Ablative Radiation Therapy in Oligometastatic Pancreatic Cancer to Delay Polyprogression, Limit Chemotherapy, and Improve Outcomes.

PURPOSE: The oligometastatic state is observed in patients across many malignancies, with increased recognition regarding improved outcomes after local therapies. However, there is limited data specifically regarding pancreatic ductal adenocarcinoma. We hypothesized that an oligometastatic pancreatic ductal adenocarcinoma (OPanc) phenotype would benefit from stereotactic ablative radiation therapy (SABR) to all active metastatic sites. Here, we report our institutional experience of SABR-treated OPanc to evaluate the feasibility of the approach. METHODS AND MATERIALS: A retrospective review of patients with synchronous or metachronous OPanc (1 to 5 metastases) who received SABR to all active metastatic sites was performed. We identified a comparable group of patients with similar metastatic burden, range of CA19-9 levels, and no progression for at least 5 months who did not receive SABR. We compared overall survival as the primary outcome, and polyprogression-free survival and time off chemotherapy as the secondary exploratory assessments. A third group presenting with stage IV pancreatic ductal adenocarcinoma and more than 5 distant lesions (polymetastatic) was identified to help define expected outcomes after polyprogression. RESULTS: Our study included 20 patients with OPanc receiving SABR and 21 who did not. SABR was delivered to 38 metastatic tumors. Out of the 20 SABR-treated OPanc patients, 17 (85%) had 6 or more months of time off chemotherapy, compared with 7 patients (33.3%) among the chemotherapy-treated group. Median polyprogression-free survival was 40 and 14 months (hazard ratio = 0.2; 95% confidence interval, 0.07-0.54; P = .0009), and overall survival was 42 and 18 months (hazard ratio = 0.21; 95% confidence interval, 0.08-0.53; P = .0003), for SABR- and chemotherapy-treated cohorts, respectively. CONCLUSIONS: Management of OPanc with SABR as local regional therapy could improve outcomes in a selected population and warrants prospective evaluation.

Racial and Ethnic Differences in Genomic Profiling of Early Onset Colorectal Cancer.

The incidence and mortality of early onset colorectal cancer (EOCRC) is rising; outcomes appear to differ by race and ethnicity. We aimed to assess differences in mutational landscape and gene expression of EOCRC by racial and ethnic groups (non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, White Hispanic) using data from the American Association for Cancer Research Project GENIE (10.2) and University of Texas Southwestern, the latter enriched in Hispanic patients. All statistical tests were 2-sided. Of 1752 EOCRC patients, non-Hispanic Black patients had higher rates of KRAS mutations (60.9%; P = .001, q = 0.015), and non-Hispanic White and non-Hispanic Black patients had higher rates of APC mutations (77.1% and 76.6% among non-Hispanic White and non-Hispanic Black patients, respectively; P = .001, q = 0.015) via the Fisher exact test with Benjamini-Hochberg correction. Using R packages DESeq2 and clusterProfiler, we found that White Hispanic patients had increased expression of genes involved in oxidative phosphorylation (P < .001, q = 0.025). Genomic profiling has the potential to identify novel diagnostics and influence individualized treatment options to address the currently limited prognosis of EOCRC.

Study of PKRBD in HCV genotype 3a infected patients in response to interferon therapy in Pakistani population.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma and infects about 3% world population. Response to interferon therapy depends upon the genotype of the virus and factors associated with the host. Despite a good response to interferon therapy, a considerable number of genotype 3a infected patients remains unalleviated. RESULTS: In total forty-nine patients including twenty-five non-responders (non-SVR) and twenty-four responders (SVR) were recruited. Patients were tested for viral status at different intervals and the isolated RNA was sequenced for the NS5A region in both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients did not confirm any significant difference in the number of mutations. However, when the sequence downstream to the PKRBD of NS5A was compared, two important statistically significant mutations were observed; at positions 2309 (Ala to Ser) and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein structure and important structural changes were observed. Statistically significant difference was also observed when age groups of patients were compared; younger patients showed better response than the older ones. CONCLUSIONS: The region between PKRBD and IRRDR may be important for prediction of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any involvement in treatment response. Further functional analyses of these findings can help in understanding the involvement of the NS5A region in interferon treatment of HCV-3a infected patients.

Tumor necrosis factor-alpha gene promoter region polymorphism and the risk of coronary heart disease.

BACKGROUND: Tumor necrosis factor-alpha (TNF- α ) gene polymorphisms have been implicated in the manifestation of atherosclerosis. Controversy exists regarding the link between the cytokine's variant genotype and CHD among different ethnic groups. There have been fewer studies on the TNF- α gene -1031T>C and -863C>A polymorphisms in relation to CHD. Therefore, the current study was designed to investigate the association of the TNF- α gene -1031T>C and -863C>A polymorphisms with CHD in a Pakistani population. METHODS: Patients with CHD (n = 310) and healthy individuals (n = 310) were enrolled in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A significant difference was observed in the -863C>A polymorphism between patients with CHD and control subjects (P < 0.0001). CHD risk was positively associated with the variant allele -863A (P < 0.0001) in the study subjects. There was no significant link between the -1031T>C polymorphism and CHD risk in the study population. Haplotypes A-T and A-C of the TNF-alpha gene loci at -863 and -1031 showed higher frequency in the patient group compared with controls (P < 0.05). CONCLUSION: The TNF- α -863C>A gene polymorphism was associated with the pathogenesis of CHD while the -1031T>C polymorphism did not show any link with the disease in a Pakistani population.

Primary Ewing sarcoma of the brain: a case report and literature review.

Ewing sarcoma, along with peripheral primitive neuroectodermal tumor, belongs to a tumor family that shares clinicopathologic and molecular genetic features, including the characteristic chromosomal translocation that results in the fusion of the EWS gene on 22q12 to either the FLI1 gene on 11q24 or other Ets family transcription factor gene, such as the ERG gene on 21q22. In contrast, such translocations are not found in central primitive neuroectodermal tumors (cPNETs), such as medulloblastoma and supratentorial PNET. Ewing sarcoma has only rarely been noted to primarily involve the central nervous system-extraosseous Ewing sarcoma (CNS-EES). We report a case of a 7-year-old girl with an anterior cranial fossa mass. Pathology showed a primitive small blue cell tumor with focal Homer Wright rosette formation. The positive membranous immunostaining for CD99 and the EWS-FLI1 fusion demonstrated by fluorescence in situ hybridization studies confirmed the diagnosis of CNS-EES. Although CNS-EES may look identical to cPNETs, these tumors differ in histogenesis, molecular characteristics, and clinical behavior. Demonstration of characteristic translocations by molecular studies differentiates CNS-EES from cPNET and help clinicians make informed decisions regarding therapy.