Use Dose Bricks Concept to Implement Nasopharyngeal Carcinoma Treatment Planning

Purpose. A “dose bricks” concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. Materials and Methods. Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. Results. The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10–15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. Conclusions. Compared with IMRT, the expenditure of planning time and costing, “dose bricks” may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed

RUNX1 deficiency cooperates with SRSF2 mutation to induce multilineage hematopoietic defects characteristic of MDS.

Myelodysplastic syndromes (MDSs) are a heterogeneous group of hematologic malignancies with a propensity to progress to acute myeloid leukemia. Causal mutations in multiple classes of genes have been identified in patients with MDS with some patients harboring more than 1 mutation. Interestingly, double mutations tend to occur in different classes rather than the same class of genes, as exemplified by frequent cooccurring mutations in the transcription factor RUNX1 and the splicing factor SRSF2. This prototypic double mutant provides an opportunity to understand how their divergent functions in transcription and posttranscriptional regulation may be altered to jointly promote MDS. Here, we report a mouse model in which Runx1 knockout was combined with the Srsf2 P95H mutation to cause multilineage hematopoietic defects. Besides their additive and synergistic effects, we also unexpectedly noted a degree of antagonizing activity of single mutations in specific hematopoietic progenitors. To uncover the mechanism, we further developed a cellular model using human K562 cells and performed parallel gene expression and splicing analyses in both human and murine contexts. Strikingly, although RUNX1 deficiency was responsible for altered transcription in both single and double mutants, it also induced dramatic changes in global splicing, as seen with mutant SRSF2, and only their combination induced missplicing of genes selectively enriched in the DNA damage response and cell cycle checkpoint pathways. Collectively, these data reveal the convergent impact of a prototypic MDS-associated double mutant on RNA processing and suggest that aberrant DNA damage repair and cell cycle regulation critically contribute to MDS development

Real-world anti-viral treatment decisions among chronic hepatitis C patients in Taiwan: The INITIATE study

Background/Purpose: While direct-acting antiviral regimens have been approved for chronic hepatitis C (CHC) patients in Taiwan, reimbursement is limited to certain populations. Thus, pegylated interferon plus ribavirin (PEG-IFN/RBV) remains the standard of care for many patients. The aim of this study was to investigate the percentage of CHC patients who were recommended and willing to receive PEG-IFN/RBV, and to identify reasons why patients were not recommended or unwilling to receive treatment. Methods: 822 Taiwanese CHC patients were enrolled from May–August 2016 in this cross-sectional study. PEG-IFN/RBV recommendation and patient willingness to receive treatment were evaluated through surveys. Patient characteristics associated with treatment recommendation and willingness were assessed. Results: 311 (37.8%) patients were recommended PEG-IFN/RBV while 102 (12.4%) were willing to follow treatment recommendation. Rates of recommendation and willingness were lower in treatment-experienced, hepatitis C virus genotype 1 (GT1) and cirrhotic patients, and those treated in Northern Taiwan. Multivariate analyses found factors such as prior treatment experience, GT1, cirrhosis and low hemoglobin levels to be associated with lower recommendation rates while advanced age, GT1 and low baseline viral loads were associated with lower willingness rates. Physicians' top reasons for not recommending PEG-IFN/RBV included the wish to wait for better treatment options (60.3%), prior treatment failure (21.3%) and patients’ advanced age (20.9%). Patients were unwilling to receive treatment mainly due to concerns about side effects (91.4%), the wish to wait for better treatment options (71.3%) and inconvenience (25.4%). Conclusion: A minority of Taiwanese CHC patients were recommended PEG-IFN/RBV, of which few were willing to receive treatment. Keywords: Hepatitis C, Pegylated interferon, Ribavirin, Direct acting antiviral, Taiwa