Reduced Dose Research Articles

TH-AB-207A-10: Sub-MSv Cerebral CT Perfusion Imaging Using Prior Image Constrained Compressed Sensing: A Prospective Clinical Trial

Purpose: A prospective clinical study was conducted to assess whether sub-mSv cerebral CT perfusion (CTP) imaging can be achieved using the Prior Image Constrained Compressed Sensing (PICSS) reconstruction algorithm. Methods: Following a standard dose (SD) CTP acquisition, 31 patients (median age, 62 years; 15 M/16 F; median BMI, 27) underwent an additional reduced dose (RD) CTP acquisition at 20% of the standard dose level. Several algorithms (PICCS, ASIR, and FBP) were used to reconstruct CTP source images of the RD series. SD-FBP served as the reference standard. Two clinical observers (one neuroradiologist and one neurosurgeon) scored CTP maps using qualitative scoring system and quantitative noise measurements were performed. Statistical analyses were performed to interpret the qualitative and quantitative assessments. Results: The CTDIvol and effective dose for the RD series was 44.5 mGy and 0.75 mSv respectively, compared with 222.6 mGy and 3.74 mSv respectively for the SD series. The average image quality scores of the RD-PICCS series were 3.8±0.7 for CBF, 3.5±0.9 for CBV, 3.9±0.9 for MTT. In comparison, subjective image quality scores of SD-FBP were 3.5±0.8 for CBF, 3.5±0.9 for CBV, 3.3±0.8 for MTT. The average noise of RD-PICCS (CBF, 5.8±1.9 mL/100 g/min; CBV, 0.74±0.26 mL/100 g; MTT, 5.5±1.2 s) were lower than those of SD-FBP (CBF, 8.1±2.5 mL/100 g/min; CBV, 0.86±0.28 mL/100 g; MTT, 6.4±1.2 s) with statistical significance (p < 0.001). Both subjective scores and objective noise of RD-ASIR and RD-FBP were significantly inferior to those of SD-FBP (p < 0.001). Conclusions: PICCS enables sub-mSv cerebral CTP imaging without compromising diagnostic image quality. Funding Support: 2015 AAPM Research Seed Grant. Disclosures: J. Tang: Employee, GE Healthcare; H. Rowley: Research Consultant, Bracco Group, Guerbet SA, GE Healthcare, F. Hoffmann-La Roche Ltd, W.L. Gore & Associates, Lundbeck Group; C. Strother: Research Consultant, Siemens AX; G.-H. Chen: Research funded, GE Healthcare, Siemens AX.

MP05-10 AUTOMATED STONE VOLUME MEASUREMENT USING REDUCED-DOSE (RD) CT IS COMPARABLE STANDARD-DOSE (SD) CT

You have accessJournal of UrologyImaging/Radiology: Uroradiology I1 Apr 2016MP05-10 AUTOMATED STONE VOLUME MEASUREMENT USING REDUCED-DOSE (RD) CT IS COMPARABLE STANDARD-DOSE (SD) CT John Roger Bell, Amy Lim, Perry Pickhardt, and Stephen Y Nakada John Roger BellJohn Roger Bell More articles by this author , Amy LimAmy Lim More articles by this author , Perry PickhardtPerry Pickhardt More articles by this author , and Stephen Y NakadaStephen Y Nakada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1987AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stone volume measurement via CT is more precise compared to traditional linear measurements. We have shown an automated approach is more reproducible with less inter-observer variability than uni-dimensional measurements. (Patel et al, J Urol 2011; Patel et al, Urol 2012). Our institution has developed a reduced dose sub-millisievert (mSv) CT protocol with effective doses 70-90% less than that of traditional non-contrast CT, averaging 0.9 mSv. We compared automated stone volume measurements using standard dose non-contrasted CT (SD-NCCT) vs reduced dose non-contrasted CT (RD-NCCT) in a prospective clinical trial. METHODS In this prospective trial, we studied a cohort of patients who underwent concurrent SD-NCCT and RD-NCCT scans during the same imaging session. 20 patients were identified as having urolithiasis on these imaging studies and were used in our study. All patients provided signed informed consent. Automated stone volume was assessed using previously validated software (Ziosoft) on both SD-NCCT and RD-NCCT images. SD-NCCT images were reconstructed with the standard FBP algorithm. RD-NCCT images were reconstructed using FBP, PICCS, ASiR, and Veo techniques then compared. A single reader was utilized for all patients to optimize stone matching and minimize variability. RESULTS 42 individual renal stones were identified and included in our analysis. Automated stone volumes on SD-NCCT ranged from 9.9 mm3 to 8757 mm3. Stone volumes on each of the reconstructed RD-NCCT formats were then compared against the SD-NCCT images and the percent error was calculated using absolute values to avoid cancellation. Mean percentage volume error for each RD-NCCT series compared with the reference standard SD-NCCT series was as follows: 19.9% for Veo, 23.6% for ASiR, 24.9% for PICCS, and 35.8% for FBP. The failure rate for automated calculation was significantly higher for the RD-FBP series when compared to Veo (P = 0.009). CONCLUSIONS Automated renal stone volume measurements using CT removes inter-observer variability. With the higher level iterative reconstruction methods using Veo, the error in volume with RD-NCCT measurement relative to SD-NCCT is acceptable (<20%). In comparison, RD-NCCT using standard FBP reconstruction results in much greater error. Follow-up of renal stone burden with sub-mSv RD-NCCT using Veo would provide a surveillance method that maintains accuracy at a lower dose than a 2-view KUB. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e40 Advertisement Copyright & Permissions© 2016MetricsAuthor Information John Roger Bell More articles by this author Amy Lim More articles by this author Perry Pickhardt More articles by this author Stephen Y Nakada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of dose reduction on survival in patients starting sunitinib (SU) or pazopanib (PA) as first-line for metastatic renal cell carcinoma (mRCC).

553 Background: SU and PA are both VEGFR TKI approved for treatment of mRCC. Previous studies reported that the reduced dose (RD) is not recommended for the beginning of therapy (Motzer et al. 2012) and suggested a direct correlation between dose and effectiveness of therapy (Houk et al. 2010). We aim to investigate if patients (pts) that decreased the dose during treatment have different outcomes compared to those who continue a standard dose (SD). Methods: All pts affected by mRCC who started SU or PA at SD have been included. Pts were divided into two groups: RD and SD, based on whether they reduced the therapy or not. The main reasons for dose change have been collected and the RD group was defined into 2 levels (1st level: SU37.5mg/d, 4/2 or PA 600mg/d; 2nd level: SU25mg/d, 4/2 or PA 400mg/d). Pts were stratified by IMDC prognostic criteria and differences in pts’ characteristics between RD and SD groups were evaluated as well as median PFS and OS. Results: A total of 280 pts have been included. Median age was 62y and 68% was male; 54% had good prognosis, 40% intermediate and 6% poor. First-line was SU in 84% and PA in 16% of cases. A total of 123 (44%) pts decreased the dose to first- (89%) or second-level (11%). The main reasons were hand-foot syndrome (17.9%), diarrhea (15.4%) asthenia (14.6%), mucositis (13.0%) and thrombocytopenia (11.4%). Significant differences between RD and SD groups were the female sex (40% vs. 25%; p = 0.01) and the rate of primary refractory disease (11% vs. 31%: p &lt; 0.001). Median PFS and OS were 12.4 and 34.9 mos, respectively. In RD group, the median time before dose reduction was 3.5 mos. Excluding the primary refractory pts, median PFS was 18.6 and 15.0 mos (p = 0.06) and median OS was 68.0 and 40.7 mos (p = 0.14) in RD and SD group, respectively. In RD group, no differences between 1st- and 2nd-level of dose were observed both in PFS (11.0 vs. 13.1 mos; p = 0.82) and OS (42.8 vs. 36.0 mos; p = 0.78) after reduction. Conclusions: Dose reduction is a frequent event in pts who started a first-line therapy with SU or PA. This study reports that DR does not affect the survival of pts who initially started SU and PA at standard dose.

Assessment of sub-milli-sievert abdominal computed tomography with iterative reconstruction techniques of different vendors.

To assess diagnostic image quality of reduced dose (RD) abdominal computed tomography (CT) with 9 iterative reconstruction techniques (IRTs) from 4 different vendors to the standard of care (SD) CT. In an Institutional Review Board approved study, 66 patients (mean age 60 ± 13 years, 44 men, and 22 women) undergoing routine abdomen CT on multi-detector CT (MDCT) scanners from vendors A, B, and C (≥ 64 row CT scanners) (22 patients each) gave written informed consent for acquisition of an additional RD CT series. Sinogram data of RD CT was reconstructed with two vendor-specific and a vendor-neutral IRTs (A-1, A-2, A-3; B-1, B-2, B-3; and C-1, C-2, C-3) and SD CT series with filtered back projection. Subjective image evaluation was performed by two radiologists for each SD and RD CT series blinded and independently. All RD CT series (198) were assessed first followed by SD CT series (66). Objective image noise was measured for SD and RD CT series. Data were analyzed by Wilcoxon signed rank, kappa, and analysis of variance tests. There were 13/50, 18/57 and 9/40 missed lesions (size 2-7 mm) on RD CT for vendor A, B, and C, respectively. Missed lesions includes liver cysts, kidney cysts and stone, gall stone, fatty liver, and pancreatitis. There were also 5, 4, and 4 pseudo lesions (size 2-3 mm) on RD CT for vendor A, B, and C, respectively. Lesions conspicuity was sufficient for clinical diagnostic performance for 6/24 (RD-A-1), 10/24 (RD-A-2), and 7/24 (RD-A-3) lesions for vendor A; 5/26 (RD-B-1), 6/26 (RD-B-2), and 7/26 (RD-B-3) lesions for vendor B; and 4/20 (RD-C-1) 6/20 (RD-C-2), and 10/20 (RD-C-3) lesions for vendor C (P = 0.9). Mean objective image noise in liver was significantly lower for RD A-1 compared to both RD A-2 and RD A-3 images (P < 0.001). Similarly, mean objective image noise lower for RD B-2 (compared to RD B-1, RD B-3) and RD C-3 (compared to RD C-1 and C-2) (P = 0.016). Regardless of IRTs and MDCT vendors, abdominal CT acquired at mean CT dose index volume 1.3 mGy is not sufficient to retain clinical diagnostic performance.

Evaluation of pulmonary nodules and infection on chest CT with radiation dose equivalent to chest radiography: Prospective intra-individual comparison study to standard dose CT

PurposeTo compare prospectively, in patients undergoing chest computed tomography (CT) for pulmonary-nodules or infection, image-quality and accuracy of standard dose (SD) and reduced dose (RD) CT with tin-filtration. Material and methodsThis IRB-approved study included 100 consecutive patients (36 female;median age 56 years) referred for follow-up of pulmonary-nodules (n=43) or suspicion of infection (n=57) undergoing single-energy CT with SD and RD using tin-filtration at 100kVp (CTDIvol 2.47mGy and 0.07mGy, respectively). Images were reconstructed with advanced modeled iterative reconstruction (ADMIRE) at strength 3 and 5. Image-noise was measured. Two independent readers evaluated nodules and pulmonary-infection. SD CT served as reference standard. ResultsNo significant difference was found in noise between RD with ADMIRE5 and SD with ADMIRE3 (118HU±14 vs. 120HU±17; p=0.08). Sensitivity for detection of atelectasis and interstitial lung changes was higher in images reconstructed with ADMIRE5 (93% and 88%; respectively) than in those reconstructed with ADIMRE3 (77% and 78%; respectively). Sensitivity for detection of consolidations was 90% for ADMIRE3 and 89% for ADMIRE5. Sensitivity for nodule detection was 71% for ADMIRE3 and 81% for ADMIRE5. Specificity for detection of atelectasis and interstitial lung changes was 99% and 96% with ADMIRE5 and 99% and 96% with ADMIRE3. Specificity for detection of consolidations was 99% for ADMIRE3 and 5. Specificity for detection of nodules was 87% for both ADMIRE3 and 5. ConclusionChest CT with a radiation dose equivalent to conventional radiography is feasible and allows for detection of pulmonary infection with high sensitivity, whereas the accuracy for detecting nodules is only moderate.

Clinical evaluation of image quality and radiation dose reduction in upper abdominal computed tomography using model-based iterative reconstruction; comparison with filtered back projection and adaptive statistical iterative reconstruction

PurposeTo evaluate the image quality of upper abdominal CT images reconstructed with model-based iterative reconstruction (MBIR) in comparison with filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASIR) on scans acquired with various radiation exposure dose protocols. Materials and methodsThis prospective study was approved by our institutional review board, and informed consent was obtained from all 90 patients who underwent both control-dose (CD) and reduced-dose (RD) CT of the upper abdomen (unenhanced: n=45, contrast-enhanced: n=45). The RD scan protocol was randomly selected from three protocols; Protocol A: 12.5% dose, Protocol B: 25% dose, Protocol C: 50% dose. Objective image noise, signal-to-noise (SNR) ratio for the liver parenchyma, visual image score and lesion conspicuity were compared among CD images of FBP and RD images of FBP, ASIR and MBIR. ResultsRD images of MBIR yielded significantly lower objective image noise and higher SNR compared with RD images of FBP and ASIR for all protocols (P<.01) and CD images of FBP for Protocol C (P<.05). Although the subjective image quality of RD images of MBIR was almost acceptable for Protocol C, it was inferior to that of CD images of FBP for Protocols A and B (P<.0083). The conspicuity of the small lesions in RD images of MBIR tended to be superior to that in RD images of FBP and ASIR and inferior to that in CD images for Protocols A and B, although the differences were not significant (P>.0083). ConclusionAlthough 12.5%-dose MBIR images (mean size-specific dose estimates [SSDE] of 1.13mGy) yielded objective image noise and SNR comparable to CD-FBP images, at least a 50% dose (mean SSDE of 4.63mGy) would be needed to maintain the subjective image quality and the lesion conspicuity.

Assessment of Filtered Back Projection, Adaptive Statistical, and Model-Based Iterative Reconstruction for Reduced Dose Abdominal Computed Tomography.

To compare standard of care and reduced dose (RD) abdominal computed tomography (CT) images reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), model-based iterative reconstruction (MBIR) techniques. In an Institutional Review Board-approved, prospective clinical study, 28 patients (mean age 59 ± 13 years ), undergoing clinically indicated routine abdominal CT on a 64-channel multi-detector CT scanner, gave written informed consent for acquisition of an additional RD (<1 milli-Sievert) abdomen CT series. Sinogram data of RD series were reconstructed with FBP, ASIR, and MBIR and compared with FBP images of standard dose abdomen CT. Two radiologists performed randomized, independent, and blinded comparison for lesion detection, lesion margin, visibility of normal structures, and diagnostic confidence. Mean CT dose index volume was 10 ± 3.4 mGy and 1.3 ± 0.3 mGy for standard and RD CT, respectively. There were 73 "true positive" lesions detected on standard of care CT. Nine lesions (<8 mm in size) were missed on RD abdominal CT images which included liver lesions, liver cysts, kidney cysts, and paracolonic abscess. These lesions were missed regardless of patient size and types of iterative reconstruction techniques used for reconstruction of RD data sets. The visibility of lesion margin was suboptimal in (23/28) patients with RD FBP, (15/28) patients with RD ASIR, and (14/28) patients with RD MBIR compared to standard of care FBP images (P < 0.001). Diagnostic confidence for the assessment of lesions on RD images was suboptimal in most patients regardless of iterative reconstruction techniques. Clinically significant lesions (< 8 mm) can be missed on abdominal CT examinations acquired at a CT dose index volume of 1.3 mGy regardless of patients' size and reconstruction techniques (FBP, ASIR, and MBIR).

Reduced dose of Bacillus Calmette-Guérin versus full dose of Bacillus Calmette-Guérin for non-muscle-invasive bladder cancer after transurethral resection bladder tumor: a meta-analysis of randomized controlled trials

Background Bladder cancer is widely known as the most common malignant tumor in the urinary tract, with 75%-85% of patients suffering from nonmuscle invasive bladder cancer (NMIBC). However, the optimal dose of Bacillus Calmette-Guérin (BCG) remains controversial. The aim of this study was to compare the therapeutic efficacy of full dose (FD) with the reduced dose (RD) of BCG. Methods Randomized controlled trials (RCTs) were selected through the Cochrane Library, PubMed and Embase and were supplemented by hand searching of bibliographies. The end points include overall survival rate, recurrence rate, progression rate and side effects. Results Five RCTs that included a total of 1 473 patients (727 in the reduced dose group vs 746 in the full dose group), with a median follow-up period from 33.5 month to 7.1 year. Disease in 80 of 687 (11.6%) patients assigned to the RD group progress to the muscular layer or distant metastasis, compared with 81 of 698 (11.6%) patients assigned to the FD group (RR=1.02; 95% CI, 0.77–1.36; P=0.89). The incidence of recurrence at three year was reported in all five studies to be 41.1% (299 of 727) and 36.1% (269 of 746) in the RD and FD groups, respectively (RR=1.13; 95% CI, 1.00–1.29; P=0.05). The 5-year survival rate was 75.9% (502 of 662) in the RD group, and 75.8% (510 of 673) in the FD group. In the RD group 41 of 655 (6.3%) patients and 56 of 663 (8.7%) patients in the FD group did not complete the treatment due to systemic or local side effects (RR=0.75; 95% CI, 0.51–1.10; P=0.14) Conclusions In general, the results of our study demonstrate a trend towards a reduction of the toxicity in reduced dose group without affecting the efficacy of treatment when compared with full dose. More trials with large sample size are still necessary to explore the prognosis of the patients with high risk of tumor in different dose group.

Ultra-low dose abdominal MDCT: Using a knowledge-based Iterative Model Reconstruction technique for substantial dose reduction in a prospective clinical study

PurposeTo assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reconstruction (IMR) in reduced dose (RD) abdominal CT examinations. Materials and methodsThis IRB-approved prospective study included 82 abdominal CT examinations performed for 41 consecutive patients (mean age, 62±12 years; F:M 28:13) who underwent a RD CT (SSDE, 1.5mGy±0.4 [∼0.9mSv] at 120kV with 17–20mAs/slice) immediately after their standard dose (SD) CT exam (10mGy±3 [∼6mSv] at 120kV with automatic exposure control) on 256 MDCT (iCT, Philips Healthcare). SD data were reconstructed using filtered back projection (FBP). RD data were reconstructed with FBP and IMR. Four radiologists used a five-point scale (1=image quality better than SD CT to 5=image quality unacceptable) to assess both subjective image quality and artifacts. Lesions were first detected on RD FBP images. RD IMR and RD FBP images were then compared side-by-side to SD-FBP images in an independent, randomized and blinded fashion. Friedman's test and intraclass correlation coefficient were used for data analysis. Objective measurements included image noise and attenuation as well as noise spectral density (NSD) curves to assess the noise in frequency domain were obtained. In addition, a low-contrast phantom study was performed. ResultsAll true lesions (ranging from 32 to 55) on SD FBP images were detected on RD IMR images across all patients. RD FBP images were unacceptable for subjective image quality. Subjective ratings showed acceptable image quality for IMR for organ margins, soft-tissue structures, and retroperitoneal lymphadenopathy, compared to RD FBP in patients with a BMI ≤25kg/m2 (median-range, 2–3). Irrespective of patient BMI, subjective ratings for hepatic/renal cysts, stones and colonic diverticula were significantly better with RD IMR images (P<0.01). Objective image noise for RD FBP was 57–66% higher, and for RD IMR was 8–56% lower than that for SD-FBP (P<0.01). NSD showed significantly lower noise in the frequency domain with IMR in all patients compared to FBP. ConclusionIMR considerably improved both objective and subjective image quality parameters of RD abdominal CT images compared to FBP in patients with BMI less than or equal to 25kg/m2.

Less is better? Intraindividual and interindividual comparison between 0.075 mmol/kg of gadobenate dimeglumine and 0.1 mmol/kg of gadoterate meglumine for cranial MRI

PurposeTo retrospectively compare a reduced dose (RD) (0.075mmol/kg) of gadobenate dimeglumine (RD-gadobenate) with standard single dose (SSD) (0.1mmol/kg) of gadoterate meglumine (SSD-gadoterate) for cranial MRI. Materials and methodsThirty-one patients (12 males; aged 52±16 years) underwent cranial MRI with SSD-gadoterate and repeated the examination with RD-gadobenate after a median interval of 10 months. Signal-to-noise ratio (SNR) was obtained on contrast-enhanced images for enhancing lesions (n=10) as well as for right and left transverse venous sinuses, internal carotid arteries, and parotid glands. Moreover, a consecutive series of 100 cranial MRI with SSD-gadoterate (49 males; aged 51±19 years) was compared with a consecutive series of 100 cranial MRI with RD-gadobenate (45 males; aged 54±18 years). Two blinded neuroradiologists (R1, R2) judged contrast enhancement as sufficient, good, or optimal. Wilcoxon, Mann–Whitney, χ2, and Cohen κ statistics were used. ResultsAt intraindividual analysis, median SNR ranged 57–88 for SSD-gadoterate and 79–99 for RD-gadobenate, the latter being systematically higher, the difference being significant for both transverse venous sinuses (p≤0.011), not significant for both internal carotid arteries and both parotid glands, and enhancing lesions (p≤0.101). The two series of interindividual analysis were not significantly different for gender/age (p>0.415). Contrast enhancement was optimal in 59% (R1) and 76% (R2) of patients using RD-gadobenate, in 39% (R1) and 49% (R2) of patients using SSD-gadoterate (p≤0.016), with substantial reproducibility (κ≥0.606). ConclusionBoth analyses showed an equal or better contrast enhancement when using RD-gadobenate compared to SSD-gadoterate for routine cranial MRI. The high relaxivity of gadobenate allowed for a 25% dose reduction.

Hybrid iterative reconstruction algorithm in brain CT: a radiation dose reduction and image quality assessment study

Iterative reconstruction (IR) algorithms improve image quality and allow for radiation dose reduction in CT. Dose reduction is particularly challenging in brain CT where good low-contrast resolution is essential. Ideally, evaluation of image quality combines objective measurements and subjective assessment of clinically relevant quality criteria. Subjective assessment is associated with various pitfalls and biases. To evaluate the potential of the hybrid IR algorithm iDOSE(4) to preserve image quality in phantom and clinical brain CT acquired with 30% reduced radiation dose, and to discuss the image quality assessment methods. Forty patients underwent two consecutive brain CTs with normal radiation dose (ND) and 30% reduced dose (RD). Both ND and RD were reconstructed with FBP. In addition the reduced dose CTs were reconstructed with two levels of IR (ID2, ID4). Three image quality criteria (grey-white-matter discrimination, basal ganglia delineation, general image quality) were graded and ranked by six neuroradiologists. Noise levels and contrast-to-noise ratios (CNR) were measured in clinical data. Noise, signal-to-noise ratio (SNR), spatial resolution, and noise-power spectrum (NPS) were also assessed in a phantom. Subjective image quality was considered adequate for clinical use for all reconstructions, graded good or excellent in 93% of cases for ND, 83% for ID4, 79% for ID2, and 67% for RD. For all quality parameters, ID4 and ID2 were graded better than RD (P < 0.0055 and P < 0.035), but worse than ND (P < 0.001). In clinical images, objective measurements showed lower noise and significantly higher CNR in ID4 compared with ND and RD (P < 0.001). CNR was similar for ID2 and ND. In the phantom, IR reduced noise while maintaining spatial resolution and NPS. The IR algorithm improves image quality of reduced dose CTs and consistently delivers sufficient image quality for clinical purposes. Pitfalls related to subjective assessment can be addressed with careful study design.

Everolimus is associated with a reduced incidence of cytomegalovirus infection following de novo cardiac transplantation

Cytomegalovirus (CMV) causes several complications following cardiac transplantation including cardiac allograft vasculopathy. Previous studies suggested that immunosuppressive treatment based on everolimus might reduce CMV infection. Aiming to better characterize the action of everolimus on CMV and its interplay with patient/recipient serology and anti-CMV prophylaxis, we analyzed data from 3 large randomized studies comparing various everolimus regimens with azathioprine (AZA)- and mycophenolate mofetil (MMF)-based regimens. CMV data were analyzed from 1009 patients in 3 trials of de novo cardiac transplant recipients who were randomized to everolimus 1.5mg/day, everolimus 3mg/day, or AZA 1-3mg/kg/day, plus standard-dose (SD) cyclosporine (CsA; study B253, n=634); everolimus 1.5mg/day plus SD- or reduced-dose (RD)-CsA (study A2403, n=199); and everolimus 1.5mg/day plus RD-CsA or MMF plus SD-CsA (study A2411, n=176). In study B253, patients allocated to everolimus experienced almost a 70% reduction in odds of experiencing CMV infection compared with AZA (P<0.001). In study A2403, CMV infection was low in both everolimus arms, irrespective of CsA dosing, and in study A2411, patients allocated to everolimus experienced an 80% reduction in odds of experiencing CMV infection, compared with MMF (P<0.001). CMV syndrome/disease was rare and less frequent in everolimus-treated patients. Subgroup analyses showed that the benefit everolimus provides, in terms of CMV events, is retained in CMV-naïve recipients and is independent of anti-CMV prophylaxis or preemptive approaches. Everolimus is associated with a lower incidence of CMV infection compared with AZA and MMF, which combined with its immunosuppressive efficacy and antiproliferative effects may positively impact long-term outcomes.

Addition of rituximab to reduced-dose CHOP chemotherapy is feasible for elderly patients with diffuse large B-cell lymphoma

The aim of this study was to evaluate the efficacy and toxicity of reduced-dose (RD) RCHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy for elderly patients with diffuse large B-cell lymphoma (DLBCL). This study comprised 85 patients, aged ≥ 60 years, who were diagnosed with DLBCL; patients were enrolled at a single center between June 2004 and December 2009. Patients received either 6 or 8 cycles of RD-RCHOP, spaced 3 weeks apart, at the physician's discretion. The RD-RCHOP regimen consisted of 375 mg/m(2) rituximab, 600 mg/m(2) cyclophosphamide, 30 mg/m(2) doxorubicin, and 1-mg vincristine on day 1 of each cycle, and 40-mg prednisone on days 1-5. The patients received granulocyte colony-stimulating factor if they experienced grade 4 neutropenia or febrile neutropenia during any cycle. The average relative dose intensity was 97.3% for doxorubicin and 97.4% for cyclophosphamide. The complete remission (CR) and overall response rate were 67.1 and 89.5%, respectively. The 3-year event-free survival and overall survival rates were 71.9% ± 5.1% and 83.3% ± 5.1%. By using multivariate analyses, we determined that C-reactive protein levels greater than 1.31 mg/dl and the absence of CR were poor prognostic factors. Grade 3 or 4 neutropenia occurred in 35.3% of patients, and febrile neutropenia occurred in only 3 (3.5%) patients. RD-RCHOP chemotherapy is well tolerated and effective in elderly patients with DLBCL.

Improved tolerance of primary chemotherapy with reduced-dose carboplatin and paclitaxel in elderly ovarian cancer patients

Objective Elderly cancer patients are less likely to tolerate chemotherapy. We sought to compare the toxicity profiles and outcomes of elderly ovarian cancer patients treated with standard versus reduced-dose IV carboplatin/paclitaxel. Methods A retrospective, multi-center analysis of women ≥ 70 years with papillary serous ovarian/primary peritoneal cancers diagnosed from 1994–2005 was performed. Reduced-dose (RD) patients received carboplatin AUC 4–5 and paclitaxel 135 mg/m 2; standard-dose (SD) patients received carboplatin AUC 5–6 and paclitaxel 175 mg/m 2. Patient variables collected included age, stage, performance status (PS), cytoreductive status, Charlson comorbidity scores, and growth factor administration. Results One-hundred patients met the study criteria. RD patients ( n = 26) were significantly older than SD patients ( n = 74; median age 77.0 versus 74.7, respectively, p = 0.014). No differences were noted in stage, comorbidity scores, cytoreductive status or growth factor administration between cohorts. Incidence of grade 3–4 neutropenia was higher in the SD group (54.1% versus 19.2%; p = 0.002). SD patients were more likely to experience cumulative toxicity ( p = 0.003) and required delays in therapy ( p = 0.05). Although PS was poorer in SD patients ( p = 0.02), on multivariate analysis, only the administration of the SD regimen predicted toxicity ( p = 0.008). There were no differences in progression-free or overall survival between cohorts (median follow-up: 34 months). On multivariate analysis, age ( p = 0.004) and PS ( p = 0.008) had a significant impact on survival. Conclusion(s) This preliminary data suggests that reduced-dose carboplatin/paclitaxel may be better tolerated but equally effective as the standard regimen in elderly ovarian cancer patients. Age, performance status and other geriatric parameters should be considered when dosing chemotherapy in the elderly.

Reduced dose OKT3 prophylaxis in sensitised kidney recipients

Abstract Prophylactic use of the monoclonal antibody OKT3 has been studied for the prevention of rejection in sensitised renal transplant recipients. Patients receiving a full dose (FD) regimen were compared to a subsequent consecutive group of patients receiving a reduced dose (RD) regimen. The characteristics of the two groups were not significantly different with regard to age, HLA mismatch and panel-reactive antibody (PRA) status. The number of days that OKT3 was given was 12.9 ± 1.8 for the FD regimen and 11.3 ± 2.8 for the RD regimen. The total dose of OKT3 given was 64.4 ± 9 mg (FD) and 38.3 ± 8.5 mg (RD). Patient survival at 12 months was 8/8 for FD and 17/17 for RD. Graft survival at 12 months was 7/8 for FD and 17/17 for RD. Creatinine at 24 months was 185 ± 68 and 201 ± 81 µmol/l for FD and RD, respectively. A reduced dose regimen of OKT3 produced excellent and comparable results to the standard recommended full-dose regimen. The cost per patient was reduced 40 % from £5676 for FD to £3344 for RD.