Approximately one-third of all borderline ovarian tumours (BOT) are diagnosed in patients with child-bearing potential. Detailed information regarding their specific characteristics and prognostic ...factors is limited.
Clinical parameters of BOT patients treated between 1998 and 2008 in 24 German centres were retrospectively investigated. Central pathology review and prospective follow-up were carried out. Patients <40 versus ≥40 years were analysed separately and then compared regarding clinico-pathological variables and prognosis.
A total of 950 BOT patients with a median age of 49.1 (14.1–91.5) years were analysed 280 patients <40 years (29.5%), 670 patients ≥40 years (70.5%). Fertility-preserving surgery was carried out in 53.2% (149 of 280) of patients <40 years with preservation of the primarily affected ovary in 32 of these 149 cases (21.5%). Recurrence was significantly more frequent in patients <40 years (19.0% versus 10.1% 5-year recurrence rate, P < 0.001), usually in ovarian tissue, whereas disease-specific overall survival did not differ between the subgroups. In case of recurrent disease, malignant transformation was less frequent in younger than in older patients (12.0% versus 66.7%, P < 0.001), mostly presenting as invasive peritoneal carcinomatosis. Multivariate analysis for patients <40 years identified advanced International Federation of Gynecology and Obstetrics (FIGO) stage and fertility-sparing approach as independent prognostic factors negatively affecting progression-free survival (PFS) while, for patients ≥40 years, higher FIGO stage and incomplete staging was associated with impaired PFS.
Despite favourable survival, young BOT patients with child-bearing potential are at higher risk for disease recurrence. However, relapses usually remain BOT in the preserved ovaries as opposed to older patients being at higher risk for malignant transformation in peritoneal or distant localisation. Therefore, fertility-sparing approach can be justified for younger patients after thorough consultation.
Simultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may ...offer further advantages regarding toxicity.
An open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m2) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m2/week) (arm-B) in patients with stage IB–IIB CC after surgery. Primary objective was progression-free survival (PFS).
Overall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% 95% confidence interval (CI) 74.4–89.1 in arm-B versus 87.2% (95% CI 81.2–93.3) in arm-A (P=0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P=0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P<0.001) and neurotoxicity (65.9% versus 15.6%; P<0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P=0.001).
Sequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.
Introduction
Late-stage ovarian cancer patient’s survival depends on complete cytoreduction and chemotherapy. Complete cytoreduction is more often achieved in institutions with a case volume of >20 ...cases per year. The Integrated care program Ovar (IgV Ovar) was founded in 2005 and started recruiting in 2006 with 21 health insurances and six expert centers of ovarian cancer treatment as a quality initiative. Results of the pilot and outcomes of patients of three participating centers will be presented here.
Methods
Data of 1038 patients with ovarian cancer were collected. Adjuvant patients (
n
= 505) stage FIGO IIB-IV (
n
= 307) were analyzed for cytoreduction and survival. FIGO IIIC patients were analyzed separately.
Results
Median follow-up was 32.7 months. Progression-free survival (PFS) was 23.1 months and overall survival (OS) was 53.6 months for stage IIB-IV. Patients with FIGO IIIC were completely cytoreduced in 48 %. PFS was 21, 29 months if completely cytoreduced. OS was 47.4, 64.9 months if completely cytoreduced.
Discussion
Although the IgV Ovar Rhineland proved to have some structural problems with recruitment and prospective data collection, cytoreduction rates and outcome of patients prove treatment of patients in expert centers is superior to the national and international mean. Therefore, a new quality initiative will be started to bring more awareness to women and to their gynecologists and general practitioners of just how important a good referral strategy is.
Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging ...procedure.
Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS).
For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation.
Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.
Einleitung:
Das Ovarialkarzinom ist aufgrund seiner diagnostischen und therapeutischen Limitationen das prognostisch ungünstigste gynäkologische Malignom. Daher sind neue Behandlungsansätze ...wünschenswert. Zu deren präklinischer Evaluation werden Mausmodelle verwendet. In dieser Arbeit haben wir ein subkutanes Xenograft-Mausmodell mit primären Ovarialkarzinomzellen etabliert.
Material und Methoden:
Primäre Ovarialkarzinomzellen wurden aus Aszites von unbehandelten Patientinnen mit
high-grade
serös-papillärem Ovarialkarzinom gewonnen und
in vitro
propagiert. Es wurden 5 × 10
5
Zellen subkutan in die Flanke von CD-1 (Nu/Nu) Mäuse injiziert. Als Kontrolle wurden Mesothelzellen, die aus dem jeweilig selben Aszites gewonnen und
in vitro
propagiert worden waren, verwendet. Das Tumorwachstum wurde in 2 bis 3-tägigen Abständen gemessen. Bei Erreichen eines Tumordurchmessers von 500 mm
3
erfolgte die Tumorexplantation. Die Tumorproben wurden immunhistochemisch mit den monoklonalen Antikörpern gegen Ca12–5-, FRα-, Ber-EP4- und Calretinin gefärbt, sowie durchflusszytometrisch auf die Expression von Ca12 – 5 und FRα untersucht.
Ergebnisse:
Alle Mäuse, denen Ovarialkarzinomzellen injiziert worden waren, entwickelten einen Tumor mit einem kontinuierlichen und aggressiven Wachstum. Mäuse, denen nur Mesothelzellen injiziert worden waren, blieben tumorfrei. Die explantierten Tumore zeigten immunhistochemisch eine positive Reaktion für Ca12 – 5, FRα und Ber-EP4 und durchflusszytometrisch eine hohe Ca12 – 5- und FRα-Expression. Dieser Phänotyp entspricht den
in vitro
propagierten primären Ovarialkarzinomzellen.
Diskussion:
Diese Arbeit zeigt, dass im Vergleich zu
patient-derived xenograft-
(PDX) Mausmodellen, bei denen frisch präparierte Tumore ohne
in vitro
Verarbeitungsschritte in Mäuse injiziert werden, primäre Ovarialkarzinomzellen auch nach
in vitro
Kultur in immundefizienten Mäusen wachsen und hierbei denselben Phänotyp behalten. Unser subkutanes Xenograft-Mausmodell bildet somit die Basis für die Evaluation zukünftiger Behandlungsansätze beim Ovarialkarzinom.
Fragestellung:
In frühen Stadien des Vulvakarzinoms besitzt die aktuelle Standardtherapie hohe Heilungsraten. Die Behandlung des fortgeschrittenen oder rezidivierten Vulvakarzinoms bleibt jedoch ...weiterhin eine klinische Herausforderung und neue therapeutische Ansätze werden daher dringend benötigt. Zielgerichtete Therapien mit Wirkung auf
immune checkpoints
, wie den
programmed death-ligand 1
(PD-L1), haben bereits bei vielen unterschiedlichen Tumorentitäten aussichtsvolle therapeutische Ergebnisse gezeigt. Darüber hinaus scheint die Expression von PD-L1 ein wichtiger Biomarker für die Prognose von malignen Erkrankungen zu sein. Bisher liegen noch keine Daten zur Expression von PD-L1 beim Plattenepithelkarzinom der Vulva vor.
Methodik:
Nach Validierung des monoklonalen PD-L1 Antikörpers führten wir eine immunhistochemische Analyse der tumoralen PD-L1 Expression an einem Kollektiv von 126 Patientinnen mit primärem Plattenepithelkarzinom der Vulva durch. Die Ergebnisse wurden mit klinischen und immunologischen Parametern sowie dem
Outcome
korreliert.
Ergebnisse:
Wir konnten in unserem Kollektiv darstellen, dass PD-L1 von Vulvakarzinomzellen exprimiert wird. Darüber hinaus war eine hohe Expression von PD-L1 mit einem kürzeren rezidivfreien (p < 0,01) und Gesamtüberleben (p < 0,01) korreliert. Das mediane Gesamtüberleben bei hoher PDL-1 Expression betrug 30,28 Monate und bei niedriger bzw. fehlender Expression 128,55 Monate (Medianes Follow-up 70,42 Monate).
Schlussfolgerung:
Unsere Daten lassen vermuten, dass PD-L1 beim Plattenepithelkarzinom der Vulva eine prognostische Rolle spielt. Eine zielgerichtete Therapie gegen den PD-L1 Rezeptor erscheint daher zukünftig auch beim Vulvakarzinom sinnvoll.
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