Phase i study of \u27dose-dense\u27 pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma.

BACKGROUND: This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). METHODS: Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m2) q3 weeks × 2 -3 cycles. RESULTS: Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. CONCLUSIONS: Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC

A Learning-Based Automatic Segmentation and Quantification Method on Left Ventricle in Gated Myocardial Perfusion SPECT Imaging: A Feasibility Study

Background: The performance of left ventricular (LV) functional assessment using gated myocardial perfusion SPECT (MPS) relies on the accuracy of segmentation. Current methods require manual adjustments that are tedious and subjective. We propose a novel machine-learning-based method to automatically segment LV myocardium and measure its volume in gated MPS imaging without human intervention. Methods: We used an end-to-end fully convolutional neural network to segment LV myocardium by delineating its endocardial and epicardial surface. A novel compound loss function, which encourages similarity and penalizes discrepancy between prediction and training dataset, is utilized in training stage to achieve excellent performance. We retrospectively investigated 32 normal patients and 24 abnormal patients, whose LV myocardial contours automatically segmented by our method were compared with those delineated by physicians as the ground truth. Results: The results of our method demonstrated very good agreement with the ground truth. The average DSC metrics and Hausdorff distance of the contours delineated by our method are larger than 0.900 and less than 1 cm, respectively, among all 32 + 24 patients of all phases. The correlation coefficient of the LV myocardium volume between ground truth and our results is 0.910 ± 0.061 (P \u3c 0.001), and the mean relative error of LV myocardium volume is − 1.09 ± 3.66%. Conclusion: These results strongly indicate the feasibility of our method in accurately quantifying LV myocardium volume change over the cardiac cycle. The learning-based segmentation method in gated MPS imaging has great promise for clinical use

Improved hippocampal dose with reduced margin radiotherapy for glioblastoma multiforme

BACKGROUND: To dosimetrically evaluate the effect of reduced margin radiotherapy on hippocampal dose for glioblastoma multiforme (GBM) patients. METHODS: GBM patients enrolled on the Radiation Therapy Oncology Group (RTOG) 0825 trial at our institution were identified. Standard RTOG 0825 expansions were 2 cm + 3-5 mm from the gross tumor volume (GTV) to the clinical tumor volume (CTV) and from the CTV to the planning tumor volume (PTV), respectively. These same patients also had reduced margin tumor volumes generated with 8 mm (GTV to CTV) + 3 mm (CTV to PTV) expansions. Individual plans were created for both standard and reduced margin structures. The dose-volume histograms were statistically compared with a paired, two-tailed Student’s t-test with a significance level of p < 0.05. RESULTS: A total of 16 patients were enrolled on RTOG 0825. The reduced margins resulted in statistically significant reductions in hippocampal dose at all evaluated endpoints. The hippocampal D(max) was reduced from a mean of 61.4 Gy to 56.1 Gy (8.7%), D(40%) was reduced from 49.9 Gy to 36.5 Gy (26.9%), D(60%) was reduced from 32.7 Gy to 18.7 Gy (42.9%) and the D(80%) was reduced from 27.3 Gy to 15.3 Gy (44%). CONCLUSIONS: The use of reduced margin PTV expansions in the treatment of GBM patients results in significant reductions in hippocampal dose. Though the exact clinical benefit of this reduction is currently unclear, this study does provide support for a future prospective trial evaluating the neurocognitive benefits of reduced margin tumor volumes in the treatment of GBM patients

Measuring space-time variation of the fundamental constants with redshifted submillimetre transitions of neutral carbon

We compare the redshifts of neutral carbon and carbon monoxide in the redshifted sources in which the fine structure transition of neutral carbon, [CI], has been detected, in order to measure space-time variation of the fundamental constants. Comparison with the CO rotational lines measures gives the same combination of constants obtained from the comparison fine structure line of singly ionised carbon, [CII]. However, neutral carbon has the distinct advantage that it may be spatially coincident with the carbon monoxide, whereas [CII] could be located in the diffuse medium between molecular clouds, and so any comparison with CO could be dominated by intrinsic velocity differences. Using [CI], we obtain a mean variation of dF/F = (-3.6 +/- 8.5) x 10^-5, over z = 2.3 - 4.1, for the eight [CI] systems, which degrades to (-1.5+/- 11) x 10^-5, over z = 2.3 - 6.4 when the two [CII] systems are included. That is, zero variation over look-back times of 10.8-12.8 Gyr. However, the latest optical results indicate a spatial variation in alpha, which describes a dipole and we see the same direction in dF/F. This trend is, however, due to a single source for which the [CI] spectrum is of poor quality. This also applies to one of the two [CII] spectra previously used to find a zero variation in alpha^2/mu. Quantifying this, we find an anti-correlation between |dF/F| and the quality of the carbon detection, as measured by the spectral resolution, indicating that the typical values of >50 km/s, used to obtain a detection, are too coarse to reliably measure changes in the constants. From the fluxes of the known z > 1 CO systems, we predict that current instruments are incapable of the sensitivities required to measure changes in the constants through the comparison of CO and carbon lines. We therefore discuss in detail the use of ALMA for such an undertaking ... ABRIDGEDComment: Accepted for publication in Section 3 - Cosmology (including clusters of galaxies) of Astronomy and Astrophysic

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

<p>Abstract</p> <p>Background</p> <p>This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m². Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m², but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m²) q3 weeks × 2 -3 cycles.</p> <p>Results</p> <p>Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients.</p> <p>Conclusions</p> <p>Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m²with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00330044">NCT00330044</a></p