| 1. |
- Graflund, Marianne, et al.
(författare)
-
Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma : Correlation with clinical outcome
- 2002
-
Ingår i: International Journal of Gynecological Cancer. - Malden, USA : BMJ. - 1048-891X .- 1525-1438. ; 12:3, s. 290-298
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.
|
|
| 2. |
- Graflund, Marianne, et al.
(författare)
-
MIB-1, p53, bcl-2 and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas : Correlation with clinical outcome
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A complete series of 40 cervical carcinomas with pelvic lymph node rnetastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamouscarcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 twnors (30%) were moderately differentiated, and 27 tumors (67 .5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymphnode metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and mu!tivariate proportional hazard Cox analyses.
|
|
| 3. |
- Graflund, Marianne, et al.
(författare)
-
MIB-1, p53, bcl-2, and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas : correlation with clinical outcome
- 2002
-
Ingår i: International Journal of Oncology. - Athens, Greece : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 20:5, s. 1041-1047
-
Tidskriftsartikel (refereegranskat)abstract
- A complete series of 40 cervical carcinomas with pelvic lymph node metastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamous carcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 tumors (30%) were moderately differentiated, and 27 tumors (67.5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymph node metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and multivariate proportional hazard Cox analyses.
|
|
| 4. |
- Graflund, Marianne
(författare)
-
Prognostic Factors in Early Stage Cervical Carcinomas Treated with Wertheim-Meigs Surgery
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cervical cancer is the second most common malignancy and a leading cause of morbidity and mortality among women worldwide. In Sweden, cervical cancer constitutes 2.4% of all newly diagnosed cancers and is the fifteenth cause of death.An improved estimation of the prognosis in early stages of cervical carcinomas is desirable. The most important of the established prognostic factors are tumor size, radical excision margins, and lymph node status. The objectives of this study were to assess the value of oncogene and tumor suppressor gene products, angiogenesis, proliferation markers and histopathological malignancy grading systems as predictors of pelvic lymph node metastases (LNM), tumor recurrences and death due to the disease in early stage (FIGO I-II).In a complete geographic series of cervical carcinomas treated by Wertheim-Meigs surgery, a number of clinical, biological, and histopathological prognostic factors were evaluated and long-term survival data were presented. In all, 367 woman with FIGO stage I-II cervical tumors were included.Significant prognostic factors for disease-free survival were lymph node status, radical surgical margins, and tumor size. In a multivariate Cox analysis, it was shown that lymph node status was the single most important prognostic factor (P < 0.0000001). Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage. There was also a significant (P = 0.002) association between the vascular space invasion of tumor cells and the presence of lymph node metastases.The complete malignancy grading system (MGS), partial index (PI), and invasive front grading (IFG) scores were highly significantly (P = 0.0001, P = 0.0001, P = 0.002) associated with the presence of pelvic LNM and with the disease-free survival rate. No pelvic lymph node metastases were encountered in tumors with MGS scores below 16. The predictive value (the specificity) for no pelvic lymph node metastases was 97%. The complete IFG score and the individual scores of the two variables, pattern of invasion and host response, were all significantly (P = 0 .002, P = 0.007, P = 0.0001) associated with pelvic LNM. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting LNM.The activity of the proliferation marker MIB-1 was lower in pelvic lymph node metastases than in the primary tumors. The expression ofMIB-1 in lymph nodes was a prognostic factor for disease-free survival in both univariate and multivariate analyses.In our series, it was concluded that microvessel density (CD31) and expressions of p53, bcl-2, p21 (WAF1), DNA ploidy, and S-phase fraction (FCM) did not add any further predictive or prognostic information.In conclusion, this study has confirmed that histopathological malignancy grading (MGS), the partial index (PI), and invasive front grading (IFG) in the original or modified versions can predict low and high-risk groups of tumors and therefore be of value in planning the treatment of early stage squamous cell carcinomas of the uterine cervix. The expression of the proliferative marker MIB-1 in primary tumors and in LNM seems to be a factor that should be studied further in an attempt to identify different prognostic groups of tumors requiring more individualized postoperative treatment planning.
|
|
| 5. |
- Graflund, Marianne, et al.
(författare)
-
The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas
- 2002
-
Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:2, s. 149-157
-
Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim-Meigs) for FIGO stage I-II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables-pattern of invasion and host response-were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients.
|
|
| 6. |
- Graflund, Marianne, et al.
(författare)
-
The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix
- 2002
-
Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:1, s. 32-41
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the prognostic importance of clinical and histopathologic factors, including malignancy grading systems (MGS), partial index (PI), invasive front grading (IFG), and microvessel density. A complete geographic series of 172 early stage (FIGO I-II) cervical carcinomas treated by Wertheim-Meigs surgery during the period 1965-1990 was studied. The patients were followed up for at least 10 years. Significant prognostic factors for disease-free survival were lymph node status (P < 0.0000001), radical surgical margins (P = 0.00003), and tumor size (P = 0.008). In a multivariate Cox analysis it was shown that lymph node status was the single most important prognostic factor with regard to disease-free survival. The total MGS and the PI scores were highly significantly (P = 0.0001) associated with pelvic lymph node metastases and disease-free survival rate in squamous cell carcinomas. The MGS and the PI systems were superior to the IFG system in predicting lymph node metastases. The total IFG score was also a statistically highly significant (P = 0.003) prognostic factor with regard to disease-free survival in both univariate and multivariate analyses. Microvessel density was a nonsignificant prognostic factor. There was a highly significant (P = 0.002) association between vascular space invasion of tumor cells and the presence of lymph node metastases. In conclusion, histopathologic malignancy grading systems provide valuable prognostic information in patients with early stage squamous cell carcinomas of the uterine cervix.
|
|
| 7. |
- Sorbe, Bengt, et al.
(författare)
-
A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: Neurological toxicity and quality-of-life evaluation
- 2012
-
Ingår i: International Journal of Oncology. - Athens : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 40:3, s. 773-781
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to assess the response rate, toxicity, progression-free survival (PFS) and overall survival (OS) in a series of advanced stage ovarian carcinoma patients treated with a first-line weekly docetaxel and three weekly carboplatin regimens. All eligible patients were treated with intravenous docetaxel (30 mg/m(2)) on Days 1, 8 and 15, and carboplatin (area under the curve, 5) on Day 1; Q21 days for at least 6 cycles. Neurological tests, questionnaires, and the EORTC QLQ-C30 and OV28 were used for quality-of-life assessments. One hundred and six patients received at least one cycle of primary chemotherapy (median 6.0; range, 1-9) and they were evaluable for toxicity assessment. Eighty-five patients had evaluable disease and received at least 3 courses of chemotherapy and were evaluable for clinical response rate. The overall response rate was 78.8% (95% CI 70.1-87.5%) and the biochemical response was 92.8% (95% CI 87.2-98.4%). The median PFS was 12.0 months and the median OS was 35.3 months. Thirty-six patients (34.0%) experienced grades 3 and 4 neutropenia, which resulted in the removal of 3 patients. Six patients (5.7%) experienced grades 3 or 4 thrombocytopenia. No patients experienced grade 3-4 sensory neuropathy. Epiphora, nail changes and fatigue were frequently recorded non-hematological side effects. The tolerable hematological toxicity (no need for colony-stimulating factors) and the low rate of severe neurotoxicity (only grade 1-2) and response rates in line with the standard 3-week paclitaxel-carboplatin regimen for advanced primary ovarian carcinoma after suboptimal cytoreductive surgery make this regimen an interesting alternative in selected patients.
|
|
| 8. |
- Sorbe, Bengt, et al.
(författare)
-
A study of docetaxel weekly or every three weeks in combination with carboplatin as first line chemotherapy in epithelial ovarian cancer : Hematological and non-hematological toxicity profiles
- 2013
-
Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 5:4, s. 1140-1148
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to compare the toxicity profiles of docetaxel administered on a weekly schedule and the standard three-week schedule in the treatment of advanced primary ovarian carcinoma. Eligible patients were treated with intravenous docetaxel (30 mg/m(2)) on days 1, 8 and 15, and carboplatin (AUC 5) on day 1 or with docetaxel (75 mg/m(2)) and carboplatin (AUC 5) on day 1; Q21 days for 6 cycles. This study was a pooled study of two primary phase II studies. A total of 108 patients received the weekly schedule and 59 patients received the three-week schedule. All patients were evaluated for toxicity. The overall response rate was 79% and the biochemical response 93% for the weekly schedule. The median overall survival rate was 35.3 months. Neutropenia was significantly more common (ANOVA; p<0.0001) in the three-week group than in the weekly group during all six courses of chemotherapy. Fever and infections were also more common in this group. Thrombocytopenia and anemia were slightly more common in the weekly group. Fatigue, epiphora, nail changes and taste disturbances were specific side-effects following weekly docetaxel. Peripheral sensory neuropathy (grade 1-2) increased with every cycle of treatment, but in a similar manner in the two groups. Grade 3-4 neuropathy was not recorded. Oral mucositis and myalgia were two side-effects associated with the three-week schedule. Nausea and vomiting, diarrhea and dyspnea were a limited problem in both groups. Cardiac toxicity was rare and did not differ between the two docetaxel schedules. The weekly administration was favored due to the lower rates of neutropenia, fever, infections, oral mucositis and myalgia. However, epiphora and nail changes were specific side-effects of the weekly treatment. Both regimens appeared to be rather well tolerated with similar compliance (66 and 70%) with regard to completion of the planned six courses of chemotherapy.
|
|
| 9. |
- Sorbe, Bengt, et al.
(författare)
-
Phase II Study of Docetaxel Weekly in Combination With Carboplatin Every 3 Weeks as First-Line Chemotherapy in Stage IIB to Stage IV Epithelial Ovarian Cancer
- 2012
-
Ingår i: International Journal of Gynecological Cancer. - : Lippincott, Williams and Wilkins / Wiley-Blackwell. - 1048-891X .- 1525-1438. ; 22:1, s. 47-53
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to assess the response rate, toxicity, progression-free survival, and overall survival in a series of patients with advanced-stage ovarian carcinoma treated with a first-line weekly docetaxel and 3 weekly carboplatin regimen. less thanbrgreater than less thanbrgreater thanMethods: All eligible patients were treated with intravenous docetaxel (30 mg/m(2)) on days 1, 8, and 15, and carboplatin (area under the curve, 5) on day 1; every 21 days for at least 6 cycles. less thanbrgreater than less thanbrgreater thanResults: One hundred six patients received at least one cycle of primary chemotherapy (median, 6.0; range, 1-9), and they were evaluable for toxicity assessment. Eighty-five patients had evaluable (measurable) disease and received at least 3 courses of chemotherapy and were evaluable for clinical response rate. The overall response rate was 78.8% (95% confidence interval, 70.1%-87.5%), and the biochemical response 92.8% (95% confidence interval, 87.2%-98.4%). The median progression-free survival was 12.0 months and the median overall survival was 35.3 months. Thirty-six patients (34.0%) experienced grades 3 and 4 neutropenia, which resulted in the removal of 3 patients. Six patients (5.7%) experienced grades 3 or 4 thrombocytopenia. No patients experienced grade 3 to grade 4 sensory neuropathy. Epiphora, nail changes, and fatigue were frequently recorded nonhematologic adverse effects. less thanbrgreater than less thanbrgreater thanConclusions: The tolerable hematologic toxicity (no need for colony-stimulating factors) and the low rate of neurotoxicity (only grades 1-2) and response rates in line with the standard 3-week paclitaxel-carboplatin regimen for advanced primary ovarian carcinoma after suboptimal cytoreductive surgerymake this regimen an interesting alternative in selected patients.
|
|
| 10. |
- Sorbe, Bengt, et al.
(författare)
-
Treatment of cervical carcinoma by Wertheim-Meigs surgery : Long-term follow-up results in a well-defined Swedish region
- 1995
-
Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 6:4, s. 817-823
-
Tidskriftsartikel (refereegranskat)abstract
- In a retrospective analysis of a complete geographic series of cervical carcinomas treated by Wertheim-Meigs radical surgery, a number of important prognostic factors were evaluated and long-term survival data are presented. In all, 367 women with FIGO stage I-II tumors were included. The main histopathologic types were squamous cell carcinoma in 84% and adenocarcinoma in 12%. The mean age of the patients was 42.5 (range 19-68) years. In 125 women (34%), adjuvant radiotherapy was administered pre- or postoperatively. The median period of follow-up was 12 (range 2-27) years. In 88% of the specimens surgery (93% in stage I and 66% in stage II) was classified as radical with regard to the excision margins. This was an important and highly significant prognostic factor. If the margins were wide and free of tumor, the 10-year survival rate was 93%, but if margins were infiltrated by the tumor, the survival rate was 14%. Pelvic lymph node involvement was recorded in 52 cases (14%). The frequency of lymph node spread was associated with tumor stage (IA O%, IB 14%, IIA 32%). The probability of survival of the complete series was 93% at 5 years and 84% at 10 years. In cases of lymph node involvement, the 10-year survival rate was 57%. The preoperative tumor stage had a highly significant influence on long-term tumor-specific survival. Tumor grade was also a significant prognostic factor, but not the histologic type (squamous, adenosquamous, or adenocarcinoma). Age and parity were also insignificant prognostic factors. The tumor recurred in 59 cases (16%). The mean time to relapse was 28 months. The 10-year survival was 29% for this group of patients. Peroperative complications were recorded in 50 patients (14%). Excessive bleeding (11%) and urinary tract injuries (3%) were most frequent. Postoperatively, 101 patients (28%) had some kind of complication associated with the surgical procedure. Surgical complications were more frequent among women over 50 years of age. Bladder dysfunction (11%) and obstruction of the ureter (8%) were recorded most frequently. In 19 cases (5.2%), urinary tract or intestinal fistulas were diagnosed during the period of follow-up. With increasing experience of the surgeons and fewer stage II tumors, the frequency of fistulas associated with the surgical procedure decreased to 2.4% during the latter part (1975-90) of the period. Adjunctive postoperative radiotherapy increased the risk of late complications. In 8 cases (6.4%), serious complications associated with the combination of surgery and radiotherapy were reported.
|
|
