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Background There are only scarce data on treatment of elderly patients with nab-paclitaxel for metastatic breast cancer, especially from the real-world setting. Here we present data from the noninterventional study NABUCCO with special focus on taxane-induced peripheral neuropathy (TIPN) in younger and elderly patients. Patients and Methods A total of 407 patients with HR-positive/HER2-negative metastatic breast cancer were enrolled between April 2012 and April 2015 into the prospective, multicenter, noninterventional study NABUCCO. Details on effectiveness, tolerability, and safety of nab-paclitaxel were evaluated for younger ( Results Neither median time to progression (TTP, younger 6.0 months, 95% confidence interval [CI], 5.5-7.1; elderly 6.9 months, 95% CI, 5.5-8.6) nor median overall survival (younger 16.4 months, 95% CI, 14.2-18.1; elderly 14.5 months, 95% CI, 11.9-17.4) differed by age group, also not in view of prior treatments. A multivariate regression model revealed that age did not significantly influence the TTP. TIPN was reported by 49.0% younger (44.3% common terminology criteria for adverse events [CTCAE] grade 1/2, 4.7% grade 3/4) and 45.8% elderly patients (41.1% CTCAE grade 1/2, 4.7% grade 3/4). The cumulative nab-paclitaxel dose did not correlate with the severity/grading of TIPN. Conclusion Treatment with nab-paclitaxel in first- or further-line of metastatic HR-positive/HER2-negative breast cancer resulted in similar effectiveness and safety, irrespective of age. Therefore, nab-paclitaxel is a valid treatment option for elderly and partially heavily pretreated patients. However, incidence of TIPN is high, influencing the patients’ quality of life. A close monitoring and awareness for early TIPN symptoms is warranted.

Objectives Despite intensive research, the therapeutic options in extensive-stage small cell lung cancer (SCLC) are still limited. Data from routine clinical practice, so-called “real-world data”, are centrally important to assess and improve the standard of care. We present prospectively documented data on systemic first-, second- and third-line treatment, number of treatment lines and outcome parameters of patients treated by medical oncologists in Germany. Materials and methods This is a descriptive analysis on 432 patients with extensive-stage SCLC enrolled at start of first-line therapy into the prospective German clinical cohort study TLK (Tumour Registry Lung Cancer). Patients were recruited by 87 sites between February 2010 and December 2013 and followed-up individually for 3 years. Results The majority of patients (93%) received a first-line platinum-based combination therapy. Carboplatin plus etoposide was documented more frequently than cisplatin plus etoposide (46 vs. 35%); patients receiving carboplatin were older (68 vs. 63 years) and more often presented with poorer performance status (17 vs. 11% ECOG ≥ 2). Both regimens yielded similar response and survival rates. Median first-line overall survival (OS) was 10.2 months (95% confidence interval [CI] 8.6–12.3) for carboplatin plus etoposide and 12.2 months (95% CI 10.1–14.7) for cisplatin plus etoposide. Most patients (77%) would have been eligible for participation in a clinical trial. 50% of the patients received a second and 22% a third line of treatment. Median second-line OS was 5.8 months (95% CI 4.8–7.5), median third-line OS 5.7 months (95% CI 3.8–7.0). Conclusion To our knowledge, this is the first study of prospectively documented patients with extensive-stage SCLC in routine clinical practice. We present treatment algorithms as well as outcome parameters for a large cohort in first-, second- and third-line treatment. The survival times and response rates reported in this routine setting correspond to the respective measures from large prospective trials.

Purpose Quality of life (QoL) plays an important role in recovery—especially after an incisive diagnosis such as breast cancer. Here, we present a comprehensive assessment of QoL for pre- and postmenopausal patients, starting from initial systemic treatment of early breast cancer until 3 years later, in patients from a so-called “real-world” setting. Methods 251 premenopausal and 478 postmenopausal patients with early breast cancer have been recruited into the longitudinal MaLife project within the prospective, multicentre, German Tumour Registry Breast Cancer between 2011 and 2015. The questionnaires FACT-G, FACT-Taxane, FACT-ES, EORTC QLQ-BR23, BFI and HADS were filled in at start of treatment (T0), 6, 12, 24 and 36 months later. The proportion of patients with clinically meaningful changes at 36 months was determined. Results This first interim analysis shows that the FACT-G global QoL improved over time regardless of the menopausal status. However, clinically meaningful decrease of social/family well-being (48–51%), arm symptoms (44–49%) and symptoms of neurotoxicity (55–56%) was frequently reported 3 years after start of treatment. Many premenopausal patients also reported a clinically meaningful worsening of endocrine symptoms (64%), emotional well-being (36%) and fatigue intensity (37%). Additionally, 3 years after start of treatment, 15% of the patients were classified as doubtful cases and 18% as definite cases of anxiety. Conclusions Despite improvements in global QoL, breast cancer survivors report worsened ailments 3 years after start of therapy. Follow-up care should distinguish between premenopausal patients needing special attention for emotional/menopausal issues, and postmenopausal patients needing particular care regarding physical concerns. Electronic supplementary material The online version of this article (10.1007/s10549-019-05197-whttps://doi.org/10.1007/s10549-019-05197-w) contains supplementary material, which is available to authorized users.

Objectives: After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the mutation subtype G12C emerge. Since little is known about outcome with standard treatment of patients with G12C mutated non-small cell lung cancer (NSCLC), we analyzed a large, representative, real-world cohort from Germany. Patients and methods: A total of 1039 patients with advanced KRAS-mutant or -wildtype NSCLC without druggable alterations have been recruited in the prospective, observational registry CRISP from 12/2015 to 06/2019 by 98 centers in Germany. Details on treatment, best response, and outcome were analyzed for patients with KRAS wildtype, G12C, and non-G12C mutations. Results: Within the study population, 160 (15.4 %) patients presented with KRAS G12C, 251 (24.2 %) with non-G12C mutations, 628 (60.4 %) with KRAS wildtype. High PD-L1 expression (Tumor Proportion Score, TPS > 50 %) was documented for 28.0 %, 43.5 %, and 28.9 % (wildtype, G12C, non-G12C) of the tested patients; 68.8 %, 89.3 %, and 87.7 % of the patients received first-line treatment combined with an immune checkpoint-inhibitor in 2019. TPS > 50 % vs. TPS < 1 % was associated with a significantly decreased risk of mortality in a multivariate Cox model (HR 0.39, 95 % CI 0.26−0.60, p=

Despite increasing treatment options, multiple myeloma (MM) remains incurable for most patients. Data on improvement of outcomes are derived from selected patient populations enrolled in clinical trials and might not be conferrable to all patients. Therefore, we assessed the trial eligibility, sequential treatment, and survival of non-transplant patients with MM treated in German routine care. The prospective clinical cohort study TLN (Tumour Registry Lymphatic Neoplasms) recruited 285 non-transplant patients with symptomatic MM at start of first-line treatment in 84 centres from 2009 to 2011. Demographic and clinical data were collected until August 2016. Trial-ineligibility was determined by presence of at least one of the common exclusion criteria: heart/renal failure, liver/renal diseases, polyneuropathy, HIV positivity. All other patients were considered potentially trial-eligible. Thirty percent of the patients in our study were classified as trial-ineligible. Median first-line progression-free survival (PFS) and overall survival (OS) of trial-ineligible patients were inferior to that of potentially trial-eligible patients: PFS 16.2 months (95% CI (confidence interval) 11.1–20.4) vs. 27.3 months (95% CI 23.3–33.0); OS 34.2 months (95% CI 21.6–48.1) vs. 58.6 months (95% CI 48.6–64.4). A high percentage of non-transplant patients with MM in German routine care would be ineligible for participation in clinical trials. Despite similar treatment algorithms, their first-line PFS and OS were shorter than those of potentially trial-eligible patients; the survival data of the latter were similar to results from clinical trials. Physicians should be aware of the fact that results from clinical trials may not mirror “real world” patient outcomes when discussing outcome expectations with patients. Trial registration: Clinicaltrials.gov identifier: NCT00889798.

Importance: Mortality, morbidity, and health-related quality of life (HRQoL) are patient-relevant end points generally considered in the early benefit assessments of new cancer treatments. Progression-related end points, such as time to progression or progression-free survival, are not included, although patients and physicians testify to the detrimental association of disease progression with HRQoL. Objective: To examine the association of disease progression and HRQoL in 4 prevalent solid-cancer entities in routine clinical practice. Design, Setting, and Participants: This cohort study evaluated data from 4 prospective, nonintervention, multicenter registries collected between 2011 and 2018 in 203 centers in Germany. Patients' HRQoL was assessed regularly for up to 5 years. The change in HRQoL scores after disease progression was examined with linear mixed models, adjusting for demographic and clinical covariates. Patients with metastatic breast, pancreatic, lung, and colorectal cancer were recruited at the start of systemic first-line treatment. Data analysis was performed from February 2019 to April 2019. Exposures: All patients received systemic, palliative first-line treatment according to their physician's choice. Main Outcomes and Measures: The primary outcome was deterioration of HRQoL associated with disease progression, as measured by 4 validated questionnaires: Functional Assessment of Cancer Therapy-General version 4, European Organization for Research and Treatment of Cancer QLQ-C30 version 3.0, European Organization for Research and Treatment of Cancer QLQ-C15-PAL version 1, and Hospital Anxiety and Depression Scale. Results: More than 8000 questionnaires from 2314 patients with 2562 documented disease progressions were analyzed. In total, 464 patients had breast cancer (464 [100.0%] female; median [range] age, 61.6 [26.4-90.1] years), 807 patients had pancreatic cancer (352 [43.6%] female; median [range] age, 70.0 [39.0-93.0] years), 341 patients had lung cancer (118 [34.6%] female; median [range] age, 65.9 [28.4-88.2] years), and 702 patients had colorectal cancer (248 [35.3%] female; median [range] age, 66.9 [26.9-92.1] years). The first disease progression was associated with a statistically significant worsening of 37 of 45 HRQoL scales; for 17 of these scales, the worsening was clinically meaningful. Scale scores for appetite loss (pancreatic cancer, 10.2 points [95% CI, 6.8-13.5 points]; lung cancer, 10.8 points [95% CI, 5.4-16.2 points]; colorectal cancer, 8.8 points [95% CI, 5.5-12.2]; all P

The Chlamydiales are an order of obligate intracellular bacteria sharing a developmental cycle inside a cytosolic vacuole, with very diverse natural hosts, from amoebae to mammals. The clinically most important species is Chlamydia trachomatis . Many uncertainties remain as to how Chlamydia organizes its intracellular development and replication. The discovery of new Chlamydiales species from other families permits the comparative analysis of cell-biological events and may indicate events that are common to all or peculiar to some species and more or less tightly linked to “chlamydial” development. We used this approach in the infection of human cells with Waddlia chondrophila , a species from the family Waddliaceae whose natural host is uncertain. Compared to C. trachomatis , W. chondrophila had slightly different growth characteristics, including faster cytotoxicity. The embedding in cytoskeletal structures was not as pronounced as for the C. trachomatis inclusion. C. trachomatis infection generates proteolytic activity by the protease Chlamydia protease-like activity factor (CPAF), which degrades host substrates upon extraction; these substrates were not cleaved in the case of W. chondrophila . Unlike Chlamydia , W. chondrophila did not protect against staurosporine-induced apoptosis. C. trachomatis infection causes Golgi apparatus fragmentation and redirects post-Golgi sphingomyelin transport to the inclusion; both were absent from W. chondrophila -infected cells. When host cells were infected with both species, growth of both species was reduced. This study highlights differences between bacterial species that both depend on obligate intracellular replication inside an inclusion. Some features seem principally dispensable for intracellular development of Chlamydiales in vitro but may be linked to host adaptation of Chlamydia and the higher virulence of C. trachomatis .