Radiotherapy quality assurance review in a multi-center randomized trial of limited-disease small cell lung cancer: the Japan Clinical Oncology Group (JCOG) trial 0202

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to analyze the radiotherapy (RT) quality assurance (QA) assessment in Japan Clinical Oncology Group (JCOG) 0202, which was the first trial that required on-going RT QA review in the JCOG.</p> <p>Methods</p> <p>JCOG 0202 was a multi-center phase III trial comparing two types of consolidation chemotherapy after concurrent chemoradiotherapy for limited-disease small cell lung cancer. RT requirements included a total dose of 45 Gy/30 fx (bis in die, BID/twice a day) without heterogeneity correction; elective nodal irradiation (ENI) of 30 Gy; at least 1 cm margin around the clinical target volume (CTV); and interfraction interval of 6 hours or longer. Dose constraints were defined in regards to the spinal cord and the lung. The QA assessment was classed as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable (I/NE).</p> <p>Results</p> <p>A total of 283 cases were accrued, of which 204 were fully evaluable, excluding 79 I/NE cases. There were 18 VU in gross tumor volume (GTV) coverage (8% of 238 evaluated); 4 VU and 23 DA in elective nodal irradiation (ENI) (2% and 9% of 243 evaluated, respectively). Some VU were observed in organs at risk (1 VU in the lung and 5 VU in the spinal cord). Overall RT compliance (PP + DA) was 92% (187 of 204 fully evaluable). Comparison between the former and latter halves of the accrued cases revealed that the number of VU and DA had decreased.</p> <p>Conclusion</p> <p>The results of the RT QA assessment in JCOG 0202 seemed to be acceptable, providing reliable results.</p

Dynamic conformal arc radiotherapy for locally advanced lung cancer: a comparison with static-beam conformal radiotherapy

Background: This study investigated whether the dose distribution of lung cancer can be improved by dynamic arc conformal radiotherapy (dynamic CRT) compared with static multiple-beam radiotherapy (static CRT). Materials and methods: A dummy study of static CRT and dynamic CRT was performed, designed to meet the predetermined dose constraints. A dose of 60 Gy in 30 fractions was administered using two dose prescription methods: dose prescribed to the isocenter (IC prescription), and dose prescribed to &gt; 50% of the planning target volume (D50 prescription). Dose–volume parameters were compared between the plans. Results: Among 20 patients with locally advanced lung cancer, dose conformity was significantly better with dynamic CRT than static CRT (median conformity index: 1.3 vs. 2.2; p &lt; 0.01). As for the lung dose, compared with static CRT, dynamic CRT did not increase the percentage lung volume receiving ≥ 20 Gy (18.9% vs. 19.3%, p = 0.09). The maximum spinal cord dose was significantly reduced by dynamic CRT (static vs. dynamic CRT: 44.1 vs. 25.2 Gy, p &lt; 0.001). With the change from IC to D50 prescription, the 95% isodose volume increased by 18.3 cc in static CRT and by 4.1 cc in dynamic CRT, while doses to the lung and spinal cord remained within the acceptable ranges. Conclusion: The dynamic CRT technique showed better target coverage and lower doses to the spinal cord in exchange for increased low-dose lung area, compared with static CRT. Dynamic CRT with D50 prescription instead of prescription to the isocenter has excellent dose distribution profiles without compromising doses to organs at risk for lung cancer at favorable locations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Analysis of porcine optineurin and myocilin expression in trabecular meshwork cells and astrocytes from optic nerve head. Invest Ophthalmol Vis Sci 45

PURPOSE. To determine the cDNA sequences and analyze the expression of porcine optineurin and myocilin in trabecular meshwork cells (TMCs) and astrocytes from the optic nerve head under normal and experimental conditions. METHODS. Both porcine optineurin and myocilin were cloned to determine the cDNA sequences. Porcine TMCs and astrocytes were isolated and treated with dexamethasone (500 nM) for 2 weeks, incubated under hypoxic conditions (7% O 2 ) for 72 hours, or exposed to 33 mm Hg hydrostatic pressure for 72 hours. A 10% mechanical stretch for 24 hours was also performed on TMCs. The expression level of the optineurin and myocilin transcripts was analyzed by real-time quantitative PCR. RESULTS. The sequences of porcine optineurin and myocilin cDNA were determined, and the expression of both genes was confirmed in both TMCs and astrocytes. Amino acid sequences of porcine optineurin and myocilin were homologous to those of humans by 84% and 82%, respectively, and shared protein motifs and modification sites. The expression of myocilin mRNA by TMCs and astrocytes was increased by 8.0-and 5.5-fold, respectively, after exposure to dexamethasone. In contrast, the expression of optineurin was suppressed to 68% in TMCs and 48% in astrocytes after exposure to dexamethasone. A significant reduction of myocilin expression was observed after 72 hours of incubation under hypoxic conditions in both types of cells, whereas optineurin was not affected. Hydrostatic pressure for 72 hours and mechanical stretching for 24 hours had minimal affects on gene expression of both optineurin and myocilin. CONCLUSIONS. The high homology of porcine optineurin and myocilin to the comparable human genes indicates that pigs can be used to study changes in gene expression in hypertensive eyes. The alterations in expression of myocilin but not of optineurin under stress suggest that different mechanisms in the phenotype of glaucoma associated with the two genes are involved in development of glaucoma. (Invest Ophthalmol Vis Sci

Relationship between Dose Prescription Methods and Local Control Rate in Stereotactic Body Radiotherapy for Early Stage Non-Small-Cell Lung Cancer: Systematic Review and Meta-Analysis

Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable