Two patients of recurrent breast cancer with carcinomatous pleurisy well controlled pleural effusion

We report two patients of recurrent breast cancer with carcinomatous pleurisy well controlled pleural effusion. One patient is a 49-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy and extended right lobectomy of the liver were performed in December 2001. Right pleural effusion was detected in December 2003, then, pleurodesis was carried out with OK-432 after thoracic drainage. After pleurodesis, a weekly paclitaxel therapy was started and she was taking the regimen continuously. Another patient is a 55-year-old woman. She underwent radical mastectomy for left breast cancer in September 1999. Local recurrent lesions on the left chest and left pleural effusion were found in May 2003. After thoracic drainage, infectious pleurisy was complicated, so the drainage tube was removed after the therapy for preventing infection. After pleurodesis, CE therapy followed by peroral chemo-endocrine therapy was performed. Both of the two patients are receiving outpatient treatment without recurrent pleural effusion as of July 2005.     

Two cases of lung cancer patients with postoperative brain metastases obtaining long-term survival after gamma knife radiosurgery

We report two cases of lung cancer patients with postoperative solitary brain metastases obtaining long-term survival after gamma knife stereotactic radiosurgery. Both were seventies men and had good performance status without active extracranial disease. In one case, an asymptomatic metastatic brain tumor 1.8 cm in maximum diameter appeared one year and two months after the operation and was irradiated with gamma knife resulting in complete local control for seven years. He is alive with solitary lung metastasis in good performance status. In the other case, gamma knife was employed for a metastatic brain tumor 2.7 cm in maximum diameter that appeared nine months after the operation accompanying incomplete left hemiplegia. Six months later, the tumor was enlarged and gamma knife was repeated, but the tumor growth could not be suppressed. Following deterioration of hemiplegia and appearance of convulsion, he died of neurological disorder three years and two months after the onset of brain metastasis. Gamma knife stereotactic radiosurgery for metastatic brain tumors is less invasive and a repeatable technique, and is expected to provide a good local control and a survival benefit for appropriately selected patients.     

Leptomeningeal seeding in patients with brain metastases treated by gamma knife radiosurgery

To characterize the development of leptomeningeal seeding (LMS) in patients with brain metastases after gamma knife radiosurgery (GKRS). Eight hundred and twenty-seven patients that underwent GKRS as a part of an initial treatment plan for brain metastases between January 2002 and December 2010 were included in the study. Six hundred and fifty patients were treated with GKRS alone and 177 patients received GKRS combined with upfront whole brain radiation therapy (WBRT). Actuarial curves for overall survival (OS) and the development of LMS were plotted using the Kaplan-Meier method. Median overall survival for all patients was 55?weeks (95 % CI, 47.8-62.2), and the overall incidence of LMS was 5.3 %. The actuarial rates for LMS at 6 and 12 months were 3.1 and 5.8, respectively. Uni- and multivariate analysis suggested that breast cancer and a large number of metastases (n ≥ 4) are significant risk factors of LMS (P < 0.05). Regarding treatment modalities, the addition of WBRT was found to have a significant impact on lowering the risk of LMS by multivariate analysis (P = 0.045). LMS is an important pattern of CNS failure. The risk of LMS following GKRS may be associated with multiple lesions, breast cancer, and the omission of WBRT. Additional data from large-scale, randomized controlled trials are required to identify risk factors associated with the LMS more accurately.     

The efficacy of gamma knife radiosurgery for advanced gastric cancer with brain metastases

The aim of this study was to retrospectively investigate the efficacy of gamma knife radiosurgery for brain metastases from advanced gastric cancer (AGC) comparing whole brain radiotherapy (WBRT). Between January 1991 and May 2008, 56 patients with brain metastases from AGC, treated with GKR or WBRT, were reviewed to assess prognostic factors affecting survival. Most brain metastases were diagnosed based on MRI, both metachronous and synchronous brain metastases, adenocarcinoma and signet ring carcinoma were included, but excluded cases of gastric lymphoma. Fifteen patients with a median age of 54.0 years (range, 42–67 years) were treated with GKR: 11 were treated with GKR only, 2 with surgery plus GKR, 1 with repeated GKR, 1 with GKR plus WBRT, and the other 1 with WBRT plus GKR. Forty-one were treated with WBRT only. The median number of metastatic brain lesions was 3 (range, 1–15), and treatment involved 17.0 Gy (range 14–23.6 Gy), or 30 Gy with fractionated radiotherapy. The median survival after brain metastases for GKR treatment was 40.0 weeks [95% confidence interval (CI) 44.9–132.1 weeks] and WBRT was 9.0 weeks 95% CI, 8.8–21.9 weeks). The progression free survival of 15 GKR treated patients was 56.5 weeks (95% CI 33.4–79.5 weeks). The recursive partitioning analysis (RPA) (class 2 vs. class 3) and use of GKR were correlated with prolonged survival in univariate and multivariate analyses. Age, sex, pathology, leptomeningeal seeding, tumor size (≥3 cm), extracranial metastases, single metastasis, chemotherapy, and synchronous metastases were not correlated with a good prognosis in both univariate and multivariate analysis. Based on our study, the use of GKR and RPA class 2 resulted in more favorable clinical outcomes in patients with brain metastases from AGC.     

Predictive factors of early distant brain failure after gamma knife radiosurgery alone in patients with brain metastases of non-small-cell lung cancer

The objective of this study was to elucidate the predictive factors for early distant brain failure in patients with brain metastases of non-small-cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKRS) without previous whole-brain radiotherapy (WBRT) or surgery. We retrospectively reviewed clinical and imaging data of 459 patients with brain metastases of NSCLC who underwent GKRS from June 2008 to December 2013. The primary end-point was early distant brain failure, defined as the detection of newly developed metastatic lesions on magnetic resonance imaging (MRI) 3 months after GKRS. Factors such as tumor pathology subtype, concurrent systemic chemotherapy, epidermal growth factor receptor (EGFR) mutation status, use of EGFR tyrosine kinase inhibitors (TKIs), systemic disease status, presence of a metastatic lesion only in delayed MRI, and volume and number of metastases were analyzed. There were no statistically significant differences with respect to pathologic subtype, concurrent systemic chemotherapy, EGFR mutation, and early distant brain failure. Patients treated with EGFR-TKIs (p?=?0.004), with a stable systemic disease status (p?=?0.028) and 3 or fewer brain lesions (p?=?0.000) experienced a significantly lower incidence of early distant brain failure. This study suggests that GKRS alone could be considered for patients treated with EGFR-TKIs who have a stable systemic disease status and 3 or fewer brain lesions. WBRT should be considered for other patients.     

Long-term survivors after gamma knife radiosurgery for brain metastases

BACKGROUND: Stereotactic radiosurgery, with or without whole-brain radiation therapy, has become a valued management choice for patients with brain metastases, although their median survival remains limited. In patients who receive successful extracranial cancer care, patients who have controlled intracranial disease are living longer. The authors evaluated all brain metastasis in patients who lived for > or = 4 years after radiosurgery to determine clinical and treatment patterns potentially responsible for their outcome. METHODS: Six hundred seventy-seven patients with brain metastases underwent 781 radiosurgery procedures between 1988 and 2000. Data from the entire series were reviewed; and, if patients had > or = 4 years of survival, then they were evaluated for information on brain and extracranial treatment, symptoms, imaging responses, need for further care, and management morbidity. These long-term survivors were compared with a cohort who lived for < 3 months after radiosurgery (n = 100 patients). RESULTS: Forty-four patients (6.5%) survived for > 4 years after radiosurgery (mean, 69 mos with 16 patients still alive). The mean age at radiosurgery was 53 years (maximum age, 72 yrs), and the median Karnofsky performance score (KPS) was 90. The lung (n = 15 patients), breast (n = 9 patients), kidney (n = 7 patients), and skin (melanoma; n = 6 patients) were the most frequent primary sites. Two or more organ sites outside the brain were involved in 18 patients (41%), the primary tumor plus lymph nodes were involved in 10 patients (23%), only the primary tumor was involved in 9 patients (20%), and only brain disease was involved in 7 patients (16%), indicating that extended survival was possible even in patients with multiorgan disease. Serial imaging of 133 tumors showed that 99 tumors were smaller (74%), 22 tumors were unchanged (17%), and 12 tumors were larger (9%). Four patients had a permanent neurologic deficit after brain tumor management, and six patients underwent a resection after radiosurgery. Compared with the patients who had limited survival (< 3 mos), long-term survivors had a higher initial KPS (P = 0.01), fewer brain metastases (P = 0.04), and less extracranial disease (P < 0.00005). CONCLUSIONS: Although the expected survival of patients with brain metastases may be limited, selected patients with effective intracranial and extracranial care for malignant disease can have prolonged, good-quality survival. The extent of extracranial disease at the time of radiosurgery was predictive of outcome, but this does not necessarily mean that patients cannot live for years if treatment is effective.     

Influence of gamma knife radiosurgery on the quality of life in patients with brain metastases

Quality of life (QOL) is an important issue in the treatment of patients with brain metastases. With median survival times often less than 4 months, less invasive treatment options that maximize QOL parameters are essential. In recent years, stereotactic radiosurgery (SRS) has been commonly used as a noninvasive alternative to surgical resection for such patients. This prospective study was undertaken to evaluate QOL in patients undergoing SRS for brain metastases. Between 1999 and 2000, 20 patients with metastatic disease to the brain were evaluated and treated in our Gamma Knife unit. All patients performed the Spitzer QOL survey (10-point scale) both before stereotactic radiosurgery and at each follow-up visit. Primary sites of disease included lung (n = 10), breast (n = 5), melanoma (n = 2), thyroid (n = 1), uterine (n = 1), and kidney (n = 1). Fifteen (75%) had prior whole brain radiotherapy (median dose: 35 Gy). The median age and Karnofsky Performance Status were 58 years and 80, respectively. The median Spitzer score before SRS was 9 (range: 7-10), and the median follow-up time of the patients in this series was 7 months. The median posttreatment Spitzer score at 1 and 3 months after SRS was 9 (range: 5-10) and 8 (range: 4-10), respectively. Crude intracranial tumor control in this cohort of patients was 90%. Extracranial tumor progression was noted in 8 patients (40%), and in these patients, Spitzer scores tended to decrease in value. In those patients who had no evidence of intracranial or extracranial tumor progression, Spitzer scores remained either unchanged or improved. Gamma knife SRS is an appropriate treatment modality for maintaining QOL parameters in patients with brain metastases. Tumor progression both intracranially and extracranially influences QOL parameters. Confirmation of this finding will require further investigation.     

Solitary brain metastases treated with the Leksell gamma knife: prognostic factors for patients.

PURPOSE: To analyze treatment results, complications, prognostic factors and their statistical significance in surviving patients treated with the Leksell gamma knife (LGK) for solitary brain metastases. MATERIALS AND METHODS: Between 1992-1998, 237 patients were treated with solitary brain metastasis (SBM). The histological subtypes were as follows: 101 patients (42.6%) non small-cell lung cancer, 42 (17.7%) renal cell carcinoma, 36 (15.2%) breast carcinoma, 30 (12.7%) colorectal carcinomas and 28 (11.8%) melanoma. RESULTS: A complete or partial regression was observed in 193 (81.4%) patients, cessation of growth activity in 32 (13.5%) and local progression in 12 (5.1%). Local recurrence was observed in nine (4.7%) of 193 patients with complete or partial regression. Acute toxicity appeared in 24 (10%) patients (score 3.4), late complications (score 3.4) were observed in 13 patients (5.5%). Out of 237 patients, 182 patients died with a median survival of 6 months and 55 patients are still alive with a median survival 12 months and with a minimal follow up period of 10 months. The significant prognostic factors for longer survival in these series of patients were: Karnofsky performance status (70% or more), the extent of extra-cerebral disease (no extra-cerebral disease), pretreatment neurological symptoms neurological functional class (NFC 1), histology (renal cell and breast carcinomas) and the dose to the planning target volume (20 Gy and higher). CONCLUSIONS: Radiosurgery provides an effective local control for 90% of treated patients with low morbidity. Several significant prognostic factors were detected for patients' survival. These factors can help to predict better patients' survival after the LGK treatment.     

非小细胞肺癌脑转移行伽马刀及全脑放射#br# 治疗的效果及预后的影响因素分析#br# #br#

目的探讨立体定向放射治疗(SRT)及全脑放射治疗(WBRT)对非小细胞肺癌(NSCLC)脑转移患者的疗效,分析患者生存预后的影响因素。方法选择2014年6月至2016年1月在东北国际医院接受放疗的140例NSCLC脑转移患者,根据放疗方式不同分为WBRT组(59例)和SRT组(伽马刀,81例)。比较两组患者放疗后3个月的近期疗效、不良反应发生情况及生存情况,绘制Kalpan Meier生存曲线比较两组患者的颅内疾病无进展生存期(PFS)和总生存期(OS);通过Cox比例风险回归模型分析患者生存预后的影响因素。结果SRT组的总有效率高于WBRT组(7531％ vs. 5085％),SRT组的不良反应中恶心呕吐(7531％ vs. 8983％)、昏迷(7037％ vs. 8474％)及急性放射性神经系统损害发生率(7901％ vs. 9322％)显著低于WBRT组,差异均有统计学意义(P<005)。SRT组的中位OS、PFS分别为140(75,285)、75(30,210)个月,均长于WBRT组的60(35,105)、30(15,55)个月,差异均有统计学意义(P<005)。GPA评分低、有颅外转移和颅脑放疗方式WBRT均为NSCLC脑转移患者预后的危险因素。结论伽马刀放射治疗NSCLC脑转移的近期疗效显著,可延长患者生存期并减少不良反应,对具有良好预后因素的患者施行伽马刀放射治疗可能会收到更好的临床疗效。     

脑转移瘤伽玛刀配合全脑放疗的临床研究

目的探讨脑转移瘤伽玛刀治疗配合全脑放疗的疗效。方法自2002年3月至2006年3月收治脑转移瘤患者79例。原发灶控制稳定,脑转移患者中,44例采用伽玛刀配合全脑放疗,35例单纯给予伽玛刀治疗。伽玛刀治疗处方等剂量线采用45%～75%等剂量包绕计划靶区,边缘剂量15～20 Gy,中心30～45 Gy;全脑放疗每次分割剂量为2～3 Gy,1次/d,每周照射5次,总剂量25～30 Gy。结果伽玛刀治疗开始后3个月,复查MRI,影像学结果显示总的有效率为83.5%（66/79）。伽玛刀配合全脑放疗组的1年生存率为29.5%,2年生存率9.1%;单纯伽玛刀组患者的1年生存率为17.1%,2年生存率2.9%。随访期内未见严重放射性并发症。结论对脑转移瘤采用伽玛刀配合全脑放疗是较有效的局部治疗方式,副反应轻,均能耐受治疗。     

乳腺癌脑转移67例临床分析

背景与目的:随着乳腺癌全身治疗疗效的提高和患者生存期的延长,乳腺癌脑转移在临床上越来越常见。本研究通过分析乳腺癌脑转移的临床特点,探讨其治疗方式及预后因素。方法:67例患者出现脑转移距离确诊乳腺癌的时间为0～15年,中位时间为2.5年。治疗方式为手术加放疗3例,单纯放疗30例,单纯化疗3例,放疗加化疗26例,未治疗5例。采用SPSS10.0统计软件进行生存分析,采用Kaplan-Meier分析和log-rank检验进行生存预后分析。结果:乳腺癌脑转移最常见的症状是头痛,脑实质为最常受累部位。全组患者中位生存期为4年,出现脑转移后的中位生存时间为11个月。月经状况、脑转移数目、合并全身转移情况及治疗方式对患者的生存时间均无明显影响。结论:乳腺癌脑转移预后差,目前治疗仍以全脑放疗为主,化疗的作用还需进一步研究。     

The natural history of breast cancer patients with brain metastases.

One hundred one breast cancer patients with brain metastases (BM) were reviewed. The median survival from BM was 4.0 months. Seventy percent were receiving chemotherapy at the diagnosis of BM and 43% were showing a clinical response. Prolonged survival was seen in patients who underwent surgical resection, those with the brain as site of first metastasis, and those with a long free interval who survived the initial 5 months after BM. Long-term survivors (greater than 18 months from BM) demonstrated indolent disease by all parameters measured.     

Tumor-associated fever in recurrent breast cancer with liver metastases

Of 67 patients with recurrent breast cancer accompanied by liver metastases admitted to our facility between January 1990 and August 1993, 8(12%) were found to have tumor-associated fever. We examined the characteristics of these patents. These patients had fever (over 38 degrees C) for more than one week. Their leukocyte counts did not exceed 10000/mm(3), and C-reactive protein (CRP) was below 5 mg/dl in 6 patients. ALL 8 patients had extensive liver metastases. Six patients had massive metastatic lesions, while the remaining 2 had diffuse metastases. Following systemic chemotherapy, 3 patients showed a reduction in tumor size and remission of fever; they remain alive at 14, 16 and 19 months after treatment. Of the remaining 5 patients who did not respond to systemic chemotherapy, 4 died within 6 months. The results of this study suggest that unexplained fever in patients with recurrent breast cancer is closely related to liver metastases.     

Radiation therapy for brain metastases in breast cancer patients

Most randomized comparison trials (RCTs) investigating treatments for brain metastases (BM) have included BM from any origin; as a result, more than half (52.4–77.0%) of the BM in these trials originated from the lungs (mostly non-small-cell lung cancer, NSCLC), with the breasts being the origin in only 6.8–19.0% of cases. In addition, patients with poor systemic status (KPS < 70) were not included in these trials. Hence, before we can apply RCT-based information to the daily clinical treatment of BM from breast cancers, it will be crucial to differentiate the characteristics of BM originating from NSCLC and BM originating from breast cancer. Although stereotactic radiosurgery (SRS) is widely used in Japan, level-1 evidence suggests that the benefit of using SRS in addition to whole-brain radiation therapy (WBRT) has been proven only for patients with a single BM. Treatment with SRS alone, which is widely used in Japan, seems attractive because it could avoid the risk of long-term adverse effects of WBRT. However, level-1 evidence suggests that the omission of WBRT results in a high frequency of brain tumor recurrence (BTR). In an RCT between SRS-alone and SRS + WBRT conducted in Japan, we found that patients who had a single BM and no extracranial metastases had a low risk of developing BTR after initial brain management (low-risk group) compared with those who had 2 or more BM and extracranial metastases (high-risk group). In order to meet the criteria of “low-risk” BTR, patients also should have good systemic status (KPS ≧ 70). Epidemiologic data suggest that the prognosis is twice as likely to be poor in patients with BM from breast cancer (RPA III = KPS < 70) than in patients with BM from NSCLC (40 vs. 20%); in addition, the probability of brain-only metastases in patients with breast cancer is less than half that in patients with NSCLC (20–25 vs. 60–75%). Considering these findings, we should be aware that most patients with BM from breast cancer are not good candidates for SRS alone, and, therefore, the role of WBRT is still important in the era of modern radiation techniques.     

Results of whole brain radiotherapy in patients with brain metastases from breast cancer: a retrospective study

PURPOSE: To analyze the factors that affect survival in patients with brain metastases (BM) from breast cancer who were treated with whole brain radiotherapy (WBRT). METHODS AND MATERIALS: We identified 116 women with breast cancer who were treated with WBRT alone between February 1984 and September 2000. All patients had treatment and follow-up data available in their medical charts, which we extracted for this retrospective study. We evaluated a number of potential predictors of survival after WBRT: age, primary tumor stage, control of primary tumor, presence of other systemic metastases, site of systemic metastases, Karnofsky performance status, Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, total dose of WBRT, and number of BM. Eighteen patients received a total dose >3000 cGy and 7 received a partial brain boost. RESULTS: For the entire cohort, the median survival from the start of WBRT was 4.2 months. The 1-year survival rate was 17%, and the 2-year survival rate was 2%. Using univariate analysis, only Karnofsky performance status (p = 0. 0084), recursive partitioning analysis class (p = 0. 0147), and total WBRT dose (p = 0.0001) were predictive of longer survival. In multivariate analysis, Karnofsky performance status was the only significant predictor. CONCLUSION: Overall survival in breast cancer patients with BM treated with WBRT is poor. We recommend breast cancer patients with BM be enrolled in prospective trials to improve results.     

Chemotherapy for breast cancer brain metastases

Breast cancer is the second most common cause of brain metastases, and 10-15% of patients develop clinically overt central nervous system disease. Radiotherapy is the standard treatment for patients with brain metastases. Surgical resection should be considered in patients with isolated brain metastasis and no extracranial disease. The role of chemotherapy in breast cancer brain metastases is not clearly defined; the results of the 8 trials found in the literature are reported. Most experience has been gained with the CMF (cyclophosphamide, methotrexate and fluorouracil) and PE (cisplatin and etoposide) regimens; here the median survival of 6 months is similar to radiotherapy. The blood-brain barrier, maintained by tight endothelial junctions and active transport mechanisms, is a major reason for the lower activity of most chemotherapeutic agents compared to other sites of metastatic disease. Most substances with good penetration of the blood-brain barrier have limited activity against breast cancer and some of the most active substances in breast cancer - including doxorubicine, the taxanes and trastuzumab - appear not to reach the central nervous system in sufficient concentrations. Approaches to overcome the blood-brain barrier are still experimental, and more research is clearly needed to identify chemotherapeutic agents both active in breast cancer and with good penetration of the blood-brain barrier. With the exception of patients with resectable brain metastases, danger of cranial herniation or poor general condition, chemotherapy should be offered to breast cancer patients with brain metastases that have progressive extracranial metastatic disease or relapse after radiotherapy.