Abstract
Background/Aim: The curative treatment for solitary fibrous tumors (SFTs) consists of surgery. However, surgery for SFTs in the skull base is difficult due to the anatomy and curative surgery may not be possible. Carbon-ion radiotherapy (C-ion RT) might be useful in the treatment of inoperable SFTs in the skull base because of its biological and physical nature. This study presents the clinical outcomes of C-ion RT for an inoperable SFT of the skull base. Case Report: A 68-year-old female patient experienced hoarseness, deafness on the right side, right facial nerve paralysis, and dysphagia. Magnetic resonance imaging revealed a tumor located in the right cerebello-pontine angle with destruction of the petrous bone, and immunohistochemical studies of the biopsy specimen showed a grade 2 SFT. Firstly, the patient underwent tumor embolization and surgery. However, 5 months after surgery, magnetic resonance imaging revealed regrowth of residual tumor. Subsequently, the patient was referred to our hospital for C-ion RT because curative surgery was unsuitable. The patient received 64 Gy (relative biological effectiveness) of C-ion RT in 16 fractions. Two years after C-ion RT, the tumor showed a partial response. The patient was still alive at the last follow-up without evidence of local recurrence, distant metastasis, or late toxicities. Conclusion: These findings suggest that C-ion RT is a suitable treatment option for inoperable SFTs of the skull base.
Solitary fibrous tumors (SFTs) of the skull base are rare and are detected by patient-referred headache or symptoms of compression of the adjacent brain or cranial nerves. Most cases of SFT are considered to be benign due to histological features and the recommended treatments are gross total or subtotal resection with or without adjuvant radiotherapy (1). While reports of surgery with adjuvant radiotherapy showed favorable clinical results, most of them are case reports with limited numbers of coherent studies (2, 3), and surgery with adjuvant radiotherapy is not a well-established treatment. In the treatment for SFTs of the skull base, although surgery is the most recommended treatment option, is often difficult for SFTs of the skull base due to the anatomy. Therefore, the development of a curative treatment for inoperable SFT of the skull base is needed.
Carbon-ion radiotherapy (C-ion RT) is expected to be a curative treatment for inoperable tumors because it has higher dose localization properties and a higher cytotoxic effect compared with X-rays due to the nature of C-ion RT (4-6). Murata et al. reported salvage C-ion RT for recurrent SFT of the thoracic spinal cord achieved 40 months of local control following treatment (7). However, reports of C-ion RT for SFT are limited and the efficacy and safety are not well understood. Furthermore, as far as we are aware, there are no reports of C-ion RT for unresectable SFT of the skull base. Here, we present a patient who underwent C-ion RT for an inoperable SFT located in the petrous bone.
Case Report
Patient characteristics. A 68-year-old female patient experienced hoarseness, deafness on the right side, right facial nerve paralysis, and dysphagia. The patient underwent magnetic resonance imaging (MRI) which revealed a tumor located in the right cerebello-pontine angle with destruction of the petrous bone. The tumor showed good contrast in gadolinium-enhanced T1-weighted images (70×36×36 mm) (Figure 1A). Immunohistological analysis of the biopsy specimen showed disorganized round- to spindle-cell proliferation with uniform nuclei, arranged randomly in a collagenous background. The mitotic index was low, and the Ki-67 index was approximately 5%. Immunohistochemical studies showed negative reactions for cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, and S-100 protein, and positive reactions for CD34, signal transducer and activator of transcription 6, and vimentin, leading to the diagnosis of grade 2 SFT/hemangiopericytoma (HPC). After the diagnosis, the patient underwent tumor embolization and subtotal resection. Figure 1B shows MRI 1 day after surgery. Postoperatively, hoarseness, deafness, facial paralysis, and dysphagia remained.
Gadolinium-enhanced T1-weighted magnetic resonance images (MRI). A: MRI before embolization and subtotal resection. The tumor (70×36×36 mm) was located in the right cerebello-pontine angle with destruction of the petrous bone. B: MRI 1 day after embolization and subtotal resection. C: MRI 5 months after embolization and subtotal resection. The residual tumor (45×26×28 mm) exhibited regrowth in the right petrous bone.
Five months after surgery, follow-up MRI showed regrowth of residual tumor (45×26×28 mm) in the right petrous bone (Figure 1C). Subsequently, the patient was referred to our hospital for C-ion RT because curative surgery was unsuitable. Informed consent for this treatment was obtained from the patient prior to the initiation of therapy, and the Ethics Committee of Kanagawa Cancer Center approved this case report (approval number: 2022-113).
C-ion RT. Prior to C-ion RT, the patient was immobilized using tailor-made fixation cushions and thermoplastic shells to acquire treatment planning computed tomographic images. The treatment planning computed tomographic images were merged with MRI to precisely delineate the gross tumor volume. The clinical target volume had a margin to include microscopic disease. The planning target volume was defined as the sum of the clinical target volume, internal margin, and setup margin. The administered C-ion RT dose was 64 Gy [relative biological effectiveness (RBE)] of C-ion RT in 16 fractions. The dose constraints were defined as a maximum dose (Dmax) of <30 Gy (RBE) to the brain stem and the dose delivered to a 0.5 cm3 volume (D0.5cc) of <54 Gy (RBE) to the skin. The tumor volume was 30.2 cm3 and the normal brain volume that received at least 50 Gy (RBE) [V50 Gy(RBE)] was 18.9 cm3. Figure 2A and B show diagnostic images before C-ion RT and Figure 2C shows the dose distribution of C-ion RT. The tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1) (8) and toxicities were assessed using the Common Terminology Criteria for Adverse Effects (version 4.0) (9).
Magnetic resonance images (MRI) before and after carbon-ion radiotherapy (C-ion RT) and treatment planning computed tomographic image with dose distribution of C-ion RT. A: Gadolinium-enhanced T1-weighted MRI before C-ion RT. The tumor (46×31×39 mm) was located in the right petrous bone. B: T2-Weighted MRI before C-ion RT. C: Dose distribution on axial computed tomographic images. The area within the red outline is the gross tumor volume. The 95% (red), 90% (yellow), 80% (light green), 70% (green), 50% (blue), and 30% (purple), and 10% (light purple) isodose curves are outlined [100% was 64.0 Gy (relative biological effectiveness)]. D: Gadolinium-enhanced T1-weighted MRI 6 months after C-ion RT. Tumor shrinkage and reduced contrast effect were observed. E: T2-weighted MRI 2 years after C-ion RT. There was no evidence of tumor regrowth.
Results. During C-ion RT, the patient experienced no acute toxicities. Six months after C-ion RT, MRI detected tumor shrinkage and reduction of contrast effect (Figure 2D). Two years after C-ion RT, the tumor showed a partial response (Figure 2E). Facial nerve paralysis and dysphagia improved slightly. The patient was still alive at the time of the last follow-up without evidence of local recurrence, distant metastasis, or late toxicities.
Discussion
The patient experienced favorable clinical outcomes after C-ion RT for inoperable SFT of the petrous bone. These results suggest that C-ion RT, which has a high dose concentration and higher cell-killing effect than other RT modalities, exerts a safe and favorable local effect, even at the skull base where high dose administration is difficult due to critical organs such as the brain or cranial nerves in close proximity; moreover, SFT has a histologically radioresistant nature.
The World Health Organization restructured the classification of both SFT and HPC in 2016 as variants of a single pathological entity, SFT/HPC, which is a rare neoplasm of mesenchymal origin (10). In the systematic review on the treatment of SFT/HPC of the skull base, the main treatment was surgery, and limited numbers of studies reported surgery and postoperative RT of 46-52 Gy (11). Furthermore, stereotactic body radiotherapy (SBRT) is sometimes used in curative treatment for intracranial SFT/HPC. Cohen-Inbar et al. reported SBRT for intracranial HPC in a multicenter study and showed that local progression-free survival at 4 years was 66% (12). The median tumor volume was 4.9 cm3 in their report, however, the tumor volume in our case was larger than the median tumor volume reported by Cohen-Inbar et al. Additionally, tumor in the current case had an irregular shape which may have been difficult to treat with SBRT. In our case, C-ion RT for SFT of the skull base showed a favorable clinical outcome, even in a large and radioresistant tumor. Therefore, we believe that C-ion RT might be a curative treatment option for inoperable SFT. Further studies, including multicenter studies, on the efficacy and safety of C-ion RT for inoperable SFT are needed to increase experience.
SFT occurs across multiple generations (median age=50 years), with an equal distribution in both sexes (13). Surgical resection is usually considered feasible, however, in cases where the patient has complications or in older patients, the tumor may be inoperable regardless of the tumor location. In recent years, especially as Japan is becoming an aging society, the development of non-invasive treatments for patients where surgery is unsuitable due to complications or being elderly is of great importance. C-Ion RT has been reported as a curative treatment for elderly patients because of its less invasive nature (14, 15). Therefore, C-ion RT might be a promising noninvasive and curative treatment option for SFT.
Regarding its safety, there are previous reports of C-ion RT for skull base tumors (16, 17). Although there are no studies comparing dose distribution and safety between C-ion RT and X-ray RT, including SBRT, for skull base tumors, it is expected that physical characteristics of C-ion RT allow organs at risks to be spared due to its higher dose localization compared with X-rays, resulting in fewer toxicities. The dose-–volume histogram analysis of radiation-induced brain injury (RIBI) in C-ion RT reported that grade 2 or higher RIBI significantly occurs when V50 Gy(RBE) ≥4.6 cm3 (16). In the present case, V50 Gy(RBE) was 18.9 cm3, therefore the risk of development of RIBI might be high. Additionally, the report indicated that grade 2 or higher symptomatic RIBI may continue to occur up to 5 years after C-ion RT (16). Therefore, the patient should be carefully monitored after therapy.
In conclusion, the case findings suggest that C-ion RT is a suitable treatment option for inoperable SFT of the skull base.
Acknowledgements
The Authors would like to thank Editage (www.editage.com) for English language editing.
Footnotes
Authors’ Contributions
Conceptualization: S. Shiba and Y.T.; methodology: S. Shiba; investigation: S. Shiba; resources: S. Shiba, Y.T., and H. Katoh; data curation: S. Shiba; writing – original draft preparation: S. Shiba; writing – review and editing: Y.T., N.M., K.T., S. Shima, K.K., H. Koge, D.Y., T.K., and H. Katoh; visualization: S. Shiba; supervision: H. Katoh; project administration: H. Katoh. The Authors read and approved the final article and agreed to the published version.
Conflicts of Interest
Hiroyuki Katoh and Daisaku Yoshida received research funding from Toshiba Energy Systems and Solutions Corporation (Kanagawa, Japan). All other Authors declare no conflicts of interest.
- Received January 7, 2023.
- Revision received January 21, 2023.
- Accepted January 24, 2023.
- Copyright © 2023 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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