Exploratory and inferential analysis of gene cluster neighborhood graphs

Many different cluster methods are frequently used in gene expression data analysis to find groups of co–expressed genes. However, cluster algorithms with the ability to visualize the resulting clusters are usually preferred. The visualization of gene clusters gives practitioners an understanding of the cluster structure of their data and makes it easier to interpret the cluster results. In this paper recent extensions of R package gcExplorer are presented. gc-Explorer is an interactive visualization toolbox for the investigation of the overall cluster structure as well as single clusters. The different visualization options including arbitrary node and panel functions are described in detail. Finally the toolbox can be used to investigate the quality of a given clustering graphically as well as theoretically by testing the association between a partition and a functional group under study. It is shown that gcExplorer is a very helpful tool for a general exploration of microarray experiments. The identification of potentially interesting gene candidates or functional groups is substantially accelerated and eased. Inferential analysis on a cluster solution is used to judge its ability to provide insight into the underlying mechanistic biology of the experiment

Stereotactic or conformal radiotherapy for adrenal metastases: patient characteristics and outcomes in a multicenter analysis

To report outcome (freedom from local progression: FFLP, overall survival: OS, and toxicity) after stereotactic, palliative, or highly conformal fractionated (> 12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤ 12 fractions, biologically effective dose, (BED10) ≥ 50 Gy), 3DCRT/IMRT (> 12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/Log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). 326 patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT, and Pall-RT in 260, 27, and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%), and melanoma (6.7%). Unadjusted FFLP was higher after SBRT v. Pall-RT (p = 0.026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4%, and 27.7%). OS was longer after SBRT v. other groups (p < 0.05) and increased in patients with locally-controlled metastases in a landmark analysis (p < 0.0001). Toxicity was mostly mild; notably, 4 cases of adrenal insufficiency occurred, 2 of which were likely caused by immunotherapy or tumor progression. RT for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. 1-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway

Analysis of using high-precision radiotherapy in the treatment of liver metastases regarding toxicity and survival

Background!#!Hepatic metastases occur frequently in the context of many tumor entities. Patients with colorectal carcinoma have already developed liver metastases in 20% at the time of diagnosis, and 25-50% develop metastases in the further course of the disease and therapy. The frequent manifestation and the variable appearance of liver metastases result in an interdisciplinary challenge, regarding treatment management. The aim of this study was to evaluate high-precision stereotactic body radiotherapy (SBRT) for liver metastases.!##!Methods!#!A cohort of 115 patients with 150 irradiated liver metastases was analyzed. All metastases were treated between May 2004 and January 2020 using SBRT. A contrast-enhanced computed tomography (CT) was performed in all patients for treatment planning, followed by image-guided high-precision radiotherapy using cone-beam CT. A median cumulative dose of 35 Gy and a median single dose of 7 Gy was applied.!##!Results!#!Median OS was 20.4 months and median LC was 35.1 months with a 1-year probability of local failure of 18% (95%-CI: 12.0-24.3%). In this cohort, 18 patients were still alive at the time of evaluation. The median FU-time in total was 11.4 months and for living patients 26.6 months. 70.4% of patients suffered from acute toxicities. There were several cases of grade 1 and 2 toxicities, such as constipation (13.9%), nausea (24.4%), loss of appetite (7.8%), vomiting (10.4%), diarrhea (7.8%), and abdominal pain (16.5%). 10 patients (8.7%) suffered from grade 3 toxicities. Late toxicities affected 42.6% of patients, the majority of these affected the gastrointestinal system.!##!Conclusion!#!SBRT is becoming increasingly important in the field of radiation oncology. It has evolved to be a highly effective treatment for primary and metastasized tumors, and offers a semi-curative treatment option also in the case of oligometastatic patients. Overall, it represents a very effective and well-tolerated therapy option to treat hepatic metastases. Based on the results of this work and the studies already available, high-precision radiotherapy should be considered as a valid and promising treatment alternative in the interdisciplinary discussion