| 21. |
- Cibula, David, et al.
(author)
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The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer
- 2018
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In: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 472:6, s. 919-936
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Journal article (peer-reviewed)abstract
- The European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide. The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives. The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.
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| 22. |
- Corvigno, Sara, et al.
(author)
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High density of stroma-localized CD11c-positive macrophages is associated with longer overall survival in high-grade serous ovarian cancer.
- 2020
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 159:3, s. 860-868
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Pre-clinical studies have identified marker- and tumor compartment-defined functionally distinct macrophage subsets. Our study analyzes marker-defined macrophage subsets in different tumor compartments of high-grade serous ovarian cancer (HGSC).METHODS: A discovery cohort (N = 113) was subjected to immunohistochemistry (IHC) analyses. CD68-positivity was confirmed for CD11c-, CD80- and CD163-positive cells. Subset-marker-positive cells were scored in the total tumor and in four tumor compartments. Correlation analyses investigated co-expression of subsets, relationship to CD8+ cells and survival associations. A validation cohort (N = 121) was used to confirm selected findings from the discovery cohort.RESULTS: CD163-positve cells was the most abundant subtype in all compartments. CD11c and CD163 subsets were strongly correlated with each other in stroma and epithelial areas, whereas CD80 and CD163 were correlated in epithelial areas. CD80 and CD11c in perivascular areas showed low correlations. Strong associations were detected between CD8 and CD80 in the tumor epithelium-dominated areas, and between CD8 and CD11c in stroma areas. High stromal CD11c density was associated with a longer median overall survival in the discovery cohort (HR 0.39; CI 95%, 0.23-0.68; p = 0.001) and in the validation cohort (HR 0.46; CI 95%, 0.22-0.93; p = 0.03).CONCLUSIONS: Our study supports the existence of clinically relevant marker- and localization defined macrophage subsets in HGSC, which are independently regulated. Moreover, it suggests stromal CD11c as a novel prognostic marker in HGSC.
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| 23. |
- Corvigno, Sara, et al.
(author)
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Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival
- 2016
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In: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:14, s. 18573-18584
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Journal article (peer-reviewed)abstract
- Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers alpha-SMA, PDGF beta R and desmin. Images were digitally analyzed to yield "metrics" related to vasculature and stroma features. Intra-case analyses showed that PDGF beta R in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning `-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGF beta R-positive stroma fraction and high PDGF beta FR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGF beta R- and alpha-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGF beta R in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer.
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| 24. |
- Dahm-Kähler, Pernilla, 1964, et al.
(author)
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Has time to chemotherapy from primary debulking surgery in advanced ovarian cancer an impact on survival?- A population-based nationwide SweGCG study
- 2024
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In: GYNECOLOGIC ONCOLOGY. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 186, s. 69-76
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Journal article (peer-reviewed)abstract
- Objective. The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). Methods. Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008-2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; <= 21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. Results. In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0-21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC <= 21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0-21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. Conclusions. For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 25. |
- Dahm-Kähler, Pernilla, 1964, et al.
(author)
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Implementation of National Guidelines increased survival in advanced ovarian cancer-A population-based nationwide SweGCG study
- 2021
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 161:1, s. 244-250
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Journal article (peer-reviewed)abstract
- Aim. The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation. Method. Women with primary epithelial ovarian cancer, FIGO stage IIIC?IV, registered in the Swedish Quality Registry for Gynecologic Cancer 2008?2011 and 2013?2016 were included. Surgical outcomes were analyzed, including frequency of complete cytoreduction (R0). Relative survival (RS) and excess mortality rate ratios (EMRRs) were computed as measures of survival. Univariable and multivariable regression (Poisson) were calculated. Results. In total, 3728 women were identified, 1746 before and 1982 after NGOC. After adjusting for age and stage, survival was improved 2013?2016 vs. 2008?2011 (EMRR 0.89; 95%CI:0.82?0.96, p < 0.05). For women undergoing primary debulking surgery (PDS), R0 frequency (28.9% vs. 53.3%; p < 0.001) and 5-year RS (29.6% (95% CI:26.8?32.8) vs. 37.4% (95%CI:33.6?41.7)) were increased, but fewer patients (58% vs. 44%, p < 0.001) underwent PDS after NGOC implementation. Median survival for the PDS cohort increased from 35 months (95%CI,32.8?39.2) to 43 months (95%CI,40.9?46.4). In the neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) cohort, R0 increased (36.8% to 50.1%, p < 0.001), but not 5-year RS (17.5% vs. 20.7%,ns). Compared to PDS, the EMRR was 1.32 (95%CI,1.19 & ndash;1.47, p < 0.001) for NACT+IDS and 3.00 (95% CI,2.66 & ndash;3.38, p < 0.001) for chemotherapy alone. In multivariable analyses, PDS, R0, age <= 70 years, and stage IIIC were found to be independent factors for improved RS. Conclusion. Implementation of the first National Guidelines for Ovarian Cancer improved relative survival in advanced ovarian cancer. (c) 2021 Published by Elsevier Inc.
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| 26. |
- Dahm-Kähler, Pernilla, 1964, et al.
(author)
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Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG)
- 2017
-
In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 144:1, s. 167-173
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Journal article (peer-reviewed)abstract
- Objective. The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Methods. Nation-wide population-based study of women 18 years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. Results. Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulldng surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. Conclusion. Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer. (C) 2016 Elsevier Inc. All rights reserved.
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| 27. |
- Dillner, L, et al.
(author)
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Association of serum antibodies against defined epitopes of human papillomavirus L1, E2, and E7 antigens and of HPV DNA with incident cervical cancer.
- 1995
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In: Cancer Detection and Prevention. - 0361-090X .- 1873-443X. ; 19:5, s. 381-93
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Journal article (peer-reviewed)abstract
- In order to provide a large-scale evaluation of the association with cervical cancer of antibodies against human papillomavirus (HPV) antigens, sera from 233 patients with primary, untreated cervical cancer and from 157 healthy age- and sex-matched blood donors were analyzed for IgG and IgA antibodies against HPV-derived peptide antigens and against bovine papillomavirus. Several serological responses were strongly associated with cervical cancer, notably the IgG response against the HPV 16 epitopes L1:13 (Relative risk [RR]: 5.3), E2:9 (RR: 2.9), and E7:5 (RR: 4.3), and the IgA response against an HPV 18 E2-derived antigen (245:18, RR: 3.1). HPV DNA in corresponding cervical tumors was analyzed by Southern blotting (SB) and polymerase chain reaction (PCR) in 47 patients. Sixty-six percent of the patients carried HPV DNA as determined by SB, 91% of patients analyzed by PCR. Neither the antibody responses, nor the presence of HPV DNA were significantly associated with the biological properties of the tumors.
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| 28. |
- Dostalek, Lukas, et al.
(author)
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ESGO Survey on Current Practice in the Management of Cervical Cancer
- 2018
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In: International Journal of Gynecological Cancer. - : LIPPINCOTT WILLIAMS & WILKINS. - 1048-891X .- 1525-1438. ; 28:6, s. 1226-1231
-
Journal article (peer-reviewed)abstract
- Objective The aim of this survey was to acquire an overview of the current management of cervical cancer with an emphasis on the early disease stages. Materials and Methods A hyperlink to the survey was sent to the European Society of Gynaecological Oncology Office database. The survey contained 6 groups of questions regarding the characteristics of respondents, pretreatment workup, management of the early stages of cervical cancer, adjuvant treatment, fertility-sparing treatment, and surveillance. Results In total, 566 responses were collected. The most frequent imaging method used in the workup was magnetic resonance imaging (74%), followed by computed tomography (54%) and positron emission tomography/computed tomography (25%). Conization or simple hysterectomy was a preferred procedure in stage T1a1 lymphovascular space invasion (LVSI)-positive for 79% of respondents, in stage T1a2 LVSI-negative for 58%, and in stage T1a2 LVSI-positive for 28%. Sentinel lymph node biopsy alone was reported in stage T1a1 by 17% and in stage T1b1 less than 2 cm by 9%, whereas systematic lymphadenectomy by 29% and 90% of respondents. Macrometastases, micrometastases, and isolated tumor cells in lymph nodes were considered indications for adjuvant treatment by 96%, 93%, and 68% of respondents, respectively. Neoadjuvant chemotherapy was reported by 28% and 19% of respondents in fertility-sparing and nonsparing management in stage T1b1. Over 60% of respondents recommend primary surgery for their patients with T1b2 N0 disease and 81% of them use a combination of adverse prognostic factors as indication for adjuvant radiotherapy in pN0 disease. Conclusions The results of this survey indicate considerable differences in the workup and treatment of cervical cancer in current clinical practice.
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| 29. |
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| 30. |
- du Bois, Andreas, et al.
(author)
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Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer.
- 2010
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In: Journal of Clinical Oncology. - : American society of clinical oncology. - 0732-183X .- 1527-7755. ; 28:27, s. 4162-4169
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Journal article (peer-reviewed)abstract
- PURPOSE: One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.PATIENTS AND METHODS: We performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m(2), respectively) with the same combination and additional gemcitabine 800 mg/m(2) on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.RESULTS: Between 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).CONCLUSION: The addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.
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