scholarly journals 16. GAMMA KNIFE CLINICAL DOSE PROFILE FOR EXTENSIVE BRAIN METASTASES

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii2-ii2
Author(s):  
Greg Bowden ◽  
Jong Kim ◽  
Andrew Faramand ◽  
Kevin Fallon ◽  
John Flickinger ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Gamma Knife ◽  
Tumor Volume ◽  
Median Number ◽  
Median Percentage ◽  
Whole Brain Radiation ◽  
Clinical Scenarios ◽  
The Mean ◽  
Gamma Knife Stereotactic Radiosurgery ◽  
The Brain

Abstract BACKGROUND The 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. We endeavored to calculate the radiation dose to the brain when treating >15 brain metastases with GKSRS. METHODS This retrospective analysis reviewed dosage characteristics for patients requiring single session GKSRS for the treatment of 315 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 (15–39) which accounted for 865 tumors in this study. The median aggregate tumor volume was 3.1cm3(0.13–13.26) and the median marginal dose was 16Gy (14-19Gy). RESULTS The median of the mean brain dose was 2.58Gy (range 0.95–3.67Gy) and 79% of patients had a dose <3Gy. The 12Gy dose volume was a median of 12.45cm3, which was equivalent to 0.9% of the brain volume. The median percentage of brain receiving 5Gy and 3Gy was 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 higher 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 2.3Gy. Sixteen patients had supplementary GKSRS, resulting in an additional mean dose of 1.4Gy (0.2–3.8Gy) to the brain. CONCLUSION GKSRS is a viable means of managing extensive brain metastases. This procedure provides a relatively low dose of radiation to the brain, especially when compared to traditional whole brain radiation protocols.

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 Mean Brain Dose Remains Uninfluenced by Lesion Number for Gamma Knife Stereotactic Radiosurgery for Ten+ Metastases

2021 ◽  
Author(s):  
Sean Sachdev ◽  
Timothy L. Sita ◽  
Mahesh Gopalakrishnan ◽  
Michael K. Rooney ◽  
Alexander Ho ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Gamma Knife ◽  
Chart Review ◽  
Tumor Volume ◽  
Median Number ◽  
Single Institution ◽  
Whole Brain ◽  
Lesion Number ◽  
The Mean ◽  
Gamma Knife Stereotactic Radiosurgery

Abstract Purpose:Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with ten or more brain metastases (BM). However, the clinical and dosimetric consequences of this practice are not well established.Methods: We performed a single institution, retrospective analysis of 30 patients who received GK SRS for ten or more BM in one session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review. Results: Our cohort had a median number of 13 treated lesions (range 10 to 26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8 ± 0.91 Gy (range 0.70 to 3.8 Gy). Mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r=0.23, p=0.21), but was closely associated with tumor volume (Pearson r=0.95, p<0.0001). There were no significant correlations between overall survival and number of lesions or aggregate tumor volume. Fourteen patients (47%) underwent additional SRS sessions and six patients (20%) underwent WBRT a median of 6.6 months (range 3.0-50 months) after SRS. Two patients (6.6%) developed grade 2 radionecrosis following SRS beyond earlier WBRT.Conclusion: The mean dose to the whole brain in patients treated with GK SRS for 10 or more BM remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent WBRT.

scholarly journals RADI-27. ROLE OF STEREOTACTIC RADIOSURGERY IN THE CARE OF PATIENTS WITH >/= 25 CUMULATIVE BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i27-i27
Author(s):  
Carolina Benjamin ◽  
Monica Mureb ◽  
Bernadine Donahue ◽  
Erik Sulman ◽  
Joshua Silverman ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Tumor Volume ◽  
Median Number ◽  
Median Dose ◽  
Total Tumor Volume ◽  
Whole Brain Radiation ◽  
Brain Radiation

Abstract INTRODUCTION: Stereotactic radiosurgery (SRS) is an accepted treatment for multiple brain metastases. However, the upper limit of the number of brain metastases over the course of care suitable for this approach is controversial. METHODS: From a review of our prospective registry, 48 patients treated with SRS for ≥ 25 brain metastases in either single or multiple sessions between 2013 and 2019 were identified. Patient, tumor, and treatments characteristics were evaluated. Clinical outcomes and overall survival (OS) were analyzed. RESULTS: Thirty-one females (64.6%) and 17 males (35.4%) with a median age of 56 years (25–91) were included. Primary diagnoses included lung (n=23, 47.9%), breast (n=13, 27.1%), melanoma (n=8, 16.7%), and other (n=4, 8.33%). Initial median GPA index was 2 (0.5–3). Nine patients (18.8%) had received whole brain radiation therapy (WBRT) prior to first SRS treatment, with a median dose of 35Gy (30–40.5Gy). Ten patients (20.8%) received WBRT after initial SRS, with a median dose of 30Gy (20-30Gy). Thus, only 19 patients (40%) ever received WBRT. Median number of radiosurgeries per patient was 3 (1–12). Median number of cumulative tumors irradiated was 31 (25–110). Median number of tumors irradiated at first SRS was 10 (1–35). Median marginal dose for the largest tumor per session was 16Gy (10-21Gy). Median SRS total tumor volume was 6.8cc (0.8–23.4). Median follow-up since initial SRS was 16 months (1–71). At present, 21 (43.7%) are alive. Median OS from the diagnosis of brain metastases was 31 months (2–97), and OS from the time of first SRS, 22 months (1–70). Median KPS at first SRS and last follow-up was the same (90). Sixty-three percent did not require a corticosteroid course. CONCLUSION: In selected patients with a large number of cumulative brain metastases (≥ 25), SRS is effective and safe. Therefore, WBRT may not be required in this population.

Gamma Knife Stereotactic Radiosurgery for Brain Metastases Using Only 3 Pins

Neurosurgery ◽  
2016 ◽  
Vol 78 (6) ◽  
pp. 877-882 ◽  
Author(s):  
Jennifer C. Ho ◽  
Dershan Luo ◽  
Nandita Guha-Thakurta ◽  
Sherise D. Ferguson ◽  
Amol J. Ghia ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Gamma Knife ◽  
Local Control ◽  
Internal Control ◽  
Occipital Lobe ◽  
Median Number ◽  
Posterior Lesion ◽  
Control Lesion ◽  
Gamma Knife Stereotactic Radiosurgery

Abstract BACKGROUND: Removal of a pin during Gamma Knife stereotactic radiosurgery (GK-SRS) may be necessary to prevent collision and allow treatment. OBJECTIVE: To investigate outcomes after GK-SRS for treatment of brain metastases using a head frame immobilized to the skull with only 3 pins. METHODS: Between 2009 and 2014, we retrospectively reviewed the records of 1971 patients and identified 20 patients with multiple brain metastases treated with GK-SRS in which 1 anterior pin was removed immediately before treatment of a single posterior lesion. GK-SRS was also delivered to 116 other lesions in these 20 patients using the standard 4 pins during the same session, serving as an internal control for comparison. Endpoints included local control, dosimetric parameters, toxicity, and overall survival. RESULTS: The median number of lesions treated per session was 6 (range, 2-14). The lesions treated using 3 pins were located in the occipital lobe (n = 14) or the cerebellum (n = 6). Median follow-up was 12.3 months. There was 1 local failure involving a control lesion. Lesions treated using 3 pins had a lower prescription isodose line. GK-SRS of a lesion using 3 pins did not cause any clinical toxicities or increase in radiographic edema or hemorrhage. CONCLUSION: Treating posteriorly located brain metastases with GK-SRS using only 3 pins provided excellent local control and no difference in treatment toxicity, which may make it a safe and reasonable option for lesions that may otherwise be difficult to treat.

Stereotactic drainage and Gamma Knife radiosurgery of cystic brain metastasis

2008 ◽  
Vol 109 (2) ◽  
pp. 259-267 ◽  
Author(s):  
Alberto Franzin ◽  
Alberto Vimercati ◽  
Piero Picozzi ◽  
Carlo Serra ◽  
Silvia Snider ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastasis ◽  
Confidence Interval ◽  
Gamma Knife ◽  
Tumor Volume ◽  
Whole Brain Radiation Therapy ◽  
Whole Brain ◽  
Whole Brain Radiation ◽  
The Mean ◽  
Brain Radiation

Object Treatment options for patients with brain metastasis include tumor resection, whole-brain radiation therapy, and radiosurgery. A single treatment is not useful in cases of multiple tumors, of which at least 1 is a cystic tumor. The purpose of this study was to assess the role of stereotactic drainage and Gamma Knife surgery (GKS) in the treatment of cystic brain metastasis. Methods Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 ± 11 years, range 38–75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score ≥ 70; and 5) histological diagnosis of a malignant tumor. Results Non–small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8–68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2–32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12–25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3–64.1%) and 34.2% (95% confidence interval 23.1–45.3%). Local tumor control was achieved in 91.3% of the patients. Conclusions The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis.

Gamma Knife surgery for the treatment of 5 to 15 metastases to the brain

2013 ◽  
Vol 118 (6) ◽  
pp. 1250-1257 ◽  
Author(s):  
David J. Salvetti ◽  
Tara G. Nagaraja ◽  
Ian T. McNeill ◽  
Zhiyuan Xu ◽  
Jason Sheehan
Keyword(s):  
Brain Metastases ◽  
Gamma Knife ◽  
Recursive Partitioning ◽  
Median Number ◽  
Local Tumor Control ◽  
Gamma Knife Surgery ◽  
Tumor Control ◽  
Prognostic Assessment ◽  
Treatment Volume ◽  
The Brain

Object It has been generally accepted that Gamma Knife surgery (GKS) is an effective primary or adjunct treatment for patients with 1–4 metastases to the brain. The number of studies detailing the use of GKS for 5 or more brain metastases, however, remains minimal. The aim of the current retrospective study was to elucidate the utility of GKS in patients with 5–15 brain metastases. Methods Patients were chosen for GKS based on prior MRI of these metastatic lesions and a known primary cancer diagnosis. Magnetic resonance imaging was used post-GKS to assess tumor control; patients were also followed up clinically. Overall survival (OS) from the date of GKS was used as the primary end point. Statistical analysis was performed to identify prognostic factors related to OS. Results Between 2003 and 2012, 96 patients were treated for a total of 704 metastatic brain lesions. The histology of these lesions varied among non–small cell lung cancer (NSCLC), breast cancer, melanoma, renal cancer, and other more rare carcinomas. At the initial treatment, 18 of the patients (18.8%) were categorized in Recursive Partitioning Analysis (RPA) Class 1 and 77 (80.2%) in RPA Class 2; none were in RPA Class 3. The median number of treated lesions was 7 (mean 7.13), and the median planned treatment volume was 6.12 cm3 (range 0.42–57.83 cm3) per patient. The median clinical follow-up was 4.1 months (range 0.1–40.70 months). Actuarial tumor control was calculated to be 92.4% at 6 months, 84.8% at 12 months, and 74.9% at 24 months post-GKS. The median OS was found to be 4.73 months (range 0.4–41.8 months). Multivariate analysis demonstrated that RPA class was a significant predictor of death (HR = 2.263, p = 0.038). Number of lesions, tumor histology, Graded Prognostic Assessment score, prior whole-brain radiation therapy, prior resection, prior chemotherapy, patient age, patient sex, controlled primary tumor, extracranial metastases, and planned treatment volume were not significant predictors of OS. Conclusions In patients with 5–15 brain metastases at presentation, the number of lesions did not predict survival after GKS; however, the RPA class was predictive of OS in this group of patients. Gamma Knife surgery for such patients offers an excellent rate of local tumor control.

Dosimetric comparison of fractionated radiosurgery plans using frameless Gamma Knife ICON and CyberKnife systems with linear accelerator–based radiosurgery plans for multiple large brain metastases

2020 ◽  
Vol 132 (5) ◽  
pp. 1473-1479 ◽  
Author(s):  
Eun Young Han ◽  
He Wang ◽  
Dershan Luo ◽  
Jing Li ◽  
Xin Wang
Keyword(s):  
Brain Metastases ◽  
Gamma Knife ◽  
Linear Accelerator ◽  
Treatment Time ◽  
Target Volume ◽  
Planning System ◽  
Treatment Planning System ◽  
Normal Brain ◽  
Large Brain ◽  
The Mean

OBJECTIVEFor patients with multiple large brain metastases with at least 1 target volume larger than 10 cm3, multifractionated stereotactic radiosurgery (MF-SRS) has commonly been delivered with a linear accelerator (LINAC). Recent advances of Gamma Knife (GK) units with kilovolt cone-beam CT and CyberKnife (CK) units with multileaf collimators also make them attractive choices. The purpose of this study was to compare the dosimetry of MF-SRS plans deliverable on GK, CK, and LINAC and to discuss related clinical issues.METHODSTen patients with 2 or more large brain metastases who had been treated with MF-SRS on LINAC were identified. The median planning target volume was 18.31 cm3 (mean 21.31 cm3, range 3.42–49.97 cm3), and the median prescribed dose was 27.0 Gy (mean 26.7 Gy, range 21–30 Gy), administered in 3 to 5 fractions. Clinical LINAC treatment plans were generated using inverse planning with intensity modulation on a Pinnacle treatment planning system (version 9.10) for the Varian TrueBeam STx system. GK and CK planning were retrospectively performed using Leksell GammaPlan version 10.1 and Accuray Precision version 1.1.0.0 for the CK M6 system. Tumor coverage, Paddick conformity index (CI), gradient index (GI), and normal brain tissue receiving 4, 12, and 20 Gy were used to compare plan quality. Net beam-on time and approximate planning time were also collected for all cases.RESULTSPlans from all 3 modalities satisfied clinical requirements in target coverage and normal tissue sparing. The mean CI was comparable (0.79, 0.78, and 0.76) for the GK, CK, and LINAC plans. The mean GI was 3.1 for both the GK and the CK plans, whereas the mean GI of the LINAC plans was 4.1. The lower GI of the GK and CK plans would have resulted in significantly lower normal brain volumes receiving a medium or high dose. On average, GK and CK plans spared the normal brain volume receiving at least 12 Gy and 20 Gy by approximately 20% in comparison with the LINAC plans. However, the mean beam-on time of GK (∼ 64 minutes assuming a dose rate of 2.5 Gy/minute) plans was significantly longer than that of CK (∼ 31 minutes) or LINAC (∼ 4 minutes) plans.CONCLUSIONSAll 3 modalities are capable of treating multiple large brain lesions with MF-SRS. GK has the most flexible workflow and excellent dosimetry, but could be limited by the treatment time. CK has dosimetry comparable to that of GK with a consistent treatment time of approximately 30 minutes. LINAC has a much shorter treatment time, but residual rotational error could be a concern.

Gamma knife radiosurgery for craniopharyngiomas

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 47-56 ◽  
Author(s):  
Wen-Yuh Chung ◽  
David Hung-Chi Pan ◽  
Cheng-Ying Shiau ◽  
Wan-Yuo Guo ◽  
Ling-Wei Wang
Keyword(s):  
Clinical Outcome ◽  
Gamma Knife ◽  
Tumor Volume ◽  
Gamma Knife Radiosurgery ◽  
Tumor Control ◽  
Content Type ◽  
Stereotactic Aspiration ◽  
Cystic Component ◽  
The Mean ◽  
Fine Print

Object. The goal of this study was to elucidate the role of gamma knife radiosurgery (GKS) and adjuvant stereotactic procedures by assessing the outcome of 31 consecutive patients harboring craniopharyngiomas treated between March 1993 and December 1999. Methods. There were 31 consecutive patients with craniopharyngiomas: 18 were men and 13 were women. The mean age was 32 years (range 3–69 years). The mean tumor volume was 9 cm3 (range 0.3–28 cm3). The prescription dose to the tumor margin varied from 9.5 to 16 Gy. The visual pathways received 8 Gy or less. Three patients underwent stereotactic aspiration to decompress the cystic component before GKS. The tumor response was classified by percentage reduction of tumor volume as calculated based on magnetic resonance imaging studies. Clinical outcome was evaluated according to improvement and dependence on replacement therapy. An initial postoperative volume increase with enlargement of a cystic component was found in three patients. They were treated by adjuvant stereotactic aspiration and/or Ommaya reservoir implantation. Tumor control was achieved in 87% of patients and 84% had fair to excellent clinical outcome in an average follow-up period of 36 months. Treatment failure due to uncontrolled tumor progression was seen in four patients at 26, 33, 49, and 55 months, respectively, after GKS. Only one patient was found to have a mildly restricted visual field; no additional endocrinological impairment or neurological deterioration could be attributed to the treatment. There was no treatment-related mortality. Conclusions. Multimodality management of patients with craniopharyngiomas seemed to provide a better quality of patient survival and greater long-term tumor control. It is suggested that GKS accompanied by adjuvant stereotactic procedures should be used as an alternative in treating recurrent or residual craniopharyngiomas if further microsurgical excision cannot promise a cure.

Prolonged survival in a subgroup of patients with brain metastases treated by gamma knife surgery

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 262-265
Author(s):  
C. P. Yu ◽  
Joel Y. C. Cheung ◽  
Josie F. K. Chan ◽  
Samuel C. L. Leung ◽  
Robert T. K. Ho
Keyword(s):  
Brain Metastases ◽  
Gamma Knife ◽  
Patient Survival ◽  
Gamma Knife Surgery ◽  
Prolonged Survival ◽  
Organ Involvement ◽  
Lesion Volume ◽  
Content Type ◽  
The Mean ◽  
Fine Print

Object. The authors analyzed the factors involved in determining prolonged survival (≥ 24 months) in patients with brain metastases treated by gamma knife surgery (GKS). Methods. Between 1995 and 2003, a total of 116 patients underwent 167 GKS procedures for brain metastases. There was no special case selection. Smaller and larger lesions were treated with different protocols. The mean patient age was 56.9 years, the mean number of initial lesions was 3.15, and the mean lesion volume was 10.45 cm.3 The mean follow-up time was 9.2 months. The median patient survival was 8.68 months. One-, 2-, 3-, 4-, and 5-year actuarial survival rates were 31.8%, 19.8%, 14.6%, 7.7%, and 6.9%, respectively. Patient age, number of lesions at presentation, and lesion volume had no influence on patient survival. Twenty-three (19.8%) patients survived for 24 months or more. Certain factors were associated with increased survival time. These were stable primary disease (21 of 23 patients), a long latency between diagnosis of the primary tumor and the occurrence of brain metastases (mean 28.4 months, median 16 months), absence of third-organ involvement, and repeated local procedures. Ten patients underwent repeated GKS (mean 3.4 per patient). Seven patients required open surgery for local treatment failures (recurrence or radiation necrosis). Two patients had both. Fifteen patients underwent repeated procedures. Conclusions. Aggressive local therapy with GKS, repeated GKS, and GKS plus surgery can achieve increased survival in a subgroup of patients with stable primary disease, no third-organ involvement, and long primary-brain secondary intervals.

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.

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