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Theresa M. Thole Joern Toedling Annika Sprüssel Sebastian Pfeil Larissa Savelyeva David Capper Clemens Messerschmidt Dieter Beule Stefanie Groeneveld-Krentz Cornelia Eckert Guido Gambara Anton G. Henssen Sabine Finkler Johannes H. Schulte Anja Sieber Nils Bluethgen Christian R. A. Regenbrecht Annette Künkele Marco Lodrini Angelika Eggert Hedwig E. Deubzer 《International journal of cancer. Journal international du cancer》2020,146(4):1031-1041
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system. 相似文献
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Zschoche Marco Emmert Steffen von Bubnoff Nikolas Ranjbar Mahdy Grisanti Salvatore Heindl Ludwig M. Fend Falko Adamietz Irenäus A. Kakkassery Vinodh 《Der Onkologe》2020,26(11):1056-1064
Die Onkologie - Das okuläre Lymphom wird anhand seiner anatomischen Lokalisation in die intraokulären und periokulären Lymphome eingeteilt. Intraokulär kann die Uvea mit ihren... 相似文献
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Walker Mainwaring John Bowers Ngoc Pham Todd Pezzi Mihir Shukla Mark Bonnen Michelle Ludwig 《Clinical breast cancer》2019,19(2):e343-e351
Background
Metastases to the brain occur in 10%-16% of patients with breast cancer, with incidence reportedly increasing. Historically, brain metastases (BM) have been treated with whole-brain radiation therapy (WBRT), but stereotactic radiosurgery (SRS) is an increasingly favored treatment option. In this study we used a population-level database to compare patterns of care and survival between WBRT and SRS for BM from breast cancer.Materials and Methods
The National Cancer Database was used to select patients treated with radiation for BM from primary breast cancer. Groups were classified on the basis of the modality of radiation delivered to the brain and compared across several demographic factors. A Kaplan–Meier survival curve and Cox multivariate analysis were used to compare overall survival. A matched analysis using propensity scores was used to further reduce confounders and compare survival.Results
The treatment groups were significantly different across several socioeconomic variables including income, insurance status, and treatment setting. The percentage of patients who received SRS increased dramatically in the second half of the analyzed time period (P < .001). Unadjusted median survival was significantly longer for patients who received SRS versus those who received WBRT (P < .001). This finding persisted after propensity score-matching.Conclusion
Receipt of SRS was associated with different socioeconomic variables and longer overall survival compared with WBRT, highlighting the need for less toxic treatment for patients who are now living longer. The results revealed important socioeconomic differences between patients selected for SRS versus WBRT and emphasizes disparities in access to modern radiation techniques across the United States. 相似文献6.
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Volker Heinemann Ludwig Fischer von Weikersthal Thomas Decker Alexander Kiani Florian Kaiser Salah-Edin Al-Batran Tobias Heintges Christoph Lerchenmüller Christoph Kahl Gernot Seipelt Frank Kullmann Markus Moehler Werner Scheithauer Swantje Held Lisa Miller-Phillips Dominik Paul Modest Andreas Jung Thomas Kirchner Sebastian Stintzing 《British journal of cancer》2021,124(3):587
Background Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.Methods The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated.Results Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours.Conclusions FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases.ClinicalTrials.gov identifier .Subject terms: NCT00433927Oncology, Biomarkers 相似文献
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Puhr Hannah C. Eischer Lisbeth Šinkovec Hana Traby Ludwig Kyrle Paul A. Eichinger Sabine 《Journal of thrombosis and thrombolysis》2020,49(4):505-510
Journal of Thrombosis and Thrombolysis - Patients with unprovoked deep-vein thrombosis (DVT) of the leg or pulmonary embolism (PE) have a high recurrence risk. How often these recurrences are... 相似文献
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