Multi-omic based molecular profiling of advanced cancer identifies treatable targets and improves survival in individual patients.

A proof-of-concept study was conducted to assess whether patients with advanced stage IV cancer for whom predominantly no standard therapy was available could benefit from comprehensive molecular profiling of their tumor tissue to provide targeted therapy. Tumor samples of 83 patients were collected under highly standardized conditions and analyzed using immunohistochemistry, next-generation sequencing and phosphoprotein profiling. Expression and phosphorylation of key oncogenic pathways were measured to identify targets at the (phospho-) proteomic level. At genomic level, 50 oncogenes and tumor suppressor genes were analyzed. Based on molecular profiling, targeted therapies were decided by the attending oncologist. Accordingly, 28 patients who met the defined criteria fell in two equal-sized groups. One group received targeted therapies while the other did not. Following six months of treatment, disease control was achieved by 49% of patients receiving targeted therapy (complete remission, 14%; partial remission, 21%; stable disease, 14%; disease progression, 36%; death, 14%) and 21% of patients receiving non-targeted therapy (stable disease, 21%; disease progression, 64%; death, 14%). Individual patients experienced dramatic responses to a therapy which otherwise would not have been applied. This approach clarifies the value of multi-omic molecular profiling for cancer diagnostics.

Symptoms and clinical course of EHEC O104 infection in hospitalized patients: a prospective single center study.

OBJECTIVES: Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli (STEC/EHEC) is one of the most common causes of Haemolytic Uraemic Syndrome (HUS) related to infectious haemorrhagic colitis. Nearly all recommendations on clinical management of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first to be caused by the serotype O104:H4. This EHEC strain was found to carry genetic features of Entero Aggregative E. coli (EAEC) and extended spectrum ß lactamase (ESBL). We report symptoms and complications in patients at one of the most affected centres of the 2011 EHEC O104 outbreak in Northern Germany. METHODS: The courses of patients admitted to our hospital due to bloody diarrhoea with suspected EHEC O104 infection were recorded prospectively. These data include the patients' histories, clinical findings, and complications. RESULTS: EHEC O104 infection was confirmed in 61 patients (female = 37; mean age: 44±2 years). The frequency of HUS was 59% (36/61) in our cohort. An enteric colonisation with co-pathogens was found in 57%. Thirty-one (51%) patients were treated with plasma-separation/plasmapheresis, 16 (26%) with haemodialysis, and 7 (11%) with Eculizumab. Patients receiving antibiotic treatment (n = 37; 61%) experienced no apparent change in their clinical course. Twenty-six (43%) patients suffered from neurological symptoms. One 83-year-old patient died due to comorbidities after HUS was successfully treated. CONCLUSIONS: EHEC O104:H4 infections differ markedly from earlier reports on O157:H7 induced enterocolitis in regard to epidemiology, symptomatology, and frequency of complications. We recommend a standard of practice for clinical monitoring and support the renaming of EHEC O104:H4 syndrome as "EAHEC disease".

Differentiation of benign from malignant focal splenic lesions using sulfur hexafluoride-filled microbubble contrast-enhanced pulse-inversion sonography.

OBJECTIVE: The purpose of our study was to evaluate whether sonographic characterization of focal splenic lesions could be improved by using low mechanical index pulse-inversion sonography after sulfur hexafluoride-filled microbubble injection. MATERIALS AND METHODS: One hundred forty-seven splenic lesions (68 benign, 79 malignant) in 147 patients (81 men, 66 women; mean age, 51 years) underwent baseline gray-scale sonography and sulfur hexafluoride-enhanced low-acoustic-power pulse-inversion sonography (mechanical index < 0.1). Two site investigators assessed in consensus lesion and splenic enhancement during arterial and parenchymal phases. Four readers (readers 1 and 2, blinded; and readers 3 and 4, unblinded to clinical data) independently reviewed baseline and contrast-enhanced sonograms and provided confidence rating for diagnosis of malignancy or benignancy. Accuracy, sensitivity, specificity, positive and negative predictive values, and areas under the receiver operating characteristic curves (A(z)) were calculated by considering biopsy results or splenectomy (51 patients) or CT or MR images followed by serial sonography 6-12 months apart (96 patients) as reference standards. RESULTS: Benign lesions appeared predominately non- or isoenhancing relative to splenic parenchyma, whereas malignant lesions appeared predominately progressively hypoenhancing. For correct diagnosis of benignancy or malignancy, review of contrast-enhanced sonography after baseline sonography yielded significantly improved diagnostic performance (overall accuracy, 51%, 43%, 70%, and 74% before vs 83%, 81%, 92%, and 91% after contrast-enhanced sonography for readers 1, 2, 3, and 4; p < 0.05; respectively) and significantly improved diagnostic confidence (A(z), 0.770, 0.678, 0.900, and 0.917 before vs 0.935, 0.917, 0.984, and 0.959 after contrast-enhanced sonography for readers 1, 2, 3, and 4; p < 0.05; respectively). CONCLUSION: Sulfur hexafluoride-filled microbubble-enhanced sonography improves characterization of focal splenic lesions with and without the availability of clinical data.

Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma.

PURPOSE: This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study. PATIENTS AND METHODS: Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged