Results of whole brain radiation therapy in patients with brain metastases from colorectal carcinoma

AIMS AND BACKGROUND: Carcinoma of the colon-rectum is an infrequent cause of brain metastases, constituting 1.5% of all metastatic lesions to the brain. We reviewed our experience in the treatment of brain metastases from colorectal cancer to define the efficacy of whole brain radiation therapy as a palliative measure in this setting of patients. METHODS: Twenty-three consecutive cases of brain metastasis from colorectal cancer treated between 1999 and 2004 were identified in the files of the Division of Radiotherapy of the A Businco Regional Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor characteristics and categorized according to the RTOG RPA classes. RESULTS: Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed extracranial metastases. Fourteen patients were classified as RTOG RPA class II and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic improvement was observed. The median follow-up and survival time for all the patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of death was the brain metastasis. CONCLUSIONS: Despite the disappointing survival time, external radiation therapy to the whole brain proved to be an efficacious palliative treatment for patients with multiple or inoperable brain metastasis from colorectal cancer.     

Resection of synchronous liver metastases from colorectal cancer

Background: The prognosis for patients with liver metastasesfrom colorectal cancer is still poor. Thus, patient selectionfor hepatic resection is essential to improve the poor resultsof the procedure. Some reports have shown that the prognosisfor patients with synchronous liver metastases is worse thanthat for those with metachronous liver metastases. Therefore,determination of the factors that influence outcome after resectionof synchronous liver metastases is more important than withmetachronous liver metastasis. Method: We studied patients who had been followed for more than5 years after undergoing resection of synchronous liver metastasesfrom colorectal cancer. Results: Among the 12 prognostic factors studied (age, gender,adjuvant chemotherapy, tumor site, CEA level, tumor differentiation,tumor size, regional lymph node metastatic status, distributionof liver metastases, number of liver metastases, tumor sizeand pathological margin), regional lymph node metastatic statusand pathological margin were significant prognostic factorsby univariate analysis (p = 0.0002 and 0.005, respectively).Regional lymph node metastatic status was a significant prognosticfactor by multivariate analysis (p = 0.031). The survival curveof patients with six or more regional lymph node metastaseswas similar to that of patients with non-resectable liver metastasis. Conclusion: The resection of synchronous liver metastases inpatients with six or more regional lymph node metastases isrelatively contraindicated. For these patients, other treatmentmodalities should be considered. ⁺ For reprints and all correspondence: Shin Fujita, Departmentof Surgery, National Cancer Center Hospital, 1–1 Tsukiji5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: sfujita@gan2.ncc.go.jp     

Resection of hepatic and pulmonary metastases from colorectal cancer

Resection of hepatic metastases of colorectal origin has gained wide acceptance, but when patients have synchronous or metachronous pulmonary metastases, they are often considered incurable and are offered systemic therapy only. We performed a retrospective review of the patients at Memorial Sloan-Kettering Cancer Center who underwent resection of both hepatic and pulmonary metastases of colorectal origin between 1970 and 1990. Ten patients were identified who met the above criteria. Median survival after hepatic and pulmonary resections were 34 and 18 months, respectively. Actuarial 1-, 3- and 5-year survivals are 89%, 78% and 52%, respectively. With a median of 18 months after second operation, three patients have no evidence of disease (NED), four are alive with disease (AWD) and three are dead of disease (DOD). In the absence of effective chemotherapy, selected patients with hepatic and pulmonary metastases of colorectal origin should be considered for resection as it offers the only possibility for long-term survival.     

Resection versus radiosurgery for patients with brain metastases

Brain metastases occur in 20-40% of adult cancer patients and the incidence is apparently increasing. Despite advances in treatment, the prognosis of these patients is poor, with a median survival of approximately 4 months. Whole brain radiation therapy is the standard of care for most patients with brain metastases. Randomized trials have demonstrated that focal treatments, such as resection and radiosurgery, yield significant improvement in the survival of patients with a single metastasis. The utility of these strategies, specifically in terms of increased survival, is unclear in patients with more than one metastasis. In addition to focal treatments, future directions in the treatment of brain metastases include the development of intraoperative imaging capabilities, improved methods of identifying patients who are likely to benefit from treatment, systemic agents, such as chemotherapy and radiosensitizers, and the incorporation of targeted and antiangiogenic therapies.     

Brain metastases from colorectal carcinoma.

AIMS AND BACKGROUND: Brain metastases are an unusual finding in patients with colorectal carcinoma. We wished to determine the clinical presentation, the time interval between the diagnosis of colorectal carcinoma and the appearance of brain metastases, and the overall survival. PATIENT CHARACTERISTICS: The median age of our patients was 61 years. Brain metastases developed subsequently to the diagnosis of colorectal cancer in nine patients. All patients had neurologic symptoms. All patients had progressing systemic disease at the moment of intracranial presentation. Four patients received whole brain radiation therapy. The median survival was 11 weeks. DISCUSSION: The development of brain metastasis is a late event in the course of colorectal carcinoma and occurs most often in patients with extensive systemic disease that contraindicates surgical resection. Radiotherapy can improve the survival of this group of patients whereas the role of chemotherapy is still unclear due to the low frequency of such cases.     

Prognostic factors in patients with brain metastases from lung carcinoma

Between September 1980 to December 1984, 85 patients with brain metastases from lung carcinoma were consecutively evaluated and were entered into the first prospective randomized trial. Since January 1985, the second prospective randomized trial was started based on the result of the first trial, i.e., lactate dehydrogenase (LDH) as the most important prognostic factor. We analyzed neurological improvement and survival of 79 patients, who were entered into the second trial until November 1988, compared with the first trial. This preliminary result suggests that LDH may also be an important prognostic factor in the second trial.     

Resection of hepatic and pulmonary metastases in patients with colorectal cancer.

The resection of liver and lung metastases is now regarded as valid therapy, although the surgical procedure of both metastatic sites has not been clearly defined. Nine consecutive patients who underwent resection of both liver and lung metastases from colorectal cancer (5 Dukes' stage B, 3 C, 1 D) between 1986 and 1999 were studied retrospectively. A total of 19 resections were performed: 8 hepatectomies, 2 liver wedge resections, and 9 lung lobectomies. No operative or hospital deaths occurred, and mean postoperative hospital stay per procedure was 12 days. Mean survival after resection of the primary colorectal tumor was 66.3 (range: 26-96) months. The median interval was 24.2 (range: 2-39) months from resection of the liver metastasis and 30.4 (range: 3-45) months from resection of the lung metastasis. At the last follow-up, 6 patients were still alive, 4 of whom were free of recurrence 59, 69, 74, and 76 months, respectively, after resections. Three patients died with metastases. Aggressive treatment of liver and lung secondaries from colorectal cancer was performed without hospital mortality and acceptable morbidity. Longer survival times warrant the use of this alternative therapy for selected patients. In association with new effective chemotherapies, it will be possible to select patients who will benefit from surgery.     

直肠癌脑转移患者预后的影响因素分析

目的：分析影响直肠癌脑转移患者预后的相关因素。方法：搜集2008年6月－2010年6月期间来我院治疗的100例直肠癌脑转移患者的临床资料,根据治疗方法分为实验组和对照组,实验组为行手术治疗的46例患者,对照组为行放化疗的54例患者。采用Logistic逐步回归分析,分析影响脑卒中瘫痪经手术治疗患者预后的因素。结果：实验组患者的平均生存时间、1年生存率、3年生存率以及5年生存率均优于对照组患者,具有明显差异（P＜0．05）。Logistic回归分析示,性别、原发肿瘤组织学分级等因素不是影响直肠癌脑转移患者预后的因素;影响直肠癌脑转移患者预后的相关因素是原发肿瘤直径、脑转移灶数目、血清CEA水平、治疗方法、脑转移灶治疗与否以及年龄。经Logistic回归逐步分析可知,血清CEA水平对患者预后的影响最大（OR＝3．743）,其次是脑转移灶数目（OR＝3．153）、治疗方法（OR＝2．946）,年龄（＞60岁）影响最小（OR＝1．900）。结论：影响直肠癌脑转移患者预后的相关因素是原发肿瘤直径、脑转移灶数目、血清CEA水平、治疗方法、脑转移灶治疗与否以及年龄等。及时掌握这些预后影响因素能够显著提高直肠癌脑转移患者生存状况,在临床上具有重要的临床意义。     

Surgical resection of pulmonary metastases from colorectal carcinoma

Twelve patients with pulmonary metastases of recurrent colorectal carcinoma underwent pulmonary resection at National Ohkura Hospital. The Cumulative five-year survival rate was 60 per cent. No correlation was found between the disease-free interval and survival following thoracotomy. There was a statistically significant difference in survival rates corresponding to Duke's classification of the primary lesion. Patients with solitary lesions had a better survival rate than patients with multiple lesions. We believe that the surgical treatment of pulmonary metastases in a select group of patients, i.e., those with solitary pulmonary lesions, will prolong survival and be curative in a number of patients.     

Detection of occult nodal metastases in patients with colorectal carcinoma

Immunohistochemical study may be used for detecting micrometastases by their expression of tumor-associated antigens. In 48 specimens of colorectal cancer from 47 patients, 49 of 249 lymph nodes (median, five per patient; range, 2-11) examined by light microscopic study contained tumor deposits. Sections of all lymph nodes were also examined by immunohistochemical study for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression using the indirect immunoperoxidase staining method. All 49 lymph node metastases (100%) from 20 patients stained positively for CEA and 45 (92%) expressed EMA. Of the 200 lymph nodes without metastases on light microscopic examination, anti-CEA revealed a single micrometastasis in a patient staged as Dukes' B. No additional metastases were detected with anti-EMA. In this series of patients immunohistochemical study has, therefore, influenced the histologic staging in only one patient (2%) and thus does not offer a significant benefit over conventional histologic staging.     

A multifactorial analysis of prognostic factors in patients with liver metastases from colorectal carcinoma

A multifactorial analysis was used to identify the dominant prognostic variables predicting survival rates of 175 patients with hepatic metastases from colorectal carcinoma. Seven of 22 parameters examined simultaneously were found to independently influence the median survival rate in these patients: (1) elevated alkaline phosphatase (p = 0.0004), (2) elevated serum bilirubin level (p = 0.0005), (3) location of hepatic metastases (unilateral or bilateral, p = 0.0022), (4) number of metastatic nodes involved (0, 1-5, greater than 5; p = 0.0148), (5) depressed serum albumin (p = 0.0217), (6) whether or not the primary colorectal tumor was resected (p = 0.0013), and (7) chemotherapy (given or withheld, p = 0.0439). The prothrombin time, serum lactic dehydrogenase, and the number of hepatic metastases also correlated with survival, but they did not independently predict survival rates after other more dominant factors were accounted for. A mathematical equation for predicting an individual patient's clinical course once they developed hepatic metastases was derived from this statistical analysis. In addition, a simple and clinically useful guide for predicting outcome was developed that integrated the two most important risk factors, alkaline phosphatase and bilirubin.     

Radiofrequency ablation of liver metastases from colorectal carcinoma.

BACKGROUND: Most patients with colorectal carcinoma will develop liver metastases. Radiofrequency ablation (RFA) has been utilized in metastatic CRC to help improve the survival gap between resectable and unresectable tumor. METHODS: The current use of RFA in selected patient populations is reviewed. RESULTS: RFA provides a survival benefit in patients with unresectable hepatic metastases from CRC compared with chemotherapy alone. It offers effective local tumor destruction in appropriately selected lesions and minimizes the morbidity and mortality of an open resection. Common complications are abdominal bleeding (1.6%), abdominal infection (1.1%), and injury to the biliary tree (1.0%). Mortality ranges from 0% to 0.5%. CONCLUSIONS: Trials are underway to compare chemotherapy plus local ablation to chemotherapy alone. RFA is a tool that should be utilized by experienced individuals to achieve optimal oncologic outcomes.     

Resection of colorectal liver metastases: current perspectives.

BACKGROUND: Metastases to the liver is the leading cause of death in patients with colorectal cancer. METHODS: The authors review the data on diagnosis and management of this clinical problem, and they discuss management options that can be considered. RESULTS: Complete surgical resection of metastases from colorectal cancer that are localized to the liver results in 5-year survival rates ranging from 26% to 40%. CONCLUSIONS: By adding modalities such as targeted systemic therapy and other "local" treatments for liver metastases, further gains in survival are anticipated.     

Solitary brain metastases from carcinoma of the bladder

Summary We report 6 cases of solitary brain metastasis from bladder carcinoma. Although systemic metastases from this cancer are frequent, central nervous system metastases are rare. Analysis of our material and of published cases shows that the tumor is resistant to therapy and the prognosis is consequently very poor.     

Bevacizumab in the treatment of a patient with metastatic colorectal carcinoma with brain metastases

The development of brain metastases originating from colorectal cancer (CRC) is an infrequent phenomenon occurring in < 5% of patients. Yet, it is feasible that physicians will be diagnosing more patients with brain metastases because of the prolonged survival in our current patient population. The anti-angiogenic agent bevacizumab is currently approved in bevacizumab-naive patients with metastatic CRC (mCRC). Initially, precautionary measures regarding the use of bevacizumab were recommended for patients at risk of bleeding based on earlier incidents of intracranial hemorrhage, hemoptysis, and pulmonary hemorrhage. However, recent data support the use of bevacizumab in the treatment of high-grade gliomas. We present a challenging case of a treatment-naive patient with mCRC with brain metastases and the challenges involved in weighing the risks and benefits of systemic chemotherapy when combined with a biologic agent.     

Sunitinib in metastatic renal cell carcinoma patients with brain metastases

BACKGROUND:

In a broad patient population with metastatic renal cell carcinoma (RCC), enrolled in an open‐label, expanded access program (EAP), the safety profile of sunitinib was manageable, and efficacy results were encouraging. Here, the authors report results for patients with baseline brain metastases participating in this global EAP.

METHODS:

Previously treated and treatment‐naive metastatic RCC patients ≥18 years received sunitinib 50 mg orally, once daily, on Schedule 4/2. Safety was assessed regularly, tumor measurements done per local practice, and survival data collected where possible. Analyses were done in the modified intention‐to‐treat (ITT) population, consisting of all patients who received ≥1 dose of sunitinib.

RESULTS:

As of December 2007, 4564 patients had enrolled in 52 countries. Of these enrollees, 4371 were included in the modified ITT population, of whom 321 (7%) had baseline brain metastases and had received a median of 3 treatment cycles (range 1‐25). Reasons for their discontinuation included lack of efficacy (32%) and adverse events (8%). The most common grade 3‐4 treatment‐related adverse events were fatigue and asthenia (both 7%), thrombocytopenia (6%), and neutropenia (5%), the incidence of which were comparable to that for the overall EAP population. Of 213 evaluable patients, 26 (12%) had an objective response. Median progression‐free survival and overall survival were 5.6 months (95% CI, 5.2‐6.1) and 9.2 months (95% CI, 7.8‐10.9), respectively.

CONCLUSIONS:

In patients with brain metastases from RCC, the safety profile of sunitinib was comparable to that in the general metastatic RCC population, and sunitinib showed evidence of antitumor activity. Cancer 2011. © 2010 American Cancer Society.     

Stereotactic radiosurgery for brain metastases from hepatocellular carcinoma

The purpose of this study is to investigate the possible role of stereotactic radiosurgery (SRS) in the management of patients with brain metastases from hepatocellular carcinoma (HCC). Thirty-two consecutive patients with 80 brain metastases from HCC were treated with SRS. Twenty-eight (87.5 %) patients were male, and the mean age of the patients was 54 ± 12 years (range 22–73). Twenty-seven (84.4 %) patients were classified as RTOG RPA Class 2. The mean tumor volume was 6.14 ± 11.3 cm³ (range 0.01–67.3). The mean marginal dose prescribed was 20.1 ± 3.6 Gy (range 10.0–25.0). The median overall survival time after SRS was 11.3 ± 5.8 weeks (95 % CI 0–22.7). A greater total volume of brain metastases (>14 cm³) was the only independent prognostic factor (HR = 2.419; 95 % CI 1.040–5.624; p = 0.040). The actuarial control rate of brain metastases was 51.3 % at 4 months after SRS. The prescribed marginal dose (>18 Gy) was significantly related with the actuarial tumor control (HR = 0.254; 95 % CI 0.089–0.725; p = 0.010). The prognosis of patients with brain metastases from HCC is dismal even with the modern technology of radiosurgery. The marginal dose prescribed should be reevaluated to improve upon the current poor local control rates.