Project description:Purpose:Proton therapy can potentially improve the therapeutic ratio over conventional radiation therapy for oropharyngeal squamous cell cancer (OPSCC) by decreasing acute and late toxicity. We report our early clinical experience with intensity-modulated proton therapy (IMPT). Materials and Methods:We retrospectively reviewed patients with OPSCC treated with IMPT at our center. Endpoints include local regional control (LRC), progression-free survival (PFS), overall survival (OS), tumor response, and toxicity outcomes. Toxicity was graded as per the Common Terminology Criteria for Adverse Events v4.03. Descriptive statistics and Kaplan-Meier method were used. Results:We treated 46 patients from March 2015 to August 2017. Median age was 58 years, 93.5% were male, 67% were nonsmokers, 98% had stage III-IVB disease per the 7th edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual, and 89% were p16 positive. Twenty-eight patients received definitive IMPT to total dose of 70 to 74.4 Gy(RBE), and 18 patients received postoperative IMPT to 60 to 66 Gy(RBE) following transoral robotic surgery (TORS). Sixty-four percent of patients received concurrent systemic therapy. There were no treatment interruptions or observed acute grade 4 or 5 toxicities. Eighteen patients had percutaneous endoscopic gastrostomy (PEG) tube placement; the majority (14) were placed prophylactically. The most common grade 3 acute toxicities were dermatitis (76%) and mucositis (72%). The most common late toxicity was grade 2 xerostomia (30%). At a median follow-up time of 19.2 months (interquartile range [IQR], 11.2-28.4), primary complete response was 100% and nodal complete response was 92%. One patient required a salvage neck dissection owing to an incomplete response at 4 months. There were no recorded local regional or marginal recurrences, PFS was 93.5%, and OS was 95.7%. Conclusion:Our early results for IMPT in OPSCC are promising with no local regional or marginal recurrences and a favorable toxicity profile. Our data add to a body of evidence that supports the clinical use of IMPT. Randomized comparative trials are encouraged.

Project description:This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Richard Sandstrom mailto:sull@u.washington.edu). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu). This track contains chromatin interaction data from the University of Washington ENCODE group generated using 5C (Chromatin Conformation Capture Carbon Copy). The 5C method is used here to define short and long-range range interactions between transcription start sites (TSS) and DNaseI hypersensitive sites (DHS) or other genomic features. The 5C method is summarized below. Transcription factors bind to promoter-associated proteins, bringing the associated DNA sequences in close proximity to each other. Cross linking the DNA and proteins immobilizes these interactions and thus maintains their close proximity. Cleavage of the sample with restriction endonuclease followed by ligation results in hybrid molecules where a fragment with a regulatory element is physically associated with a fragment containing a TSS. The interactions are then detected by oligonucleotide-dependent, ligation-mediated assays, where one set of primers is complementary to the end of fragments with a TSS and the second set of primers are complementary to fragments with a feature. Primers are designed to the forward strand of the feature and the reverse strand of the TSS so that ligation only occurs between TSS and feature, not between different features. Specific interactions are detected by massively parallel sequencing. The data in this track comprises two different experiment types focusing on targeted regions: Gene-targeted project: Analysis of DNase I hypersensitive sites reveals many genes where there are multiple sites restricted to the cell type where a protein is observed to be expressed. These sites potentially identify regulatory sites for the gene. This set of experiments attempts to observe interactions between these DHS sites and transcription starts in 25 regions selected based on genes expressed in GM06990 (B-lymphocyte), BJ (foreskin fibroblast), HepG2 (liver cancer cell line), or SK-N-SH_RA (neuroblastoma cell line, SKNSH, differentiated with retinoic acid). Myc project: Genome wide association studies have identified SNPs linked to prostate, colon, and breast cancer in the gene desert region upstream of the myc gene. 5C of HindIII fragments interacting with those containing refSeq txStarts in this region were performed in 5 cell types: GM12878 (B-lymphocyte), CaCo2 (colon cancer cell line), LNCaP (prostate cancer cell line), MCF7 (breast cancer cell line), and K562 (erythroleukemia cell line). For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

Project description:This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Richard Sandstrom mailto:sull@u.washington.edu). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu). This track, produced as part of the ENCODE Project, contains deep sequencing DNase data that will be used to identify sites where regulatory factors bind to the genome (footprints). Footprinting is a technique used to define the DNA sequences that interact with and bind DNA-binding proteins, such as transcription factors, zinc-finger proteins, hormone-receptor complexes, and other chromatin-modulating factors like CTCF. The technique depends upon the strength and tight nature of protein-DNA interactions. In their native chromatin state, DNA sequences that interact directly with DNA-binding proteins are relatively protected from DNA degrading endonucleases, while the exposed/unbound portions are readily degraded by such endonucleases. A massively parallel next-generation sequencing technique to define the DNase hypersensitive sites in the genome was adopted. Sequencing these next-generation-sequencing DNase samples to significantly higher depths of 300-fold or greater produces a base-pair level resolution of the DNase susceptibility maps of the native chromatin state. These base-pair resolution maps represent and are dependent upon the nature and the specificity of interaction of the DNA with the regulatory/modulatory proteins binding at specific loci in the genome; thus they represent the native chromatin state of the genome under investigation. The deep sequencing approach has been used to define the footprint landscape of the genome by identifying DNA motifs that interact with known or novel DNA binding proteins. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

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