Efficacy and safety of linear accelerator-based fractionated stereotactic radiotherapy for small volume brain metastases / 国际肿瘤学杂志

Objective:To investigate the efficacy and safety of fractionated stereotactic radiotherapy (FSRT) based on linear accelerator for small volume brain metastases.Methods:A total of 21 patients with small volume brain metastases who received FSRT from August 2020 to June 2022 were enrolled as subjects, including 45 lesions. Small-volume brain metastases were defined as ≤3 cm in diameter and ≤6 cm 3 in volume, and the dose/fractionation scheme was 27-30 Gy/3 F or 30-40 Gy/5 F. Three months after radiotherpy, the efficacy of FSRT in small brain metastases and the incidence of radiation brain injury were evaluated, and the incidence of radiation brain injury in subgroup analysis was performed according to the diameter, volume, dose/fractionation scheme, biological effective dose (BED) 10, and location of lesions. Results:Twenty-four lesions (53.33%, 24/45) were evaluated as complete response, another 13 lesions (28.89%, 13/45) were evaluated as partial response, and in the remaining 8 lesions (17.78%, 8/45) were evaluated as stable disease. The local control rate was 100% (45/45), the objective remission rate was 82.22% (37/45), and the intracranial distant progression rate was 23.81% (5/21). During the treatment and follow-up, there were 7 lesions (15.56%, 7/45) of radiation-induced brain injury, and the incidence of symptomatic radiation-induced brain injury was 11.11% (5/45). Subgroup analysis showed that the incidence of radiation brain injury in the group with a lesion diameter of 2-3 cm was higher than that with a lesion diameter of <2 cm group, with a statistically significant difference [80.00% (4/5) vs. 7.50% (3/40), χ2=12.69, P<0.001]; the incidence rate of radiation brain injury in the group with lesion volume of 4-6 cm 3 was higher than that with lesion volume of <4 cm 3 group, with a statistically significant difference [57.14% (4/7) vs. 7.89% (3/38), χ2=7.49, P=0.006]. There was no significant difference in the incidence of radiation brain injury between the dose/fractionation scheme of lesions 27-30 Gy/3 F and 30-40 Gy/5 F [9.52% (2/21) vs. 20.83% (5/24), χ2=0.40, P=0.527]. There was no significant difference in the incidence of radiation brain injury between the BED 10<60 Gy and ≥60 Gy [28.57% (2/7) vs. 13.16% (5/38), χ2=0.22, P=0.641]. There was no significant difference in the incidence of radiation brain injury between the lesions in the same lobe and the single or multiple lesions in different lobes [28.57% (4/14) vs. 9.68% (3/31), χ2=1.38, P=0.240) . Conclusion:FSRT based on linear accelerator is effective for small volume brain metastases. Brain metastases with the diameter <2 cm or volume <4 cm 3 are associated with a lower incidence of radiation brain injury than that of lesions with the diameter of 2-3 cm or volume of 4-6 cm 3.

Effects of flattening filter on dosimetry in fractionated stereotactic radiotherapy for brain metastases / 中国辐射卫生

@#<b>Objective</b> To investigate the dosimetric differences between volumetric modulated arc therapy (VMAT) with a flattening filter (FF) and flattening filter-free (FFF) VMAT in fractionated stereotactic radiotherapy for brain metastases. <b>Methods</b> Seventeen patients with brain metastases were divided into FF-VMAT group (VMAT plans with the FF mode) and FFF-VMAT group (VMAT plans with the FFF mode). The two groups were compared in terms of target volume dose parameters (<i>D</i>_98%, <i>D</i>_2% and <i>D</i>_mean), the conformal index (<i>CI</i>), the gradient index (<i>GI</i>), the gradient, normal brain tissue dose parameters (<i>V</i>_5Gy, <i>V</i>_10Gy, <i>V</i>_12Gy and <i>D</i>_mean), monitor units, and beam-on time. <b>Results</b> Compared with the FF-VMAT group, the FFF-VMAT group had significantly lower <i>GI</i> (3.33 ± 0.37 <i>vs</i> 3.27 ± 0.35, <i>P</i> = 0.001), a significantly lower gradient [(0.85 ± 0.20) cm <i>vs</i> (0.84 ± 0.19) cm, <i>P</i> = 0.002], a significantly shorter beam-on time [(177.05 ± 62.68) s <i>vs</i> (142.71 ± 34.59) s, <i>P</i> = 0.001], and significantly higher <i>D</i>_2% [(65.69 ± 2.15) Gy <i>vs</i> (66.99 ± 2.03) Gy, <i>P</i> = 0.001] and <i>D</i>_mean [(58.77 ± 1.60) Gy <i>vs</i> (59.95 ± 1.43) Gy, <i>P</i> <0.001]. There were no significant differences in the <i>CI</i>, the<i> D</i>_98%of the target volume, the <i>V</i>_5Gy, <i>V</i>_10Gy, <i>V</i>_12Gy and <i>D</i>_mean of the normal brain tissue, and monitor units between FFF-VMAT and FF-VMAT. <b>Conclusion</b> FFF-VMAT can better protect the normal tissue around the target volume, reduce the beam-on time, and improve treatment efficiency.

Case-control study of fractionated stereotactic radiotherapy combined with temozolomide for large brain metastases / 中华放射肿瘤学杂志

Objective To retrospectively analyze and compare the clinical efficacy and safety between fractionated stereotactic radiotherapy (FSRT) combined with and without temozolomide in the treatment of large brain metastases.Methods Between 2009 and 2017,84 patients with large brain metastases (tumor size ≥ 6 cm3) were recruited and assigned into the CRT group (concurrent TMZ and FSRT,n=42) and RT group (FSRT alone,n=42).The radiation dose was 52.0 Gy in 13 fractions or 52.5 Gy in 15 fractions.Patients were reexamined by magnetic resonance imaging (MRI) during treatment.The radiation field would be shrunk if the gross target volume (GTV) was reduced.The clinical efficacy was evaluated at postoperative 2 to 3 months.The primary end-point event was local recurrence-free survival (LRFS) and the secondary end-point events included intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),brain metastasis-specific survival (BMSS) and adverse events.The survival rates were assessed with Kaplan-Meier method and log-rank test and monovariate analysis.Results The median GTV in the CRT and RT groups was 16.9 cm3 and 15.7 cm3.During the treatment,75％ of the lesions in the CRT group were reduced compared with 34％ in the RT group (P=0.000).The local control (LC) rate in the CRT and RT groups was 100％ and 98％.The median follow-up time was 16.1 months (range,2.1-105.7 months).In the CRT group,the LRFS (P=0.040),IPFS (P=0.022),PFS (P=0.045),OS (P=0.013) and BMSS (P=0.006) were significantly better than those in the RT group,respectively.In the CRT group,the incidence of grade Ⅰ-Ⅱ gastrointestinal adverse events was 33％,significantly higher compared with 26％ in the RT group (P=0.006).No grade Ⅳ-Ⅴ adverse events occurred in both groups.Conclusion Combined application of temozolomide and FSRT can further enhance the LC and survival rates and do not increase the risk of severe adverse events in patients diagnosed with large brain metastases.

Physical and Biological Background of Radiosurgery

Radiosurgery is a highly precise form of radiation therapy for the treatment of vascular lesions, certain primary or metastatic neoplasms, or functional disorders. Either intracranial or extracranial, which are inaccessible or unsuitable for surgical or other management. As the basis of radiation physics for radiosurgery, this article introduces radiation history, the method of radiation production, interaction mode of radiations with human, transfer of radiation energy to the tissue, and dose planning to generate a desirable dose distribution on the target site. Biologically, the goal of radiosurgery is to cause a precise damage only to the limited tissue within the target volume without exceeding the acceptable rate of complications. As the therapeutic ratio is a function of the volume irradiated, the total dose and dose per fraction used, and the level of acceptable risk, radiation oncologists or practitioners should consider various radiobiologic factors when using radiosurgery to obtain the maximum therapeutic ratio.

Radiotherapy and radiosurgery for Cushing's disease

Patients with residual or recurrent Cushing's disease receive external beam radiotherapy (RT) with the aim of achieving long-term tumour control and normalization of elevated hormone levels. Treatment is given either as conventional radiotherapy using conformal techniques or as stereotactic radiotherapy, which is either used as fractionated treatment (SCRT) or as single fraction radiosurgery (SRS). We describe the technical aspects of treatment and report a systematic review of the published literature on the efficacy and toxicity of conventional RT, SCRT and SRS. There are no studies directly comparing the different radiation techniques and the reported results are inevitably of selected patients by investigators with interest in the treatment tested. Nevertheless the review of the published literature suggests better hormone and tumour control rates after fractionated irradiation compared to single fraction radiosurgery. Hypopituitarism represents the most commonly reported late complication of radiotherapy seen after all treatments. Although the incidence of other late effects is low, the risk of radiation injury to normal neural structures is higher with single fraction compared to fractionated treatment. Stereotactic techniques offer more localized irradiation compared with conventional radiotherapy, however longer follow-up is necessary to confirm the potential reduction of long-term radiation toxicity of fractionated SCRT compared to conventional RT. On the basis of the available literature, fractionated conventional and stereotactic radiotherapy offer effective treatment for Cushing's disease not controlled with surgery alone. The lower efficacy and higher toxicity of single fraction treatment suggest that SRS is not the appropriate therapy for the majority of patients with Cushing's disease.

Pacientes com doença de Cushing residual ou recorrente recebem radioterapia externa em feixe (RT) com o objetivo de alcançar um controle tumoral prolongado e a normalização dos níveis hormonais elevados. O tratamento é realizado tanto com RT convencional, usando técnicas conformacionais, ou com RT estereotáxica, que é usada tanto como tratamento fracionado (RTF) ou como radiocirurgia em procedimento único (RCU). Descreveremos os aspectos técnicos do tratamento e mostraremos uma revisão sistemática da literatura sobre a eficácia e toxicidade da RT convencional, da RTF e da RCU. Não existem estudos comparando diretamente as diferentes técnicas de radiação, e os resultados reportados são inevitavelmente os de pacientes selecionados pelos investigadores com interesse no tratamento testado. De qualquer maneira, a revisão dos dados publicados sugere que há melhores taxas de controle hormonal e tumoral após RTF em comparação com RCU. O hipopituitarismo representa a complicação tardia mais comumente relatada da RT, vista após todos os tipos de tratamento. Embora a incidência de outros efeitos tardios seja baixa, o risco de a radiação comprometer estruturas neurais normais é mais elevado com RCU do que com RTF. Técnicas estereotáxicas oferecem irradiação mais localizada se comparadas com a RT convencional, embora um acompanhamento prolongado seja necessário para confirmar a possível redução da toxicidade continuada da radiação na RTF em comparação com a RT convencional. Com base na literatura disponível, a RT fracionada convencional e a estereotáxica oferecem tratamento efetivo para a doença de Cushing não controlada isoladamente pela cirurgia. A baixa eficácia e alta toxicidade do tratamento em dose única sugere que a RCU não seja a terapia mais apropriada para a maioria dos pacientes com doença de Cushing.

Effects of Fractionated Stereotactic Radiotherapy for Primary Hepatocellular Carcinoma / 대한방사선종양학회지

PURPOSE: Reports on the outcome of curative radiotherapy for the primary hepatocellular carcinoma (HCC) are rarely encountered in the literature. In this study, we report our experience of a clinical trial where fractionated stereotactic radiotherapy (SRT) was used in treating a primary HCC. MATERIALS AND METHODS: A retrospective analysis was performed on 20 patients who had been histologically diagnosed as HCC and treated by fractionated SRT. The long diameter of tumor measured by CT was 2~6.5 cm (average: 3.8 cm). A single dose of radiation used in fractionated SRT was 5 or 10 Gy; each dose was prescribed based on the planning target volume and normalized to 85~99% isocenter dose. Patients were treated 3~5 times per week for 2 weeks, with each receiving a total dose of 50 Gy (the median dose: 50 Gy). The follow up period was 3~55 months (the median follow up period: 23 months). RESULTS: The response rate was 60% (12 patients), with 4 patients showing complete response (20%), 8 patients showing partial response (40%), and 8 patients showing stable disease (40%). The 1-year and 2-year survival rates were 70.0% and 43.1%, respectively, and the median survival time was 20 months. The 1-year and 2-year disease free survival rates were 65% and 32.5%, respectively, and the median disease-free survival rate was 19 months. Some acute complications of the treatment were noted as follows: dyspepsia in 12 patients (60%), nausea/emesis in 8 patients (40%), and transient liver function impairment in 6 patients (30%). However, there was no treatment related death. CONCLUSION: The study indicates that fractionated SRT is a relatively safe and effective method for treating primary HCC. Thus, fractionated SRT may be suggested as a local treatment for HCC of small lesion and containing a single lesion, when the patients are inoperable or operation is refused by the patients. We thought that fractionated SRT is a challenging treatment modality for the HCC.

Clinical Study of Lung Metastases Treated by Fractionated Stereotactic Radiotherapy / 医疗卫生装备

Objective To explore the methods and effects of body fractionated stereotactic radiotherapy(X-knife) in the treatment of lung metastases.Methods There were 50 cases with lung metastases were treated by fractionated stereotactic radiotherapy using CT orientation and WiMRT model body X-knife.The diameter of the metastases was 1.0cm-5.0cm.The linear accelerator was 6Mv X-ray.The dose per fraction was 5-12Gy,and the total prescribed dose was 30-52Gy at the margin of the PTV enveloped by 90% insodose curve.Results The metastases complete regression was found 21 fo-cus(18.3%)in CT image,partial regression in 70 focus(60.9%),and the overall effective rate was 79.1%.The effective rate for the focus with diameter less than 3cm was 88.5%,and 59.4% equal or more than 3cm,there was significan differ-ence(P

Preliminary Results of Fractionated Stereotactic Radiotherapy for Benign Brain Tumors / 대한방사선종양학회지

PURPOSE: To evaluate the role of fractionated stereotactic radiotherapy (FSRT) in the management of benign brain tumors, we reviewed the clinical, and radiographic responses of patients treated. METHODS AND MATERIALS: Between March 1996 and March 2002, 36 patients with benign brain tumors were treated by FSRT. The pathological diagnoses consisted of pituitary adenomas (12 patients), craniopharyngiomas (5 patients), meningiomas (10 patients), and acoustic neurinomas (9 patients). Radiotherapy doses of 25 to 35 Gy (3~6 Gy/fraction, 5~10 fractions) were prescribed to the 85~90% isodose line, depending upon the location, size and volume of the tumors. The median clinical and radiographical follow- up periods were 31 (range, 2~74) and 21 (range, 4~56) months, respectively. RESULTS: In the 35 patients that could be evaluated for their clinical response, 13 (37.1%) were considered improved, 16 (45.7%) stable and 6 (17.2%) worse. Of the 33 patients who had radiographic studies, tumor shrinkage was noted in 17 (51.5%), tumor stabilization in 13 (39.4%), and tumor progression in 3 (9.1%). Of the 17 tumor shrinkage patients, 7 (21.2%) showed a complete response. Acute radiation-induced complications occurred in 11 (30.6%) patients. CONCLUSION: FSRT is considered a safe and effective treatment method for benign brain tumors, but large numbers of patients, with relatively long follow-up periods are needed to assess the exact role or effect of FSRT.

Fractionated Stereotactic Radiotherapy for Metastatic Brain Tumor in Non-Small Cell Lung Cancer

PURPOSE: To evaluate the results of treatment with fractionated stereotactic radiotherapy for metastatic brain tumors in non-small cell lung cancer. MATERIALS AND METHODS: Between August 1997 and August 2001, 17 patients, with metastatic brain tumors in non-small cell lung cancer (26 lesions), completed frameless fractionated stereotactic radiotherapy. All patients received a 30~36 Gy/10~20 fx external beam irradiation to the whole brain. Twelve received fractionated stereotactic radiotherapy for a single lesion, 3 for 2 lesions and 1 each for 3 and 5 lesions. The median tumor volume was 1.7 cc (0.3~55.2 cc). The fractionation schedule for the fractionated stereotactic radiotherapy was 21 Gy/3 fx in 8 lesions, 25 Gy/5 fx in 7, 18 Gy/1 fx in 6, 30 Gy/5 fx in 4 and 15 Gy/5 fx in 1. Multiple-arc, and 3D conformal, fractionated stereotactic radiotherapy, were delivered to 24 and 2 lesions, respectively. Follow-up was possible in all patients. RESULTS: Nine out of 13 patients with follow-up radiological evaluations achieved a complete response (CR). The overall median survival, and 1 and 2 year survival rates were 20 months, and 64 and 28%, respectively. The median survival, and the 1 and 2 year survival rate of CR group were 20 months, and 73 and 22%, respectively. No patient has experienced any acute side reactions or late complications from the fractionated stereotactic radiotherapy. CONCLUSION: Although the number of patients treated with fractionated stereotactic radiotherapy was small, and follow-up period short, this study suggests that external beam irradiation to the whole brain, with 30 Gy/10 fx followed by fractionated stereotactic radiotherapy, could be a good treatment option for patients with metastatic brain tumors in non-small cell lung cancer.

Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy for Intracranial Schwannoma / 대한암학회지

PURPOSE: To assess the radiologic response and cranial nerve morbidity in intracranial schwannoma patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). MATERIALS AND METHODS: Twenty-six patients with intracranial schwannoma were treated with linear accelerator- based SRS or FSRT between February 1995 and October 1999. The origin of schwannoma was acoustic nerve in twenty-one patients, facial nerve in two, trigeminal nerve in two, and glossopharyngeal nerve in one. SRS were performed with the median peripheral dose of 14 Gy (range 12-16), and FSRT were done with the median peripheral dose of 25 2 Gy (range 50-60). RESULTS: With a median follow-up period of 33 months (range 12-67), the local control rate was 100%. Tumorregression was noted in eleven patients, and tumor stabilization was found in the remaining fifteen. Useful hearing preservation was achieved in two of three patients. Facial nerve neuropathy was shown in two patients and one patients developed trigeminal nerve neuropathy. CONCLUSION: Stereotactic radiotherapy including SRS and FSRT provided excellent local control in intracranial schwannoma. It shows the possibility of a high rate of hearing preservation and an acceptable neurotoxicity, although the number of patients are small and follow-up is relatively short.

Initial Experience of Fractionated Stereotactic Radiotherapy for Metastatic Brain Tumors / 대한암학회지

PURPOSE: This study aimed to evaluate the preliminary treatment results of fractionated stereotactic radiotherapy (FSRT) for metastatic brain tumors. MATERIALS AND METHODS: Between August 1997 and December 1998, frameless FSRT was performed in 11 patients with metastatic brain tumor (1S lesions). Primary sites were lung in 7 patients, breast in 2, stomach in 1, and malignant melanoma in 1, All patients received 30-36 Gy/10-20 fx external beam irradiation to whole brain. Eight patients received FSRT for 1 lesion, one for 2 lesions, and two for 4 lesions. Fractionation schedule was 25 Gy/5 fx in 11 lesions, 18 Gy(1 fx in 3, 30 Gy/5 fx in 2, 15 Gy/5 fx in 1. Mean tumor volume was 7.0 cc (0.39~55.23 cc). Multiple-arc FSRT was delivered to 16 lesions and conformal FSRT through irregular ports shaped to tumor profile to 2 lesions. RESULTS: No patient experienced any acute side reaction from FSRT. Follow-up radiologic evaluation was available in 9 patients. Six of nine patients achieved the complete response, but two showed the partial response and one showed no response on follow-up radiologic studies. Among six patients with complete response, 5 patients survived from 5 to 15 months and showed no evidence of metastatic brain d#isease clinically and/or radiologically at last follow-up. Among two patients who did not have radiologic evaluation, one showed clinically complete response until death and the other died just after FSRT caused by intercurrent disease. One patient with no response radiologically survived 7 months and showed nearly complete disappearance of clinical symptom with stable status radiologically, CONCLUSION: Initial experience in this study suggests that the external beam irradiation to whole brain with 30 Gy/10 fx followed by FSRT with 20~30 Gy/5~6 fx could be the good treatment option to the patients with metastatic brain tumor. This study suggests that the fractionation schedule for FSRT should be determined in consideration of performance status, number of metastasis, tumor volume, location, presence of extracranial disease, and age.

Stereotactic Radiotherapy for the Treatment of Brain Metastases / 대한암학회지

PURPOSE: To evaluate the clinical results of stereotactic radiosurgery (SRS) and frac- tionated stereotactic radiotherapy (FSRT) for metastatic brain tumors. MATERIALS AND METHODS: Nineteen patients with brain metastases (34 lesions) were treated with LINAC-based SRS or FSRT with or without whole brain radiotherapy between October 1995 and February 1998. SRS was preferred to FSRT in cases with three or more lesions and poor performance status. FSRT was preferred to SRS in cases with lesions larger than 3 cm and lesions located near or at the eloquent areas such as thalamus, brain stem, and optic apparatus. Single isocenter was used both in SRS and FSRT, and the median peripheral dose in SRS was 15 Gy (range 13~20 Gy), while that in FSRT was 21 Gy (range 15~24 Gy) by 3 Gy per fraction. RESULTS: Local control was achieved in 79% (27/34 treated lesions) and 1-year over- all survival rate was 58% with the median survival of 12 months. Lethal progressive brain metastases, both local and regional, were in four patients (27% of all deaths). No significant differences in local control and survival was observed with histology, age, sex, performance status, tumor volume, number of lesions, or treatment modality. Unacceptable acute or late complications did not occur. CONCLUSION: Stereotactic radiotherapy including SRS and FSRT is effective, non-invasive therapy for brain metastases. This study suggests that stereotactic radiotherapy might be an alternative to surgical resection in selected patients of brain metastases.