Determinants of early distant metastatic disease in elderly patients with breast cancer

BACKGROUND: The purpose of this analysis was to determine predictors of early distant metastasis in elderly breast cancer patients receiving hormonal therapy. METHODS: We analyzed data from 938 patients in the North American Fareston Tamoxifen Adjuvant Trial>or=65 years old to determine predictors of early metastatic disease. RESULTS: The median patient age was 73 (range 65 to 100). With a median follow-up of 34 months, 17 patients (1.8%) developed distant metastases. The median time to distant metastasis was 21 months. On univariate analysis, significant predictors of distant metastatic disease were as follows: progesterone receptor status (P=.032), lymphovascular invasion (P=.020), tumor grade (P=.007), tumor size (P<.01), and number of metastatic nodes (P<.01). On multivariate analysis, only the number of positive nodes (P=.029) remained significant. Patients with >or=4 positive nodes were more likely to develop early metastases than those with 0 to 3 positive nodes (odds ration 20.304; 95% confidence interval 2.777-148.456, P=.003). CONCLUSIONS: Lymph node status in the elderly breast cancer patient treated with hormonal therapy alone is a strong predictor of early distant recurrence.     

Stage III non-small cell lung cancer and metachronous brain metastases

OBJECTIVES: This study was undertaken to identify management strategies that maximize survival of patients with stage III non-small cell lung cancer and metachronous brain metastases and to determine whether any apparent improved survival was due to treatment or simply to patient selection. METHODS: Treatment evaluations of both primary non-small cell lung cancer and brain metastases were performed in 91 patients. Optimal treatment was identified by multivariable analysis. Propensity scoring and multivariable analysis were used to separate treatment benefit from patient selection. RESULTS: Risk-unadjusted median, 12-, and 24-month survivals were 5.2 months, 22%, and 10%, respectively. Younger age (P =.006), good performance status (P =.003), stage IIIA (P =.001), lung resection (P =.02), no other systemic metastases at time of diagnosis of brain metastases (P =.02), and either metastasectomy (P <.001) or stereotactic radiosurgery (P <.001) predicted best survival. However, metastasectomy or stereotactic radiosurgery was more common after lung resection (P =.02) and in patients with good performance status (P =.006), no other systemic metastases at time of diagnosis of brain metastases (P =.01), and fewer brain metastases (P <.001), suggesting that the patients with the best risk profile were selected for aggressive therapy of both lung primary and brain metastases. Despite this selection, analysis of propensity-matched patients demonstrated the benefit of lung resection and metastasectomy or stereotactic radiosurgery (P <.001). CONCLUSIONS: Younger patients with resected stage IIIA non-small cell lung cancer who have isolated metachronous brain metastases and good performance status do best when treated with metastasectomy or stereotactic radiosurgery. This survival benefit is a brain treatment effect, not the result of selecting the best patients for aggressive therapy.     

An optimal follow-up protocol for renal cell carcinoma based on the occurrence of recurrences after surgery

INTRODUCTION AND OBJECTIVE: The tumor biology of renal cell carcinoma (RCC) remains poorly understood and the prognosis of which is unpredictable. To define an optimal follow-up protocol in nonmetastatic RCC, tumor recurrences and the clinical course were assessed in the patients who had undergone nephrectomy. PATIENTS AND METHODS: Between March 1972 to July 1999, 265 patients with PT1-3N0 (Nx) M 0 RCC underwent radical or partial nephrectomy. Clinicopathological variables were compares with the time of the first recurrence, site of metastasis and reason for diagnosis. RESULTS: In July 1999, the median (range) follow-up for the surviving patients was 50 (1-244) months. Metastases were diagnosed in 45 of the 265 patients (17%). Sixty percent of the patients had their metastases diagnosed within 3 years and 87% by 6 years. The incidence and the mean time to first diagnosis of recurrence were 9.0% and 43.6 months for pT1, 32.4% and 39.6 months for pT2, and 32.7% and 25.0 months for pT3. Metastatic sites and the mean time of diagnosis were 40.6 months in lung (46.7%), 26.1 months in bone (17.8%), 18.6 months in retroperitoneal organs (11.1%), 38.0 months in liver (6.7%), 51.0 months in thyroid gland (4.4%) and 31.0 months in brain (2.2%). Most recurrence in lung, retroperitoneal organs and liver were incidentally diagnosed, whereas recurrences in bone, thyroid gland and brain had some symptoms associated with metastases. Incidence of lung metastasis in pT1 (9 patients, 56%) and pT2 (6, 55%) was greater than that in PT3 (6, 33%). In contrast, incidence of abdominal metastasis (retroperitoneal organs and the liver) in pT3 (4 patients, 33%) was grater than pT1 (2, 12%) and PT2 (1, 16%). CONCLUSIONS: The results indicate that the risk of tumor progression and site of metastasis seemed to depend on original TNM stage. Therefore stage specific postoperative follow-up protocol should be considered. The yearly follow-up may suffice for pT1a patients after surgery. For pT1b and pT2 patients, the follow-up should be intense during the first 3 years by a routine chest X-ray. For pT3 patients, the follow-up during the first 2 years may be important. Particularly, considering the high incidence of abdominal metastasis in these patients, examination by CT scan is recommended every 6 months in the first 2 years. No need for bone scintigraphy and brain CT was indicated for asymptomatic patients.     

Repeat hepatic surgery for colorectal cancer metastasis to the liver.

OBJECTIVE: The authors addressed whether a repeat hepatic operation is warranted in patients with recurrent isolated hepatic metastases. Are the results as good after second operation as after first hepatic operation? SUMMARY BACKGROUND DATA: Five-year survival after initial hepatic operation for colorectal metastases is approximately 33%. Because available alternative methods of treatment provide inferior results, hepatic resection for isolated colorectal metastasis currently is well accepted as the best treatment option. However, the main cause of death after liver resection for colorectal metastasis is tumor recurrence. METHODS: Records of 95 patients undergoing initial hepatic operation and 10 patients undergoing repeat operation for isolated hepatic metastases were reviewed for operative morbidity and mortality, survival, disease-free survival, and pattern of failure. The literature on repeat hepatic resection for colorectal metastases was reviewed. RESULTS: The mean interval between the initial colon operation and first hepatic resection was 14 months. The mean interval between the first and second hepatic operation was 17 months. Operative mortality was 0%. At a mean follow-up of 33 +/- 27 months, survival in these ten patients was 100% at 1 year and 88% +/- 12% at 2 years. Disease-free survival at 1 and 3 years was 60% +/- 16% and 45% +/- 17%, respectively. After second hepatic operation, recurrence has been identified in 60% of patients at a mean of 24 +/- 30 months (median 9 months). Two of these ten patients had a third hepatic resection. Survival and disease-free survival for the 10 patients compared favorably with the 95 patients who underwent initial hepatic resection. CONCLUSIONS: Repeat hepatic operation for recurrent colorectal metastasis to the liver yields comparable results to first hepatic operations in terms of operative mortality and morbidity, survival, disease-free survival, and pattern of recurrence. This work helps to establish that repeat hepatic operation is the most successful form of treatment for isolated recurrent colorectal metastases.     

Brain metastases from colorectal cancer: the role of surgical resection in selected patients

Aim Brain metastasis is infrequent in colorectal cancer patients, and the prognosis is poor. In this retrospective study survival and prognostic factors were determined in patients with brain metastasis from colorectal cancer. Method Between 1997 and 2006, 39 patients with brain metastasis from colorectal cancer who survived more than 1 month were identified. Data were collected with regard to patient characteristics, location and stage of the primary tumour, extent and location of metastatic disease, and treatment modalities used. Results Most (79.5%) patients had pulmonary metastases before brain metastasis, and the brain was the site of solitary metastasis in only one patient. The most frequent symptom was weakness [18 (43.6%) patients]. Overall median survival was 5.0 months and the 1‐ and 2‐year survival rates were 21.8 and 9.1%, respectively. Univariate analysis revealed uncontrolled extracranial metastases (P = 0.019), multiple brain lesions (P = 0.026), bilateral brain metastases (P = 0.032) and serum carcinoembryonic antigen levels greater than 5 ng/ml (P = 0.008) to be poor prognostic factors. The median survival after the diagnosis of brain metastasis was significantly longer in patients who underwent surgical resection (15.2 ± 8.0 months) than in those treated by other modalities (P = 0.001). Treatment modality was the only independent prognostic factor for overall survival in patients with brain metastases from colorectal cancers (P = 0.015). Conclusion Aggressive surgical resection in selected patients with brain metastases from colorectal cancer may prolong survival, even in the presence of extracranial metastatic lesions.     

Benefit of postoperative adjuvant chemoradiotherapy in locoregionally advanced esophageal carcinoma

OBJECTIVE: We sought to determine whether chemoradiotherapy after esophagectomy improves survival. METHODS: From 1994 to 2000, 31 patients with locoregionally advanced esophageal carcinoma (90% pT3, 81% pN1, and 13% pM1a) received postoperative adjuvant chemoradiotherapy. Concurrently, 52 patients with advanced carcinoma underwent esophagectomy alone and survived at least 10 weeks, the time frame for adjuvant therapy. A propensity score based on demographic, tumor, and surgical factors was used to identify matched pairs to determine the association of adjuvant therapy with outcomes. RESULTS: For patients receiving adjuvant therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year survivals were 28 versus 14 months, 68% +/- 8.4% versus 60% +/- 6.8%, and 44% +/- 9.0% versus 17% +/- 5.6%, respectively (P =.05). Similarly, risk-unadjusted median time to recurrence was 25 versus 13 months (P =.15), and median recurrence-free survival was 22 versus 11 months (P =.04). Among propensity-matched patients, median, 1-year, and 4-year survivals for those receiving adjuvant therapy versus esophagectomy were 28 versus 15 months, 60% +/- 11.0% versus 65% +/- 10.7%, and 44% +/- 11.3% versus 0% (P =.05). Median time to recurrence was 25 versus 13 months (P =.04), and recurrence-free survival was 22 versus 10 months (P =.02). CONCLUSION: In patients with locoregionally advanced esophageal carcinoma, addition of postoperative adjuvant chemoradiotherapy to esophagectomy alone doubled survival time, time to recurrence, and recurrence-free survival. Patients with locoregionally advanced carcinoma after esophagectomy should be considered for adjuvant therapy.     

STAGE SPECIFIC GUIDELINES FOR SURVEILLANCE AFTER RADICAL NEPHRECTOMY FOR LOCAL RENAL CELL CARCINOMA

Purpose

We report stage specific followup guidelines based on our evaluation of the pattern of recurrence in 286 patients treated for local N0 or Nx renal cell carcinoma.

Materials and Methods

We retrospectively reviewed the clinical records of 286 patients with pT1 to pT3N0 or Nx renal cell carcinoma who underwent nephrectomy at our center between February 1985 and December 1994. In cases of later metastases the median interval to first metastasis, site of metastasis and method of diagnosis were correlated with the primary lesion stage.

Results

Metastases developed in 68 patients a median of 23 months after nephrectomy. Eight of the 113 patients with pT1 disease had metastases (median time to diagnosis 38 months), while 17 of 64 with pT2 disease and 43 of 109 with pT3 disease had metastases (medians 32 and 17 months, respectively). Of the 92 metastases 59 (64%) were asymptomatic, including 44 detected on routine chest x-rays (32) and blood tests (12). Isolated asymptomatic intra-abdominal metastases were diagnosed by surveillance computerized tomography in only 6 patients (9%). The remaining patients with metastases had associated clinical symptoms and/or abnormal results on interval tests that prompted further diagnostic studies.

Conclusions

We confirmed that the risk of metastatic renal cell carcinoma is stage dependent. Therefore, surveillance protocols should be based on the pathological stage of the primary tumor. We recommend an annual chest x-ray, and serum liver function and alkaline phosphatase level tests for patients with pT1 disease. These studies are indicated beginning at 6 and 3 months for pT2 and pT3 disease, respectively, continuing every 6 months for 3 years and then annually. Surveillance computerized tomography should be performed at 24 and 60 months in patients with pT2 and pT3 disease or earlier when the results of any routine study are abnormal or clinical symptoms are present. Bone and brain surveillance studies should be prompted by site specific symptoms, elevated alkaline phosphatase levels or the diagnosis of metastasis at another site.     

Contemporary surgical treatment of advanced-stage melanoma

HYPOTHESIS: The clinical treatment of patients with stage IV melanoma according to criteria of the American Joint Committee on Cancer (AJCC) is controversial because the 5-year survival rate is approximately 5%. Specific clinicopathologic factors are predictive of survival following curative surgery. DESIGN: Cohort analysis of 1574 successive patients undergoing surgical resection of metastatic melanoma for a 29-year period. Patients received follow-up on a routine basis with serial examinations and radiographic studies. The median follow-up time was 19 months (range, 1-382 months). SETTING: Tertiary cancer center. PATIENTS: Surgical resection was performed in 1574 patients. The decision to perform surgery was individualized for each patient. INTERVENTION: The technique of surgical resection was based on the site of metastasis.Main Outcome Measure Computer-assisted database with statistical analyses using log-rank tests and Cox regression models. RESULTS: Of the 4426 patients with AJCC stage IV melanoma, 1574 (35%) underwent surgical resection; 970 (62%) were men, with a median age of 50 years. Of the primary melanomas, 46% arose on the trunk, and 56% were Clark level IV or V with a median thickness of 2.2 mm. We found 697 patients (44%) to have AJCC stage III melanoma (lymph node) prior to the development of stage IV metastases. The most common site for resection was the lung (42%), followed by the skin or lymph node (19%) and the alimentary tract (16%). Of our patients, 877 (56%) had melanoma at a single site. The 5-year survival rate was significantly (P<.001) better for patients with a solitary melanoma (mean +/- SD, 29% +/- 2%) than those with 4 or more metastases (n = 147; mean +/- SD, 11% +/- 3%). Skin and lymph node metastases had the most favorable survival rate (median, 35.1 months). Multivariate analyses identified an earlier primary tumor stage (I vs II) (P<.001), an absence of intervening stage III metastases (P =.02), solitary metastasis (P<.001), and a long (>36 months) disease-free interval from AJCC stage I or II to stage IV (P =.005) as predictive of survival. CONCLUSIONS: Our results demonstrate the benefit of surgical resection for advanced-stage melanoma. Patients with limited sites and numbers of metastases should be considered for curative resection regardless of the location of the disease.     

Vater壶腹腺癌胰十二指肠切除后复发转移的危险因素

目的 研究Vater壶腹腺癌在胰十二指肠切除后复发转移的危险因素. 方法 回顾性分析1980年1月至2003年12月收治的胰十二指肠切除后存活的101例Vater壶腹腺癌的临床病理资料.结果 本组患者中TNM分期Ⅰ期42例(41.6%),Ⅱ期32例(31.7%),Ⅲ期27例(26.7%).中位随访时间为46(2～192)个月,25例(24.8%)复发转移,中位复发转移时间为20(2～93)个月.局部复发11例(10.8%),远处转移20例(19.6%),其中6例同时出现局部复发与远处转移.复发转移的25例患者与未复发转移的76例患者的肿瘤最大直径>2 cm(64%比39%,X2=4.56,P=0.033)、淋巴结阳性率(52%比17%,X2=11.98,P=0.001)和手术并发症发生率(51%比20%,X2=7.50,P=0.006)之间相比差异有统计学意义.Logsitic回归分析发现,只有淋巴结转移(0R=5.14,P=0.0037)是复发转移的独立预后因素.未出现淋巴结转移患者中位无复发生存时间为49(2～192)个月,淋巴结转移患者为32(12～152)个月,两者相比差异有统计学意义(X2=5.43,P=0.0198).结论 Vater壶腹腺癌在胰十二指肠切除后复发转移较为常见;淋巴结转移是术后复发转移的独立危险因素.     

The neurosurgical management of brain metastasis from colorectal cancer: A report of three cases

We report herein three cases of brain metastasis from primary colorectal cancer in which the metastatic lesion was resected to effectively relieve neurological symptoms. Case 1 was a 61-year-old woman with a solitary brain metastasis from colorectal cancer and no other metastases; case 2 was a 59-year-old woman who died from liver metastasis 11 months after resection of the metastatic brain tumor; and case 3 was a 68-year-old woman with multiple metastases to the lungs and bones detected before the brain metastasis. According to 16 cases previously reported in the Japanese literature and our 3 cases, the interval between diagnosis of the primary cancer and discovery of brain metastasis was 23 months on average, while the median survival after the discovery of brain metastasis was 7 months. Brain metastases with liver and lung metastases were seen more frequently than brain metastases alone. In these three cases, chemotherapy appears to have been of no use in preventing recurrence. Thus, we believe neurosurgical management to be appropriate for a solitary lesion and that it should be actively pursued to prolong survival and improve quality of life.     

Treatment of metastatic brain tumor from renal cell carcinoma

Twenty-eight patients with metastatic brain tumor from renal cell carcinoma were treated at the National Cancer Hospital, Tokyo, between 1962 and March 1989. In 13 patients, the median time interval between the initial diagnosis and pulmonary metastasis was 18 months, and the interval between pulmonary metastasis and brain metastasis was 13 months. In 10 patients, whose initial diagnosis was pulmonary metastasis, the median interval between pulmonary metastasis and brain metastasis was also 13 months. There were 2 patients who presented brain metastasis initially. The median survival time from the diagnosis of brain metastasis was 17 months for the patients whose brain tumors were surgically resected, but only 4 months for the patients who didn't receive surgery. The median survival time of the patients who received postoperative radiation was 20 months, while it was 10.5 months for the patients who received radiation therapy alone. Repeated serial CT scans of 7 patients with measurable brain metastases revealed partial response (PR) to radiotherapy in 2 patients (28.6%), no change (NC) in 4 patients (57.2%), and progressive disease (PD) in one patient (14.3%). BrdU labeling indices of resected brain metastases were about 2%, and the doubling time calculated on repeated serial CT scans was about 20 days. As these lesions are rather resistant to radiotherapy and grow relatively slowly they should be resected as much as possible.     

163例乳腺癌肝脏转移临床资料和预后因素分析

【摘要】〓目的〓探讨乳腺癌肝脏转移的临床特点、治疗情况以及预后。方法〓回顾性分析2006年1月至2016年1月中山大学附属第一医院收治的乳腺癌肝脏转移病例,总结该部分患者的临床病理特征、治疗方式、生存期以及影响预后的因素。结果〓共163例患者入组,其中初诊合并肝脏转移69例(A组),乳腺癌术后复发累及肝脏94例(B组)。所有患者均行以全身治疗为主的综合治疗,其中35.6%的患者行手术、消融或TACE局部治疗。B组患者中位生存时间较A组患者延长12.0个月(P=1.83×10-10),相应的1年、2年、3年生存率也明显高于A组(A组:1年79.44%,2年40.54%,3年9.20%;B组:1年98.94%,2年84.92%,3年40.54%)。而有机会局部治疗的患者生存期明显延长:局部治疗组中位生存时间为33.0个月(95%CI, 30.0~39.4个月),未能局部治疗组中位生存时间仅为26.4个月(95%CI, 23.6~29.7个月),(P=9.95×10-3)。单因素分析显示激素受体状态、HER-2表达情况、Ki67增殖情况、分子分型、肝脏多发转移灶是否局限以及是否有机会局部治疗均与乳腺癌肝脏转移患者的预后相关。多因素分析则提示HER-2表达情况、肝脏多发转移灶是否局限以及是否有机会局部治疗是乳腺癌肝脏转移患者的独立预后因素。结论〓乳腺癌肝脏转移一旦发生,预后较差。临床工作中应注重乳腺癌患者的肝脏筛查,以期早期发现、早期治疗。治疗应以全身综合治疗为主,对于孤立的单一转移灶或局限的多发转移灶,局部治疗可以取得良好的效果。     

Surgical treatment for brain metastases: prognostic factors and survival in 177 patients

Brain metastases are an increasingly frequent complication of cancer. Advances in diagnosis and treatment have led to wider indications for surgery. We present a single-institution series of 177 patients and discuss our results with regard to the literature. Special focus is on patients with advanced age, multiple brain metastases, extracranial metastases, and brain metastasis recurrence. All patients underwent craniotomy for the resection of solid tumor brain metastases between 1994 and 2001 in our department. Perioperative morbidity and mortality as well as survival were evaluated. The median patient age was 59 years (range 32–86 years). In 177 patients, 348 brain metastases were detected, of which 68.0% were supratentorial and 32.0% were infratentorial. According to univariate analysis, the following parameters were significantly associated with prolonged patient survival: (1) age <70 years, (2) one to three intracranial metastases, (3) favorable postoperative performance, (4) resection of all intracranial lesions, and (5) recraniotomy for brain metastasis recurrence. In contrast, the presence of extracranial metastases, metachronous diagnosis, and solitary brain metastases had no influence on survival. As expected, younger age and limited number of brain metastases (up to three) are favorable prognostic factors. Remarkably, the presence of extracranial metastases had no influence on patient survival.     

Brain metastases from bladder carcinoma: presentation, treatment and survival

PURPOSE: We report the presentation of brain metastases from bladder carcinoma. We investigated the role of whole brain radiation therapy for treating this disease. MATERIALS AND METHODS: Between January 1982 and November 1999, 16 patients with brain metastases from bladder carcinoma were treated at our institution. We reviewed patient and tumor characteristics at the time of the primary diagnosis and the brain metastasis diagnosis. We analyzed treatment results in regard to survival and local metastasis control. RESULTS: Brain metastases from bladder carcinoma were commonly accompanied by uncontrolled systemic metastases. Multiple brain lesions developed in 14 of the 16 patients. Of the 16 patients 14 received radiation therapy with or without surgery, 1 was treated surgically and 1 did not receive any treatment. The 11 patients treated with whole brain radiation therapy had a median survival of only 2 months (range 0.5 to 11). A patient who received stereotactic radiosurgery survived 12 months after the brain metastasis diagnosis and 2 treated with radiation therapy after surgery survived 12.75 and 2.75 months, respectively (median 7.75). The patient treated with surgery alone survived 1.25 months after the brain metastasis diagnosis and 1 who received no treatment survived 1.75 months. Patients with multiple brain metastases had shorter survival than those with a single metastasis. CONCLUSIONS: Overall survival after brain metastasis development in patients with bladder carcinoma was poor. Although the number of patients in this study was small, results indicate that radiation therapy alone is inadequate treatment. Therefore, when possible, we advocate more effective treatment by combining radiation therapy with other treatment modalities, as recommended in ongoing clinical trials.     

Efficacy and limitations of salvage gamma knife radiosurgery for brain metastases of small-cell lung cancer after whole-brain radiotherapy

Background

The efficacy and limitations of salvage gamma knife surgery (GKS) have not been thoroughly described. This study evaluated the efficacy of GKS for treating brain metastases associated with small-cell lung cancer (SCLC) after whole-brain radiotherapy (WBRT) as the first-line radiation therapy.

Methods

Forty-four patients with recurrent or new SCLC-associated brain metastases underwent GKS after receiving WBRT (median age, 62 years; median duration between WBRT and first GKS, 8.8 months). The median Karnofsky performance status (KPS) score was 100 (range, 40–100), and the median number of brain metastases at the first GKS was five. Ten patients who partially or completely responded to chemotherapy received prophylactic cranial irradiation (PCI) for limited disease.

Results

The median prescribed dose and number of lesions treated with the initial GKS were 20.0 Gy and 3.5, respectively, and the tumor control rate was 95.8 % (median follow-up period, 4.0 months). The 6-month new lesion-free survival, functional preservation rates, and overall survival were 50.0 %, 94.7 %, and 5.8 months, respectively. Neurological death occurred in 17.9 % of cases. The poor prognostic factors for new lesion-free survival time and functional preservation were >5 brain metastases and carcinomatous meningitis, respectively. Poor prognostic factors for survival time were KPS <70, >10 brain metastases, diameter of the largest tumor >20 mm, and carcinomatous meningitis. Median overall survival time from brain metastasis diagnosis was 16.9 months.

Conclusions

GKS may be an effective option for controlling SCLC-associated brain metastases after WBRT and for preventing neurological death in patients without carcinomatous meningitis.     

Comparison of mutational changes in involved N1 lymph nodes with those in primary tumors in stage II non-small cell lung cancer: a pilot study

OBJECTIVES: Surgical resection is the standard treatment for stage II non-small cell lung cancer, but recurrence rates approach 60%. This study compared mutational changes in involved lymph nodes and primary tumors from patients with stage II non-small cell lung cancer to determine whether risk factors for recurrence could be identified. METHODS: Forty patients with resected stage II non-small cell lung cancer (excluding T3 N0 disease) were studied. Microdissection was performed on primary tumors and lymph nodes. Analysis was performed across 9 genomic loci by using polymerase chain reaction amplification. The ratio of fractional allelic loss between involved lymph nodes and primary tumors was used to stratify patients into high-risk (fractional allelic loss ratio of >or=1) and low-risk (fractional allelic loss ratio of <1) groups. RESULTS: The median age of the patients was 68 years (range, 42-85 years). Median follow-up was 30 months. Fractional allelic loss was greater in patients with squamous carcinomas compared with that in adenocarcinomas, but survival was similar (35 vs 39 months). The median survival was 35 months in high-risk patients and was not reached in low-risk patients (P =.3). Disease-free survival was 24 months in high-risk patients and was not reached in low-risk patients (P =.35). In the subset with adenocarcinoma (n = 18), median survival was 24 months in the high-risk group; no deaths occurred in low-risk patients (P =.01). Also, disease-free survival was 14 months in high-risk patients and was not reached in the low-risk patients (P =.05). CONCLUSIONS: Squamous cancers demonstrate greater mutational changes than adenocarcinomas; this does not affect outcome. The patients with low-risk adenocarcinomas demonstrated superior outcomes compared with those of other patients. These results should be confirmed in larger studies.     

Pulmonary metastasectomy of renal cell carcinoma: Local experience

Objective: Up until now, the prognosis of a patient with disseminated renal cell carcinoma is poor with 5‐year survival less than 2%. In a small subset of patients with isolated pulmonary metastasis, long‐term survival after pulmonary metastasectomy has been reported to be acceptable. The purpose of the present study was to evaluate the result of pulmonary metastasectomy in a local cardiothoracic surgical centre. Methods: Patients who had renal cell carcinoma and pulmonary metastasectomy for isolated pulmonary metastasectomy were recruited for the study. Their survival was analysed. Results: Between 1992 and 2004, 13 patients underwent 15 operative procedures for pulmonary metastases from renal cell carcinoma. The median follow up was 39.8 months (from 4.6 to 127.5 months). The five‐year survival after pulmonary metastasectomy was 48.3% and median survival was 25.4 months. There was no postoperative mortality. Pulmonary recurrence was the commonest recurrent site after pulmonary metastasectomy. Conclusion: Pulmonary metastasectomy for renal cell carcinoma is a safe and effective procedure. And, as the lung is the commonest site of first recurrence after pulmonary metastasectomy, the present study on the control of these occult metastases is necessary.     

Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab

PurposeThe aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab.MethodsMedical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively.ResultsMedian follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER− and PR−) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33–8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33–8.71) were significant risk factors for development of brain metastasis as the first site of recurrence.ConclusionsIn patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER− and PR−) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.     

Resection of brain metastases from non-small-cell lung carcinoma. Results of therapy. Memorial Sloan-Kettering Cancer Center Thoracic Surgical Staff.

The treatment of patients with a solitary brain metastasis has been evolving, with most centers recommending resection in patients with good performance status. To evaluate the results of resection of brain metastases from non-small-cell lung cancer, we reviewed our 16-year experience with 185 consecutive patients undergoing resection of brain metastases from 1974 to 1989, inclusive. There were 89 men and 96 women; ages ranged from 34 to 75 years (median 54). Sixty-five (35%) had synchronous and 120 (65%) metachronous brain metastases. Discounting the brain metastasis, 68 patients (37%) had stage I, 13 (7%) stage II, 62 (33%) stage IIIA, 30 (16%) stage IIIB, and 12 (6%) stage IV carcinoma. There was no significant difference in age, locoregional stage (TN), or histologic features in patients with synchronous versus metachronous lesions. The overall survival rates (n = 185) were as follows: 1 year, 55%; 2 years, 27%; 3 years, 18%; 5 years, 13%; and 10 years, 7% (median 14 months). There was no significant difference in survival between patients with synchronous and metachronous lesions. To evaluate the impact of locoregional stage and treatment of the primary site, we analyzed only those patients with synchronous brain metastases. Multivariate analysis demonstrated that locoregional stage had no significant effect on survival (p = 0.97), but complete resection of the primary disease significantly prolonged survival (p = 0.002). Therefore complete resection, and not stage, of the locoregional primary lesion is the primary determinant of survival in patients undergoing resection of brain metastases from non-small-cell lung cancer.     

Predicting the sites of metastases from lung cancer using molecular biologic markers

BACKGROUND: The use of molecular markers in staging non-small cell lung cancer (NSCLC) has been supported in retrospective prognostic models but has not been evaluated in predicting sites of metastases. METHODS: Pathologic specimens were collected from 202 patients after complete resection for stage I NSCLC, who were subsequently found to have no metastases at 5 years (n = 108), isolated brain metastases (n = 25), or other distant metastases (n = 69). A panel of eight molecular markers of metastatic potential was chosen for immunohistochemical analysis of the tumor: p53, erbB2, angiogenesis factor viii, EphA2, E-cadherin, urokinase plasminogen activator (UPA), UPA receptor, and plasminogen activator inhibitor. RESULTS: Patients with isolated brain relapse had significantly higher expression of p53 (p = 0.02) and UPA (p = 0.002). The quantitative expression of E-cadherin was used to predict the site of metastases using recursive partitioning: 0 of 92 patients with E-cadherin expression of 0, 1, or 2 developed isolated cerebral metastases; 0 of 33 patients with E-cadherin expression of 3 with UPA of 1 or 2 and ErbB2 of 0 developed brain metastases. Of the remaining patients at risk (UPA = 3), the risk of isolated cerebral metastases was 21 of 57 patients (37%). CONCLUSIONS: This study demonstrates that molecular markers may predict the site of relapse in early stage NSCLC. If validated in an ongoing prospective study, these results could be used to select patients with isolated brain metastases for adjuvant therapy, such as prophylactic cranial irradiation.