Clinical outcomes of HER2-positive metastatic breast cancer patients with brain metastasis treated with lapatinib and capecitabine: an open-label expanded access study in Korea

ABSTRACT: Purpose: To evaluate efficacy in patients with brain metastasis (BM) on entry into the lapatinib expanded access program (LEAP). METHODS: LEAP is a worldwide, single-arm, open-label study. HER2-positive, locally-advanced or metastatic breast cancer patients with progression after an anthracycline, taxane, and trastuzumab were eligible. Patients received capecitabine 2000 mg/m2 daily in two divided doses, days 1-14, every 21 days and lapatinib 1250 mg once daily. RESULTS: Among 186 patients enrolled in 6 Korean centers, 58 had BM. Progression-free survival (PFS) was 18.7 weeks in patients with BM and 19.4 weeks without BM (P=0.88). In patients with BM, brain response was synchronized with systemic responses (P=0.0001). Overall survival (OS) was 48.9 weeks in patients with BM and 64.6 weeks without BM (P=0.23). Multivariable analysis found hormone receptor positivity (P=0.003) and clinical benefit rate (CBR) of combined systemic and brain disease (P<0.0001) significantly associated with prolonged brain PFS, and CBR of combined systemic and brain disease (P=0.03) and longer trastuzumab use (P=0.047) associated with prolonged OS in patients with BM; prior capecitabine did not affect PFS or OS in patients with BM. CONCLUSION: Lapatinib plus capecitabine is equally effective in patients with or without BM.     

Safety of concurrent bevacizumab therapy and anticoagulation in glioma patients

Venous thromboembolic events (VTE) are common in glioma patients and are typically treated with anticoagulant medications. The anti-angiogenic agent bevacizumab (BVZ) increases the risks of both VTE and hemorrhagic complications. Little is known about the hemorrhagic risk of anticoagulation in glioma patients receiving BVZ. We reviewed medical records from 282 BVZ-treated patients at our center and identified 64 who received concurrent anticoagulant therapy. The risk and severity of hemorrhagic complications were assessed. Fisher??s exact test was used to compare the risk of hemorrhage between subjects who received and did not receive anticoagulants. Forty-seven patients (73%) had glioblastoma, 15 (23%) anaplastic glioma, and 2 (3%) other tumors. Thirteen (20%) and 51 (80%) patients received warfarin and low-molecular-weight heparin, respectively. The indication for anticoagulation was deep venous thrombosis in 37 patients (58%), pulmonary embolism in 22 (34%), and both in 5 (8%). Thirteen patients (20%) experienced hemorrhage, of which four hemorrhages (6%) were serious (grade????3): one patient had grade 5 intracerebral hemorrhage (ICH), one grade 4 ICH, one grade 3 epistaxis, and one grade 3 gastrointestinal hemorrhage. ICH was seen in seven patients (11%), of which five (8%) were grade 1. Among 218 patients who did not receive anticoagulants, there were two (1%) serious hemorrhages (both grade 4 ICH). Both the serious hemorrhage rate and overall ICH rate were higher in patients who received anticoagulants (P?=?0.03 and 0.02, respectively). Anticoagulant use during BVZ therapy may increase the risk of hemorrhage in glioma patients, although it is generally well tolerated.     

Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis

Aim

We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy.

Methods

This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013.

Results

The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS.

Conclusion

Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

     

全脑放疗对广泛期小细胞肺癌脑转移的生存影响北大核心CSCD

目的探索现代诊疗条件下,全脑放疗(WBRT)能否延长小细胞肺癌(SCLC)脑转移患者的生存期。方法回顾性分析天津医科大学肿瘤医院2010—2020年245例伴有脑转移的广泛期SCLC患者的病历资料,其中WBRT组168例(剂量30 Gy分10次),无WBRT组77例。所有患者均接受了至少2个周期的化疗,化疗方案均为顺铂或卡铂联合依托泊苷,115例接受了胸部放疗。研究终点为脑转移后生存期(BM-OS),采用卡方检验对分类数据进行比较,采用稳健逆概率处理加权(sIPTW)方法对组间变量进行匹配,采用Kaplan-Meier方法进行生存分析,log-rank检验进行生存曲线比较。结果全组患者中位BM-OS为9.1个月。有无WBRT患者的中位BM-OS分别为10.6、6.7个月(P=0.003),应用sIPTW平衡两组影响因素后,两组的BM-OS差异仍具有统计学意义(P=0.02)。其中,首诊广泛期伴脑转移患者118例,有无WBRT的中位BM-OS分别为13.0、9.6个月(P=0.007);广泛期疗中出现脑转移患者127例,有无WBRT的中位BM-OS分别为8.0、4.1个月(P=0.003)。在50例单纯脑转移患者中,有无WBRT的中位BM-OS为13.3、10.9个月(P=0.259);在195例伴有颅外转移的患者中,有无WBRT的中位BM-OS分别为9.5、5.9个月(P=0.009)。结论广泛期小细胞肺癌脑转移患者行全脑放疗能够为患者带来生存获益。     

全脑放疗对广泛期小细胞肺癌脑转移的生存影响

目的 探索现代诊疗条件下,全脑放疗（WBRT）能否延长小细胞肺癌（SCLC）脑转移患者的生存期。方法 回顾性分析天津医科大学肿瘤医院2010—2020年245例伴有脑转移的广泛期SCLC患者的病历资料,其中WBRT组168例（剂量30 Gy分10次）,无WBRT组77例。所有患者均接受了至少2个周期的化疗,化疗方案均为顺铂或卡铂联合依托泊苷,115例接受了胸部放疗。研究终点为脑转移后生存期（BM‐OS）,采用卡方检验对分类数据进行比较,采用稳健逆概率处理加权（sIPTW）方法对组间变量进行匹配,采用Kaplan‐Meier方法进行生存分析,log‐rank检验进行生存曲线比较。结果 全组患者中位BM‐OS为9.1个月。有无WBRT患者的中位BM‐OS分别为10.6、6.7个月（P=0.003）,应用sIPTW平衡两组影响因素后,两组的BM‐OS差异仍具有统计学意义（P=0.02）。其中,首诊广泛期伴脑转移患者118例,有无WBRT的中位BM‐OS分别为13.0、9.6个月（P=0.007）;广泛期疗中出现脑转移患者127例,有无WBRT的中位BM‐OS分别为8.0、4.1个月（P=0.003）。在50例单纯脑转移患者中,有无WBRT的中位BM‐OS为13.3、10.9个月（P=0.259）;在195例伴有颅外转移的患者中,有无WBRT的中位BM‐OS分别为9.5、5.9个月（P=0.009）。结论 广泛期小细胞肺癌脑转移患者行全脑放疗能够为患者带来生存获益。     

Prognostic factors for survival in melanoma patients with brain metastases

BACKGROUND:

One of the most common and deadly complications of melanoma is brain metastases. The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS).

METHODS:

An institutional database of advanced melanoma patients enrolled on clinical trials in the Department of Melanoma Medical Oncology from 1986 to 2004 was reviewed and patients who developed brain metastases were identified. Date of diagnosis, patient age, pattern of brain involvement, timing relative to extracranial metastases, prior response to systemic therapy, and treatments given for brain metastases were assessed as potential prognostic factors for OS.

RESULTS:

Among 743 melanoma patients enrolled in clinical trials for regional or systemic metastatic disease, 330 (44%) patients developed brain metastases. The median OS after the diagnosis of brain metastases was 4.7 months. Diagnosis before 1996, increased number of parenchymal brain metastases, leptomeningeal involvement, and development of brain metastases after receiving systemic therapy for extracranial metastases were found to be significant prognostic factors for OS. Among patients who received systemic therapy as the initial treatment of brain metastases, patients who previously responded to systemic therapies had longer survival than patients who had not responded.

CONCLUSIONS:

The era, pattern, and timing of melanoma brain metastases were found to be strongly associated with survival. Previous responsiveness to systemic therapies did not predict better outcomes overall, but it did correlate with improved survival for patients with brain metastases who were treated with systemic therapies. These factors may be used in guiding patient management and for stratifying patients in clinical trials. Cancer 2011. © 2010 American Cancer Society.     

Understanding Treatment Patterns and Outcomes among Patients with De Novo Unresectable Locally Advanced or Metastatic Urothelial Cancer: A Population-Level Retrospective Analysis from Alberta,Canada

Despite a high disease burden, real-world data on treatment patterns in patients with unresectable locally advanced or metastatic urothelial carcinoma (la/mUC) in Canada are limited. This retrospective, longitudinal cohort study describes treatment patterns and survival in a population of patients with de novo unresectable la/mUC from Alberta, Canada, diagnosed between 1 January 2015 and 31 December 2019, followed until mid-2020. The outcomes of interest were systemic therapy treatment patterns and overall survival (OS). Of 206 patients, most (65.0%, n = 134) did not receive any systemic therapies. Of 72 patients (35.0%) who received first-line systemic therapy, the median duration of treatment was 2.8 months (IQR 3.3). Thirty-five patients (48.6% of those who received first-line therapy) received subsequent second-line therapy, for a median of 3.0 months (IQR 3.3). In all patients (n = 206), the median OS from diagnosis was 5.3 months (95% CI, 4.5–7.0). In patients who received treatment, the median OS from the initiation of first-line and second-line systemic therapy was 9.1 (6.4–11.6) and 4.6 months (3.9–19.2), respectively. The majority of patients did not receive first-line systemic therapy, and, in those who did, survival outcomes were poor. This study highlights the significant unmet need for safe and efficacious therapies for patients with la/mUC in Canada.     

The combined use of steroids and immune checkpoint inhibitors in brain metastasis patients: a systematic review and meta-analysis

BackgroundImmune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI.MethodsA systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies.ResultsAfter screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07).ConclusionsAdministration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.     

Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy

BackgroundThe anti-programmed death-1 (anti-PD-1) therapy nivolumab has significant clinical activity in patients with metastatic melanoma. However, little is known about the safety and outcomes in patients receiving anti-PD-1 therapy and stereotactic radiation for the treatment of brain metastases (BMs).Patients and methodsData were analyzed retrospectively from two prospective nivolumab protocols enrolling 160 patients with advanced resected and unresectable melanoma at a single institution. Patients were included if BMs were diagnosed and treated with stereotactic radiation within 6 months of receiving nivolumab. The primary end point of this study was neurotoxicity; secondary end points included BM control and survival.ResultsTwenty-six patients with a total of 73 BMs treated over 30 sessions were identified. Radiation was administered before, during and after nivolumab in 33 lesions (45%), 5 lesions (7%), and 35 lesions (48%), respectively. All BMs were treated with stereotactic radiosurgery (SRS) in a single session except 12 BMs treated with fractionated stereotactic radiation therapy, nine of which were in the postoperative setting. One patient experienced grade 2 headaches following SRS with symptomatic relief with steroid treatment. No other treatment-related neurologic toxicities or scalp reactions were reported. Eight (11%) local BM failures with a ≥20% increase in volume were noted. Of these lesions, hemorrhage was noted in 4, and edema was noted in 7. Kaplan–Meier estimates for local BM control following radiation at 6 and 12 months were 91% and 85%, respectively. Median overall survival (OS) from the date of stereotactic radiation and nivolumab initiation was 11.8 and 12.0 months, respectively, in patients receiving nivolumab for unresected disease (median OS was not reached in patients treated in the resected setting).ConclusionsIn our series, stereotactic radiation to melanoma BMs is well tolerated in patients who received nivolumab. BM control and OS appear prolonged compared with standard current treatment. Prospective evaluation is warranted.     

Biochemotherapy for metastatic melanoma with limited central nervous system involvement

OBJECTIVES: Biochemotherapy outcomes were examined in stage IV melanoma patients with previously treated or active central nervous system (CNS) metastases prior to systemic therapy. PATIENTS AND METHODS: Patients who received biochemotherapy for metastatic melanoma with active or pretreated CNS metastases were compared to patients without evidence of CNS metastases in terms of response, time to progression (TTP), overall survival (OS), and treatment toxicity. RESULTS: Twenty-six (16%) of 159 total patients began biochemotherapy with previously treated or active CNS metastases (group I), compared to 133 (84%) who were radiographically free of CNS involvement (group II). A partial or complete response to biochemotherapy was seen in 13 (50%) group I patients, compared to 56 (42%) group II patients (p = 0.243). The median TTP and median survival were 5.5 and 7.0 months, respectively, for group I patients and 6.0 and 9.9 months, respectively, for group II patients (p = 0.222 and 0.434 for TTP and OS, respectively). Five (19%) group I patients survived longer than 24 months. Gamma Knife radiosurgery or surgical resection of CNS disease prior to biochemotherapy improved survival versus delayed treatment (p = 0.017 and 0.005, respectively). CONCLUSION: Patients with limited CNS metastases and widespread systemic disease can achieve prolonged survival with targeted treatment of CNS lesions and aggressive systemic therapy.     

550例局限期小细胞肺癌放化疗达缓解者预防性脑照射后脑转移风险评估

目的:评价影响放化疗后达完全缓解、部分缓解(CR/PR)的局限期小细胞肺癌(SCLC)患者预防性脑照射(PCI)后脑转移(BM)风险、预后因素。方法:收集2002—2017年间在浙江省肿瘤医院治疗疗效达CR/PR且经PCI治疗的550例局限期SCLC患者的基本资料,回顾分析PCI后BM风险因素及预后。采用 ...     

Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients.

BACKGROUND: The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. METHODS: This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). RESULTS: Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) < or = 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42-6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69-3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04-2.58, P = 0.032). CONCLUSIONS: Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis.     

Spinal meningioma and factors predictive of post-operative deterioration

Administration of bevacizumab to patients with brain metastases (BM) is controversial due to concerns about the increased risk of intracranial hemorrhage (ICH). This meta-analysis assessed whether the risk of ICH increases in BM patients receiving treatments that contain bevacizumab versus without. PubMed, Embase, Cochrane Library and annual meeting abstracts of the American Society of Clinical Oncology up to 13 November 2016 were searched for studies that referred to ICH complications due to bevacizumab in patients with BM. Eight studies involving 8713 patients were included in this analysis. Compared with the control arm without bevacizumab, the bevacizumab treatment arm did not exhibit a significant increase in ICH [odds ratio (OR) 1.20; 95% confidence intervals (CI) 0.69–2.09; P?=?0.53]. Subgroup analyses with retrospective studies showed a similar result, although subgroup analyses with prospective studies failed. This meta-analysis revealed that bevacizumab does not significantly increase the risk of ICH in solid tumor patients with BM.     

Brain metastases in breast cancer: clinical and pathologic characteristics associated with improvements in survival

BACKGROUND: As breast cancer patients live longer with control of systemic disease, survival after the diagnosis of brain metastases (BM) also appears to be improving. METHODS: The authors conducted a retrospective review of 112 breast cancer patients diagnosed with BM from 1997 to 2007 and correlated clinical and pathologic characteristics including hormone receptor (HR) and Her2/neu status with outcomes. FINDINGS: Median time to BM diagnosis (TTBM) was 38 months (range, 0-204 months). TTBM was shorter for patients with HR- versus HR+ disease (median 28.8 vs. 61.2 months, P < 0.001, Wilcoxon test). No difference in TTBM was observed for patients with HER2- versus HER2+ disease (median 37.4 vs. 34.9 months, P = 0.81). Median survival after the diagnosis of BM was 14.4 months. There was no significant difference in median survival after BM diagnosis for patients with HR+ versus HR- cancers (19.9 vs. 11.0 months, P = 0.18, log rank) or for patients with HER2+ versus HER2- disease (23.1 vs. 13.3 months, P = 0.11, log rank). Survival was significantly longer in patients with stable or responding systemic disease at BM diagnosis compared to patients with progressing systemic disease (31 vs. 6.3 months, P < 0.001). Multivariate analysis revealed that HR positivity, age <50, Karnofsky Performance Score (KPS) > or =80, and stable or responding systemic disease at BM diagnosis were associated with improved survival. INTERPRETATION: Subsets of patients with breast cancer BM are surviving longer. Control of systemic disease was most strongly associated with improved outcomes, and HER2/neu overexpression did not shorten survival after the diagnosis of BM.     

Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine.

PURPOSE: The curative effect of surgery in certain patients with metastatic melanoma suggests the presence of endogenous antitumor responses. Because melanoma is immunogenic, we investigated whether a therapeutic cancer vaccine called Canvaxin (CancerVax Corporation, Carlsbad, CA) could enhance antitumor immune responses and thereby prolong survival. PATIENTS AND METHODS: Of 263 patients who underwent complete resection of American Joint Committee on Cancer stage IV melanoma, 150 received postoperative adjuvant vaccine therapy and 113 did not. The overall survival (OS) for the two groups was compared by Cox regression. Further survival analysis was performed by matched-pair analysis according to three prognostic variables: sex, metastatic site, and number of tumor-involved organ sites. RESULTS: Five-year OS rates were 39% for vaccine and 19% for nonvaccine patients. On multivariate analysis, vaccine therapy was the most significant prognostic variable in this cohort (P =.0001). Analysis of 107 matched pairs of vaccine and nonvaccine patients revealed a significant OS advantage for vaccine therapy (P =.0009): 5-year OS was 39% for vaccine patients versus 20% for nonvaccine patients. There was a significant delayed-type hypersensitivity (DTH) response to adjuvant vaccine therapy (P =.0001), and OS was significantly correlated with DTH to vaccine (P =.0001) but not with DTH to purified protein derivative (PPD), a control antigen. CONCLUSION: Prolonged survival was observed in patients who received postoperative active immunotherapy with Canvaxin therapeutic cancer vaccine. The correlation of survival with vaccine-DTH responses but not PPD-DTH indicates a treatment-specific effect. These findings suggest that adjuvant active specific immunotherapy should be considered after cytoreductive surgery for advanced melanoma.     

Management of venous thromboembolism in high-grade glioma: Does low molecular weight heparin increase intracranial bleeding risk?

BackgroundVenous thromboembolism (VTE) occurs in up to 30% of patients with high-grade glioma (HGG). Concern for increased risk of intracranial hemorrhage (ICH) with therapeutic anticoagulation (AC) complicates VTE treatment. Some retrospective studies have reported an increased risk of ICH associated with therapeutic AC; however, effective alternatives to AC are lacking. The aim of our study is to assess the risk of ICH in HGG patients with VTE on low molecular weight heparin (LMWH).MethodsWe performed a retrospective matched cohort study of HGG patients from January 2005 to August 2016. Blinded review of neuroimaging for ICH was performed. For analysis of the primary endpoint, estimates of cumulative incidence (CI) of ICH were calculated using competing risk analysis with death as competing risk; significance testing was performed using the Gray’s test. Median survival was estimated using the Kaplan-Meier method.ResultsTwo hundred twenty patients were included, 88 (40%) with VTE treated with LMWH, 22 (10%) with VTE, not on AC, and 110 (50%) without VTE. A total of 43 measurable ICH was recorded: 19 (26%) in LMWH, 3 (14%) in VTE not on AC, and 21 (19%) in non-VTE cohort. No significant difference was observed in the 1-year CI of ICH in the LMWH cohort and non-AC with VTE group (17% vs 9%; Gray’s test, P = .36). Among patients without VTE, the 1-year CI of ICH was 13%. Median survival was similar among all 3 cohorts.ConclusionsOur data suggest that therapeutic LMWH is not associated with substantially increased risk of ICH in HGG patients.     

The management of thromboembolic disease in patients with central nervous system malignancies

Opinion statement Venous thromboembolic disease (VTE) is a common complication of malignancies affecting the central nervous system (CNS), both in the perioperative period and throughout the disease course. Until recently, the perceived risk of intracranial hemorrhage in patients with CNS malignancies was felt to be a relative contraindication to systemic anticoagulation, and most patients were managed with nonpharmacologic methods in both the prophylactic and treatment setting. However, several studies of the safety and efficacy of anticoagulation in both neurosurgical and cancer patients have challenged the previous dogma, and routine use of unfractionated heparin or low molecular weight heparin (LMWH) for VTE prophylaxis in patients undergoing craniotomy for CNS malignancy is recommended. Likewise, treatment of established VTE in this population with heparins is recommended, at least initially, followed by long-term treatment either with heparin or oral warfarin. Complications of inferior vena cava (IVC) filters, used as an alternative to systemic anticoagulation, appear to be more common in brain tumor patients with VTE, lending further support to treatment with systemic anticoagulation when possible. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, LMWH is recommended in brain tumor patients with newly diagnosed VTE, followed by long-term warfarin or LMWH.     

Real-world data on patterns and outcomes of radiation therapy for brain metastases in a population-based cohort of lung cancer patients in Victoria

Introduction

We evaluated real-world data on the patterns and outcomes of radiotherapy (RT) for brain metastases (BM) in a population-based cohort of patients with lung cancer (LC) in Victoria.

Methods

The Victorian Radiotherapy Minimum Data set (VRMDS) and the Victorian Cancer Registry (VCR) were linked to identify patients with LC who underwent RT for BM between 2013 and 2016. We determined: (i) proportion of patients treated with stereotactic radiosurgery (SRS); (ii) overall survival (OS); and (iii) 30-day mortality (30M) following RT for BM.

Results

Of the 1001 patients included in the study, 193 (19%) had SRS. There was no significant increase in SRS use over time – from 18% in 2013 to 21% in 2016 (P-trend = 0.8). In multivariate analyses, increased age (P = 0.03) and treatment in regional centres (P < 0.001) were independently associated with lower likelihood of SRS treatment. The median OS following RT for BM was 3.6 months. Patients who had SRS had better OS than those who did not have SRS (median OS 8.9 months vs. 3 months, P < 0.01). SRS use, age, sex and year of treatment were independently associated with OS in multivariate analyses. A total of 184 (18%) patients died within 30 days of RT for BM, and the proportion was higher in older (P = 0.001) and male patients (P = 0.004).

Conclusion

One-in-five LC patients who received RT for BM had SRS. The improved OS with SRS is likely confounded by patient selection. It is important to reduce 30M by better selecting patients who may not benefit from RT for BM.     

非小细胞肺癌脑转移放疗时机的选择及疗效预后分析

背景与目的放疗联合化疗或靶向治疗仍然是非小细胞肺癌脑转移患者的首选治疗。本研究旨在探讨脑放疗时机的选择及推迟脑放疗对于患者疗效和生存期的影响。方法2003年5月-2015年12月,就诊于我中心确诊为非小细胞肺癌脑转移且接受过脑放疗及全身治疗（包括化疗和靶向治疗）的患者共198例入组了本研究。127例接受了同时性的全身治疗和脑放疗（早放疗组）。71例患者接受了延迟性的脑放疗：完成至少2周期全身治疗后才接受脑放疗（晚放疗组）。早放疗组和晚放疗组患者治疗前的脑转移预后评分（DS-GPA评分）均衡无偏倚。结果早放疗组患者的中位生存时间（overall survival, OS）与晚放疗组相比明显延长（17.9个月vs 12.6个月,P=0.038）,早放疗组患者的无进展生存期（progression-free survival, PFS）也优于晚放疗组（4.0个月vs 3.0个月,P<0.01）。3级-4级放化疗不良反应的发生率两组间无明显差异。确诊脑转移后,一线使用酪氨酸激酶抑制剂（ tyrosine kinase inhibitor, TKI）药物可能延长患者的OS（17.9个月vs 15.2个月,P=0.289）,但无明显统计学差异。在整个疾病进展过程中曾经使用TKI类药物与从未使用过TKI药物相比,患者的OS延长（20.0个月vs 10.7个月,P<0.01）。结论对于非小细胞肺癌脑转移患者,推迟脑放疗可能会影响患者的生存期。这一发现仍需要前瞻性多中心的随机对照研究来证实。     

Optimal strategy of gamma knife radiosurgery for craniopharyngiomas

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), frequently complicates the postoperative course of primary malignant brain tumor patients. Thromboprophylactic anticoagulation is commonly used to prevent VTE at the risk of intracranial hemorrhage (ICH). We extracted all patients who underwent craniotomy for a primary malignant brain tumor from the National Surgical Quality Improvement Program (NSQIP) registry (2005–2015) to perform a time-to-event analysis and identify relevant predictors of DVT, PE, and ICH within 30 days after surgery. Among the 7376 identified patients, the complication rates were 2.6, 1.5, and 1.3% for DVT, PE, and ICH, respectively. VTE was the second-most common major complication and third-most common reason for readmission. ICH was the most common reason for reoperation. The increased risk of VTE extends beyond the period of hospitalization, especially for PE, whereas ICH occurred predominantly within the first days after surgery. Older age and higher BMI were overall predictors of VTE. Dependent functional status and longer operative times were predictive for VTE during hospitalization, but not for post-discharge events. Admission two or more days before surgery was predictive for DVT, but not for PE. Preoperative steroid usage and male gender were predictive for post-discharge DVT and PE, respectively. ICH was associated with various comorbidities and longer operative times. This multicenter study demonstrates distinct critical time periods for the development of thrombotic and hemorrhagic events after craniotomy. Furthermore, the VTE risk profile depends on the type of VTE (DVT vs. PE) and clinical setting (hospitalized vs. post-discharge patients).