Clinical outcome and prognostic factors for central neurocytoma: twenty year institutional experience

Central neurocytomas are uncommon intraventricular neoplasms whose optimal management remains controversial due to their rarity. We assessed outcomes for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, size, resection extent, and adjuvant radiotherapy. Progression-free survival (PFS) was measured by Kaplan-Meier and Cox proportional hazards methods. A total of 28 patients (15 males, 13 females) were treated between 1995 and 2014, with a median age at diagnosis of 26 years (range 5-61). Median follow-up was 62.2 months and 3 patients were lost to follow-up postoperatively. Thirteen patients experienced recurrent/progressive disease and 2-year PFS was 75% (95% CI 53-88%). Two-year PFS was 48% for MIB-1 labeling >4% versus 90% for ≤4% (HR 5.4, CI 2.2-27.8, p = 0.0026). Nine patients (32%) had gross total resections (GTR) and 19 (68%) had subtotal resections (STR). PFS for >80% resection was 83 versus 67% for ≤80% resection (HR 0.67, CI 0.23-2.0, p = 0.47). Three STR patients (16%) received adjuvant radiation which significantly improved overall PFS (p = 0.049). Estimated 5-year PFS was 67% for STR with radiotherapy versus 53% for STR without radiotherapy. Salvage therapy regimens were diverse and resulted in stable disease for 54% of patients and additional progression for 38 %. Two patients with neuropathology-confirmed atypical neurocytomas died at 4.3 and 113.4 months after initial surgery. For central neurocytomas, MIB-1 labeling index >4% is predictive of poorer outcome and our data suggest that adjuvant radiotherapy after STR may improve PFS. Most patients requiring salvage therapy will be stabilized and multiple modalities can be effectively utilized

Chemoprevention of Colonic Polyps with Balsalazide: An Exploratory, Double-Blind, Placebo-Controlled Study

A number of agents, including aspirin, nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, folic acid, calcium, and vitamins, have been evaluated for their potential in chemoprevention of sporadic colorectal adenomas or cancer. Preclinical data suggest that 5-aminosalicylates also may have a chemopreventive effect. To investigate chemoprevention of colonic polyps with balsalazide, a 5-aminosalicylate prodrug. In this randomized, double-blind, placebo-controlled study, adults diagnosed with small polyps in the rectosigmoid colon were treated with either balsalazide 3 g/d or placebo for 6 months. Follow-up lower endoscopy was performed, and all polyps were measured and analyzed histologically. The primary endpoint was reduction in mean size of the largest polyp per subject. Among 241 participants screened, 86 were randomized to treatment, with 75 subjects evaluable. Balsalazide 3 g/d (n = 38) did not significantly reduce the mean size of the largest colonic polyp or the number of polyps compared with placebo (n = 37). Although not significant, post-hoc analysis revealed that total adenoma burden per subject, calculated as the sum of the volumes of all adenomas in mm3, increased by 55% in the balsalazide group compared with 95% in the placebo group. Although balsalazide did not have significant chemopreventive effects on established colonic polyps, these results can aid in designing future prospective studies

Bacterial Lifestyle in a Deep-sea Hydrothermal Vent Chimney Revealed by the Genome Sequence of the Thermophilic Bacterium Deferribacter desulfuricans SSM1

The complete genome sequence of the thermophilic sulphur-reducing bacterium, Deferribacter desulfuricans SMM1, isolated from a hydrothermal vent chimney has been determined. The genome comprises a single circular chromosome of 2 234 389 bp and a megaplasmid of 308 544 bp. Many genes encoded in the genome are most similar to the genes of sulphur- or sulphate-reducing bacterial species within Deltaproteobacteria. The reconstructed central metabolisms showed a heterotrophic lifestyle primarily driven by C1 to C3 organics, e.g. formate, acetate, and pyruvate, and also suggested that the inability of autotrophy via a reductive tricarboxylic acid cycle may be due to the lack of ATP-dependent citrate lyase. In addition, the genome encodes numerous genes for chemoreceptors, chemotaxis-like systems, and signal transduction machineries. These signalling networks may be linked to this bacterium's versatile energy metabolisms and may provide ecophysiological advantages for D. desulfuricans SSM1 thriving in the physically and chemically fluctuating environments near hydrothermal vents. This is the first genome sequence from the phylum Deferribacteres

Gene Expression and Biological Pathways in Tissue of Men with Prostate Cancer in a Randomized Clinical Trial of Lycopene and Fish Oil Supplementation

Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by these micronutrients.Global gene expression analysis revealed no significant individual genes that were associated with high intake of fish or tomato at baseline or after 3 months of supplementation with lycopene or fish oil. However, exploratory pathway analyses of rank-ordered genes (based on p-values not corrected for multiple comparisons) revealed the modulation of androgen and estrogen metabolism in men who routinely consumed more fish (p = 0.029) and tomato (p = 0.008) compared to men who ate less. In addition, modulation of arachidonic acid metabolism (p = 0.01) was observed after 3 months of fish oil supplementation compared with the placebo group; and modulation of nuclear factor (erythroid derived-2) factor 2 or Nrf2-mediated oxidative stress response for either supplement versus placebo (fish oil: p = 0.01, lycopene: p = 0.001).We did not detect significant individual genes associated with dietary intake and supplementation of lycopene and fish oil. However, exploratory analyses revealed candidate in vivo pathways that may be modulated by these micronutrients.ClinicalTrials.gov NCT00402285

Sentinel lymph node imaging guided IMRT for prostate cancer: Individualized pelvic radiation therapy versus RTOG guidelines.

Purpose/objectivesCurrent Radiation Therapy Oncology Group (RTOG) guidelines for pelvic radiation therapy are based on general anatomic boundaries. Sentinel lymph node (SLN) imaging can identify potential sites of lymph node involvement. We sought to determine how tailored radiation therapy fields for prostate cancer would compare to standard RTOG-based fields. Such individualized radiation therapy could prioritize the most important areas to irradiate while potentially avoiding coverage in areas where critical structures would be overdosed. Individualized radiation therapy could therefore increase the therapeutic index of pelvic radiation therapy.Methods and materialsTen intermediate or high-risk prostate cancer patients received androgen deprivation therapy with definitive radiation therapy, including an SLN imaging-tailored elective nodal volume (ENV). For dosimetric analyses, the ENV was recontoured using RTOG guidelines (RTOG_ENV) and on SLNs alone (SLN_ENV). Separate intensity modulated radiation therapy (IMRT) plans were optimized using RTOG_ENV and SLN_ENV for each patient. Dosimetric comparisons for these IMRT plans were performed for each patient. Dose differences to targets and critical structures among the different IMRT plans were calculated. Distributions of dose parameters were analyzed using non-parametric methods.ResultsSixty percent of patients had SLNs outside of the RTOG_ENV. The larger volume IMRT plans covering SLN imaging-tailored elective nodal volume exhibited no significant dose differences versus plans covering RTOG_ENV. IMRT plans covering only the SLNs had significantly lower doses to bowel and femoral heads.ConclusionsSLN-guided pelvic radiation therapy can be used to either treat the most critical nodes only or as an addition to RTOG guided pelvic radiation therapy to ensure that the most important nodes are included

Long-term disease-specific and cognitive quality of life after intensity-modulated radiation therapy: a cross-sectional survey of nasopharyngeal carcinoma survivors.

BackgroundThere is a lack of data on quality of life in long-term survivors of nasopharyngeal carcinoma (NPC) who have been treated with intensity-modulated radiation therapy (IMRT). We characterized long-term disease-specific and cognitive QoL in NPC survivors after IMRT.MethodsWe conducted a cross-sectional study of surviving patients diagnosed and treated for NPC at our center with curative-intent IMRT, with or without chemotherapy. Patients who were deceased, still undergoing treatment, with known recurrent disease, or treated with RT modality other than IMRT were excluded. QoL was measured by FACT-NP and FACT-Cog.ResultsBetween May and November 2013, 44 patients completed cognitive (FACT-Cog), general (FACT-G), and NPC-specific (NPCS) QoL assessments. Patients were categorized into 4 cohorts based on duration since IMRT (≤2.5, >2.5-6, >6-10, and >10-16 years). There was no significant difference in age (p = 0.20) or stage ((I/II vs III/IV: p = 0.78) among the cohorts. The 4 cohorts differed overall for all QoL measures (ANOVA: p < 0.02 for each), due to improved scores >2.5-6 years post-IMRT compared with ≤2.5 years post-IMRT (post hoc tests: p ≤ 0.04 for each). No differences were observed between >2.5-6 and >6-10 years post-IMRT, but lower mean FACT-Cog and NPCS scores were observed for >10 years compared to >2.5-6 years post-IMRT (post hoc: p < 0.05 for each).ConclusionsAll QoL measures were low during the initial recovery period (≤2.5 years) and were higher by 6 years post-IMRT. At >10 years post-IMRT, lower scores were observed in the domains of NPC-specific and cognitive QoL. Survivors of NPC, even if treated with IMRT, are at risk for detriment in domain-specific QoL measures at very long-term follow-up

Long-term disease-specific and cognitive quality of life after intensity-modulated radiation therapy: a cross-sectional survey of nasopharyngeal carcinoma survivors.

BackgroundThere is a lack of data on quality of life in long-term survivors of nasopharyngeal carcinoma (NPC) who have been treated with intensity-modulated radiation therapy (IMRT). We characterized long-term disease-specific and cognitive QoL in NPC survivors after IMRT.MethodsWe conducted a cross-sectional study of surviving patients diagnosed and treated for NPC at our center with curative-intent IMRT, with or without chemotherapy. Patients who were deceased, still undergoing treatment, with known recurrent disease, or treated with RT modality other than IMRT were excluded. QoL was measured by FACT-NP and FACT-Cog.ResultsBetween May and November 2013, 44 patients completed cognitive (FACT-Cog), general (FACT-G), and NPC-specific (NPCS) QoL assessments. Patients were categorized into 4 cohorts based on duration since IMRT (≤2.5, >2.5-6, >6-10, and >10-16 years). There was no significant difference in age (p = 0.20) or stage ((I/II vs III/IV: p = 0.78) among the cohorts. The 4 cohorts differed overall for all QoL measures (ANOVA: p < 0.02 for each), due to improved scores >2.5-6 years post-IMRT compared with ≤2.5 years post-IMRT (post hoc tests: p ≤ 0.04 for each). No differences were observed between >2.5-6 and >6-10 years post-IMRT, but lower mean FACT-Cog and NPCS scores were observed for >10 years compared to >2.5-6 years post-IMRT (post hoc: p < 0.05 for each).ConclusionsAll QoL measures were low during the initial recovery period (≤2.5 years) and were higher by 6 years post-IMRT. At >10 years post-IMRT, lower scores were observed in the domains of NPC-specific and cognitive QoL. Survivors of NPC, even if treated with IMRT, are at risk for detriment in domain-specific QoL measures at very long-term follow-up