Effects of radiotherapy planning with a dedicated combined PET-CT-simulator of patients with non-small cell lung cancer on dose limiting normal tissues and radiation dose-escalation: a planning study.

BACKGROUND AND PURPOSE: To investigate the effect of radiotherapy planning with a dedicated combined PET-CT simulator of patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Twenty-one patients underwent a pre-treatment simulation on a dedicated hybrid PET-CT-simulator. For each patient, two 3D conformal treatment plans were made: one with a CT based PTV and one with a PET-CT based PTV, both to deliver 60Gy in 30 fractions. The maximum tolerable prescribed radiation dose for CT versus PET-CT PTV was calculated based on constraints for the lung, the oesophagus, and the spinal cord, and the Tumour Control Probability (TCP) was estimated. RESULTS: For the same toxicity levels of the lung, oesophagus and spinal cord, the dose could be increased from 55.2+/-2.0Gy with CT planning to 68.9+/-3.3Gy with the use of PET-CT (P=0.002), with corresponding TCP's of 6.3+/-1.5% for CT and 24.0+/-5.6% for PET-CT planning (P=0.01). CONCLUSIONS: The use of a combined dedicated PET-CT-simulator reduced radiation exposure of the oesophagus and the lung, and thus allowed significant radiation dose escalation whilst respecting all relevant normal tissue constraints.     

The metabolism of 2,3,4-trimethylpentane in male Fischer-344 rats

The urinary metabolites of the potent nephrotoxic hydrocarbon 2,3,4-trimethylpentane (2,3,4-TMP) given Fischer-344 male rats by gavage included 1-hydroxy-2,3,4-trimethylpentane, 2,3,4-trimethyl-1-pentanoic acid and 2,3,4-trimethyl-5-hydroxy-1-pentanoic acid. Analyses were performed by gas-liquid chromatography (GC) and gas-liquid chromatography/mass spectrometry (GC/MS). A comparison of the urinary metabolites of 2,3,4-TMP with those of 2,2,4-trimethylpentane (2,2,4-TMP) showed that more monocarboxylic acid was produced with 2,3,4-TMP.     

A scoring system for AML patients aged 70 years or older,eligible for intensive chemotherapy: a study based on a large European data set using the DATAML,SAL, and PETHEMA registries

In a context of therapeutic revolution in older adults with AML, it is becoming increasingly important to select patients for the various treatment options by taking account of short-term efficacy and toxicity as well as long-term survival. Here, the data from three European registries for 1,199 AML patients aged 70 years or older treated with intensive chemotherapy were used to develop a prognostic scoring system. The median follow-up was 50.8 months. In the training set of 636 patients, age, performance status, secondary AML, leukocytosis, and cytogenetics, as well as NPM1 mutations (without FLT3-ITD), were all significantly associated with overall survival, albeit not to the same degree. These factors were used to develop a score that predicts long-term overall survival. Three risk-groups were identified: a lower, intermediate and higher-risk score with predicted 5-year overall survival (OS) probabilities of ≥12% (n = 283, 51%; median OS = 18 months), 3–12% (n = 226, 41%; median OS = 9 months) and <3% (n = 47, 8%; median OS = 3 months), respectively. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n = 563) and showed a lower false-positive rate than previously published scores. The European Scoring System ≥70, easy for routine calculation, predicts long-term survival in older AML patients considered for intensive chemotherapy.Subject terms: Acute myeloid leukaemia, Risk factors     

In vivo analyses of UV-irradiation-induced p53 promoter binding using a novel quantitative real-time PCR assay

The p53 tumor suppressor protein mediates cell cycle arrest and apoptosis through transactivation of downstream target genes. While many target genes have been identified to date, the mechanisms and time course of their induction are still unclear. We investigated the kinetics of p53 binding to the p21CIP1, MDM2, BAX and PIG3 promoters in vivo using a novel quantitative real-time chromatin immunoprecipitation-PCR assay. Our results demonstrate distinct kinetics of p53 promoter binding dependent on the target gene promoters. The timed induction of target genes due to genotoxic stress is likely to play a pivotal role for the divergent functions of p53.     

Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT

Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA (p = 0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects (p = 0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease.