المؤلفون: Kurth, Florian, Tober-Lau, Pinkus, Lingscheid, Tilman, Bardtke, Lara, Kim, Johanna, Angheben, Andrea, Gobbi, Federico G, Mbavu, Lena, Stegemann, Miriam S, Heim, Katrin M, Pfäfflin, Frieder, Menner, Nikolai, Schürmann, Mariana, Mikolajewska, Agata, Witzenrath, Martin, Sander, Leif E, Mayer, Beate, Zoller, Thomas

المصدر: Journal of Travel Medicine; Apr2023, Vol. 30 Issue 3, p1-9, 9p

مصطلحات موضوعية: MALARIA, ARTEMISININ, ERYTHROCYTES, LACTATE dehydrogenase

مصطلحات جغرافية: ITALY, GERMANY

مستخلص: Background Artemisinin-based combination therapy (ACT) for the treatment of malaria is highly effective, well tolerated and safe. Episodes of delayed haemolysis occur in up to 57.9% of patients with severe malaria treated with intravenous artesunate, mainly caused by 'pitting' of infected red blood cells in the spleen and the delayed loss of these once-infected RBCs (oiRBCs). Several reports indicate that post-treatment haemolysis (PTH) also occurs in uncomplicated malaria treated with oral ACT, calling for systematic investigation. Methods A prospective observational study to identify the incidence of PTH after oral ACT, defined as increased lactate dehydrogenase activity and low haptoglobin level on Day 14 after treatment. Patients were enrolled at two study centres in Germany and Italy. Study visits took place on Days 1, 3, 7, 14 and 28. Laboratory investigations included extended clinical routine laboratory tests, quantitative Pf HRP2, anti-RBC antibodies and oiRBCs. The state of semi-immunity to malaria was assessed from childhood and ongoing exposure to Plasmodium spp. as per patient history. Results A total of 134 patients with uncomplicated malaria and 3-day ACT treatment were recruited. Thirty-seven (37.4%) of 99 evaluable patients with Pf and none of 9 patients with non- Pf malaria exhibited PTH on d14. Patients with PTH had higher initial parasitaemia, higher oiRBC counts on d3 and a 10-fold decrease in oiRBCs between d7 and d14 compared with patients without PTH. In patients with PTH, loss of haemoglobin was 4-fold greater in non-Africans than in Africans (−1.3 vs −0.3 g/dl). Semi-immune African patients with PTH showed markedly increased erythropoiesis on d14 compared with not semi-immune African and non-African patients with PTH. Conclusions PTH is common in patients with uncomplicated malaria and oral ACT. While the observed loss of haemoglobin will often not be clinically relevant, it could aggravate pre-existing anaemia, warranting follow-up examinations in populations at risk. [ABSTRACT FROM AUTHOR]

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المؤلفون: Ruzicka, Michael, Wurm, Sonja, Lindner, Lars, Dreyling, Martin, von Bergwelt-Baildon, Michael, Boeck, Stefan, Giessen-Jung, Clemens, Milani, Valeria, Stemmler, Joachim H., Subklewe, Marion, Weigert, Oliver, Spiekermann, Karsten

المصدر: Infection; Feb2023, Vol. 51 Issue 1, p231-238, 8p, 3 Charts, 2 Graphs

مصطلحات موضوعية: PREVENTION of infectious disease transmission, PATIENT aftercare, PROTHROMBIN time, PNEUMONIA, IMMUNIZATION, COVID-19, HOSPITAL emergency services, BLOOD vessels, PREDNISOLONE, COVID-19 vaccines, DISEASE vectors, DEXAMETHASONE, THROMBOPENIC purpura, CELL receptors, JOINT pain, VITAMIN C, TREATMENT effectiveness, SEVERITY of illness index, MESSENGER RNA, PLATELET count, DESCRIPTIVE statistics, FIBRINOGEN, LACTATE dehydrogenase, ASPIRIN, RESEARCH funding, BLOOD cell count, FATIGUE (Physiology), HEADACHE, COMPUTED tomography, DATA analysis software, HEMORRHAGE, FIBRIN fibrinogen degradation products

مصطلحات جغرافية: GERMANY

مستخلص: Purpose: Following the emergency use authorization of BNT162b2 by the Food and Drug administration (FDA) in early December 2020, mRNA- and vector-based vaccines became an important means of reducing the spread and mortality of the COVID-19 pandemic. The European Medicines Agency labelled immune thrombocytopenia (ITP) as a rare adverse reaction of unknown frequency after vector-, but not mRNA-vaccination. Here, we report on the long-term outcome of 6 patients who were diagnosed with de-novo, vaccine-associated ITP (VA-ITP), and on the outcome of subsequent SARS-CoV-2 re-vaccinations. Methods: Patients were included after presenting to our emergency department. Therapy was applied according to ITP guidelines. Follow-up data were obtained from outpatient departments. Both mRNA- or vector-based vaccines were each used in 3 cases, respectively. Results: In all patients, the onset of symptoms occurred after the 1st dose of vaccine was applied. 5 patients required treatment, 3 of them 2nd line therapy. All patients showed a complete response eventually. After up to 359 days of follow-up, 2 patients were still under 2nd line therapy with thrombopoietin receptor agonists. 5 patients have been re-vaccinated with up to 3 consecutive doses of SARS-CoV-2 vaccines, 4 of them showing stable platelet counts hereafter. Conclusion: Thrombocytopenia after COVID-19 vaccination should trigger a diagnostic workup to exclude vaccine-induced immune thrombotic thrombocytopenia (VITT) and, if confirmed, VA-ITP should be treated according to current ITP guidelines. Re-vaccination of patients seems feasible under close monitoring of blood counts and using a vaccine that differs from the one triggering the initial episode of VA-ITP. [ABSTRACT FROM AUTHOR]

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المؤلفون: Schönfeld, Leon¹ (AUTHOR), Hinrichs, Jan B.² (AUTHOR), Marquardt, Steffen^1,3 (AUTHOR), Voigtländer, Torsten¹ (AUTHOR), Dewald, Cornelia² (AUTHOR), Koppert, Wolfgang⁴ (AUTHOR), Manns, Michael P.¹ (AUTHOR), Wacker, Frank² (AUTHOR), Vogel, Arndt¹ (AUTHOR), Kirstein, Martha M.^1,5 (AUTHOR) kirstein.martha@mh-hannover.de

المصدر: Journal of Cancer Research & Clinical Oncology. Nov2020, Vol. 146 Issue 11, p3003-3012. 10p.

مصطلحات موضوعية: *LIVER metastasis, *LACTATE dehydrogenase, *LIVER cancer, *PERFUSION, *MELANOMA

مصطلحات جغرافية: GERMANY

مستخلص: Background: Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT® Delivery System; Delcath Systems Inc, USA) is a novel interventional procedure, which delivers high doses of melphalan directly to the liver in patients with liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. We have previously shown promising efficacy for patients with ocular melanoma (OM) and cholangiocarcinoma (CCA) within our single-center and multi-center experiences. The aim of this study was to analyze the safety and efficacy of CS-PHP after 141 treatments at Hannover Medical School, Germany. Methods: Overall response rates (ORR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median Overall survival (mOS), median progression-free survival (mPFS), and median hepatic PFS (mhPFS) were analyzed using the Kaplan–Meier estimation. Results: Overall, 60 patients were treated with CS-PHP in the salvage setting from October 2014 until January 2019 at Hannover Medical School with a total of 141 procedures. Half of the patients were patients with hepatic metastases of ocular melanoma (OM) (n = 30), 14 patients had CCA (23.3%), 6 patients had hepatocellular carcinoma (10%), and 10 patients were treated for other secondary liver malignancies (16.7%). In total, ORR and disease stabilization rate were 33.3% and 70.3% (n = 25), respectively. ORR was highest for patients with OM (42.3%), followed by patients with CCA (30.8%). Independent response-associated factors were normal levels of lactate dehydrogenase (odds ratio (OR) 13.7; p = 0.015) and diagnosis with OM (OR 9.3; p = 0.028). Overall, mOS was 9 months, mPFS was 4 months, and mhPFS was 5 months. Patients with OM had the longest mOS, mPFS, and mhPFS with 12, 6, and 6 months, respectively. Adverse events included most frequently significant, but transient, hematologic toxicities (80% of grade 3/4 thrombopenia), less frequently hepatic injury up to liver failure (3.3%) and cardiovascular events including two cases of ischemic insults (5%). Conclusion: Salvage treatment with CS-PHP is safe and effective particularly in patients OM and CCA. Careful attention should be paid to possible, serious hepatic, and cardiovascular complications. [ABSTRACT FROM AUTHOR]

المؤلفون: Nieder, Carsten^1,2 (AUTHOR), Hess, Sebastian³ (AUTHOR), Lewitzki, Victor³ (AUTHOR)

المصدر: Oncology Research & Treatment. 2020, Vol. 43 Issue 5, p221-227. 7p.

مصطلحات موضوعية: *BRAIN metastasis, *LACTATE dehydrogenase, *SERUM albumin, *LOG-rank test, *BLOOD testing

مصطلحات جغرافية: GERMANY

مستخلص: Purpose: The aim of our study was the external validation of an extended variant of the four-tiered diagnosis-specific graded prognostic assessment (DS-GPA) that includes more information about extracranial disease burden and blood test results, and predicts survival of patients with brain metastases. The extracranial DS-GPA (EC-GPA) includes serum albumin, lactate dehydrogenase, and number of extracranial organs involved. Originally, the score was developed in Germany. Patients and Methods: A retrospective analysis of 236 patients with brain metastases treated with primary whole-brain radiotherapy in North-Norway was performed (independent external validation cohort). Results: The four-tiered EC-GPA score showed good discrimination between all prognostic groups (log-rank test p < 0.05 for all pairwise comparisons). One-year survival was 0, 11, 30, and 100%, respectively. Median survival was 0.7 months (95% CI, 0.5–0.9) in the worst prognostic group, with a hazard ratio for death of 44.31 (95% CI, 5.78–339.50) compared to the best group. In the German database, the corresponding HR was 31.64 (median survival 0.4 months). The remaining hazard ratios in this validation study were 7.13 and 12.10, compared with 4.84 and 9.26 in the score development study. Conclusions: This study provides an independent validation of the EC-GPA, which was the best prognostic model for defining patients who did not benefit from radiation therapy of brain metastases in terms of overall survival in the original German study. The proposed modification of the established DS-GPA should undergo further validation in multi-institutional databases. [ABSTRACT FROM AUTHOR]

المؤلفون: Röhrig, Gabriele, Becker, Ingrid, Hagemeier, Anna, Gutensohn, Kai, Nebe, Thomas

المصدر: Journal of Laboratory Medicine; Apr2019, Vol. 43 Issue 2, p57-65, 9p

مصطلحات موضوعية: ELDER care, BASOPHILS, C-reactive protein, CONFIDENCE intervals, EOSINOPHILS, GLOMERULAR filtration rate, INTERNAL medicine, LACTATE dehydrogenase, NEUTROPHILS, REFERENCE values, SEX distribution, CROSS-sectional method, GAMMA-glutamyltransferase, LEUKOCYTE count, LYMPHOCYTE count, PLATELET count

مصطلحات جغرافية: GERMANY

مستخلص: Background: Hematological abnormalities are frequently found in geriatric patients. However, little data is available on reference values for total blood cell counts in older patients. This study is focused on the analysis of reference values for white blood cell counts in aged persons ≥60 years. Methods: This was a cross-sectional study of outpatient laboratory data of 2015 from a German countrywide working laboratory company; inclusion criteria: age ≥60 years, parameters evaluated by the laboratory company between 1.1.2015 and 31.12.2015; exclusion criteria: glomerular filtration rate (GFR) <60 mL/min, lack of inclusion criteria; primary objective: mean leukocyte count; secondary objective: mean counts of lymphocytes, eosinophil, neutrophil and basophil leukocytes as well as platelets, C-reactive protein (CRP), γ-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) in hematologically healthy persons aged ≥60 years. Results: Data of 30,611 persons aged ≥60 years were evaluated by age groups. Results for leukocytes, basophils, eosinophils, neutrophils and lymphocytes remained within the reference ranges recommended by the German Society of Hematology and Oncology (DGHO) and the German Association of Specialists in Internal Medicine (BDI); the lower reference limit for normal platelet values in males was below the DGHO reference value with 136,000/μL (confidence interval [CI] 129,000;142,000); similarly, our results for normal monocyte values were above the DGHO reference values with 6.0% (5.7;6.2) to 14.3% (13.9;14.8) in males and 5.4% (5.2;5.6) to 12.9% (12.6;13.4) in females; CRP, GGT and LDH values were above the BDI reference values, comparable with the previous data of a senior patient cohort analysis. Conclusions: Adaptation of reference values for selected laboratory parameters in older German patients should be well considered. [ABSTRACT FROM AUTHOR]

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المؤلفون: Röhrig, Gabriele, Becker, Ingrid, Gutensohn, Kai, Nebe, Thomas

المصدر: Journal of Laboratory Medicine; Aug2018, Vol. 42 Issue 4, p131-139, 9p

مصطلحات موضوعية: ERYTHROCYTES, ANEMIA, BLOOD testing, BLOOD proteins, C-reactive protein, GLOBULINS, GLOMERULAR filtration rate, HEMATOCRIT, HEMATOLOGY, HEMOGLOBINS, LACTATE dehydrogenase, RETICULOCYTES, TRANSFERRIN, CROSS-sectional method, RETROSPECTIVE studies

مصطلحات جغرافية: GERMANY

الشركة/الكيان: WORLD Health Organization

مستخلص: Background: Data on peripheral blood cell values in older subjects are rare. While hemoglobin (Hb) values are supposed to change with rising age, little is known about reference values for other erythrocytic blood cell counts. This cross-sectional study was initiated to analyze hematologic laboratory parameters among subjects aged ≥60 years. Methods: This was a retrospective cross-sectional study of outpatient laboratory data between January 1^st and December 31^st, 2015 originating from a German countrywide laboratory group; inclusion criteria: age ≥60 years, normal C-reactive protein (CRP), transferrin saturation, reticulocytes, lactate dehydrogenase, haptoglobin and soluble transferrin receptor; exclusion criteria: glomerular filtration rate (GFR)<60 mL/min, lack of inclusion criteria; primary objective: assessment of the mean Hb value; secondary objective: assessment of mean values of red blood cell (RBC) counts. Results: Of 30,611 subjects ≥60 years, 4641 met the inclusion criteria and were thus considered hematologically healthy; the following age groups were formed: 60–69 years (2094), 70–79 years (2171), 80–89 years (360), >90 years (16); median values for male/female subjects were: Hb 15.2/14.0 g/dL, RBC 5.0/4.6/μL, mean cellular volume (MCV) 89/89/fl, mean corpuscular hemoglobin (MCH) 31/30 pg/RBC, mean corpuscular hemoglobin concentration (MCHC) 34/34 g/dL, hematocrit (hct) 44/41%. Statistical evaluation revealed a slight but significant decrease in values over age decades for all parameters except for MCH. However, all values remained within the recommended German Society of Hematology and Oncology (DGHO) reference ranges. Hb values remained above the recommended World Health Organization (WHO) cut-offs for definition of anemia. Conclusions: The results confirm the WHO reference values and are in accordance with the recommended DGHO reference values and previous results of other study cohorts outside Germany. There seems to be no need for establishing age-specific RBC or erythrocytic reference ranges for subjects >60 years. [ABSTRACT FROM AUTHOR]

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المؤلفون: Poeschel, Viola¹ (AUTHOR) viola.poeschel@uks.eu, Held, Gerhard^1,2 (AUTHOR) gheld@westpfalz-klinikum.de, Ziepert, Marita^1,3 (AUTHOR), Witzens-Harig, Mathias⁴ (AUTHOR), Holte, Harald⁵ (AUTHOR), Thurner, Lorenz¹ (AUTHOR), Borchmann, Peter⁶ (AUTHOR), Viardot, Andreas⁷ (AUTHOR), Soekler, Martin⁸ (AUTHOR), Keller, Ulrich⁹ (AUTHOR), Schmidt, Christian¹⁰ (AUTHOR), Truemper, Lorenz¹¹ (AUTHOR), Mahlberg, Rolf¹² (AUTHOR), Marks, Reinhard¹³ (AUTHOR), Hoeffkes, Heinz-Gert¹⁴ (AUTHOR), Metzner, Bernd¹⁵ (AUTHOR), Dierlamm, Judith¹⁶ (AUTHOR), Frickhofen, Norbert¹⁷ (AUTHOR), Haenel, Mathias¹⁸ (AUTHOR), Neubauer, Andreas¹⁹ (AUTHOR)

المصدر: Lancet. 12/21/2019, Vol. 394 Issue 10216, p2271-2281. 11p.

مصطلحات موضوعية: *RESEARCH, COMBINATION drug therapy, BODY surface area, LACTATE dehydrogenase, PROGRESSION-free survival, LYMPHOMAS, THERAPEUTIC use of antineoplastic agents, ANTINEOPLASTIC agents, B cell lymphoma, COMPARATIVE studies, DOXORUBICIN, DRUG administration, INTRAVENOUS therapy, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, ORAL drug administration, PREDNISONE, SURVIVAL analysis (Biometry), TUMOR classification, VINCRISTINE, EVALUATION research, RANDOMIZED controlled trials, TREATMENT effectiveness, CYCLOPHOSPHAMIDE

مصطلحات جغرافية: DENMARK, GERMANY, ISRAEL, ITALY, NORWAY

مستخلص: Background: Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis.Methods: This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of -5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421.Findings: Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy.Interpretation: In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population.Funding: Deutsche Krebshilfe. [ABSTRACT FROM AUTHOR]

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المؤلفون: Relja, Borna, Töttel, Eva, Breig, Lara, Henrich, Dirk, Schneider, Heinz, Marzi, Ingo, Lehnert, Mark

المصدر: European Journal of Nutrition; Apr2012, Vol. 51 Issue 3, p311-321, 11p, 1 Color Photograph, 1 Chart, 5 Graphs

مصطلحات موضوعية: LIVER injuries, ANALYSIS of variance, ANIMAL experimentation, APOPTOSIS, BIOPHYSICS, COMPARATIVE studies, HEMODYNAMICS, HEMORRHAGE, HISTOLOGICAL techniques, INTERLEUKINS, LACTATE dehydrogenase, LIVER, RESEARCH methodology, LIPID peroxidation (Biology), NECROSIS, POLYMERASE chain reaction, POLYPHENOLS, RATS, RESEARCH funding, RESUSCITATION, STAINS & staining (Microscopy), STATISTICS, WESTERN immunoblotting, GREEN tea, PLANT extracts, DATA analysis, ALANINE aminotransferase, REVERSE transcriptase polymerase chain reaction, DATA analysis software, DESCRIPTIVE statistics

مصطلحات جغرافية: GERMANY

مستخلص: Purpose: Oxidative stress and inflammation contribute to hepatic injury after hemorrhage/resuscitation (H/R). Natural plant polyphenols, i.e., green tea extract (GTE) possess high anti-oxidant and anti-inflammatory activities in various models of acute inflammation. However, possible protective effects and feasible mechanisms by which plant polyphenols modulate pro-inflammatory, apoptotic, and oxidant signaling after H/R in the liver remain unknown. Therefore, we investigated the effects of GTE and its impact on the activation of NF-kappaB in the pathogenesis of hepatic injury induced by H/R. Methods: Twenty-four female LEWIS rats (180-250 g) were fed a standard chow (ctrl) or a diet containing 0.1% polyphenolic extracts (GTE) from Camellia sinensis starting 5 days before H/R. Rats were hemorrhaged to a mean arterial pressure of 30 ± 2 mmHg for 60 min and resuscitated (H/R and GTE H/R groups). Control groups (sham, ctrl, and GTE) underwent surgical procedures without H/R. Two hours after resuscitation, tissues were harvested. Results: Plasma alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increased 3.5-fold and fourfold, respectively, in vehicle-treated rats as compared to GTE-fed rats. Histopathological analysis revealed significantly decreased hepatic necrosis and apoptosis in GTE-fed rats after H/R. Real-time PCR showed that GTE diminished gene expression of pro-apoptotic caspase-8 and Bax, while anti-apoptotic Bcl-2 was increased after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress as well as systemic IL-6 level and hepatic IL-6 mRNA were markedly reduced in GTE-fed rats compared with controls after H/R. Plant polyphenols also decreased the activation of both JNK and NFκB. Conclusions: Taken together, GTE application blunts hepatic damage, apoptotic, oxidative, and pro-inflammatory changes after H/R. These results underline the important roles of JNK and NF-kappaB in inflammatory processes after H/R and the beneficial impact of plant polyphenols in preventing their activation. [ABSTRACT FROM AUTHOR]

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المؤلفون: Salzmann, Martin¹ (AUTHOR) martin.salzmann@med.uni-heidelberg.de, Pawlowski, Johannes² (AUTHOR), Loquai, Carmen² (AUTHOR), Rafei-Shamsabadi, David A.³ (AUTHOR), Meiss, Frank³ (AUTHOR), Ugurel, Selma⁴ (AUTHOR), Schadendorf, Dirk⁴ (AUTHOR), Meier, Friedegund^5,6 (AUTHOR), Enk, Alexander H.¹ (AUTHOR), Hassel, Jessica C.¹ (AUTHOR)

المصدر: European Journal of Cancer. May2022, Vol. 166, p24-32. 9p.

مصطلحات موضوعية: *MELANOMA prognosis, *THERAPEUTIC use of antineoplastic agents, *DRUG efficacy, *RESEARCH, *GENETIC mutation, *CONFIDENCE intervals, *PROTEIN kinase inhibitors, *MELANOMA, *METASTASIS, *RETROSPECTIVE studies, *CANCER patients, *BRAIN tumors, *PROTEIN-tyrosine kinase inhibitors, *SEX distribution, *LACTATE dehydrogenase, *DESCRIPTIVE statistics, *MITOGEN-activated protein kinases, *PROGRESSION-free survival, *CHEMICAL inhibitors, *EVALUATION

مصطلحات جغرافية: GERMANY

مستخلص: MEK inhibitors (MEKi) have shown clinical efficacy for NRAS-mutated, metastasized melanoma in randomised controlled trials, yet their clinical use is currently restricted to advanced, pre-treated patients, which is a different situation compared to previous trials. Data on their efficacy in the current real-world use are scarce. In this retrospective, multi-centre study, we evaluated the clinical course of disease of patients treated with MEKi with at least one previous treatment line in five German cancer centres. Thirty-three patients were included, 19 males (58%) and 14 females (42%), with a median age of 64 years. Ninety-one percent of patients were pre-treated with immune checkpoint inhibitors, 90% of patients had elevated serum lactate dehydrogenase (LDH) levels at treatment initiation, 33% suffered from cerebral metastases and 30% had an Eastern Cooperative Oncology Group performance status of 2 or higher. The response rate was 18.2%; the disease control rate was 48.5%. Median progression-free survival was 2.8 months (95% confidence interval (CI): 1.6–3.9 months), and median overall survival was 7.1 months (95% CI: 5.8–8.3 months). In subgroup analysis, clinical efficacy was similar also in patients with high LDH levels and cerebral metastases, and there was a better outcome in males and in patients treated with trametinib vs. other MEKi, which may be based on selection bias. Overall, the clinical efficacy was similar compared to previous clinical trials in earlier treatment lines. MEKi fulfil the need for an in-between treatment to stabilise the course of disease in advanced NRAS-mutated melanoma, but expectations regarding ongoing tumour response should be tempered. • Thirty-three patients with off-label MEK inhibitor monotherapy in NRAS-mutated melanoma. • Pre-treated and highly progressed patient cohort of 5 German skin cancer centres. • The overall response rate was 18%; the disease control rate was 49%. • Overall, results are comparable to available early-line randomised controlled trials. • MEK inhibitors may provide stabilisation of disease in this challenging cohort. [ABSTRACT FROM AUTHOR]

المؤلفون: Heppt, Markus V.¹ Markus.Heppt@med.uni-muenchen.de, Heinzerling, Lucie² Lucie.Heinzerling@uk-erlangen.de, Kähler, Katharina C.³ kkaehler@dermatology.uni-kiel.de, Forschner, Andrea⁴ andrea.forschner@med.uni-tuebingen.de, Kirchberger, Michael C.² Michael.Kirchberger@uk-erlangen.de, Loquai, Carmen⁵ Carmen.Loquai@unimedizin-mainz.de, Meissner, Markus⁶ Markus.Meissner@kgu.de, Meier, Friedegund⁷ Friedegund.Meier@uniklinikum-dresden.de, Terheyden, Patrick⁸ Patrick.Terheyden@uksh.de, Schell, Beatrice⁹ Beatrice.Schell@wkg.srh.de, Herbst, Rudolf¹⁰ rudolf.herbst@helios-kliniken.de, Göppner, Daniela¹¹ Daniela.Goeppner@med.ovgu.de, Kiecker, Felix¹² felix.kiecker@charite.de, Rafei-Shamsabadi, David¹³ david.rafei-shamsabadi@uniklinik-freiburg.de, Haferkamp, Sebastian¹⁴ Sebastian.Haferkamp@klinik.uni-regensburg.de, Huber, Margit A.¹⁵ margit.huber@uniklinik-ulm.de, Utikal, Jochen¹⁶ Jochen.Utikal@umm.de, Ziemer, Mirjana¹⁷ Mirjana.Ziemer@medizin.uni-leipzig.de, Bumeder, Irmgard¹⁸ praxis@onkologie-ebersberg.de, Pfeiffer, Christiane¹⁹ Christiane.Pfeiffer@klinikum-augsburg.de

المصدر: European Journal of Cancer. Sep2017, Vol. 82, p56-65. 10p.

مصطلحات موضوعية: *ANTIGENS, *APOPTOSIS, *C-reactive protein, *EOSINOPHILS, *LACTATE dehydrogenase, *MELANOMA, *METASTASIS, *MULTIVARIATE analysis, *REGRESSION analysis, *T cells, *UVEA, *TUMORS

مصطلحات جغرافية: GERMANY

مستخلص: Background Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date. Patients and methods Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres. Records from 96 cases were analysed for treatment outcomes. Clinical and blood parameters associated with overall survival (OS) or treatment response were identified with multivariate Cox regression and binary logistic regression. Results Eighty-six patients were treated with PD-1 inhibitors only ( n = 54 for pembrolizumab, n = 32 for nivolumab) with a centrally confirmed response rate of 4.7%. Median OS was 14 months for pembrolizumab-treated and 10 months for nivolumab-treated patients ( p = 0.765). Fifteen patients were treated with combined immune checkpoint blockade with partial response observed in two cases. Median OS was not reached in this group. Multivariate Cox regression identified Eastern Cooperative Oncology Group (ECOG) performance status ( p = 0.002), elevated serum levels of lactate dehydrogenase (LDH) ( p = 0.002) and C-reactive protein (CRP) ( p = 0.001), and a relative eosinophil count (REC) <1.5% ( p = 0.002) as independent risk factors for poor survival. Patients with elevated CRP and LDH and a REC <1.5% were at highest risk for disease progression and death ( p = 0.001). Conclusions Blood markers predict survival in metastatic UM treated with immune checkpoint blockade. Normal serum levels of LDH and CRP and a high REC may help identify patients with better prognosis. [ABSTRACT FROM AUTHOR]