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Safi S.,University of Heidelberg | Benner A.,German Cancer Research Center | Walloschek J.,University of Heidelberg | Renner M.,German Cancer Research Center | And 6 more authors.
PLoS ONE | Year: 2015

Pneumonectomy is associated with significant postoperative mortality. This study was undertaken to develop and validate a risk model of mortality following pneumonectomy. We reviewed our prospective database and identified 774 pneumonectomies from a total of 7792 consecutive anatomical lung resections in the years 2003 to 2010 (rate of pneumonectomy: 9.9%). Based on data from 542 pneumonectomies between 2003 and 2007 (i.e., the "discovery set"), a penalized multivariable logistic regression analysis was performed to identify preoperative risk factors. A risk model was developed and validated in an independent data set of 232 pneumonectomies that were performed between 2008 and 2010 (i.e., the "validation set"). Of the 542 patients in the discovery set (DS), 35 patients (6.5%) died after pneumonectomy during the same admission. We developed a risk prediction model for inhospital mortality following pneumonectomy; that model included age, current alcohol use, coronary artery disease, preoperative leukocyte count and palliative indication as possible risk factors. The risk model was subsequently successfully validated in an independent data set (n = 232) in which 18 patients (7.8%) died following pneumonectomy. For the validation set, the sensitivity of the model was 53.3% (DS: 54.3%), the specificity was 88.0% (DS: 87.4%), the positive predictive value was 26.7% (DS: 22.9%) and the negative predictive value was 95.8% (DS: 96.5%). The Brier score was 0.062 (DS: 0.054). The prediction model is statistically valid and clinically relevant. © 2015 Safi et al.

Emons G.,University of Gottingen | Gorchev G.,University Hospital Dr Gregory Stranski | Sehouli J.,Charite - Medical University of Berlin | Wimberger P.,Universitatsklinikum Essen | And 8 more authors.
Gynecologic Oncology | Year: 2014

Objectives To evaluate the activity and toxicity of AEZS-108 (Zoptarelin Doxorubicin Acetate) an LHRH agonist linked to doxorubicin in women with platinum refractory or resistant ovarian cancer expressing LHRH receptors. Methods Women with epithelial ovarian, fallopian tube or primary peritoneal cancer, expressing LHRH receptors were eligible for this trial, when they had progression during treatment with a platinum based regimen or within 6 months after receiving a platinum based regimen and a previous taxane treatment. At least one measurable target lesion (RECIST) or CA-125 levels higher than twice the upper limit of normal range (GCIG-criteria) were required. Patients received AEZS-108 (267 mg/m2 equimolar to 76.8 mg/m2 of free doxorubicin) every 3 weeks as a two hour i.v. infusion. Results Fifty-five of 59 (93%) of ovarian cancer samples screened expressed LHRH receptors. 42 patients were enrolled in this study and received at least 1 infusion of AEZS-108 (ITT population). Of these 42 patients 6 (14.3%) had a partial response, 16 (38%) stable disease, 16 (38%) progressive disease and 4 patients were not evaluable. Median time to progression was 12 weeks (95% CI: 8-20 weeks), and median overall survival was 53 weeks (95% CI: 39-73 weeks). Toxicity profile was favorable. Conclusion AEZS-108 has a clinical activity in platinum refractory/resistant ovarian cancer which seems to be comparable to that of pegylated liposomal doxorubicin or to topotecan. Toxicity was comparably low. These data support the concept of a targeted chemotherapy for tumors expressing LHRH receptors. © 2014 Elsevier Inc.

Graeter T.P.,Klinik Loewenstein | Sebastian B.,Klinik Loewenstein | Bischof M.,Institute for Radiation Therapy | Kugler G.,Klinik Loewenstein | And 2 more authors.
Thoracic and Cardiovascular Surgeon | Year: 2015

Objectives The role of postoperative mediastinal radiotherapy in completely resected non-small cell lung cancer (NSCLC) and pathological N2 disease is controversial. In clinical practice, not all lung cancer patients with histologically confirmed N2 disease and a high risk for local recurrence are able to undergo postoperative concurrent radio/chemotherapy due to their physical condition or postoperative morbidities. Mediastinal radiotherapy is less compromising than a combination of radio/chemotherapy and seems likely to be tolerable for limited patients to achieve better local tumor control. Materials and Methods All patients included in this retrospective analysis were excluded from postoperative adjuvant combination chemo/radiotherapy due to their comorbidity, advanced age, or a complicated postoperative course. Three-dimensional conformal radiotherapy of the mediastinal lymph node stations (mean dose: 50 Gy; range: 50–54 Gy) in patients with R0 resection, additional boost of 10 Gy in patients with R1 or R2 resection, was performed postoperatively. Results A total of 110 patients were included in this analysis. Mean survival was 25.5 ± 19.2 months. The 1-, 3-, and 5-year survival was 75.4, 38.7, and 26.2%, respectively. Postoperative complications and the development of distant metastases did not correlate (p = 0.7). Distant metastases proved to be a significant prognostic factor of survival (p < 0.0001). Local recurrence was seen in a total of three patients (2.7%). Five-year survival of patients developing major postoperative complications was significantly inferior (p = 0.04) to those without postoperative complications. The extent of surgery had a significant impact on survival—5-year survival after lobectomy was significantly longer than after pneumonectomy (p = 0.029). R1 resection had no significant impact on the survival rates (p = 0.67). Discussion Stage III–N2 NSCLC patients with multiple comorbidities or a complicated postoperative course after surgery may benefit from modern mediastinal radiotherapy. Surgery and postoperative mediastinal radiotherapy can achieve local tumor control. Distant metastases have the highest impact on the prognosis. Pneumonectomy, however, should be avoided in stage III NSCLC, when possible. Copyright © 2015, Georg Thieme Verlag KG. All rights reserved.

Schneider T.,St. Vincentius Kliniken Karlsruhe | Schneider T.,Thoracic Surgery Center | Heussel C.P.,University of Heidelberg | Herth F.J.F.,University of Heidelberg | Dienemann H.,University of Heidelberg
Deutsches Arzteblatt International | Year: 2013

Background: About 50 000 new cases of non-small-cell carcinoma of the lung are diagnosed in Germany each year. More than 20% of the affected patients cannot be offered radical resection because of comorbidity alone. The lung is also the second most common site of distant metastases of extrathoracic tumors; it is the only site of such metastases in 20% of cases. In recent years, image-guided thermoablation has been used with increasing frequency in patients who are unable to undergo surgery for medical reasons.Methods: The PubMed database was selectively searched for publications on the indications, complications, and results of the thermoablative techniques currently in clinical use, with special attention to radiofrequency ablation (RFA).Results: There is only a small evidence base to date concerning the treatment of malignant lung tumors with thermoablation. Retrospective and prospective case series have been published, but no randomized controlled trials have yet been conducted. RFA, the most common technique, involves the image-guided percutaneous placement of one or more probes in the tumor, to which thermal energy is then applied. For peripherally located tumors that measure less than 3 cm in diameter, local control of tumor growth can be achieved in about 90% of cases. The long-term results that are now available from smaller series provisionally indicate 5-year survival rates of 20% to 61%. The most common complication is pneumothorax requiring drainage, which occurs in about 10% of cases. In the intermediate term, thermoablation does not cause any clinically relevant loss of pulmonary function.Conclusion: Image-guided thermoablation cannot now be considered an alternative to surgery for the treatment of malignant lung tumors with curative intent. It does, however, widen the spectrum of therapeutic options for patients who are medically unable to undergo a surgical procedure. © Dtsch Arztebl 2013.

Von Pawel J.,Asklepios Fachkliniken | Jotte R.,Rocky Mountain Cancer Center | Spigel D.R.,Sarah Cannon Research Institute | O'Brien M.E.R.,Royal Marsden National Health Service NHS Foundation Trust | And 15 more authors.
Journal of Clinical Oncology | Year: 2014

Purpose: Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC. Patients and Methods: A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m2 intravenously (IV) on days 1 to 3 or topotecan 1.5 mg/m2 IV on days 1 to 5. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival (PFS), and safety. Results: Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan (HR, 0.802; P < .018). ORR was 31.1% with amrubicin and 16.9% with topotecan (odds ratio, 2.223; P < .001). Grade ≥ 3 treatment-emergent adverse events in the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004), thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001), respectively. NQO1 polymorphisms did not influence safety outcomes. Conclusion: Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC. OS did not differ significantly between treatment groups, although an improvement in OS was noted in patients with refractory disease treated with amrubicin. © 2014 by American Society of Clinical Oncology.

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