N Ewald-Riegler

Clinical management of borderline ovarian tumors

Borderline ovarian tumors (BOTs) are epithelial tumors of the ovaries characterized by cellular proliferation and nuclear atypia but without an infiltrative growth pattern. As they frequently affect younger patients the clinical management is complicated by considerations such as preserving fertility and reducing postoperative morbidity. Over the past several decades surgical therapy has shifted from a radical approach to more conservative treatment. There are various modes of surgery applied to the patients. All these developments have to be considered from an oncologic standpoint as BOTs represent a potentially malignant disease. Oncologic safety, as well as patients’ desires and expectations, have to be balanced to reach the most appropriate treatment for BOTs. For this reason current literature will be discussed in this review to give a thorough overview of this topic and to develop recommendations for the surgical management of these patients. Open questions will be identified to elaborate the need for future surveys and research.

Poly(ADP-ribosyl)ation polymerases: mechanism and new target of anticancer therapy

Poly(ADP-ribose)polymerase (PARP) is a ubiquitously present nuclear enzyme that is not only involved in many important cellular pathways but also contributes to chromosomal structure and genomic stability. The development of highly selective and potent PARP inhibitors has become of increasing clinical interest because of their promising efficacy in patients with breast or ovarian cancer. Furthermore, recent Phase I and hase II trials have demonstrated that PARP inhibitors have low toxicity rates. In particular patients with either deficiency or dysfunction of BRCA, which is involved in DNA double strand break repair, appear to benefit from PARP inhibition. This article summarizes the present knowledge regarding the physiological function of PARP and ([poly]ADP-ribose) PAR, the functional product of PARP, the development of PARP inhibitors, the recent clinical data of PARP inhibitors in cancer treatment and the selection of patients who may benefit from PARP inhibition.

Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Borderline tumors of the ovary: clinical course and prognostic factors.

Background: The prognosis in borderline tumors of the ovary (BOT) is generally favorable. However, some patients experience recurrence, and mortalities occur. There is a need to better characterize prognostic factors to be considered for individualized treatment planning. Patients and Methods: The data of 158 consecutive patients who underwent surgery for BOT at a tertiary referral center for gynecologic oncology between 1997 and 2008 were retrospectively analyzed. Results: Most patients had early stage disease, and advanced stages FIGO II/III only occurred in 23.4%. Serous histology was most frequent (68%), followed by mucinous histology (22%). All patients received surgery as initial treatment with no adjuvant systemic therapy. 37 patients (40.7% of the patients under the age of 50) had fertility-sparing surgery (FSS). Recurrent disease occurred in 18 (11.4%) patients, and 4 (2.5%) patients died. Independent risk factors for recurrence were FIGO stages > I (hazard ratio (HR) 37.1; 95% confidence interval (CI) 4.5–155.5), tumor rupture (HR 12.4; 95% CI 1.5–61.5), incomplete staging (HR 5.9; 95% CI 1.6–21.3), and FSS in patients < 50 years (HR 8.0; 95% CI 2.0–31.6). Conclusion: Intraoperative tumor rupture, incomplete staging, and FSS – all influenced by the surgeon – may impose a substantial recurrence risk. Therefore, careful counseling and balancing of risk and benefit are mandatory before therapy is applied, especially if FSS is planned.

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study

Background: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.Methods: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).Results: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.Conclusion: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.

Impact of treatment guidelines and implementation of a quality assurance program on quality of care in endometrial cancer.

Background: The treatment guidelines in the last decade have shown a trend towards increasing surgical radicality in endometrial cancer. Little information is available on the implementation of standards into clinical reality. We evaluated the adherence to standard therapy before and after introduction of an internal quality management system and determined the reasons for non-adherence. Patients and Methods: A retrospective analysis of the inhouse tumor registry was performed. Included were all patients with Federation of Gynecology and Obstetrics (FIGO) I–III endometrial cancer and therapy at the Dr. Horst Schmidt Klinik (HSK) from 1997 to 2007. Results: 206 patients with epithelial endometrial cancer in stage FIGO I–III underwent primary surgery at the HSK. 140 (68%) patients were operated as recommended by the guidelines. 20% of patients were operated less radically (17% vs. 22% before and after introduction of guidelines; p = 0.33) and 12% more radically. The latter was significantly reduced after implementation of quality management (21% vs. 7%; p = 0.004). Comorbidities and age played an important role in less-than-standard treatment. Conclusions: Adherence to guideline-based therapy for endometrial cancer can be achieved in most patients. Implementation of standards and quality assurance primarily helps to avoid surgical overtreatment but failed to reduce less-than-standard treatment radicality. The latter seemed to be more defined by patient characteristics than by institution standards.