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.

Secondary cancer risk from modern external-beam radiotherapy of prostate cancer patients: Impact of fractionation and dose distribution.

Modern radiotherapy (RT) uses altered fractionation, long beam-on time and image-guided procedure. This study aimed to compare secondary cancer risk (SCR) associated with primary field, scatter/leakage radiations and image-guided procedure in prostate treatment using intensity-modulated RT (IMRT), CyberKnife stereotactic body RT (CK-SBRT) in relative to 3-dimensional conformal RT (3D-CRT). Prostate plans were generated for 3D-CRT, IMRT (39 fractions of 2 Gy), and CK-SBRT (five fractions of 7.25 Gy). Excess absolute risk (EAR) was calculated for organs in the primary field using Schneider's mechanistic model and concept of organ equivalent dose (OED) to account for dose inhomogeneity. Doses from image-guided procedure and scatter/leakage radiations were determined by phantom measurements. The results showed that hypofractionation relative to conventional fractionation yielded lower SCR for organs in primary field (p ≤ 0.0001). SCR was further modulated by dose-volume distribution. For organs near the field edge, like the rectum and pelvic bone, CK-SBRT plan rendered better risk profiles than IMRT and 3D-CRT because of the absence of volume peak in high dose region (relative risk [RR]: 0.65, 0.22, respectively, p ≤ 0.0004). CK-SBRT and IMRT generated more scatter/leakage and imaging doses than 3D-CRT (p ≤ 0.0002). But primary field was the major contributor to SCR. EAR estimates (risk contributions, primary field: scatter/leakage radiations: imaging procedure) were 7.1 excess cases per 104 person-year (PY; 3.64:2.25:1) for CK-SBRT, 9.93 (7.32:2.33:1) for IMRT and 8.24 (15.99:2.35:1) for 3D-CRT (p ≤ 0.0002). We conclude that modern RT added more but small SCR from scatter/leakage and imaging doses. The primary field is a major contributor of risk which can be mitigated by the use of hypofractionation.

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.

Clinical Outcomes of Intracranial Nonvestibular Schwannomas Treated with LinacBased Stereotactic Radiosurgery and Radiotherapy.

BACKGROUND: Intracranial nonvestibular schwannomas arising from various cranial nerves excluding CN VIII are uncommon. Recently, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) have been widely reported as effective treatment modalities for nonvestibular schwannomas. The purpose of this study was to study the long term clinical outcome for nonvestibular schwannomas treated with both XKnife and CyberKnife (CK) radiosurgery at one institution. MATERIALS AND METHODS: From 2004 to 2013, fiftytwo nonvestibular schwannoma patients were included in this study, 33 patients (63%) were treated with CK, and 19 (37%) were treated with XKnife. The majority of the tumors were jugular foramen schwannomas (38%) and trigeminal schwannomas (27%). HSRT was given for 45 patients (86%), whereas CSRT was for 6 (12%) and SRS for 1 (2%). RESULTS: The median pretreatment volume was 9.4 cm3 (range, 0.5752 cm3). With the median follow up time of 36 months (range, 3135), the 3 and 5 year progression free survival was 94 % and 88%, respectively. Tumor size was decreased in 13 (25%), stable in 29 (56%), and increased in 10 (19%). Among the latter, 3 (30%) required additional treatment because of neurologic deterioration. No patient was found to develop any new cranial nerve deficit after SRS/SRT. CONCLUSIONS: These data confirmed that SRS/ SRT provide high tumor control rates with low complications. Large volume tumors and cystic expansion after radiation should be carefully followed up with neurological examination and MRI, because it may frequently cause neurological deterioration requiring further surgery.

The Clinical Outcome of Hypofractionated Stereotactic Radiotherapy With CyberKnife Robotic Radiosurgery for Perioptic Pituitary Adenoma.

Stereotactic radiation technique including single fraction radiosurgery and conventional fractionated stereotactic radiotherapy is widely reported as an effective treatment of pituitary adenomas. Because of the restricted radiation tolerance dose of the optic pathway, single fraction radiosurgery has been accepted for small tumor located far away from the optic apparatus, while fractionated stereotactic radiotherapy may be suitable for larger tumor located close to the optic pathway. More recently, hypofractionated stereotactic radiotherapy has become an alternative treatment option that provides high rate of tumor control and visual preservation for the perioptic lesions within 2 to 3 mm of the optic pathway. The objective of the study was to analyze the clinical outcomes of perioptic pituitary adenomas treated with hypofractionated stereotactic radiotherapy. From 2009 to 2012, 40 patients with perioptic pituitary adenoma were treated with CyberKnife robotic radiosurgery. The median tumor volume was 3.35 cm3 (range, 0.82-25.86 cm3). The median prescribed dose was 25 Gy (range, 20-28 Gy) in 5 fractions (range, 3-5). After the median follow-up time of 38.5 months (range, 14-71 months), 1 (2.5%) patient with prolactinoma had tumor enlargement, 31 (77.5%) were stable, and the remaining 8 (20%) tumors were smaller in size. No patient's vision deteriorated after hypofractionated stereotactic radiotherapy. Hormone normalization was observed in 7 (54%) of 13 patients. No newly developed hypopituitarism was detected in our study. These data confirmed that hypofractionated stereotactic radiotherapy achieved high rates of tumor control and visual preservation. Because of the shorter duration of treatment, it may be preferable to use hypofractionated stereotactic radiotherapy over fractionated stereotactic radiotherapy for selected pituitary adenomas immediately adjacent to the optic apparatus.

Outcomes for Pituitary Adenoma Patients Treated with Linac- Based Stereotactic Radiosurgery and Radiotherapy: a Long Term Experience in Thailand.

BACKGROUND: The study analyzed the long term clinical outcomes of pituitary adenoma cases treated with the first Thailand installation of a dedicated Linac-based stereotactic radiation machine (X-Knife). MATERIALS AND METHODS: A retrospective review of 115 consecutive pituitary adenoma patients treated with X-Knife at the Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand from 1997 to 2003 was performed. Stereotactic radiosurgery (SRS) was selected for 21 patients (18%) including those with small tumors (≤3 cm) located ≥5 mm. from the optic apparatus, whereas the remaining 94 patients (82%) were treated with fractionated stereotactic radiotherapy (FSRT). RESULTS: With a median follow-up time of 62 months (range, 21-179), the six-year progression free survival was 95% (93% for SRS and 95% for FSRT). The overall hormone normalization at 3 and 5 years was 20% and 30%, respectively, with average time required for normalization of approximately 16 months for SRS and 20 months for FSRT. The incidence of new hypopituitarism was 10% in the SRS group and 9% in the FSRT group. Four patients (5%) developed optic neuropathy (1 in the SRS group and 3 in the FSRT group). CONCLUSIONS: Linac-based SRS and FSRT achieved similar high local control rates with few complications in pituitary adenoma cases. However, further well designed, randomized comparative studies between SRS versus FSRT particularly focusing on hormone normalization rates are required.

Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannomas: comparative observations of 139 patients treated at a single institution.

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) have been recognized as an alternative to surgery for small to medium sized vestibular schwannoma (VS). This study analysed and compared the outcomes of VS treated with the first Thailand installation of a dedicated Linac-based stereotactic radiation machine using single-fraction radiosurgery (SRS), hypofraction stereotactic radiotherapy (HSRT) and conventional fraction stereotactic radiotherapy (CSRT). From 1997 to 2010, a total of 139 consecutive patients with 146 lesions of VS were treated with X-Knife at Ramathibodi hospital, Bangkok, Thailand. SRS was selected for 39 lesions (in patients with small tumors ≤3 cm and non-serviceable hearing function), whereas HSRT (79 lesions) and CSRT (28 lesions) were given for the remaining lesions that were not suitable for SRS. With a median follow-up time of 61 months (range, 12-143), the 5-year local control rate was 95, 100 and 95% in the SRS, HSRT and CSRT groups, respectively. Hearing preservation was observed after SRS in 75%, after HSRT in 87% and after CSRT in 63% of the patients. Cranial nerve complications were low in all groups. There were no statistically significant differences in local control, hearing preservation or complication between the treatment schedules. In view of our results, it may be preferable to use HSRT over CSRT for patients with serviceable hearing because of the shorter duration of treatment.

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.

Preliminary experience of CyberKnife treatment of primary non-small cell lung cancer.

OBJECTIVE: Provide the effectiveness of treatment protocol, radiotherapy plan, technique, and early clinical results of inoperable primary non-small cell lung cancer (NSCLC) in patients who received CyberKnife treatment at Ramathibodi Hospital. MATERIAL AND METHOD: Six cases of inoperable primary NSCLC patients were evaluated for tumor response after having received CyberKnife treatment. The prescribed radiation dose was 45 gray (Gy) in three consecutive fractions for peripherally located tumor and 50 Gy in five fractions within two weeks for centrally located tumor (biological equivalent dose, BED, 112.5 Gy 10, and 100 Gy 10, respectively). The response to treatment was evaluated from roentgenographic study during follow-up period along with clinical outcome and adverse event. RESULTS: Overall response after the treatment was demonstrated in five cases with roentgenographic complete response (CR, disappearance of tumor) and partial response (PR, 50% decrease in size) in two and three cases, respectively without any severe adverse event. The treatment planning parameters demonstrated the effectiveness of radiation dose homogeneity and conformity coverage of the target volume. CONCLUSION: This preliminary report has provided the effectiveness of treatment plan and local tumor controlled without severe adverse event for primary inoperable NSCLC patients receiving CyberKnife treatment.

Comparison of conventional external radiotherapy and stereotactic radiotherapy in the treatment of pituitary adenoma.

OBJECTIVE: To compare the results of pituitary adenoma treated with conventional external beam radiotherapy (EBRT) versus stereotactic radiosurgery and stereotactic radiotherapy (SRS/SRT). METHOD AND MATERIAL: Data of patients with pituitary adenoma treated at Radiotherapy and Oncology unit, Ramathibodi Hospital between 1990 from 2003 were retrospectively collected and analyzed. Twenty-two patients were treated with EBRT and 51 patients were treated with SRS/SRT. RESULTS: The 5-year overall survival and local control rates were not different between the EBRT and SRS/SRT group (91% vs 100%, p = 0.10; 95% vs 96%, p = 0.33). The 5-year freedom from newly initiated hormonal replacement was 50% in EBRT and 75% in SRS/SRT group (p = 0.38). CONCLUSION: At a similar outcome but with lower expense of resources, EBRT should be considered an acceptable radiation technique for patients with pituitary adenoma, especially in developing countries such as Thailand.

Fractionated stereotactic radiotherapy in residual or recurrent nasopharyngeal carcinoma.

The aim of this study was to evaluate results of fractionated stereotactic radiotherapy (FSRT) in patients with residual or recurrent nasopharyngeal carcinoma (NPC) in terms of local progression-free (LPFS) and overall survival (OS) rate and complications after treatment. There were 32 residual or recurrent NPC patients treated with FSRT using linac-based radiosurgery system. Time from the previous radiotherapy to FSRT was 1-165 months (median, 15). Two patients were treated for the second and one for the third recurrence. Thirteen patients (40.6%) also received chemotherapy with FSRT. Tumor volume ranged from 6.2-215 cc (median, 44.4). Average FSRT dose was 17-59.4 Gy (median, 34.6) in 4-25 fractions (median,6) in 1-5.5 weeks (median, 3). Median follow-up time was 25.5(3-67) months. LPFS rate at 1 and 3 years after FSRT was 67.8% and 37.9%. OS rate at 1 and 3 years was 89.7% and 71.2%. If all patients who had tumor progression with no further follow-up were assumed dead, the OS rate at 1 and 3 years would be 75.0% and 37.9%. Univariate analysis showed better local tumor control in patients with tumor volume

Fractionated stereotactic radiotherapy for bilateral vestibular schwannomas associated with neurofibromatosis type 2: early experiences in Ramathibodi Hospital.

PURPOSE: To evaluate the rates of tumor control and useful hearing preservation in patients with bilateral vestibular schwannomas (VSs) associated with neurofibromatosis type 2 (NF-2) treated with fractionated stereotactic radiotherapy (FSRT). MATERIAL AND METHOD: From August 1998--December 2002 there were 5 patients with NF-2 who underwent FSRT (Linac-based system) for bilateral CP angle tumors. Median age was 28 (18-47) years. Median tumor volume was 5.4 (2.2-9.4) cc. Eight lesions received a marginal dose of 44.2-59.9 (median = 46.2) Gy in 25-33 fractions. The other 2 lesions received 4.4 and 4.9 Gy/fraction for 6 fractions in 3 and 2 weeks. Median follow-up was 19 (14-44) months. RESULTS: Radiographic and clinical tumor control rate was 90%. One lesion progressed at 7 months after FSRT and was completely resected Of the 5 lesions with Gardner-Robertson class I-II hearing before FSRT 2 (40%) retained useful hearing at the last follow-up. One patient had left facial spasm at 10 months after FSRT which gradually improved. No patient had facial palsy, facial numbness or pain. CONCLUSIONS: FSRT provided good tumor control and hearing preservation rate in NF-2 patients with minimal morbidity. However, a longer follow-up is needed to evaluate long term results.