Hypofractionated Radiation Therapy for Large Brain Metastases

Masucci, Giuseppina Laura

doi:10.3389/fonc.2018.00379

Cited by 40 publications

(34 citation statements)

References 70 publications

(138 reference statements)

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“…Our results are consistent with literature showing that size is a robust prognosis factor of local control upon SRS and HFSRT [8,27]. However, definition of large BM is heterogeneous among studies, making the comparison difficult [6].…”

Section: Discussionsupporting

confidence: 91%

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Brain metastases treated with hypofractionated stereotactic radiotherapy: 8 years experience after Cyberknife installation

Mengue

Bertaut

Mbus³

et al. 2020

Radiat Oncol

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Background: Hypofractionated stereotactic radiotherapy (HFSRT) is indicated for large brain metastases (BM) or proximity to critical organs (brainstem, chiasm, optic nerves, hippocampus). The primary aim of this study was to assess factors influencing BM local control after HFSRT. Then the effect of surgery plus HFSRT was compared with exclusive HFSRT on oncologic outcomes, including overall survival. Materials and methods: Retrospective study conducted in Léon Bérard Cancer Center, included patients over 18 years-old with BM, secondary to a tumor proven by histology and treated by HFSRT alone or after surgery. Three different dose-fractionation schedules were compared: 27 Gy (3 × 9 Gy), 30 Gy (5 × 6 Gy) and 35 Gy (5 × 7 Gy), prescribed on isodose 80%. Primary endpoint were local control (LC). Secondary endpoints were overall survival (OS) and radionecrosis (RN) rate. Results: A total of 389 patients and 400 BM with regular MRI follow-up were analyzed. There was no statistical difference between the different dose-fractionations. On multivariate analysis, surgery (p = 0.049) and size (< 2.5 cm) (p = 0.01) were independent factors improving LC. The 12 months LC was 87.02% in the group Surgery plus HFSRT group vs 73.53% at 12 months in the group HFSRT. OS was 61.43% at 12 months in the group Surgery plus HFSRT group vs 50.13% at 12 months in the group HFSRT (p < 0.0085). Prior surgery (OR = 1.86; p = 0.0028) and sex (OR = 1.4; p = 0.0139) control of primary tumor (OR = 0.671, p = 0.0069) and KPS < 70 (OR = 0.769, p = 0.0094) were independently predictive of OS. The RN rate was 5% and all patients concerned were symptomatic. Conclusions: This study suggests that HFSRT is an efficient and well-tolerated treatment. The optimal dosefractionation remains difficult to determine. Smaller size and surgery are correlated to LC. These results evidence the importance of surgery for larger BM (> 2.5 cm) with a poorer prognosis. Multidisciplinary committees and prospective studies are necessary to validate these observations.

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Section: Discussionsupporting

confidence: 91%

“…The use of SRS is however correlated to a high risk of radionecrosis [5]. Large lesions distant from critical structures are preferably treated by surgery [6]. In case of surgical contraindication HFSRT may be an option [7].…”

Section: Introductionmentioning

confidence: 99%

Brain metastases treated with hypofractionated stereotactic radiotherapy: 8 years experience after Cyberknife installation

Mengue

Bertaut

Mbus³

et al. 2020

Radiat Oncol

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“…A significant difference in morphology between those irradiated with FLASH-RT or CONV-RT was only apparent at doses ≥ 10 Gy. Even when accounting for the dose modifying factor of FLASH-RT, an equivalent dose per fraction of 6-8 Gy given by CONV-RT may still be considered as too large a dose in various clinical scenarios (58)(59)(60), such as in the treatment of larger, locally advanced tumors. A previous phase I dose escalation study in locally advanced non-small cell lung cancer (NSCLC) utilized hypofractionated treatment with doses per fraction well-below those required for a FLASH effect (58).…”

Section: Clinical Applications Of Flash-rtmentioning

confidence: 99%

“…Six patients developed late onset, grade 4-5 toxicities that were attributed to damage to the proximal bronchial tree, ergo highlighting the need for caution when employing hypofractionated regimes. Hypofractionation is nevertheless getting more widely used in the clinic for a variety of treatments sites (59,(61)(62)(63)(64), and could be proven even more useful together with FLASH-RT and its (potentially) lower level of normal tissue toxicity.…”

Section: Clinical Applications Of Flash-rtmentioning

confidence: 99%

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

et al. 2020

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Radiotherapy is a cornerstone of both curative and palliative cancer care. However, radiotherapy is severely limited by radiation-induced toxicities. If these toxicities could be reduced, a greater dose of radiation could be given therefore facilitating a better tumor response. Initial pre-clinical studies have shown that irradiation at dose rates far exceeding those currently used in clinical contexts reduce radiation-induced toxicities whilst maintaining an equivalent tumor response. This is known as the FLASH effect. To date, a single patient has been subjected to FLASH radiotherapy for the treatment of subcutaneous T-cell lymphoma resulting in complete response and minimal toxicities. The mechanism responsible for reduced tissue toxicity following FLASH radiotherapy is yet to be elucidated, but the most prominent hypothesis so far proposed is that acute oxygen depletion occurs within the irradiated tissue. This review examines the tissue response to FLASH radiotherapy, critically evaluates the evidence supporting hypotheses surrounding the biological basis of the FLASH effect, and considers the potential for FLASH radiotherapy to be translated into clinical contexts.

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“…A study suggests employing multifractionated SRS in three to five fractions rather than single fraction SRS as a means of decreasing the risk of radiation necrosis and improving local control [26] . The use of fractionated SRS also allows for the safe treatment of larger BM (> 3 cm) [26,27] . Data on long-term effects of SRS on neurocognition is limited but reassuring [25] .…”

Section: Adverse Effects Of Srsmentioning

confidence: 99%

Stereotactic radiosurgery in the era of novel systemic therapy for lung cancer brain metastases

Mudra¹,

Bhandari²,

Tripathi³

et al. 2019

JCMT

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The emergence of novel systemic therapies has spurred a dramatic paradigm shift in lung cancer treatment. Research has revealed greater intracranial efficacy in targeted agents and immune checkpoint inhibitors (ICI) compared to conventional chemotherapy. Concurrently, advances in stereotactic radiosurgery (SRS) have contributed to the increased use of this highly localized, minimally-invasive treatment modality for local tumor control. In this era of precision medicine, the combination of these novel agents and SRS demands further prospective explorationparticularly as questions regarding their sequence of administration and the risk of neurotoxicity remain unanswered. Presently, although data are limited and largely retrospective, literature supports the concurrent administration of ICI and radiation, with no observed increases in immune-related adverse events or acute neurologic toxicities. In the case of patients with driver mutations, newer generations of tyrosine kinase inhibitors (TKI) display improved intracranial efficacy and are currently preferred alone upfront in patients with asymptomatic brain metastases (BM) due to lack of data. Evidence of combining TKI and SRS is limited with mixed results. In this review, we explore the evidence regarding the use of novel systemic agents and SRS for treatment of lung cancer BM. Clinical practice will continue to be refined as larger, prospective studies yield results.

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Hypofractionated Radiation Therapy for Large Brain Metastases

Cited by 40 publications

References 70 publications

Brain metastases treated with hypofractionated stereotactic radiotherapy: 8 years experience after Cyberknife installation

Brain metastases treated with hypofractionated stereotactic radiotherapy: 8 years experience after Cyberknife installation

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

Stereotactic radiosurgery in the era of novel systemic therapy for lung cancer brain metastases

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