SHORT COMMUNICATION |
https://doi.org/10.5005/jp-journals-10003-1352 |
Usefulness of CyberKnife Therapy in Patients with Differentiated Thyroid Cancer with Distant Metastases
1,2,5Department of Nuclear Medicine, Osaka City University, Graduate School of Medicine, Osaka-City, Osaka-Fu, Japan
3,4Department of Radiology, Osaka City University Hospital, Osaka-City, Osaka-Fu, Japan
Corresponding Author: Shigeaki Higashiyama, Department of Nuclear Medicine, Osaka City University, Graduate School of Medicine, Osaka-City, Osaka-Fu, Japan, Phone: +816-6645-3885, e-mail: higashiya@med.osaka-cu.ac.jp
How to cite this article: Higashiyama S, Yoshida A, Katayama Y, et al. Usefulness of CyberKnife Therapy in Patients with Differentiated Thyroid Cancer with Distant Metastases. Int J Otorhinolaryngol Clin 2020;12(2):38–41.
Source of support: Nil
Conflict of interest: None
ABSTRACT
Aim and objective: We reported seven cases in which external beam radiotherapy (EBRT) with CyberKnife therapy was effective against distant metastases from differentiated thyroid carcinoma (DTC).
Materials and methods: The subjects included seven patients (6 males, 1 female; age 53–77 years, average age 65.85 years) who underwent CyberKnife therapy for metastatic lesions of DTC (pathological diagnosis: differentiated papillary carcinoma). The target lesions included 12 lymph node, 6 bone, and 2 brain metastases. All patients had previously undergone total thyroidectomy, followed by radioactive iodine therapy (RAIT). Since RAIT was not expected to have a therapeutic effect, CyberKnife treatment was selected. CyberKnife irradiation was performed 1–5 times. The radiation doses covering 95% of the planning target volume (D95) ranged from 15 to 26 gray (Gy). To determine the therapeutic effect, lesion size was evaluated by computed tomography (CT) and magnetic resonance imaging (MRI) before and 6–12 months after treatment.
Results: No increase in size was observed in the brain and bone metastases. Among the lymph node metastatic lesions, a therapeutic effect involving internal necrosis without an increase in size was noted in two lymph node metastases in the cervix. Additionally, two lymph node metastases in the neck had reduced in size. No increases in size were observed in the other lymph node lesions, reflecting the therapeutic effect of CyberKnife.
Conclusions: CyberKnife may be useful in treating distant metastatic lesions of papillary thyroid cancer.
Clinical significance: CyberKnife is useful as a multidisciplinary treatment for cases in which radioactive iodine therapy is maladjusted.
Keywords: CyberKnife, Differentiated thyroid carcinoma, Distant metastases, External beam radiotherapy, Papillary adenocarcinoma, Radioactive iodine therapy.
INTRODUCTION
Radioactive iodine therapy (RAIT) is administered for lung and bone metastases from differentiated thyroid carcinomas (DTCs).1,2 DTCs may become malignant in cases involving undifferentiated cell carcinomas or metastasize to the brain during follow-up.1,2 In these cases, multidisciplinary treatment, including palliative surgery, external beam radiotherapy (EBRT),3,4 and molecular-targeted drug treatment, is required.5,6 Among EBRT techniques, CyberKnife provides accurate irradiation in a small number of treatment sessions,7,8 and radiation damage to the surrounding tissues is also limited.9,10
We report 20 distant metastases in seven cases of DTC, against which CyberKnife treatment showed therapeutic effects.
MATERIALS AND METHODS
Patients
The subjects included seven patients (6 males, 1 female; age 53–77 years, average age 65.85 years) who underwent CyberKnife therapy for metastatic lesions of thyroid cancer between October 2012 and March 2019. All patients had undergone total thyroidectomy for thyroid cancer and were pathologically diagnosed with papillary cancer (Table 1). The target lesions included 12 lymph node lesions, 6 bone metastases, and 2 brain metastases. For metastatic lesions other than brain metastases, RAIT was performed before CyberKnife treatment. Scintigraphy performed after RAIT showed no significant RI accumulation at the treated site. The brain metastases were detected during the follow-up after RAIT for cervical lymph node metastases.
Patient | Sex | Age | Pathological subtype |
---|---|---|---|
1 | M | 71 | Papillary carcinoma |
2 | M | 53 | Papillary carcinoma |
3 | F | 64 | Papillary carcinoma |
4 | M | 62 | Papillary carcinoma |
5 | M | 65 | Papillary carcinoma |
6 | M | 77 | Papillary carcinoma |
7 | M | 69 | Papillary carcinoma |
All procedures in this study were performed in accordance with the ethical standards of our institutional research committee and in accordance with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
At our facility, we obtained written informed consent from all patients undergoing RAIT to use clinical data from their visits for educational and research purposes.
Follow-up and Evaluation
The sizes of the bone metastases and lymph node lesions on computed tomography (CT) were compared before and 6–12 months after CyberKnife treatment. The sizes of the brain metastases, as measured using contrast-enhanced T1-weighted fat suppression magnetic resonance imaging (MRI), were compared before and 6 months after treatment.
Radioiodine and CyberKnife Treatments
All patients received I-131 as RAIT before CyberKnife treatment. The cumulative dose of I-131 ranged from 80 mCi (2.96 GBq) to 780 mCi (28.86 GBq), with an average dose of 267 mCi (9.88 GBq). Scintigraphy after RAIT showed no RI accumulation of I-131 in the treated area, indicating a therapeutic effect. Therefore, we determined that RAIT could not provide a further therapeutic effect.8 The lymph node lesions on the cervical surface had developed after multiple surgical treatments. Conventional EBRT, which uses high doses and irradiates a large area, has a risk of radiation skin damage. Therefore, we opted for CyberKnife treatment.7,8 CyberKnife was selected to provide immediate treatment to prevent pathological fractures of the vertebral bones due to bone metastases. RAIT requires iodine restriction before treatment.8 Moreover, RAIT is performed at our facility if brain metastases are found, as brain metastases are associated with a risk of bleeding under iodine-limited conditions. CyberKnife treatment was performed based on the potential for an increase in brain metastases.
CyberKnife treatment was performed at Osaka Medical College Mishima-Minami Hospital CyberKnife Center. Irradiation planning, including planning regarding the fraction and dosage, was performed by experienced radiologists based on lesion size and location. The gross tumor volume (GTV) was defined based on the tumors visible on CT or MRI. The GTV was considered to be the same as the clinical target volume (CTV). The planning target volume (PTV) included the CTV with a 1.2- to 2.0-mm margin.
RESULTS
Table 2 shows the details of the treated lesions and the CyberKnife treatments. CyberKnife irradiation was performed 1–5 times (average: 3.14). The radiation dose covering 95% of the PTV (D95), considered the actual dose to the lesion, ranged from 15 to 26 Gy (average: 18.86 Gy). No lesions, including six bone metastasis lesions, showed an increase in size during follow-up. Figure 1 shows the CyberKnife dose distribution for the brain metastasis in the right cerebellar hemisphere in Patient 3. The metastatic lesion in the right cerebellar hemisphere before treatment appeared as a 7 × 6-mm2 mass lesion showing a contrast effect on contrast-enhanced T1-weighted fat suppression MRI (arrow in the upper image of Fig. 2). MRI performed 6 months after treatment showed no clear tendency to an increase in size, surrounding edematous changes, or bleeding (arrowhead in the lower image of Fig. 2). In two lymph node metastases in the left cervical region (arrow in the left image of Fig. 3) in Patient 3, a therapeutic effect involving internal necrosis (arrowhead in the right image of Fig. 3) was seen. In Patient 5, two lymph nodes in the left cervical region showed size reduction (Table 2).
Fig. 1: CyberKnife dose distribution in the cerebellar hemisphere of Patient 3. The planning target volume is indicated by the thin orange line
Fig. 2: Metastatic brain lesion in the left cerebellar hemisphere before treatment in Patient 3. The white arrow in the contrast-enhanced, T1-weighted, fat suppression magnetic resonance on the upper image indicates metastatic lesions. Contrast-enhanced, T1-weighted, fat suppression magnetic resonance image taken 6 months after treatment. The metastatic lesions (white arrowhead) show no increase in size
Fig. 3: Cervical-enhanced computed tomography scans of Patient 3. On the left image, white arrows indicate two lymph node metastatic lesions in the left neck before CyberKnife treatment. Contrast-enhanced computed tomography scans after treatment showing a therapeutic effect involving internal necrosis in the cervical lymph node metastases (white arrowheads on the right image)
Patient | Sites | Details of CyberKnife | Lesion size (mm) | ||
---|---|---|---|---|---|
Fr | D95(Gy) | Pre | Post | ||
1 | Pretracheal LN | 3 | 21.8 | 18 × 11 | 18 × 11 |
Lt submandibular LN | 1 | 22 | 9 × 8 | 8 × 8 | |
Lt supraclavicular LN | 5 | 23 | 10 × 11 | 10 × 11 | |
2 | Rt side of Cl | 3 | 18 | 15 × 11 | 12 × 9 |
Lt side of Cl | 4 | 16 | 25 × 12 | 25 × 11 | |
Rt side of C3 | 3 | 20 | 17 × 11 | 15 × 12 | |
3 | Rt cerebellar hemisphere | 3 | 26 | 7 × 6 | 7 × 6 |
Lt corona radiata | 3 | 25 | 2 × 2 | 2 × 2 | |
Lt nasopharyngeal LN | 3 | 24 | 19 × 10 | 15 × 5 | |
Rt neck LN | 1 | 22 | 9 × 6 | 9 × 6 | |
Lt neck LN | 1 | 18 | 7 × 6 | 7 × 6* | |
Lt lower neck LN | 2 | 23 | 9 × 9 | 8 × 6* | |
4 | Rt submandibular LN | 3 | 21 | 8 × 8 | 7 × 6 |
5 | Lt petroclival—Cl | 4 | 15 | 58 × 31 | 55 × 30 |
Lt side of C4/5 | 3 | 15 | 38 × 28 | 34 × 24 | |
Lt upper neck LN | 1 | 21 | 15 × 9 | 6 × 3 | |
Lt lower neck LN | 1 | 21 | 13 × 7 | 7 × 4 | |
6 | Lt side of tracheal LN | 5 | 17 | 14 × 11 | 12 × 11 |
Rt nasopharyngeal LN | 3 | 22 | 25 × 17 | 22 × 11 | |
7 | C7 | 5 | 21 | 19 × 20 | 19 × 20 |
DISCUSSION
We reported on the cases of seven patients who underwent CyberKnife treatment for distant metastatic lesions of papillary thyroid cancer. We observed no bone metastases and no increase in brain metastases within the follow-up period. Two lymph node metastases were reduced in size, and a therapeutic effect involving internal necrosis was seen in two other lymph node metastases.
Distant metastatic lesions of DTC are less sensitive to EBRT.1 In particular, RAIT and EBRT are reported to have low therapeutic effects on bone metastases.4 In contrast, high doses of EBRT for distant metastatic lesions are reportedly useful in controlling locoregional thyroid cancer.11,12
Among the modalities used for high-dose radiation therapy, CyberKnife treatment is reportedly useful for spinal metastases and recurrent lesions of DTC.13,14 With CyberKnife treatment, the reduced irradiation frequency, compared to that for normal EBRT, decreases the burden of going to the hospital.8 In addition, CyberKnife treatment minimizes the irradiation of surrounding tissues by enabling stereotactic, accurate, and high-dose irradiation of the target lesion.9,10 This is useful in avoiding side effects such as skin damage due to long-term irradiation with conventional EBRT.9,10 Our patients showed no symptoms of radiation damage, such as acute skin damage, after CyberKnife treatment. It was possible to treat multiple lesions such as brain and cervical lymph node metastases in the same patient, suggesting that CyberKnife treatment may be useful for local control.
Treatment of DTC with molecular-targeted drugs is premised on total thyroidectomy and RAIT.15,16 In addition, starting the administration of molecular-targeted drugs is recommended when the tumor becomes refractory to RAIT or when the thyroid cancer is undifferentiated and the disease progresses rapidly.17 Our institution selects the best treatment method for patients as a part of multimodal treatment comprising surgical treatment, RAIT, and EBRT for thyroid cancer, in anticipation of the initiation of treatment with molecular-targeted drugs as the final treatment method.
Although many studies have demonstrated the usefulness of molecular-targeted drugs for the treatment of DTC lesions, various side effects can cause the deterioration of patients’ quality of life.18 Additionally, once targeted therapy is started, it is difficult to discontinue medication or change to another treatment method.19 Therefore, for the control of locally recurrent lesions and the treatment of multiple metastatic lesions, we believe that it is important to use treatments other than molecular-targeted drugs as much as possible and to delay the introduction of molecular-targeted drugs. The results of this study demonstrated the usefulness of CyberKnife treatment for local control of multiple metastatic lesions including brain metastases.
In patients with thyroid cancer, lymph node metastatic lesions in the deep cervical region and mediastinum may invade the blood vessels and bronchi if they increase in size. The safest treatment is surgical removal; however, additional surgical treatment is often difficult due to reasons such as total thyroid cancer removal.20 A risk of bleeding has been reported with the use of molecular-targeted drugs for the treatment of lymph node lesions adjacent to major blood vessels.21 The accurate irradiation provided by CyberKnife treatment may be useful in such instances.
CONCLUSION
CyberKnife may be useful in treating distant metastatic lesions of papillary thyroid cancer.
CLINICAL SIGNIFICANCE
CyberKnife is useful as a multidisciplinary treatment for cases in which radioactive iodine therapy is maladjusted.
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