, they can rarely house masses descending from a base of skull tumour. Chordoma is an uncommon tumour of the skull base and sacrococcyx. Originating from the notochordal remnants, they are locally aggressive causing lytic destruction of the adjacent bony structures, particularly in the base of the skull. The use of surgery and adjuvant high-dose proton RT is documented to produce best results. Here we report a diagnostic challenge posed by a chordoma occurring as a parapharyngeal mass in a 68 year old male.</p>

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Clinical Outcomes Following Dose-Escalated Proton Therapy for Skull-Base Chordoma

International Journal of Particle Therapy ◽

10.14338/ijpt-20-00066.1 ◽

2021 ◽

Vol 8 (1) ◽

pp. 179-188

Author(s):

Adam L. Holtzman ◽

Ronny L. Rotondo ◽

Michael S. Rutenberg ◽

Daniel J. Indelicato ◽

Alexandra De Leo ◽

...

Keyword(s):

Overall Survival ◽

Skull Base ◽

Local Control ◽

Subtotal Resection ◽

High Dose ◽

Disease Specific Survival ◽

Total Resection ◽

Skull Base Chordoma ◽

Disease Specific

Abstract Purpose To evaluate the effectiveness of external-beam proton therapy (PT) on local control and survival in patients with skull-base chordoma. Materials and Methods We reviewed the medical records of patients with skull-base chordoma treated with definitive or adjuvant high-dose PT and updated their follow-up when feasible. We assessed overall survival, disease-specific survival, local control, and freedom from distant metastasis. Radiotherapy toxicities were scored using the Common Terminology Criteria for Adverse Events, version 4.0. Results A total 112 patients were analyzed, of whom 105 (94%) received PT and 7 (6%) received combined proton-photon therapy between 2007 and 2019. Eighty-seven patients (78%) underwent a subtotal resection, 22 (20%) a gross total resection, and 3 (3%) a biopsy alone. The median radiotherapy dose was 73.8 Gy radiobiologic equivalent (GyRBE; range, 69.6-74.4). Ninety patients (80%) had gross disease at radiotherapy and 7 (6%) were treated for locally recurrent disease following surgery. Median follow-up was 4.4 years (range, 0.4-12.6); for living patients, it was 4.6 years (range, 0.4-12.6), and for deceased patients, 4.1 years (range, 1.2-11.2). At 5 years after radiotherapy, the actuarial overall survival, disease-specific survival, local control, and freedom from distant metastasis rates were 78% (n = 87), 83% (n = 93), 74% (n = 83), and 99% (n = 111), respectively. The median time to local progression was 2.4 years (range, 0.8-7). Local control and disease-specific survival by resection status was 95% versus 70% (P = 0.28) and 100% versus 80% (P = 0.06) for gross total, versus subtotal, resection or biopsy alone, respectively. There were no serious acute toxicities (grade ≥ 3) related to radiotherapy. Conclusion High-dose PT alone or after surgical resection for skull-base chordoma reaffirms the favorable 5-year actuarial local control rate compared with conventional techniques with acceptable late-complication–free survival. Outcomes following gross total resection and adjuvant PT were excellent. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

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