Re: new guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]. Gynecologic Cancer Intergroup.
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Biomarkers, Tumor↗
Biomedical subjects
G B Kristensen
Publications and source records attributed to G B Kristensen.
Histopathologic subtyping of cervical adenocarcinoma reveals increasing incidence rates of endometrioid tumors in all age groups: a population based study with review of all nonsquamous cervical carcinomas in Norway from 1966 to 1970, 1976 to 1980, and 1986 to 1990.
BACKGROUND: The effect of histopathologic review and subclassification on incidence rates for nonsquamous cell carcinoma (non-SCC) of the uterine cervix in the Norwegian population was evaluated. METHODS: All non-SCC from three 5-year periods (1966-70, 1976-80, and 1986-90) were reviewed, classified, and graded. RESULTS: Incidence rates were 1.2, 1.2, and 1.7 per 100,000 for adenocarcinoma and 0.1, 0.3, and 0.5 per 100,000 for other carcinomas in the three periods. Adenocarcinomas increased in all age groups, most markedly in women younger than 35 years. Incidence rates for both major subgroups of endocervical (EC) and endometrioid (EM) carcinomas increased for women younger than 55 years. After 1976-80, the incidence rate for EC, but not for EM, decreased in women older than 55 years. Endometrioid carcinoma became the dominant histologic subtype in 1986-90. Shifts toward lower clinical stages and younger age were found for EC, EM, and carcinoma not otherwise specified (NOS). Patients with NOS, clear cell, serous, or glassy cell/undifferentiated carcinoma were older, and their disease was diagnosed at higher stages. Distribution of International Federation of Gynecology and Obstetrics (FIGO) stages was: Stage I: 62%; Stage II: 21%; Stage III: 12%; and Stage IV: 5%. Distribution of histologic subgroups was: EC:, 24%; EM: 21%; NOS: 16%; clear cell: 7%; adenosquamous: 7%; small cell: 6%; serous: 4%; undifferentiated: 3%; and villoglandular carcinoma: 2%. Other subgroups were seen only sporadically. CONCLUSIONS: Incidence rates of non-SCC of the uterine cervix are increasing in Norway. Improvements in diagnostic procedures may explain shifts toward lower stage and age of patients but not the observed differences between histologic subgroups.
Adenocarcinoma↗
E-cadherin and alpha-, beta-, and gamma-catenin protein expression is up-regulated in ovarian carcinoma cells in serous effusions.
The aims of this study were firstly, to investigate the expression of E-cadherin complex proteins in ovarian carcinoma cells in serous effusions and in primary and metastatic lesions; and secondly to study the value of these four proteins and calretinin, a mesothelial marker, in the differential diagnosis of ovarian carcinoma cells from reactive mesothelial cells in effusions. Sixty-seven malignant effusions and 97 corresponding primary (n=36) and metastatic (n=61) lesions were immunohistochemically stained for E-cadherin and alpha-, beta-, and gamma-catenin. Staining extent and intensity were scored. Effusion specimens were additionally analysed for calretinin immunoreactivity. Membrane immunoreactivity for E-cadherin and alpha-, beta-, and gamma-catenin was detected on carcinoma cells in the majority of the effusions, but rarely on reactive mesothelial cells (p<0.001 for all markers). Calretinin immunoreactivity was confined to mesothelial cells (p<0.001). An association was seen between E-cadherin and alpha-catenin expression, in both effusions and solid tumours, and for beta-catenin in solid tumours (range p<0. 001 to p=0.014). Up-regulation of all four cadherin complex proteins was seen in carcinoma cells in effusions, when compared with corresponding primary tumours (range p<0.001 to p=0.028). As with effusions, metastatic lesions showed up-regulation of alpha-, beta-, and gamma-catenin when compared with primary carcinomas (p=0.002-0. 015). Carcinoma cells in effusions showed in addition elevated levels of E-cadherin when compared with metastatic lesions (p<0.001). Staining results in effusions showed no association with effusion site, tumour type or histological grade. Immunoblotting on 29 malignant effusions confirmed the presence of all four proteins in the majority of samples and co-precipitation of E-cadherin and beta-catenin was seen in ten specimens examined. E-cadherin complex proteins are widely expressed in ovarian carcinoma cells. Together with calretinin, they form a powerful battery of markers for the cytological diagnosis of carcinoma cells in effusions. The up-regulation of E-cadherin complex proteins in serous effusions and metastatic lesions may mark an early metastatic phenotype and possibly mediates survival of tumour cells at these sites through the inhibition of apoptosis.
Ascitic Fluid↗
Effects of paclitaxel on CA-125 serum levels in ovarian cancer patients.
OBJECTIVE: As in vitro activation of ovarian carcinoma cells in terms of CA-125 secretion by taxanes has been demonstrated, we were interested in whether taxanes also modulate CA-125 expression in vivo. METHODS: Serum CA-125 was determined immediately before and 24 h after paclitaxel-containing chemotherapy in 53 ovarian carcinoma patients. To test the quality of the analysis methods and the biological variation of untreated patients, serum CA-125 levels of two control groups were analyzed. RESULTS: Median CA-125 concentration was 107 kU/liter 24 h after chemotherapy treatment compared with 99 kU/liter the day before paclitaxel treatment. Changes in CA-125 serum levels observed immediately after paclitaxel treatment were not correlated to treatment response. However, overall change in CA-125 serum concentration was a good predictor of response to paclitaxel containing treatment. Patients achieving a complete or partial response had a significant reduction of median CA-125 levels, whereas tumor progression was associated with increased CA-125 levels. Only for the group of patients obtaining a complete response was a decrease in the median relative CA-125 value observed. CONCLUSION: Paclitaxel-induced modulation of CA-125 expression could not be confirmed in vivo.
Adult↗
Expression of CD44 in effusions of patients diagnosed with serous ovarian carcinoma--diagnostic and prognostic implications.
CD44 is a family of cell adhesion molecules involved in a variety of cellular functions. The present study analysed the expression of two CD44 isoforms in serous effusions of patients diagnosed with ovarian carcinoma and corresponding primary and metastatic lesions. Fifty-eight effusions, 23 primary ovarian tumours, and 44 metastatic lesions were studied for protein expression of CD44s and v3-10 using immunohistochemistry. Results were correlated with clinical parameters. CD44v3-10 was seen in carcinoma cells in the majority of cases at all sites. Malignant effusions showed an up-regulation of CD44s compared to both primary tumours and metastatic solid lesions. Mesothelial cells frequently expressed CD44s, but were rarely immunoreactive for v3-10. CD44s immunoreactivity in cancer cells in effusions was significantly more often observed in patients with FIGO stage 3 than in stage 4 patients (P = 0.045). Staining results did not correlate with age, effusion site, metastatic site, tumour grade or residual tumour mass after initial surgery. Likewise, comparison of overall and disease-free survival with expression of the CD44 isoforms studied did not reveal any statistically significant associations. The up-regulation in CD44 levels in effusions, primarily in stage 3 disease, suggests that adhesion of ovarian carcinoma cells to mesothelium may be regulated at the level of CD44s expression, and provides further evidence of phenotypic alteration in the transition from primary tumour cell clones to effusions. The similar expression profile of CD44 in carcinoma cells in peritoneal and pleural effusions supports our previous observations and the hypothesis that carcinoma cells in peritoneal effusions are truly metastatic.
Ascitic Fluid↗
Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous effusions from patients diagnosed with epithelial ovarian carcinoma: evidence of up-regulated Tn and Sialyl Tn antigen expression in effusions.
The object of this study was the investigation of carbohydrate antigen expression in malignant epithelial cells and benign mesothelial cells in serous effusions from patients diagnosed with epithelial ovarian carcinomas. In addition, to compare antigen expression in carcinoma cells in effusions with those of corresponding primary tumors and metastatic lesions. Sections from 63 malignant effusions from ovarian carcinoma patients and 15 reactive effusions were immunohistochemically stained, using 5 monoclonal antibodies for Lewis(y), Sialyl Lewis(x), Tn, and Sialyl Tn antigens. Tissue sections (n = 97) from corresponding primary ovarian carcinomas and metastatic lesions, as well as from 12 malignant mesotheliomas, were additionally stained using the above panel. Staining for the 4 antigens was seen in carcinoma cells in serous effusions in the majority of cases (range = 71% to 85%). In contrast, immunoreactivity was detected in mesothelial cells in only 6% to 23% of the specimens studied (P < .001 for all 5 markers). With the exception of B3 antibody against Lewis(y) antigen, malignant mesotheliomas stained negative, infrequently showing focal immunoreactivity. An up-regulation of Tn and Sialyl Tn expression was detected in carcinoma cells in effusions when compared with both primary tumors (P < .003 and P < .007, respectively) and metastatic lesions (P < .034 and .041, respectively). Cancer-associated carbohydrate antigens can thus be used as an adjunct in the differentiation between malignant epithelial and reactive mesothelial cells. Ovarian carcinoma cells in effusions show up-regulation of Tn and Sialyl Tn, possibly representing a transient phenotypic alteration facilitating metastasis.
Antigens, Tumor-Associated, Carbohydrate↗
TP53 alterations in relation to the cell cycle-associated proteins p21, cyclin D1, CDK4, RB, MDM2, and EGFR in cancers of the uterine corpus.
In the present study, TP53 alterations have been analysed and compared with the expression of the proteins p21, cyclin D1, cdk4, RB, EGFR, and MDM2 in 53 cancers of the uterine corpus. TP53 gene mutations analysed by CDGE/DGGE and direct sequencing showed a TP53 gene mutation in 18 per cent of the cases. TP53 gene mutations were not significantly related to overexpression or down-regulation of any of the proteins. Immunohistochemically, there was an increased protein level of TP53 in 77 per cent, p21 in 36 per cent, cyclin D1 in 45 per cent, cdk4 in 77 per cent, EGFR in 8 per cent, and MDM2 in 32 per cent of the cases. Expression of RB protein was normal in all cancers. Significant association of protein expression was seen between TP53 and MDM2 (p=0.005) and p21 and MDM2 (p=0.001). Furthermore, there may be an association between TP53 and p21 (p=0. 038) and cyclin D1 and cdk4 (p=0.045). The results revealed increased levels of TP53 protein in all MDM2-positive cases that did not show TP53 mutations, indicating TP53 protein stabilization and inactivation by complex formation with MDM2. In summary, the high number of cases showing an increased level of TP53 and cdk4 proteins suggests that these proteins play an important role in the neoplastic process in cancers of the uterine corpus.
Carcinoma↗
Aberrant expression of the cell cycle associated proteins TP53, MDM2, p21, p27, cdk4, cyclin D1, RB, and EGFR in cervical carcinomas.
OBJECTIVE: The aims of this study were to study aberrant expression and coexpression of the cell cycle associated proteins TP53, p21, p27, cyclin D1, cdk4, RB, EGFR, and MDM2 in cervical carcinomas, to correlate protein alterations with histopathological and clinical parameters, and to evaluate whether these alterations provide prognostic information. METHODS: Seventy-four cervical carcinomas and 10 cases of normal cervical epithelium from patients with benign uterine leiomyomas were investigated immunohistochemically for aberrant expression of the cell cycle associated proteins using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system. RESULTS: In normal cervical epithelium p27 immunostaining was identified in more than 50% of the cells, cdk4 in 5-50% of the cells, and EGFR in less than 5% of the cells, whereas no immunostaining for TP53, p21, MDM2, or cyclin D1 was detected. Positive RB protein staining was identified in all cases of normal cervical epithelium. RB protein staining was also identified in all carcinomas of the cervix uteri. Overexpression of p21 was found in 96% of the tumors, MDM2 in 35%, cdk4 in 69%, cyclin D1 in 3%, and EGFR in 20% of the tumors. A low level of p27 was observed in 65% of the cases. In a previous study, the TP53 protein level has been found to be elevated in 41 of the 74 (55%) cases included in this work. Significant coexpression was seen for TP53 and MDM2 (P = 0. 001); concording results were observed in 67% of the cases. There was no difference in aberrant expression or coexpression of any of the cell cycle regulatory proteins related to histological type, grade of differentiation, FIGO stage, or relapse-free survival. CONCLUSION: The high number of cases showing increased levels of p21 and cdk4 and decreased levels of p27 suggests that these proteins may be important in the pathogenesis of cervical carcinoma. Furthermore aberrant expression of MDM2 in a smaller but significant fraction of cases indicates that these proteins could also be involved in the development of these cancers. Finally our results indicate that MDM2 may protect against HPV-induced TP53 protein degradation.
Adult↗
Tumor size, depth of invasion, and grading of the invasive tumor front are the main prognostic factors in early squamous cell cervical carcinoma.
OBJECTIVE: The objective of this study was to evaluate the prognostic significance of clinical and histopathologic factors, including a new grading system focusing on the invasive tumor front. METHOD: A retrospective analysis of 125 surgically treated patients with squamous cell cervical carcinoma FIGO stage IB was conducted. For each tumor, the degree of keratinization, nuclear polymorphism, pattern of invasion, and degree of lymphoid infiltration at the invasive tumor front were graded and given scores between 1 and 4. RESULTS: Clinical tumor size, depth of invasion, and grading of the invasive front had prognostic significance in multivariate analysis, while lymph vascular space involvement, lymph node status, and grade of differentiation did not. Based on clinical tumor size, depth of invasion, and grading of the invasive tumor front, patients could be separated into three groups: One group with minimal risk of recurrence (5-year disease-free survival (DFS) of 100%) consisting of 24% of the patients, an intermediate group with a fairly low risk of recurrence (5-year DFS of about 92%), and a high risk group with a 5-year DFS of 45%. This latter group contained 26% of the patients with 78% of all relapses occurring in the total group of patients. The invasive tumor front grading was reliably reproducible, with inter- and intraobserver agreement of 79 to 87% and kappa values of 0.47 to 0.66. CONCLUSION: Clinical tumor size, depth of invasion, and grading of the invasive tumor front were the main predictors of prognosis in patients with stage IB squamous cell cancer of the cervix.
Adult↗
Karyotypic findings in tumors of the vulva and vagina.
Neoplasms of the vulva and vagina together account for less than 5% of all female genital tract cancers, and very few cases have been analyzed using chromosome banding techniques. We report the karyotypic findings in a consecutive series of ten tumors of the vulva and vagina; in addition to five squamous cell carcinomas of the vulva, we present the first cytogenetic analysis of two malignant melanomas and a Paget disease of the vulva, as well as an adenocarcinoma and a squamous cell hyperplasia of the vagina. Whereas no clonal karyotypic changes were found in the squamous cell hyperplasia of the vagina, the remaining nine malignant tumors showed clonal chromosome abnormalities. An inverse correlation was found between the degree of histologic differentiation and karyotypic complexity in the squamous cell carcinomas of the vulva. The malignant melanomas had chromosomal aberrations that have previously been described in malignant melanomas occurring elsewhere, but were less karyotypically complex. Cytogenetically unrelated clones were detected in the Paget disease of the vulva but not in any of the other tumors; this finding is consonant with the interpretation that at least a proportion of Paget disease of the vulva arises multicentrically within the epidermis from pluripotent stem cells.
Adenocarcinoma↗
Allelic imbalance at chromosome region 11q23 in cervical carcinomas.
The long arm of chromosome 11 has received much scrutiny as a high frequency of deletions of various sites has been observed in different tumour types, indicating the presence of putative tumour suppressor genes. In the present study, 81 primary cervical carcinomas were examined for allelic imbalance (AI) using nine microsatellite markers, mapping to the chromosomal region 11q23.1 where the ATM gene is located. AI at any locus in the region was found in 34 of 81 (42%) tumours. AI frequencies varied from 12 to 31% for the different markers used, with the highest frequency at marker D11S1294. Based on the findings of 17 cases with restricted areas of deletions, four chromosomal regions of possible importance in cervical carcinomas could be distinguished. The first region is located between the markers D11S1325 and D11S1819, the second region between D11S2179 and D11S1294, the third region between D11S1778 and D11S1818 and the fourth region between D11S1818 and D11S1347. The second region may thus contain part of the ATM gene. No association between AI of any marker and histopathological or clinical parameters was seen. When comparing the AI findings of the different loci with TP53 protein overexpression, the only significant association found was with D11S2179 located within the ATM gene. The results indicate that a tumour suppressor gene (or genes) on chromosome 11q.23.1 may be involved in carcinogenesis of the cervix and the involvement of the ATM gene remains a possibility.
Adult↗
The significance of metastasis-related factors cathepsin-D and nm23 in advanced ovarian cancer.
BACKGROUND: Different regulators or effectors of the metastatic cascade can be of prognostic and/or predictive significance. Cathepsin-D and nm23 operate at different levels of the metastatic process and have not yet been analyzed in combination in ovarian cancer. PATIENTS AND METHODS: The prevalence of cathepsin-D and nm23 expression was studied with immunohistochemistry in a cohort of 185 previously untreated cases of FIGO stage III ovarian cancer. Correlations with known prognostic factors were examined, and both uni- and multivariate survival analyses were performed. RESULTS: Epithelial cell cathepsin-D expression was found in 58% of cases, stromal cell cathepsin-D expression in 20%, and nm23 expression in 72%. Epithelial cell cathepsin-D expression was positively correlated with better differentiation of the tumor tissue (P = 0.034). No correlation was found between epithelial and stromal cell cathepsin-D expression, but a striking degree of positive correlation was demonstrated between epithelial cell cathepsin-D and nm23 expression (P = 0.005). None of the factors studied was of any value in predicting the response to platinum and anthracyclin combination chemotherapy, as assessed by second look laparotomy. In univariate analysis age, FIGO substage, histological type, differentiation grade, ascites, residual disease and epithelial cathepsin-D were associated with corrected survival. Neither stromal cell cathepsin-D, nor nm23 expression were of prognostic significance. However, in multivariate analysis the combination of epithelial and stromal cell cathepsin-D expression (P = 0.030), residual disease (P = 0.002) and differentiation grade (P = 0.007) were the only remaining independent prognostic factors in this patient group. CONCLUSIONS: Our results support a favourable prognostic significance of cathepsin-D expression in advanced ovarian cancer, but underscore the importance of considering both epithelial and stromal cell expression. We could not confirm the prognostic significance of nm23 expression in the present cohort of advanced ovarian cancer patients.
Adult↗
Clinical significance of apoptosis-related factors p53, Mdm2, and Bcl-2 in advanced ovarian cancer.
PURPOSE: To investigate the prognostic and predictive relevance of p53, Mdm2, and Bcl-2 protein expression in advanced ovarian cancer. PATIENTS AND METHODS: Tumor biopsy specimens from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for expression of p53, Mdm2, and Bcl-2 proteins. Both uni- and multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters and response to chemotherapy were examined. RESULTS: Forty-nine percent and 39% of cases were considered positive for expression of p53 and Bcl-2, respectively. p53 expression was correlated with loss of histologic differentiation and Bcl-2 expression with smaller residual disease after primary surgery. The absence of p53 expression and the presence of Bcl-2 expression were associated with improved survival but not with overall response to chemotherapy, although a positive correlation was found between Bcl-2 expression and the possibility of obtaining a completely negative second-look laparotomy. Expression of Mdm2 was found in 17% of cases. Although correlations were found with known favorable clinicopathologic factors, no prognostic significance was demonstrated for Mdm2 in this patient group. In multivariate analyses, histologic type, degree of differentiation, residual disease, and p53 alone or combined with Bcl-2 expression were found to be independently associated with overall survival. CONCLUSION: p53, and especially the combination of p53 and Bcl-2 expression data, represents an independent prognostic predictor in stage III ovarian cancer. Despite their role in the apoptotic process, p53 and Bcl-2 do not seem to be clinically useful predictors of response to combination chemotherapy in these patients.
Adult↗
Lack of independent prognostic significance of p21 and p27 expression in advanced ovarian cancer: an immunohistochemical study.
The eukaryotic cell cycle is controlled by protein complexes consisting of cyclin-dependent kinases and cyclins. The cyclin-dependent kinases are in turn negatively regulated by a family of cyclin-dependent kinase inhibitors, comprising, among others, the p21 and p27 proteins. p21 and p27 have been shown to be of prognostic significance in a broad array of human tumors. Using immunohistochemistry, the frequency of expression and the possible prognostic and predictive significance of these proteins were examined in a series of 185 uniformly treated patients with stage III ovarian cancer. We found p21 to be overexpressed in 48% of cases. No significant correlation was found between the expression of p21 and p53 proteins (P = 0.273). A low level of p27 was demonstrated in 48.5% of cases. p21 overexpression correlated with lower Fédération Internationale des Gynaecologistes et Obstetristes substage, lower patient age, and absence of ascites, but neither p21 nor p27 expression was of prognostic significance for the whole group of patients. Only a trend toward reduced survival (P = 0.092) was noticed for the small subgroup of patients (6%), whose tumors lacked p27 expression completely. A clear positive correlation could be found between p21 and p27 protein expression (P = 0.012). Despite the suggested role of the 21 and p27 proteins in determining drug sensitivity, they were not found to be predictive for response to chemotherapy, as assessed by second-look laparotomy in this large group of patients with advanced ovarian cancer.
Adult↗
Immunohistochemical analysis of p53 protein in uterine sarcomas.
This study was undertaken to evaluate the frequency and prognostic significance of p53 protein accumulation in uterine sarcomas. Immunostaining for p53 protein was performed on formalin-fixed, paraffin-embedded sections from 158 patients with verified uterine sarcomas using monoclonal p53 antibody (DO-1). Antigen retrieval was performed with microwave oven technique. Nuclear p53 protein accumulation was demonstrated in 45% of the cases, more often in carcinosarcomas (73%) than in leiomyosarcomas (38%) and endometrial stromal sarcomas (27%). A significant correlation was found between p53 protein accumulation and malignancy grade (P = 0.003), mitotic count (P = 0.007), and DNA ploidy (P = 0.007), but not to FIGO stage (P = 0.6). The 5-year survival was not influenced by level of p53 protein accumulation. In Cox multivariate analysis, free resection margins at primary surgery (P < 0.0001), tumor diameter (P = 0.002), malignancy grade (P = 0.0004), and age at diagnosis (P = 0.0001) were found to be of independent prognostic significance while p53 protein accumulation had no significance (P = 0.022). Our results indicate that p53 alterations may play an important role in the carcinogenesis of uterine sarcomas, but in our study p53 protein accumulation had no impact on prognosis.
Adult↗
Controlled multicentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy.
This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl (P < 0.001 and < 0.05, respectively). A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.
Anemia↗
Ten-year results of a randomised trial comparing cisplatin with cisplatin and cyclophosphamide in advanced, suboptimally debulked ovarian cancer.
176 eligible patients with advanced suboptimally operated ovarian carcinoma were randomly allocated to receive either cisplatin 75 mg/m2 or cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 (CP) every 28 days for six courses. The overall clinical response rates (complete response plus partial response) were 52 and 63% for CP and cisplatin, respectively (non-significant). Including results obtained by second-look laparotomy, we did not observe a statistically significant difference in response rates in the two treatment groups. Median progression-free survival was 10 and 11.9 months for CP and cisplatin, respectively (non-significant). No significant difference was observed in overall survival, with a median of 19.4 and 21.5 months for CP and cisplatin, respectively. Thirty-seven platinum-resistant and 27 platinum-sensitive tumours were treated with carboplatin or cisplatin as second-line therapy. Response rates to platinum second-line therapy were 6 and 50% for resistant and sensitive tumours, respectively (P < 0.001). This difference in response rate was also confirmed by survival analysis. Patients with platinum-sensitive tumours survived longer when they were treated with platinum-containing chemotherapy (P = 0.005). Median survival was 22.8 and 8.5 months after initiation of second-line treatment for the platinum-containing and platinum-free regimens, respectively. In summary, we observed in suboptimally operated ovarian carcinoma patients similar response rates, progression-free interval, and overall survival for equitoxic cisplatin and CP. However, the doses of cisplatin and cyclophosphamide chosen were substantially lower than current standard doses of CP. Our study demonstrates, therefore, that a suboptimal dose of CP is as effective as optimal dose monotherapy cisplatin. Patients with recurrences considered as platinum-sensitive had a significantly higher response rate and improved survival when retreated with platinum-containing therapy.
Adult↗
A review of caveats in statistical nuclear image analysis.
A large body of the published literature in nuclear image analysis do not evaluate their findings on an independent data set. Hence, if several features are evaluated on a limited data set over-optimistic results are easily achieved. In order to find features that separate different outcome classes of interest, statistical evaluation of the nuclear features must be performed. Furthermore, to classify an unknown sample using image analysis, a classification rule must be designed and evaluated. Unfortunately, statistical evaluation methods used in the literature of nuclear image analysis are often inappropriate. The present article discusses some of the difficulties in statistical evaluation of nuclear image analysis, and a study of cervical cancer is presented in order to illustrate the problems. In conclusion, some of the most severe errors in nuclear image analysis occur in analysis of a large feature set, including few patients, without confirming the results on an independent data set. To select features, Bonferroni correction for multiple test is recommended, together with a standard feature set selection method. Furthermore, we consider that the minimum requirement of performing statistical evaluation in nuclear image analysis is confirmation of the results on an independent data set. We suggest that a consensus of how to perform evaluation of diagnostic and prognostic features is necessary, in order to develop reliable tools for clinical use, based on nuclear image analysis.
Data Interpretation, Statistical↗