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BackgroundPeripheral blood leucocyte telomere length (PBL-TL) is associated with outcomes in patients with idiopathic pulmonary fibrosis. Whether PBL-TL is associated with progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unknown.MethodsA retrospective observational cohort study was performed using prospectively collected data from 213 patients with SSc followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by quantitative PCR of DNA isolated from peripheral blood. Associations between PBL-TL and pulmonary function test trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalised Linear Mixed Models. Findings were validated in a cohort of 61 patients with SSc-ILD enrolled in the Stanford University Scleroderma Center database.ResultsPatients with UCSF SSc with ILD were found to have shorter PBL-TL compared with those without ILD (6554±671 base pairs (bp) vs 6782±698 bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted OR 2.1 per 1000 bp TL decrease, 95% CI [1.25 to 3.70], p=0.006). PBL-TL was shorter in patients with SSc-ILD lacking SSc-specific autoantibodies compared with seropositive subjects (6237±647 bp vs 6651±653 bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67 mL greater loss in per year for every 1000 bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95% CI -104 mL to -33 mL, p<0.001).ConclusionsThese findings suggest that telomere dysfunction may be associated with SSc-ILD progression and that PBL-TL measurement may be useful for stratifying risk for SSc-ILD progression.

BackgroundPeripheral blood leucocyte telomere length (PBL-TL) is associated with outcomes in patients with idiopathic pulmonary fibrosis. Whether PBL-TL is associated with progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unknown.MethodsA retrospective observational cohort study was performed using prospectively collected data from 213 patients with SSc followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by quantitative PCR of DNA isolated from peripheral blood. Associations between PBL-TL and pulmonary function test trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalised Linear Mixed Models. Findings were validated in a cohort of 61 patients with SSc-ILD enrolled in the Stanford University Scleroderma Center database.ResultsPatients with UCSF SSc with ILD were found to have shorter PBL-TL compared with those without ILD (6554±671 base pairs (bp) vs 6782±698 bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted OR 2.1 per 1000 bp TL decrease, 95% CI [1.25 to 3.70], p=0.006). PBL-TL was shorter in patients with SSc-ILD lacking SSc-specific autoantibodies compared with seropositive subjects (6237±647 bp vs 6651±653 bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67 mL greater loss in per year for every 1000 bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95% CI -104 mL to -33 mL, p<0.001).ConclusionsThese findings suggest that telomere dysfunction may be associated with SSc-ILD progression and that PBL-TL measurement may be useful for stratifying risk for SSc-ILD progression.

PurposeTo determine the utility of focal high-dose-rate brachytherapy for localized prostate cancer, we investigated the impact on target coverage and dose to organs at risk (OARs) with hemigland (HG) compared with whole-gland (WG) treatment.Methods and materialsA total of 10 WG implants were used to generate 10 WG and 20 HG (left and right) treatment plans optimized with the inverse planning simulation annealing algorithm using Oncentra MasterPlan (Nucletron B.V., Veenendaal, The Netherlands). The standard distribution of 17-18 catheters designed for WG was used to generate HG plans. The same OARs namely bladder, rectum, and urethra contours and dose constraints were applied for HG and WG plans. The HG contour was a modification of the WG contour whereby the urethra divided the prostate into HGs. The prescription dose was 7.25 Gy×6. Evaluated dose parameters were target dose D90, V100, and V150 and D0.1 cc, D1 cc, and D2 cc to OARs.ResultsThe HG plans had a D90, V100, and V150 to the HG target of 112%, 97.6%, and 33.8%, respectively. The WG plans had a D90, V100, and V150 to the WG target of 108%, 98.8%, and 26.5%, respectively. The OAR D2 cc doses were significantly lower in HG vs. WG plans: rectum (53.1% vs. 64.1%, p<0.0001), bladder (55.9% vs. 67.5%, p<0.0001), and urethra (69.3% vs. 95.2%, p<0.0001).ConclusionsIn the present model, HG plans yielded a statistically significant decreased radiation dose to OARs and provided complete target coverage with a catheter array designed for WG coverage. The good dosimetry results obtained in this study support the feasibility of HG brachytherapy by using a subset of the WG catheter array. Catheter distribution and dosimetry refinements tailored to subtotal prostate brachytherapy should be explored to see if further improvements in dosimetry can be achieved.

PurposeTo determine the utility of focal high-dose-rate brachytherapy for localized prostate cancer, we investigated the impact on target coverage and dose to organs at risk (OARs) with hemigland (HG) compared with whole-gland (WG) treatment.Methods and materialsA total of 10 WG implants were used to generate 10 WG and 20 HG (left and right) treatment plans optimized with the inverse planning simulation annealing algorithm using Oncentra MasterPlan (Nucletron B.V., Veenendaal, The Netherlands). The standard distribution of 17-18 catheters designed for WG was used to generate HG plans. The same OARs namely bladder, rectum, and urethra contours and dose constraints were applied for HG and WG plans. The HG contour was a modification of the WG contour whereby the urethra divided the prostate into HGs. The prescription dose was 7.25 Gy×6. Evaluated dose parameters were target dose D90, V100, and V150 and D0.1 cc, D1 cc, and D2 cc to OARs.ResultsThe HG plans had a D90, V100, and V150 to the HG target of 112%, 97.6%, and 33.8%, respectively. The WG plans had a D90, V100, and V150 to the WG target of 108%, 98.8%, and 26.5%, respectively. The OAR D2 cc doses were significantly lower in HG vs. WG plans: rectum (53.1% vs. 64.1%, p<0.0001), bladder (55.9% vs. 67.5%, p<0.0001), and urethra (69.3% vs. 95.2%, p<0.0001).ConclusionsIn the present model, HG plans yielded a statistically significant decreased radiation dose to OARs and provided complete target coverage with a catheter array designed for WG coverage. The good dosimetry results obtained in this study support the feasibility of HG brachytherapy by using a subset of the WG catheter array. Catheter distribution and dosimetry refinements tailored to subtotal prostate brachytherapy should be explored to see if further improvements in dosimetry can be achieved.

Rationale and objectivesA novel ventilation imaging method based on four-dimensional (4D) computed tomography (CT) has been applied to the field of radiation oncology. Understanding its reproducibility is a prerequisite for clinical applications. The purpose of this study was to quantify the reproducibility of 4D CT ventilation imaging over different days and the same session.Materials and methodsTwo ventilation images were created from repeat 4D CT scans acquired over the average time frames of 15 days for 6 lung cancer patients and 5 minutes for another 6 patients. The reproducibility was quantified using the voxel-based Spearman rank correlation coefficients for all lung voxels and Dice similarity coefficients (DSC) for the spatial overlap of segmented high-, moderate-, and low-functional lung volumes. Furthermore, the relationship between the variation in abdominal motion range as a measure of the depth of breathing and variation in ventilation was evaluated using linear regression.ResultsThe voxel-based correlation between the two ventilation images was moderate on average (0.50 ± 0.15). The DSCs were also moderate for the high- (0.60 ± 0.08), moderate- (0.46 ± 0.06), and low-functional lung (0.58 ± 0.09). No patients demonstrated strong correlations. The relationship between the motion range variation and ventilation variation was found to be moderate and significant.ConclusionsWe investigated the reproducibility of 4D CT ventilation imaging over the time frames of 15 days and 5 minutes and found that it was only moderately reproducible. Respiratory variation during 4D CT scans was found to deteriorate the reproducibility. Improvement of 4D CT imaging is necessary to increase the reproducibility of 4D CT ventilation imaging.