Preoperative Radiosurgery in Management of Brain Metastases

2020 ◽  
pp. 1-11
Author(s):  
Erkan Topkan ◽  
Ahmet Kucuk ◽  
Sukran Senyurek ◽  
Duygu Sezen ◽  
Nulifer Kilic Durankus ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Local Treatment ◽  
Treatment Strategies ◽  
Whole Brain Radiotherapy ◽  
Active Management ◽  
The Novel ◽  
Leptomeningeal Dissemination ◽  
Brain Radiotherapy ◽  
Increased Risk ◽  
Neurotoxic Effects

Brain metastases (BMs), the most frequent intracranial tumors, are diagnosed in approximately 30% of all adult patients over the span of planned treatment against a broad spectrum of solid cancers. The prognosis of patients presenting with BM is bleak with an expected median OS of only 4-7 months. However, some particular patients’ groups may enjoy longer survival durations with effective systemic and local therapies. At present, the feasible alternatives for active management of BMs typically include the whole-brain radiotherapy (WBRT), surgery, definitive SRS, postoperative SRS, systemic chemotherapy, targeted therapies, and their combination variants. Considering the local treatment, the severe neurotoxic effects of WBRT, and the increased risk for radionecrosis and leptomeningeal dissemination after postoperative SRS and together with the ineligibility of certain patients during the postoperative period prompted the energetic quest of alternative treatment strategies for such patients. In this respect, the novel preoperative SRS (PO-SRS) was proposed to provide at least equivalent local control rates with lesser radionecrosis and leptomeningeal dissemination risk. Respecting the scarcity of related literature, the present review aimed to meticulously detail theplausible rationale and accessible evidence for the novel PO-SRS in the management of patients presenting with BMs.

Hemorrhagic and Cystic Brain Metastases Are Associated With an Increased Risk of Leptomeningeal Dissemination After Surgical Resection and Adjuvant Stereotactic Radiosurgery

Neurosurgery ◽  
2018 ◽  
Vol 85 (5) ◽  
pp. 632-641 ◽  
Author(s):  
Robert H Press ◽  
Chao Zhang ◽  
Mudit Chowdhary ◽  
Roshan S Prabhu ◽  
Matthew J Ferris ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Cumulative Incidence ◽  
Postoperative Radiotherapy ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Competing Risk ◽  
Leptomeningeal Dissemination ◽  
Increased Risk

Abstract BACKGROUND Brain metastases (BM) treated with surgical resection and focal postoperative radiotherapy have been associated with an increased risk of subsequent leptomeningeal dissemination (LMD). BMs with hemorrhagic and/or cystic features contain less solid components and may therefore be at higher risk for tumor spillage during resection. OBJECTIVE To investigate the association between hemorrhagic and cystic BMs treated with surgical resection and stereotactic radiosurgery and the risk of LMD. METHODS One hundred thirty-four consecutive patients with a single resected BM treated with adjuvant stereotactic radiosurgery from 2008 to 2016 were identified. Intracranial outcomes including LMD were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis and multivariable analysis were assessed using the Fine & Gray model. Overall survival was analyzed using the Kaplan-Meier method. RESULTS Median imaging follow-up was 14.2 mo (range 2.5-132 mo). Hemorrhagic and cystic features were present in 46 (34%) and 32 (24%) patients, respectively. The overall 12- and 24-mo cumulative incidence of LMD with death as a competing risk was 11.0 and 22.4%, respectively. On multivariable analysis, hemorrhagic features (hazard ratio [HR] 2.34, P = .015), cystic features (HR 2.34, P = .013), breast histology (HR 3.23, P = .016), and number of brain metastases >1 (HR 2.09, P = .032) were independently associated with increased risk of LMD. CONCLUSION Hemorrhagic and cystic features were independently associated with increased risk for postoperative LMD. Patients with BMs containing these intralesion features may benefit from alternative treatment strategies to mitigate this risk.

scholarly journals A Case of Brain Metastases from Breast Cancer Treated with Whole-Brain Radiotherapy and Eribulin Mesylate

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Carsten Nieder ◽  
Gro Aandahl ◽  
Astrid Dalhaug
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Metastatic Disease ◽  
Local Treatment ◽  
Whole Brain Radiotherapy ◽  
Maximum Size ◽  
Newly Diagnosed ◽  
Eribulin Mesylate ◽  
Whole Brain ◽  
Brain Radiotherapy

Patients with triple receptor-negative breast cancer often develop aggressive metastatic disease, which also might involve the brain. In many cases, systemic and local treatment is needed. It is important to consider the toxicity of chemo- and radiotherapy, especially when newly approved drugs become available. Randomised studies leading to drug approval often exclude patients with newly diagnosed brain metastases. Here we report our initial experience with eribulin mesylate and whole-brain radiotherapy (WBRT) in a heavily pretreated patient with multiple brain, lung, and bone metastases from triple receptor-negative breast cancer. Eribulin mesylate was given after 4 previous lines for metastatic disease. Two weeks after the initial dose, that is, during the first cycle, the patient was diagnosed with 5 brain metastases with a maximum size of approximately 4.5 cm. She continued chemotherapy and received concomitant WBRT with 10 fractions of 3 Gy. After 3 cycles of eribulin mesylate, treatment was discontinued because of newly diagnosed liver metastases and progression in the lungs. No unexpected acute toxicity was observed. The only relevant adverse reactions were haematological events after the third cycle (haemoglobin 9.5 g/dL, leukocytes3.1×109/L). The patient died from respiratory failure 18.5 months from diagnosis of metastatic disease, and 2.7 months from diagnosis of brain metastases. To the best of our knowledge, this is the first report on combined WBRT and eribulin mesylate.

Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases

Neurosurgery ◽  
2018 ◽  
Vol 85 (2) ◽  
pp. 257-263 ◽  
Author(s):  
Ryan T Hughes ◽  
Emory R McTyre ◽  
Michael LeCompte ◽  
Christina K Cramer ◽  
Michael T Munley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Outcomes ◽  
Whole Brain Radiotherapy ◽  
Cox Proportional Hazards ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Increased Risk

Abstract BACKGROUND The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial. OBJECTIVE To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group. METHODS A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan–Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox proportional hazards. RESULTS Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respectively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume parameters predicted for death, neurologic death or toxicity. CONCLUSION SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

scholarly journals Is local radiotherapy a viable option for patients with an opening of the ventricles during surgical resection of brain metastases?

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sophia Scharl ◽  
Kerstin A. Kessel ◽  
Christian Diehl ◽  
Jens Gempt ◽  
Bernhard Meyer ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Surgical Resection ◽  
Local Treatment ◽  
Whole Brain Radiotherapy ◽  
Standard Of Care ◽  
Neurological Impairment ◽  
Distant Recurrence ◽  
Tumor Bed ◽  
Resection Cavity ◽  
Brain Radiotherapy

Abstract Background Local hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity is emerging as the standard of care in the treatment of patients with a limited number of brain metastases as it warrants less neurological impairment compared to whole brain radiotherapy. In periventricular metastases surgical resection can lead to an opening of the ventricles and subsequently carries a potential risk of cerebrospinal tumour cell dissemination. The aim of this study was to assess whether local radiotherapy of the resection cavity is viable in these cases. Methods From our institutional database we analyzed the data of 125 consecutive patients with resected brain metastases treated in our institution with HFSRT between 2009 and 2017. The incidence of LMD, overall survival (OS), local recurrence (LC) and distant recurrence were evaluated depending on ventricular opening (VO) during surgery. Results From all 125 patients, the ventricles were opened during surgery in 14 cases (11.2%). None of the patients with VO and 7 patients without VO during surgery developed LMD (p = 0.371). OS (p = 0.817), LC (p = 0.524) and distant recurrence (p = 0.488) did not differ in relation to VO during surgical resection. However, the incidence of distant intraventricular recurrence was slightly increased in patients with VO (14.3% vs. 2.7%, p < 0.01). Conclusion VO during neurosurgical resection did not affect the outcome after HFSRT of the resection cavity in patients with brain metastases. Particularly, the incidence of LMD was not increased in patients receiving local HFSRT after VO. HFSRT can therefore be offered independently of VO as a local treatment of tumor bed after resection of brain metastases.

Toward Precision Medicine in Brain Metastases

2018 ◽  
Vol 38 (01) ◽  
pp. 095-103 ◽  
Author(s):  
Anna Berghoff ◽  
Priscilla Brastianos
Keyword(s):  
Brain Metastases ◽  
Genetic Divergence ◽  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Whole Brain Radiotherapy ◽  
Genetic Alterations ◽  
Brain Radiotherapy ◽  
Genomic Technologies ◽  
New Treatment ◽  
The Brain

AbstractBrain metastases (BMs) reflect an area of high clinical need, as up to 40% of patients with metastatic cancer will develop this morbid and highly fatal complication. Historically, treatment strategies have relied on local approaches including radiosurgery, whole-brain radiotherapy, and neurosurgical resection. Recently, targeted and immune-modulating therapies have shown promising responses and have been introduced in the clinical management of patients with BMs. Recent improvements in genomic technologies have enriched our understanding of BMs and have demonstrated that BMs present with significant genetic divergence from the originating primary tumor, such that potentially targetable genetic alterations are detected only in the BMs. However, this genetic divergence also results in genetic alterations associated with resistance to targeted therapies. A deeper insight on the genetic alterations of BMs and the interaction with the brain microenvironment will likely reveal new treatment targets, moving toward more precision therapies for patients with BMs.

scholarly journals Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Gerald Fogarty ◽  
Rachael L Morton ◽  
Janette Vardy ◽  
Anna K Nowak ◽  
Catherine Mandel ◽  
...  
Keyword(s):  
New Zealand ◽  
Brain Metastases ◽  
Local Treatment ◽  
Whole Brain Radiotherapy ◽  
Neurocognitive Function ◽  
Cerebral Metastases ◽  
Phase Iii ◽  
Leptomeningeal Disease ◽  
Whole Brain ◽  
Brain Radiotherapy

Abstract Background Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete. Methods/Design This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function. Discussion Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain metastases. The trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG-study 01-07), and the Trans Tasman Radiation Oncology Group (TROG) but international participation is encouraged. Twelve sites are open to date with 43 patients randomised as of the 31st March 2011. The target accrual is 200 patients. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000512426

Whole-Brain Radiotherapy and Stereotactic Radiosurgery in Brain Metastases: What Is the Evidence?

2015 ◽  
pp. e99-e104 ◽  
Author(s):  
Minesh P. Mehta ◽  
Manmeet S. Ahluwalia
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Performance Status ◽  
Local Treatment ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Disease Status ◽  
Tumor Type ◽  
Whole Brain ◽  
Brain Radiotherapy

The overall local treatment paradigm of brain metastases, which includes whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS), continues to evolve. Local therapies play an important role in the management of brain metastases. The choice of local therapy depends on factors that involve the patient (performance status, expected survival, and age), the prior treatment history, and the tumor (type and subtype, number, size, location of metastases, and extracranial disease status). Multidisciplinary collaboration is required to facilitate an individualized plan to improve the outcome of disease in patients with this life-limiting complication. There has been concern about the neurocognitive effects of WBRT. A number of approaches that mitigate cognitive dysfunction, such as pharmacologic intervention (memantine) or a hippocampal-sparing strategy, have been studied in a prospective manner with WBRT. Although there has been an increase in the use of SRS in the management of brain metastases in recent years, WBRT retains an important therapeutic role.

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