A diagnostic model to detect silent brain metastases in patients with non-small cell lung cancer

We aimed to discriminate subgroups according to the risk of brain metastases in patients with non-small cell lung cancer (NSCLC) lacking neurological symptoms. We performed a retrospective review of 433 patients with NSCLC who underwent chest computed tomography (CT), brain magnetic resonance imaging (MRI) and bone scans at an initial staging work-up between April 2003 and April 2007. Brain metastases were determined by MRI. Patients were stratified into groups according to the number of risk factors (0-3) identified by multivariate analysis. In multivariate analysis, histopathology with non-squamous cell carcinoma, nodal stage 2 on CT and presence of bone metastases were three risk factors for brain metastases. Patients were divided into four groups according to the number (0-3) of these predictive factors. The proportions of patients with brain metastases in the four groups were 2%, 3%, 17% and 35%, respectively, and these differences were significant (P<0.001). When analysis was performed in patients with localised disease, the number of risk factors was correlated with the prevalence of brain metastases (P=0.013) but stage was not (P=0.153). Although this diagnostic model should be validated through further studies, our data suggest that the number of risk factors might be a useful tool to identify silent brain metastases in patients with NSCLC.     

Prospective comparison of the impact on treatment decisions of whole-body magnetic resonance imaging and computed tomography in patients with metastatic malignant melanoma

Patient management and treatment strategies for metastatic melanoma depend largely on the stage of metastatic disease. The aim of this study was to compare contrast-enhanced whole-body magnetic resonance imaging (wbMRI) and whole-body computed tomography (wbCT) to detect distant metastases for staging. A total of 43 patients (41 with completed wbCT and wbMRI examination) with known American Joint Committee on Cancer (AJCC) stage III-IV malignant melanoma were examined and 775 metastases were identified by both methods. Whole-body CT was able to detect 522 metastases, whereas wbMRI found 730 metastases. Whole-body CT identified 188 pulmonary metastases, compared with 143 metastases detected by wbMRI. In kidneys, adrenal glands and lymph nodes, respectively, wbCT and wbMRI detected the same number of lesions. Whole-body MRI detected more metastases than wbCT in liver (detection rate 122/199), spleen (26/54), subcutaneous tissue (39/61), muscle (4/11), bone marrow (23/132) and brain (15/25). Therapy was modified as a consequence of wbMRI findings in 10/41 (24%) patients. In conclusion, wbMRI detected clearly more malignant melanoma metastases in most organ systems with the exception of lung metastases. More accurate and complete staging by wbMRI has an impact on treatment strategy in about one-quarter of the patients.     

Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with brain metastases from non-small cell lung cancer

BACKGROUND: Brain metastases develop frequently in patients with non-small cell lung cancer (NSCLC), and the prognosis for these patients is very poor. We evaluated the role of chemotherapy for patients with brain metastases from NSCLC. METHODS: We analyzed 30 patients who were discovered to have brain metastases during the diagnosis of 121 patients enrolled in three consecutive clinical trials on advanced NSCLC assessing combination chemotherapy of cisplatin, ifosfamide and irinotecan with rhG-CSF support. Response in the brain lesions was evaluated by contrast-enhanced MRI scans after at least two courses. RESULTS: Fourteen patients achieved a partial response (PR) but there was no change (NC) in 13 patients and progressive disease (PD) in 1. Among patients with extracranial lesions, 18 had a PR and 11 had NC. The response rate in brain metastases was 50.0%, and that in extracranial primary and metastatic lesions was 62.1%. The median duration of response for intra- and extracranial lesions was 140 and 147 days, respectively. After completing chemotherapy, Gamma Knife radiosurgery was performed on 2 patients in remission and 8 patients at disease progression. The median survival time and 1-year survival rate were 382 days and 56.1%, respectively. CONCLUSIONS: Both the response rate and survival data in this retrospective study suggest a high degree of activity of this combination chemotherapy in patients with brain metastases from NSCLC.     

Additional value of whole-body fluorodeoxyglucose positron emission tomography in the detection of distant metastases of non-small-cell lung cancer

The purpose of this work was to evaluate the additional value of whole-body positron emission tomography (WB-PET) in the distant staging of non-small-cell lung cancer (NSCLC). One hundred forty-four patients with NSCLC in whom conventional staging (CS) was negative or equivocal for metastases, and who underwent WB-PET as part of their initial work-up, were retrospectively analyzed. Conventional staging consisted of thoracic computed tomography (CT), upper abdominal ultrasound and/or CT, and bone scintigraphy or brain CT on indication. Final M stage was based on histology, additional imaging, or follow-up of = 18 months. An additional lesion suspect for metastasis was found on WB-PET in 11 patients. This was true positive in 7 (3 bone, 1 retroperitoneal lymph nodes, 1 lung, and 2 asymptomatic coexisting colorectal cancer) and false positive in 4 patients (3 bowel, 1 breast). Twenty-four lesions in 21 patients remained equivocal after CS. Whole- body PET correctly characterized 20 lesions in 18 patients as true positive (n = 1) or true negative (n = 19). Whole-body PET was false positive in one patient (adrenal adenoma) and false negative in 2 patients (2 bone, 1 lung lesion). Despite negative results of modern CS and WB-PET, 16 of 86 patients (19%) who underwent a curative resection, experienced a systemic relapse. After thorough modern CS, WB-PET correctly detected additional distant malignant lesions in only 5% of the patients, while the combined staging strategy probably still misses micrometastatic disease in one fifth of the patients. The most important contribution of WB-PET was its ability to exclude malignancy in the majority of distant lesions with equivocal CS.     

EGFR不同突变亚型与肺腺癌脑转移预后的相关性分析

目的 探讨肺腺癌脑转移患者EGFR不同突变亚型与预后的相关性。方法 回顾分析2010—2015年本院收治的经EGFR基因突变检测的肺腺癌脑转移患者256例临床资料,筛选脑转移的预后影响因素。Kaplan-Meier法计算生存率Logrank法检验和单因素预后分析,Cox模型多因素预后分析。结果 全组患者中位生存期为10.13个月。单因素分析显示性别、EGFR突变状态、19外显子缺失突变、脑转移时KPS评分、靶向治疗与预后有关(P=0.006、0.001、0.010、0.000、0.003),多因素分析显示脑转移时KPS评分、19外显子缺失突变为脑转移患者预后影响因素(P=0.000、0.045)。将全组病例纳入RPA预后分级指数,检验显示差异有统计学意义(P=0.000)。结论 19外显子缺失突变是肺腺癌脑转移患者的预后影响因素,可以考虑将其纳入肺腺癌脑转移瘤预后评分系统。EGFR-TKI使EGFR基因突变肺腺癌脑转移患者生存获益,尤其是19外显子缺失突变患者。     

ALK阳性非小细胞肺癌脑转移患者的治疗

背景与目的间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）阳性非小细胞肺癌（non-small cell lung cancer, NSCLC）是肺癌的一个重要亚型。ALK阳性NSCLC脑转移患者的治疗尚无标准模式。方法本研究对我院2013年3月-2016年3月期间确诊的ALK阳性NSCLC脑转移患者的临床资料和治疗情况进行回顾性分析,探讨不同治疗模式患者的转归。结果84例晚期ALK阳性NSCLC患者中,22例初诊时有脑转移,剔除3例合并表皮生长因子受体（epidermal growth factor receptor, EGFR）双突变患者,共19例纳入分析。中位颅内疾病进展时间（progression-free survival, PFS）为12.0个月,一线脑部局部治疗（P=0.021）及一线克唑替尼治疗（P=0.030）可延长PFS;一线克唑替尼联合脑部局部治疗的中位颅内PFS为27.0个月,而单纯克唑替尼治疗的PFS仅为4.2个月。结论一线克唑替尼联合脑部局部治疗有助于延长ALK阳性晚期NSCLC患者的颅内PFS,因例数少,尚有待大样本多中心前瞻性临床研究证实。     

Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI)

BACKGROUND: The aims of this study were to show 1) the effect of changing from computed tomography (CT) to magnetic resonance imaging (MRI) on the prevalence of detected brain metastases (BM) in patients with newly diagnosed small cell lung cancer (SCLC); 2) the difference in survival between patients with single and multiple BM; and 3) the effect of the change in patient labeling on eligibility for prophylactic brain irradiation. METHODS: From 1980 to 2004, 481 consecutive patients with SCLC were enrolled. Brain imaging was routinely performed after diagnosis of SCLC. At the start of 1991, MRI replaced CT in almost all patients. All patients were regularly examined by a neurologist. RESULTS: The prevalence of detected BM was 10% in the CT era and 24% in the MRI era. In the CT era, all detected BM were symptomatic, whereas in the MRI era, 11% were asymptomatic. In both periods, patients labeled as single BM survived longer than those labeled as multiple BM. For patients labeled as single BM or multiple BM, survival was longer in the MRI era than in the CT era. The proportion of patients who were eligible for prophylactic cranial irradiation was lower in the MRI era. CONCLUSIONS: The estimated prevalence of BM increases when MRI is used instead of CT. Patients with a detected single BM survive longer than patients with multiple BM. The apparently increased survival in the MRI era can be attributed to the "Will Rogers phenomenon". The use of MRI makes fewer patients eligible for prophylactic cranial irradiation.     

Significance of Brain Imaging for Staging in Patients With Clinical Stage T1-2 N0 Non–Small-Cell Lung Cancer on Positron Emission Tomography/Computed Tomography

BackgroundRoutine positron emission tomography/computed tomography (PET/CT) has been recommended even for clinical stage I non–small-cell lung cancer (NSCLC). In spite of the progress in the screening procedure, and revisions to TNM classification, there is no evidence to support brain imaging screening of patients assessed with the current staging protocol including PET/CT.Materials and MethodsWe retrospectively investigated the frequency of extrathoracic metastasis in 466 consecutive patients with clinical stage T1-2 N0 NSCLC with the complete staging assessment comprised of thin-section CT, PET/CT, and brain contrast-enhanced magnetic resonance imaging between 2008 and 2016. All patients were reclassified according to the eighth edition of the tumor, node, and metastasis (TNM) classification.ResultsAmong all patients, 70% of the tumors were pure solid and 30% had part-solid ground-glass opacity on thin-section CT, and 388 (83%) and 78 (17%) were classified into clinical stages T1 and T2, respectively. Eight patients (1.7%) had extrathoracic metastasis, including 3 (0.6%) with brain metastasis, and all showed pure-solid tumors. The frequency of extrathoracic and brain metastasis was 1.0% and 0.5% in 388 T1 patients, and 5.0% and 3.0% in 78 T2 patients. Although brain metastases were detected in 2 of 7 patients (29%) with PET/CT detectable extrathoracic metastases and 1 of 459 patients (0.2%) without PET/CT detectable extrathoracic metastasis, there were no neurologically asymptomatic brain metastases in patients with early-stage NSCLC confirmed by PET/CT.ConclusionRoutine screening of brain imaging is unnecessary in patients with early-stage NSCLC, assessed with the current staging protocol including PET/CT.     

Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging.

PURPOSE: To compare the respective sensitivity of somatostatin receptor scintigraphy (SRS), computed tomography (CT), and magnetic resonance imaging (MRI) in the detection of liver metastases from well-differentiated gastroenteropancreatic endocrine tumor (WDGEP ET) patients. To define predictive factors for "high-sensitivity SRS." PATIENTS AND METHODS: Sixty-four patients with WDGEP ET underwent SRS with abdominal single-photon emission computed tomography (SPECT), spiral CT, and 1.5-T MRI within a 15-day interval, the order of which was randomized. Two readers analyzed images of each modality, blindly and independently. RESULTS: Hepatic metastases were present in 40 of the 64 patients and confirmed by pathology after liver biopsy or surgery in 32 and eight patients, respectively. SRS, CT, and MRI detected a total of 204, 325, and 394 metastases, respectively. The number of detected metastases was significantly higher with MRI than with CT (P = .02) and SRS (P < 10(-4)) and higher with CT than with SRS (P < 10(-4)). SRS was negative in seven patients with a positive CT and/or MRI. More lesions were detected in 10 patients by SPECT compared with static views. The median metastasis size was significantly correlated (P = .04) with the sensitivity of SRS. CONCLUSION: MRI seems to have an edge over CT and SRS for the detection of liver metastases from endocrine tumors. We recommend the systematic performance of liver MRI at WDGEP ET initial staging and before major therapeutic events. The low performance of SRS was mainly explained by the impact of the metastasis size on the detection capacity of SRS.     

Ferumoxide-enhanced magnetic resonance imaging techniques in pre-operative assessment for colorectal liver metastases.

AIM: The objective was to evaluate whether contrast-enhanced magnetic resonance imaging (MRI) techniques used in a pre-operative assessment protocol for colorectal liver metastases are as accurate as spiral computer tomography during arterial portography (CTAP). Pre-operative accuracy and clinical consequences of MRI are described and compared with CTAP. Moreover, post-operative survival rate and tumour recurrence were studied. METHODS: The study group comprised 84 patients which were possible candidates for a partial hepatectomy for colorectal liver metastases. Patients were pre-operatively evaluated by CT of the abdomen, CT of the thorax and spiral CTAP and ferumoxide-enhanced MRI was performed in routine way for all patients. Following this selection, 35 patients underwent a partial hepatectomy with curative intent. All patients were retrospectively evaluated. RESULTS: Ferumoxide-enhanced MRI proved to be at least as accurate as spiral CTAP in 81% of patients. In nine patients (11%) spiral CTAP revealed more intrahepatic lesions than MRI; in only two patients (2%) did these foundings influenced the clinical decision. These patients were considered to have irresectable disease. In seven patients (8%) MRI detected more lesions than spiral CTAP and influenced the clinical decision in three patients (4%) and these did not undergo a laparotomy. The actuarial 3 year overall survival of operated patients was 41% and the actuarial 3 year disease-free survival was 19%. CONCLUSION: Evaluation of the clinical impact of a pre-operative assessment protocol extended with ferumoxide MRI techniques demonstrated that this non-invasive MRI technique is safe and at least as accurate as spiral CTAP. This MRI technique results in comparable clinical decisions and outcome after hepatectomy. We suggest that the performance of routine contrast-enhanced MRI should instead be used in the pre-operative evaluation of colorectal liver metastases.     

Coregistered whole body magnetic resonance imaging‐positron emission tomography (MRI‐PET) versus PET‐computed tomography plus brain MRI in staging resectable lung cancer

BACKGROUND:

The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging‐positron emission tomography (MRI‐PET) would increase the number of correctly upstaged patients compared with WB PET‐computed tomography (PET‐CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC).

METHODS:

From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI‐PET or WB PET‐CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging.

RESULTS:

Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI‐PET group and in 26 of 120 patients (21.7%) in the PET‐CT plus brain MRI group (4.2% difference; 95% confidence interval, ?6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI‐PET group and in 7 of 120 patients (5.8%) in the PET‐CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%‐20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (?10.7% difference; 95% confidence interval, ?20.1% to ?1.4%; P = .022).

CONCLUSIONS:

Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI‐PET did not appear to help identify significantly more correctly upstaged patients than PET‐CT plus brain MRI in patients with NSCLC. Cancer 2013. © 2013 American Cancer Society.     

Is early recognition of radiologically silent brain metastasis from breast cancer beneficial? A retrospective study of 22 cases

Over a period of 10 years, twenty-two patients with T2-3N2Mx breast cancer presented with symptoms of increased intracranial pressure (ICP), but brain CT scan and/or MRI did not reveal any signs of a space occupying lesion. A brain CT scan and an MRI study were performed every 15 days. Ten patients refused this close follow up. Thus, two groups were formed group A (n = 12) included the patients who were close's followed and group B (n = 10) consisted of those patients who were not. Therefore, Group A, being under careful follow-up, initiated radiotherapy were quickly. The median time from the presentation of increased ICP symptoms until the appearance of metastases on CT and/or MRI directly followed by brain irradiation was 48 days (SE = 6.1) for group A and 72 days (SE = 0.7) for group B (p = 0.0085, log-rank test). In group A, median Overall Survival (OS) was 171.0 (SE = 21.5) days, and was 99.0 (SE = 6.3) days (p = 0.014) for group B. Volumetric analysis of the secondary brain lesions at the initiation of radiotherapy showed a total volume of metastatic lesions of 19.5 +/- 13.9 cm3 versus 65.3 +/- 20.7 cm3 for groups A and B, respectively (p < 0.001, Mann-Whitney test). Post-radiotherapy, Karnofsky Performance Status and Visual Analogue Score were also improved for group A versus B (p = 0.002). Group A appeared to benefit from close follow-up since the metastases were detected and irradiation was given sooner compared with group B, thus achieving better performance status and prolonged survival. Radiologically silent brain metastases from breast cancer should not be ignored because timely whole brain irradiation should be the goal of clinicians. Clinical suspicion should lead to close follow-up with multiple CT/MRI studies and cerebral spinal fluid cytology until the final diagnosis.     

18F-FDG PET/CT在鼻咽癌诊断及分期中的临床价值

背景与目的:PET/CT能够通过准确显示肿瘤形态、大小及相邻关系从而对鼻咽癌(NPC)进行诊断及分期研究.本研究结合PET/CT、MRI结果及部分颈部小淋巴结病理结果,探讨18SF-FDG PET/CT在鼻咽癌TNM分期中的价值.方法:从2005年9月至2007年3月.选取行PET/CT和MRI检查的鼻咽癌患者68例.PET数据采用2D采集模式,CT扫描电压140 kV,采用自动毫安量跟踪扫描加血管增强的扫描方案,18F-FDG按3.7～5.5 MBq/kg剂量静脉注射.MRI检查采用T1W和T2W成像及T1W增强扫描成像.并对其中10例患者颈部小淋巴结切除和穿刺组织病理检查,进行图像与病理对照.结果:68例鼻咽癌患者所有鼻咽区域的病灶PET/CT均可以清晰显示,MRI和PET/CT显示病灶一致:对于直径≤1 cm的138枚PET/CT示阳性小淋巴结,MRI仅有约28%可作不肯定提示.10例鼻咽癌患者颈部16枚PET/CT显示阳性小淋巴结与病理结果相符14枚,符合率达87.5%.对于颈部肿大淋巴结PET/CT.和MRI均能显示,对部分放疗过程PET/CT示增殖活性明显受抑制的肿大淋巴结,MRI和PET/CT增强扫描可见强化.对于其中8例Ⅳb期鼻咽癌患者肺、骨、肝脏等转移灶,PET/CT全身扫描可清晰显示病灶,而MRI具有较多限制.由于18F-FDG PET/CT检查使其中24例的分期进行调整.结论:18F-FDG-PET/CT扫描采用自动毫安量跟踪扫描加血管增强的扫描方案,充分利用PET/CT信息进行鼻咽癌的临床分期,其结果较MRI全面、可靠.     

SPECT骨显像联合血清碱性磷酸酶检测评估肺癌患者骨转移负荷的价值

目的:探讨SPECT骨显像结合碱性磷酸酶(ALP)评估初诊肺癌骨转移负荷的价值.方法:109例初诊未治疗肺癌患者行99Tcm-MDP SPECT全身骨显像,其中发生骨转移51例,无骨转移58例;根据骨显像发现骨病灶数目及受累情况,将骨显像分为0-3级,并检测血清ALP水平;比较各组骨显像分级ALP水平,进行相关分析.结果:109例初诊肺癌患者,转移率46.8％ (51/109);骨显像1-3级患者存在外周血ALP不同程度增高,波动范围127 ～ 782 U/L;0-3级各组ALP检测值分别为[(110.26 ±42.13) U/L,58例]、[(138.85±86.72) U/L,16例]、[(267.84±147.52) U/L,15例]、[(481.46 ±289.73) U/L,20例].各组ALP水平除骨显像0级组与1级组之间差异无统计学意义(t=1.346,P＞0.05);其它各组随着骨显像分级升高,ALP值逐渐增高,且各组间差异有统计学意义(P＜0.05).血清ALP水平与骨显像分级呈正相关(r=0.945,P＜0.01).骨显像1级组中有4例患者,每例有2个异常浓聚灶,其中1个病灶经CT或MRI确定为骨转移,但另外1个病灶不能确定是否骨转移;2例患者ALP升高,2例ALP正常;随访半年,2例ALP正常患者的病灶排除骨转移,另外2例ALP升高患者的病灶确定为转移.结论:SPECT骨显像结合初诊肺癌ALP水平对评估肺癌骨转移负荷存在一定价值;值得临床重视与应用,以合理地肺癌分级等.     

Cerebrospinal fluid M staging for medulloblastoma: reappraisal of Chang's M staging based on the CSF flow

Tumor seeding is a strong negative prognostic factor for patients with medulloblastoma. Because Chang's M staging is based primarily on CT and myelographic findings and might be contradictory to the direction of normal cerebrospinal fluid (CSF) flow, seeding patterns and appropriate staging of medulloblastoma need to be revisited in patients diagnosed in the MRI era. We retrospectively reviewed the clinical and radiological data of 86 patients with a diagnosis of medulloblastoma who were treated in the MRI era. The presence of seeding in each subarachnoid space compartment and the patterns of seeding were analyzed in correlation with patient survival data. Thirty-four patients had gross seeding on perioperative MRI. Thirty-two patients had seeding in the spinal compartment. Sixteen and 12 patients had seeding in the infratentorial and supratentorial compartments, respectively. There was an apparent hierarchy of seeding (ie, from seeding in the spinal compartment up to the supratentorial compartment). Patients with seeding in the spinal compartment had longer progression-free survival (P = .038) and a tendency toward better overall survival (P = .053) compared with patients with seeding in intracranial compartments. We modified Chang's M staging based on the CSF flow and termed this approach "CSF M staging." CSF M staging for medulloblastoma, in which intracranial seeding occupies a higher rank than spinal seeding, was a better predictor of patient prognosis. This modified staging method may be applied to metastatic staging of brain tumors located in the fourth ventricle.     

Near Total Regression of Diffuse Brain Metastases in Adenocarcinoma of the Lung with an EGFR Exon 19 Mutation: A Case Report and Review of the Literature

We report the case of a woman with diffuse brain metastases from lung cancer who experienced total regression of the metastases under gefitinib treatment. The 58-year-old woman was referred to our hospital with a complaint of severe headache. A brain MRI revealed diffuse metastatic lesions in the cerebra and cerebellum. Adenocarcinoma of the lung with multiple brain metastases was diagnosed. The tumor was positive for an epidermal growth factor receptor (EGFR) exon 19 deletion mutation. She was treated with gefitinib 250 mg per day. One year later, the diffuse brain metastases had totally resolved. EGFR-tyrosine kinase inhibitor therapy could be a first-line treatment for patients with advanced adenocarcinoma of the lung with EGFR mutation, especially in those with brain metastases.     

Brain metastases following radical surgical treatment of non-small cell lung cancer: Is preoperative brain imaging important?

Objectives

There is a lack of good quality evidence or a clear consensus of opinion internationally regarding who should receive preoperative imaging of the brain prior to radical treatment for non-small cell lung cancer (NSCLC). We aimed to establish the proportion of patients who developed brain metastases following curative surgery and to estimate how many could have been detected by preoperative magnetic resonance imaging (MR).

Methods

We performed a retrospective analysis of 646 patients who underwent surgery for lung cancer with curative intent at a regional thoracic surgical centre in the United Kingdom. We identified those who developed brain metastases in the postoperative period and, by using volume doubling times, estimated the size of the metastasis at the time of surgery. We then determined the proportion of metastases that would have been seen on preoperative MR brain at detection thresholds of 2 and 5 mm diameter.

Results

There was a 6.3% incidence of postoperative brain metastases, with the majority occurring within 12 months of surgery. Those who developed metastases were more likely to have adenocarcinoma and the majority had early stage malignancy (73% stage I or stage II).We estimate that 71% of those who developed cerebral metastases might have been detected had they undergone MR brain as part of their staging (4.4% of all patients).

Conclusion

Based on our findings we suggest that, in addition to standard staging investigations, patients have brain imaging (MR or equivalent) prior to curative surgery in NSCLC regardless of preoperative stage.     

A study of patients with brain metastases as the initial manifestation of their systemic cancer in a Chinese population

To investigate the clinical characteristics of patients with brain metastases as the initial manifestation of their systemic cancer in a Chinese population, a retrospective study of 254 such patients admitted to Huashan Hospital, Fudan University, Shanghai, China between January 1, 2003 and December 30, 2008 was performed. Data were collected to determine the features of this group (i.e., manifesting signs and symptoms, imaging studies, extracerebral metastases, primary tumor sites, initial diagnosis, and survival data). Common symptoms included headache and motor impairment. The distribution of brain metastases paralleled blood flow, and the majority of brain metastases were located in the cerebral hemispheres. Magnetic resonance imaging (MRI) was more sensitive than computed tomography (CT) for confirming presence of brain lesions. This distinct clinical entity exhibited high rates of misdiagnosis at initial presentation. Pathology varied, and adenocarcinomas were most commonly observed. Underlying primary tumors were identified in 84.2% of patients, most often located in lung (71.7%), followed by digestive tract. Chest CT had high yield. Sixty-two patients presented with silent extracerebral metastases at initial presentation. Median survival time was 15 months (95% confidence interval, 12.2–17.8 months). Survival rates for 1, 2, and 5 years were 59.2%, 23.2%, and 15.1%, respectively. Contrast-enhanced MRI had high yield for detection of brain metastases. Adenocarcinoma was the most common histologic type. Given the high frequency of primary lung tumors and the sensitivity of chest CT, chest CT should be a part of the initial screen of primary site with brain metastases as the initial manifestation. Metastatic dissemination of malignancy to the brain as the initial manifestation is generally associated with dismal prognosis, with the exception of a minority who experience long survival.     

Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response.

PURPOSE: Whole-brain radiation therapy (WBRT) has been applied to inoperable brain metastases in lung adenocarcinoma. Recently, an in vitro study showed reduced clonogenic survival of mutant epidermal growth factor receptor (EGFR) lung cancer cell lines in response to ionizing radiation compared with that of the wild type. To elucidate the role of EGFR mutations in radiation treatment, we evaluated the clinical response to WBRT and survival of lung adenocarcinoma patients with brain metastases. EXPERIMENTAL DESIGN: This was a retrospective analysis of 63 patients with brain metastases from lung adenocarcinoma who were treated with WBRT. Demographic data, EGFR mutation status, response to WBRT, and survival data were collected. Clinical response was assessed 1 month after the start of WBRT. Univariate and logistic regression models were used to test potential predictive factors associated with clinical response. Log-rank test and Cox regression were analyzed to identify factors that affected survival. RESULTS: Clinical response to WBRT was observed in 29 patients (46%), with 34 nonresponder patients (54%). Patients with EGFR mutations had higher response rates to WBRT compared with those with the wild-type (54% versus 24%; P = 0.045). Both the administration of EGFR tyrosine kinase inhibitor (P = 0.034) and EGFR mutation (P = 0.029) were independently associated with response to WBRT. In Cox regression analysis, WBRT responder (P = 0.010) and absence of extracranial metastases (P = 0.002) were associated with better survival. CONCLUSIONS: Both the EGFR mutations and the administration of EGFR TKI during WBRT were independent predictors of response to WBRT in brain metastases of lung adenocarcinoma.     

Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer

Background  Recently, a high rate of brain metastases has been reported among patients with human epidermal growth factor receptor (HER2)-overexpressing metastatic breast cancer who were treated with trastuzumab. The present study examined risk factors for the development of brain metastasis in patients with HER2-overexpressing breast cancer who were treated with trastuzumab. Methods  We retrospectively reviewed 204 patients with HER-2-overexpressing breast cancer who were treated with a trastuzumab-containing regimen between 1999 and 2006. Patients with clinical symptoms were diagnosed as having brain metastases when brain magnetic resonance imaging (MRI) or a computed tomography (CT) scan revealed positive findings for brain metastases. The median follow-up time of this cohort was 53.6 months. Results  Among the patients who received a trastuzumabcontaining regimen, 74 patients (36.3%) developed brain metastases. The median survival from the diagnosis of brain metastases was 13.5 months (95% confidence interval [CI], 12.2–14.7 months). The median time interval between the beginning of trastuzumab treatment and the diagnosis of brain metastases was 13.6 months (range, 0.0–45.8 months). Among patients with brain metastases, the median overall survival period was 39 months. A multivariate logistic regression analysis showed that age (≤50 years), recurrent breast cancer, and liver metastases were significant risk factors for the development of brain metastases. Conclusion  Patients with HER2-overexpressing breast cancer treated with trastuzumab had a high incidence of brain metastases (36.3%). Routine screening for brain metastases 1 year after the start of trastuzumab treatment, may be warranted in younger patients (≤50 years) who had recurrent breast cancer with liver metastases.