B. Beutel

Bevacizumab in the Treatment of Ovarian Cancer

IntroductionIn the past decade there have been many attempts to improve systemic treatment and thus the outcome of patients with ovarian cancer. However, neither the sequential addition of non cross-resistant drugs to standard chemotherapy comprising carboplatin and paclitaxel, nor triplet combination therapies with conventional chemotherapeutic drugs have improved outcomes. Instead, such approaches have led to an increase in the incidence of side effects. We are currently experiencing a shift toward the addition of molecularly targeted and biological anticancer therapies to standard treatment. Vascular endothelial growth factor (VEGF), which improves vitally important tumor vasculature, is secreted by a range of tumors, and a high level of VEGF is known to be an independent risk factor for aggressive disease in ovarian cancer. This finding led to the development in the 1990s of bevacizumab, a humanized monoclonal antibody against VEGF.DiscussionSeveral phase II trials and four phase III trials have demonstrated that bevacizumab is active in patients with advanced and recurrent ovarian cancer. Both phase III trials of bevacizumab as first-line therapy in advanced ovarian cancer (ICON 7/AGOOVAR 11 and GOG-0218) have shown that the addition of bevacizumab to chemotherapy and as maintenance therapy improves progressionfree survival (PFS). The phase III trials in platinum-sensitive (OCEANS) and platinumresistant, relapsed disease (AURELIA) have also demonstrated a benefit for bevazicumab with respect to PFS. The administration of bevacizumab to improve survival in patients with ovarian cancer is not without side effects and a broad discussion on the cost-effectiveness of this approach is ongoing.ConclusionThis article presents clinical trial data on bevacizumab in the treatment of ovarian cancer and discusses the indication and pitfalls in the application of bevacizumab in patients with this malignancy.

Prognostic and predictive value of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score in surgery for recurrent ovarian cancer

OBJECTIVES The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score was developed as selection criteria and validated as predictor of a high probability for complete resection in recurrent ovarian cancer. It is not defined whether the predictive value is independent from underlying tumor biology or is solely based on a selection of good prognostic risks. METHODS We performed an exploratory analysis of all consecutive patients with cytoreductive surgery in recurrent ovarian cancer in a tertiary referral center 1999-2013, before and after introduction of the AGO score. RESULTS 217 consecutive patients were included of whom 112 patients were AGO score positive and 105 patients were score negative. Corresponding complete resection rates were 89.3% and 66.7%, respectively, and confirm the scores predictive value. However, a positive AGO score was also associated with better outcome after adjustment for surgical outcome. Patients with complete resection and a positive AGO score showed a median overall survival of 63.9 months (95% CI 48.1-79.6) compared to 48.4 months (95% CI 30.3-66.5) after complete resection and negative score (log-rank p=0.10). However, in multivariate analysis the only independent prognostic factor was complete resection (HR 2.450; 95% CI: 1.542-3.891). CONCLUSIONS The AGO score could identify suitable candidates for secondary cytoreductive surgery but failed to prove an independent prognostic value thus suggesting an effect of successful surgery on its own. However, the latter has to be proven prospectively. In addition, further studies should evaluate the predictive and prognostic impact of a negative score.

Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery

OBJECTIVE Describing the pattern of and reasons for post-operative tumor residuals in patients with advanced epithelial ovarian cancer (AOC) operated in a specialized gynecologic cancer center following a strategy of maximum upfront debulking followed by systemic chemotherapy. METHODS All consecutive AOC-patients treated between 2005 and 2015 due to stages FIGO IIIB/IV were included in this single-center analysis. RESULTS 739 patients were included in this analysis. In 81 (11.0%) patients, chemotherapy had already started before referral. Of the remaining 658 patients, upfront debulking was indicated in 578 patients (87.8%), while 80 patients (12.8%) were classified ineligible for upfront debulking; mostly due to comorbidities. A complete tumor resection was achieved in 66.1% of the 578 patients with upfront surgery, 25.4% had residuals 1-10mm and 8.5% had residuals exceeding 10mm, and 12.5% of patients had multifocal residual disease. Most common localization was small bowel mesentery and serosa (79.8%), porta hepatis/hepatoduodenal ligament (10.1%), liver parenchyma (4.3%), pancreas (8.0%), gastric serosa (3.2%), and tumor surrounding/infiltrating the truncus coeliacus (2.7%); 14.9% of the patients had non-resectable supra diaphragmatic lesions. Size of residual tumor was significantly associated with progression-free and overall survival. CONCLUSIONS Upfront debulking for AOC followed by systemic chemotherapy was our main treatment strategy in almost 90% of all patients. The majority experienced a benefit by this approach; while 11.7% of patients probably did not. Understanding sites and reason for residual disease may help to develop adequate surgical training programs but also to identify patients that would better benefit from alternative treatment strategies.

Assessment of the sentinel lymph node in patients with invasive squamous carcinoma of the vulva

Objective. This study aims to evaluate the feasibility and diagnostic validity of the sentinel lymph node technique in detecting inguinal lymph node metastases in patients with invasive squamous cancer of the vulva. Design. Retrospective analysis of the in‐house tumor registry. Setting. Dr. Horst Schmidt Klinik, a tertiary gynecologic oncology unit in Wiesbaden, Germany, June 2000–May 2008. Population. All consecutive operated patients with primary envisaged diagnosis were included. Methods. The sentinel node identification technique was performed and patients were informed accordingly. Patients who consented and were found eligible underwent preoperative lymphscintigraphy on the day before surgery. Main outcome measures. Sentinel node detection in specimen from sentinel lymph node biopsy and from full lymphadenectomy (LNE); sentinel lymph node biopsy as a sole surgical groin procedure in patients with histological negative sentinel node; benefit with respect to side effects for sentinel lymph node biopsy compared to full LNE; complication rates; and recurrences of vulvar cancer. Results. In all, 46 of 59 patients with vulvar malignancy underwent inguinofemoral LNE, sentinel lymph node biopsy (SLB) of the groin followed by LNE, or SLB alone. Most patients had been diagnosed in the early stages of the disease. Since no false positive or false negative results were recorded, the sensitivity, specificity, positive predictive value and negative predictive value of the sentinel lymph node were 100%. However, in 6%, a sentinel lymph node could not be detected intraoperatively indicating a feasibility of 94%. Conclusion. The implementation of sentinel lymph node technique for groin staging in squamous cell vulvar cancer seems to provide a feasible and safe technique in tertiary gynecologic oncology.

Operatives Management präkardialer Lymphknoten bei fortgeschrittenem Ovarialkarzinom

Fragestellung: Neben dem Tumorstadium ist der postoperative Tumorrest der wichtigste Prognosefaktor beim fortgeschrittenen Ovarialkarzinom. Die Exzision radiologisch nachweisbarer bulky nodes im Mediastinum wird meist als inoperabel eingestuft. Isoliert, basal/prakardial im Mediastinum liegende suspekte Lymphknoten erscheinen einer operativen Therapie im Rahmen einer Debulking-Operation zuganglich. Erste Erfahrungen mit der operativen Therapie solcher Befunde werden berichtet. Methodik: Analyse unserer Tumordatenbank bezuglich Resektion mediastinaler Lymphknoten im Rahmen einer Debulking-Operation zwischen 2011 und 02/2014. Ergebnis: Insgesamt wurde bei 6 Patientinnen wahrend der zytoreduktiven Operation eine mediastinale Lymphadenektomie durchgefuhrt. Das mediane Alter lag bei 59 (range 43 – 75) Jahren. Die Resektion der prakordialen Lymphknoten erfolgte nach Eroffnung des Zwerchfells von abdominal, Palpation/Inspektion von Pleurahohle und Mediastinum. Intraoperativ wurde bei 5 Patientinnen eine Thoraxsaugdrainage vor Verschluss des Zwerchfells eingelegt. Komplikationen wie Pneumothorax, thorakale Lymphorrhoe etc. wurden nicht beobachtet. Es wurden zwischen einem und funf Lymphknoten entfernt. Alle entnommen Lymphknoten waren tumorbefallen. Die endgultige FIGO-Klassifikation anderte sich in 3 der 6 Falle von FIGO-Stadium III C zu FIGO-Stadium IV. Bei den restlichen 3 Fallen blieb es wegen maligner Pleuraergusse beim FIGO-Stadium IV. Bei 5 Patientinnen konnte hierdurch eine Komplettresektion erreicht werden. Eine Patientin wies multiple prakardiale/mediastinale Lymphknoten (Tumorrest > 2 cm; Komplettresektion nicht moglich) auf. Bei dieser Patientinnen erfolgte die LK-Exzision zur histologischen Sicherung, um uber die intraabdominale OP-Radikalitat zu entscheiden. Schlussfolgerung: Die Erfahrungen zum Management prakardialer Lymphknoten sind limitiert. Bei ihrem Nachweis in der praoperativen Bildgebung, sollte eine Exzision erfolgen, sofern der Allgemeinzustand der Patientin dies zulasst und hierdurch Tumorfreiheit erzielt werden kann.