Impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion in patients with suspected stroke.

PURPOSE: CT perfusion of the brain is a powerful tool in stroke imaging, though the radiation dose is rather high. Several strategies for dose reduction have been proposed, including increasing the intervals between the dynamic scans. We determined the impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion from a large dataset of patients with suspected stroke. METHODS: We retrospectively included 3555 perfusion scans from our clinical routine dataset. All cases were processed using the perfusion software VEOcore with a standard sampling of 1.5 s, as well as simulated reduced temporal resolution of 3.0, 4.5, and 6.0 s by leaving out respective time points. The resulting perfusion maps and calculated volumes of infarct core and mismatch were compared quantitatively. Finally, hypothetical decisions for mechanical thrombectomy following the DEFUSE-3 criteria were compared. RESULTS: The agreement between calculated volumes for core (ICC = 0.99, 0.99, and 0.98) and hypoperfusion (ICC = 0.99, 0.99, and 0.97) was excellent for all temporal sampling schemes. Of the 1226 cases with vascular occlusion, 14 (1%) for 3.0 s sampling, 23 (2%) for 4.5 s sampling, and 63 (5%) for 6.0 s sampling would have been treated differently if the DEFUSE-3 criteria had been applied. Reduction of temporal resolution to 3.0 s, 4.5 s, and 6.0 s reduced the radiation dose by a factor of 2, 3, or 4. CONCLUSION: Reducing the temporal sampling of brain perfusion CT has only a minor impact on image quality and treatment decision, but significantly reduces the radiation dose to that of standard non-contrast CT.

Predictive factors for dose reduction and discontinuation of nintedanib in fibrotic interstitial lung diseases: Real life data.

Nintedanib, an intracellular inhibitor targeting multiple tyrosine kinases, has emerged as a standard treatment for various fibrotic lung diseases. Despite its efficacy, side effects such as nausea, diarrhea, and hepatotoxicity often lead to dose reduction or discontinuation. In this retrospective analysis at an university hospital's interstitial lung disease clinic, we aimed to identify baseline characteristics associated with dose adjustment or treatment discontinuation. Of the 58 patients included, 41.4% maintained the full nintedanib dose, while 31.0% required dosage reduction, and 27.6% discontinued treatment due to adverse events, predominantly gastrointestinal and hepatotoxic effects. Multivariate analysis revealed body surface area (BSA) as an independent and significant baseline risk factor (adjusted Odds Ratio [aOR] 0.22), suggesting a 78% decreased chance of requiring dose modification for every decimal point increase in BSA. A BSA cutoff of ≤1.73 m [2] exhibited a sensitivity of 73% and specificity of 91.7%, with significant impact on one-year survival under full-dose treatment (p < 0.001). Lower BSA was associated with early onset adverse effects, particularly gastrointestinal, supporting the need for regular clinical monitoring. The study emphasizes the importance of recognizing baseline factors to ensure the safety and tolerability of nintedanib, thereby preventing the progression of pulmonary fibrosis. These findings contribute to the evolving understanding of nintedanib management in fibrotic interstitial lung diseases, guiding clinicians in personalized treatment approaches.

Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study.

BACKGROUND: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. AIMS: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. METHODS: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. RESULTS: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m2, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m2, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. CONCLUSION: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m2, which are achieved by smaller dose reductions.

Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose in young women aged 15-20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials.

BACKGROUND: The first randomised controlled trial of single-dose human papillomavirus (HPV) vaccine efficacy, the Kenya single-dose HPV-vaccine efficacy (KEN SHE) trial, showed greater than 97% efficacy against persistent HPV16 and HPV18 infection at 36 months among women in Kenya. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), the first randomised trial of the single- dose regimen in girls aged 9-14 years, the target age range for vaccination, with those after one dose of the same vaccine in KEN SHE. METHODS: In the DoRIS trial, 930 girls aged 9-14 years in Tanzania were randomly assigned to one, two, or three doses of the 2-valent vaccine (Cervarix) or the 9-valent vaccine (Gardasil-9). The proportion seroconverting and geometric mean concentrations (GMCs) at month 24 after one dose were compared with those in women aged 15-20 years who were randomly assigned to one dose of the same vaccines at the same timepoint in KEN SHE. Batched samples were tested together by virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial:KEN SHE) was predefined as a lower bound of the 95% CI less than 0·50. FINDINGS: Month 24 HPV16 and HPV18 antibody GMCs in DoRIS were similar or higher than those in KEN SHE. 2-valent GMC ratios were 0·90 (95% CI 0·72-1·14) for HPV16 and 1·02 (0·78-1·33) for HPV18. 9-valent GMC ratios were 1·44 (95% CI 1·14-1·82) and 1·47 (1·13-1·90), respectively. Non-inferiority of antibody GMCs and seropositivity was met for HPV16 and HPV18 for both vaccines. INTERPRETATION: HPV16 and HPV18 immune responses in young girls 24 months after a single dose of 2-valent or 9-valent HPV vaccine were comparable to those in young women who were randomly assigned to a single dose of the same vaccines and in whom efficacy had been shown. A single dose of HPV vaccine, when given to girls in the target age range for vaccination, induces immune responses that could be effective against persistent HPV16 and HPV18 infection at least two years after vaccination. FUNDING: The UK Department of Health and Social Care, the Foreign, Commonwealth, & Development Office, the Global Challenges Research Fund, the UK Medical Research Council and Wellcome Trust Joint Global Health Trials scheme, the Bill and Melinda Gates Foundation, the US National Cancer Institute; the US National Institutes of Health, and the Francis and Dorothea Reed Endowed Chair in Infectious Diseases. TRANSLATION: For the KiSwahili translation of the abstract see Supplementary Materials section.

Primary Treatment Modification and Treatment Tolerability Among Older Chemotherapy Recipients With Advanced Cancer.

Importance: Older adults with advanced cancer are less likely to tolerate treatment with cytotoxic chemotherapy compared with younger patients due to their aging-related conditions. Hence, oncologists sometimes opt to employ primary treatment modifications (deviation from standard of care) during the first cycle of chemotherapy. Objective: To examine the association between primary treatment modification and treatment tolerability in older adults with advanced cancer who were starting new palliative chemotherapy regimens. Design, Setting, and Participants: This cohort study was a secondary analysis of the GAP70+ (Geriatric Assessment Intervention for Reducing Toxicity in Older Patients with Advanced Cancer) trial, which was conducted between July 2014 and March 2019. The GAP70+ trial included patients aged 70 years or older who had advanced (ie, incurable) cancer, had 1 or more geriatric assessment domain impairments, and planned to start a new palliative chemotherapy regimen. Data analysis was conducted in November 2022. Exposures: Receipt of standard-of-care chemotherapy regimens vs primary treatment modification defined as any change from National Comprehensive Cancer Network guidelines or published clinical trials (eg, primary dose reduction, schedule change). Main Outcomes and Measures: Tolerability outcomes were assessed within 3 months of treatment. These outcomes included the following: (1) any grade 3 to 5 toxic effect, according to the National Cancer Institute Common Terminology Criteria for Adverse Events; (2) patient-reported functional decline, defined as the development of worse dependency in activities of daily living using scale scores; and (3) a composite adverse outcome (an end point that combined toxic effects, functional decline, and 6-month overall survival). Multivariable cluster-weighted generalized estimating equation models examined the association between primary treatment modification and outcomes adjusting for covariates. Results: This study included 609 patients with a mean (SD) age of 77.2 (5.2) years; more than half (333 [54.7%]) were men. Race and ethnicity was available for 607 patients: 39 (6.4%) were Black, 539 (88.5%) were non-Hispanic White, and 29 (4.8%) were of other race or ethnicity. Nearly half (281 [46.1%]) received a primary modified treatment regimen. The most common cancer types were gastrointestinal cancer (228 [37.4%]) and lung cancer (174 [28.6%]). In multivariable analysis, primary treatment modification was associated with a reduced risk of grade 3 to 5 toxic effects (relative risk [RR], 0.85 [95% CI, 0.77-0.94]) and functional decline (RR, 0.80 [95% CI, 0.67-0.95]). Patients who received primary treatment modification had 32.0% lower odds of having a worse composite adverse outcome (odds ratio, 0.68 [95% CI, 0.48-0.97]). Conclusions and Relevance: In this cohort study, primary treatment modification was associated with improved tolerability of chemotherapeutic regimens among older adults with advanced cancer and aging-related conditions. These findings may help optimize cancer treatment dosing in older adults with advanced cancer and aging-related conditions.

Implementing a coronary CT angiography protocol based on the body mass index: Radiation dose reduction, image quality, and diagnostic performance.

OBJECTIVES: To evaluate the relation between the coronary calcium score and the posterior choice of kilovoltage according to radiologists' criteria in a standard coronary CT angiography protocol to rule out coronary disease. To quantify the reduction in ionizing radiation after linking kilovoltage to patients' body mass index in a low-dose protocol with iterative model reconstruction. To evaluate the image quality and diagnostic performance of the low-dose protocol. MATERIAL AND METHODS: We compared anthropometric characteristics, calcium score, kilovoltage levels, size-specific dose estimates (SSDE), and the dose-length product (DLP) between a group of 50 patients who were prospectively recruited to undergo coronary CT angiography with a low-dose protocol and a historical group of 50 patients who underwent coronary CT angiography with the standard protocol. We correlated these parameters, the number of coronary segments that could not be evaluated with and without temporal padding, the attenuation, and the signal-to-noise ratio in the ascending aorta in the low-dose protocol with excellent imaging quality according to a semiquantitative scale. To calculate the diagnostic performance per patient, we used 24-month clinical follow-up including all tests as the gold standard. RESULTS: In the standard protocol, the presence of coronary calcium correlated with the selection of high kilovoltage (p = 0.02); this correlation was not found in the low-dose protocol (p = 0.47). Median values of SSDE and DLP were significantly (p < 0.001) lower and less dispersed in the low-dose protocol [9.22 mGy (IQR 7.84-12.1 mGy) vs. 26.5 mGy (IQR 21.3-36.3 mGy) in the standard protocol] and [97 mGy cm (IQR 78-134 mGy cm) vs. 253 mGy cm (IQR 216-404 mGy cm) in the standard protocol], respectively. The overall quality of the images obtained with the low-dose protocol was considered good or excellent in 96% of the studies. The parameters associated with image quality in a multivariable model (C statistic = 0.792) were heart rate (estimated coefficient, -0,12 [95% confidence interval: -0.2, -0.04]; p < 0.01) and the SSDE (estimated coefficient, -0,26 [95% confidence interval: -0.51, -0.01]; p < 0.05). The CAD-RADS modifier for a not fully evaluable or diagnostic study was used on two occasions (4%); the final measures for the diagnosis of coronary disease were sensitivity 100%, specificity 94%, and efficacy 94%. CONCLUSIONS: In the standard protocol, the radiologist selects higher kilovoltage for CT angiography studies for patients whose previous calcium score indicates the presence of coronary calcium. In the low-dose protocol, linking kilovoltage with body mass index enables the dose of radiation to be reduced by 65% while obtaining excellent or good image quality in 96% of studies and excellent diagnostic performance.

Off-isocentric VMAT technique for breast cancer: Effective dose reduction to organs at risk and its applicability based on patient anatomy.

PURPOSE: This study aims to explore the off-isocentric volumetric modulated arc therapy (offVMAT) technique for breast cancer and determine its applicability based on patient anatomical parameters. METHODS: We retrospectively analyzed 44 breast cancer patients with varied lymph node involvement using different arc designs. Off-isocentric techniques were benchmarked against previously published arc techniques: classic arcs (clVMAT), tangential arcs (tVMAT), and split arcs (spVMAT). During optimization, target coverage was made for all plans as close as possible to the criteria D99% > 95% and Dmax < 110% of the prescribed dose. A novel patient categorization, based on anatomical parameters (auxiliary structures) rather than lymph node involvement, is introduced. This categorization considers the volume of ipsilateral organs at risk (OARs) adjacent to the target. A binary regression model was developed on these anatomical parameters. It predicts the likelihood of offVMAT (P[offVMAT]) achieving better criteria. RESULTS: Using the regression model, patients were divided into two groups: P(offVMAT) > 0.5 and P(offVMAT) < 0.5. For the P(offVMAT) > 0.5 group, most tVMAT plans are unable to achieve the clinical objectives. Comparing offVMAT with spVMAT, offVMAT exhibited better dose parameters for the heart (V20, V10, and D2 are 7.1, 2.4, and 1.5 times lower respectively), ipsilateral lung (V20, V10, V5 and the mean dose are 1.4, 1.3, 1.2, and 1.2 times lower respectively). The average doses to the contralateral side are consistent. In the P(offVMAT) < 0.5 group, the tVMAT technique showed increased doses at medium and high levels, yet reduced doses in contralateral OARs compared to spVMAT and offVMAT. spVMAT showed lower doses in the contralateral lung relative to the offVMAT technique, while clVMAT trailed in both groups. Validation of the model yielded a 90% accuracy rate. CONCLUSIONS: The new off-isocentric breast planning technique effectively reduces doses to ipsilateral OARs, maintaining acceptable contralateral mean doses. This technique has an advantage over other techniques for patients with intricate anatomies. It is evaluated using anatomical parameters, which are also used to build binary regression model, which shows the dependence of anatomical parameters on whether offVMAT is preferred for individual patients. Also, such anatomical parameters provide a more objective and precise comparison between different planning techniques.

The boundary of posterior to level V region and the theoretical feasibility of irradiation dose reduction of level Va in nasopharyngeal carcinoma.

The lymph node involvement in the posterior to level V (PLV) region is mainly observed in nasopharyngeal carcinoma (NPC). Recently, we have reported the distribution of metastatic lymph nodes in the PLV region and there are correlations between the neck node levels (NNL) of NPC, but what is the boundary of the PLV region and how to delineate it remains unclear, and we further to elaborate whether the bilateral level Va should be covered as intermediate-risk nodal regions (CTVn2, about 60 Gy equivalent) for all T and N categories based on these correlations. A total of 1021 consecutive NPC patients with N1-3 stage from January 2012 to December 2020 were reviewed. The lymph node metastasis level of each patient was evaluated according to the updated guidelines proposed in 2013. According to the distribution pattern of lymph node metastasis and the anatomical structure in the PLV region, the boundaries of PLV region was delineated, and whether it is appropriate to cover the bilateral level Va as CTVn2 for all the NPC patients was further discussed. The correlations of level Va with other NNL were studied using logistic regression model. The cranial boundary of PLV region is the caudal border of cricoid cartilage, the caudal boundary is the plane serratus anterior muscle begins to appear, the anterior boundary is the anterior border of trapezius, and the posterior boundary is the convergence of levator scapulae and trapezius. Laterally, the PLV region is limited by the medial edge of trapezius and medially by the lateral surface of levator scapulae. The nodal spread in level Va is based on the lymph node metastasis of level IIb in NPC. The PLV region is a missing NNL of head and neck tumors, especially in NPC. The proposed boundaries of the PLV region can provide a preliminary proposal for the further revision of NNL in head and neck tumors. It is theoretically feasible to reduce the prophylactic irradiation dose of the bilateral level Va in patients with N0 stage or with isolated metastases in level VIIa.

CT image denoising methods for image quality improvement and radiation dose reduction.

With the ever-increasing use of computed tomography (CT), concerns about its radiation dose have become a significant public issue. To address the need for radiation dose reduction, CT denoising methods have been widely investigated and applied in low-dose CT images. Numerous noise reduction algorithms have emerged, such as iterative reconstruction and most recently, deep learning (DL)-based approaches. Given the rapid advancements in Artificial Intelligence techniques, we recognize the need for a comprehensive review that emphasizes the most recently developed methods. Hence, we have performed a thorough analysis of existing literature to provide such a review. Beyond directly comparing the performance, we focus on pivotal aspects, including model training, validation, testing, generalizability, vulnerability, and evaluation methods. This review is expected to raise awareness of the various facets involved in CT image denoising and the specific challenges in developing DL-based models.

Early recapture of response with tofacitinib 10 mg twice daily in patients with ulcerative colitis in OCTAVE Open following dose reduction or treatment interruption in OCTAVE Sustain.

BACKGROUND AND AIM: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis. These post hoc analyses evaluated early improvement in patient-reported outcomes with tofacitinib 10 mg twice daily (BID) in OCTAVE Open among patients with ulcerative colitis who experienced treatment failure with placebo (retreatment subpopulation) or tofacitinib 5 mg BID (dose escalation subpopulation) during maintenance. METHODS: Endpoints based on Mayo subscores (rectal bleeding improvement, stool frequency improvement, and symptomatic [both rectal bleeding and stool frequency] improvement) were analyzed overall and by prior tumor necrosis factor inhibitor (TNFi) failure status from month (M)1-M6 in OCTAVE Open. Changes from baseline in partial Mayo score, rectal bleeding subscore, and stool frequency subscore at M1 were also analyzed, by M2 clinical response status. RESULTS: At M1 of OCTAVE Open, 83.2%, 70.3%, and 64.4% of patients in the retreatment subpopulation (n = 101) had rectal bleeding improvement, stool frequency improvement, and symptomatic improvement, respectively. Corresponding values in the dose escalation subpopulation (n = 57) were 59.6%, 50.9%, and 38.6%. For both subpopulations, results were generally consistent regardless of prior TNFi failure. In the dose escalation subpopulation, mean decrease from baseline in partial Mayo score and stool frequency subscore at M1 was greater in patients with versus without a clinical response at M2. CONCLUSIONS: Rectal bleeding improvement and stool frequency improvement were achieved by M1 in many patients receiving tofacitinib 10 mg BID in both subpopulations, with no apparent difference by prior TNFi failure. Analyses were limited by small sample sizes for some subgroups.

Assessment of breast cancer chemotherapy dose reduction in an integrated healthcare delivery system.

PURPOSE: Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear. METHODS: In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy. RESULTS: Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years. CONCLUSION: Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women.

Dosimetric impact of adding non-coplanar arcs for scalp-avoidance whole-brain irradiation with volumetric-modulated arc radiotherapy on scalp dose reduction in pediatric patients with medulloblastomas.

PURPOSE: We performed scalp-avoidance whole-brain irradiation with volumetric-modulated arc therapy (SAWB-VMAT) as a component of craniospinal irradiation. In SAWB-VMAT with two coplanar arcs, radiation oncologists and medical physicists sometimes experience difficulty in reducing the dose to the scalp to below the cut-off equivalent dose in 2 Gy per fraction (assuming α/ß = 2) to 50% (EQD50%scalp ). To investigate the advantage of adding coplanar or non-coplanar arcs in reducing the dose to the scalp in SAWB-VMAT, we conducted a planning study to compare the EQD50%scalp , the dose to other organs at risk (OARs), and target coverage in VMAT with two coplanar arcs (Co2arcVMAT), VMAT with three coplanar arcs (Co3arcVMAT), and VMAT with two coplanar and two non-coplanar arcs (NcVMAT). METHODS: Co2arcVMAT, Co3arcVMAT, and NcVMAT plans were created for 10 pediatric patients with medulloblastoma. The planned target volume (PTV) included the regions of the whole brain, cervical spinal cord, cerebrospinal fluid space, and intervertebral foramen. The EQD50%scalp was evaluated separately for four areas (top, back, left, and right) in each case. The prescribed dose for the PTV was 35.2 Gy in 22 fractions. RESULTS: The median EQD50%scalp of the top area was 21.9 , 22.1 , and 18.3 Gy for Co2arcVMAT, Co3arcVMAT, and NcVMAT, respectively. The EQD50%scalp of the top area was significantly reduced in NcVMAT compared to those in Co2arcVMAT and Co3arcVMAT (p < 0.05). The median EQD50%scalp of the top area for NcVMAT was < 19.9 Gy, which is the cut-off dose for severe permanent alopecia. There were no significant differences in EQD50%scalp in the three other areas, the dose to other OARs, or the dose coverage of PTV among the three techniques. CONCLUSION: NcVMAT could reduce the EQD50%scalp of the top area below the cut-off dose of 19.9 Gy. NcVMAT appears to be a promising treatment technique for SAWB-VMAT.

Factors Associated With Cardiac Radiation Dose Reduction After Hypofractionated Radiation Therapy for Localized, Left-Sided Breast Cancer in a Large Statewide Quality Consortium.

PURPOSE: Limiting cardiac radiation dose is important for minimizing long-term cardiac toxicity in patients with left-sided early-stage breast cancer. METHODS AND MATERIALS: Prospectively collected dosimetric data were analyzed for patients undergoing moderately hypofractionated radiation therapy to the left breast within the Michigan Radiation Oncology Quality Consortium from 2016 to 2022. The mean heart dose (MHD) goal was progressively tightened from ≤2 Gy in 2016 to MHD ≤ 1.2 Gy in 2018. In 2021, a planning target volume (PTV) coverage goal was added, and the goal MHD was reduced to ≤1 Gy. Multivariate logistic regression models were developed to assess for covariates associated with meeting the MHD goals in 2016 to 2020 and the combined MHD/PTV coverage goal in 2021 to 2022. RESULTS: In total, 4165 patients were analyzed with a median age of 64 years. Overall average cardiac metric compliance was 91.7%. Utilization of motion management increased from 41.8% in 2016 to 2020 to 46.5% in 2021 to 2022. Similarly, use of prone positioning increased from 12.2% to 22.2% in these periods. On multivariate analysis in the 2016 to 2020 cohort, treatment with motion management (odds ratio [OR], 5.20; 95% CI, 3.59-7.54; P < .0001) or prone positioning (OR, 3.21; 95% CI, 1.85-5.57; P < .0001) was associated with meeting the MHD goal, while receipt of boost (OR, 0.25; 95% CI, 0.17-0.39; P < .0001) and omission of hormone therapy (OR, 0.65; 95% CI, 0.49-0.88; P = .0047) were associated with not meeting the MHD goal. From 2021 to 2022, treatment with motion management (OR, 1.89; 95% CI, 1.12-3.21; P = .018) or prone positioning (OR, 3.71; 95% CI, 1.73-7.95; P = .0008) was associated with meeting the combined MHD/PTV goal, while larger breast volume (≥1440 cc; OR, 0.34; 95% CI, 0.13-0.91; P = .031) was associated with not meeting the combined goal. CONCLUSIONS: In our statewide consortium, high rates of compliance with aggressive targets for limiting cardiac dose were achievable without sacrificing target coverage.

Feasibility and outcomes after dose reduction of immunochemotherapy in young adults with Burkitt lymphoma and leukemia: results of the BURKIMAB14 trial.

High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).

Effect of nicotine expectancy and nicotine dose reduction on cigarette demand, withdrawal alleviation, and puff topography.

BACKGROUND: Current FDA plans include proposed nicotine reduction mandates by the end of 2023. Most research on reduced nicotine cigarettes has been dose-blinded, while a mandate would be known to the public. Few laboratory studies have examined specifically how low nicotine content labeling impacts behavioral response. The purpose of this within-subject, balanced-placebo, human laboratory study was to evaluate the main and interactive effects of nicotine dose expectancy and dose reduction on cigarette reinforcement, withdrawal alleviation, and puff topography. METHODS: Participants who smoke daily (N=21; 9 female) completed one practice and four experimental sessions in which expectancy (labeled "average" versus "very low" nicotine) and nicotine dose (0.80mg versus 0.03mg yield) were manipulated. Participants in acute withdrawal sampled experimental cigarettes followed by withdrawal alleviation and puff topography measures. Cigarette demand was measured using an incentivized purchase task. Analyses evaluated main and interactive effects of expectancy and nicotine dose. RESULTS: Nicotine dose manipulation produced expected physiological effects (e.g., heart rate increases) and both reduced nicotine dose and expectation manipulations reduced perceived nicotine content. Expectation of reduced nicotine alone or in combination with reduced nicotine dose did not alter demand, withdrawal alleviation, or topography. Effective withdrawal alleviation was observed in all conditions. CONCLUSIONS: These data inform nicotine regulation policy by suggesting limited compensatory harms caused by reduced nicotine expectations. The minimal acute effects of reduced nicotine expectancy or exposure on demand suggests that reduced nicotine standards are likely to generate their greatest public health benefit through the slowing of newly initiating cigarette smoking.

Radiation Dose Reduction in Digital Breast Tomosynthesis by MTANN with Multi-scale Kernels.

Digital breast tomosynthesis (DBT) is an advanced three-dimensional screening modality for the early detection of breast cancer. DBT is able to reduce the problem of tissue overlap in standard two-dimensional mammograms, thus improving the sensitivity and specificity of cancer detection. Although DBT can improve diagnostic accuracy, it leads to higher radiation dose to patients compared to two-dimensional mammography. In this paper, we propose a novel radiation dose reduction technique that introduces multi-scale kernels to our original massive-training artificial neural network (MTANN) to reduce radiation dose substantially, while maintaining high image quality in DBT. After training our new MTANN with low-dose (LD) images and the corresponding "teaching" high-dose (HD) images, we can convert new LD images to "virtual" high-dose (VHD) images where noise and artifact in the LD images are significantly reduced. In VHD images, it is critical to preserve subtle structures and tiny patterns such as microcalcifications (MCs) which are essential for breast cancer diagnosis. We developed anatomical MTANN experts including an MC-specific expert with multi-scale kernels, which are combined by gating layers to generate whole VHD images. Our MTANN scheme was able to achieve a 79% dose reduction while preserving details of MCs. Experimental results demonstrated that our method achieved the highest performance among the best-known noise-reduction techniques and state-of-the-art deep-learning techniques.Clinical Relevance- Our method can decrease the dose radiation dose in DBT and maintain the image quality.

Potential for Dose Reduction in CT-Derived Left Ventricular Ejection Fraction: A Simulation Study.

BACKGROUND: Measuring left ventricular ejection fraction (LVEF) is important for detecting heart failure, e.g., in treatment with potentially cardiotoxic chemotherapy. MRI is considered the reference standard for LVEF, but availability may be limited and claustrophobia or metal implants still present challenges. CT has been shown to be accurate and would be advantageous, as LVEF could be measured in conjunction with routine chest-abdomen-pelvis oncology CT. However, the use of CT is not recommended due to the excessive radiation dose. This study aimed to explore the potential for dose reduction using simulation. Using an anthropomorphic heart phantom scanned at 13 dose levels, a noise simulation algorithm was developed to introduce controlled Poisson noise. Filtered backprojection parameters were iteratively tested to minimise differences in myocardium-to-ventricle contrast/noise ratio, as well as structural similarity index (SSIM) differences between real and simulated images at all dose levels. Fifty-one clinical CT coronary angiographies, scanned with full dose through end-systolic and -diastolic phases, were located retrospectively. Using the developed algorithm, noise was introduced corresponding to 25, 10, 5 and 2% of the original dose level. LVEF was measured using clinical software (Syngo.via VB50) with papillary muscles in and excluded from the LV volume. At each dose level, LVEF was compared to the 100% dose level, using Bland-Altman analysis. The effective dose was calculated from DLP using a conversion factor of 0.026 mSv/mGycm. RESULTS: In the clinical images, mean CTDIvol and DLP were 47.1 mGy and 771.9 mGycm, respectively (effective dose 20.0 mSv). Measurements with papillary muscles excluded did not exhibit statistically significant LVEF bias to full-dose images at 25, 10 and 5% simulated dose. At 2% dose, a significant bias of 4.4% was found. With papillary muscles included, small but significant biases were found at all simulated dose levels. CONCLUSION: Provided that measurements are performed with papillary muscles excluded from the LV volume, the dose can be reduced by a factor of 20 without significantly affecting LVEF measurements. This corresponds to an effective dose of 1 mSv. CT can potentially be used for LVEF measurement with minimal excessive radiation.

Dose reduction in sequence scanning 4D CT imaging through respiratory signal-guided tube current modulation: A feasibility study.

BACKGROUND: Respiratory signal-guided 4D CT sequence scanning such as the recently introduced Intelligent 4D CT (i4DCT) approach reduces image artifacts compared to conventional 4D CT, especially for irregular breathing. i4DCT selects beam-on periods during scanning such that data sufficiency conditions are fulfilled for each couch position. However, covering entire breathing cycles during beam-on periods leads to redundant projection data and unnecessary dose to the patient during long exhalation phases. PURPOSE: We propose and evaluate the feasibility of respiratory signal-guided dose modulation (i.e., temporary reduction of the CT tube current) to reduce the i4DCT imaging dose while maintaining high projection data coverage for image reconstruction. METHODS: The study is designed as an in-silico feasibility study. Dose down- and up-regulation criteria were defined based on the patients' breathing signals and their representative breathing cycle learned before and during scanning. The evaluation (including an analysis of the impact of the dose modulation criteria parameters) was based on 510 clinical 4D CT breathing curves. Dose reduction was determined as the fraction of the downregulated dose delivery time to the overall beam-on time. Furthermore, under the assumption of a 10-phase 4D CT and amplitude-based reconstruction, beam-on periods were considered negatively affected by dose modulation if the downregulation period covered an entire phase-specific amplitude range for a specific breathing phase (i.e., no appropriate reconstruction of the phase image possible for this specific beam-on period). Corresponding phase-specific amplitude bins are subsequently denoted as compromised bins. RESULTS: Dose modulation resulted in a median dose reduction of 10.4% (lower quartile: 7.4%, upper quartile: 13.8%, maximum: 28.6%; all values corresponding to a default parameterization of the dose modulation criteria). Compromised bins were observed in 1.0% of the beam-on periods (72 / 7370 periods) and affected 10.6% of the curves (54/510 curves). The extent of possible dose modulation depends strongly on the individual breathing patterns and is weakly correlated with the median breathing cycle length (Spearman correlation coefficient 0.22, p < 0.001). Moreover, the fraction of beam-on periods with compromised bins is weakly anti-correlated with the patient's median breathing cycle length (Spearman correlation coefficient -0.24; p < 0.001). Among the curves with the 17% longest average breathing cycles, no negatively affected beam-on periods were observed. CONCLUSION: Respiratory signal-guided dose modulation for i4DCT imaging is feasible and promises to significantly reduce the imaging dose with little impact on projection data coverage. However, the impact on image quality remains to be investigated in a follow-up study.

Impact of Tracer Dose Reduction in [18 F]-Labelled Fluorodeoxyglucose-Positron Emission Tomography ([18 F]-FDG)-PET) on Texture Features and Histogram Indices: A Study in Homogeneous Tissues of Phantom and Patient.

BACKGROUND: Histogram indices (HIs) and texture features (TFs) are considered to play an important role in future oncologic PET-imaging and it is unknown how these indices are affected by changes of tracer doses. A randomized undersampling of PET list mode data enables a simulation of tracer dose reduction. We performed a phantom study to compare HIs/TFs of simulated and measured tracer dose reductions and evaluated changes of HIs/TFs in the liver of patients with PETs from simulated reduced tracer doses. Overall, 42 HIs/TFs were evaluated in a NEMA phantom at measured and simulated doses (stepwise reduction of [18 F] from 100% to 25% of the measured dose). [18 F]-FDG-PET datasets of 15 patients were simulated from 3.0 down to 0.5 MBq/kgBW in intervals of 0.25 MBq/kgBW. HIs/TFs were calculated from two VOIs placed in physiological tissue of the right and left liver lobe and linear correlations and coefficients of variation analysis were performed. RESULTS: All 42 TFs did not differ significantly in measured and simulated doses (p > 0.05). Also, 40 TFs showed the same behaviour over dose reduction regarding differences in the same group (measured or simulated), and for 26 TFs a linear behaviour over dose reduction for measured and simulated doses could be validated. Out of these, 13 TFs could be identified, which showed a linear change in TF value in both the NEMA phantom and patient data and therefore should maintain the same informative value when transferred in a dose reduction setting. Out of this Homogeneity 2, Entropy and Zone size non-uniformity are of special interest because they have been described as preferentially considerable for tumour heterogeneity characterization. CONCLUSIONS: We could show that there was no significant difference of measured and simulated HIs/TFs in the phantom study and most TFs reveal a linear behaviour over dose reduction, when tested in homogeneous tissue. This indicates that texture analysis in PET might be robust to dose modulations.

Dose reduction of olaparib in older patients: Insights from an analysis of a National Database in Japan.

AIM: Although the advent of a poly polymerase inhibitors has greatly advanced the tailoring of cancer treatment, there is a dearth of real-world evidence on the actual use of olaparib in aging populations, especially those using national-level data. METHODS: We extracted and analyzed all prescriptions of olaparib in female outpatients from the National Database Open Data Japan (NDB Open Data) from April 2019 to March 2021. The recommended standard dose of olaparib is four tablets of the 150 mg formulation per day, while the 100 mg formulation of olaparib can be considered as an alternative dose in the occurrence of hematologic toxicity. We calculated the proportion of 100 mg compared to the 150 mg prescriptions across age groups. A Cochrane-Armitage trend test was used to examine the association of age groups with the proportion of 100 mg prescriptions. RESULTS: The total number of prescriptions of the 100 mg formulation and the 150 mg formulation were 1449 222, and 4233 625, respectively. Overall, 45.1% (2567 513/5682 847 prescriptions) of olaparib were prescribed for patients 65 years of age or older in females. Stratified by age group, the proportion of 100 mg compared to the 150 mg prescriptions significantly increased with age (p < 0.0001). CONCLUSIONS: Given that the 100 mg formulation of olaparib can be considered as an alternative dose in Japan in the occurrence of hematologic toxicity, our observations indicate the dose reduction of olaparib in older patients in Japan. Further investigations are necessary to assess its efficacy and safety at a reduced dose.