Acid ceramidase (AC)--a key enzyme of sphingolipid metabolism--correlates with better prognosis in epithelial ovarian cancer.

Acid ceramidase (AC), a key enzyme of sphingolipid metabolism, seems to play an important role in cancer progression. The objective of this study was to explore the expression of AC in ovarian cancer and its impact on prognosis. Expression analysis of AC in n=112 ovarian cancer patients was performed by immunohistochemical analysis of primary paraffin-embedded tumor samples. The results were scored on the basis of the staining intensity and percentage of positive tumor cells, resulting in an immunoreactive score from 0 to 12. These results were correlated to clinical and pathologic characteristics and survival. AC expression correlated significantly only with FIGO stage (0.047). In serous carcinoma, low level of AC was independently associated with reduced progression-free survival and overall survival of 12.0 mo [95% confidence interval (CI), 5.78-18.23] versus 18.1 mo (95% CI, 11.61-24.59; P=0.008) and 35.7 mo (95% CI, 22.24-47.16) versus 58.7 mo (95% CI, 36.48-80.91; P=0.032), respectively. In multivariate analysis, AC presents as an independent prognostic factor for progression-free survival (hazard ratio 1.88; 95% CI, 1.13-3.11; P=0.015). AC is a prognostic factor in epithelial ovarian cancer. Low AC expression can be associated with tumor progression in carcinoma of the ovaries. These results are in contrast to the concept of AC as a promoter for cancer progression. Nevertheless, they are supported by the lately discovered tumor-suppressing function of sphingosine, the enzymatic product of AC.

Resumption of Trastuzumab in Patients With Disease Recurrence After (Neo-) Adjuvant Anti-HER2-therapy in Patients With HER2-positive Breast Cancer.

BACKGROUND/AIM: HER2-positive breast cancers eventually relapse in about one third of patients. Is anti-HER2-directed therapy with Herceptin® (trastuzumab) effective in re-treatment? Between 2008 and 2018, 216 patients with recurrent HER2-positive breast cancer (BC) were re-treated with Herceptin (HER) during first-line therapy. This study assessed the effectiveness and tolerability of re-treatment with HER. PATIENTS AND METHODS: After approval from Ethical committee, the NIS was conducted according to German Drug Act. Re-treatment with HER was documented at routine visits starting with a basic observational period of maximum 12 months and a follow-up period of maximum additional four years. RESULTS: HER2-positive BC relapsed after a median of 36.5 months (mos). Patients were re-treated with HER +/- chemotherapy +/- endocrine therapy. HER-containing regimens resulted in median progression-free survival (mPFS) of 12.7 (95%CI=10.5-14.8) mos and overall survival (OS-2) of 31.6 mos (95%CI=28.8-38.4) since recurrence diagnosis. Differentiation of recurrence types (local, visceral, non-visceral) unfolded worst prognosis for patients with visceral metastases. Cardiac monitoring within this non-interventional study (NIS) did not result in new safety concerns. CONCLUSION: Re-therapy with HER in the first-line setting of advanced HER2-positive breast cancer is effective and without unexpected or intensified adverse events.

Preference of elderly patients' to oral or intravenous chemotherapy in heavily pre-treated recurrent ovarian cancer: final results of a prospective multicenter trial.

BACKGROUND: Palliative systemic treatment in elderly gynaecological cancer patients remains a major challenge. In recurrent ovarian cancer (ROC), treosulfan an active alkylating drug showed similar cytotoxicity whether as oral (p.o.) or intravenous (i.v.) application. The aim of this innovative trial was to evaluate the preference of elderly patients (≥65 years) for p.o. or i.v. chemotherapy focusing compliance, outcome, toxicities, and geriatric aspects as secondary endpoints. METHODS: Patients with ROC had the free choice between treosulfan i.v. (7000 mg/m2 d1, q29d) or p.o. (600 mg/m2 daily d1-28, q57d). Only indecisive participants were randomized. RESULTS: Overall 123 patients with 2nd to 5th recurrence were registered and 119 received at least one cycle of chemotherapy. 85.7% preferred treosulfan i.v. and 14.3% oral, where only three patients were randomized. Main reasons for i.v. preference associated with individual expectations of lower rate of gastrointestinal disorders, higher activity and tolerability of treatment. Median of applied chemotherapies was three (range 1-12 cycles), with most common grade 3/4 toxicities thrombopenia (18.7%), leukopenia (15.7%), ascites (7.6%), bowel obstruction (6.7%), and abdominal pain (4.2%). Median time until progression/overall survival was 5.2/7.8 months (i.v.), and 5.6/10.4 months (p.o.), respectively, without significant differences in efficacy. CONCLUSIONS: Elderly patients with recurrent ovarian cancer asked and demonstrated active participation in the decision-making process of their oncological treatment and favoured predominantly the i.v. application. Treosulfan was generally well-tolerated despite comorbidities and heavy pre-treatment. Our study demonstrates that patients' preference did not influence prognosis negatively and remains important in gynaecologic oncology decision practice. EUDRACT NR: 2004-000719-25; NCT 00170690.

Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynäkologische Onkologie CaRE-1 multicenter study.

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. METHODS: AGO-CaRE-1 is a large retrospective study. Patients (n = 1618) with vulvar cancer ≥ FIGO stage IB treated at 29 German gynecologic-cancer-centres 1998-2008 were included. This subgroup analysis focuses on solely surgically treated node-negative patients with complete tumour resection (n = 289). RESULTS: Of the 289 analysed patients, 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumours. One hundred twenty-five (43.3%) underwent complete vulvectomy, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1 mm-33 mm); all patients received groin staging, in 86.5% with full dissection. Median follow-up was 35.1 months. 46 (15.9%) patients developed recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in patients with a margin <8 mm and 10.2% in patients with a margin ≥8 mm. When analysed as a continuous variable, the margin distance had no statistically significant impact on local recurrence (HR per mm increase: 0.930, 95% CI: 0.849-1.020; p = 0.125). Multivariate analyses did also not reveal a significant association between the margin and local recurrence neither when analysed as continuous variable nor categorically based on the 8 mm cutoff. Results were consistent when looking at disease-free-survival and time-to-recurrence at any site (HR per mm increase: 0.949, 95% CI: 0.864-1.041; p = 0.267). CONCLUSIONS: The need for a minimal margin of 8 mm could not be confirmed in the large and homogeneous node-negative cohort of the AGO-CaRE database.