Fabinshy Thangarajah

Evaluation of QTc Interval Prolongation in Breast Cancer Patients after Treatment with Epirubicin, Cyclophosphamide, and Docetaxel and the Influence of Interobserver Variation.

Background: Chemotherapy with anthracyclines is associated with life-threatening electrocardiographic alterations including corrected QT (QTc) interval prolongation. Patients and Methods: In this study we assessed the effect of epirubicin, cyclophosphamide, and docetaxel (EC-Doc) on the QTc interval in 10 patients with early breast cancer. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography (ECG), and serum cardiac markers at baseline and after 4 cycles of EC and 4 cycles of docetaxel. To evaluate the influence of interobserver variation, the QTc interval was analyzed by a cardiologist, a gynecologist, and with automated ECG interpretation software. Results: There was a significant QTc prolongation after EC treatment independent of the investigator. In addition, a significant increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels was noted after EC treatment. QTc prolongation and NT-proBNP levels normalized after docetaxel treatment. Other biochemical markers were within normal ranges. No clinically relevant effect on left ventricular ejection fraction was observed. Conclusion: This prospective study demonstrated that EC treatment increases the QTc interval and NT-proBNP levels in women with early breast cancer. This effect was reversible and independent of docetaxel administration. Moreover, the treating physician can safely perform QTc interval evaluation as part of clinical routine independent of his/her specialty. Due to the small number of patients, further conclusions are limited at this point.

Neoadjuvant Therapy of Cervical Carcinoma with the Angiogenesis Inhibitor Bevacizumab: a Single-Centre Analysis

Introduction Cervical cancer is the fourth most frequent cancer in women worldwide. Addition of the VEGF antibody bevacizumab in combination with platinum-containing chemotherapy achieved an improvement in overall survival in advanced cervical cancer. To date there are no data on neoadjuvant use of bevacizumab. We therefore studied the benefit of neoadjuvant combined therapy with bevacizumab in a group of cervical cancer patients. Patients and Methods This retrospective cohort study analysed 14 patients with cervical cancer FIGO stages 1b1 to IV who received neoadjuvant platinum-containing chemotherapy in combination with bevacizumab. The comparative cohort consisted of 16 patients who were treated with neoadjuvant platinum-containing chemotherapy alone. The response rates were determined by means of preoperative clinical examination, diagnostic imaging (RECIST), changes in tumour markers (SCC) and by histopathology. Results A clinical response was found in 93.8% (n = 15) of patients after bevacizumab-free therapy and in 100% (n = 14) of the patients who were treated with bevacizumab in addition. Combined therapy with bevacizumab led to a higher rate of clinical complete remission (42.9 vs. 12.5%; p = 0.072) and significantly improved the reduction in tumour size (Δ longest diameter: 3.7 vs. 2.5 cm; p = 0.025). Downgrading was observed in 100% of all patients treated with bevacizumab compared with 75% in the control arm. The rate of pathological complete remission (pCR) was not altered significantly (28.6% [n = 4] vs. 37.5% [n = 6]; p = 0.460). Discussion Overall, combined therapy with bevacizumab led to a better clinical response. Operability was therefore improved more often. Because of the small patient cohort, larger prospective studies are necessary to validate the effect of neoadjuvant combined therapy with bevacizumab.

Profile and Outcome of Supraclavicular Metastases in Patients with Metastatic Breast Cancer: Discordance of Receptor Status Between Primary and Metastatic Site

Background: Breast cancer is a heterogenous and complex disease. A rare site of metastatic breast cancer disease is the neck. Data about supraclavicular metastases in patients with metastatic breast cancer are still lacking. Hence, our study aimed to analyze histological subtypes of supraclavicular metastases compared to the primary site. Materials and Methods: This was a retrospective hospital-based cohort study of patients with breast cancer who developed supraclavicular metastases. Diagnosis of supraclavicular metastases was confirmed by biopsy or diagnostic lymph node extirpation. Histological subtypes were analyzed and Kaplan–Meier estimates were calculated for overall survival. Results: A total of 20 patients were included in the analysis. The majority of the patients (12/20) had hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative supraclavicular metastases, disease in 3/20 patients was HR-positive/HER2-positive, HR-negative/HER2-positive in 1/20 patients and basal-like in 4/20 patients. Total discordance rates for estrogen receptor, progesterone receptor and HER2 between primary and metastatic tumors were 20.0%, 36.8% and 29.4%, respectively. The 5-year overall survival was 80%, whereas the 5-year survival after the onset of neck metastasis was 45%. Conclusion: As a rare site of metastatic breast cancer, supraclavicular metastases are associated with a worse median overall survival from their onset. The high rate of discordance of histological subtype stresses the necessity for biopsies in patients with supraclavicular metastasis.

Klinische Erfahrungen zum Einsatz von Bevacizumab in der Primärtherapie des fortgeschrittenen Zervixkarzinoms

Eine neoadjuvante Systemtherapie kann nach den aktuellen S3-Leitlinien fur Patientinnen mit einer primar fortgeschrittenen Erkrankung unter bestimmten Bedingungen empfohlen werden. Fur dieses verhaltnismasig kleine Kollektiv kann der zytoreduktive Effekt einer neoadjuvanten Systemtherapie bei Vorhandensein definierter Risikofaktoren wie einem Bulky Disease oder einem positiven Lymphknotenstatus einen moglichen Benefit hinsichtlich des chirurgischen Outcomes bedeuten. Ziel ist es, die Operabilitat zu verbessern und die Notwendigkeit einer adjuvanten Radiochemotherapie zu reduzieren. Ziel dieser Analyse war es den Effekt von Bevacizumab analog der Ergebnisse der GOG 240 Studie in der Primartherapie des Zervixkarzinoms zu evaluieren. Alle Patientinnen mit der Diagnose eines lokal fortgeschrittenen oder metastasierten Zervixkarzinom welche zwischen 2008 und 2015 in der onkologischen Ambulanz der Universitatsfrauenklink Koln eine primar systemische, platin- und taxanbasierte Polychemotherapie mit oder ohne Bevacizumab erhielten wurden in diese retrospektive Evaluation eingeschlossen. Die primar systemische Polychemotherapie ist definiert als eine Kombination aus Cisplatin (40 mg/m2/KOF) und Docetaxel (35 mg/m2/KOF) appliziert in einem wochentlichen Schema. Insgesamt wurden 32 Patientinnen primar chemotherapiert bzw. radiochemotherapiert. 26 Patientinnen erhielten eine Polychemotherapie mit Cisplatin/Taxotere (40/35 mg/m2/KOF/q7). 3 weitere Patientinnen erhielten dieses Schema erganzt durch eine VEGF-Blockade mit Bevacizumab 5 mg/Kg/KG/q7. Fur eine Patientin im FIGO Stadium IV (M1 hepatisch) erfolgte eine Modifikation des definierten Schemas zu Gunsten eines dosisintensivierten Protokolls mit 12x Paclitaxel 90 mg/m2/KOF/q7, Carboplatin AUC6/q28 und Bevacizumab 15 mg/Kg/KG/q21. In der Gesamtschau ergab sich, dass Patientinnen ohne VEGF-gerichteter Therapie im Stadium I allesamt eine postoperative Komplettremission zeigten. Im Stadium II zeigte sich bei gleicher Therapie nur in 12,5% der Falle eine Komplettremission, in 50% eine partielle und in 37,5 5 keinerlei Therapieansprechen. Ahnliche Ergebnisse stellten sich fur die Stadien III und IV ein. Insgesamt erhielten 4 Patientinnen im Stadium II-IV die zusatzliche VEGF-gerichtete Therapie. Im Einzelnen ergab sich fur eine 29-jahrige Patientin eine postoperative Komplettremission im Stadium IIb. Fur die zwei Patientinnen im Stadium IVa ergaben sich eine komplette und eine Teilremission bei nicht komplettierter Chemotherapie. Fur die Patientin im Stadium IVb, welche ein dosisintensiviertes Schema erhielt stellte sich ebenfalls die Komplettremission ein. In fruhen Erkrankungsstadien (<FIGO II) kann die alleinige platinbasierte Chemotherapie zu einer Komplettremission fuhren. Mittels kombinierter VEGF-gerichteter Therapie ist im Rahmen der Primartherapie eine Komplettremission auch in fortgeschrittenen Stadien FIGOIV moglich und sollte in klinischen Studien weiter untersucht werden.