dose levels
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2022 ◽  
Vol 11 ◽  
Yaru Pang ◽  
Hui Wang ◽  
He Li

Intensity-modulated radiation therapy (IMRT) has been used for high-accurate physical dose distribution sculpture and employed to modulate different dose levels into Gross Tumor Volume (GTV), Clinical Target Volume (CTV) and Planning Target Volume (PTV). GTV, CTV and PTV can be prescribed at different dose levels, however, there is an emphasis that their dose distributions need to be uniform, despite the fact that most types of tumour are heterogeneous. With traditional radiomics and artificial intelligence (AI) techniques, we can identify biological target volume from functional images against conventional GTV derived from anatomical imaging. Functional imaging, such as multi parameter MRI and PET can be used to implement dose painting, which allows us to achieve dose escalation by increasing doses in certain areas that are therapy-resistant in the GTV and reducing doses in less aggressive areas. In this review, we firstly discuss several quantitative functional imaging techniques including PET-CT and multi-parameter MRI. Furthermore, theoretical and experimental comparisons for dose painting by contours (DPBC) and dose painting by numbers (DPBN), along with outcome analysis after dose painting are provided. The state-of-the-art AI-based biomarker diagnosis techniques is reviewed. Finally, we conclude major challenges and future directions in AI-based biomarkers to improve cancer diagnosis and radiotherapy treatment.

2022 ◽  
Vol 11 ◽  
Justin Watts ◽  
Tara L. Lin ◽  
Alice Mims ◽  
Prapti Patel ◽  
Cynthia Lee ◽  

APVO436 is a recombinant bispecific antibody designed to direct host cytotoxic T-cells to CD123-expressing blast cells in patients with hematologic malignancies. APVO436 showed promising tolerability and single-agent activity in relapsed or refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The primary purpose of this post-hoc analysis was to evaluate the therapeutic and pharmacodynamic effects of APVO436 in 14 R/R AML/MDS patients who had failed treatment with hypomethylating agents (HMA) or venetoclax plus HMA prior to being enrolled in the APVO436 Phase 1 dose-escalation study that was recently completed. Eight of these 14 patients had R/R AML and had failed treatment with HMA (N=2) or venetoclax plus HMA (N=6). The remaining 6 patients had R/R MDS and had also failed treatment with HMA (N=5) or venetoclax plus HMA (N=1). They were treated with APVO436 at submicrogram dose levels >0.08 mcg/kg that were active in preclinical NOD/SCID mouse xenograft models of AML. APVO436 activated patients’ T-cells as evidenced by reduced numbers of circulating CD123+CD34+ and CD33+CD34+ peripheral blasts. Single-agent activity was observed at dose levels ranging from 0.1 mcg/kg to 0.7 mcg/kg in 4 R/R AML patients (50%), including 3 patients with prolonged stable disease (SD) and one patient with complete remission (CR). Likewise, 3 MDS patients had SD (50%) and 3 additional MDS patients (50%) had a marrow CR at dose levels ranging from 0.1 mcg/kg to 0.8 mcg/kg. The median survival for the combined group of 14 R/R AML/MDS patients was 282 days. This early evidence of single-agent activity of APVO436 in R/R AML/MDS patients who failed HMA with or without venetoclax provides proof of concept supporting its in vivo immunomodulatory and anti-leukemic activity and warrants further investigation of its clinical impact potential.

2021 ◽  
pp. 096228022110649
Sean M Devlin ◽  
Alexia Iasonos ◽  
John O’Quigley

Many clinical trials incorporate stopping rules to terminate early if the clinical question under study can be answered with a high degree of confidence. While common in later-stage trials, these rules are rarely implemented in dose escalation studies, due in part to the relatively smaller sample size of these designs. However, even with a small sample size, this paper shows that easily implementable stopping rules can terminate dose-escalation early with minimal loss to the accuracy of maximum tolerated dose estimation. These stopping rules are developed when the goal is to identify one or two dose levels, as the maximum tolerated dose and co-maximum tolerated dose. In oncology, this latter goal is frequently considered when the study includes dose-expansion cohorts, which are used to further estimate and compare the safety and efficacy of one or two dose levels. As study protocols do not typically halt accrual between escalation and expansion, early termination is of clinical importance as it either allows for additional patients to be treated as part of the dose expansion cohort to obtain more precise estimates of the study endpoints or allows for an overall reduction in the total sample size.

2021 ◽  
Vol 23 (1) ◽  
pp. 49
Zoi Skaperda ◽  
Fotios Tekos ◽  
Periklis Vardakas ◽  
Charitini Nepka ◽  
Demetrios Kouretas

Cellular adaptive mechanisms emerging after exposure to low levels of toxic agents or stressful stimuli comprise an important biological feature that has gained considerable scientific interest. Investigations of low-dose exposures to diverse chemical compounds signify the non-linear mode of action in the exposed cell or organism at such dose levels in contrast to the classic detrimental effects induced at higher ones, a phenomenon usually referred to as hormesis. The resulting phenotype is a beneficial effect that tests our physiology within the limits of our homeostatic adaptations. Therefore, doses below the region of adverse responses are of particular interest and are specified as the hormetic gain zone. The manifestation of redox adaptations aiming to prevent from disturbances of redox homeostasis represent an area of particular interest in hormetic responses, observed after exposure not only to stressors but also to compounds of natural origin, such as phytochemicals. Findings from previous studies on several agents demonstrate the heterogeneity of the specific zone in terms of the molecular events occurring. Major factors deeply involved in these biphasic phenomena are the bioactive compound per se, the dose level, the duration of exposure, the cell, tissue or even organ exposed to and, of course, the biomarker examined. In the end, the molecular fate is a complex toxicological event, based on beneficial and detrimental effects, which, however, are poorly understood to date.

Marcel Opitz ◽  
Georgios Alatzides ◽  
Sebastian Zensen ◽  
Denise Bos ◽  
Axel Wetter ◽  

Abstract Purpose The aim of this study was to determine local diagnostic reference levels (DRLs) during endovascular diagnostics and therapy of carotid-cavernous fistulas (CCF). Methods In a retrospective study design, DRLs, achievable dose (AD) and mean values were assessed for all patients with CCF undergoing diagnostic angiography (I) or embolization (II). All procedures were performed with the flat-panel angiography system Allura Xper (Philips Healthcare). Interventional procedures were differentiated according to the type of CCF and the type of procedure. Results In total, 86 neurointerventional procedures of 48 patients with CCF were executed between February 2010 and July 2021. The following DRLs, AD and mean values could be determined: (I) DRL 215 Gy ∙ cm2, AD 169 Gy ∙ cm2, mean 165 Gy ∙ cm2; (II) DRL 350 Gy ∙ cm2, AD 226 Gy ∙ cm2, mean 266 Gy ∙ cm2. Dose levels of embolization were significantly higher compared to diagnostic angiography (p < 0.001). No significant dose difference was observed with respect to the type of fistula or the embolization method. Conclusion This article reports on diagnostic and therapeutic DRLs in the management of CCF that could serve as a benchmark for the national radiation protection authorities. Differentiation by fistula type or embolization method does not seem to be useful.

ناصر محمود أحمد ◽  
عباس راشد هاتف ◽  
علاء فالح ◽  
حميزه بنتي قمرالدين

Radon sources can be found in external and internal radiation. Lead pencil (LP) is often used for drawing, sketching, etc. regardless of age nowadays. Paracetamol (PC) is commonly used around the world especially to treat fever, headache, menstrual pain, and common pain. Hence, the aim is to study the procedures for determining the radon gas comes out from different types of lead pencil and paracetamol. Eight and five samples were collected from different companies of lead pencil and paracetamol, respectively. The samples were measured using the sealed technique in cylindrical plastic containers with CN–85 detectors. After irradiation, the detectors were chemically etched using 2 N sodium hydroxide (NaOH) solution at a temperature of 70 ºC for 62 min. The alpha track density on the surface of detectors was measured using an optical microscope at a magnification of 100×. Tracks on detectors were counted using Image software. Radon concentration values including all samples in this study are within the limits of international which is 1000 Bq/m3. The concentration of radium in LP and PC samples are lower than those reported in previous study. The result of the uranium concentration of both samples is quite low compared with the allowed limit which is 11.7 ppm. Annual effective dose levels are all below the dose limit which is 10 mSv/y. Lastly, there was a linear relationship between radium activity and radon exhalation rate. Therefore, using LP and eating PC cause no danger to humans. All results showed in this study are within internationally permissible limits, and therefore not a threat to human health.

2021 ◽  
Vol 11 ◽  
Edoardo Mastella ◽  
Silvia Molinelli ◽  
Giuseppe Magro ◽  
Stefania Russo ◽  
Maria Bonora ◽  

PurposeIn carbon ion radiotherapy (CIRT), a simultaneous integrated boost (SIB) approach has not been fully exploited so far. The feasibility of a CIRT-SIB strategy for head and neck adenoid cystic carcinoma (ACC) patients was investigated in order to improve treatment planning dose distributions.Methods and MaterialsCIRT plans of 10 ACC patients treated at the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy) with sequential boost (SEQ) irradiation and prescription doses of 41.0 Gy [relative biological effectiveness (RBE)]/10 fractions to low-risk (LR) clinical target volume (CTV) plus 24.6 Gy(RBE)/6 fractions to the high-risk (HR) CTV were re-planned with two SIB dose levels to the LR-CTV, namely, 48.0 Gy(RBE) and 54.4 Gy(RBE). While planning with SIB, the HR-CTV coverage had higher priority, with fixed organ-at-risk dose constraints among the SIB and SEQ plans. The homogeneity and conformity indexes were selected for CTV coverage comparison. The biologically effective dose (BED) was calculated to compare the different fractionation schemes.ResultsComparable HR-CTV coverage was achieved with the treatment approaches, while superior conformality and homogeneity were obtained with the SIB technique in both CTVs. With the SEQ, SIB48.0, and SIB54.4, the LR-CTV median doses were respectively 50.3%, 11.9%, and 6.0% higher than the prescriptions. Significant reductions of the median and near-maximum BEDs were achieved with both SIB dose levels in the LR-CTV.ConclusionsThe SIB approach resulted in highly conformal dose distributions with the reduction of the unintended dose to the LR-CTV. A prescription dose range for the LR-CTV will be clinically defined to offer tailored personalized treatments, according to the clinical and imaging characteristics of the patients.

Debra L. Barton ◽  
Stephanie L. Pugh ◽  
Patricia A. Ganz ◽  
Steven C. Plaxe ◽  
Bridget F. Koontz ◽  

PURPOSE Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities. METHODS Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t-tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t-test. RESULTS Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups. CONCLUSION Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0006542020
Diane M Hamlin ◽  
A. Eric Schultze ◽  
Michael J. Coyne ◽  
Donald J. McCrann ◽  
Rebekah Mack ◽  

Symmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney were performed. Prior to biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50 mg/kg and the 100 mg/kg dosage levels in the 4 and 10-dose treatment groups compared to controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with µALB being most responsive and OPN least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA as compared to other excretory renal function markers in a rat gentamicin acute toxicity model. In this study serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.

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