Effective method to reduce the normal brain dose in single-isocenter hypofractionated stereotactic radiotherapy for multiple brain metastases

Lai, Jialu; Liu, Jia; Zhao, Jianling; An, Li; Liu, Shoupeng; Deng, Zhonghua; Tan, Qiaoyue; Wang, Haitao; Jia, Yuming; Lei, Kaijian; Zhou, Lin

doi:10.1007/s00066-021-01757-6

Cited by 11 publications

(8 citation statements)

References 35 publications

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“…Corresponding to 15-17.7, 7.1-12.4, and 23-25 months for patients who received upfront TKI treatment, respectively. [11][12][13]26 The superiority of upfront brain radiotherapy in intracranial disease control, overall disease control, and OS was consistent in these studies, especially for patients with limited BMs (≤3 or 4). [11][12][13] However, in these studies, the intracranial and overall disease control time after receiving brain radiotherapy for progressed intracranial disease, which was considered in iPFS2 and PFS2 of the present study, for patients in the upfront TKI treatment group was not clear.…”

Section: Discussionsupporting

confidence: 62%

“…The incidence rates of CRN after brain HSRT/SRS for BMs have been reported to be 6.3%-34%. 16,26,29,30 However, no information on CRN has been provided in previous similar studies. [11][12][13] In the present study, the incidence of CRN in all patients was 14.3% and was lowest in the consolidative HRST group compared to the upfront and salvage groups (3.6% vs. 16% and 21.9%), even with no statistical significance among the groups (p = 0.124).…”

Section: Discussionmentioning

confidence: 99%

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Optimal timing of hypofractionated stereotactic radiotherapy for epidermal growth factor receptor‐mutated non‐small‐cell lung cancer patients with brain metastases

Liang

Liu

Liu³

et al. 2023

Asia-Pac J Clncl Oncology

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BackgroundFor epidermal growth factor receptor (EGFR)‐mutated non‐small‐cell lung cancer (NSCLC) patients with limited brain metastases (BMs), who eventually receive both tyrosine kinase inhibitors (TKIs) treatment and brain radiotherapy, the optimal timing of radiotherapy is not clear. The present retrospective analysis aimed to partly solve this problem.MethodsIn total 84 EGFR‐mutated NSCLC patients with limited BMs, who received both TKI treatment and brain hypofractionated stereotactic radiotherapy (HSRT), were enrolled. Patients were divided into three groups based on whether the HSRT was administrated 2 weeks before or after the beginning of TKI treatment (upfront HSRT), when intracranial lesions stabilized after TKI treatment (consolidative HSRT), or when the intracranial disease progressed after TKI treatment (salvage HSRT). The clinical efficacy and toxicities were evaluated.ResultsThe median intracranial progression‐free survival (iPFS) and overall PFS calculated from the initiation of HSRT (iPFS1 and PFS1) of all patients were 17.5 and 13.1 months, respectively. The median iPFS and PFS calculated from the initiation of TKI treatment (iPFS2 and PFS2) of all patients were 24.1 and 18.4 months, respectively. Compared to consolidative and salvage HSRT, upfront HSRT improved iPFS1 (not reached vs. 17.5 months vs. 11.0 months, p < 0.001) and PFS1 (18.4 months vs. 9.1 months vs. 7.9 months, p < 0.001), and reduced the initial intracranial failure rate (12.5% vs. 48.1% vs. 56%, p < 0.001). However, there were no significant differences between the three groups for iPFS2, PFS2, and overall survival. Hepatic metastases and diagnosis‐specific Graded Prognostic Assessment (ds‐GPA) at 2–3 were poor prognostic factors.ConclusionFor patients who receive both TKI treatment and brain HSRT, the timing of HSRT does not seem to influence the eventual therapeutic effect. Further validation in prospective clinical studies is needed.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Optimal timing of hypofractionated stereotactic radiotherapy for epidermal growth factor receptor‐mutated non‐small‐cell lung cancer patients with brain metastases

Liang

Liu

Liu³

et al. 2023

Asia-Pac J Clncl Oncology

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“…This is the first study to address the potential impact of repeated irradiation to multiple BMs. Moreover, no study has investigated the dose to the brain and to the healthy brain in cases of repeated SRT [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Acute toxicities and cumulative dose to the brain of repeated sessions of stereotactic radiotherapy (SRT) for brain metastases: a retrospective study of 184 patients

et al. 2023

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Background Stereotactic radiation therapy (SRT) is a focal treatment for brain metastases (BMs); thus, 20 to 40% of patients will require salvage treatment after an initial SRT session, either because of local or distant failure. SRT is not exempt from acute toxicity, and the acute toxicities of repeated SRT are not well known. The objective of this study was to analyze the acute toxicities of repeated courses of SRT and to determine whether repeated SRT could lead to cumulative brain doses equivalent to those of whole-brain radiotherapy (WBRT). Material and methods Between 2010 and 2020, data from 184 patients treated for 915 BMs via two to six SRT sessions for local or distant BM recurrence without previous or intercurrent WBRT were retrospectively reviewed. Patients were seen via consultations during SRT, and the delivered dose, the use of corticosteroid therapy and neurological symptoms were recorded and rated according to the CTCAEv4. The dosimetric characteristics of 79% of BMs were collected, and summation plans of 76.6% of BMs were created. Results 36% of patients developed acute toxicity during at least one session. No grade three or four toxicity was registered, and grade one or two cephalalgy was the most frequently reported symptom. There was no significant difference in the occurrence of acute toxicity between consecutive SRT sessions. In the multivariate analysis, acute toxicity was associated with the use of corticosteroid therapy before irradiation (OR = 2.6; p = 0.01), BMV grade (high vs. low grade OR = 5.17; p = 0.02), and number of SRT sessions (3 SRT vs. 2 SRT: OR = 2.64; p = 0.01). The median volume equivalent to the WBRT dose (VWBRT) was 47.9 ml. In the multivariate analysis, the VWBRT was significantly associated with the total GTV (p < 0.001) and number of BMs (p < 0.001). Even for patients treated for more than ten cumulated BMs, the median BED to the brain was very low compared to the dose delivered during WBRT. Conclusion Repeated SRT for local or distant recurrent BM is well tolerated, without grade three or four toxicity, and does not cause more acute neurological toxicity with repeated SRT sessions. Moreover, even for patients treated for more than ten BMs, the VWBRT is low.

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“…Meanwhile, there is also a large body of evidence suggesting progressive use of SRS as the primary treatment option in combination with systemic treatment [ 33 ]. This does not only include a limited number of 1–3 brain metastases; SRS can currently be used safely in up to 15 brain metastases [ 34 – 36 ]. While radionecrosis may be a factor to consider in SRS [ 37 ], the main advantage of SRS versus WBRT is reduced neurotoxicity, which has been demonstrated in several studies, especially confirming short-term neurocognitive decline induced by WBRT [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Long-term neurocognitive function after whole-brain radiotherapy in patients with melanoma brain metastases in the era of immunotherapy

et al. 2022

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Background Whole-brain radiotherapy (WBRT) used to be standard of care for patients suffering from melanoma brain metastases (MBM) and may still be applicable in selected cases. Deterioration of neurocognitive function (NCF) is commonly seen during and after WBRT. Knowledge on long-term effects in melanoma patients is limited due to short survival rates. With the introduction of immune checkpoint inhibitors, patients may experience ongoing disease control, emphasizing the need for paying more attention to potential long-term adverse effects. Methods In this single-center study, we identified in a period of 11 years all long-term survivors of MBM who received WBRT at least 1 year prior to inclusion. NCF was assessed by Neuropsychological Assessment Battery (NAB) screening and detailed neurological exam; confounders were documented. Results Eight patients (median age 55 years) could be identified with a median follow-up of 5.4 years after WBRT. Six patients reported no subjective neurological impairment. NAB screening revealed an average-range score in 5/8 patients. In 3/8 patients a NAB score below average was obtained, correlating with subjective memory deficits in 2 patients. In these patients, limited performance shown in modalities like memory function, attention, and spatial abilities may be considerably attributed to metastasis localization itself. Six out of 8 patients were able to return to their previous work. Conclusion Five of 8 long-term survivors with MBM after WBRT experienced little to no restriction in everyday activities. In 3 out of 8 patients, cognitive decline was primarily explained by localization of the metastases in functionally relevant areas of the brain. The results of our small patient cohort do not support general avoidance of WBRT for treatment of brain metastases. However, long-term studies including pretreatment NCF tests are needed to fully analyze the long-term neurocognitive effects of WBRT

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Effective method to reduce the normal brain dose in single-isocenter hypofractionated stereotactic radiotherapy for multiple brain metastases

Cited by 11 publications

References 35 publications

Optimal timing of hypofractionated stereotactic radiotherapy for epidermal growth factor receptor‐mutated non‐small‐cell lung cancer patients with brain metastases

Optimal timing of hypofractionated stereotactic radiotherapy for epidermal growth factor receptor‐mutated non‐small‐cell lung cancer patients with brain metastases

Acute toxicities and cumulative dose to the brain of repeated sessions of stereotactic radiotherapy (SRT) for brain metastases: a retrospective study of 184 patients

Long-term neurocognitive function after whole-brain radiotherapy in patients with melanoma brain metastases in the era of immunotherapy

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