Reduction In Effective Dose Research Articles

Assessing causality in deprescribing studies: A focus on adverse drug events and adverse drug withdrawal events.

Generating real-world evidence about the effect of medication discontinuation or dose reduction on outcomes, such as reduction of adverse drug effects (ADE; intended benefit) and occurrence of adverse drug withdrawal events (ADWE; unintended harm), is crucial to informing deprescribing decisions. Determining the causal effects of deprescribing is difficult for many reasons, including lack of randomization in real-world study designs and other design and measurement issues that pose threats to internal validity. The inherent challenge is how to identify the effects, both intended benefits and unintended harms, of a new medication stoppage or reduction when implemented in patients with many potential clinical and social risks that may influence the likelihood of deprescribing as well as outcomes. We discuss methodological issues of estimating the effect of medication discontinuation or reduction on risk of ADEs and ADWEs considering: (1) sampling study populations of sufficient size with the potential to demonstrate clinically meaningful and quantifiable outcomes, (2) accurate and appropriately timed measurement of covariates, outcomes, and discontinuation, and (3) statistical approaches to managing confounding and other biases inherent in long-term medication use by individuals with multiple morbidities. Designing rigorous deprescribing studies that address internal validity threats will support evidence generation by improving the ability to assess benefits and harms when the exposure of interest is the absence of a medication. Iterative learnings about data quality, variable definition, variable measurement, and exposure-outcome associations will inform strategies to improve the causal inferences possible in real-world deprescribing studies.

Overall survival after CDK4/6 inhibitor dose reduction in women with metastatic breast cancer

BackgroundBreast cancer is the most common cancer in women, and the first-line treatment for patients with hormone-receptor positive/HER2-negative metastatic breast cancer is CDK4/6 inhibitor plus endocrine therapy. Understanding the impact of CDK4/6 inhibitor dose reduction, which occurs in about half of the patients, is important.MethodsThis real-world cohort study is based on electronic health records from Capital Region of Denmark. All women with metastatic breast cancer initiating first-line treatment with CDK4/6 inhibitor between May 2017 and October 2022 were included.ResultsA total of 546 patients were eligible for inclusion in the 12-week landmark analysis and 192 (35%) experienced dose reduction. These patients were older, had worse ECOG PS, more received prior adjuvant endocrine treatment, and more received fulvestrant as the endocrine backbone. Dose reduction was associated with reduced overall survival (39.9 vs. 54.3 months) and shorter treatment duration (18.0 vs. 26.9 months). Adjusted hazard ratio for death was 1.38 (95% CI: 1.01–1.89).ConclusionsDose reduction of CDK4/6 inhibitors within the first 12 weeks of treatment was associated with significantly higher mortality and shorter treatment duration. These findings contrast with previous analyses showing no effect of dose reduction, likely due to considering immortal time bias in this study.

Comparing organ and effective dose of various CT localizer acquisition strategies: A Monte Carlo study.

CT examinations commonly start with the acquisition of one or two localizer radiographs (2D localizers). Recently, a manufacturer introduced the option to perform a heavily filtrated low-dose helical scan as a localizer acquisition. To compare the dose of one or two 2D localizer acquisitions to the dose of a 3D localizer acquisition, one cannot simply compare the CTDIs of the different acquisition techniques, because of the use of different geometries and spectra. To compare the organ and effective dose for various CT localizer acquisition techniques. A Geant4-based Monte Carlo simulation, replicating a clinical wide-area CT scanner was developed and validated. Various localizer acquisition strategies were simulated: Anterior-posterior (AP) alone, PA alone, combined AP+lateral (LAT), and PA+LAT 2D localizers, and an Ag-filtered 3D localizer acquisition. Validation was performed by measuring and simulating CTDI100 in both the periphery and the center of a CTDI phantom. The software was subsequently used to estimate organ and effective doses for localizers for chest, abdomen+pelvis, and the combined chest, abdomen, and pelvis exams. As representations of patients, eight ICRP computational phantoms (adult, 15-, 10-, and 5-year, both male and female) and five female and five male XCAT phantoms with various BMIs were used. The dose of the various strategies was compared to the current clinically-implemented AP+LAT localizers. CTDI100-measurements and simulations within the CTDI-phantom differs by a maximum of 8.1% and by an average of 0.9%. For chest, the average effective doses for AP, PA, AP+LAT, and the 3D localizer are 0.10, 0.07, 0.32, and 0.22 mSv, respectively. The organ dose to the breast varies the most across the various localizer strategies and is, on average, 0.17, 0.03, 0.44, and 0.33 mGy, in the same order. For abdomen, the average effective doses are 0.11, 0.07, 0.36, and 0.25 mSv for the AP, PA, AP+LAT and the 3D localizer, respectively. The organ dose to the stomach varies the most across the various localizers and is on average 0.14, 0.08, 0.58, and 0.30 mGy, in the same order. The PA-only localizer results in the lowest organ dose to the most radiosensitive organs and the lowest effective dose. For the chest exam, compared to AP+LAT, the PA+LAT results in a 7±2% effective dose reduction (mean±standard deviation), while the 3D localizer results in a 21±3% effective dose reduction. Using AP or PA only would result in 69±2% and 76±2% reduction, respectively. For the abdomen exam, also compared to AP+LAT, PA+LAT results in 6±2% effective dose reduction, while the 3D localizer results in a 20±5% reduction. Using AP or PA only would result in 69±5% and 76±4% reduction, respectively. Using a PA localizer results in a lower or equivalent organ dose in the most radiosensitive organs, and a lower effective dose compared to an AP localizer for both chest and abdomen+pelvis exams. Compared to a two-localizer strategy, the 3D localizer results in a lower effective dose in both the chest and abdomen+pelvis region.

Evaluation of the detector linearity response of the DR system in different x-ray bean filters

In the recent past, at Brazilian radiology services, direct digital radiography (DR) systems are replacing Computed Radiography (CR). This situation provides several significant advantages such as improving digital image quality, patient effective dose reduction, and improved speed of examinations performed. To evaluate DR systems, various organizations have published protocols with guidelines concerning quality assurance and acceptance tests for DRs. In these protocols, there are methodologies for evaluating several parameters, such as the detector linearity response (DLR). To test the DLR, different methodologies are proposed by the organizations, such as the application of different additional filters on the X-ray beams spectrum to promote the X-ray doses suitable to produce the latent image in the DR. The objective of this work was to evaluate the results of different protocol methodologies for carrying out the DLR test of a DR flat panel. An analogic radiology equipment, a primary ionization chamber, a DR system and images unprocessed were used in this study. As indicated by the protocols, the spectra of the X-rays were modified by additional filters of copper (Cu) with aluminum (Al); Al; Cu; and polymethylmethacrylate (PMMA). The spectra of the X-rays were modified to achieve the exposure range of 0.1 to 7 mR. The results showed that the DLR curves adjustment were R²>0.99, for a logarithmic equation, type y=a.ln(x)+b. For the filters of 0.5 mmCu with 1.0 mmAl; 11.5 mmAl; 1.0 mmCu; 21 mmAl the mean pixel values showed 0.9% of the coefficient of variation (COV), while for 10 cm PMMA filters, the COV increased to 2.7%. The study showed that methodologies using Al, Cu and Al with Cu filters DLR have similar responses while using PMMA, the response was slightly different.

Dose-Reduction of Bevacizumab in Atezolizumab plus Bevacizumab Therapy Extends Treatment duration with Disease Control in Patients with Hepatocellular Carcinoma

Introduction: Atezolizumab (ATZ) and bevacizumab (BEV) combination therapy is widely used in patients with unresectable hepatocellular carcinoma (HCC). However, combination therapy is typically interrupted or discontinued owing to BEV-related adverse events. In this study, we examined the effects of BEV dose-reduction on the treatment of unresectable HCC using propensity score matching (PSM). Method: Overall, 119 patients with HCC who were treated with ATZ + BEV between November 2020 and October 2022 were enrolled retrospectively at our institute. The therapeutic effects and safety of BEV dose-reduction and non-dose reduction after PSM were compared. Decision-tree analysis was used to investigate treatment duration in the patients. Results: Significant differences were not observed between the two groups after PSM. The objective response rate (ORR) and disease control rate (DCR) assessed by modified RECIST did not differ significantly between the two groups (BEV non-dose-reduction/dose-reduction: ORR; 46/34%, DCR; 80/91%). Progression-free survival (PFS) and overall survival (OS) also did not differ significantly between the two groups (BEV non-dose-reduction/dose-reduction: PFS; 5.6/8.6 months, OS; 18.6/15.5 months). The median duration of treatment in the BEV dose-reduction group was significantly longer than that in the non-dose-reduction group (BEV non-dose-reduction/dose-reduction: 4.8/9.1 months, p = 0.038). Decision-tree analysis revealed that dose-reduction of BEV was the first distinguish factor for the extension of treatment duration with ATZ + BEV. Conclusion: BEV dose-reduction can be effectively used in maintaining the treatment duration of ATZ + BEV while maintaining therapeutic effects and safety in real-world clinical practice.

Decreased Autophagic Activity in Triple-Negative Breast Cancer Cells upon Hydroxychloroquine and Thymoquinone Combination Treatment

Objective: Autophagy plays a significant role in breast cancer tumorigenesis, including triple-negative breast cancer. Research indicates that hydroxychloroquine and thymoquinone modulate autophagy, potentially suppressing its activity. However, their combined effects on autophagy in triple-negative breast cancer remain unexplored. In this study, we investigated the potential anti-cancer and autophagy-modulating effects of hydroxychloroquine-thymoquinone combination on triple-negative breast cancer cells in vitro. Material and Method: The viability of MDA-MB-231 cells was evaluated after treatment with hydroxychloroquine (10-210 µM) and thymoquinone (5-45 µM) for 24 and 48 hours using the WST-1 assay. Combination effects were analyzed using the Chou-Talalay method with CompuSyn (v.10). Autophagic vesicles were visualized using an Autophagy Detection Kit and fluorescence microscopy to investigate their role in the decrease in cell viability. Statistical analysis was performed with GraphPad Prism (v.8.3.0). Results: At both 24- and 48-hour intervals post-treatment, a significant decrease in viability was observed for both hydroxychloroquine and thymoquinone treatments individually (p1). At 24 hours, favorable dose reduction effects were evident (dose reduction index >1), while the 48-hour results showed an unfavorable reduction (dose reduction index

Evaluation of X-ray protective goggles in mitigating eye lens radiation exposure during radiopharmaceutical handling and patient care in nuclear medicine.

The aim of this study is to estimate eye lens exposure dose when handling radiopharmaceuticals and interacting with patients receiving radiopharmaceuticals, and to verify the usefulness of X-ray protective goggles in mitigating such radiation exposure using phantoms. To evaluate radiation exposure during the handling of radiopharmaceuticals, we employed a fluorescent glass dosimeter to measure the radiation doses associated with 99mTc, 123I, 131I, 111In, and 18F at distances of 30 cm and 60 cm, followed by calculation of the 3 mm dose equivalent rate (3DER). We then estimated the dose reduction rates for various scenarios, including the use of syringe shields and X-ray protective goggles with lead equivalences of 0.07, 0.15, 0.75, and 0.88 mmPb, as well as their combined application. X-ray protective goggles with lead equivalence of 0.75 mmPb outperformed those with 0.07 mmPb and 0.15 mmPb, for all radionuclides and at both source distances. X-ray protective goggles with 0.88 mmPb outperformed those with 0.75 mmPb during handling of 131I and 111In at a distance of 30 cm. In the remaining scenarios, X-ray protective goggles with 0.88 mmPb resulted in marginal reductions or no discernible additional effects. The overall shielding effect of X-ray protective goggles was less pronounced for 131I and 18F, but the combined use of a syringe shield with X-ray protective goggles with 0.75 or 0.88 mmPb improved the dose reduction rate for all scenarios. In simulating patient care, X-ray protective goggles with 0.88 mmPb demonstrated a dose reduction effect of approximately 50% or more. X-ray protective goggles could reduce the 3DER for the eye lens, and were more effective when combined with a syringe shield. It is valid to use a lead equivalence of 0.88 mmPb to fully harness the protective capabilities of X-ray shielding goggles when dealing with all five types of nuclides in clinical settings.

Variations in head tilt during the acquisition of CBCT scans and their effects on effective radiation dose.

This study evaluated the impact of variations in anteroposterior and lateral tilts of patients' head on radiation-weighted doses to organs/tissues and effective doses using three different cone beam computed tomography machines. An anthropomorphic phantom was used to estimate radiation doses in three CBCT machines (OP300, Eagle X 3D, and Eagle Edge). Thermoluminescent dosimeters were placed in regions corresponding to pre-stablished organ/tissues. CBCT examinations from the posterior mandible and anterior maxilla regions were acquired, with three different anteroposterior angulations (0°, 30°, and 45°), and from the posterior mandible in three different lateral angulations (0°, 20° to the left, and 20° to the right side). Radiation-weighted doses for each organ/tissue and effective doses were calculated for each machine and angulation. For the posterior mandible acquisitions, anteroposterior angulations of the head at 30° and 45° yielded a reduction in effective doses in all three devices. A 20° tilt to the right side resulted in lower doses than to the left (same side as the FOV). For the anterior maxilla, increased anteroposterior angulation was associated with reduction in effective dose in two devices. Effective doses are lower when small FOV CBCT exams of the posterior mandible and anterior maxilla are acquired with increased anteroposterior head angulation at 30° and 45°. For FOV in the posterior mandible, a 20° lateral tilt towards the side opposite to the FOV also yields lower effective doses. The main contribution to these dose reductions is the decrease in dose to salivary glands.

The reduction of LEDD leads to visual dysfunction in patients with PD after STN-DBS: a randomized clinical trial

Background: Medication adjustment after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson’s disease (PD) may influence visual function. However, no clinical trials have been designed specifically to investigate this effect. Objectives: To compare the effects of levodopa equivalent daily dose (LEDD) reduction and non-reduction on visual function in patients with Parkinson’s disease (PD) following STN-DBS. Methods: This was a multi-center, prospective, randomized, double-blinded clinical trial. A total of 208 patients with Parkinson’s disease were referred for DBS between June 2019 and July 2021 and analyzed between June 2023 and July 2023. STN-DBS was performed, and the LEDD was reduced in one study arm but not in the other. The primary outcome measure was visual impairment in Parkinson’s disease questionnaire (VIPD-Q) with or without LEDD reduction 12 months postoperatively, and the secondary outcomes included retinal nerve fiber layer (RNFL) thickness, vessel density, eye-tracking system results, contrast sensitivity and visual field. Results: During the short-term follow-up, DBS implantation and stimulation did not significantly affect visual function (VIPD-Q, baseline vs. 1 month, 9.269±8.385 vs. 8.938±7.666, Mann–Whitney U tests; P=0.6746). In the long-term follow-up, the reduction group demonstrated a significant decline in visual function, RNFL thickness, and vessel density after STN-DBS compared with the control group without STN-DBS (P<0.001). Conclusions: Visual dysfunction, particularly a thinner RNFL and lower vessel density, is related to LEDD reduction after STN-DBS. Prolonged administration of dopamine-mimetic drugs prevents visual symptoms. Thus, physicians should consider LEDD adjustment when patients report visual dysfunction before surgery or severe visual symptoms after STN-DBS.

MDB-100. RETROSPECTIVE ANALYSIS OF CUMULATIVE DOSING OF CHEMOTHERAPY AGENTS AND THE EFFECT ON SURVIVAL IN PATIENTS WITH AVERAGE RISK MEDULLOBLASTOMA TREATED ON CHILDRENS ONCOLOGY GROUP STUDY ACNS0331

Abstract BACKGROUND Although survival outcomes for average risk (AR) medulloblastoma remain good, patients may experience significant acute and long-term toxicities from therapy. To evaluate the effect of dose modifications among children with AR medulloblastoma, we examined the effect of cumulative chemotherapy dose on overall and event-free survival. METHODS We retrospectively examined the association between the proportion of scheduled chemotherapy dose received on survival outcomes (OS and EFS) using Cox regression models and log-rank tests for patients treated on ACNS0331. We evaluated all chemotherapy agents for the group as a whole and within the four major subgroups. Dose intensity was analyzed continuously and categorically (>75% or <75% of planned dose) for each agent. RESULTS 274 evaluable children (medulloblastoma by methylation, received standard dose craniospinal radiation and chemotherapy) were followed for a median of 9.3 years (range, 7.0-10.4 years). Vincristine and cisplatin showed the most variable dose intensity (25.2% and 31.8% of patients received <75% of expected dosing, respectively). Cyclophosphamide and lomustine were not examined due to low dose variability (17.2% and 11.7%, respectively). The effect of dose intensity was evaluated in 235 patients who completed planned therapy. Molecular subgroup remained a significant predictor of outcome in AR medulloblastoma (EFS (p=0.012) and OS (p=0.008)). Although survival curves were lower for less dose intense treatments, no significant difference in EFS or OS was found due to reduced dose intensity for vincristine (p=0.36 EFS, p=0.35 OS) or cisplatin (p=0.49 EFS, p=0.52 OS). The hazard ratio [95% confidence interval] for chemotherapy proportion and EFS was 0.998[0.977-1.019] (vincristine) and 0.989[0.966-1.012] (cisplatin). There was no difference in the effect of dose reductions by molecular subgroup. CONCLUSIONS Moderate reductions in vincristine and cisplatin dose intensity do not significantly affect survival in AR medulloblastoma. It is unknown whether this reduction would reduce chemotherapy-related toxicity.

Enhanced brain-targeting and efficacy of cannabidiol via RVG-Exo/CBD nanodelivery system

This study introduces an innovative brain-targeted drug delivery system, RVG-Exo/CBD, utilizing rabies virus glycoprotein (RVG)-engineered exosomes for encapsulating cannabidiol (CBD). The novel delivery system was meticulously characterized, confirming the maintenance of exosomal integrity, size, and successful drug encapsulation with a high drug loading rate of 83.0 %. Evaluation of the RVG-Exo/CBD's brain-targeting capability demonstrated superior distribution and retention in brain tissue compared to unmodified exosomes, primarily validated through in vivo fluorescence imaging. The efficacy of this delivery system was assessed using a behavioral sensitization model in mice, where RVG-Exo/CBD notably suppressed methamphetamine-induced hyperactivity more effectively than CBD alone, indicating a reduction in effective dose and enhanced bioavailability. Overall, the RVG-Exo/CBD system emerges as a promising strategy for enhancing the therapeutic efficacy and safety of CBD, particularly for neurological applications, highlighting its potential for addressing the limitations associated with traditional CBD administration in clinical settings.

Effects of niraparib dose reduction on short-term outcomes in ovarian cancer patients

ObjectivesDespite the individualized starting dose for maintenance therapy in ovarian cancer, the niraparib dose reduction rate remains high. The aim of this study was to evaluate the impact of niraparib...

Recommendation for reducing the crystalline lens exposure dose by reducing imaging field width in cone-beam computed tomography for image-guided radiation therapy: an anthropomorphic phantom study.

In cone-beam computed tomography (CBCT) for image-guided radiation therapy (IGRT) of the head, we evaluated the exposure dose reduction effect to the crystalline lens and position-matching accuracy by narrowing one side (X2) of the X-ray aperture (blade) in the X-direction. We defined the ocular surface dose of the head phantom as the crystalline lens exposure dose and measured using a radiophotoluminescence dosimeter (RPLD, GD-352M) in the preset field (13.6cm) and in each of the fields when blade X2 aperture was reduced in 0.5cm increments from 10.0 to 5.0cm. Auto-bone matching was performed on CBCT images acquired five times with blade X2 aperture set to 13.6cm and 5.0cm at each position when the head phantom was moved from -5.0 to + 5.0mm in 1.0mm increment. The maximum reduction rate in the crystalline lens exposure dose was -38.7% for the right lens and -13.2% for the left lens when blade X2 aperture was 5.0cm. The maximum difference in the amount of position correction between blade X2 aperture of 13.6cm and 5.0cm was 1mm, and the accuracy of auto-bone matching was similar. In CBCT of the head, reduced blade X2 aperture is a useful technique for reducing the crystalline lens exposure dose while ensuring the accuracy of position matching.

Patient radiation exposure dose reduction using stent-enhanced image processing in percutaneous coronary intervention.

We investigated the reduction in patient radiation exposure dose during percutaneous coronary intervention (PCI) by stent enhancement processing. We examined the effects of dose reduction based on the image quality of stent enhancement processing using a purpose-built dynamic phantom. We evaluated the image contrast (IC) of the stent in stent-enhanced images (SVref), digital angiography (DA), and stent-enhanced images with a 20%, 40%, and 60% lower imaging doses (SV20, SV40, and SV60). We visually evaluated graininess and stent shape using the mean opinion score (MOS) and retrospectively evaluated the acquisition duration of stent enhancement in PCI cases; finally, we estimated the decrease in patient radiation exposure due to stent enhancement. The image contrast of SVref at phantom thicknesses of 20cm was 51.25 ± 3.82, while the image contrast of DA was significantly reduced at 14.90 ± 1.57 (p < 0.05). We observed a significant decrease in the MOS of graininess in SV60 and MOS of stent shape in DA (p < 0.05). Furthermore, the average imaging duration for stent enhancement using PCI was 22.65 ± 7.43s, and the maximum imaging duration was 68.07s. We hypothesize that patient radiation exposure dose can be reduced by up to 60.17mGy by lowering the imaging dose during the stent enhancement process. Stent enhancement processing improves the visibility of stent images, and can reduce radiation exposure by approximately 40% during confirmation imaging of stents. Our study contributes to the reduction of radiation exposure dose for operators and patients in PCI.

Robustness of carbon-ion radiotherapy against DNA damage repair associated radiosensitivity variation based on a biophysical model.

Interpatient variation of tumor radiosensitivity is rarely considered during the treatment planning process despite its known significance for the therapeutic outcome. To apply our mechanistic biophysical model to investigate the biological robustness of carbon ion radiotherapy (CIRT) against DNA damage repair interference (DDRi) associated patient-to-patient variability in radiosensitivity and its potential clinical advantages against conventional radiotherapy approaches. The "UNIfied and VERSatile bio response Engine" (UNIVERSE) was extended by carbon ions and its predictions were compared to a panel of in vitro and in vivo data including various endpoints and DDRi settings within clinically relevant dose and linear energy transfer (LET) ranges. The implications of UNIVERSE predictions were then assessed in a clinical patient scenario considering DDRi variance. UNIVERSE tests well against the applied benchmarks. While in vitro survival curves were predicted with an R2>0.92, deviations from in vivo RBE data were less than 5.6% The conducted paradigmatic patient plan study implies a markedly reduced significance of DDRi based radiosensitivity variability in CIRT (13% change of in target) compared to conventional radiotherapy (62%) and that boosting the LET within the target further amplifies this robustness of CIRT (8%). In the case of heightened tumor radiosensitivity, a dose de-escalation strategy for photons allows a reduction of the maximum effective dose within the normal tissue (NT) from a of 2.65 to 1.64Gy, which lies below the level found for CIRT ( =2.41Gy) for the analyzed plan and parameters. However, even after de-escalation, the integral effective dose in the NT is found to be substantially higher for conventional radiotherapy in comparison to CIRT ( of 0.75, 0.46, and 0.24Gy for the conventional plan, its de-escalation and CIRT, respectively). The framework offers adequate predictions of in vitro and in vivo radiation effects of CIRT while allowing the consideration of DRRi based solely on parameters derived from photon data. The results of the patient planning study underline the potential of CIRT to minimize important sources of interpatient divergence in therapy outcome, especially when combined with techniques that allow to maximize the LET within the tumor. Despite the potential of de-escalation strategies for conventional radiotherapy to reduce the maximum effective dose in the NT, CIRT appears to remain a more favorable option due to its ability to reduce the integral effective dose within the NT.

The Real-world Experiences of Abemaciclib for Estrogen Receptor-positive Human Epidermal Growth Factor Receptor-negative-2 Metastatic Breast Cancer – Sharing from a Single Institute in Southern Taiwan

Abstract Background: CDK 4/6 inhibitor (CDK4/6i) is the first-line therapeutic drug to treat ER-positive (ER+) HER2-negative (HER2 -) metastatic breast cancer (MBC) now. We have three CDK4/6i: Palbociclib, Ribociclib, and Abemaciclib. In the long-term follow-up study, there are some different results among the three CDK4/6i. Some real-world reports demonstrated some patients would have clinical benefits from Abemaciclib in the ER+ HER2- metastatic BC patients who had priorly received the other CDK 4/6 inhibitor (Palbociclib). In Taiwan, Abemaciclib is the third available CDK 4/6 inhibitor behind the other two CDK4/6i. However, Abemaciclib was not reimbursed in ER+ HER2- MBC by Taiwan Health Insurance until now. Most doctors in Taiwan have the less therapeutic experiences for Abemaciclib. In this article, we would share the clinical experiences for the first thirteen patients who were prescribed with Abemaciclib to treat ER+ HER2- MBC. Materials and Methods: This chart review study was conducted from January 1, 2020, to May 31, 2023. We reviewed the medical charts at National Cheng Kung University Hospital (NCKUH) and identified 13 patients who had received abemaciclib treatment for ER+ HER2− MBC. The study was approved by the Institutional Review Board at NCKUH (approval number: B-ER-112-220). All of the 13 patients were treated with abemaciclib (150 mg twice daily initially), in combination with other anti-cancer medications. We recorded the clinical parameters, including sex, age, treatments in neoadjuvant/adjuvant setting, metastatic sites, other prior CDK4/6i therapy, treatment lines of abemaciclib in the metastatic setting, survival period before abemaciclib treatment, time to treatment failure for abemaciclib, causes of abemaciclib discontinuation, dose reduction, and adverse effects (AEs) related to abemaciclib. Results: Up to the cut-off date (May 31, 2023), four (4/13) patients were still receiving therapy and nine patients (9/13) had discontinued abemaciclib therapy. Five (5/9) patients discontinued abemaciclib due to disease progression (PD), and two (2/9) patients interrupted abemaciclib treatment due to personal reasons. Two (2/9) patients stopped abemaciclib early because of AEs, and one patient died due to PD. The time to treatment failure for abemaciclib ranged from 1 to 41 months (average: 19.2 months, median: 14 months). AEs were noted in 12 patients (no recording in one patient), of which diarrhea (10/12), anemia (4/12), and neutropenia (3/12) were the most common. Conclusion: According to our real-world data, Abemaciclib is effective and safe for the ER+ HER2- metastatic BC cancer patients who they were heavily treated.

Effect of dose reduction of dutasteride in combination with alpha-blockers in patients with lower urinary tract symptoms/benign prostatic enlargement.

Dutasteride is used in the treatment of benign prostate enlargement with reported many side effects. The purpose of this study is to examine how different doses of dutasteride (0.5 mg) in combination with tamsulosin affect the outcome of treatment of benign prostatic enlargement (BPE). Prospective study (phase III trial). Between April 2017 and March 2020, this randomized study was conducted on 300 patients with moderate-to-severe lower urinary tract symptoms attributable to BPE and a prostate volume of more than 40 cc. The patients were divided into three therapy groups at random (one-to-one randomization), each with 100 patients: (Group I) daily tamsulosin 0.4 mg plus dutasteride (0.5 mg). (Group II) every other day tamsulosin 0.4 mg plus dutasteride 0.5 mg. (Group III) once a week tamsulosin 0.4 mg plus dutasteride 0.5 mg. Statistical analysis was carried out with the help of the SPSS program 22. (IBM, Armonk, NY, USA). The mean and standard deviation (SD) are used to express quantitative data (SD). When comparing two means, an independent-samples t-test of significance was used. To compare more than two means, a one-way analysis of variance was utilized. For multiple comparisons between distinct variables, a post hoc test was performed. Patients were followed up every 3 months, with a 1-year follow-up to examine the medications' efficacy, prostate size reduction, and erectile function. After 1 year of treatment, all groups showed significant improvement in their symptom scores. However, Groups I and II experienced a considerable reduction in prostate size after therapy, but Group III experienced no meaningful reduction. In terms of sexual dysfunction, there was a considerable shift in Group I after 12 months. Dutasteride treatment on the other day schedule has the same efficacy as the daily dose on prostate size at the same time; the other day scheduled dose has better preservation of sexual function.

Effect of early dose reduction of osimertinib on efficacy in the first-line treatment for EGFR-mutated non-small cell lung cancer

SummaryOsimertinib is used as the first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, early dose reduction is often required due to adverse events (AEs). This study aimed to evaluate the effect of early dose reduction of osimertinib on efficacy and safety. This was a retrospective study including patients with EGFR-mutated NSCLC who were started on osimertinib as the first-line therapy between August 2018 and December 2021. Patients whose doses were reduced to less than 80 mg/day within 6 months of osimertinib initiation or started at 40 mg/day were defined as the dose reduction group. The primary endpoint was progression-free survival (PFS). Factors affecting PFS were explored using the Cox proportional hazards model. A total of 85 patients were included in this study. No significant differences in patient characteristics were observed between the dose reduction (n = 25) and standard dose groups (n = 60). The median PFS in the dose reduction group was significantly prolonged compared with that in the standard dose group (26.0 months vs. 12.0 months, p = 0.03). Multivariable analysis of 84 patients, excluding a patient with unknown brain metastasis, revealed that EGFR exon 21 L858R mutation, malignant pleural effusion or pleural metastasis, liver metastasis, and dose reduction within 6 months were independent factors affecting PFS. Early dose reduction of osimertinib is an effective therapeutic strategy for prolonging PFS in patients with EGFR-mutated NSCLC.

Effect of radioprotective curtain length on the scattered dose rate distribution and endoscopist eye lens dose with an over-couch fluoroscopy system

Sufficient dose reduction may not be achieved if radioprotective curtains are folded. This study aimed to evaluate the scattered dose rate distribution and physician eye lens dose at different curtain lengths. Using an over-couch fluoroscopy system, dH*(10)/dt was measured using a survey meter 150 cm from the floor at 29 positions in the examination room when the curtain lengths were 0% (no curtain), 50%, 75%, and 100%. The absorbed dose rates in the air at the positions of endoscopist and assistant were calculated using a Monte Carlo simulation by varying the curtain length from 0 to 100%. The air kerma was measured by 10 min fluoroscopy using optically stimulated luminescence dosimeters at the eye surfaces of the endoscopist phantom and the outside and inside of the radioprotective goggles. At curtain lengths of 50%, 75%, and 100%, the ratios of dH*(10)/dt relative to 0% ranged from 80.8 to 104.1%, 10.5 to 61.0%, and 11.8 to 24.8%, respectively. In the simulation, the absorbed dose rates at the endoscopist’s and assistant’s positions changed rapidly between 55 and 75% and 65% and 80% of the curtain length, respectively. At the 0%, 50%, 75%, and 100% curtain lengths, the air kerma at the left eye surface of the endoscopist phantom was 237 ± 29, 271 ± 30, 37.7 ± 7.5, and 33.5 ± 6.1 μGy, respectively. Therefore, a curtain length of 75% or greater is required to achieve a sufficient eye lens dose reduction effect at the position of the endoscopist.

Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.