Resection Of Brain Metastases Research Articles

Risk for leptomeningeal seeding after resection for brain metastases: implication of tumor location with mode of resection

Surgical spillage has been one of the causative factors for the development of leptomeningeal seeding (LMS) after resection of brain metastases. In this paper, the authors' goal was to define the factors related to the development of LMS and to evaluate the difference according to tumor location. The authors retrospectively analyzed 242 patients who had undergone resection for brain metastases. The factors investigated included tumor location with proximity to the CSF pathway (that is, contacting, involved with, or separated from the CSF pathway), the method of resection, and the use of the Cavitron Ultrasonic Surgical Aspirator (CUSA). A total of 39 patients (16%) developed LMS at a median of 6.0 months (range 1-42 months) after resection. The risk of developing LMS was significantly higher in patients whose tumors were resected piecemeal than in those whose tumors were removed en bloc, with a hazard ratio (HR) of 4.08 (p < 0.01). The incidence of LMS was significantly higher in patients in whom the CUSA was used, and the HR was 2.64 (p < 0.01). The proximity of tumor to the CSF pathway in the involved group conferred an increased risk of LMS compared with the separated group (HR 11.36, p < 0.01). The risk of piecemeal resection for LMS was significant only in involved lesions (p < 0.01), and the use of the CUSA in both contact and involved lesions increased the incidence of LMS (p < 0.01 and p < 0.03, respectively). The authors suggest that piecemeal resection using the CUSA should be limited because of the risk of postsurgical LMS, especially when the tumor is in contact with the CSF pathway.

Resection plus whole-brain irradiation versus resection plus whole-brain irradiation plus boost for the treatment of single brain metastasis

The optimal treatment for patients with a single brain metastasis is controversial. This study investigated the value of a radiation boost given in addition to neurosurgerical resection and whole-brain irradiation (WBI). In this retrospective study, outcome data of 105patients with a single brain metastasis receiving metastatic surgery plus WBI (S + WBI) were compared to 90patients receiving the same treatment plus a boost to the metastatic site (S + WBI + B). The outcomes that were compared included local control of the resected metastasis (LC) and overall survival (OS). In addition to the treatment regimen, eight potential prognostic factors were evaluated including age, gender, performance status, extent of metastatic resection, primary tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from first diagnosis of cancer to metastatic surgery. The LC rates at 1year, 2years, and 3years were 38%, 20%, and 9%, respectively, after S + WBI, and 67%, 51%, and 33%, respectively, after S + WBI + B (p = 0.002). The OS rates at 1year, 2years, and 3years were 52%, 25%, and 19%, respectively, after S + WBI, and 60%, 40%, and 26%, respectively, after S + WBI + B (p = 0.11). On multivariate analyses, improved LC was significantly associated with OP + WBI + B (p = 0.006) and total resection of the metastasis (p = 0.014). Improved OS was significantly associated with age ≤ 60years (p = 0.028), Karnofsky Performance Score > 70 (p = 0.015), breast cancer (p = 0.041), RPA class 1 (p = 0.012), and almost with the absence of extracerebral metastases (p = 0.05). A boost in addition to WBI significantly improved LC but not OS following resection of a single brain metastasis.

Long-term survival of a case of rectal cancer discovered after resection of a single brain metastasis

Long-term survival of a case of rectal cancer discovered after resection of a single brain metastasis

Third Report of CK-brain Mets-01: A Phase II Consensus Multi-institutional Trial Of Frameless Stereotactic Radiosurgery To The Operative Cavity In Patients With Resected Brain Metastases

Third Report of CK-brain Mets-01: A Phase II Consensus Multi-institutional Trial Of Frameless Stereotactic Radiosurgery To The Operative Cavity In Patients With Resected Brain Metastases

Two cases of plasmacytoid variant of urothelial carcinoma of urinary bladder: systemic chemotherapy might be of benefit

We report two cases of the plasmacytoid variant of urothelial carcinoma of urinary bladder in which systemic chemotherapy was effective. In the first case, a 76-year-old man presented with dysphasia. Magnetic resonance imaging (MRI) and computed tomography revealed a brain tumor and a bladder tumor. Resection of the brain tumor and transurethral resection of the bladder tumor were performed. The pathological diagnosis was plasmacytoid variant of urothelial carcinoma of urinary bladder with brain metastasis (pT1N0M1). Three cycles of adjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) chemotherapy were performed. He has no evidence of recurrence 96 months after resection of brain metastasis. In the second case, a 76-year-old man presented with hematuria. MRI revealed a bladder tumor with abdominal wall invasion, and a transurethral biopsy was performed. The pathological diagnosis was plasmacytoid variant of urothelial carcinoma of urinary bladder (cT4bN0M0). After three cycles of neoadjuvant GC (gemcitabine and cisplatin) chemotherapy, MRI demonstrated a complete response. Radical cystectomy was performed, and the pathological diagnosis was pT0pN0. Although there was no evidence of recurrence 9 months after radical cystectomy, he died from other causes. Our two cases suggest that systemic chemotherapy might be effective for the plasmacytoid variant of urothelial carcinoma.

Factors influencing survival in patients with breast cancer and single or solitary brain metastasis

Aim To perform a comprehensive analysis of patients with breast cancer and solitary or single brain metastasis and to analyze factors influencing survival from brain metastasis. Methods One hundred consecutive patients with single or solitary brain metastasis were treated in one institution in the years 2003–2009. Brain lesions were diagnosed by magnetic resonance imaging (MRI). A total of 57% of patients underwent resection of brain metastasis, 95% of patients received whole-brain radiation therapy (WBRT) and 67% were treated systemically after WBRT. Results Median survival from the detection of brain metastasis was 13 months and 28% of patients survived for 2 years. In 29 patients with solitary brain metastasis, median survival was 20 months (2–80 months) and in 71 patients with single brain metastasis it was 11 months (1–79 months) p = 0.01. Median survival from brain metastasis in patients with Recursive Partitioning Analysis Radiation Therapy Oncology Group (RPA RTOG) prognostic class I, II and III was 22 months (4–80 months), 13 months (2–79 months) and 6 months (0.4–28 months), respectively, p < 0.0001. Median survival from brain metastasis in triple-negative, HER2, luminal B and luminal A subtypes was 11 months, 13 months, 16 months and 15 months, respectively ( p = 0.60). Multivariate analysis revealed that RPA RTOG prognostic class I, neurosurgery and systemic therapy after WBRT were factors that correlated with survival. Conclusions In patients with one metastatic lesion in the brain, affiliation to RPA RTOG prognostic class I and intensive local and systemic treatment had a strong correlation with survival. There was no significant correlation between biological subtype of cancer and survival.

The neuronal cell adhesion molecule L1CAM as a therapeutic targe in breast cancer.

e21138 Background: Brain metastases of breast cancer occurs in approximately one-third of metastatic triple negative and HER2+ breast cancer patients and contributes to patient morbidity and mortality. The identification and validation of molecular pathways underlying brain metastases of breast cancer may lead to the development of effective therapeutics. Methods: We have identified 23 sets of matched primary breast tumors and resected brain metastases, and determined their gene expression profiles using the DASL platform on formalin-fixed, paraffin embedded tumor sections. Multiple independent shRNAs to L1CAM or a control shRNA were transfected into a brain metastatic derivative (231-BR) of human MDA-MB-231 breast carcinoma cells. Brain metastases were quantified one month after intracardiac injection. Results: Patient characteristics: mean age at diagnosis of brain metastases: 48 years (range 29-68 years); 10 HER2+(3+)/ER- (43.5%), 1 HER2(2+)/ER- (4.4%), 2 HER2(2+)/ER+ (8.7%), 3 HER2-/ER+ (13%), 2 HER2(3+)/ER+ (8.7%) 5 triple negative (22%), median time from diagnosis to brain metastases was 2.5 years (range 0 to 11.8 years). Of 502 genes, 12 were significantly overexpressed in brain metastases as compared to matched primary tumors by >1.5 fold; each of the 12 genes was also overexpressed in resected brain metastases as compared to systemic human metastases in an online microarray database. One of these, L1CAM, a neuronal cell adhesion molecule involved in axon motility and tracking, was upregulated 1.6-fold in the brain metastases relative to the primary tumors (p= 0.037). L1CAM protein was upregulated 6.4-fold in 231-BR cells relative to MDA-MB-231. Control shRNA- and L1CAM shRNA transfected 231-BR cells produced equivalent numbers of brain micrometastases; knockdown of L1CAM inhibited the development of large (>1 mm) metastases in a mouse brain by 2-fold (p= 0.038). Conclusions: L1CAM neuronal cell adhesion protein is acquired in human brain metastases of breast cancer and functionally promotes the formation of large brain metastases, identifying it as a new therapeutic target.

Quality of life in patients treated with stereotactic radiosurgery following resection of brain metastases.

e19726 Background: This multi-institutional study analyzes QOL in pts tx with stereotactic r(SRS) to the tumor bed following gross total resection (GTR) of brain mets. Health-related qualify of life (HRQL) is defined as

Management of Patients with Brain Metastases Receiving Trastuzumab Treatment for Metastatic Breast Cancer

Background: With the more effective control of visceral metastases in patients with metastatic breast cancer (MBC), an increasing number of patients face brain metastases (BM). The aim of this retrospective analysis was to investigate the incidence and factors affecting the prognosis of patients with BM under trastuzumab treatment for MBC. Patients and Methods: A total of 75 HER2positive patients treated with trastuzumab for MBC were included. Results are discussed in the context of the current literature. Results: Patients who developed BM (n = 29) had longer median progression-free survival (PFS) during first-line chemotherapy and longer overall survival (OS) after diagnosis of MBC than 46 patients without BM (PFS: 27 vs. 14 months, p = 0.039; OS: 46 vs. 18 months, p = 0.067). Median survival of patients with continuation of trastuzumab after diagnosis of BM was longer than survival of patients with discontinuation of trastuzumab treatment after BM (18 vs. 3 months, p = 0.006). Survival of patients who were treated with surgery and radiotherapy for BM was better compared with radiotherapy alone (9 vs. 5 months, p = not significant) or best supportive care (9 vs. 2 months, p = 0.049). Conclusions: Continuation of trastuzumab treatment as well as resection of BM seem to give further benefit in the treatment of patients with HER2-overexpressing MBC.

Abstract 2667: L1CAM neural adhesion molecule is overexpressed in human brain metastases of breast cancer and contributes to colony formation efficiency

Abstract To investigate the molecular mechanisms responsible for breast cancer metastasis to the brain, a gene expression analysis was performed using formalin-fixed, paraffin embedded sections of matched primary breast tumors and resected brain metastases. The neuronal cell adhesion molecule L1CAM was upregulated by approximately 1.57 fold in the brain metastases relative to the primary tumors (p=0.037). This trend was most apparent in Her-2+ tumors (p=0.044) and did not extend to ER+ patients (p=0.42). L1CAM has been correlated to decreased patient survival in breast cancer. MDA-MB-231 breast cancer cells selected to grow in the brain (231-BR) expressed 6.4 fold greater L1CAM on western blots than the parental cell line (231-P). Using three shRNA constructs, L1CAM expression was decreased by 1.76, 3.82, and 63.3 fold in the 231-BR cell line. Decreased L1CAM expression inhibited the clonogenic formation of 231-BR cells by 40-50% (p&amp;lt;0.002); however, increased proliferation by MTT assay by 30-60% (p&amp;lt;0.002). The most efficient L1CAM knockdown also showed a 30% decrease in migration via scratch assay relative to the non-targeting control, suggesting that L1CAM may be involved in 231-BR cell migration (p&amp;lt;0.03). Studies are underway to determine the effect of L1CAM down-regulation on the development of breast cancer brain metastases. These results suggest L1CAM may be a potential novel therapeutic target for metastatic breast cancer in the brain. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2667. doi:10.1158/1538-7445.AM2011-2667

DIAGNOSTIC PITFALLS OF BRAIN METASTASES AFTER BRAIN IRRADIATION

Although brain metastases are one of the most frequently diagnosed sequelae of systemic malignancy, their optimal management still is not well defined. In that respect the different diagnostic and therapeutic approaches of BMs patients is an issue for serious discussions. Among the most commonly used diagnostic tools are computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, single photon emission computed tomography (SPECT) and positron emission tomography (PET) scans etc. Nowadays the aforementioned diagnostic modalities are usually combined in order to obtain complete diagnostic information important for establishing the optimal treatment. With the present report we try to elaborate on the value of the modern diagnostic tools in differentiating between tumor progression versus radiation necrosis in irradiated patients with resected brain metastases. Although the present advancement of the modern imaging modalities differentiating between tumor progression versus radiation necrosis is often difficult. Application of the metabolic imaging modalities like SPECT, PET and proton magnetic resonance spectroscopy (1H-MRS) contributes for the diagnose but still pathological specimens remain a gold standard for distinguishing tumor from necrosis, because none of the imaging modalities is possible to reliably differentiate necrosis from progression in 100% of the cases.

Tumor Bed Radiosurgery following Resection of Brain Metastases: A Review

There is a growing interest in adjuvant radiosurgery following resection of hematogenous brain metastases. We have identified 12 series reporting on a total of 480 patients treated to a tumor bed following microsurgery. These cases fall into 3 paradigms: adjuvant radiosurgery as an alternative to whole-brain radiotherapy (WBRT), radiosurgery as an intensification of adjuvant WBRT and adjuvant radiosurgery for patients having failed prior WBRT. For these paradigms the reported crude local control rates are 79%, 92% and 95%, respectively. The procedure appears well tolerate with approximately a 5% risk of late radiation necrosis. Prospective data is lagging behind clinical practice and plans for prospective trials are discussed.

Postoperative treatment and prognosis of patients with resected single brain metastasis: How useful are established prognostic scores?

Objective To evaluate postoperative prognosis and the performance of known prognostic scores in patients treated with surgical resection for single brain metastasis. Methods We evaluated prognostic factors and five previously published prognostic scores in a group of 74 patients with single brain metastasis treated with surgery with or without immediate whole-brain radiotherapy (WBRT). Results In multivariate analysis, good performance status, absence of extracranial metastases and primary tumor control were significantly associated with improved overall survival. Survival (median 10.8 months) was not significantly prolonged by immediate WBRT. Salvage treatment was necessary in 87% of patients without immediate WBRT. All five scores identified groups of patients with superior prognosis. The recursive partitioning analysis (RPA) classes, the graded prognostic assessment (GPA) score and the score developed by Rades et al. identified a poor prognosis group, but the numbers of poor prognosis patients were very small. Conclusions RPA and GPA appear to have the most utility in delineating exceptionally good or poor prognosis patients after resection of single brain metastasis, but this finding remains to be validated in a larger study population. Identification and validation of suitable prognostic scores hopefully will guide decision making regarding local treatment of solitary brain metastasis.

Local Control and Long-term Survival for Patients with a Single Brain Metastasis Treated with Surgery followed by Stereotactic Radiosurgery to the Resection Cavity

The need for adjuvant radiation after surgical resection of brain metastases is well established, but the ideal radiation volume is not known. While whole brain radiation therapy (WBRT) is commonly given adjuvantly, focal radiation to only the tumor bed has the potential to spare more normal tissue and limit late effects of WBRT. The authors report institutional experience with this technique, focusing on local control and long term survival in patients with a single resected brain metastasis treated with adjuvant stereotactic radiosurgery (SRS) to the tumor bed.

Factors influencing the risk of local recurrence after resection of a single brain metastasis

Local recurrence (LR) of a resected brain metastasis occurs in up to 46% of patients. Postoperative whole-brain radiation therapy (WBRT) reduces that incidence. To isolate factors associated with the risk of LR after resection, the authors only studied patients who did not receive adjuvant radiotherapy. The authors reviewed data from 570 cases involving patients who had undergone resection of a previously untreated single brain metastasis at The University of Texas M. D. Anderson Cancer Center between 1993 and 2006 without receiving postoperative WBRT. All tumors were measured preoperatively on MR images. The resection method (en bloc resection [EBR] or piecemeal resection [PMR]) was noted at the time of surgery. Predictors of LR were assessed using the Cox proportional hazards model. The median patient age was 58 years, 55% were male, and 88% had a Karnofsky Performance Scale Score > or = 80. The most common primary cancers were those of the lung (28%), skin (melanoma, 21%), kidney (19%), and breast (11%). Piecemeal resection was performed in 201 patients (35%) and EBR in 369 (65%). Local recurrence developed in 84 patients (15%). The histological type of the primary cancer did not significantly predict LR; however, 7 of 22 patients with sarcoma developed LR (p = 0.16). The authors identified 2 variables that increased the risk of LR. Undergoing PMR carried a significantly higher LR risk than EBR (crude hazard ratio [HR] 1.7, 95% CI 1.1-2.6, p = 0.03). Tumors exceeding the median volume (9.7 cm(3)) had a significantly higher LR risk than those that were < 9.7 cm(3) (crude HR 1.7; 95% CI 1.1-2.6; p = 0.02). In the multivariate analysis, small tumors removed by EBR had a significantly lower LR risk. The LR risk of a single brain metastasis is influenced by biological factors (such as tumor volume) and treatments (such as the resection method). Early administration of postoperative WBRT may be particularly warranted when such negative tumor-related prognostic factors are noted or when treatment-related ones such as PMR are unavoidable.

Trimodality therapy for locally advanced non-small cell lung cancer.

e17529 Background: Management of locally advanced non-small cell lung cancer (LA-NSCLC) lacks consensus. Trimodality therapy is promising, but concerns about its safety and deliverability persist. A retrospective analysis of patients treated with trimodality therapy for LA-NSCLC at our institution to determine outcomes was conducted. Methods: All patients with LA-NSCLC treated with neoadjuvant chemoradiation (2-3 cycles of a platinum-based doublet with 45 Gy concurrent thoracic radiation) followed by resection performed by one of two thoracic surgeons (RL, KT). Two cycles of the same chemotherapy regimen were planned post-resection. Age at diagnosis, gender, smoking history, disease stage, treatment received, surgical complications and overall survival were collected. Outcomes were compared using log- rank test. Results: This analysis includes 35 patients who met the inclusion criteria. Median age of the patients was 63 years (range: 39-84 years). Clinical stage at diagnosis was IB – 1; IIB – 1; IIIA - 23; IIIB – 9; IV – 1 (resected brain metastasis). Carboplatin/paclitaxel was administered to 27 patients. Of these 23 received standard doses (AUC 5 and 175 mg/m2 respectively), while 4 received low-dose weekly therapy. Other regimens were carboplatin/gemcitabine (n=1), cisplatin/vinblastine (n=1), cisplatin/etoposide (n=3), carboplatin/etoposide (n=1), cisplatin/VP16 (n=1). Data on 1 patient was unavailable. Resection included pneumonectomy (n=5), bilobectomy (n=3) and lobectomy (n=27). Post-operative complications were atrial fibrillation (11), pneumonia (4), ARDS (4), air leak and recurrent laryngeal nerve injury (3 each). Surgical mortality at 28 days was 8.6% (n=3). Survival ranged from 4-54.6 months (median: 15.6 months). Median survival of 27 patients (77%) receiving postoperative chemotherapy was 31.9 months. Survival at 1, 2 and 3 years was 60%, 29% and 17% respectively. Conclusions: Trimodality therapy is feasible in locally advanced NSCLC. Patients who received their entire planned treatment had a prolonged median survival. Studies evaluating proper patient selection for trimodality therapy for LA-NSCLC are needed. No significant financial relationships to disclose.

Comparison of hormone receptor and HER2 status in resected brain metastases and primary breast cancer.

1117 Background: HER2 overexpresion and negative hormone receptors are reported as factors contributing to higher incidence of brain metastases (BM) in metastatic breast carcinoma. Therefore it could be expected that biological marker characteristics (BMC) of BM is consistent with primary breast carcinoma (PBC). Because few patients are eligible for surgery, BMC of BM is usually unknown. Methods: The aim of this analysis is to compare BMC in PBC and completely resected BM. Among 97 breast carcinoma patients with BM, 21 (21.6%) had 1-3 metastases, and underwent BM surgery. Results: All patients had pathologically confirmed BC metastases. BM BMC was known in 10/21 (47.6%). BMC is defined as ER/PR receptors (HR), (Quick score 0-8) and HER2 status (IHC 0-3+/CISH±). The only one HR+ PBC changed to HR – in BM. Among 8 HER2- PBC, 2 (25%) changed to HER2+ BM. All HR-, HER2+, and triple-negative PBC retained these BMC in BM (Table). Conclusions: According to our results, it could be expected that BM BMC profile is unchanged if PBC is HR-, HER2+ or triple-negative. PBC with more favorable BMC could change to less favorable in BM. Although obtained in small, selected subgroup of patients with resectable BM, these results should be considered in systemic treatment choice. BMC PBC No. (%) BM No. (%) No. (%) of changed BMC in BM HR+ (ER or PR≥ 4) 1/10 (10) 0/10 (0) 1/1(100) changed to HR- HR- (ER and PR ≤ 3) 9/10 (90) 10/10 (100) 0/9 (0) HER2- (0, 1+, 2+) 8/10 (80) 6/10 (60) 2/8 (25) changed to HER2+ HER2+ (3+, CISH +) 2/10 (20) 4/10 (40) 0/2 (0) Triple-negative (ER, PR, HER2 0) 6/10 (60) 6/10 (60) 0/6 (0) No significant financial relationships to disclose.

Comparison between Steroid Receptors and Her2 Status in Primary Breast Carcinoma and Completely Resected Breast Carcinoma Metastases from Different Visceral Organ Sites.

Abstract Background: Metastases biopsy are seldom performed in metastatic breast carcinoma (MBC) and hormonal, and anti-Her2 therapy are given upon biological markers of the primary breast cancer (PBC).However, there are reports about discrepancies in biological markers between PBC and MBC that could significantly influence treatment outcome.Aim: The aim of this paper is to compare steroid receptors and Her2 status of the PBC and of resected metastases (MBC) Patients and methods: Pathology reports were analyzed for all patients who underwent resection of PBC and resection of liver, brain or lung metastases. Rationale for this patients selection is the assumption that BC, as a heterogeneous malignancy might have differently expressed biological markers in different parts of metastases and therefore, biopsy only might not be completely informative about biological marker status of MBC. Results: 36 pts were identified: 27 with liver metastasis resection; 8 with brain metastasis resection; and 1 patient with lung metastasis resection. Median age was 51,5 years (31-73) Median DFI was 36 months (0-144) ER/PGR status of PBC was known for 32/36 pts and for 30/36 pts in metastasis (MBC). HER2 status of PBC was known for 30/36 pts and for 29/36 in MBC. To facilitate results interpretation, steroid receptor status is divided in 2 groups upon indication for hormonal treatment: A. hormone dependent, (one or both receptors score ≥ 4): B. hormone independent, (both receptors ≤ score 3). Her2 status is also divided in 2 groups upon indication for trastuzumab as: C. Her2 negative if IHC Her 2 was 0+,1+, or 2 + D. Her2 positive, if IHC was 3+ or CISH +; E. Triple negative if both steroid receptors were score 0 and Her2 0+ Results are presented at table 1.ResultsInitial biological markers status in PBCNo of pts (%)Changed biological markers status in MBC (%)CommentA. ER or PGR ≥ 421 (65,6%)12 (57%)12/21 (57%) hormone dependent PBC become hormone independent in MBCB.ER and PGR ≤ 311 (34,3%)1 (9 %)1/11 (9%) hormone independent PBC become hormone dependent in MBCC. Her2 0+,1+,2+24 (80%)0 (0%)0/24 (0%) Her2 0+,1+,2+ PBC has changed status to Her2 3+ in MBCD.Her2 3+6 (20%)1 (16,6%)1/6 (16,6%) Her2 3+ PBC has changed status in Her2 1+ in MBCE.Triple negative3 (10%)0 (0%)0/3 (0%) triple negative PBC has changed status in MBC Conclusion: Biological markers, that are considered as poor prognostic factors are more stable characteristics of BC hence they tends to change in MBC in much lesser degree than biological markers that are considered as good prognostic factors. Although obtained in selected subgroup of BC patients who developed resectable BC metastases, these results could be implemented in every day clinical practice, hence triple negative, steroid receptor negative and Her2 positive PBC almost always retains these characteristics in MBC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4048.

Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy

Whole-brain radiation therapy (WBRT) has been the traditional approach to minimize the risk of intracranial recurrence following resection of brain metastases, despite its potential for late neurotoxicity. In 2007, the authors demonstrated an equivalent local recurrence rate to WBRT by using stereotactic radiosurgery (SRS) to the operative bed, sparing 72% of their patients WBRT. They now update their initial experience with additional patients and more mature follow-up. The authors performed a retrospective review of all cases involving patients with limited intracranial metastatic disease (< or = 4 lesions) treated at their institution with SRS to the operative bed following resection. No patient had prior cranial radiation and WBRT was used only for salvage. From November 2000 to June 2009, 52 patients with a median age of 61 years met inclusion criteria. A single metastasis was resected in each patient. Thirty-four of the patients each had 1 lesion, 13 had 2 lesions, 3 had 3 lesions, and 2 had 4 lesions. A median dose of 1500 cGy (range 800-1800 cGy) was delivered to the resection bed targeting a median volume of 3.85 cm(3) (range 0.08-22 cm(3)). With a median follow-up of 13 months, the median survival was 15.0 months. Four patients (7.7%) had a local recurrence within the surgical site. Twenty-three patients (44%) ultimately developed distant brain recurrences at a median of 16 months postresection, and 16 (30.7%) received salvage WBRT (8 for diffuse disease [> 3 lesions], 4 for local recurrence, and 4 for diffuse progression following salvage SRS). The median time to WBRT administration postresection was 8.7 months (range 2-43 months). On univariate analysis, patient factors of a solitary tumor (19.0 vs 12 months, p = 0.02), a recursive partitioning analysis (RPA) Class I (21 vs 13 months, p = 0.03), and no extracranial disease on presentation (22 vs 13 months, p = 0.01) were significantly associated with longer survival. Cox multivariate analysis showed a significant association with longer survival for the patient factors of no extracranial disease on presentation (p = 0.01) and solitary intracranial metastasis (p = 0.02). Among patients with no extracranial disease, a solitary intracranial metastasis conferred significant additional survival advantage (43 vs 10.5 months, p = 0.05, log-rank test). No factor (age, RPA class, tumor size or histological type, disease burden, extent of resection, or SRS dose or volume) was related to the need for salvage WBRT. Adjuvant SRS to the metastatic intracranial operative bed results in a local recurrence rate equivalent to adjuvant WBRT. In combination with SRS for unresected lesions and routine imaging surveillance, this approach achieves robust overall survival (median 15 months) while sparing 70% of the patients WBRT and its potential acute and chronic toxicity.

Disruption of the blood brain barrier by brain metastases of triple‐negative and basal‐type breast cancer but not HER2/neu‐positive breast cancer

Generally, the blood-brain barrier (BBB) of brain metastasis was thought to be disrupted. We retrospectively performed immunohistochemical staining for glucose transporter 1 (GLUT1) and breast cancer resistance protein (BCRP) to evaluate the status of the BBB in resected brain metastases. Associations between expression of GLUT1 and/or BCRP and the immunohistochemical profiles of breast cancers, such as the statuses of hormone receptors, human epidermal growth factor receptor 2 (HER2/neu), and a basal-type marker (cytokeratin 5/6, HER1), were also analyzed. The study included 29 breast cancer patients with brain metastasis who had undergone brain tumor resections. Among the 29 patients, there was no expression of GLUT1 and BCRP in the intratumor microvessels of 9 (32%) and 11 (38%) patients, respectively. There was no expression of both GLUT1 and BCRP in 8 patients (28%). The expression of GLUT1 was significantly associated with that of BCRP (P < .001). A positive correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of HER2/neu-positive breast cancer (P = .012), while a negative correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of triple negative or basal-type breast cancer (P = .014 and P = .003 for triple negative and basal-type, respectively). Brain metastases of triple negative or basal-type breast cancers may often disrupt the BBB, whereas brain metastases of HER2/neu-positive breast cancer tend to preserve the BBB.