Systemic therapy in metastatic renal cell carcinoma (mRCC): an evidence-based recommendation of the German interdisciplinary RCC guidelines group.

PURPOSE: The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations. METHODS: A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate. RESULTS: Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated. CONCLUSION: ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.

[Pancytopenia, hepatosplenomegaly and dry cough after breast cancer]. / Panzytopenie, Hepatosplenomegalie und Reizhusten nach Mamma-Karzinom.

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman had suffered for 6 weeks from fatigue, dry cough and fever. Five years previously breast cancer had been diagnosed and had been successfully treated with subtotal mastectomy and postoperative radiotherapy, as well as aromatase inhibitor until shortly before the present admission. There was no history of travel to tropical countries, but during the last summer she had spent two weeks in Northern Italy. [corrected] INVESTIGATIONS: On admission the body temperature was 38,5 C with a mild tachycardia (108/min). Laboratory findings revealed a pancytopenia and slightly elevated liver enzymes. The ultrasound showed a hepatosplenomegaly. The investigation of the bone marrow showed a great amount of parasitic forms due to visceral leishmaniasis [corrected] TREATMENT, COURSE AND DIAGNOSIS: Treatment with liposomal amphotericin B brought about rapid improvement, the dry cough subsided and the laboratory results became normal. CONCLUSION: Pancytopenia, fever, dry cough and hepatosplenomegaly after travelling to Mediterranean countries should raise suspicion of visceral leishmaniasis. This diagnosis is confirmed by direct detection of the parasite in the bone marrow. Administration of liposomal amphotericin B is efficacious and safe, bringing about full recovery in up to 90% of cases.

Heart and muscle involvement by extra-medullary myeloid leukemia: a case report and review of the literature.

Extra-medullary myeloid tumours (EMT) have been described after curative treatment for acute myeloid leukaemia (AML) in increasing numbers after allogeneic stem cell transplantation. The sites of manifestations are ubiquitous and the discovery is most frequently guided by symptoms reported by the patient or by findings on clinical examination. This study reports a case of EMT in muscles and the heart 1.5 years after allogeneic transplantation for an AML with t(8;21)(q22;23) who achieved a complete remission by use of an idarubicine-based combination chemotherapy. Pathological and imaging findings are presented and treatment options are discussed.

DNA methylation changes in multiple myeloma.

Using a candidate gene approach, we analyzed the methylation status of the promoter-associated CpG islands of 11 well-characterized tumor suppressor genes by methylation-specific polymerase chain reaction in five multiple myeloma (MM) cell lines and 56 patients with malignant plasma cell disorders. The frequency of aberrant methylation among the patient samples was 46.4% for SOCS-1, 35.7% for p16, 21.4% for E-cadherin, 12.5% for DAP kinase and p73, 1.8% for p15, MGMT as well as RARbeta, and 0% for TIMP-3, RASSF1A and hMLH1. We found at least one hypermethylated gene in 80.4% of the primary patient samples, while 33.9% harbored two or more hypermethylated genes. For the first time, we show that p73 may be hypermethylated in MM and thus be involved in the pathogenesis of plasma cell disorders. Hypermethylation of p16 at diagnosis was associated with a poorer prognosis. In patients with plasma cell leukemia, we found frequent simultaneous hypermethylation of p16, E-cadherin and DAP kinase. We conclude that aberrant methylation of tumor suppressor genes is a common event in malignant plasma cell disorders and that there is a correlation between methylation patterns and clinical characteristics in MM patients.

Multidetector CT of the spine in multiple myeloma: comparison with MR imaging and radiography.

OBJECTIVE: The purpose of this study was to compare multidetector CT (MDCT) of the thoracic and lumbar segments of the spine with MR imaging and conventional radiography for bone lesion detection and for evaluating the risk of vertebral fracture in multiple myeloma. SUBJECTS AND METHODS: Eighteen patients with multiple myeloma stage III (according to the criteria of Durie and Salmon) underwent MDCT, conventional radiography, and MR imaging of the lumbar and thoracic spine. MDCT was performed using a standard protocol with no contrast material. Source images were reconstructed using an effective slice thickness of 3 mm with an overlapping reconstruction increment (0.8 mm). Secondary coronal and sagittal multiplanar reformations were exclusively used for establishing the diagnosis. Findings were compared with those of MR imaging and conventional radiography. RESULTS: In all patients, coronal and sagittal multiplanar reformations depicted the extent of osseous destruction and provided detailed information about osseous infiltration and potential bone instability. Compared with conventional radiography, an additional 24 affected vertebrae, 15 additional vertebral fractures, and six vertebrae at further risk of fracture were detected on MDCT. Compared with MR imaging, three additional endangered vertebrae were detected on MDCT. MR imaging alone would have lead to an understaging of five (27.8%) of 18 patients. Using combined radiography and MR imaging, disease in three (16.7%) of 18 patients would have been understaged. CONCLUSION: MDCT seems to be preferable to conventional radiography in evaluating bone destruction in multiple myeloma. In combination with MR imaging, detailed information for staging these tumors is obtained. For the initial staging in patients with multiple myeloma, MDCT in combination with MR imaging seems to be the method of choice.