Publications by authors named "Canzler U"
Background: In PAOLA-1/ENGOT-ov25, the addition of olaparib to bevacizumab maintenance improved overall survival in patients with newly diagnosed advanced ovarian cancer. We describe the safety profile and quality of life (QoL) of this combination in older patients in PAOLA-1.
Methods: Safety (CTCAE v4.
Context.—: A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported.
Objective.
Article Synopsis
- Survival rates for ovarian cancer are influenced by the success of primary surgery in removing tumors.
- Researchers conducted genome-wide studies on 7,705 ovarian cancer patients to find genetic variants linked to resection status, particularly focusing on high-grade serous carcinoma (HGSOC).
- The study highlighted significant associations with the rs72845444 variant and the genes MGMT (involved in DNA repair) and PPP2R5C (a tumor suppressor), correlating with disease outcomes and patient survival.*
With more novel drugs being approved for the treatment of ovarian carcinoma, the question remains to what extent patients benefit from antiangiogenic treatment with bevacizumab, either in combination with poly-(ADP-ribose) polymerase inhibitors or as single-agent maintenance. As fibroblast growth factor receptors and their ligands (FGFRs/FGFs) are key players in angiogenic signaling and have been linked to resistance to several drugs, we investigated the prognostic or predictive potential of FGFs/FGFRs signaling in the context of bevacizumab treatment within the prospective phase III AGO-OVAR11/ICON-7 study. FGFR1, FGFR2, FGFR3, FGFR4, FGF1, and FGF19 gene expressions were determined in 380 ovarian carcinoma tumor samples collected from German centers in the multicenter phase III AGO-OVAR11 trial/ICON-7 trial.
View Article and Find Full Text PDFPurpose: Pazopanib has promising antiangiogenetic activity in solid cancers. The investigator-initiated phase I/II trial evaluated the combination of Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC).
Methods: Patients (≥ 18 years) with first or second recurrence were enrolled in this multicentre open-label trial.
Unlabelled: In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline -mutated (non-gm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gm cohort. Niraparib demonstrated PFS benefit in patients with either somatic mutated (sm; HR, 0.
View Article and Find Full Text PDFBackground: The phase III PAOLA-1/ENGOT-ov25 study (NCT02477644) showed that addition of olaparib to bevacizumab maintenance improved progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer. We evaluated maintenance olaparib plus bevacizumab in older patients in PAOLA-1.
Methods: Baseline clinical and molecular data, and PFS, were compared between older (aged ≥65 years) and younger patients (<65 years).
Purpose: To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer.
Methods: In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks).
Background: PAOLA-1/ENGOT-ov25 (NCT02477644) demonstrated a significant progression-free survival (PFS) benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in newly diagnosed, advanced ovarian cancer. We report the prespecified main second progression-free survival (PFS2) analysis for PAOLA-1.
Methods: This randomised, double-blind, phase III trial was conducted in 11 countries.
Article Synopsis
- The study investigates the immune environment in high grade serous ovarian carcinoma (HGSOC) patients to find alternative immune targets after PD-1/PD-L1 inhibitors did not yield favorable results.
- Analysis of tumor samples from 103 HGSOC patients showed that higher levels of intratumoral CD3 T lymphocytes and HLA-E expression were linked to better progression-free and overall survival rates.
- The findings suggest that targeting the HLA-E/CD94-NKG2A/2C pathway could be a promising strategy, especially for patients with genomic instability indicated by homologous recombination deficiency (HRD).
Article Synopsis
- * In a study of 306 patients, pelvic LAE was performed in 35.6% of cases, with pelvic nodal involvement found in 18.5%, primarily in patients with more advanced nodal status (≥pN2a).
- * Adjuvant RT was given to 64.4% of the patients, but only half of those with pelvic nodal involvement received it, highlighting a significant risk of recurrence, particularly in cases with higher nodal status, while suggesting that
Background: There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma-a human papillomavirus-dependent pathway characterized by p16 overexpression and a human papillomavirus-independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed.
Objective: The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance.
Pelvic Lymphadenectomy in Vulvar Cancer - Does it make sense?
Geburtshilfe Frauenheilkd
December 2020
Article Synopsis
- The 2015 updated German guidelines on pelvic lymphadenectomy (LAE) for vulvar cancer patients recommend surgical lymph node staging for those at higher risk, but defining this risk is still unclear.
- Two German patient populations have been analyzed to study the impact of lymph node metastasis, one including 1,618 patients and another 514 patients, with a small number undergoing pelvic LAE.
- Findings indicate that about 80% of patients who had pelvic LAE were also positive for inguinal lymph nodes, and pelvic lymph node staging may not be necessary for many node-positive patients, especially those with low-grade disease.
Background: State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab.
Methods: This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK.
Purpose: Although thrombocytosis in patients with primary ovarian cancer has been widely investigated, there are only very few data about the role of thrombocytosis in recurrent ovarian cancer. The aim of our study was to investigate the impact of pretreatment thrombocytosis prior to chemotherapy on clinical outcome in patients with recurrent platinum eligible ovarian cancer.
Methods: In our retrospective analysis we included 300 patients who were treated by AGO Study Group Centers within three prospective, randomized phase-III-trials.
Background: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of mutation status is unknown.
Methods: We conducted a randomized, double-blind, international phase 3 trial.
Purpose: Predicting surgical outcome could improve individualizing treatment strategies for patients with advanced ovarian cancer. It has been suggested earlier that gene expression signatures (GES) might harbor the potential to predict surgical outcome.
Experimental Design: Data derived from high-grade serous tumor tissue of FIGO stage IIIC/IV patients of AGO-OVAR11 trial were used to generate a transcriptome profiling.
Article Synopsis
- Lymph node metastasis is crucial for determining prognosis in vulvar cancer, and understanding risk factors can improve treatment strategies.
- A study analyzed 1162 patients undergoing radical groin dissection, identifying factors linked to the prevalence and extent of lymph node metastases.
- Key findings revealed that lymphovascular space invasion, tumor stage, and depth of infiltration significantly correlate with the likelihood of lymph node metastasis, with tumor stage also affecting the number of metastases.
Purpose: In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy.
View Article and Find Full Text PDFObjective: Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings.
Methods: Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle.
Recent progress in understanding the molecular biology of epithelial ovarian cancer has not yet translated into individualized treatment for these women or improvements in their disease outcome. Gene expression has been utilized to identify distinct molecular subtypes, but there have been no reports investigating whether or not molecular subtyping is predictive of response to bevacizumab in ovarian cancer. DASL gene expression arrays were performed on FFPE tissue from patients enrolled on the ICON7 trial.
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- The AGO-CaRE-1 study compared the outcomes of two surgical approaches for vulvar cancer: isolated sentinel lymph node dissection (SLND) and radical lymph node dissection (LND), focusing on patient recurrence rates and survival outcomes.
- Data was retrospectively collected from 772 patients treated between 1998 and 2008 at 29 centers, specifically looking at those with FIGO stage ≥1B and tumors smaller than 4 cm.
- Results showed no significant differences in recurrence rates or progression-free survival between patients who underwent SLND and those who had LND, suggesting both methods are similarly effective for node-negative patients with smaller tumors.
Aim Of The Study: A tumour-free pathological resection margin of ≥8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer.
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- Propensity scoring (PS) helps address confounding factors in observational studies, especially when randomization isn't an option.
- This study explores how to handle missing data in these analyses using multiple imputation and different PS techniques.
- The authors re-evaluate the impact of radiotherapy on survival outcomes in vulvar cancer patients, employing IPTW and PS stratification, while also discussing methodological challenges and results limitations.
Background: Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC).
Patients And Methods: Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m/ days 1-3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization.