• Journal of Korean Neurosurgical Society
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• v.67 no.5
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• pp.560-567
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• 2024

Objective : We investigated how treating large brain metastasis (LBM) using 2-day fraction Gamma Knife radiosurgery (GKRS) affects tumor control and patient survival. A prescription dose of 10.3 Gy was applied for 2 consecutive days, with a biologically effective dose equivalent to a tumor single-fraction dose of 16.05 Gy and a brain single-fraction dose of 15.12 Gy. Methods : Between November 2017 and December 2021, 42 patients (mean age, 68.3 years; range, 50-84 years; male, 29 [69.1%]; female, 13 [30.9%]) with 44 tumors underwent 2-day fraction GKRS to treat large volume brain metastasis. The main cancer types were non-small cell lung cancer (n=16), small cell lung cancer (n=7), colorectal cancer (n=7), breast cancer (n=3), gastric cancer (n=2), and other cancers (n=7). Twenty-one patients (50.0%) had a single LBM, 19 (46.3%) had a single LBM and other metastases, and two had two (4.7%) large brain metastases. At the time of the 2-day fraction GKRS, the tumors had a mean volume of 23.1 mL (range, 12.5-67.4). On each day, radiation was administered at a dose of 10.3 Gy, mainly using a 50% isodose-line. Results : We obtained clinical and magnetic resonance imaging follow-up data for 34 patients (81%) with 35 tumors, who had undergone 2-day fraction GKRS. These patients did not experience acute or late radiation-induced complications during follow-up. The median and mean progression-free survival (PFS) periods were 188 and 194 days, respectively. The local control rates at 6, 9, and 12 months were 77%, 40%, and 34%, respectively. The prognostic factors related to PFS were prior radiotherapy (p=0.019) and lung cancer origin (p=0.041). Other factors such as tumor volumes, each isodose volumes, and peri-GKRS systemic treatment were not significantly related to PFS. The overall survival period of the 44 patients following repeat stereotactic radiosurgery (SRS) ranged from 15-878 days (median, 263±38 days; mean, 174±43 days) after the 2-day fraction GKRS. Eight patients (18.2%) were still alive. Conclusion : Considering the unsatisfactory tumor control, a higher prescription dose should be needed in this procedure as a salvage management. Moreover, in the treatment for LBM with fractionated SRS, using different isodoses and prescription doses at the treatment planning for LBMs should be important. However, this report might be a basic reference with the same fraction number and prescription dose in the treatment for LBMs with frame-based SRS.

• Radiation Oncology Journal
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• v.34 no.1
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• pp.1-9
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• 2016

Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.911-915
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• 2014

Aim: This study was to evaluate the effect of whole brain radiation (WBRT) combined with stereotactic radiotherapy (SRS) versus stereotactic radiotherapy alone for patients with brain metastases using a meta-analysis. Materials and Methods: We searched PubMed, EMBASE, Cochrane Library from their inception up to October 2013. Randomized controlled trials involving whole brain radiation combined with stereotactic radiotherapy versus stereotactic radiotherapy alone for brain metastases were included. Statistical analyses were performed using RevMan5.2 software. Results: Four randomized controlled trials including 903 patients were included. The meta-analysis showed statistically significant lowering of the local recurrence rate (OR=0.29, 95%CI: 0.17~0.49), new brain metastasis rate (OR=0.45, 95%CI: 0.28~0.71) and symptomatic late neurologic radiation toxicity rate (OR=3.92, 95%CI: 1.37~11.20) in the combined group. No statistically significant difference existed in the 1-year survival rate (OR=0.78, 95%CI: 0.60~1.03). Conclusions: The results indicate that whole brain radiotherapy combined with stereotactic radiotherapy has advantages in local recurrence and new brain metastasis rates, but stereotactic radiotherapy alone is associated with better neurological function. However, as the samples included were not large, more high-quality, large-sample size studies are necessary for confirmation.

• Archives of Craniofacial Surgery
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• v.24 no.5
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• pp.240-243
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• 2023

Metastasis of lung cancer to the skin is uncommon, presenting in 0.22% to 12% of lung cancer patients, and it is extremely rare for skin metastasis to be the first clinical manifestation of lung cancer. In the few cases where skin metastasis has been reported as the first sign of lung cancer, the patients were typically heavy smokers or had preexisting respiratory diseases and symptoms. This prompted clinicians to consider skin metastasis of a pulmonary malignancy. Large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer that accounts for approximately 3% of lung cancers. LCNEC mainly metastasizes to visceral organs, such as the liver, bone, and brain, and it only shows metastasis to the skin in very rare cases. Herein, we report an unusual case of a metastatic skin lesion as the first sign of primary pulmonary LCNEC, in a 63-year-old woman with no pulmonary symptoms or personal history of smoking or pulmonary disease.

• Journal of Korean Neurosurgical Society
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• v.48 no.2
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• pp.166-169
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• 2010

Spontaneous intracranial epidural hematoma (EDH) due to dural metastasis of hepatocellular carcinoma is very rare. A 53-year-old male patient with hepatocellular carcinoma, who was admitted to the department of oncology, was referred to department of neurosurgery because of sudden mental deterioration to semicoma with papillary anisocoria and decerebrate rigidity after transarterial chemoembolization for hepatoma. Brain computed tomography (CT) revealed large amount of acute EDH with severe midline shifting. An emergent craniotomy and evacuation of EDH was performed. Active bleeding from middle cranial fossa floor was identified. There showed osteolytic change on the middle fossa floor with friable mass-like lesion spreading on the overlying dura suggesting metastasis. Pathological examination revealed anaplastic cells with sinusoidal arrangement which probably led to spontaneous hemorrhage and formation of EDH. As a rare cause of spontaneous EDH, dural metastasis from malignancy should be considered.

• Radiation Oncology Journal
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• v.37 no.4
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• pp.302-308
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• 2019

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain's distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient's tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms of headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient's CNS metastases improved significantly within weeks of her therapy. The patient's non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

• Journal of Korean Neurosurgical Society
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• v.51 no.2
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• pp.94-97
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• 2012

Tumors that metastasize to the pituitary gland are unusual, and are typically seen in elderly patients with diffuse malignant disease. The most common metastases to the pituitary are from primary breast and lung cancers. We report a 65-year-old woman with pituitary metastasis from breast cancer who presented with recent-onset left progressive deterioration of visual acuity and visual field. The clinical diagnosis was made after brain and sellar magnetic resonance imaging showed a large sellar mass compressing the optic chiasm and invading the pituitary stalk. An otorhinolaryngology and neurosurgery team removed the tumor via a transsphenoidal approach, and this procedure obtained symptomatic relief. Postoperatively, metastasis from breast invasive ductal adenocarcinoma was confirmed histologically. We report this unusual case with a review of the relevant literature.

• Journal of Korean Neurosurgical Society
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• v.61 no.4
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• pp.525-529
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• 2018

Objective : To evaluate the efficacy of fractionated stereotactic radiosurgery (FSRS) performed using the Novalis $Tx^{(R)}$ system (BrainLAB AG, Feldkirchen, Germany; Varian Medical Systems, Palo Alto, CA, USA) for brain metastases. Methods : Between March 2013 and July 2016, 23 brain metastases patients were admitted at a single institute. Twenty-nine lesions too large for single session stereotactic radiosurgery or located in the vicinity of eloquent structures were treated by FSRS. Based on the results obtained, we reviewed the efficacy and toxicity of FSRS for the treatment of brain metastases. Results : The most common lesion origin was lung (55%) followed by breast (21%). Median overall survival was 10.0 months (95% confidence interval [CI], 4.9-15.0), and median progression-free survival was 10.0 months (95% CI, 2.1-13.9). Overall survival rates at 1 and 2 years were 58.6% and 36.0%, respectively. Local recurrence and neurological complications affecting morbidity each occurred in two cases. Conclusion : FSRS using the $Novalis-Tx^{(R)}$ system would appear to be an effective, safe noninvasive treatment modality for large and eloquently situated brain metastases. Further investigation is required on a larger number of patients.

• Journal of Chest Surgery
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• v.25 no.10
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• pp.1082-1086
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• 1992

Adenosquamous carcinoma of the lung is a rare disease entity and its clinical characteristics, treatment, and prognosis are poorly described. Stage I disease are amenable to operation as in bronchogenic carcinoma of non-small cell type, but stage III adenosquamous carcinoma shows highly aggressive behavior with rapid progression. We have experienced a case of stage III adenosquamous carcinoma of the lung in a 38-year-old male with a large mass in the right upper lobe with multiple metastasis in the mediastinal lymph nodes. Interestingly, all of the metastatic lymph nodes proved to be adenous component histologically. After right pneumonectomy and extensive lymph node dissection, the patient had received one cycle of chemotherapy. However, clinical signs of distant metastasis to bone and brain were discovered within 5 months postoperatively.

• Journal of Korean Neurosurgical Society
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• v.45 no.5
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• pp.275-283
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• 2009

Objective : We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. Methods : In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was $12.4cm^3$. Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. Results : Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age(<60 years) and tumor volume affected survival rate(p=0.03, each). Acute (${\leq}$1 month) toxicity was observed in 22% of patients, subacute and chronic (>6 months) toxicity occurred in 21 %, respectively. Less acute toxicity was observed with small tumors (<$10cm^3$. p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gy${\times}cm^3$) was a significant predictor of both acute and chronic CNS toxicities. Conclusion: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.