Skip to main content
Download PDF

Dose-effect relationship of linear accelerator based stereotactic radiotherapy for brain metastases

Radiation Oncology volume 18, Article number: 177 (2023) Cite this article

Abstract

Objective

The purpose of this study is to reveal the dose-effect relationship of linear accelerator (LINAC)-based stereotactic radiotherapy (SRT) in patients with brain metastases (BM).

Materials and methods

The PubMed, Cochrane, and Web of Science databases were used to identify studies that reported local tumour control after LINAC-based SRT in patients with BMs. Studies of other approaches that could affect local tumour control, such as whole brain radiotherapy, targeted therapy, and immunotherapy, were excluded from the dose-effect relationship analysis. Data extracted included patient and treatment characteristics and tumour local control. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as the statistically significant level.

Results

After literature screening, 19 eligible studies involving 1523 patients were included in the probit model regression analysis. There was no significant dose-effect relationship between nominal BED10 and peripheral BED10 versus 12-month local control probability. There were significant dose effect relationships between the centre BED10 and the average BED10 versus the 12-month local control probability, with P values of 0.015 and 0.011, respectively. According to the model, the central BED10 and the average BED10 corresponding to probabilities of 90% 12-month local control were 109.2 GyBED10 (95% confidence interval (CI): 88.7–245.9 GyBED10) and 87.8 GyBED10 (95% CI: 74.3–161.5 GyBED10), respectively. A 12-month local control rate of 86.9% (95% CI: 81.7–89.7%) and 85.5% (95% CI: 81.2–89.2%) can be expected at a centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively.

Conclusion

For patients with BM treated with LINAC-based SRT, more attention should be given to the central and average doses of PTV. A clear definition of the dose prescription should be established to ensure the effectiveness and comparability of treatment.

Introduction

Brain metastases (BM) occur in up to one-third of adult patients with solid tumour malignancies and lead to considerable patient morbidity, anxiety, and mortality [1]. The rising incidence of brain metastases has been ascribed to the development of better imaging and screening techniques and the formulation of better systemic therapies. Radiotherapy is the most common form of local therapy used in patients with BM. Whole-brain radiotherapy (WBRT) has long been considered the cornerstone of treatment to relieve symptoms and control tumours. However, WBRT is associated with cognitive dysfunction, balance problems, and hearing loss, as well as several acute and late side effects, such as fatigue, alopecia, anorexia, xerostomia, and nausea [2].

Several comparative studies showed that stereotactic radiotherapy (SRT) showed advantages in tumour control or quality of life for patients with BM compared with WBRT [3,4,5]. In SRT for patients with BM can be delivered as either a single fraction (usually 18 to 24 Gy) of highly conformal and high-dose treatment or as a fractionated SRT, ranging from 24 to 30 Gy in 3 fractions or 25 to 35 Gy in 5 fractions [6]. Both the physical dose and biological equivalence dose (BED) of the prescription dose vary greatly. Several studies have attempted to determine the dose-effect relationship between physical dose or BED and local control in SRT for patients with BM and have obtained valuable information [6,7,8,9]. With the implementation and progress of LINAC-based SRT for patients with BM, studies including dose parameters in detail and tumour control have been increasingly reported. The purpose of this study was to reveal the dose-effect relationship of LINAC-based SRT for patients with BM.

Materials and methods

Data sources and search strategy

A comprehensive literature search was conducted using the PubMed, Web of Science and Cochrane databases to determine the published articles regarding BM patients treated with SRT. The title field were searched for “stereotactic radiosurgery,“ “stereotactic radiotherapy,“ “hypofractionated radiosurgery,“ “stereotactic body radiotherapy,“ “stereotactic ablative radiotherapy,“ “SRT,“ “SRS,“ “SBRT,“ and “SABR” to determine article set A on SRT. Similarly, the title field was searched for “brain metastases” and “brain metastasis” to determine article set B about BM. The intersection of A and B was used to determine the articles about patients with BM treated with SRT. Our last literature search was on Mar 17, 2023 (see Additional File 1: Table S1).

Inclusion criteria

  1. 1.

    The treatment conforms to the SRT technical specifications in the AAPM Task Group 101 report. For example, the dose per fraction is 6 to 30 Gy, and the number of fractions is 1 to 5.

  2. 2.

    Original studies that reported the prescription dose and 6-month and/or 12-month local tumour control rate, were included.

Exclusion criteria

  1. 1.

    Stereotactic radiotherapy is not implemented based on C-arm-mounted LINAC but is based on CyberKnife radiosurgery system, Gamma Knife, etc.

  2. 2.

    Combined with other treatment methods that may change the outcome of tumour local control, such as whole brain radiotherapy, surgery, targeted therapy, or immunotherapy, etc.

  3. 5.

    3. Studies about SRT as salvage treatment in patients with recurrent BM.

Data extraction

After removing the duplicates, we screened the literature by title and abstract, and the remaining literature was screened by full text. When the patient data reported in the literature overlapped, we selected the latest and most complete data. The bibliographic references of relevant reviews have also been reviewed and included according to the criteria. When the data originated from overlapping or almost the same patients, the most recent and comprehensive articles were included. Literature screening and data extraction were conducted independently by two authors according to the inclusion and exclusion criteria, and objections were resolved through negotiation.

The following data from all enrolled studies were extracted: (1) Study information: first author, publication year, country, and inclusion time of patients; (2) Patients and tumour characteristics: number of patients, number of metastases, median or mean age, most common histology, tumour size, and extracranial disease control; (3) Treatment characteristics: the margin from gross target volume (GTV) to planning target volume (PTV), prescription dose, peripheral dose, central dose, and median number of fractions; and treatment technology; (4) Clinical outcomes: median follow-up and local control (LC) at 6 months and 12 months. The biologically effective doses (BED) were calculated using the linear quadratic (LQ) equation: BED10 = n×d×[1 + d/(α/β)], where d represents the fraction dose, n represents the fractions. The α/β value quantifies the sensitivity to changes in fraction size, and higher α/β values (7 to 20 Gy) are typical values for tumor control, showing lower effects of fractionation. Referring to the dose-response effect and dose-toxicity study of SRT for BM [8], in our study, the α/β value was also set to 10. Due to the high heterogeneity of the PTV dose in SRT, to facilitate the dose effect analysis, we defined the nominal dose, peripheral dose, central dose and average dose as previously described [10]. Conducting dose-effect analyses of multiple BED parameters enables us to delve deeper into the factors that have a stronger correlation with tumor control.

Probit analysis

Probit model regression analysis was conducted by XLSTAT 2016 (Addinsoft, Paris, France) as previously described [11, 12]. The statistical significance was set at the level of P value < 0.05. Subgroup analysis was conducted according to country, treatment era, proportion of male patients, median age, median tumour diameter, PTV margin, fractions and treatment technology. In order to analyze the dose-response relationship of tumor size subgroups, we conducted a spherical diameter conversion for the included studies that reported tumor volumes, as most BM exhibit spherical features.

Results

Description of the included studies

After a comprehensive search, no article about regression analysis on the dose effect relationship between dose and tumour local control rate based on published data was found. A total of 2377 potential related studies were identified using a systematic literature retrieval strategy. After removal of duplicates, 19 eligible studies involving 1523 patients in total and including six bibliographic references from relevant reviews, were obtained through title, abstract and full text screening and included in probit model regression analysis, as shown in Additional File 2: Fig. S1. These included studies were from 7 countries, with the most published studies coming from Japan (five), followed by Germany (four), the United States, Italy and France (three each), and the Netherlands (one). The main characteristics of the included studies are presented in Table 1.

Table 1 The main characteristics of the included studies
Full size table

Probit analyses

The median of prescription dose was 23.1 Gy (range: 14–42 Gy), the median of fraction was one (range: 1–5), and the median of actuarial or rough 6-month and 12-month local control rates was 94% (range: 84–100%) and 86.5% (range: 70–100%), respectively.

For 12-month local control, there was no significant dose effect relationship between nominal BED10 and peripheral BED10 versus local control probability, with P values of 0.108 and 0.081, respectively. There were significant dose effect relationships between the centre BED10 and the average BED10 versus the 12-month local control probability, with P values of 0.015 and 0.011, respectively, as shown in Fig. 1. According to the model, the central BED10 and the average BED10 corresponding to probabilities of 90% 12-month local control were 109.2 GyBED10 (95% confidence interval (CI): 88.7–245.9 GyBED10) and 87.8 GyBED10 (95% CI: 74.3–161.5 GyBED10), respectively. A 12-month local control rate of 86.9% (95% CI: 81.7–89.7%) and 85.5% (95% CI: 81.2–89.2%) can be expected at centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively.

Fig. 1
figure 1

Dose-effect relationship between central (a) and average (b) biological equivalence dose (α/β = 10) and 12 months local control

Full size image

For 6-month local control, there was no significant dose effect relationship between nominal BED10 versus local control probability, with a P value of 0.074. There were significant dose effect relationships between the peripheral BED10, the centre BED10 and the average BED10 versus the 6-month local control probability, with P values of 0.041, 0.005 and 0.004, respectively, as shown in Fig. 2. According to the model, 6-month local control rates of 88.6% (95% CI: 83.8–92.2%), 93.8% (95% CI: 91.0–95.3%) and 91.8% (95% CI: 90.1–91.1%) can be expected at a peripheral BED10 of 40 Gy, a central BED10 of 80 Gy and an average BED10 of 60 Gy, respectively.

Fig. 2
figure 2

Dose-effect relationship between peripheral (a), central (b) and average (c) biological equivalence dose ( α/β= 10) and 6 months local control

Full size image

The Probit analyses based on subgroups show that the central BED10 has most cumulative number of significance (seven for 6-month and six for 12-month), followed by the average BED10 (seven for 6-month and five for 12-month), the nominal BED10 (five for 6-month and two for 12-month), and peripheral BED10 (three each for both 6-month and 12-month), as shown in Tables 2 and 3.

Table 2 The probit analyses based on subgroups between biological equivalence dose and 6-month local control
Full size table
Table 3 The probit analyses based on subgroups between biological equivalence dose and 12-month local control
Full size table

Discussion

The probability of cancer patients developing BM diseases is high, and there is a growing trend due to the support of systematic treatment and high-resolution imaging. SRT is an attractive alternative treatment option that may avoid these side effects and improve local tumour control. With the popularization of various high technologies, the application of LINAC-based SRT for BM is becoming increasingly widespread. However, there is no consensus on the prescription dose and dose heterogeneity requirements within the target volume of LINAC-based SRT for patients with BM. It is meaningful that our study tried to find the optimal prescription dose and dose heterogeneity of LINAC-based SRT for BM using probit model regression analysis based on published data.

In this study, there was no significant dose-response relationship between the nominal BED10 and the 6-month or 12-month local control, mainly due to the lack of universal representativeness of the nominal dose. There was no uniform standard for the prescription dose method of SRT for patients with BM. Some prescription doses were defined at the minimum dose [14, 16, 18, 29, 31], and some were defined at the isocentre [15, 24]. At the same time, the degree of dose heterogeneity in PTV for different studies may be diverse, even if the same clinical trial protocol is followed. For example, in the RTOG 90 − 05 protocol, the prescribed dose was defined as an isodose line of 50–90%, which meant that the maximum dose was 111–200%, with significant differences. One study among the included studies, set the prescribed dose at a 50% isodose line [14], while some set it at 80% [13, 14, 19, 20, 25], and others at 90% [17, 21] and even 95% [31]. Therefore, for the same nominal dose, it may occur that the actual dose given to PTV is not comparable.

To address this issue, we selected peripheral BED10, central BED10, and average BED10 to establish the dose-response relationship in this study. Interestingly, in this study, there were significant dose-effect relationships between the centre BED10 and the average BED10 and the 12-month local control probability. For 6-month local control, there were significant dose-effect relationships between the peripheral BED10, the centre BED10 and the average BED10 and the 6-month local control probability. Although there has been no report on dose-response relationships for patients with BM treated with LINAC-based SRT, some scholars have explored the dose-response relationship, including those based on LINAC, Gamma knife, and Cyberknife [6, 8, 9, 32], as well as confusion with other tumours [7]. These dose-effect relationships are to some extent comparable to our results.

In our study, the peripheral BED10 corresponding to probabilities of 90% 6-month local control were 45.5 GyBED10. Amsbaugh et al. [32] used a proportional hazards modelling to determine the dose-volume response relationship between the ratio of maximum lesion dose per mm-diameter (Gy/mm) versus local control for frameless SRT based on 316 BMs from 121 patients. This study followed the RTOG 90 − 05 protocol, and the prescription doses, which is the peripheral dose defined in our study, were used in the quantitative dose effect analysis. The results showed that local control of 80%, 85%, and 90% corresponded to maximum doses per millimetre of 1.67 Gy/mm, 2.86 Gy/mm, and 4.4 Gy/mm, respectively. In order to make the results comparable, we conducted diameter conversion based on the sphere model for the included studies that reported tumour volumes. The median calculated tumour diameter for 12 included studies reporting the tumour volume was 25.8 mm, the other four reported tumour diameters with a median of 17 mm; therefore, the overall average was 23.6 mm. Considering the diameter of the tumour, 6-month local control of 90% corresponded to BED10 per millimetre of 1.93 GyBED10/mm.

Redmond et al. [6] established a tumour control probability model after SRT for BMs by screening for published articles on dosimetric and tumour control data. The model results showed that for tumours ≤ 20 mm, single-fraction doses of 18 and 24 Gy corresponded with > 85% and 95% 1-year LC rates, respectively. For tumours 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumours 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction FSRT using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumours of 21 to 40 mm in diameter. The results of this study are based on Gamma Knife, Cyberknife, and LINAC-based SRT. This result indicated that tumour diameter plays an important role in tumour control in SRT for BMs.

Loo et al. [33] discussed the dose-effect relation in BMs treated by SRT accounting for fractionation and technical considerations. A BED10 of 40 to 50 Gy seemed associated with a 12-month local control rate > 70%. A BED10 of 50 to 60 Gy seemed to achieve a 12-month local control rate at least of 80% at 12 months. In our study, 12-month local control rates of 86.9% and 85.5% could be expected at a centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively. Based on the definitions of central BED10 and average BED10, it can be roughly concluded that with the assurance of higher doses given to the PTV centre, 85% 12-month local control can be expected at a peripheral BED10 of approximately 40 Gy. This dose seemed to be lower than the results of Loo et al., but our study emphasized the higher dose to the centre and average PTV.

Shuryak et al. [7] analysed published tumour control data for lung tumours and BMs and obtained dose-response relationships based on several radiobiological models. Fortunately, this study provided a dose-response relationship for the BM subgroup. It is worth noting that the isocentre dose was used for quantitation in the dose effect analysis. Although the dose-response relationship of the BM subgroup did not use a radiobiological model, BED conversion based on a single fraction curve can be compared with the results of this study. In our study a 12-month local control rate of 86.9% could be expected at the centre BED10 of 80 Gy, which is equivalent to 23.7 Gy for single fraction schedule. In Shuryak’s study, 87.5% local control probability can be expected at 23.7 Gy for single fraction dose-effect curve. Therefore, the model results of these two studies are consistent.

Wiggenraad et al.‘s dose-response results by eye fitting based on published literature showed that a BED12 of at least 40 Gy was associated with a 12–month local control rate of 70% or more [9]. This study used the LQC model for biological dose conversion and a α/β value of 12. The BED based on the LQC model is slightly smaller than that based on the LQ model, and BED12 is slightly smaller than BED10. The degree of reduction in both depends on the dose per fraction. These limitations limit the comparability of the study.

This study has some limitations that have been discussed in previous articles [10, 11]. Besides, BMs belong to the advanced stage of patients with cancer, and tumour control is influenced by many factors, such as primary tumour control, extracranial metastases, and pathology. Furthermore, the selection of α/β value is also a limitation of this study. The α/β value has been a core parameter in calculating BED in the LQ model, and there has always been controversy. Brain metastasis originates from different tumor sites and pathological types, exhibiting different α/β values, leading to a more complex scenario. For instance, melanoma, sarcoma, breast cancer, and prostate cancer are known to have lower α/β values compared to other tumors. It is worth noting that the proportion of BM originating from these specific primary tumors in the included studies in this analysis is relatively small (347/1523, 22.8%). Several studies on BM uses an α/β value of 10 [8, 34], even higher [9, 35], to calculate the BED. Consequently, while the issue of α/β value selection is a limitation, its impact on the overall conclusion of the study is somewhat limited.

In conclusion, for patients with BM treated with LINAC-based SRT, more attention should be given to the central dose and average dose of PTV. A 12-month local control rate of 86.9% (95% CI: 81.7–89.7%) and 85.5% (95% CI: 81.2–89.2%) can be expected at a centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively. A 6-month local control rate of 88.6% (95% CI: 83.8–92.2%), 93.8% (95% CI: 91.0–95.3%) and 91.8% (95% CI: 90.1–91.1%) can be expected at a peripheral BED10 of 40 Gy, a centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively. A clear definition of the dose prescription should be established to ensure the effectiveness and comparability of treatment.

Data Availability

All data, models, or code generated or used during the study are available from the corresponding author by request.

References

  1. Singh K, Saxena S, Khosla AA, et al. Update on the management of Brain Metastasis. Neurotherapeutics. 2022;19:1772–81.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wang TJC, Brown PD. Brain metastases: fractionated whole-brain radiotherapy. Handb Clin Neurol. 2018;149:123–7.

    Article  PubMed  Google Scholar 

  3. Dincer S, Gurbuz D. Treatment of brain metastases from gastrointestinal primaries: comparing whole-brain radiotherapy and stereotactic radiosurgery in terms of survival. North Clin Istanb. 2022;9:47–56.

    PubMed  Google Scholar 

  4. Mizuno T, Takada K, Hasegawa T, et al. Comparison between stereotactic radiosurgery and whole-brain radiotherapy for 10–20 brain metastases from non-small cell Lung cancer. Mol Clin Oncol. 2019;10:560–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hartgerink D, Bruynzeel A, Eekers D, et al. Quality of life among patients with 4 to 10 brain metastases after treatment with whole-brain radiotherapy vs. stereotactic radiotherapy: a phase III, randomized, Dutch multicenter trial. Ann Palliat Med. 2022;11:1197–209.

    Article  PubMed  Google Scholar 

  6. Redmond KJ, Gui C, Benedict S, et al. Tumor Control Probability of Radiosurgery and fractionated stereotactic radiosurgery for Brain metastases. Int J Radiat Oncol Biol Phys. 2021;110:53–67.

    Article  PubMed  Google Scholar 

  7. Shuryak I, Carlson DJ, Brown JM, et al. High-dose and fractionation effects in stereotactic radiation therapy: analysis of Tumor control data from 2965 patients. Radiother Oncol. 2015;115:327–34.

    Article  PubMed  Google Scholar 

  8. Loo M, Clavier JB, Attal Khalifa J et al. Dose-response effect and Dose-Toxicity in Stereotactic Radiotherapy for Brain metastases: a review. Cancers (Basel) 2021; 13.

  9. Wiggenraad R, Verbeek-de Kanter A, Kal HB, et al. Dose-effect relation in stereotactic radiotherapy for brain metastases. A systematic review. Radiother Oncol. 2011;98:292–7.

    Article  PubMed  Google Scholar 

  10. Li F, Jiang H, Bu M, et al. Dose-effect relationship of stereotactic body radiotherapy in non-small cell Lung cancer patients. Radiat Oncol. 2022;17:211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tang X, Mu X, Zhao Z, et al. Dose-effect response in image-guided adaptive brachytherapy for Cervical cancer: a systematic review and meta-regression analysis. Brachytherapy. 2020;19:438–46.

    Article  PubMed  Google Scholar 

  12. Li F, Shi D, Bu M, et al. Four-dimensional image-guided adaptive brachytherapy for Cervical Cancer: a systematic review and Meta-regression analysis. Front Oncol. 2022;12:870570.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Pirzkall A, Debus J, Lohr F, et al. Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases. J Clin Oncol. 1998;16:3563–9.

    Article  CAS  PubMed  Google Scholar 

  14. Matsuo T, Shibata S, Yasunaga A, et al. Dose optimization and indication of Linac radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 1999;45:931–9.

    Article  CAS  PubMed  Google Scholar 

  15. Aoyama H, Shirato H, Onimaru R, et al. Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain Metastasis using noninvasive fixation of the skull. Int J Radiat Oncol Biol Phys. 2003;56:793–800.

    Article  PubMed  Google Scholar 

  16. Noel G, Medioni J, Valery CA, et al. Three irradiation treatment options including radiosurgery for brain metastases from primary Lung cancer. Lung Cancer. 2003;41:333–43.

    Article  PubMed  Google Scholar 

  17. Nakayama H, Tokuuye K, Komatsu Y, et al. Stereotactic radiotherapy for patients who initially presented with brain metastases from non-small cell carcinoma. Acta Oncol. 2004;43:736–9.

    Article  PubMed  Google Scholar 

  18. Narayana A, Chang J, Yenice K, et al. Hypofractionated stereotactic Radiotherapy using intensity-modulated Radiotherapy in patients with one or two brain metastases. Stereotact Funct Neurosurg. 2007;85:82–7.

    Article  PubMed  Google Scholar 

  19. Lutterbach J, Cyron D, Henne K, et al. Radiosurgery followed by Planned Observation in patients with one to three brain metastases. Neurosurgery. 2008;62:776–84.

    Article  PubMed  Google Scholar 

  20. Fokas E, Henzel M, Hamm K, et al. Radiotherapy for brain metastases from renal cell cancer: should whole-brain radiotherapy be added to stereotactic radiosurgery? Analysis of 88 patients. Strahlenther Onkol. 2010;186:210–7.

    Article  PubMed  Google Scholar 

  21. Nath SK, Lawson JD, Simpson DR, et al. Single-isocenter frameless intensity-modulated stereotactic radiosurgery for simultaneous treatment of multiple brain metastases: clinical experience. Int J Radiat Oncol Biol Phys. 2010;78:91–7.

    Article  PubMed  Google Scholar 

  22. Saitoh J, Saito Y, Kazumoto T, et al. Therapeutic effect of linac-based stereotactic radiotherapy with a micro-multileaf collimator for the treatment of patients with brain metastases from Lung cancer. Jpn J Clin Oncol. 2010;40:119–24.

    Article  PubMed  Google Scholar 

  23. Fokas E, Henzel M, Surber G, et al. Stereotactic radiosurgery and fractionated stereotactic radiotherapy: comparison of efficacy and toxicity in 260 patients with brain metastases. J Neurooncol. 2012;109:91–8.

    Article  PubMed  Google Scholar 

  24. Feuvret L, Vinchon S, Martin V, et al. Stereotactic radiotherapy for large solitary brain metastases. Cancer Radiother. 2014;18:97–106.

    Article  CAS  PubMed  Google Scholar 

  25. Yang TJ, Oh JH, Folkert MR, et al. Outcomes and prognostic factors in women with 1 to 3 Breast cancer brain metastases treated with definitive stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2014;90:518–25.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Minniti G, Scaringi C, Paolini S, et al. Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (> 2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis. Int J Radiat Oncol Biol Phys. 2016;95:1142–8.

    Article  PubMed  Google Scholar 

  27. Navarria P, Pessina F, Cozzi L, et al. Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection. Radiat Oncol. 2016;11:76.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Aoki K, Nagatani Y, Noma K, et al. Effective control of brain metastases irrespective of Distance from Isocenter in single-isocenter Multitarget Stereotactic Radiosurgery. Anticancer Res. 2021;41:2575–81.

    Article  CAS  PubMed  Google Scholar 

  29. Badloe J, Mast M, Petoukhova A, et al. Impact of PTV margin reduction (2 mm to 0 mm) on pseudoprogression in stereotactic radiotherapy of solitary brain metastases. Tech Innov Patient Support Radiat Oncol. 2021;17:40–7.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Vigneau E, Jacquemin J, Benadon B, et al. Efficacy and safety of hypofractionated stereotactic radiotherapy for brain metastases using three fractions: a single-centre retrospective study. Cancer Radiother. 2021;25:763–70.

    Article  CAS  PubMed  Google Scholar 

  31. Piras A, Boldrini L, Menna S, et al. Five-fraction stereotactic radiotherapy for Brain metastases: a single-Institution experience on different dose schedules. Oncol Res Treat. 2022;45:408–14.

    Article  CAS  PubMed  Google Scholar 

  32. Amsbaugh M, Pan J, Yusuf MB, et al. Dose-volume response relationship for Brain metastases treated with Frameless single-fraction Linear Accelerator-based stereotactic radiosurgery. Cureus. 2016;8:e587.

    PubMed  PubMed Central  Google Scholar 

  33. Lee EJ, Choi KS, Park ES, et al. Single- and hypofractionated stereotactic radiosurgery for large (> 2 cm) brain metastases: a systematic review. J Neurooncol. 2021;154:25–34.

    Article  PubMed  Google Scholar 

  34. Gago-Arias A, Neira S, Pombar M, et al. Evaluation of indirect damage and damage saturation effects in dose–response curves of hypofractionated radiotherapy of early-stage NSCLC and brain metastases. Radiother Oncol. 2021;161:1–8.

    Article  PubMed  Google Scholar 

  35. Yuan J, Wang J, Lo S, et al. Hypofractionation regimens for stereotactic radiotherapy for large brain tumors. Int J Radiat Oncol Biol Phys. 2008;72:390–7.

    Article  PubMed  Google Scholar 

Download references

Funding

Project of Science and Technology Development Plan of Jilin Province 20200201524JC, National Natural Science Foundation of China 81201737 and Scientific Research Project of Education Department of Jilin Province JJKH20211196KJ.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Street, 130033, Changchun City, Jilin, PR China

    Ning Wu, Zhiqiang Wang, Xin Guo & Hongfu Zhao

Authors
  1. Ning Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhiqiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongfu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NW and HZ conducted literature retrieval, and ZW, XG and HZ conducted literature screening and probit model analysis. NW and HZ conducted data extraction. NW, ZW and HZ wrote the main manuscript text. All authors reviewed the manuscript.

Corresponding author

Correspondence to Hongfu Zhao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, N., Wang, Z., Guo, X. et al. Dose-effect relationship of linear accelerator based stereotactic radiotherapy for brain metastases. Radiat Oncol 18, 177 (2023). https://doi.org/10.1186/s13014-023-02360-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13014-023-02360-y

Keywords

Radiation Oncology

ISSN: 1748-717X

Contact us