Low-dose metronomic chemotherapy as an efficient treatment option in metastatic breast cancer-results of an exploratory case-control study.

PURPOSE: There is growing interest in low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case-control analysis, we compared the efficacy of LDMC and conventional chemotherapy (CCT) in MBC. METHODS: Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two controls who received CCT. Age, number of chemotherapy lines and metastatic sites as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate longer than 24 weeks (DCR). Secondary endpoints were progression-free survival (PFS), duration of response (DoR) and subgroup analyses using the matching criteria. RESULTS: 40 cases and 80 controls entered the study. 30.0% patients with LDMC and 22.5% patients with CCT showed DCR (p = 0.380). The median PFS was 12.0 weeks in both groups (p = 0.218) and the median DoR was 31.0 vs. 20.5 weeks (p = 0.383), respectively. Among younger patients, DCR was 40.0% in LDMC vs. 25.0% in the CCT group (p = 0.249). DCR was achieved in 33.3% vs. 26.2% non-heavily pretreated patients (p = 0.568) and in 36.0% vs. 18.0% patients without multiple metastases (p = 0.096), respectively. In the HR-positive group, 30.0% LDMC vs. 28.3% CCT patients showed DCR (p = 1.000). Among triple-negative patients, DCR was achieved in 30.0% LDMC and 5.0% CCT patients (p = 0.095). CONCLUSIONS: We demonstrated a similar efficacy of LDMC compared to CCT in the treatment of MBC. Thus, LDMC may be a valuable treatment option in selected MBC patients.

Only strongly enhanced residual FDG uptake in early response PET (Deauville 5 or qPET ≥ 2) is prognostic in pediatric Hodgkin lymphoma: Results of the GPOH-HD2002 trial.

PURPOSE: In 2014, we published the qPET method to quantify fluorodeoxyglucose positron emission tomography (FDG-PET) responses. Analysis of the distribution of the quantified signals suggested that a clearly abnormal FDG-PET response corresponds to a visual Deauville score (vDS) of 5 and high qPET values ≥ 2. Evaluation in long-term outcome data is still pending. Therefore, we analyzed progression-free survival (PFS) by early FDG-PET response in a subset of the GPOH-HD2002 trial for pediatric Hodgkin lymphoma (PHL). PATIENTS/METHODS: Pairwise FDG-PET scans for initial staging and early response assessment after two cycles of chemotherapy were available in 93 PHL patients. vDS and qPET measurement were performed and related to PFS. RESULTS: Patients with a qPET value ≥ 2.0 or vDS of 5 had 5-year PFS rates of 44%, respectively 50%. Those with qPET values < 2.0 or vDS 1 to 4 had 5-year PFS rates of 90%, respectively 80%. The positive predictive value of FDG-PET response assessment increased from 18% (9%; 33%) using a qPET threshold of 0.95 (vDS ≤ 3) to 30% (13%; 54%) for a qPET threshold of 1.3 (vDS ≤ 4) and to 56% (23%; 85%) when the qPET threshold was ≥ 2.0 (vDS 5). The negative predictive values remained stable at ≥92% (CI: 82%; 98%). CONCLUSION: Only strongly enhanced residual FDG uptake in early response PET (vDS 5 or qPET ≥ 2, respectively) seems to be markedly prognostic in PHL when treatment according to the GPOH-HD-2002 protocol is given.

Subtype-specific prognostic impact of different immune signatures in node-negative breast cancer.

BACKGROUND: The role of different subtypes of immune cells is still a matter of debate. METHODS: We compared the prognostic relevance for metastasis-free survival (MFS) of a B-cell signature (BS), a T-cell signature (TS), and an immune checkpoint signature (CPS) in node-negative breast cancer (BC) using mRNA expression. Microarray-based gene-expression data were analyzed in six previously published cohorts of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). The prognostic relevance of the individual immune markers was assessed using univariate analysis. The amount of independent prognostic information provided by each immune signature was then compared using a likelihood ratio statistic in the whole cohort as well as in different molecular subtypes. RESULTS: Univariate Cox regression in the whole cohort revealed prognostic significance of CD4 (HR 0.66, CI 0.50-0.87, p = 0.004), CXCL13 (HR 0.86, CI 0.81-0.92, p < 0.001), CD20 (HR 0.76, CI 0.64-0.89, p = 0.001), IgκC (HR 0.81, CI 0.75-0.88, p < 0.001), and CTLA-4 (HR 0.67, CI 0.46-0.97, p = 0.032). Multivariate analyses of the immune signatures showed that both TS (p < 0.001) and BS (p < 0.001) showed a significant prognostic information in the whole cohort. After accounting for clinical-pathological variables, TS (p < 0.001), BS (p < 0.05), and CPS (p < 0.05) had an independent effect for MFS. In subgroup analyses, the prognostic effect of immune cells was most pronounced in HER2+ BC: BS as well as TS showed a strong association with MFS when included first in the model (p < 0.001). CONCLUSION: Immune signatures provide subtype-specific additional prognostic information over clinical-pathological variables in node-negative breast cancer.

Evaluation of bone viability in patients after girdlestone arthroplasty: comparison of bone SPECT/CT and MRI.

PURPOSE: To test the diagnostic performance of bone SPECT/CT and MRI for the evaluation of bone viability in patients after girdlestone-arthroplasty with histopathology used as gold standard. MATERIALS AND METHODS: In this cross-sectional study, patients after girdlestone-arthroplasty were imaged with single-photon-emission-computed-tomography/computed-tomography (SPECT/CT) bone-scans using 99mTc-DPD. Additionally, 1.5 T MRI was performed with turbo-inversion-recovery-magnitude (TIRM), contrast-enhanced T1-fat sat (FS) and T1-mapping. All imaging was performed within 24 h prior to revision total-hip-arthroplasty in patients with a girdlestone-arthroplasty. In each patient, four standardized bone-tissue-biopsies (14 patients) were taken intraoperatively at the remaining acetabulum superior/inferior and trochanter major/minor. Histopathological evaluation of bone samples regarding bone viability was used as gold standard. RESULTS: A total of 56 bone-segments were analysed and classified as vital (n = 39) or nonvital (n = 17) by histopathology. Mineral/late-phase SPECT/CT showed a high sensitivity (90%) and specificity (94%) to distinguish viable and nonviable bone tissue. TIRM (sensitivity 87%, specificity 88%) and contrast-enhanced T1-FS (sensitivity 90%, specificity 88%) also achieved a high sensitivity and specificity. T1-mapping achieved the lowest values (sensitivity 82%, specificity 82%). False positive results in SPECT/CT and MRI resulted from small bone fragments close to metal artefacts. CONCLUSIONS: Both bone SPECT/CT and MRI allow a reliable differentiation between viable and nonviable bone tissue in patients after girdlestone arthroplasty. The findings of this study could also be relevant for the evaluation of bone viability in the context of avascular bone necrosis.

[Intradermal metal deposits in an industrial worker]. / Intradermale Metalleinsprengungen bei einem Industriearbeiter.

CASE REPORT: We describe a 75-year-old patient with asymptomatic grey pigmentation on the face and fingers. He had worked over two decades in cutting high-voltage cables. The cutting procedures were performed without a face shield or protection gloves. The patient presented with gray punctate lesions beside some homogeneously stained zones. DIAGNOSTICS: Histologically, the deposits presented in the dermal tissue in a horse-shoe, oval, or splinter-like shape. The foreign body material was embedded by a few CD68-positive macrophages. Undyed histological sections were investigated via two-dimensional micro-synchrotron X-ray fluorescence analysis (SRXRF). The deposits were identified as zinc (Zn), copper (Cu), nickel (Ni), and strontium (Sr), which were strongly associated with maximal sulfur (S) concentrations. This association is presumably induced by complex binding between thiol groups and metal ions such as Zn, Ni etc. However, the iron (Fe) distribution patterns were quite different to those of Zn, Cu, or Ni. These heavy metals are major components of the metal wires that the patient worked with in his profession. CONCLUSION: To the best of our knowledge, this is the first case report in the dermatological literature of intradermal metal deposits identified via SRXRF analysis.

Combined measurement of tumor perfusion and glucose metabolism for improved tumor characterization in advanced cervical carcinoma. A PET/CT pilot study using [15O]water and [18F]fluorodeoxyglucose.

BACKGROUND AND PURPOSE: The aim of this pilot study was (1) to evaluate the combination of [(18)F]fluorodeoxyglucose (FDG) and [(15)O]water for detection of flow-metabolism mismatch in advanced cervical carcinomas, i.e., increased glycolysis at low blood flow, as a possible parameter for prediction of response to treatment, and (2) to propose a method for automated quantification of its spatial extent. PATIENTS AND METHODS: The study retrospectively included 10 women with advanced cervical carcinoma in whom PET with both FDG and [(15)O]water had been performed prior to therapy. The metabolically active tumor volume was delineated automatically in the FDG images. For computation of the regional blood flow in the tumor, a recovery corrected image-derived arterial input function was used. A tumor voxel was classified as mismatched when the voxel SUV of FDG was larger than the median tumor SUV and the voxel perfusion (K1) was smaller than the median perfusion. The absolute mismatch volume (aMMV) was defined as the volume of all mismatched voxels in ml, and the relative mismatch volume (rMMV) as the ratio of the aMMV to the metabolic tumor volume in percent. RESULTS: The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV clustered into 2 groups: "large aMMV" ≥ 10 ml in 40 % of patients and "small aMMV" ≤ 5 ml in 60 % of patients. The rMMV ranged from 12.7-24.9 %. There was no correlation between rMMV and metabolic tumor volume. There was a tendency (p = 0.126) for an association between rMMV and histological grading, rMMV being about 20 % higher in G3 than in G2 tumors. rMMV did not correlate with SUV or perfusion. CONCLUSION: These results suggest that combined PET with FDG and [(15)O]water allows detection and quantitative characterization of flow-metabolism mismatch in advanced cervical carcinomas.

Detection of pancreatic neuroendocrine tumors (PNET) using semi-quantitative [68Ga]DOTATOC PET in combination with multiphase contrast-enhanced CT.

Aim: Pancreatic neuroendocrine tumors (PNETs) pose a diagnostic challenge with respect to the physiologic somatostatin receptor expression in the uncinate process representing a potential pitfall for receptor imaging with PET/CT. Methods: We identified 49 PNETs from a total of 316 consecutive [68Ga]DOTATOC PET/CT examinations for whom the detections rates of PET and multiphase contrast enhanced (CE-) CT could be retrospectively compared and 38 PNETs for which SUV max and SUV max target-to-liver ratios could be calculated for the tumors and the uncinate process. Results: The detection rate of PET (83.7%) was higher than of the different CT phases (arterial: 59.2%, P=0.017; portal-venous: 38.8%, P<0.001; venous: 46.9%, P=0.001; multiphase: 71.4%, P=0.286). Compared to the other method PET revealed 28.6% additional lesions and multiphase CE-CT 16.3%. The portal-venous phase revealed only lesions that were also detected in the arterial or venous phase. The detection rate for PNETs in the uncinate process (N.=9) was 66.7% for PET versus 55.6% for multiphase CE-CT. SUV max and SUV max target-to-liver ratios differed significantly (P<0.001) for PNETs (mean, range: SUV max,14.6, 1.4-69.3; SUV max target-to-liver ratio, 3.2, 0.69-23.1) and uncinate process (4.32, 0.8-13.5; 0.94, 0.51-1.56), however with a wide overlap. Conclusion: Patients with PNETs should undergo [68Ga]DOTATOC PET/CT with at least an arterial and venous phase CT scan. SUV max and SUV max target-to-liver ratios provide additional information but do no reliably separate PNETs from normal tracer uptake in the uncinate process.

FDG PET/CT in cancer therapy monitoring: computer-assisted analysis of baseline together with up to two follow-ups.

OBJECTIVES: We developed and tested a software tool for computer-assisted analysis of FDG-PET/CT in cancer therapy monitoring. The tool provides automatic semi-quantitative analysis of a baseline scan together with up to two follow-up scans (standardized uptake values, glycolytic volume). The tool also supports visual analysis by local spatial registration which allows display of tumor lesions with the same orientation in all scans. The tool's stability and accuracy was tested at typical everyday image quality. PATIENTS, METHODS: Ten unselected cancer patients in whom three FDG PET/CT scans had been performed were included. A total of 18 lesions were analyzed. RESULTS: Automatic lesion tracking worked properly in all lesions but one. In this lesion local coregistration had to be adjusted manually which, however, is easily performed with the tool. Semi-automatic lesion segmentation and fully automatic semi-quantitative analysis worked properly in all cases. Computer-assisted analysis was significantly less time consuming than manual analysis. CONCLUSIONS: The novel software tool appears useful for analysis of FDG-PET/CT in cancer therapy monitoring in clinical routine patient care.

Comparison of F-18 FET-PET with F-18 FDG-PET for biopsy planning of non-contrast-enhancing gliomas.

OBJECTIVE: The management of non-contrast-enhancing brain tumours largely depends on biopsy, which allows a differentiation of low-grade gliomas (LGG) from high-grade gliomas (HGG). The aim of this study was to compare positron emission tomography using 2-[(18)F]-fluoro-2-deoxy-D: -glucose (FDG-PET) and O-(2-[(18)F]-fluoroethyl)-L: -tyrosine (FET-PET) in terms of providing target regions for biopsies. MATERIALS AND METHODS: Fifteen consecutive patients with newly diagnosed brain tumours (n = 11) or suspected recurrence of a known LGG (n = 4), in whom MRI demonstrated no contrast enhancement, were studied by both FET-PET and FDG-PET. FET-PET, FDG-PET and MRI data were fused, and then transferred to the neurosurgical navigation system, prior to neurosurgical interventions. RESULTS: Histology showed HGG (WHO grade III) in 6/15 and LGG (WHO grade II) in 9/15 patients. FET-PET revealed an increased intratumoural tracer uptake in 8/9 LGG and in 5/6 HGG. FDG-PET depicted hypermetabolic spots in 2/9 LGG and in 4/6 HGG. In 6 patients we observed an increased intratumoural uptake of both tracers. In 4 of them, the area of highest FET accumulation in the tumour corresponded to the focus of increased FDG uptake. CONCLUSIONS: FET-PET appears to be superior to FDG-PET for biopsy planning in non-contrast-enhancing brain tumours. FDG-PET does not provide any additional information in this issue.

[Procedure guideline for sentinel lymph node diagnosis]. / Verfahrensanweisung für die nuklearmedizinische Wächter-Lymphknoten-Diagnostik.

The authors present a procedure guideline for scintigraphic detection of sentinel lymph nodes in malignant melanoma and other skin tumours, in breast cancer, in head and neck cancer, and in prostate and penile carcinoma. Important goals of sentinel lymph node scintigraphy comprise reduction of the extent of surgery, lower postoperative morbidity and optimization of histopathological examination focussing on relevant lymph nodes. Sentinel lymph node scintigraphy itself does not diagnose tumorous lymph node involvement and is not indicated when lymph node metastases have been definitely diagnosed before sentinel lymph node scintigraphy. Procedures are compiled with the aim to reliably localise sentinel lymph nodes with a high detection rate typically in early tumour stages. Radiation exposure is low so that pregnancy is not a contraindication for sentinel lymph node scintigraphy. Even with high volumes of scintigraphic sentinel lymph node procedures surgeons, theatre staff and pathologists receive a radiation exposure <1 mSv/year so that they do not require occupational radiation surveillance.

Prostate Cancer Nodal Staging: Using Deep Learning to Predict 68Ga-PSMA-Positivity from CT Imaging Alone.

Lymphatic spread determines treatment decisions in prostate cancer (PCa) patients. 68Ga-PSMA-PET/CT can be performed, although cost remains high and availability is limited. Therefore, computed tomography (CT) continues to be the most used modality for PCa staging. We assessed if convolutional neural networks (CNNs) can be trained to determine 68Ga-PSMA-PET/CT-lymph node status from CT alone. In 549 patients with 68Ga-PSMA PET/CT imaging, 2616 lymph nodes were segmented. Using PET as a reference standard, three CNNs were trained. Training sets balanced for infiltration status, lymph node location and additionally, masked images, were used for training. CNNs were evaluated using a separate test set and performance was compared to radiologists' assessments and random forest classifiers. Heatmaps maps were used to identify the performance determining image regions. The CNNs performed with an Area-Under-the-Curve of 0.95 (status balanced) and 0.86 (location balanced, masked), compared to an AUC of 0.81 of experienced radiologists. Interestingly, CNNs used anatomical surroundings to increase their performance, "learning" the infiltration probabilities of anatomical locations. In conclusion, CNNs have the potential to build a well performing CT-based biomarker for lymph node metastases in PCa, with different types of class balancing strongly affecting CNN performance.

Computer simulations suggest that acute correction of hyperglycaemia with an insulin bolus protocol might be useful in brain FDG PET.

AIM: FDG PET in hyperglycaemic subjects often suffers from limited statistical image quality, which may hamper visual and quantitative evaluation. In our study the following insulin bolus protocol is proposed for acute correction of hyperglycaemia (>7.0 mmol/l) in brain FDG PET. (i) Intravenous bolus injection of short-acting insulin, one I.E. for each 0.6 mmol/l blood glucose above 7.0. (ii) If 20 min after insulin administration plasma glucose is

Comparison between positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose, conventional imaging and computed tomography for staging of breast cancer.

BACKGROUND: The presence, extent and localization of distant metastases are key prognostic factors in breast cancer patients and play a central role in therapeutic decision making. The aim of this study was to compare the diagnostic performance of positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) with that of computed tomography (CT) and conventional imaging including chest radiography, abdominal ultrasound and bone scintigraphy. PATIENTS AND METHODS: A total of 119 consecutive patients with newly diagnosed locally advanced disease (n = 69) or previous history of breast cancer (n = 50) who had clinical suspicion of metastatic disease underwent FDG-PET, CT and conventional imaging procedures. Imaging results were retrospectively compared with histopathology and clinical follow-up which served as a reference standard. RESULTS: FDG-PET detected distant metastases with a sensitivity of 87% and a specificity of 83%. In contrast, the sensitivity and specificity of combined conventional imaging procedures were 43% and 98%, respectively. CT revealed a sensitivity of 83% and a specificity of 85%. CONCLUSIONS: In breast cancer, FDG-PET is superior to conventional imaging procedures for detection of distant metastases. Although FDG-PET and CT provided similar diagnostic accuracy, the information was often found to be complementary. With increasing availability of FDG-PET/CT, prospective studies are needed to determine whether it could potentially replace the array of conventional imaging procedures used today.

Phase I study of biweekly oxaliplatin, gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies.

BACKGROUND: Oxaliplatin, gemcitabine and capecitabine are all active agents against upper gastrointestinal and pancreaticobiliary cancers. PATIENTS AND METHODS: Patients with upper gastrointestinal malignancies treated with 0-2 prior chemotherapy regimens received oxaliplatin (85-100 mg/m(2)) as a 2-h i.v. infusion with gemcitabine (800-1000 mg/m(2)) at a constant rate i.v. infusion (CI) of 10 mg/m(2)/min on days 1 and 15 of a 28-day cycle. Capecitabine (600-800 mg/m(2)) was administered orally twice a day on days 1-7 and 15-21. A three per cohort dose escalation schema was used to determine the maximum tolerated dose (MTD) and the dose-limiting toxic effects (DLTs) of this combination regimen. RESULTS: Thirty patients with advanced upper gastrointestinal malignancies were enrolled. The MTD was defined as oxaliplatin 100 mg/m(2) i.v. over 2 h plus gemcitabine 800 mg/m(2) i.v. at a CI of 10 mg/m(2)/min on days 1 and 15 with capecitabine 800 mg/m(2) p.o. b.i.d. days 1-7 and 15-21 of a 29-day cycle. DLTs include grade 3 fatigue and grade 3 dyspnea. One complete and two partial responses were observed. CONCLUSIONS: This biweekly schedule of oxaliplatin, gemcitabine and capecitabine is tolerable and warrants further investigation in biliary and pancreatic malignancies.

[18F]-FDG-PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial.

PURPOSE: The aim of this study was to determine the predictive values of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in primary staging in patients with newly diagnosed non-seminomatous germ cell tumour (NSGCT) clinical stage I/II. PATIENTS AND METHODS: The hypothesis was that FDG-PET would improve the negative predictive value (NPV) from 70% to 90%, thus requiring a total of 169 patients. All scans underwent visual analysis by a reference team of nuclear medicine physicians. Results were validated by histology following retroperitoneal lymph node dissection. RESULTS: Only 72 of the planned 169 patients were included, due to poor accrual. The prevalence of nodal involvement was 26%. Correct nodal staging by FDG-PET was achieved in 83% compared with correct computed tomography (CT) staging in 71%. CT had a sensitivity and specificity of 41% and 95%, respectively. Positive predictive value (PPV) and NPV were 87% and 67%, respectively. FDG-PET had a sensitivity and specificity of 66% and 98%, respectively. PPV was 95%. The primary end point was not reached, with an NPV of 78%. CONCLUSION: FDG-PET as a primary staging tool for NSGCT yielded only slightly better results than CT. Both methods had a high specificity while false-negative findings were more frequent with CT. FDG-PET is mostly useful as a diagnostic tool in case of questionable CT scan.

[Detection of metastases in breast cancer patients: comparison of FDG PET with chest X-ray, bone scintigraphy and ultrasound of the abdomen]. / Nachweis von Metastasen bei Patientinnen mit Mamma - karzinom Vergleich von FDG-PET mit Röntgen-Thorax, Oberbauchsonographie und Skelett szintigraphie.

UNLABELLED: Distant metastases at primary diagnosis are a prognostic key factor in breast cancer patients and play a central role in therapeutic decisions. To detect them, chest X-ray, abdominal ultrasound, and bone scintigraphy are performed as standard of care in Germany and many centers world-wide. Although FDG PET detects metastatic disease with high accuracy, its diagnostic value in breast cancer still needs to be defined. The aim of this study was to compare the diagnostic performance of FDG PET with conventional imaging. PATIENTS, METHODS: A retrospective analysis of 119 breast cancer patients who presented for staging was performed. Whole-body FDG-PET (n = 119) was compared with chest X-ray (n = 106) and bone scintigraphy (n = 95). Each imaging modality was independently assessed and classified for metastasis (negative, equivocal and positive. The results of abdominal ultrasound (n = 100) were classified as negative and positive according to written reports. Imaging results were compared with clinical follow-up including follow-up imaging procedures and histopathology. RESULTS: FDG-PET detected distant metastases with a sensitivity of 87.3% and a specificity of 83.3%. In contrast, the sensitivity and specificity of combined conventional imaging procedures was 43.1% and 98.5%, respectively. Regarding so-called equivocal and positive results as positive, the sensitivity and specificity of FDG-PET was 93.1% and 76.6%, respectively, compared to 61.2% and 86.6% for conventional imaging. Regarding different locations of metastases the sensitivity of FDG PET was superior in the detection of pulmonary metastases and lymph node metastases of the mediastinum in comparison to chest x-ray, whereas the sensitivity of FDG PET in the detection of bone and liver metastases was comparable with bone scintigraphy and ultrasound of the abdomen. CONCLUSIONS: FDG-PET is more sensitive than conventional imaging procedures for detection of distant breast cancer metastases and should be considered for additional staging especially in patients with high risk primary breast cancer.

[Elective organ-sparing surgery for renal tumors in patients with a normal contralateral kidney: long-term results]. / Elektive organerhaltende Nierentumorchirurgie bei normaler Gegenniere : Langzeitergebnisse.

Continuous improvements in radiological imaging techniques have enabled an earlier diagnosis of incidental renal tumors. The share of small renal tumors (4 cm can also be treated with nephron-sparing surgery. We report in this article our long-term oncological results of nephron-sparing surgery in patients with an elective indication.

[Imperative nephron-sparing surgery for cases of solitary kidney/bilateral tumors: long-term results]. / Imperative organerhaltende Nierentumorchirugie bei Einzelniere bzw. bilateralen Tumoren : Langzeitergebnisse.

Renal cell carcinoma is the most lethal amongst urological malignancies. Only surgical excision of the tumor offers the chance of curative therapy for patients with localized disease. Nephron-sparing surgery is mandatory for patients with renal tumors in both kidneys or in a solitary kidney in order to preserve renal function (imperative indication). Evaluation of patients with renal tumors in both kidneys or in a solitary kidney must weigh the surgical and oncological risks of nephron-sparing surgery against the morbidity of radical nephrectomy followed by hemodialysis and possibly renal transplantation. Herein we report our oncological and functional long-term results of nephron-sparing surgery in patients with an imperative indication and review the literature.

Clinical relevance of positron emission tomography and magnetic resonance imaging in the progression of internal plexiform neurofibroma in NF1.

Neurofibromatosis type 1 (NF1) is a frequent and inherited disease with a predisposition for malignant peripheral nerve sheath tumor (MPNST) development. MPNST are soft tissue sarcomas that arise from peripheral nerves, being one of the most aggressive malignancies in humans with extremely poor prognosis. MPNST frequently arise from a previously undetected plexiform neurofibroma (PNF). The malignant transformation of an internal PNF to an MPNST is difficult to assess and requires advanced imaging techniques like magnetic resonance imaging or positron emission tomography. Despite the high quality of current diagnostics, the changing tumor biology inside a plexiform neurofibroma cannot currently be visualized accurately. We report 4 cases of NF1 patients with PNF who showed imaging findings suspicious for malignant degeneration, but proved to have MPNST in only one case. Three tumors might represent an intermediate type between PNF and MPNST. Ablative surgery and complete histological work-up of specimens is the only way to clarify tumor status, thereby enabling provision of adequate local treatment.

Prognostic significance of interferon regulating factor 4 (IRF4) in node-negative breast cancer.

PURPOSE: The transcription factor IRF4 regulates immunoglobulin class switch recombination as well as plasma cell differentiation. We examined the prognostic significance of IRF4 expression in node-negative breast cancer (BC). METHODS: IRF4 expression was evaluated by immunostaining in a cohort of 197 node-negative BC patients not treated in adjuvant setting, referred to as Mainz cohort. The prognostic significance of immunohistochemically determined IRF4 expression for metastasis-free survival (MFS) was examined by Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age, pT stage, histological grade, ER, and HER2 status. For verification of immunohistochemical results, IRF4 mRNA expression was evaluated using microarray-based gene expression profiling in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) consisting of 824 node-negative breast cancer patients in total, who were not treated with adjuvant therapy. The prognostic significance of IRF4 mRNA expression on metastasis-free survival (MFS) was examined by univariate and multivariate Cox analysis in the Mainz cohort and by a meta-analysis of all node-negative BC patients and different molecular subtypes. IRF4 mRNA levels were compared to immunohistochemically determined IRF4 expression in 140 patients of the Mainz cohort using Spearman correlation. RESULTS: Immunohistochemically determined high IRF4 expression was associated with higher MFS in univariate Cox regression (HR 0.178, 95% CI 0.070-0.453, p < 0.001). IRF4 maintained its significance independently of established clinical factors for MFS (HR 0.088, 95% CI 0.033-0.232, p < 0.001). Immunohistochemically, determined IRF4 correlated moderately with IRF4 mRNA expression (ρ = 0.589). Higher expression of IRF4 was associated with better MFS in a meta-analysis of the total cohort (HR 0.438, 95% CI 0.307-0.623, p < 0.001). Prognostic significance was more pronounced in the HER2+ molecular subtype (HR 0.215, 95% CI 0.090-0.515, p = 0.001) as compared to the luminal A (HR 0.549, 95% CI 0.248-1.215, p = 0.139), luminal B (HR 0.444, 95% CI 0.215-0.916, p = 0.028), and basal-like subtypes (HR 0.487, 95% CI 0.269-0.883, p = 0.018). Further, IRF4 expression showed independent prognostic significance in a multivariate analysis of the Mainz cohort (HR 0.236, 95% CI 0.105-0.527, p < 0.001). CONCLUSIONS: IRF4 had independent prognostic significance in node-negative BC. Higher expression of IRF4 was associated with improved outcome. The prognostic impact differed between diverse molecular subtypes and was most pronounced in HER2+ breast cancer.