子宫内膜癌脑转移的临床病理分析

目的:回顾性分析子宫内膜癌脑转移患者的临床病理特征,评估早期诊断脑转移并积极给予治疗对于预后的价值。方法:我们回顾性分析并观察2015年至2017年在南京鼓楼医院确诊的3例子宫内膜癌脑转移的病人,总结其临床症状、诊断、病理学形态和免疫组化表型特征、生物学特征及其治疗、疗效及预后等临床病理特征,并对照子宫内膜癌脑转移的相关文献报道,对其临床病理特点及治疗预后进行总结分析。结果:3例子宫内膜癌病例初治时均为早期子宫内膜样腺癌,组织学分级2例为3级,1例为2级,其中2例Ia期患者术后未接受任何辅助治疗,1例II期患者行了术后辅助化疗及同步放化疗。3例患者分别在发病60个月、12个月、32个月时发现脑转移,1例为小脑转移,2例为顶叶转移,其中有2例伴有颅外其他部位转移。确诊脑转移后1例行了手术+TOMO（螺旋断层精确放射治疗）,生存期约6个月;1例接受了IMRT（调强适形放疗）,现已存活6个月至今;1例未治疗,生存期仅12天。结论:子宫内膜癌脑转移发生率低,经过个体化多模式综合治疗可以有效地控制脑部转移病灶,缓解患者临床症状并延长患者的生存期。     

系统的淋巴结清扫术在子宫内膜癌治疗决策中的价值及可行性分析

背景与目的：淋巴结清扫术在子宫内膜癌治疗中的价值一直有争议,国内多数医院仅对部分高危型子宫内膜癌患者行淋巴结活检或选择性盆腔淋巴结切除术,罕有妇科医生对子宫内膜癌行系统的盆腔淋巴结清扫＋腹主动脉旁淋巴结清扫。本文探讨系统的淋巴结清扫术在子宫内膜痛治疗决策中的价值以及手术的可行性。方法：回顾2005年1月-2008年7月在我院行系统的腹膜后淋巴结清扫术的128例子宫内膜癌,对其临床病理特点、淋巴结转移情况、术后治疗决策改变情况以及手术并发症进行分析。结果：128例患者中19例（14．8％）出现淋巴结转移,其中盆腔淋巴结转移15例（11．7％）,腹主动脉旁淋巴结转移11例（8．6％）,7例患者同时出现盆腔及腹主动脉旁淋巴结转移,4例患者仅有腹主动脉旁淋巴结转移。病理类型、组织学分化程度、肌层浸润深度以及淋巴血管间隙浸润与淋巴结转移相关（P〈0．05）。15例患者因淋巴结转移分期升级,术后需要辅以化疗和／或放疗;另50例中危、中高危早期患者因手术排除了子宫外转移免去术后辅助治疗。8例（6．3％）患者术后出现并发症,其中盆腔感染3例,阴道残端出血2例,不全性低位肠梗阻、深静脉血栓伴淋巴囊肿和腔隙性脑梗塞各1例。中位手术时间为150min．中位出血量为300mL,其中27例（21．1％）患者接受输血治疗。结论：在子宫内膜癌患者中行系统的淋巴结清扫足安全可行的,通过全面的手术分期可以明确淋巴结转移情况,准确提供预后相关信息,指导术后辅助治疗。     

Intramedullary spinal cord metastases in breast cancer: report of four cases and review of the literature

Intramedullary spinal cord metastases (ISCM) are usually the result of rapidly progressing systemic cancer. Breast cancer represents one of the most common solid tumors associated with the development of ISCM at rather advanced stages of disease. In the present report we describe four new cases with advanced breast cancer developing ISCM. All cases presented herein indicated that ISCM is a late manifestation of disseminated breast cancer. Three of these patients had been treated for approximately 1–3 years for metastatic disease. Once ISCM developed, concurrent asymptomatic brain metastases were detected in one case, concurrent symptomatic brain disease (cerebellar) was present at the time of cervical ISCM diagnosis in another patient, and in another case, ISCM developed metachronously at 18 months after the diagnosis of symptomatic brain metastases treated by whole brain radiotherapy. One of these cases had brain metastases at presentation, while at relapse developed leptomeningeal carcinomatosis treated successfully, but followed shortly, as a terminal event, by ISCM and parenchymal brain recurrence.All but one patient experienced a rather rapidly evolving disease course leading to death after 2–5 months from widespread neuraxis dissemination of their cancer, while one patient is still alive 6 months after the diagnosis of ISCM. All four cases, added to the list of the anecdotally reported cases of ISCM after breast cancer, undermine the ominous prognosis and limited treatment options available for this disease manifestation, and an extensive literature review and discussion of similar cases is provided.     

Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy

PURPOSE: To determine the outcome of patients after radical radiotherapy (RT) for isolated vaginal recurrence of endometrial carcinoma and to determine the clinical and pathologic predictors of outcome. METHODS AND MATERIALS: We reviewed the records of 91 patients treated at our institution between 1960 and 1997 with radical RT for vaginal recurrence after definitive surgery for endometrial carcinoma. Thirty-one percent of the patients received external beam RT (EBRT) alone, 12% received brachytherapy alone, and 57% received a combination. The median dose of radiation was 75 Gy (range 34-122). All end points were measured from the time of the first recurrence. The median duration of follow-up after recurrence was 58 months (range 1-289). RESULTS: The 2- and 5-year local control (LC) rate and overall survival rate was 82% and 75% and 69% and 43%, respectively. The median time from initial diagnosis of endometrial cancer to death from disease was 38 months. On univariate analysis, a dose to the relapse site of > or =80 Gy and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved LC. On multivariate analysis, only the type of treatment correlated significantly with LC (p = 0.03). On univariate analysis, Grade 1 or 2 vs. Grade 3 tumor and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved overall survival. CONCLUSION: RT provides excellent LC of isolated vaginal recurrences of endometrial carcinoma, particularly when high doses are given using a combination of EBRT and brachytherapy. However, distant metastases frequently develop despite local disease control, contributing to a 5-year overall survival rate of <50%. For patients who have an isolated vaginal recurrence, the time from initial diagnosis of endometrial cancer to death from disease is usually >3 years. For this reason, in studies of adjuvant RT, long-term follow-up is required to permit evaluation of the impact of treatment on survival.     

Management of brain metastases from ovarian and endometrial carcinoma with stereotactic radiosurgery

BACKGROUND

Metastases to the brain from ovarian and endometrial carcinoma are uncommon and to the authors' knowledge consensus regarding optimal management is lacking. Stereotactic radiosurgery (SRS) has proven useful for the treatment of many benign and malignant brain tumors. In the current study, the authors evaluated outcomes after SRS in patients with ovarian and endometrial carcinoma.

METHODS

Twenty‐seven patients with brain metastases underwent gamma–knife SRS. Six patients had endometrial carcinoma, whereas 21 patients had ovarian carcinoma. Eighteen patients also received whole–brain radiotherapy. A total of 68 tumors were treated with gamma–knife SRS.

RESULTS

At the time of last follow–up, 1 patient was still alive and 26 had died. The median survival was 7 months after the initial diagnosis of brain metastasis and 5 months after SRS. The 1‐year survival rate after radiosurgery was 15% and that from the diagnosis of brain metastases was 22%. On final imaging, all tumors were controlled without further growth. Two patients (7.4%) developed new or progressive neurologic deficits after SRS.

CONCLUSIONS

SRS is an acceptable choice for the treatment of brain metastases resulting from ovarian and endometrial carcinoma, and provides local tumor control with limited morbidity. Careful patient selection is warranted in the setting of patients with uncontrolled systemic disease in whom a limited survival benefit is expected. Cancer 2008. © 2008 American Cancer Society.     

Two cases with long-term disease-free survival after resection and radiotherapy for solitary brain metastasis from breast cancer with extensive nodal metastases

Two rare cases, each with a solitary brain metastasis from breast cancer with extensive nodal metastases as the first site of distant metastasis, were locally treated with surgery and irradiation. The outcome of the two treated cases indicated an excellent and non-recurrent post-therapeutic survival period of more than 3 and 8 years, respectively. In a 50-year-old woman (Case 1), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with doxorubicin and tegafur-uracil (UFT) and hormonal therapy with tamoxifen for left breast cancer. The brain metastasis was treated twice surgically followed by radiotherapy. One year and 6 months later, local recurrence of the brain metastasis appeared and was treated surgically again. No other treatment was done thereafter. Since then, no other distant or lymph node metastasis occurred, and to date her outcome has been non-eventful for 8 years and 5 months. In a 63-year-old woman (Case 2), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with cyclophosphamide, epirubicin and fluorouracil (CEF) for right breast cancer. The brain metastasis was treated locally with surgery and irradiation of 50 Gy. She thereafter received no further treatments. Since then neither distant metastases nor local recurrence have developed, and to date the post-treatment outcome has been uneventful for 37 months. Our findings suggest that patients who developed a solitary brain metastasis as the first site of distant metastasis from breast cancer have a chance of achieving long-term disease-free survival when treated with aggressive local therapy, even in the presence of extensive lymph node metastases at the primary surgery site for breast cancer.     

Treatment and prognosis of brain metastases from breast cancer

Background To analyze retrospectively the results of treatments for patients with brain metastases from breast cancer. Materials and Methods The records of 65 breast cancer patients with brain metastases who were treated between 1985 and 2005 were reviewed. For brain metastases, 11 patients (17%) were treated with surgical resection followed by radiotherapy, and the remaining 54 patients were treated with radiotherapy alone. Systemic chemotherapy was also administered to 11 patients after brain radiotherapy. Results The overall median survival for all patients was 6.1 months (range, 0.4–82.2 months). In univariate analysis, treatment modality, Karnofsky performance status (KPS), administration of systemic chemotherapy, extracranial disease status and total radiation dose each had significant impact on overall survival, and in multivariate analysis, treatment modality, KPS and administration of systemic chemotherapy were significant prognostic factors. Eight patients survived for more than 2 years after the diagnosis of brain metastases, and all these patients were treated with surgical resection and/or systemic chemotherapy in addition to radiotherapy. For the 45 patients treated with palliative radiotherapy (without systemic chemotherapy), the improvements in neurological symptoms were observed in 35 patients (78%), with the median duration of improvement of 3.1 months (range, 1.5–4.4 months). Conclusions The prognoses for patients with brain metastases from breast cancer were generally poor, although selected patients may survive longer with intensive brain tumor treatment, such as surgical resection and/or systemic chemotherapy in addition to brain radiotherapy. For patients with unfavorable prognoses, palliative radiotherapy was effective in improving the quality of the remaining lifetime.     

Central nervous system metastases in women after multimodality therapy for high risk breast cancer

Background: Central nervous system (CNS) relapse is increasing in breast cancer. This increase may reflect altered failure patterns from adjuvant therapy, more effective systemic therapy with improved control in non-CNS sites, or a resistant breast cancer subtype.Methods: To determine the factors associated with clinical CNS relapse, we examined response to neoadjuvant chemotherapy (chemosensitivity), time to relapse and sites of relapse in a cohort of 140 patients without evidence of metastasis at presentation.Results: At 5 years (interquartile range 3–6 years), 44 (31%) patients developed distant metastases, including 13 with CNS metastases. CNS relapse was early (median 24 months after diagnosis) and associated with relapse in bone and liver, suggesting hematogenous dissemination. Those with CNS relapse were younger at diagnosis (40 versus 49 years) and more likely to have lymphovascular invasion in the primary tumor compared with non-CNS metastases. Response to neoadjuvant chemotherapy was not different (69% versus 73% response rate) between the two groups. Extent of residual disease after chemotherapy was strongly associated with relapse outside the CNS but not CNS relapses. The CNS was an isolated or dominant site of metastasis in 8 of 13. Despite treatment, most patients with CNS involvement died of neurologic causes a median of 6 months later.Conclusion: Breast cancers that develop CNS metastases differ from those that develop metastases elsewhere. Both tumor behavior and reduced chemotherapy accessibility to the CNS may contribute to increased CNS involvement in breast cancer patients treated with multimodality therapy.     

Intraperitoneal hyperthermic chemotherapy after cytoreduction in patients with peritoneal metastases from endometrial cancer. The next frontier?

BackgroundEndometrial cancer is the most common malignancy of the female genital tract. For cancers detected at an advanced stage or intraperitoneal relapse, the prognosis is poor. Optimal cytoreductive surgery (CRS) is the most accepted treatment; however, patients with advanced intraperitoneal disease might benefit from hyperthermic intraoperative peritoneal chemotherapy (HIPEC).The aim of this study was to analyze recurrence-free survival (RFS) after CRS and HIPEC in a large series of patients with peritoneal metastases from endometrial cancer.MethodsPatients with a diagnosis of endometrial cancer with primary or recurrent peritoneal dissemination were included. All patients underwent CRS plus HIPEC. Data were prospectively collected in the Spanish Group of Peritoneal Oncological Surgery (GECOP) database.ResultsForty-three patients with endometrial cancer and peritoneal metastasis were included. Fifteen patients (35%) were diagnosed with G3 endometrioid carcinomas and 28 (65%) with other non-endometroid histologies. A completeness of cytoreduction score of CC-0 was achieved in 41 patients (95%). RFS at 5 years was 23%, being factors related to worse RFS: treatment with preoperative chemotherapy (p = 0.027), resection of more than three peritoneal areas (p = 0.010), cytoreduction of the upper abdominal space (p = 0.023), HIPEC treatment with paclitaxel (p = 0.013), and the presence of metastatic lymph nodes (p = 0.029).ConclusionsBetter RFS rates after CRS and HIPEC were observed for patients with the following characteristics: cytoreductive surgery without preoperative chemotherapy, complete surgery performed with limited surgical maneuvers, treated with cisplatin, and no lymph node metastases.SynopsisEndometrial cancer has a poor prognosis when diagnosed at advance stage. Patients with intraperitoneal metastases from endometrial cancer may benefit from CRS plus HIPEC with improvement in the recurrence-free survival results.     

Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review

The aim of the study was to collect the available data on central nervous system (CNS) metastases from esophageal and gastric cancer. A PubMed, EMBASE, SCOPUS, Web of Science, LILACS, Ovid and Cochrane Library search was performed. Thirty-seven studies including 779 patients were considered. Among the data extracted, treatment of tumor and brain metastases (BMs), time to BMs development, number and subsite, extracerebral metastases rate, median overall survival (OS) and prognostic factors were included. For esophageal cancer, the median OS from diagnosis of BMs was 4.2 months. Prognostic factors for OS included: performance status, multimodal therapy, adjuvant chemotherapy, single BM, brain only disease and surgery. For gastric cancer, median OS was 2.4 months. Prognostic factors for OS included: recursive partitioning analysis class 2, stereotactic radiosurgery (SRT) and use of intrathecal therapy. HER2-positive gastric cancer was shown to be associated with a higher risk and shorter time to CNS relapse. Patients harboring BMs from gastric and esophageal tumors, except cases with single lesions that are treated aggressively, have a poor prognosis. SRT (plus or minus surgery and whole brain radiotherapy) seems to give better results in terms of longer OS after brain relapse.     

Adjuvant radiotherapy for stage I endometrial cancer: systematic review and meta-analysis.

The role of adjuvant radiotherapy in stage I endometrial cancer following surgery remains unclear. The management for these patients varies widely, particularly in stage I patients with different risk factors. Using the methodology of Cochrane Collaboration, we did a systematic and meta-analysis of all know randomised controlled trials which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer. The meta-analysis was carried out on four trials (three published and one unpublished) and a total of 1770 patients. The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 [95% confidence interval (CI) 0.17-0.44, P < 0.00001], which is a 72% reduction in the risk of pelvic relapse (95% CI 56% to 83%) and an absolute risk reduction of 6% (95% CI of 4% to 8%). The reduction in the risk of locoregional recurrence did not translate into a reduction in the risks of death from all causes, endometrial cancer death or distant recurrence. A subgroup analysis showed a trend towards the reduction in the risks of death from all causes and endometrial cancer in patients with multiple high risk factors (including stage 1c and grade 3). External beam pelvic radiotherapy should be considered in patients with multiple high-risk features including stage 1c and grade 3. However, it carries an inherent risk of damage and toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.     

Radiotherapy in Ewing tumors of the vertebrae: treatment results and local relapse analysis of the CESS 81/86 and EICESS 92 trials

PURPOSE: Treatment results in patients with Ewing tumors of the vertebrae enrolled in the Cooperative Ewing's Sarcoma Study (CESS) 81, 86, and the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92 trials were analyzed with special emphasis on radiation-associated factors. PATIENTS AND METHODS: A retrospective analysis was performed on 116 patients with primary tumors of the cervical, thoracic, or lumbar vertebrae treated between 1981 and 1999. Furthermore, a relapse analysis was done on those patients who underwent radiotherapy and subsequently had a local recurrence. RESULTS: A total of 64.6% of the patients received definitive radiotherapy; 27.5% of patients had surgery and radiotherapy. Only 4 patients (3.4%) underwent definitive surgery. Twenty-seven patients presented with metastases at diagnosis. 22.4% of the total group developed a local relapse. Among the subgroup with definitive radiotherapy, local recurrence was seen in 17 of 75 patients (22.6%). Event-free survival and survival at 5 years were 47% and 58%, respectively. Of the 14 evaluable patients with a local relapse after radiotherapy, 13 were in-field. No correlation between radiation dose and local control could be found. CONCLUSION: Surgery with wide resection margins is rarely possible. The results after definitive radiotherapy in vertebral tumors are comparable to those of other tumor sites when definitive radiotherapy is given. Nearly all local relapses after radiotherapy are in-field.     

Intramedullary Spinal Cord Metastases in Breast Carcinoma: Report of Two Cases and Review of the Literature

Abstract

Intramedullary spinal cord metastases (ISCM) are usually the result of rapidly progressing systemic malignancy. Breast cancer is one of the most common solid tumors with a high propensity of CNS dissemination. In the present report we describe two new cases with advanced breast cancer developing ISCM after a variable disease course. One of these patients had brain metastases at presentation, while at relapse developed leptomeningeal carcinomatosis which was treated successfully, but followed shortly, as a terminal event, by ISCM and parenchymal brain recurrence. The other patient was treated initially for locally advanced breast cancer and after multiple locoregional relapses, she developed liver metastases and subsequent ISCM and asymptomatic parenchymal brain deposits. Both patients experienced a rather rapidly evolving disease course leading to death 2 and 4 months, respectively, after widespread neuraxis dissemination of their cancer. Both these cases, added to the list of the anecdotally reported cases of ISCM after breast cancer, undermine the ominous prognosis and limited treatment options available for this disease manifestation, and an extensive literature review and discussion of similar cases is provided.     

Excessive Soft Tissue Reaction after Stereotactic Body Radiation Therapy in a Woman with Four Different Cancer Diagnoses

Patients experiencing several cancers can be a challenge, as optimal treatment options for the different cancers might interfere with each other. In this case report, we present a woman diagnosed with 4 different types of cancer. She was treated with surgery, chemotherapy and radiotherapy. Her performance status was generally good, and she tolerated the treatment very well, except some troublesome side effects in the thoracic soft tissue after stereotactic body radiotherapy.Key Words: Stereotactic body radiotherapy, Soft tissue reaction, Multiple malignancies     

Does the incidence and outcome of brain metastases in locally advanced non-small cell lung cancer justify prophylactic cranial irradiation or early detection?

OBJECTIVE: The radical treatment of locally advanced non-small cell lung cancer (LA-NSCLC) currently involves combined modality therapy (CMT) with the use of chemotherapy in addition to radiation therapy and/or surgery. Chemotherapy has been shown to improve survival, but does not alter brain relapse. We reviewed the outcomes of Stage IIIA and IIIB LA-NSCLC patients treated with CMT at our institution. We assessed the incidence of brain metastases and the management and outcome of these patients. METHODS: Using our radiation-planning database (RSTS), we identified 230 consecutive patients from the years 1999 and 2000 who received radical radiation therapy to the lung. Extracting data from the chart, we identified 83 patients who were treated radically with chemotherapy, radiation and possibly surgery. These patients form the basis of this study. RESULTS: At 2 years, the actuarial rates for any brain failure, first failure in the brain and sole failure in the brain were 34.2%, 24.6% and 11.0%, respectively. Age was the only factor among sex, histology, stage, weight loss and the timing of chemotherapy and radiation that predicted for an increased risk of first failure in the brain. Patients less than age 60 had a risk of 25.6% versus 11.4% for those greater than 60 (p = 0.022). Among the patients who failed first in the brain, those who had aggressive management of their brain metastases with surgical resection in addition to whole brain radiotherapy had a median survival of 26.3 months compared with 3.3 months for those treated with palliative whole brain radiotherapy alone. CONCLUSION: Brain metastases are common in patients with LA-NSCLC treated with CMT. These patients may benefit from either prophylactic cranial irradiation or early detection and aggressive treatment of brain metastases.     

Radiotherapy of brain metastases

The effect of radiotherapy in 254 cases of brain metastases, treated between 1977 and 1984, were studied. The cases included 141 of lung cancer, 28 of mammary cancer, and 85 of other primary sites. The percentages of patients with improvement in clinical symptoms were 8, 39, and 66, respectively. These were groups of patients irradiated with less than 30 Gy, 30 Gy to 50 Gy, and more than 50 Gy. The 50% survival periods from the start of irradiation for the last group were as follows: for radiotherapy only, 4.1 months, radiotherapy and surgery, 4.2 months, radiotherapy and chemotherapy combined, 6.9 months, radiotherapy, surgery and chemotherapy combined, 12.1 months. The intervals between the initial diagnosis and brain metastases were different in lung cancer and mammary cancer, but the prognosis after brain metastases showed little difference between them.     

Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer

Background:

The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer.

Methods:

Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed.

Results:

A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1–2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases.

Conclusions:

Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.     

Annexin‐A2 as predictor biomarker of recurrent disease in endometrial cancer

Endometrial carcinomas, the most common malignant tumour of the female genital tract, are usually diagnosed at an early stage with uterine‐confined disease and an overall favourable prognosis. However, up to 20% of endometrial carcinomas will end up in recurrent disease, associated with a drop in survival and representing the major clinical challenge. Management of this group of risk patients relies on robust biomarkers that may predict which endometrial carcinomas will relapse. For this, we performed a proteomic analysis comparing primary lesions with recurrences and identified ANXA2 as a potential biomarker associated with recurrent disease that we further validated in an independent series of samples by immunohistochemistry. We demonstrated in vitro a role for ANXA2 in the promotion of metastasis rather than interfering with sensitivity to radio/chemotherapy. In addition, ANXA2 silencing resulted in a reduced metastatic pattern in a mice model of endometrial cancer dissemination, with a limited presence of circulating tumor cells. Finally, a retrospective study in a cohort of 93 patients showed that ANXA2 effectively predicted those endometrioid endometrial carcinomas that finally recurred. Importantly, ANXA2 demonstrated a predictive value also among low risk Stage I endometrioid endometrial carcinomas, highlighting the clinical utility of ANXA2 biomarker as predictor of recurrent disease in endometrial cancer. Retrospective and prospective studies are ongoing to validate ANXA2 as a potential tool for optimal stratification of patients susceptible to receive radical surgery and radio/chemotherapy.     

Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long-term evaluation of the risk–benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted. Int. J. Cancer 76:325–330, 1998.© 1998 Wiley-Liss, Inc.     

Improved palliation of cerebral metastases in epithelial ovarian cancer using a combined modality approach including radiation therapy, chemotherapy, and surgery.

PURPOSE: Recent reports suggest an increasing incidence of CNS metastases in patients with ovarian cancer. We reviewed our experience in the management of brain metastases from ovarian carcinoma and merged our results with those of several other series reported in the literature to determine prognostic factors and the role of chemotherapy, radiation therapy, and surgery. PATIENTS AND METHODS: From 1977 to 1990, 15 of 795 patients who were treated for epithelial ovarian cancer at Duke University developed brain metastases. Fourteen of the patients were treated for their brain metastases; this included radiation therapy (RT; four), surgery and RT (one), RT and systemic chemotherapy (six), and all three treatment modalities (three). A meta-analysis was performed that combined the data from the current series with those of several recent clinical series that reviewed patients with brain metastases from ovarian carcinoma (67 patients total) to elucidate the impact of treatment and extent of disease on survival. RESULTS: In the current series, median survival (MS) after the diagnosis of brain metastases was 9 months. For the combined series, MS was 5 months. Thirteen patients who were treated with whole-brain RT and systemic chemotherapy (MS, 7 months), 10 patients who were treated with RT and surgery (MS, 10 months), and nine patients who were treated with all three modalities (MS, 16.5 months) had significantly longer survival than 19 patients who were treated with RT alone (MS, 3 months) (P = .05, P = .01, and P < .001, respectively). In a multivariate analysis, the only variable that provided prognostic information was treatment, namely the addition of systemic chemotherapy or surgery to RT for the treatment of brain metastases. CONCLUSION: Multimodal treatment of patients with brain metastases from ovarian cancer can result in significant palliation.