scholarly journals Dose-Response Effect and Dose-Toxicity in Stereotactic Radiotherapy for Brain Metastases: A Review

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6086
Author(s):  
Maxime Loo ◽  
Jean-Baptiste Clavier ◽  
Justine Attal Khalifa ◽  
Elisabeth Moyal ◽  
Jonathan Khalifa
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Stereotactic Radiotherapy ◽  
Local Control Rate ◽  
Dose Effect ◽  
Published Data ◽  
High Dose ◽  
Single Fraction ◽  
Fractionation Schedule

For more than two decades, stereotactic radiosurgery has been considered a cornerstone treatment for patients with limited brain metastases. Historically, radiosurgery in a single fraction has been the standard of care but recent technical advances have also enabled the delivery of hypofractionated stereotactic radiotherapy for dedicated situations. Only few studies have investigated the efficacy and toxicity profile of different hypofractionated schedules but, to date, the ideal dose and fractionation schedule still remains unknown. Moreover, the linear-quadratic model is being debated regarding high dose per fraction. Recent studies shown the radiation schedule is a critical factor in the immunomodulatory responses. The aim of this literature review was to discuss the dose–effect relation in brain metastases treated by stereotactic radiosurgery accounting for fractionation and technical considerations. Efficacy and toxicity data were analyzed in the light of recent published data. Only retrospective and heterogeneous data were available. We attempted to present the relevant data with caution. A BED10 of 40 to 50 Gy seems associated with a 12-month local control rate >70%. A BED10 of 50 to 60 Gy seems to achieve a 12-month local control rate at least of 80% at 12 months. In the brain metastases radiosurgery series, for single-fraction schedule, a V12 Gy < 5 to 10 cc was associated to 7.1–22.5% radionecrosis rate. For three-fractions schedule, V18 Gy < 26–30 cc, V21 Gy < 21 cc and V23 Gy < 5–7 cc were associated with about 0–14% radionecrosis rate. For five-fractions schedule, V30 Gy < 10–30 cc, V 28.8 Gy < 3–7 cc and V25 Gy < 16 cc were associated with about 2–14% symptomatic radionecrosis rate. There are still no prospective trials comparing radiosurgery to fractionated stereotactic irradiation.

Internal dose escalation associated with increased local control for melanoma brain metastases treated with stereotactic radiosurgery

2020 ◽  
pp. 1-7
Author(s):  
William R. Kennedy ◽  
Todd A. DeWees ◽  
Sahaja Acharya ◽  
Mustafaa Mahmood ◽  
Nels C. Knutson ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Treatment Planning ◽  
Local Control ◽  
Dose Escalation ◽  
High Dose ◽  
Internal Dose ◽  
Single Fraction ◽  
Dose Volume

OBJECTIVEThe internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non–small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM.METHODSThe records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC.RESULTSTwo hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31–86 years). The median follow-up was 7.6 months (range 0.5–81.6 months), and the median survival was 9.3 months (range 1.3–81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was ≥ and < 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 ≥ and < 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 ≥ and < 25%, respectively. Lesions > 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 ≥ and < 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30.CONCLUSIONSFor a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 ≥ 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation.

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin

2006 ◽  
Vol 104 (6) ◽  
pp. 907-912 ◽  
Author(s):  
Michael A. Vogelbaum ◽  
Lilyana Angelov ◽  
Shih-Yuan Lee ◽  
Liang Li ◽  
Gene H. Barnett ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Patient Survival ◽  
Radiation Therapy Oncology Group ◽  
Local Control Rate ◽  
Tumor Diameter ◽  
Tumor Margin ◽  
The Relationship

Object The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. Methods Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3–83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134–0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78–92%) in tumors treated with 24 Gy, compared with 49% (CI 30–68%) in tumors treated with 18 Gy and 45% (CI 23–67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. Conclusions Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.

scholarly journals The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 70
Author(s):  
Tyler Gutschenritter ◽  
Vyshak A. Venur ◽  
Stephanie E. Combs ◽  
Balamurugan Vellayappan ◽  
Anoop P. Patel ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Stereotactic Radiotherapy ◽  
Leptomeningeal Disease ◽  
Hypofractionated Stereotactic Radiotherapy ◽  
Treatment Techniques ◽  
Dose Volume ◽  
Clinical Scenarios ◽  
Large Brain

Brain metastases are the most common intracranial malignant tumor in adults and are a cause of significant morbidity and mortality for cancer patients. Large brain metastases, defined as tumors with a maximum dimension >2 cm, present a unique clinical challenge for the delivery of stereotactic radiosurgery (SRS) as patients often present with neurologic symptoms that require expeditious treatment that must also be balanced against the potential consequences of surgery and radiation therapy—namely, leptomeningeal disease (LMD) and radionecrosis (RN). Hypofractionated stereotactic radiotherapy (HSRT) and pre-operative SRS have emerged as novel treatment techniques to help improve local control rates and reduce rates of RN and LMD for this patient population commonly managed with post-operative SRS. Recent literature suggests that pre-operative SRS can potentially half the risk of LMD compared to post-operative SRS and that HSRT can improve risk of RN to less than 10% while improving local control when meeting the appropriate goals for biologically effective dose (BED) and dose-volume constraints. We recommend a 3- or 5-fraction regimen in lieu of SRS delivering 15 Gy or less for large metastases or resection cavities. We provide a table comparing the BED of commonly used SRS and HSRT regimens, and provide an algorithm to help guide the management of these challenging clinical scenarios.

scholarly journals Preoperative stereotactic radiosurgery for brain metastases: the STEP study protocol for a multicentre, prospective, phase-II trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Angeline Ginzac ◽  
Guillaume Dupic ◽  
Lucie Brun ◽  
Ioana Molnar ◽  
Mélanie Casile ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Phase Ii ◽  
Local Control ◽  
Stereotactic Radiotherapy ◽  
Phase Ii Trial ◽  
Combined Treatment ◽  
Prospective Trial ◽  
Total Duration ◽  
Increased Risk

Abstract Background Surgery is an important therapeutic option for brain metastases. Currently, postoperative stereotactic radiosurgery (SRT) leads to 6-month and 1-year local control estimated at 70 and 62% respectively. However, there is an increased risk of radio-necrosis and leptomeningeal relapse. Preoperative SRT might be an alternative, providing local control remains at least equivalent. It is an innovative concept that could enable the stereotactic benefits to be retained with advantages over post-operative SRT. Methods STEP has been designed as a national, multicentre, open-label, prospective, non-randomized, phase-II trial. Seventeen patients are expected to be recruited in the study from 7 sites and they will be followed for 12 months. Patients with more than 4 distinct brain metastases, including one with a surgical indication, and an indication for SRT and surgery, are eligible for enrolment. The primary objective of the trial is to assess 6-month local control after preoperative SRT. The secondary objectives include the assessment of local control, radio-necrosis, overall survival, toxicities, leptomeningeal relapse, distant control, cognitive function, and quality of life. The experimental design is based on a Flemming plan. Discussion There is very little data available in the literature on preoperative SRT: there have only been 3 American single or two-centre retrospective studies. STEP is the first prospective trial on preoperative SRT in Europe. Compared to postoperative stereotactic radiotherapy, preoperative stereotactic radiotherapy will enable reduction in the irradiated volume, leptomeningeal relapse and the total duration of the combined treatment (from 4 to 6 weeks to a few days). Trial registration number Clinicaltrials.gov: NCT04503772, registered on August 07, 2020. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2020-A00403–36, registered in February 2020. Protocol: version 4, 07 December 2020.

scholarly journals Clinical and volumetric predictors of local control after robotic stereotactic radiosurgery for cerebral metastases: active systemic disease may affect local control in the brain

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sławomir Blamek ◽  
Magdalena Stankiewicz ◽  
Bogusław Maciejewski
Keyword(s):  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Cox Model ◽  
Systemic Disease ◽  
Univariate Analysis ◽  
Effective Control ◽  
Single Fraction ◽  
Robotic Radiosurgery ◽  
Fractionation Schedule ◽  
The Brain

AbstractBackgroundThe aim of the study was to assess the association between physical and biological dose normalized to volume of the metastatic tumor as well as clinical factors with local control in patients with brain metastases who underwent robotic stereotactic radiosurgery.Patients and methodsA cohort of 69 patients consecutively treated with robotic radiosurgery between 2011 and 2016 was analyzed. The patients were treated with either single fraction radiosurgery or hypofractionated regimens. Biologically effective dose (BED) was calculated assuming alpha/beta value = 10 and both physical dose and BED were normalized to the tumor volume to allow dose-volume effect evaluation. Moreover, clinical and treatment-related variables were evaluated to asses association with local control.ResultsA total of 133 tumors were irradiated and their volumes ranged between 0.001 and 46.99 cm3. Presence of extracranial progression was associated with worse local control whereas higher total dose, BED10 > 59 Gy and single metastasis predicted statistically significantly better local outcome. BED10/cm3 > 36 Gy, and BED2 > 60 Gy negatively affected local control in univariate analysis. In multivariate analysis performed on all these variables, presence of a single metastasis, BED10 > 59 Gy and extracranial progression retained their significance. Excluding a priori the BED2/ cm3 parameter resulted with a Cox model confirming significance of all remaining variables.ConclusionsHypofractionated treatment schemes have similar efficiency to single fraction treatment in terms of local control and the effect depends on BED irrespective of fractionation schedule. Effective control of extracranial sites of the disease is associated with higher probability of local control in the brain which in turn is consistently lower in patients with multiple lesions.

Post-operative stereotactic radiosurgery of brain metastases: A single-center retrospective review of clinical outcomes

2019 ◽  
Vol 19 (2) ◽  
pp. 127-131
Author(s):  
Zachary T. Smith ◽  
Syed U. Ashruf ◽  
Charles Mylander ◽  
Kerry J. Thompson ◽  
Charles Geraghty ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Retrospective Review ◽  
Categorical Variables ◽  
Community Practice ◽  
Continuous Variables ◽  
Survival Times ◽  
Single Fraction

AbstractAim:We sought to retrospectively report our outcomes using post-operative stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) in place of whole-brain radiation therapy (WBRT) following resection of brain metastases from our hospital-based community practice.Materials and Methods:A retrospective review of 23 patients who underwent post-operative SRS at our single institution from 2013 to 2017 was undertaken. Patient records, treatment plans and diagnostic images were reviewed. Local failure, distant intracranial failure and overall survival were studied. Categorical variables were analyzed using Fisher’s exact tests. Continuous variables were analyzed using Mann–Whitney tests. The Kaplan–Meier method was used to estimate survival times.Results:16 (70%) were single-fraction SRS, whereas the remaining 7 patients received a five-fraction treatment course. The median single-fraction dose was 16 Gy (range, 16–18). The median total dose for fractionated treatments was 25 Gy (range, 25–35). Overall survival at 6 and 12 months was 95 and 67%, respectively. Comparison of SRS versus SRT local control rates at 6 and 12 months revealed control rates of 92 and 78% versus 29 and 14%, respectively. Every patient with dural/pial involvement at the time of surgery had distant intracranial failure at the 12-month follow-up.Findings:Single-fraction frameless SRS proved to be an effective modality with excellent local control rates. However, the five-fraction SRT course was associated with an increased rate of local recurrence. Dural/pial involvement may portend a high risk for distant intracranial disease; therefore, it may be prudent to consider alternative approaches in these cases.

scholarly journals Stereotactic radiotherapy using the CyberKnife is effective for local control of bone metastases from differentiated thyroid cancer

2019 ◽  
Vol 60 (6) ◽  
pp. 831-836 ◽  
Author(s):  
Takayuki Ishigaki ◽  
Takashi Uruno ◽  
Kiminori Sugino ◽  
Chie Masaki ◽  
Junko Akaishi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Adverse Events ◽  
Bone Metastases ◽  
Local Control ◽  
Stereotactic Radiotherapy ◽  
Differentiated Thyroid Cancer ◽  
Local Control Rate ◽  
High Dose ◽  
Long Term Prognosis

ABSTRACT Differentiated thyroid cancer (DTC) is associated with a good long-term prognosis, but bone metastases can adversely affect patients’ quality of life and survival. Stereotactic radiotherapy (SRT) can deliver high-dose irradiation to target lesions and it has been reported to be useful for various cancers. However, few studies have examined the efficacy of SRT for thyroid cancer. In the present study, the aim was to investigate the efficacy of SRT using the CyberKnife for bone metastases from DTC. From September 2013 to April 2018, SRT with the CyberKnife system was used to treat 60 bone metastases from DTC in 13 patients. The patients’ medical records were retrospectively reviewed to obtain information about the adverse events associated with SRT. Of the 60 lesions, 40 could be evaluated by follow-up CT for therapeutic effectiveness, and the RECIST criteria were used to assess the response. The cancers were papillary cancer in 3 patients, follicular cancer in 9 and poorly differentiated cancer in 1. SRT was delivered in 1–10 fractions, with a median dose of 27 Gy (range, 8–48 Gy). Adverse events were infrequent and mild. The median follow-up of the 40 lesions was 11 (range, 2–56) months. The responses were partial response in 2 lesions, stable disease in 37 lesions and progressive disease in 1 lesion, with a 1-year local control rate of 97.1%. The present study showed that SRT using the CyberKnife system was a feasible and effective treatment for bone metastases of DTC.

Local disease control after decompressive surgery and adjuvant high-dose single-fraction radiosurgery for spine metastases

2010 ◽  
Vol 13 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Hugh D. Moulding ◽  
James B. Elder ◽  
Eric Lis ◽  
Dale M. Lovelock ◽  
Zhigang Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Local Control ◽  
Local Tumor Control ◽  
Local Control Rate ◽  
Surgical Decompression ◽  
Local Failure ◽  
Tumor Control ◽  
High Dose ◽  
Single Fraction ◽  
Local Disease Control

Object Adjuvant radiation following epidural spinal cord decompression for tumor is a powerful tool used to achieve local disease control and preserve neurological function. To the authors' knowledge, only 1 published report addresses adjuvant stereotactic radiosurgery after this procedure, but that study used significantly lower doses than are currently prescribed. The authors review their experience using high-dose single-fraction radiosurgery as a postoperative adjuvant following surgical decompression and instrumentation to assess long-term local tumor control, morbidity, and survival. Methods A retrospective chart review identified 21 patients treated with surgical decompression and instrumentation for high-grade, epidural, spinal cord compression from tumor, followed by single-fraction high-dose spinal radiosurgery (dose range 18–24 Gy, median 24 Gy). Spinal cord dose was limited to a cord maximal dose of 14 Gy. Tumor histologies, time between surgery and radiosurgery, time to local recurrence after radiosurgery as assessed by serial MR imaging, and time to death were determined. Competing risk analysis was used to evaluate these end points. Results In this series, 20 tumors treated (95%) were considered highly radioresistant to conventional external beam radiation. The planning target volume received a high dose (24 Gy) in 16 patients (76.2%), and a low dose (18 or 21 Gy) in 5 patients (23.8%). During the study, 15 (72%) of 21 patients died, and in all cases death was due to systemic progression as opposed to local failure. The median overall survival after radiosurgery was 310 days (range 37 days to not reached). One patient (4.8%) underwent repeat surgery for local failure and 2 patients (9.5%) underwent spine surgery for other reasons. Local control was maintained after radiosurgery in 17 (81%) of 21 patients until death or most recent follow-up, with an estimated 1-year local failure risk of 9.5%. Of the failures, 3 of 4 were noted in patients receiving low-dose radiosurgery, equaling an overall failure rate of 60% (3 of 5 patients) and a 1-year local failure estimated risk of 20%. Those patients receiving adjuvant stereotactic radiosurgery with a high dose had a 93.8% overall local control rate (15 of 16 patients), with a 1-year estimated failure risk of 6.3%. Competing risk analysis showed this to be a significant difference between radiosurgical doses. One patient experienced a significant radiation-related complication; there were no wound-related issues after radiosurgery. Conclusions Spine radiosurgery after surgical decompression and instrumentation for tumor is a safe and effective technique that can achieve local tumor control until death in the vast majority of patients. In this series, those patients who received a higher radiosurgical dose had a significantly better local control rate.

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