Long-term clinical outcomes of stereotactic radiotherapy for bilateral vestibular schwannomas in neurofibromatosis type 2 patients.

PURPOSE: The evidence for treating patients with neurofibromatosis 2-related vestibular schwannoma (VS-NF2) using hypofractionated stereotactic radiation therapy (HSRT) is limited. This study aimed to investigate clinical outcomes in patients with VS-NF2 treated with Robotic HSRT. METHODS: We retrospectively analyzed 25 NF2 patients with 48 VSs who were treated using Robotic HSRT at Ramathibodi Hospital from January 2009 to January 2020. RESULTS: Median follow-up was 98 months (range, 24-155 months). Median tumor volume was 2.3 cm3 (range, 0.4-28.3 cm3). Median prescribed dose was 18 Gy (range, 18-25 Gy) in three fractions (range, 3-5). The 5- and 10-year local control rates were 87% and 80%, respectively. The 5- and 10-year hearing preservation rates were 59% and 35%, respectively. Three patients developed new symptoms associated with transient volume expansion after treatment: hydrocephalus in one, facial weakness in one, and ataxia in one. No patient developed worsening of trigeminal nerve function. No histologically confirmed of radiation induced malignancy was reported in the study. CONCLUSIONS: Robotic HSRT demonstrated excellent long-term tumor control with a low non-auditory complication rate in patients with VS-NF2. However, preservation of hearing remains a major concern.

Long-term treatment outcomes of pediatric low-grade gliomas treated at a university-based hospital.

PURPOSE: A multimodality approach is generally considered for pediatric low-grade gliomas (LGG); however, the optimal management remains uncertain. The objective of the study was to evaluate treatment outcomes of pediatric LGG, focusing on long-term survival and factors related to outcomes. METHODS: A retrospective review of 77 pediatric LGG cases treated at Ramathibodi Hospital, Thailand between 2000 and 2018 was performed. The inclusion criteria were all pediatric LGG cases aged ≤ 15 years. Diffuse intrinsic pontine gliomas and spinal cord tumors were excluded. RESULTS: The median follow-up time was 8.2 years (range, 0.6-19.7). The median age at diagnosis was 6.2 years (interquartile range, 3.6-11.4). Treatments modality included tumor surgery (93%), chemotherapy (40%), and radiation therapy (14%). The 10-year overall survival (OS) and 10-year progression-free survival were 94% and 59%, respectively, for the entire cohort. The 10-year OS was 100% in three subgroups of patients: pilocytic subtype, WHO grade 1 tumors, and recipient of gross total resection. After multivariable analysis, no tumor surgery had a significantly unfavorable influence on overall survival. CONCLUSIONS: With a multimodality approach, pediatric LGGs had excellent outcome. Gross total resection is the standard primary treatment. Chemotherapy is the alternative standard treatment in incomplete resection cases, unresectable patients, or patients with progressive disease. Radiation therapy should be reserved as a salvage treatment option because of late complications that usually affect patients' quality of life.

Long-term clinical outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy using the CyberKnife® robotic radiosurgery system for vestibular schwannoma.

AIM: The study aimed to evaluate the long-term clinical outcomes of patients with vestibular schwannoma (VS) treated with stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HSRT) with frameless robotic whole-body radiosurgery system (CyberKnife® ). METHODS: This retrospective analysis of prospectively collected data included 123 consecutive patients with VS treated at the Radiosurgery center, Ramathibodi Hospital, Bangkok, Thailand. SRS was recommended for patients with unserviceable hearing and Koos grade I-III tumors, and HSRT for patients with serviceable hearing or Koos grade III-IV tumors. Between March 2009 and December 2015, 23 patients (19%) were treated with SRS, whereas 100 (81%) received HSRT. The commonly used regimen was 12 Gy in one fraction for SRS and 18 Gy in three fractions for HSRT. RESULTS: After a median follow-up of 72 months (range: 12-123 months), the 5-year and 8-year progression-free survival (PFS) rates for the whole cohort were 96% and 92%, respectively. The PFS was not significantly different between the SRS and HSRT groups (p = 0.23). Among 28 patients with serviceable hearing in the HSRT group, the 5-year and 8-year hearing preservation rates were 87% and 65%, respectively. The rate of nonauditory complications was 14%. Koos grade III/IV was a predictor of disease progression and was associated with nonauditory complications. CONCLUSION: SRS and HSRT with the CyberKnife® system provided excellent long-term tumor control with a low rate of nonauditory complications. HSRT may result in acceptable hearing preservation rates.

Carboplatin-based regimen in pediatric intracranial germ-cell tumors (IC-GCTs): effectiveness and ototoxicity.

BACKGROUND: Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity. METHODS: The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test. RESULTS: Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%). CONCLUSIONS: Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.

Outcome of postoperative radiation therapy for pediatric intracranial ependymoma: a single-institution review.

PURPOSE: To report outcome of postoperative radiotherapy (RT) in both new and recurrent grade II and III intracranial ependymomas in children treated at Ramathibodi Hospital. MATERIALS AND METHODS: Between 2006 and 2017, 24 pediatric intracranial ependymomas treated with postoperative RT were retrospectively reviewed. The median age at diagnosis was 44.5 months (range, 4-165 months). There were 14 (58%) males. Fourteen (58%) patients had infratentorial tumor. The median maximal diameter of tumor at diagnosis was 4.45 cm (range, 2.2-10 cm). Fourteen (58%) patients had anaplastic tumor. Gross total resections were performed in 14 (58%) patients. The median prescribed dose was 54 Gy (range, 45-60 Gy). The median total treatment time was 43 days (range, 37-78 days). RESULTS: The median clinical follow-up time was 44.5 months (range, 1-146 months). There were nine recurrences, five of which occurred at the primary tumor site. The estimated 5-year progression-free survival rate was 56%. The estimated 5-year overall survival rate was 75%. Extent of resection was the only factor associated with improved progression-free survival and overall survival after univariate testing. Six from nine patients with recurrent diseases underwent further surgery or further RT. These six patients had better median overall survival than the three who did not. Acute complication was mostly transient and tolerable. No late radiation effect was found. CONCLUSIONS: Postoperative radiation is an effective treatment. GTR is associated with better PFS and OS. Aggressive salvage local treatments for recurrent patients can result in good overall survival. Longer follow-up is needed in account for late relapse.

Toxicity of Gamma Knife Radiosurgery May Be Greater in Patients with Lower Cranial Nerve Schwannomas.

Objective Gamma Knife stereotactic radiosurgery (GK-SRS) is a preferred treatment option for tumors of the jugular foramen. We hypothesized that GK-SRS toxicity is higher for lower cranial nerve schwannomas than for glomus jugulare tumors despite anatomically similar locations. Methods We performed a retrospective review of all patients who received GK-SRS for glomus jugulare tumors and lower cranial nerve schwannomas at our institution between 2006 and 2014. Because of small sample sizes, Fisher's exact tests and logistic regression techniques were employed using SPSS. Result We identified 20 glomus jugulare tumors and 6 lower cranial nerve schwannoma patients with a median follow-up of 17 months. Median marginal dose was 16 Gy (range 13-18 Gy) and 12.5 Gy (range 12-14 Gy), respectively. All except one patient had tumor control at last follow-up visit. No worsening of pre-existing neurological deficits was observed. There were seven patients who developed any new neurological deficit after GK-SRS, four from the glomus group, and three from the schwannoma group (20 and 50% of each group, respectively). Only two of seven patients had permanent new neurological deficits. Both of them were in the schwannoma group. Univariate analysis showed that only a diagnosis of schwannoma had a greater risk of permanent new cranial nerve complication after GK-SRS compared with diagnosis of glomus jugulare ( p = 0.046). Conclusion Although the marginal dose for glomus jugulare is greater, our study suggests that the risk of a new permanent neurological deficit after GK-SRS was higher in the schwannoma group compared with the glomus group.

Clinical outcomes of perioptic tumors treated with hypofractionated stereotactic radiotherapy using CyberKnife® stereotactic radiosurgery.

INTRODUCTION: Stereotactic radiation technique is widely reported as an effective treatment for various types of benign intracranial tumors. However, single fraction radiosurgery (SRS) is not recommended for tumors located close to the optic apparatus due to the restricted radiation tolerance dose of the optic pathway. Recent advances in radiotherapy include advanced frameless radiosurgery using hypofractionated stereotactic radiotherapy (HSRT), and this has become an attractive treatment option for perioptic tumors within 2-3 mm of the optic pathway. Accordingly, the aim of this study was to investigate the clinical outcomes of perioptic tumors treated with HSRT using CyberKnife® (CK) robotic radiosurgery system relative to tumor control, vision preservation and toxicity. METHODS: This retrospective analysis of prospectively collected data included consecutive 100 patients that were diagnosed with and treated for perioptic tumor at the Radiosurgery center, Ramathibodi Hospital during the January 2009 to December 2012 study period. RESULTS: The median tumor volume was 6.81 cm3 (range 0.37-51.6), and the median prescribed dose was 25 Gy (range 20-35) in 5 fractions (range 3-5). After the median follow-up time of 37.5 months (range 21-103), two patients developed tumor progression at 6 and 34 months post-HSRT. The 5-year overall survival was 97%, and the 5-year local control was 97.5%. At the last follow-up, no vision deterioration or newly developed hypopituitarism was detected in our study. CONCLUSIONS: Although a longer follow-up is needed, HSRT yields a high level of local control and vision preservation, and should be considered a treatment of choice for perioptic tumor located close to the optic apparatus.

Post-radiosurgical edema associated with parasagittal and parafalcine meningiomas: a multicenter study.

Stereotactic radiosurgery (SRS) offers a high degree of tumor control for benign meningiomas. However, radiosurgery can occasionally incite edema or exacerbate pre-existing peri-tumoral edema. The current study investigates the incidence, timing, and extent of edema around parasagittal or parafalcine meningiomas following SRS. A retrospective multicenter review was undertaken through participating centers in the International Gamma Knife Research Foundation (previously the North American Gamma Knife Consortium or NAGKC). All included patients had a parafalcine or parasagittal meningioma and a minimum of 6 months follow up. The median follow up was 19.6 months (6-158 months). Extent of new or worsening edema was quantitatively analyzed using volumetric analysis; edema indices were longitudinally computed following radiosurgery. Analysis was performed to identify prognostic factors for new or worsening edema. A cohort of 212 patients comprised of 51.9 % (n = 110) females, 40.1 % upfront SRS and 59.9 % underwent adjuvant SRS for post-surgical residual tumor. The median tumor volume at SRS was 5.2 ml. Venous sinus compression or invasion was demonstrated in 25 % (n = 53). The median marginal dose was 14 Gy (8-20 Gy). Tumor volume control was determined in 77.4 % (n = 164 out of 212 patients). Tumor edema progressed and then regressed in 33 % (n = 70), was stable or regressed in 52.8 % (n = 112), and progressively worsened in 5.2 % (n = 11). Tumor location, tumor volume, venous sinus invasion, margin, and maximal dose were found to be significantly related to post-SRS edema in multivariate analysis. SRS affords a high degree of tumor control for patients with parasagittal or parafalcine meningiomas. Nevertheless, SRS can lead to worsening peritumoral edema in a subset of patients such as those with larger tumors (>10 cc) and venous sinus invasion/compression. Long-term follow up is required to detect and appropriately manage post-SRS edema.

Clinical outcome of postoperative radiotherapy with or without chemotherapy in adult glioblastoma multiforme in Ramathibodi Hospital: a retrospective study.

OBJECTIVE: To identify the treatment outcome of glioblastoma multiforme (GBM) in Ramathibodi Hospital from overall survival rate and related prognostic factors. MATERIAL AND METHOD: Medical records of patients with histological diagnosis of GBM treated at Radiation Oncology Division, Radiology Department, Ramathibodi Hospital between 2000 and 2010 were reviewed and available data extracted for evaluation of treatment outcome. RESULTS: There were 47 patients with mean age at diagnosis of 51.9 years (range from 18 to 82 years). Surgery (partial 76.6%, total 12.8%, and biopsy 10.6%) followed by postoperative radiotherapy (mean dose 52 gray) was the treatment of choice with or without concurrent and adjuvant Temozolomide (TMZ). With median follow-up time of 0.9 years, the median survival of the patients was 2.1 years (95% CI 1.08-7.36), whereas one and two-year overall survival rates were 78.0% and 57.8%, respectively. In univariate analysis, persistent neurological deficit after surgery and presenting symptom of visual disturbance were identified to lower overall survival while multivariate analysis, younger age, and higher radiation dose were identified as favorable prognostic factors to improve overall survival. Re-surgery or re-irradiation in some selected cases of recurrent or progressive disease was considered as a choice for palliative treatment. CONCLUSION: Proper management of GBM patient was surgical removal and postoperative radiotherapy with or without chemotherapy. Proper palliative treatment modality was considered in selected cases of recurrent or progressive disease.

The clinical outcome of intracranial hemangioblastomas treated with linac-based stereotactic radiosurgery and radiotherapy.

Recent publications have reported stereotactic radiosurgery as an effective and safe treatment for intracranial hemangioblastomas. However, because of the low incidence of these particular tumors, reports on large patient number studies have not yet been available. The objective of this study was to analyze the clinical results of 14 patients with 56 intracranial hemangioblastomas treated with linear accelerator (linac)-based stereotactic radiosurgery (SRS) and radiotherapy (SRT) in the same institute. The median age of patients was 41 years (range, 28-73 years). Nine of the patients (64%) had von Hippel-Lindau disease. A total of 39 lesions (70%) were treated with CyberKnife (CK), and 17 lesions (30%) were treated with X-Knife. The median pretreatment volume was 0.26 cm(3) (range, 0.026-20.4 cm(3)). The median marginal dose was 20 Gy (range, 10-32 Gy) in 1 fraction (range, 1-10 fractions). The median follow-up time was 24 months (range, 11-89 months). At the last follow-up, 47 tumors (84%) were stable, 7 (13%) decreased and 2 (4%) increased. The 1-, 2- and 6-year local control rates were 98%, 88% and 73%, respectively. No radiation complications were observed in this study. There was a trend toward local failure only in cystic tumors, but this trend was not found to be statistically significant. SRS/SRT achieved a high local control rate in intracranial hemangioblastomas without radiation-induced complications.

Preliminary experience of CyberKnife treatment of lung metastasis: the question about real clinical benefit.

OBJECTIVE: Evaluate the effectiveness of radiotherapy plan and physical parameters including local tumor response and clinical outcome of lung metastasis in patients who received CyberKnife treatment at Ramathibodi Hospital. MATERIAL AND METHOD: Six cases with twenty lesions of lung metastasis patients were evaluated for tumor response after having received CyberKnife treatment. The prescribed radiation dose was calculated approximately to biological equivalent dose (BED) around 60 to 100 gray (Gyz). The response of each lesion to treatment was evaluated from roentgenographic study during follow-up period along with adverse event, status of patients, and disease. RESULTS: At the third month after treatment, roentgenographic partial response (PR, 50% decrease in size) was demonstrated in eight lesions and stable disease (SD, unchanged size) in eight lesions with no complete response (CR, disappearance of tumor) detected. Progressive disease (PD, 25% increase in size) of six treated lesions was detected during the follow-up period. At the time of report, two patients were alive and still received palliative chemotherapy, two patients died from uncontrolled progressive metastases and failed palliative chemotherapy, and two patients lost follow-up after progressive metastases with unknown surviving status. No severe adverse event was observed. The treatment planning parameters demonstrated borderline of radiation dose homogeneity, and conformality coverage of the target volume. CONCLUSION: This preliminary report aimed to provide the idea of choosing the appropriate lung metastasis patient to receive CyberKnife treatment that must strictly clarify the real clinical benefit of each selected case to achieve the best outcome from this special treatment procedure.