With cancer being a leading cause of death globally, epidemiological and clinical cancer registration is paramount for enhancing oncological care and facilitating scientific research. However, the heterogeneous landscape of medical data presents significant challenges to the current manual process of tumor documentation. This paper explores the potential of Large Language Models (LLMs) for transforming unstructured medical reports into the structured format mandated by the German Basic Oncology Dataset. Our findings indicate that integrating LLMs into existing hospital data management systems or cancer registries can significantly enhance the quality and completeness of cancer data collection - a vital component for diagnosing and treating cancer and improving the effectiveness and benefits of therapies. This work contributes to the broader discussion on the potential of artificial intelligence or LLMs to revolutionize medical data processing and reporting in general and cancer care in particular.

Molecular multiplex diagnostics is increasingly integrated now in routine diagnostics of lung adenocarcinoma (LAD). Although targetable aberrations are predominantly found in LAD, they have also been reported in squamous cell lung carcinoma (SQLC). We here present results of routine molecular multiplex diagnostics of advanced stage SQLC obtained within the German Network Genomic Medicine (NGM) and compare them with results reported previously in early stage SQLC in The Cancer Genome Atlas (TCGA) LUSC cohort. Tumor biopsies of 821 patients consecutively diagnosed within NGM were analyzed with next-generation parallel sequencing (NGS). The panel consisted of 102 amplicons and 14 genes: KRAS, PIK3CA, BRAF, EGFR, ERBB2, NRAS, DDR2, TP53, ALK, CTNNB1, MET, AKT1, PTEN and MAP2K1. In subsets of patients, fluorescence in-situ hybridization (FISH) was performed for amplification detection of FGFR1 and MET. We queried the TCGA dataset with respect to the panel used and compared the findings. For NGM patients, therapy and outcome are also reported. In addition to the expected frequencies of TP53, DDR2, PTEN and PIK3CA mutations, we detected EGFR mutations in 3.2% and BRAF mutations in 1.8%. Unlike the TCGA dataset, where the frequencies were 2.8% and 3.9%, respectively, the detected mutations in the NGM cohort included also activating targetable mutations (i.e., EGFR del19 and L858R, and BRAF V600E). FISH data revealed presence of MET amplification in 14.2% and of FGFR1 amplification in 20.0%. The association and correlation of these aberrations with clinical findings and prognosis as well as with PD-L1 expression status and mutational load will be presented. Our data give an overview on the presence and clinical characteristics of targetable mutations in advanced SQLC and show, that such mutations occur in a substantial amount of patients. Thus, molecular multiplex diagnostics might be indicated also in SQLC in order to use all therapeutic options available in these patients.

AbstractReasons for leukopenia can be numerous. To get close to the diagnosis it’s always useful to check previous blood counts of the patient to get a feeling for the dynamic development of the leukopenia. Furthermore, it’s important to check the red blood cell count and platelet count as well; a bi- or a pancytopenia usually implies an insufficient production in the bone marrow. Nevertheless, a manual counted peripheral blood smear is an essential step towards the right diagnosis in leukopenia: Beside cell counts of the single subgroups of leucocytes it also provides information on potential causes such as dysplasia.Leukopenia can be life-threatening for the patient especially if the patient presents with an agranulocytosis and fever: In this case admission is mandatory and the patient has to be treated immediately with broad-spectrum antibiotics to reduce mortality.

Telomeropathien sind angeborene Erkrankungen, welche durch eine gesteigerte Telomerverkürzung auf dem Boden eines molekularen Defektes im Telomerasekomplex gekennzeichnet sind. Wichtigster Vertreter der Telomeropathien ist die klassische Dyskeratosis congenita, die sich klinisch typischerweise bereits im Kindesalter durch die charakteristische Trias aus Hauthypo- oder hyperpigmentation, Nageldystrophien und Leukoplakie manifestiert, oftmals begleitet durch ein Knochenmarkversagen im Sinne einer Aplastischen Anämie. Aufgrund häufig fehlender typischer mukokutaner Befunde bei den kryptischen Telomeropathien, welche im Erwachsenenalter auftreten, sind diese wahrscheinlich deutlich unterdiagnostiziert. Kryptische Telomeropathien zeichnen sich durch einen mono- oder oligosymptomatischen Verlauf mit klinischen Manifestationen wie einer aplastischen Anämie, einer Lungenfibrose oder Leberzirrhose aus. Aufgrund fundamentaler prognostischer und therapeutischer Konsequenzen ist das Erkennen einer zugrunde liegenden Telomeropathie im Erwachsenenalter von größter klinischer Bedeutung für die Patienten und deren Angehörigen. In diesem Artikel geben wir einen Überblick über die Möglichkeiten der Erkennung mittels Telomerlängenscreening sowie über die folgenden diagnostische Schritte und therapeutische Implikationen bei erwachsenen Patienten mit kryptischer Telomeropathie.

Background: Tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) are not entirely selective for the BCR-ABL1 kinase but also inhibit a variety of other kinases, sometimes triggering unpredicted biological effects. As an example, the TKIs dasatinib and bosutinib both inhibit Src-kinases, which are important mediators of T-cell function. Earlier in vitro data has shown that dasatinib can suppress activation and proliferation of T and NK cells, but it can also elicit signs of immunostimulation in patients, including rapid mobilization of lymphocytes and LGL lymphocytosis. No extensive analyses of the immunological in vivoeffects of bosutinib have been performed thus far. Therefore, we aimed at characterizing T and NK cell phenotypes and functional features in CML patients in a clinical setting in the context of first-line bosutinib and imatinib treatment.

Es ist über 60 Jahre her, seit William Dameshek, damals Editor für die Fachzeitschrift „Blood“, 1951 in seinem Editorial mit dem Titel „Some Speculations on the Myeloproliferative Syndromes“ erstmals die Möglichkeit einer gemeinsamen Ursache für die „chronische granulozytische Leukämie, Polyzythämie, myeloische Metaplasie und diGuilielmo's Syndrom“ formulierte. Im Jahre 2005 erfuhr diese Theorie einen neuen Antrieb, als die Punktmutation im JAK2-Gen und das resultierende JAK2 V617F-Onkoprotein bei Patienten mit Polyzythämia vera, Essentieller Thrombozythämie und Primärer Myelofibrose beschrieben wurde. Die Beschreibung dieses gemeinsamen Markers hat unser Verständnis der Bcr-Abl-negativen Myeloproliferativen Neoplasien entscheidend verbessert und hat zudem in kürzester Zeit zu der Generierung, klinischen Prüfung und Zulassung einer neuen Substanzklasse von Tyrosinkinaseinhibitoren, den JAK-Inhibitoren, geführt. Gleichermaßen hat die Entdeckung des Fip1L1-PDGFRA Fusionsproteins als wichtigen Faktor bei der Pathogenese der myeloischen Neoplasien mit Eosinophilie und der Nachweis des exzellenten Ansprechens dieser Erkrankungen auf Imatinib die Behandlung dieser Erkrankungen revolutioniert. Es ist mittlerweile klar, dass diese neuen Erkenntnisse nicht nur unsere therapeutischen Möglichkeiten fundamental erweitern, sondern dass die myeloproliferativen Neoplasien (MPN) eine Gruppe von Modellerkrankungen für den Erfolg der personalisierten Medizin darstellen, welcher die Hoffnung auf eine Ausweitung dieses Prinzips auf das gesamte Gebiet der hämatologischen Neoplasien und der soliden Tumoren stützt.

The efficacy and safety of peginterferon-α-2a (40 kD) (PEG-IFNα-2a), 450 µg once weekly, versus IFNα-2a, 9 MIU once daily, for 12 months, was evaluated in a Phase II study in IFN-naïve patients with chronic-phase, Philadelphia-chromosome-positive CML. At the end of the treatment, complete hematological response was observed in 66.2% (47/71) and 45.2% (33/73) of the PEG-IFNα-2a group and IFNα-2a groups, respectively (p = 0.009), and major cytogenetic response occurred in 35.2% and 17.8%, respectively (p = 0.016). PEG-IFNα-2a was at least as effective as IFNα-2a overall, including progression-free survival at the end of treatment, and overall survival after 30 months of follow-up. Adverse events necessitated fewer withdrawals but more dose adjustments in the PEG-IFNα-2a group compared with the IFNα-2a group (11%versus 23%, and 84.5%versus 65.8%, respectively). In conclusion, PEG-IFNα-2a (40 kD), 450 µg once weekly, compared with IFNα-2a, 9 MIU once daily, resulted in higher rates of hematologic and cytogenetic response and greater overall survival.

American Journal of HematologyVolume 82, Issue 12 p. 1122-1124 Letter to the American Journal of HematologyFree Access Aprotinin-associated hemolytic thrombotic microangiopathy in a patient with acute myelogenous leukemia (AML) and systemic coagulopathy Florian Langer, Florian Langer Hematology/Oncology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorOliver Steinmetz, Oliver Steinmetz Nephrology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorGuy Marx, Guy Marx Clinical Chemistry, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorAli Amirkhosravi, Ali Amirkhosravi Florida Hospital Institute of Translational Research, Orlando, FloridaSearch for more papers by this authorBarbara Eifrig, Barbara Eifrig Hematology/Oncology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorCarsten Bokemeyer, Carsten Bokemeyer Hematology/Oncology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorTim Brümmendorf, Tim Brümmendorf Hematology/Oncology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this author Florian Langer, Florian Langer Hematology/Oncology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorOliver Steinmetz, Oliver Steinmetz Nephrology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorGuy Marx, Guy Marx Clinical Chemistry, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorAli Amirkhosravi, Ali Amirkhosravi Florida Hospital Institute of Translational Research, Orlando, FloridaSearch for more papers by this authorBarbara Eifrig, Barbara Eifrig Hematology/Oncology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorCarsten Bokemeyer, Carsten Bokemeyer Hematology/Oncology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this authorTim Brümmendorf, Tim Brümmendorf Hematology/Oncology, University Hospital Hamburg-Eppendorf, GermanySearch for more papers by this author First published: 01 November 2007 https://doi.org/10.1002/ajh.20923Citations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume82, Issue12December 2007Pages 1122-1124 ReferencesRelatedInformation

Disease progression in CML is associated with accelerated telomere shortening caused by increased turnover of Bcr-Abl positive cells. We have recently proposed a model in which continuous telomere shortening is correlated with increasing genetic instability in Bcr-Abl-positive cells thus facilitating the acquisition of secondary genetic abnormalities and, as a consequence clonal succession and eventually clinical progression of the disease. Based on this hypothesis, telomerase upregulation in late stage disease is a prerequisite for prevention of replication-induced senescence in Bcr-Abl positive cells. As a consequence, treatment of CML with Telomerase inhibitors (TI) represents an attractive strategy aiming at the potential eradication of cycling CML stem cells. Therefore, we have exploited both pharmacological (small molecule inhibitor) and genetic strategies (dominant negative hTERT mutants, DN-hTERT) of telomerase inhibition in CML cells in vitro We first treated K562 cells with the pharmacological telomerase inhibitor BIBR1532 in vitro. After around 400 population doublings (PD), no differences in growth kinetics nor signs of senescence or apoptosis were observed in BIBR1532 treated cells despite of significant telomere shortening (22 base pairs (bp) per PD) compared to control cells. Furthermore, neither significant differences in mRNA expression of telomere/telomerase-associated proteins, nor accumulation of double strand breaks (DSBs) under irradiation was observed in treated cells with short telomeres as opposed to untreated control cells. The very slow shortening rate of 22bp/PD plus the lack of stigmata pointing to induction of senescence in K562 cells lead to the assumption that telomerase activity is not complete inhibited by the compound. In order to verify the potency of telomerase directed treatments in CML, we therefore expressed DN-hTERT in K562 cells. Integration of DN-hTERT led to a significant decrease in telomerase activity (measured by RQ-TRAP). Furthermore, DN-hTERT expressing cells underwent accelerated telomere shortening at a substantially higher rate (>100 bp/PD) from 15kb to around 4kb within 110 days of culture. In contrast to BIBR1532-treated cells, DN-hTERT expressing K562 cells slowed down growth kinetic in comparison to control cells after 80 days of culture. By using Annexin 5 staining, 25% of apoptotic cells could be detected in cells with critically short telomeres as compared to control cells (<3%). Finally, a significantly increased accumulation of double strand breaks (DSBs) detected by gammaH2AX foci after exposure to irradiation was observed in DN-hTERT K562 cells as compared to control cells pointing to an impaired DNA repair machinery in Bcr-Abl positive cells with disrupted telomere maintenance. In summary, the data suggest that pharmacological telomerase inhibition by BIBR1532 is insufficient to induce telomere-mediated senescence in Bcr-Abl-positive cells. However, accelerated telomere shortening, slowing down of growth kinetics, elevated apoptosis and increased radiosensitivity induced by expression of DN-hTERT indicate a therapeutic potential for telomerase-directed treatment strategies in CML.