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.     

Prolonged survival after resection and radiotherapy for solitary brain metastases from non‐small‐cell lung cancer

Selected patients with brain metastases from non‐small‐cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose–volume considerations.     

Long-term survival after brain metastasis from endometrial cancer

A case is reported of prolonged survival after radical hysterectomy for poorly differentiated adenocarcinoma of the endometrium and resection of metastatic carcinoma of the brain followed by radiation therapy. The 43-year-old patient has survived for seven years after hysterectomy and six years 10 months after excision of the brain metastasis. Our results show that the surgical excision of a single metastatic lesion of the brain with postoperative irradiation offers hope of prolonged survival in patients with a solitary brain metastasis and no evident systemic disease.     

Long-term survival in patients with synchronous, solitary brain metastasis from non-small-cell lung cancer treated with radiosurgery

PURPOSE: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). PATIENTS AND METHODS: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. RESULTS: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS >or=90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). CONCLUSIONS: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy.     

Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer

Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients.     

乳腺癌脑转移瘤立体定向放疗预后因素分析

目的 探讨乳腺癌脑转移行立体定向放疗(SRT)的预后影响因素。方法 回顾分析 37例行SRT的乳腺癌脑转移患者,其中首程行单纯SRT 19例,首程行全脑放疗(WBRT)加SRT 8例(WBRT与SRT间隔时间<2个月),WBRT失败后行SRT挽救患者 10例。Kaplan-Meier法计算生存期,Logrank法单因素预后分析,Cox模型多因素预后分析。结果 全组患者中位随访时间11个月,仍生存患者中位随访时间15个月。全组中位生存期11个月(95% CI=6~16个月)。单因素预后分析显示三阴性乳腺癌(χ²=5.95,P=0.004)、卡氏评分低(χ²=13.85,P=0.000)、原发灶诊断至脑转移间隔时间≤30个月(χ²=6.62,P=0.010)、RPA分级差(χ²=15.35,P=0.000)及WBRT后复发(χ²=4.43,P=0.035)是SRT预后不良因素,多因素预后分析显示三阴性乳腺癌(χ²=9.58,P=0.008)、卡氏评分低(χ²=6.65,P=0.010)及WBRT后复发(χ²=3.95,P=0.047)是SRT预后不良因素。结论 三阴性乳腺癌、卡氏评分低及WBRT后复发是乳腺癌脑转移后行SRT的预后不良因素。     

A case report of long-term survival after radiotherapy for a solitary brain metastasis from breast cancer

This is the report of a patient with a solitary brain metastasis from breast cancer who survived more than 8 years after the first brain metastasis. The brain metastasis was treated with partial removal followed by 30 Gy/15 fructions of whole brain irradiation plus 20 Gy/10 fructions of local boost irradiation for 5weeks. Brain metastases from breast cancer are usually a sign of rapid systemic tumor progression and long-term survivors are extremely rare. However, this case demonstrated the possibility of long-term survival in rare cases of brain metastases from breast cancer. This suggests a need for aggressive therapy in patients with a solitary brain metastasis.     

45例肺癌脑转移放射治疗后生存期的影响因素

背景与目的脑转移在肺癌患者中发生率很高,一旦发生后生存期极短。本研究对本院放疗科治疗的肺癌脑转移患者的生存期作初步总结,为今后的临床治疗提供一些有关生存期的参考数据。方法选择我院2000年1月—2005年1月放疗科就诊的原发性肺癌,经CT或MRI证实有脑转移患者。KPS>50的患者平均年龄(60.4±8.4)岁全组病例均采用6~8MVX线,全颅两侧野对穿照射,肿瘤量40Gy/4周,对单发病灶再缩野局部追加肿瘤量10~20Gy/1~2周。从开始全脑放疗到患者死亡。结果①经过颅脑放疗,剂量在40~60Gy(均数51Gy),平均生存期可达到(8.0±5.9)个月。②肺癌原发灶是否控制,有否肺或骨转移,是影响生存期和预后的因素。③脑转移单发组的生存期比多发组略长。结论肺癌原发灶是否控制,有否肺或骨转移,是影响生存期和预后的因素。     

Correlation of changes between 2-year disease-free survival and 5-year overall survival in adjuvant breast cancer trials from 1966 to 2006.

BACKGROUND: Although disease-free survival (DFS) is accepted as a valid end point in adjuvant breast cancer trials, improvement in 2-year DFS has never been formally established as an adequate correlate for 5-year overall survival (OS). We set out to ascertain if changes in 2-year DFS can be used to accurately predict 5-year OS changes. DESIGN: We conducted a systematic Medline search (1966-2006) for randomized adjuvant breast cancer trials of >100 patients per arm with 2-year DFS and 5-year OS data. A univariate regression model weighted by trial sample size was constructed to determine whether 2-year DFS differences between treatment arms within trials were predictive of 5-year OS differences. RESULTS: A total of 126 studies containing 149 treatment comparisons met the inclusion criteria. Difference in 2-year DFS was a significant predictor of difference in 5-year OS. For every 1% increase in 2-year DFS difference, the 5-year OS difference increased by 0.5%-0.55%. The proportion of variation explained ranged from 0.38 to 0.42, with a wide prediction interval. CONCLUSION: There is a statistically significant correlation, of moderate strength, between difference in 2-year DFS between treatment comparisons and difference in 5-year OS but the correlation is not strong enough to be used as a predictor.     

Favourable long-term results after surgical removal of lung metastases of breast cancer

We retrospectively evaluated whether a surgical strategy benefits patients with operable lung metastasis of breast cancer. Between 1960 and 2000, 90 patients (mean age 55.1; range 32-77) with lung metastasis (79 solitary, 11 multiple) underwent surgery as follows: wedge resection (n = 10), segmental resection (n = 11), lobectomy (n = 68) and pneumonectomy (n = 1). The metastases were completely resected in 89% of them. One patient died due to surgical complications. The overall 5- and 10-year cumulative overall survival rates were 54% and 40%, respectively (median, 6.3 years). Fifteen patients survived without relapse for over 10 years. They were 24% of those who progressed for 10 years or more after lung surgery. The most significant prognostic factor was disease-free interval (DFI) and stage at breast surgery. The 10-year survival rates of those with >==3 and <3 years of DFI were 47% and 26%, respectively (P = 0.014). Survival times were significantly longer for patients with clinical stage I at breast surgery than those with stage II-IV (P = 0.013). Our data, although limited and highly selective, suggest that surgical approach to lung metastasis from breast cancer may prolong survival in certain subgroups of patients to a greater extent than systemic chemotherapy alone. Surgical approach to lung metastasis of breast cancer, if possible, should be a treatment of choice to a great extent.     

全脑放疗联合卡培他滨同步化疗治疗乳腺癌术后脑转移的临床观察

 目的　观察全脑放疗联合卡培他滨同步化疗治疗乳腺癌患者术后脑转移的疗效及不良反应。方法　50例乳腺癌术后脑转移患者信封法随机分为治疗组（全脑放疗联合卡培他滨同步化疗）和对照组（单纯全脑放疗）各25例。治疗组全脑照射为2 Gy／次,5次／周,总剂量40 Gy,放疗开始第1天给予卡培他滨850 mg／m2口服,2次／d,至放疗结束;对照组全脑照射同治疗组。放疗结束后3个月评价疗效。结果　治疗组和对照组1年生存率分别为60.0 %（15／25）、44.0 %（11／25）（χ2＝1.28,P＞0.05）,2年生存率分别为28.0 %（7／25）、16.0 %（4／25）（χ2＝1.05,P＞0.05）。治疗过程中的不良反应可以接受。结论　全脑放疗联合卡培他滨同步化疗治疗乳腺癌患者术后脑转移是一种安全、有效的治疗方法,不良反应小。     

Clinical features of surgical resection for pulmonary metastasis from breast cancer

Background and objectives

Metastatic breast cancer has been defined as a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. To confirm the role of resection of pulmonary metastases from breast cancer and to identify possible prognostic factors, we reviewed our institutional experience.

Methods

Between 1991 and 2007, 41 patients with pulmonary metastases from breast cancers underwent complete pulmonary resection. All patients had obtained or had obtainable locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of metastasectomy and to analyze prognostic factors for overall survival after metastasectomy.

Results

All patients were female with a median age of 55 years (range, 35–81 years). The overall survival rate after metastasectomy was 51% at 5 and 10 years. On multivariate analysis, fewer than four pulmonary metastases and a disease-free interval of more than 3 years were significantly favorable prognostic factors for overall survival (p = 0.023 and 0.024, respectively).

Conclusions

The current practice of pulmonary metastasectomy for breast cancers in our institution was well justified. Pulmonary metastasectomy in patients with previous breast cancer might be justified when fewer than four pulmonary metastases or a disease-free interval of more than 3 years.     

Radiation therapy for brain metastases from breast cancer

BACKGROUND: Breast cancer is one of the most common malignancies that metastasize to the brain. Radiation therapy plays a central role in the management of brain metastases. METHODS: The medical records of 36 patients with brain metastases from breast cancer who underwent whole-brain radiation therapy (WBRT) at Kyoto University Hospital between 1993 and 2001 were reviewed. The treatment outcomes were analyzed retrospectively. RESULTS: The median age at the time of diagnosis of brain metastases was 52 years. Only 4 patients (11%) had a single metastasis, while the others had multiple metastases. Uncontrolled extracranial metastases were present in 26 patients at the time of diagnosis of brain metastases. All patients received WBRT at a median dose of 31 Gy. Eight patients received conventional external-beam boost irradiation, and 2 received boost stereotactic radiosurgery (SRS). The overall median survival time was 7.9 months. Uncontrolled extracranial metastases except for bone metastases and old age were significantly associated with a poor survival rate. Twenty-six patients (82%) showed initial response, but 15 developed CNS failure, including 9 patients whose tumor recurred at the original site, 4 patients who developed tumors elsewhere in the brain and 3 patients who exhibited meningeal spread. The median duration of intracranial failure was 5.0 months. Whole-brain dose, and total tumor dose did not affect intracranial control. CONCLUSIONS: Radiation therapy yielded a high initial response, but the duration of effect was limited with external beam irradiation alone. New treatment strategies such as adding SRS need to be studied further.     

Identification of patients who may benefit from the prophylactic cranial radiotherapy among breast cancer patients with brain metastasis

Background To identify the candidates for prophylactic cranial radiotherapy (PCI) among the patients with early and advanced-stage breast cancer. Methods The demographic, pathologic and clinical features and survival results of 182 brain metastatic breast cancer patients treated with cranial radiotherapy were examined. Results Early stage patients who progressed with isolated brain metastasis had longer survival (13 months vs. 4 months P = 0.006). Lobular/mixed type histology (P = 0.033), high nuclear (P = 0.046) and high histological grade (P = 0.034) were the prognostic factors for isolated brain metastases. The most significant factor for the time to brain metastasis was the number of involved of lymph nodes (P = 0.004). In 60% of 148 patients with metastatic breast cancer, a progression with isolated brain metastasis was developed while the systemic disease was under control. Isolated brain metastasis progression was related to the presence of the hepatic metastasis at the first relapse (P = 0.001) and with ErbB-2 overexpression (P = 0.034). The time to the brain metastasis from the first extracerabral metastasis was associated with the high nuclear grade (P = 0.040) and with chemoresistance (P = 0.037). The median survival time after the brain metastases in chemosensitive patients was longer than in chemoresistant patients (8 months vs. 3 months P = 0.044). In chemoresistant patients (P = 0.0028) and/or in triple negative patients (P = 0.05) the development of the brain metastasis was early and the survival after brain metastasis was short. Discussions Since there is a tendency to early brain metastasis in early stage patients with high-grade, lobular/mixed type histology tumors and with a high number of involved lymph nodes, the value of PCI can be explored in these patients by a well designed prospective trial. Advanced stage chemosensitive patients with ErbB-2 over-expression and/or with hepatic metastasis at their first relapse may be candidates for PCI. There is no place for PCI in chemoresistant and triple-negative breast cancer patients.     

HER2表达强度对三阴性乳腺癌无病生存率的影响

目的：研究免疫组化中表皮生长因子受体2（HER2）表达强度与三阴性乳腺癌（TNBC）无病生存率（DFS）的关系。方法回顾性分析经病理证实的103例TNBC患者的临床病理特征,以及HER2表达强度（阴性、+、2+但HER2基因无扩增）与TNBC治疗后DFS的关系。结果103例TNBC患者的年龄为23～79岁,中位年龄52岁;随访时间60～141个月,中位随访时间90个月,无失访病例;随访期间34例（33.0%）患者出现复发转移。单因素分析显示,HER2表达强度（P=0.012）、肿块大小（P=0.037）、病理组织学分级（P=0.005）、淋巴结转移数目（P﹤0.001）与患者的DFS有关。Cox多因素分析表明,HER2表达强度（P=0.001）、病理组织学分级（P=0.001）、淋巴结转移数目（P﹤0.001）是影响TNBC患者DFS的独立危险因素。结论 HER2表达强度、病理组织学分级、淋巴结转移数目是影响TNBC患者生存独立预后因素。HER2强度越强、病理组织学分级越高、淋巴结转移数目越多,患者DFS越低。     

Characteristics of patients with short and long survivals after detection of intracranial metastases from breast cancer

Summary The clinical course of 106 patients with brain metastases from breast cancer was retrospectively studied. Median time of survival after detection of intracranial metastases (SAR(ICM)) was 14 weeks (95% confidence limits: 10–19 weeks), and 25% of the patients survived for more than 37 weeks, while only 17% survived for one year. The occurrence of clinical, pathoanatomical and therapeutical variables in these patients were analyzed in a subgroup of 57 patients, who survived for less than 16 weeks, and compared with a subgroup of 49 patients, who survived for more than 16 weeks after detection of brain metastases. None of the variables studied were associated with either of the two prognostic groups. Patients with short SAR(ICM) had, however, a greater number of extra-cranial metastases at recurrence in the brain compared to patients with SAR(ICM) more than 16 weeks (p = 0.07).Patients with SAR(ICM) less than 16 weeks had a somewhat shorter recurrence-free interval (p = 0.22) and a significantly shorter time from primary diagnosis until detection of brain metastases (p = 0.04). Probably as a consequence of this, these patients had a shorter survival from primary diagnosis as well as from first recurrence. The findings may indicate that the differences in survival of patients with brain metastases are mainly due to differences in the rate of disease progression.Abbreviations ICM intracranial metastases - RFI recurrence-free interval - RFI(ICM) time from initial diagnosis until diagnosis of ICM - SAR survival after first recurrence - SAR(ICM) survival after diagnosis of ICM