Purpose: To evaluate the efficacy of the aromatase inhibitor letrozole in preselected estrogen receptor (ER)^positive relapsed epithelial ovarian cancer patients and to identify markers that predict endocrine-sensitive disease. Experimental Design: This was a phase II study of letrozole 2.5 mg daily until clinical or marker evidence of disease progression in previously treated ER-positive ovarian cancer patients with a rising CA125 that had progressed according to Rustin's criteria. The primary end point was response according to CA125 and response evaluation criteria in solid tumors (RECIST) criteria. Marker expression was measured by semiquantitative immunohistochemistry in sections from the primary tumor. Results: Of 42 patients evaluable for CA125 response, 7 (17%) had a response (decrease of >50%), and 11 (26%) patients had not progressed (doubling of CA125) following 6 months on treatment. The median time taken to achieve the CA125 nadir was 13 weeks (range 10-36). Of 33 patients evaluable for radiological response, 3 (9%) had a partial remission, and 14 (42%) had stable disease at 12 weeks. Eleven patients (26%) had a PFS of >6 months. Subgroup analysis according to ER revealed CA125 response rates of 0% (immunoscore, 150-199), 12% (200-249), and 33% (250-300); P = 0.028, m 2 for trend. Expression levels of HER2, insulin-like growth factor binding protein 5, trefoil factor 1, and vimentin were associated with CA125 changes on treatment. Conclusions: This is the first study of a hormonal agent in a preselected group of ER-positive ovarian cancer patients. A signature of predictive markers, including low HER2 expression, predicts response.
Purified SERP-1, a virus-encoded secreted glycoprotein, reduces plaque growth after primary balloon-mediated injury. Plaque development is decreased by inhibition of serine proteinase activity and is associated with a focal reduction in macrophage infiltration immediately after injury. Investigation of serine proteinase inhibitors may provide new insight into the regulation of arterial responses to injury.
Summary Cognitive function items are increasingly included in quality of life measures, and complaints of concentration and memory difficulties are often reported by cancer patients. The aim of this study was to examine the factors influencing patients' level of complaint by comparing subjective reports with objective test performance of a sample of adult lymphoma patients, disease-free and > 6 months after treatment. There was no significant difference between complainers and non-complainers in sociodemographic or clinical characteristics or in their performance on standard neuropsychometric tests of concentration and memory. Those reporting concentration and memory difficulties had significantly higher scores on measures of anxiety, depression and fatigue. This calls into question the validity of including cognitive function items in self-report quality of life measures. Patients who report concentration and memory difficulties should be screened for clinically significant and potentially remediable mood disorder. Objective testing remains the method of choice for assessing higher mental function.
Summary The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor a (TGF-a) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-a mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-a mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-a mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-a (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-a (P = 1.00). EGF receptor mRNA expression was significantly and positively associated with serous histology (P = 0.006) but not with stage or grade. Neither EGF nor TGF-a showed any link with histological subtype or stage. The survival of patients with malignant tumours possessing EGF receptor mRNA was significantly reduced compared with that of patients whose tumours were negative (P = 0.030 for all malignant tumours; P= 0.007 for malignant epithelial tumours only). In contrast, neither the expression of TGF-a nor EGF was related to survival. These data suggest that the presence of EGF receptor mRNA is associated with poor prognosis in primary ovarian cancer.
Si.ary An audit was carried out of 51 oncology patients referred to a clinical psychology service to identify the characteristics of patients selected for referral and to assess change following psychological intervention. A survey was conducted of an unselected sample of oncology patients representative of the workload of the oncology department from which the referrals came, to determine the prevalence of comparable psychosocial problems among patients who were not referred for help and to assess whether doctors were aware of the problems patients reported. Data were collected using the Hospital Anxiety and Depression (HAD) and Mental Adjustment to Cancer (MAC) scales and a problem checklist devised for this study. Referred patients were significantly more anxious and depressed (P<0.001) and showed poorer adjustment on MAC scales than the surveyed sample, but 30% of the latter group warranted assessment for anxiety and 23% for depression. The number of psychosocial problems was the best single predictor of clinically significant mood disorder irrespective of the specific problems of their severity. Intervention was associated with a significant improvement in distress and problems for referred patients by the time of discharge. Psychosocial problems were often undetected by staff even in referred patients. The checklist is a feasible screening method for potentially remediable problems which are cumulatively a significant contributor to cancer patients' distress.
BACKGROUNDA review of clinicopathologic features and outcome in women with carcinosarcoma of the ovary (also known as malignant mixed mesodermal tumor [MMMT]) compared with a group of women with serous adenocarcinoma (SAC) of the ovary was conducted.METHODSBetween 1984 and 2002, 1568 patients with epithelial ovarian carcinoma and 70 patients with ovarian carcinosarcoma underwent treatment at the Edinburgh Cancer Centre. Analysis was performed on 65 patients with MMMT, and 746 patients with SAC were selected as a group for comparison. Baseline variables were recorded prospectively and response to chemotherapy and progression‐free and cause‐specific survival between the groups were compared.RESULTSPatients with carcinosarcoma had a mean age of 66.6 years, which is significantly older than those with SAC (62.0 years) (P < 0.001). The objective response rate to platinum‐based chemotherapy was found to be significantly lower in patients with carcinosarcoma (25% vs. 60%; P = 0.02). Cause‐specific survival in the carcinosarcoma group was poor and significantly shorter than that observed in the SAC group (median survival of 8.2 months vs. 20.7 months; P < 0.0001). Progression‐free survival in patients with carcinosarcoma also was found to be significantly shorter compared with patients with SAC (median progression‐free survival of 6.4 months vs. 12.1 months; P < 0.001). Achieving optimal debulking at the time of initial surgery was found to be a highly significant factor in patients with carcinosarcoma with regard to determining outcome (median survival of 14.8 months for patients with optimally debulked International Federation of Gynecology and Obstetrics Stage III disease vs. 3.1 months for patients with suboptimally/nondebulked Stage III disease; P < 0.001).CONCLUSIONSOvarian carcinosarcoma is a distinct entity with a poor prognosis. Patients with carcinosarcoma differ from those with SAC with regard to having an older mean age of onset, an inferior response to platinum‐based chemotherapy, and worse progression‐free and cause‐specific survival. The extent of benefit from chemotherapy is unclear. Cancer 2004. © 2004 American Cancer Society.
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