Differentiated Thyroid Cancer with Extrathyroidal Extension: Prognosis and the Role of External Beam Radiotherapy

A study was performed to identify variables that affected cause-specific survival (CSS) and local relapse-free rate (LRFR) in patients with differentiated thyroid cancer (DTC) and extrathyroid extension (ETE) and to examine the role of external beam radiotherapy (XRT). Prognostic factors were similar to those found in studies of all patients with DTC. In patients with postoperative gross residual disease treated with radiotherapy, 10-year CSS and LRFR were 48% and 90%. For patients with no residual or microscopic disease, 10-year CSS and LRFR were 92% and 93%. In patients older than 60 years with T3 ETE but no gross residual disease postoperatively there was an improved LRFR at 5 years of 96%, compared to 87.5% without XRT (P = .02). Patients with gross ETE benefit from XRT and there may be a potential benefit in reducing locoregional failure in patients over 60 years with minimal extrathyroidal extension (T3)

Design, modeling, and current interpretations of the H-19 and H-11 tracer tests at the WIPP site

Site-characterization studies at the Waste Isolation Pilot Plant (WIPP) site in southeastern New Mexico, US identified ground-water flow in the Culebra Dolomite Member of the Rustler Formation as the most likely geologic pathway for radionuclide transport to the accessible environment in the event of a breach of the WIPP repository through inadvertent human intrusion. The results of recent tracer tests, as well as hydraulic tests, laboratory measurements, and re-examination of Culebra geology and stratigraphy, have led to a significant refinement of the conceptual model for transport in the Culebra. Tracer test results and geologic observations suggest that flow occurs within fractures, and to some extent within interparticle porosity and vugs connected by microfractures. Diffusion occurs within all connected porosity. Numerical simulations suggest that the data from the tracer tests cannot be simulated with heterogeneous single-porosity models; significant matrix diffusion appears to be required. The low permeability and lack of significant tracer recovery from tracers injected into the upper Culebra suggest that transport primarily occurs in the lower Culebra

A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

BACKGROUND: Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. METHODS: Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. RESULTS: Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. CONCLUSION: The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment

Decision aid on radioactive iodine treatment for early stage papillary thyroid cancer - a randomized controlled trial

Abstract Background Patients with early stage papillary thyroid carcinoma (PTC), are faced with the decision to either to accept or reject adjuvant radioactive iodine (RAI) treatment after thryroidectomy. This decision is often difficult because of conflicting reports of RAI treatment benefit and medical evidence uncertainty due to the lack of long-term randomized controlled trials. Methods We report the protocol for a parallel, 2-arm, randomized trial comparing an intervention group exposed to a computerized decision aid (DA) relative to a control group receiving usual care. The DA explains the options of adjuvant radioactive iodine or no adjuvant radioactive iodine, as well as associated potential benefits, risks, and follow-up implications. Potentially eligible adult PTC patient participants will include: English-speaking individuals who have had recent thyroidectomy, and whose primary tumor was 1 to 4 cm in diameter, with no known metastases to lymph nodes or distant sites, with no other worrisome features, and who have not received RAI treatment for thyroid cancer. We will measure the effect of the DA on the following patient outcomes: a) knowledge about PTC and RAI treatment, b) decisional conflict, c) decisional regret, d) client satisfaction with information received about RAI treatment, and e) the final decision to accept or reject adjuvant RAI treatment and rationale. Discussion This trial will provide evidence of feasibility and efficacy of the use of a computerized DA in explaining complex issues relating to decision making about adjuvant RAI treatment in early stage PTC. Trial registration Clinical Trials.gov Identifier: NCT0108355

A Recombination Hotspot in a Schizophrenia-Associated Region of GABRB2

Background: Schizophrenia is a major disorder with complex genetic mechanisms. Earlier, population genetic studies revealed the occurrence of strong positive selection in the GABRB2 gene encoding the β2 subunit of GABAA receptors, within a segment of 3,551 bp harboring twenty-nine single nucleotide polymorphisms (SNPs) and containing schizophrenia-associated SNPs and haplotypes. Methodology/Principal Findings:In the present study, the possible occurrence of recombination in this 'S1-S29' segment was assessed. The occurrence of hotspot recombination was indicated by high resolution recombination rate estimation, haplotype diversity, abundance of rare haplotypes, recurrent mutations and torsos in haplotype networks, and experimental haplotyping of somatic and sperm DNA. The sub-segment distribution of relative recombination strength, measured by the ratio of haplotype diversity (Hd) over mutation rate (θ), was indicative of a human specific Alu-Yi6 insertion serving as a central recombining sequence facilitating homologous recombination. Local anomalous DNA conformation attributable to the Alu-Yi6 element, as suggested by enhanced DNase I sensitivity and obstruction to DNA sequencing, could be a contributing factor of the increased sequence diversity. Linkage disequilibrium (LD) analysis yielded prominent low LD points that supported ongoing recombination. LD contrast revealed significant dissimilarity between control and schizophrenic cohorts. Among the large array of inferred haplotypes, H26 and H73 were identified to be protective, and H19 and H81 risk-conferring, toward the development of schizophrenia. Conclusions/Significance: The co-occurrence of hotspot recombination and positive selection in the S1-S29 segment of GABRB2 has provided a plausible contribution to the molecular genetics mechanisms for schizophrenia. The present findings therefore suggest that genome regions characterized by the co-occurrence of positive selection and hotspot recombination, two interacting factors both affecting genetic diversity, merit close scrutiny with respect to the etiology of common complex disorders. © 2010 Ng et al

High frequency of mitochondrial genome instability in human endometrial carcinomas

To investigate the occurrence of somatic mitochondrial DNA (mtDNA) mutations in human primary endometrial carcinomas, we sequenced the D-loop region, the 12S and 16S rRNA genes of mtDNA of cancer tissues and their matched normal controls. About 56% (28 out of 50) of cases carry one or more somatic changes in mtDNA including deletion, point mutation and mitochondrial microsatellite instability (mtMSI), namely the change in length of short base-repetitive sequences of mtDNA. In particular, mtMSI was frequently detected in 89% (25 out of 28) of all the cases carrying somatic changes followed by point mutations (25%; seven out of 28) and deletion (3.5%; one out of 28). The CCCCCTCCCC sequences located in the Hypervariable Regions I and II of the D-loop and 12S rRNA gene are instability hot spot regions in endometrial carcinomas. It is suggested that errors in replication may account for the high frequency of mtMSI in human endometrial carcinomas. The relatively high prevalence of mtMSI may be a potential new tool for detection of endometrial cancer. © 2003 Cancer Research UK.link_to_subscribed_fulltex