Untch M.,Helios Klinikum |
Loibl S.,German Breast Group |
Bischoff J.,Universitats Frauenklinik |
Eidtmann H.,Universitats Frauenklinik |
And 15 more authors.
The Lancet Oncology | Year: 2012
Background: We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy. Methods: In the GeparQuinto randomised phase 3 trial, patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7, 2007, and July 9, 2010. Patients were eligible if their tumours were classified as cT3/4a-d, or hormone receptor (HR)-negative, HR-positive with clinically node-positive and cT2 disease (cT2 cN+), or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease (cT1 pN SLN+). Patients were randomly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC (epirubicin [90 mg/m 2 intravenously] plus cyclophosphamide [600 mg/m 2 intravenously], every 3 weeks), and four cycles of docetaxel (100 mg/m 2 intravenously every 3 weeks) with either trastuzumab (6 mg/kg intravenously, with a starting loading dose of 8 mg/kg, for eight cycles, every 3 weeks) or lapatinib (1000-1250 mg per day orally) throughout all cycles before surgery. Randomisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site, HR status, and extent of disease (cT1-3 cN0-2 vs T4 or N3). The primary endpoint was pathological complete response (defined as ypT0 and ypN0) and was analysed in all patients who received at least one cycle of EC. Participants and investigators were not masked to treatment assignment. Pathologists in centres assessing surgery outcomes were masked to group assignment. This trial is registered with ClinicalTrials.gov, number NCT00567554. Findings: Of 620 eligible patients, 309 were randomly assigned to chemotherapy with trastuzumab (ECH-TH group) and 311 to chemotherapy with lapatinib (ECL-TL group). Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery. 93 (30·3%) of 307 patients in the ECH-TH group and 70 (22·7%) of 308 patients in the ECL-TL group had a pathological complete response (odds ratio [OR] 0·68 [95%CI 0·47-0·97]; p=0·04). Chemotherapy with trastuzumab was associated with more oedema (119 [39·1%] vs 88 [28·7%]) and dyspnoea (90 [29·6%] vs 66 [21·4%]), and ECL-TL with more diarrhoea (231 [75·0%] vs 144 [47·4%]) and skin rash (169 [54·9%] vs 97 [31·9%]). 43 (14·0%) patients discontinued in the ECH-TH group and 102 (33·1%) in the ECL-TL group. 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group. Interpretation: This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab. Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy. Funding: GlaxoSmithKline, Roche, and Sanofi-Aventis. © 2012 Elsevier Ltd.
Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: Initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial
Rodel C.,Goethe University Frankfurt |
Liersch T.,University of Gottingen |
Becker H.,University of Gottingen |
Fietkau R.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 19 more authors.
The Lancet Oncology | Year: 2012
Background: Preoperative chemoradiotherapy, total mesorectal excision surgery, and adjuvant chemotherapy with fluorouracil is the standard combined modality treatment for rectal cancer. With the aim of improving disease-free survival (DFS), this phase 3 study (CAO/ARO/AIO-04) integrated oxaliplatin into standard treatment. Methods: This was a multicentre, open-label, randomised, phase 3 study in patients with histologically proven carcinoma of the rectum with clinically staged T3-4 or any node-positive disease. Between July 25, 2006, and Feb 26, 2010, patients were randomly assigned to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (1000 mg/m2 days 1-5 and 29-33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m2 days 1-5 and 29; fluorouracil group); and an experimental group receiving preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (250 mg/m2 days 1-14 and 22-35) and oxaliplatin (50 mg/m2 days 1, 8, 22, and 29), followed by surgery and eight cycles of adjuvant chemotherapy with oxaliplatin (100 mg/m2 days 1 and 15), leucovorin (400 mg/m2 days 1 and 15), and infusional fluorouracil (2400 mg/m2 days 1-2 and 15-16; fluorouracil plus oxaliplatin group). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1-4 vs cT4), and clinical N category (cN0 vs cN1-2) without masking. DFS is the primary endpoint. Secondary endpoints, including toxicity, compliance, and histopathological response are reported here. Safety and compliance analyses included patients as treated, efficacy endpoints were analysed according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT00349076. Findings: Of the 1265 patients initially enrolled, 1236 were evaluable (613 in the fluorouracil plus oxaliplatin group and 623 in the fluorouracil group). Preoperative grade 3-4 toxic effects occurred in 140 (23%) of 606 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 127 (20%) of 624 patients who actually received fluorouracil chemoradiotherapy. Grade 3-4 diarrhoea was more common in those who received fluorouracil and oxaliplatin during chemoradiotherapy than in those who received fluorouracil during chemoradiotherapy (73 patients [12%] vs 52 patients [8%]), as was grade 3-4 nausea or vomiting (23 [4%] vs nine [1%]). 516 (85%) of the 606 patients who received fluorouracil and oxaliplatin-based chemoradiotherapy had the full dose of chemotherapy, and 571 (94%) had the full dose of radiotherapy; as did 495 (79%) and 601 (96%) of 624 patients who received fluorouracil-based chemoradiotherapy, respectively. A pathological complete response was achieved in 103 (17%) of 591 patients who underwent surgery in the fluorouracil and oxaliplatin group and in 81 (13%) of 606 patients who underwent surgery in the fluorouracil group (odds ratio 1·40, 95% CI 1·02-1·92; p=0·038). In the fluorouracil and oxaliplatin group, 352 (81%) of 435 patients who began adjuvant chemotherapy completed all cycles (with or without dose reduction), as did 386 (83%) of 463 patients in the fluorouracil group. Interpretation: Inclusion of oxaliplatin into modified fluorouracil-based combined modality treatment was feasible and led to more patients achieving a pathological complete response than did standard treatment. Longer follow-up is needed to assess DFS. Funding: German Cancer Aid (Deutsche Krebshilfe). © 2012 Elsevier Ltd.
Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: Final results of a randomised phase 3 trial of the arbeitsgemeinschaft internistische onkologie (AIO-PK0104)
Heinemann V.,Ludwig Maximilians University of Munich |
Vehling-Kaiser U.,Practice for Medical Oncology |
Waldschmidt D.,University of Cologne |
Marten A.,University of Heidelberg |
And 16 more authors.
Gut | Year: 2013
AIO-PK0104 investigated two treatment strategies in advanced pancreatic cancer (PC): a reference sequence of gemcitabine/erlotinib followed by 2nd-line capecitabine was compared with a reverse experimental sequence of capecitabine/erlotinib followed by gemcitabine. Methods 281 patients with PC were randomly assigned to 1st-line treatment with either gemcitabine plus erlotinib or capecitabine plus erlotinib. In case of treatment failure (eg, disease progression or toxicity), patients were allocated to 2nd-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was time to treatment failure (TTF) after 1st- and 2nd-line therapy (TTF2; non-inferiority design). KRAS exon 2 mutations were analysed in archival tumour tissue from 173 of the randomised patients. Results Of the 274 eligible patients, 43 had locally advanced and 231 had metastatic disease; 140 (51%) received 2nd-line chemotherapy. Median TTF2 was estimated with 4.2 months in both arms; median overall survival was 6.2 months with gemcitabine/erlotinib followed by capecitabine and 6.9 months with capecitabine/erlotinib followed by gemcitabine, respectively (HR 1.02, p=0.90). TTF for 1st-line therapy (TTF1) was significantly prolonged with gemcitabine/ erlotinib compared to capecitabine/erlotinib (3.2 vs 2.2 months; HR 0.69, p=0.0034). Skin rash was associated with both TTF2 (rash grade 0/1/2e4:2.9/4.3/ 6.7 months, p<0.0001) and survival (3.4/7.0/ 9.6 months, p<0.0001). Each arm showed a safe and manageable toxicity profile during 1st- and 2nd-line therapy. A KRAS wild-type status (52/173 patients, 30%) was associated with an improved overall survival (HR 1.68, ps0.005). Conclusion Both treatment strategies are feasible and demonstrated comparable efficacy; KRAS may serve as biomarker in patients with advanced PC treated with erlotinib.
PubMed | University of Tübingen, Klinikum Esslingen, Regional Hospital of Liberec and Semmelweis University
Type: Journal Article | Journal: European journal of orthopaedic surgery & traumatology : orthopedie traumatologie | Year: 2016
To present a method of posterior arch and lateral mass screw (PALMS) insertion and to prove its feasibility.Four formalin-fixed specimens and 40 macerated atlas vertebras were used to describe the relevant anatomy. The height of the posterior arch was measured on 42 consecutive patients using standard CT of the cervical spine. The operative technique and the special CT reconstructions used for preoperative planning are described. Eight patients underwent posterior fixation using this technique.We described the relevant anatomy and important anatomical landmarks of the posterior arch of the atlas. PALMS placement was modified according to these anatomical findings. Fifteen PALMSs were placed in eight patients using this technique without vascular or neural injury.It is feasible to place PALMS using the described technique. CT angiography is of crucial importance for preoperative planning using the described special reconstructions. The arch posterior to the lateral mass (APLM) is defined as the bone stock situated posterior to the lateral mass, respecting its convergence. The ideal entry point for a PALMS is on the APLM above the center of the converging lateral mass. A complete or incomplete ponticulus posticus and a retrotransverse foramen or groove can be used as an accessory landmark to refine the entry point.
Bodon G.,Klinikum Esslingen |
Glasz T.,Semmelweis University |
Olerud C.,Uppsala University Hospital
European Spine Journal | Year: 2013
Purpose The purpose of this study was to examine the anatomic changes in a case of occipitalization of the atlas. Methods Occipitalization of the atlas was found accidentally in a 64-year-old male cadaver. Anatomic dissection was carried out to examine the posterior aspect of the upper cervical region and craniocervical junction. The occipitalized atlas was then harvested and macerated to study the bony anomaly. Results In this case of occipitalization, fusion was observed at both lateral masses and at the left posterior hemiarch of the atlas. We found the following soft tissue changes: the rectus capitis posterior minor muscle was lacking on the left side and was atrophic on the right, the obliquus capitis superior muscle was present on both sides showing moderate atrophy and fatty changes. The posterior atlanto-axial membrane was thinner and asymmetric, had a free edge on the right side. Lateral to this edge the dura was lying free. We believe that these changes of the posterior atlanto-axial membrane together with the increased distance between the fused posterior arch of the atlas and the lamina of the axis could cause the observed dura bulge at this level. The vertebral artery was entering the skull through a canal on the left side. Conclusions In our case, occipitalization considerably changed the anatomy of the upper cervical spine and craniocervical junction. Special care must be taken when using the posterior approach to avoid neurovascular injury in cases with occipitalization. © Springer-Verlag Berlin Heidelberg 2013.
Blohmer J.U.,Brustzentrum City am Sankt Gertrauden Krankenhaus |
Rezai M.,Luisenkrankenhaus Dusseldorf |
Kummel S.,Kliniken Essen Mitte |
Kuhn T.,Klinikum Esslingen |
And 6 more authors.
Journal of Medical Economics | Year: 2013
Objective: The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany. Methods: A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually. Results: The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care. Limitations: Country-specific data on the risk of distant recurrence and quality-of-life were not available. Conclusions: Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current standard of care women with ER+, HER2- early-stage breast cancer. © 2013 Informa UK Ltd.
Faehling M.,Klinikum Esslingen |
Eckert R.,Onkologische Schwerpunktpraxis |
Kuom S.,Klinikum Esslingen |
Kamp T.,Onkologische Schwerpunktpraxis |
And 2 more authors.
Oncology | Year: 2010
Background: Erlotinib is a standard of treatment for metastatic non-small-cell lung cancer after failure of initial therapy. Patient selection based on clinical factors is under discussion. Methods: We analyzed the outcome in relation to clinical factors of 121 consecutive Caucasian patients treated with erlotinib in a routine clinical setting in a comprehensive cancer center and 2 regional oncology centers. Results: For patients with erlotinib treatment at the 1st/2nd/3rd/≥4th line, progression-free survival (PFS) was 4.5/3.5/2.5/3.0 months, and overall survival (OS) was 8.0/8.5/7.8/6.5 months. Patients with adenocarcinoma had an improved PFS, but a similar OS. Never-smokers had longer PFS (7 months) and OS (13 months) than smokers and ex-smokers. Male patients had a slightly longer survival than female patients (PFS 3.0 vs. 2.5 months, OS 8.5 vs. 7.0 months). After adjustment for smoking and histology, the gender difference in OS was significant (adjusted hazard ratio 0.57). Patients with clinically relevant skin toxicity (grade 2, 3) had a significantly prolonged PFS and OS. Patients with partial response on 1st radiological evaluation had a significantly prolonged PFS and OS. Conclusion: Among clinical factors, never-smoking status and male gender predicted a prolonged survival. During treatment, skin toxicity and radiological response were related to better survival. © 2010 S. Karger AG, Basel.
Janni W.,University of Ulm |
Kuhn T.,Klinikum Esslingen |
Schwentner L.,University of Ulm |
Kreienberg R.,University of Ulm |
And 2 more authors.
Deutsches Arzteblatt International | Year: 2014
Background: Increasing evidence suggests that surgical removal of the axillary lymph nodes (axillary dissection, ALD) in early breast cancer yields no advantage in terms of either overall or disease-free survival, even in women with involvement of sentinel nodes. The optimal role of sentinel node biopsy (SNB) in neo-adjuvant therapy is currently under discussion. Methods: This review is based on a selective search in the Medline, EMBASE, Cochrane Library, and G.I.N. (Guidelines International Network) databases for relevant articles on the role of axillary dissection in node-positive breast cancer and the role of SNB in neo-adjuvant chemotherapy. Results: Although no single study provides adequate evidence, the available literature increasingly casts doubt on the putative therapeutic benefit of ALD as part of a multimodal treatment strategy for breast cancer. It is currently unclear what group of patients, if any, might benefit from ALD. Nor is any definitive judgment possible, from the available evidence, regarding the optimal role of SNB in neo-adjuvant therapy. The most recent evidence indicates that SNB after neo-adjuvant chemotherapy in ycN0 patients who had suspect lymph nodes before systemic treatment has a low rate of sensitivity. Conclusion: Current evidence indicates that the radicality of lymph node surgery in the treatment of breast cancer can be reduced, even if the node status is positive.
PubMed | Medical Scientific Affairs B.Braun Vascular Systems, Klinikum Esslingen and University of Malaya
Type: Journal Article | Journal: SpringerPlus | Year: 2016
Percutaneous coronary interventions (PCI) in coronary artery disease (CAD) with very small vessel diameters remains controversial and challenging. These lesions are usually more diffuse, calcified and tortuous. The usage of thin strut bare metal stents (BMS) with excellent crossing profiles in a very small caliber coronary lesions has increased the likelihood of procedural success.This observational study assessed the 9-month clinical outcomes in an all-comers population with very small caliber CAD after implantation of thin strut cobalt chromium BMS.Thin strut cobalt chromium BMS implantation in a priori pre-defined subgroups was investigated in a non-randomized, international, multi-center all-comers observational study. Primary end-point was the 9-month clinically driven target lesion revascularization (TLR) rate. Secondary end-points included the 9-month major adverse cardiac event (MACE) and procedural success rates. Data collection was done using an established electronic data acquisition form with built-in plausibility checks.A total of 783 patients with a mean age of 70.412.8years were enrolled, 205 (26.2%) of them had vessel diameters of 2.5mm and smaller which was defined as CAD with very small reference vessel calibers. Older age and diabetics were associated with higher incidences of very small caliber vessels. The mean reference vessel diameter in the very small vessel group was 2.050.27mm and mean diameter for vessels >2.5mm was 3.410.55mm. Pre-dilatation was performed more often in the very small vessel patients (52.2 vs. 42.2%; p value 0.007). There was no difference in the overall technical success rates in very small vessel disease group (97.9 vs. 97.7%). The 9-month TLR rate was 6.3% for the very small vessels and 3.7% for vessels >2.5mm (p=0.129). The 9-month and in-hospital MACE rates in the very small vessel group and patient with vessel diameters >2.5mm were not significantly different (13.1 vs. 9.2%; p=0.1265 and 5.2 vs. 3.7%; p=0.349) respectively.This study has demonstrated that the use of thin strut cobalt chromium BMS in very small vessel CAD was reasonably safe and efficacious in the context of real-world practice.
Kuhn T.,Klinikum Esslingen
Gynakologe | Year: 2011
The removal of axillary lymph nodes has been an important component of primary breast cancer surgery for more than a century. The clinical objective of lymph node surgery has, however, changed with the understanding of the biological behaviour of the disease and the modification of treatment strategies. Axillary lymph node dissection (ALD) was primarily regarded as a therapeutic procedure to remove all reachable tumour cells. ALD then changed to become a diagnostic tool when breast cancer was identified as a systemic disease and the lymph node status became the most important prognostic factor to determine systemic treatment decisions. For node-positive patients ALD remained the treatment of choice in order to ensure regional control. During the last decade the diagnostic role of ALD to identify node-positive patients was replaced by sentinel lymph node biopsy (SLNB), a targeted procedure that is associated with less morbidity compared to ALD. Recently the benefit of ALD has been questioned even for SLN-positive patients. However, ALD is still an important diagnostic tool for the cohort of node-positive patients. Women with pN2/3 disease derive benefit from a more intensive local and systemic treatment. Furthermore the data from a meta-analysis and a randomized trial indicate that patients with positive SLNs require regional treatment. Omission of SLNB requires new tools to define patients who derive a benefit from an intensified local and systemic treatment. Since local treatment is effective in node-positive patients, this treatment (radiotherapy vs surgery) must be clearly defined. © Springer-Verlag 2011.