scholarly journals It Is Time to Reevaluate the Management of Patients With Brain Metastases

Neurosurgery ◽  
2014 ◽  
Vol 75 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Douglas Kondziolka ◽  
Steven N. Kalkanis ◽  
Minesh P. Mehta ◽  
Manmeet Ahluwalia ◽  
Jay S. Loeffler
Keyword(s):  
Brain Metastases ◽  
Cognitive Dysfunction ◽  
Clinical Care ◽  
Radiation Risk ◽  
Whole Brain Radiation ◽  
Metastatic Lesions ◽  
Response To Chemotherapy ◽  
Impact On Survival ◽  
The Impact ◽  
The Brain

Abstract There are many elements to the science that drives the clinical care of patients with brain metastases. Although part of an understanding that continues to evolve, a number of key historical misconceptions remain that commonly drive physicians' and researchers' attitudes and approaches. By understanding how these relate to current practice, we can better comprehend our available science to provide both better research and care. These past misconceptions include: Misconception 1: Once a primary cancer spreads to the brain, the histology of that primary tumor does not have much impact on response to chemotherapy, sensitivity to radiation, risk of further brain relapse, development of additional metastatic lesions, or survival. All tumor primary histologies are the same once they spread to the brain. They are the same in terms of the number of tumors, radiosensitivity, chemoresponsiveness, risk of further brain relapse, and survival. Misconception 2: The number of brain metastases matters. This number matters in terms of subsequent brain relapse, survival, and cognitive dysfunction; the precise number of metastases can also be used as a limit in determining which patients might be eligible for a particular treatment option. Misconception 3: Cancer in the brain is always a diffuse problem due to the presence of micrometastases. Misconception 4: Whole-brain radiation therapy invariably causes disabling cognitive dysfunction if a patient lives long enough. Misconception 5: Most brain metastases are symptomatic. Thus, it is not worth screening patients for brain metastases, especially because the impact on survival is minimal. The conduct and findings of past clinical research have led to conceptions that affect clinical care yet appear limiting.

scholarly journals BSCI-20. THERAPEUTIC TARGETING OF HLA-G IN BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i5-i5
Author(s):  
Sheila Singh ◽  
Blessing Bassey-Archibong ◽  
Nikoo Aghaei ◽  
Agata Kieliszek ◽  
Chitra Venugopal ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Systemic Disease ◽  
Human Leukocyte ◽  
Genetic Profile ◽  
Whole Brain Radiation ◽  
Metastatic Cells ◽  
Metastatic Process ◽  
Xenograft Models ◽  
Sphere Formation ◽  
The Brain

Abstract Brain metastases (BM) are the most common brain tumor in adults, with an incidence ten times greater than that of primary brain tumors. The most common sources of BM in adult cancer patients include cancers of the lung, breast and melanoma, which together account for almost 80% of all BM. Current clinical modalities for BM include surgery, whole brain radiation therapy and stereotactic radiosurgery but these therapies still offer limited efficacy and reduced survival of only months in treated patients, emphasizing the need for novel BM research approaches and better therapeutic strategies. Our laboratory recently discovered that stem-like cells exist in patient-derived BM from lung, breast and melanoma cancers, which we termed “brain metastasis-initiating cells” or BMICs. Through clinically relevant human-mouse xenograft models established with these patient-derived BMICs, we captured lung, breast and melanoma BMICs at pre-metastasis – a key stage where circulating metastatic cells extravasate and initially seed the brain, prior to organization into micro-metastatic foci. Transcriptome analysis of pre-metastatic BMICs revealed a unique genetic profile and several genes commonly up-regulated among lung, breast and melanoma BM, including the non-classical human leukocyte class I antigen-G (HLA-G). Loss of HLA-G in lung, breast and melanoma BMICs using two HLA-G specific shRNAs attenuated sphere formation, migratory and tumor initiating abilities of lung, breast and melanoma BMICs compared to control BMICs. HLA-G knockdown also resulted in reduced phospho(p)-STAT3 expression in patient-derived BMICs suggesting a potential cooperative role between HLA-G and pSTAT3 in BM. Since HLA-G is highly expressed at the cell surface in control tumors, ongoing experiments are focused on developing HLA-G specific chimeric antigen receptor -T cells (CAR-Ts) and determining their efficacy in targeting lung-, breast- and melanoma-BM as blocking the brain metastatic process will markedly extend patient survival and ultimately transform a fatal systemic disease into a more treatable one.

Metastatic Liposarcoma of the Brain with Response to Chemotherapy: Case Report

Neurosurgery ◽  
1988 ◽  
Vol 23 (6) ◽  
pp. 777-780 ◽  
Author(s):  
Harold Haft ◽  
George C. Wang
Keyword(s):  
Case Report ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Abdominal Mass ◽  
Response To Chemotherapy ◽  
History Of ◽  
In The Beginning ◽  
The Brain

Abstract Metastatic liposarcomas to the brain are rare. The authors describe a patient with a 20-year history of liposarcoma originating in the thigh and metastatic to the brain 18 years later. The brain metastasis was removed by surgery. Nine months later, the patient developed metastases to the retroperitoneum and liver. At that same time, she had recurrent brain metastasis. She was then treated with chemotherapy. The abdominal mass shrank considerably in the beginning, and the recurrent brain metastases totally disappeared. The patient eventually succumbed to widespread liposarcoma. Autopsy revealed extensive liposarcoma involving the retroperitoneum, liver, and lung, but no trace of tumor was found in the brain.

The impact of radiosurgery fractionation and tumor radiobiology on the local control of brain metastases

2013 ◽  
Vol 119 (5) ◽  
pp. 1131-1138 ◽  
Author(s):  
Eric K. Oermann ◽  
Marie-Adele S. Kress ◽  
Jonathan V. Todd ◽  
Brian T. Collins ◽  
Riane Hoffman ◽  
...  
Keyword(s):  
Local Control ◽  
Local Tumor Control ◽  
Dose Fractionation ◽  
Tumor Control ◽  
Metastatic Tumors ◽  
Single Fraction ◽  
Frameless Radiosurgery ◽  
Whole Brain Radiation ◽  
The Impact ◽  
The Brain

Object Experience with whole-brain radiation therapy for metastatic tumors in the brain has identified a subset of tumors that exhibit decreased local control with fractionated regimens and are thus termed radioresistant. With the advent of frameless radiosurgery, fractionated radiosurgery (2–5 fractions) is being used increasingly for metastatic tumors deemed too large or too close to crucial structures to be treated in a single session. The authors retrospectively reviewed metastatic brain tumors treated at 2 centers to analyze the dependency of local control rates on tumor radiobiology and dose fractionation. Methods The medical records of 214 patients from 2 institutions with radiation-naive metastatic tumors in the brain treated with radiosurgery given either as a single dose or in 2–5 fractions were analyzed retrospectively. The authors compared the local control rates of the radiosensitive with the radioresistant tumors after either single-fraction or fractionated radiosurgery. Results There was no difference in local tumor control rates in patients receiving single-fraction radiosurgery between radioresistant and radiosensitive tumors (p = 0.69). However, after fractionated radiosurgery, treatment for radioresistant tumors failed at a higher rate than for radiosensitive tumors with an OR of 5.37 (95% CI 3.83–6.91, p = 0.032). Conclusions Single-fraction radiosurgery is equally effective in the treatment of radioresistant and radiosensitive metastatic tumors in the brain. However, fractionated stereotactic radiosurgery is less effective in radioresistant tumor subtypes. The authors recommend that radioresistant tumors be treated in a single fraction when possible and techniques for facilitating single-fraction treatment or dose escalation be considered for larger radioresistant lesions.

scholarly journals Neuritin inhibits astrogliosis to ameliorate diabetic cognitive dysfunction

2021 ◽  
Vol 66 (4) ◽  
pp. 259-272
Author(s):  
Zuo Zhang ◽  
Hongli Zhou ◽  
Jiyin Zhou
Keyword(s):  
Signaling Pathway ◽  
Cognitive Dysfunction ◽  
Diabetic Rats ◽  
Protective Mechanism ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
The Impact ◽  
The Brain ◽  
Central Neuropathy

Earlier, it was shown that reversing the downregulation of neuritin expression in the brain improves central neuropathy in diabetic rats. We investigated the protective mechanism of neuritin in diabetic cognitive dysfunction via astrocytes. Further, the impact of the overexpression of neuritin in the cortex and the hippocampus on diabetic cognitive dysfunction and astrogliosis in type 2 diabetic (db/db) mice was assessed. Antagonists were used to inhibit the JAK2/STAT3 signaling pathway in U-118MG, an astrocyte cell line. Immunofluorescence, Western blotting, and real-time PCR were performed. Neuritin overexpression in the hippocampus of db/db mice significantly ameliorated cognitive dysfunction, hippocampal neuronal impairment, and synaptic plasticity deterioration, and inhibited astrogliosis and the JAK2/STAT3 signaling pathway in the hippocampus. Neuritin suppressed the JAK2/STAT3 signaling pathway to inhibit lipopolysaccharide-induced gliosis in U-118MG cells. It was observed that neuritin regulates the JAK2/STAT3 signaling pathway in astrocytes to inhibit astrogliosis and improve diabetic cognitive dysfunction.

scholarly journals OTHR-02. Engineered “of the shelf” allogeneic cellular therapies for metastatic brain tumors

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii14-iii14
Author(s):  
Khalid Shah ◽  
Yohei Kitamura ◽  
Wanlu Du ◽  
Nobu Kanaya
Keyword(s):  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Mouse Models ◽  
Therapeutic Option ◽  
Cell Surface Receptor ◽  
Systemic Delivery ◽  
Melanoma Tumor ◽  
Cellular Therapies ◽  
Metastatic Lesions ◽  
The Brain

Abstract Brain metastatic patients have multiple metastatic lesions or diagnostically challenging asymptomatic lesions, making surgery an inadequate therapeutic option. Given the challenges related to systemic delivery of a majority of therapeutic agents across the BBB, engineered cell based therapies offer an excellent platform to target metastatic tumors in the brain. We have established the use tumor cell surface receptor targeted allogeneic “off the shelf” gene engineered cellular therapies and developed two different approaches to treat brain metastases. In one approach, we have armed allogenic stem cells (SC) with oncolytic herpes virus (oHSV) variants and tested them in different mouse models of brain metastatic (BM) tumor derived from brain seeking metastatic melanoma tumor cells from patients. We show that intracarotid artery administration of SC-oHSV effectively tracks metastatic tumor lesions and significantly prolongs the survival of brain tumor bearing mice. We also show that a combination of SC-oHSV and PD-L1 blockade increases IFNγ-producing CD8+ tumor-infiltrating T lymphocytes and results in a profound extension of the median survival in syngeneic brain metastatic melanoma mouse models. In another approach, we have explored the versatility of cell mediated bi-functional EGFR and DR4/5-targeted treatment in basal like breast cancer (BLBC) mouse models featuring different patterns of brain metastasis. Most BLBC lines demonstrated a high sensitivity to EGFR and DR4/5 bi-targeting therapeutic protein, EVDRL [anti-EGFR VHH (EV) fused to DR ligand (DRL)]. Functional analyses using inhibitors and CRISPR-Cas9 knockouts revealed that the EV domain facilitated in augmenting DR4/5-DRL binding and enhancing DRL-induced apoptosis. EVDRL releasing allogeneic SCs alleviated tumor-burden and significantly increased survival in mouse models of residual-tumor after macrometastasis resection, perivascular niche micrometastasis, and leptomeningeal metastasis. These findings provide a clinically applicable therapeutic platform to target disseminated metastatic lesions in the brain and define a new paradigm for treatment of brain metastases.

scholarly journals Clinical dose profile of Gamma Knife stereotactic radiosurgery for extensive brain metastases

2020 ◽  
pp. 1-5
Author(s):  
Gregory Neil Bowden ◽  
Jong Oh Kim ◽  
Andrew Faramand ◽  
Kevin Fallon ◽  
John Flickinger ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Gamma Knife ◽  
Tumor Volume ◽  
Median Number ◽  
Whole Brain Radiation ◽  
Clinical Scenarios ◽  
The Mean ◽  
Gamma Knife Stereotactic Radiosurgery ◽  
The Brain

OBJECTIVEThe use of Gamma Knife stereotactic radiosurgery (GKSRS) for the treatment of extensive intracranial metastases has been expanding due to its superior dosimetry and efficacy. However, there remains a dearth of data regarding the dose parameters in actual clinical scenarios. The authors endeavored to calculate the radiation dose to the brain when treating ≥ 15 brain metastases with GKSRS.METHODSThis retrospective analysis reviewed dosage characteristics for patients requiring single-session GKSRS for the treatment of ≥ 15 brain metastases. Forty-two patients met the inclusion criteria between 2008 and 2017. The median number of tumors at the initial GKSRS procedure was 20 (range 15–39 tumors), accounting for 865 tumors in this study. The median aggregate tumor volume was 3.1 cm3 (range 0.13–13.26 cm3), and the median marginal dose was 16 Gy (range 14–19 Gy).RESULTSThe median of the mean brain dose was 2.58 Gy (range 0.95–3.67 Gy), and 79% of patients had a dose < 3 Gy. The 12-Gy dose volume was a median of 12.45 cm3, which was equivalent to 0.9% of the brain volume. The median percentages of brain receiving 5 Gy and 3 Gy were 6.7% and 20.4%, respectively. There was no correlation between the number of metastases and the mean dose to the brain (p = 0.8). A greater tumor volume was significantly associated with an increased mean brain dose (p < 0.001). The median of the mean dose to the bilateral hippocampi was 2.3 Gy. Sixteen patients had supplementary GKSRS, resulting in an additional mean dose of 1.4 Gy (range 0.2–3.8 Gy) to the brain.CONCLUSIONSGKSRS is a viable means of managing extensive brain metastases. This procedure provides a relatively low dose of radiation to the brain, especially when compared with traditional whole-brain radiation protocols.

scholarly journals Trends in peri-operative performance status following resection of high grade glioma and brain metastases: The impact on survival

2018 ◽  
Vol 164 ◽  
pp. 67-71 ◽  
Author(s):  
Chirag K. Patel ◽  
Ravi Vemaraju ◽  
James Glasbey ◽  
Joanne Shires ◽  
Tessa Northmore ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Performance Status ◽  
High Grade Glioma ◽  
High Grade ◽  
Impact On Survival ◽  
Operative Performance ◽  
The Impact

Results of Whole Brain Radiation Therapy in Patients with Brain Metastases from Colorectal Carcinoma

2005 ◽  
Vol 91 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Maurizio Amichetti ◽  
Giancarlo Lay ◽  
Marina Dessì ◽  
Silvia Orrù ◽  
Roberta Farigu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Radiation Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Survival Time ◽  
Whole Brain Radiation Therapy ◽  
Whole Brain ◽  
Whole Brain Radiation ◽  
Brain Radiation ◽  
The Brain

Aims and background Carcinoma of the colon-rectum is an infrequent cause of brain metastases, constituting 1-5% of all metastatic lesions to the brain. We reviewed our experience in the treatment of brain metastases from colorectal cancer to define the efficacy of whole brain radiation therapy as a palliative measure in this setting of patients. Methods Twenty-three consecutive cases of brain metastasis from colorectal cancer treated between 1999 and 2004 were identified in the files of the Division of Radiotherapy of the A Businco Regional Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor characteristics and categorized according to the RTOG RPA classes. Results Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed extracranial metastases. Fourteen patients were classified as RTOG RPA class II and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic improvement was observed. The median follow-up and survival time for all the patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of death was the brain metastasis. Conclusions Despite the disappointing survival time, external radiation therapy to the whole brain proved to be an efficacious palliative treatment for patients with multiple or inoperable brain metastasis from colorectal cancer.

Sign in / Sign up

Export Citation Format

Share Document