Dosymmetric estimates of 99mTc (MAA) and 133Xe in newborn lungs using Cristy-Eckerman / Segars representations

Using the Cristy-Eckerman (C-E) / Segars anatomical representations and the MIRD formalism, the Absorbed doses in lungs of newborn patients scanned with radiopharmaceuticals 133Xe (ventilation) and 99mTc (MAA) (perfusion) are estimated. These representations are phantoms used in Monte Carlo calculations to determine specific absorbed fractions, which, associated with the pharmaceutical residence time, determine the absorbed dose. Concerns about the dosimetric impact of using these ventilation / perfusion agents, as well as the use of different phantoms, were explored in newborn patients. When the lungs were scanned with 99mTc (MAA), the relative difference in total dose between the C-E / Segars anatomical representations was 1.0%. When the lungs were scanned with 133Xe, the relative difference in total dose between the anthropomorphic representations of C-E / Segars was 0.5%. Regardless of the radiopharmaceutical used for the pulmonary studies of a newborn patient, the substitution of the C-E representation for that of Segars does not reflect very significant changes in the calculation of the absorbed dose in the lungs, where the greatest dosimetric contribution is its self-dose, which is supplied mainly by the electrons produced during the 99mTc and 133Xe decay.

Dose selection of Incobotulinumtoxin A for the treatment of spasticity and sialorrhea in cerebral palsy: results of a retrospective multicenter study

Introduction. In patients with infantile cerebral palsy (CP), botulinum therapy is used to treat both muscle tone disorders and sialorrhea. Therefore, it is logical to use one preparation of botulinum toxin type A to treat spasticity and sialorrhea in one injection procedure. The aim of the work is to conduct a retrospective analysis of data from 15 centres that treat patients with cerebral palsy and use the botulinum therapy method to determine the optimal doses of IncobotulinumtoxinA (IBTA) for the treatment of spasticity and chronic sialorrhea in real clinical practice. Materials and methods. The treatment results of 389 children with cerebral palsy (including 211 (54.2%) boys) with IBTA were analyzed. The majority were children with bilateral forms of cerebral palsy - 312 (80.2%). The average age of the patients was 5.27 ± 3.71 years, the average weight of the patients was 18.8 ± 10.9 kg. Results. The total dose of IBTA in the group of 389 patients with cerebral palsy for the treatment of spasticity was 163.74 ± 80.65 U (25-550; 95% CI 155.7-171.7) and 10.4 ± 5.4 U/kg body weight (1,25-29.7; 95% CI 9.8-10.9). The total dose of IBTA in the group of patients with cerebral palsy with simultaneous treatment of spasticity and chronic sialorrhea (n = 16) was significantly higher: 267.18 ± 124.57 U (115-570; 95% CI 200.8-333.6) and 13, 0 ± 7.1 U/kg (5.8-24.6; 95% CI 9.2-16.8). In the lower extremities, the most frequent target muscles were the gastrocnemius (55.0% of cases; 95% CI 49.9-60.0) and semitendinosus / semimembranous muscle (46.3% of cases; 95% CI 41.2-51.4 ), and in the upper limbs - pronator teres (48.6% of cases; 95% CI 43.5-53.7) and biceps brachii (28.8% of cases; 95% CI 24.3-33.6). Limitations of the study. The limitations of our work are the use of an open retrospective study format, a relatively small sample of patients with chronic sialorrhea, the absence of long-term follow-up of patients and the results of repeated IBTA injections. Conclusion. If it is necessary to use botulinum therapy for the treatment of spasticity and sialorrhea in a child with CP, it is optimal to use the product IncobotulinumtoxinA, which will allow correction of two pathological manifestations in one procedure and can shorten the intervals between repeated injection cycles.

Colistin-Induced Acute Kidney Injury and the Effect on Survival in Patients with Multidrug-Resistant Gram-Negative Infections: Significance of Drug Doses Adjusted to Ideal Body Weight

Background. Colistin is a lifesaving treatment for multidrug-resistant Gram-negative bacterial (MDR-GNB) infections along with its well-known nephrotoxicity. The controversy of colistin-induced acute kidney injury (AKI) on mortality is noted. This study aimed to determine the risk factors and impact of AKI on the survival and significance of colistin dosage. Methods. A retrospective cohort study was performed in adult patients who received intravenous colistin for MDR-GNB treatment between June 2015 and June 2017. Factors influencing colistin-induced AKI and survival were evaluated by Cox regression analysis. Cut-off levels of the colistin dose per ideal body weight (IBW) that significantly affected clinical outcomes were assessed with linearity trends and receiver operating characteristic analyses. Results. AKI occurred in 68.5% of 412 enrolled patients with an incidence rate of 10.6 per 100 patients-days and a median time was 6 (3–13) days. Stages I–III of AKI were 38.3, 24.5, and 37.2%. Factors associated with colistin-induced AKI were advanced age, high serum bilirubin, AKI presented before colistin administration, increased daily colistin doses per IBW, and concomitant use of nephrotoxic drugs. Colistin-induced AKI was related to mortality (HR 1.74, 95% CI 1.06–2.86, p = 0.028 ). In the non-AKI before colistin usage subgroup, the total dose and total dose/IBW were >1,500–2,000 mg and 30–35 mg/kg to benefit mortality reduction but were <2,500–3,000 mg and 45–50 mg/kg for risk reduction of AKI. A daily colistin dose/IBW >4.5 mg/kg/day also increased the risk of AKI. In the AKI developed before colistin subgroup, the cut-off values of total colistin dose >1250–1350 mg and total dose/IBW >23.5–24 mg/kg demonstrated significant risks of AKI. Conclusion. The incidence of AKI after colistin administration was high and impacted mortality. Prevention and early correction of these related factors are mandatory. Careful use of colistin was also both beneficial in mortality and AKI reductions.

Fast Improvement of TEM Images with Low-Dose Electrons by Deep Learning

Low electron dose observation is indispensable for observing various samples using a transmission electron microscope; consequently, image processing has been used to improve transmission electron microscopy (TEM) images. To apply such image processing to in situ observations, we here apply a convolutional neural network to TEM imaging. Using a dataset that includes short-exposure images and long-exposure images, we develop a pipeline for processed short-exposure images, based on end-to-end training. The quality of images acquired with a total dose of approximately $5$ $e^{-}$ per pixel becomes comparable to that of images acquired with a total dose of approximately $1{,}000$ $e^{-}$ per pixel. Because the conversion time is approximately 8 ms, in situ observation at 125 fps is possible. This imaging technique enables in situ observation of electron-beam-sensitive specimens.

The Evolving Strategy of Californium-252 Neutron Intracavitary Brachytherapy in Treating Patients With Low-Lying T2 or T3 Rectal Adenocarcinoma: From Fixed to Individualized Regime With Intrarectal Peritumoral Injection of Amifostine

PurposeTo retrospectively and comparatively evaluate the improvement of the efficacy and safety on the addition of 252Cf neutron intracavitary brachytherapy (ICBT), individualized or individualized with intrarectal peritumoral injection of amifostine (IPIA) to external-beam radiotherapy (EBRT) or concurrent chemo-EBRT in 314 patients with T2N0-1 or T3N0-1 low-lying rectal adenocarcinoma.MethodsPhase I: from 2009 to 2011, 157 patients were treated with additional 252Cf neutron ICBT for four fixed fractions with a total dose of 40–45 Gy-eq during the EBRT. Phase II: from 2011 to 2013, 75 patients were treated with individualized neutron ICBT delivered for two to five fractions with a total dose of 26–45 Gy-eq according to the response of tumor after concurrent chemo-EBRT. Phase III: from 2013 to 2014, 82 patients were treated with individualized ICBT protected by pretreatment IPIA.ResultsThe 4-year local control rates for the entire T2 and T3 patients were 69.4, 72.0, and 79.3%, while the 4-year overall survival rates were 63.1, 54.7, and 72.0% (P=0.08), and the 4-year disease-free survival rates were 55.4, 52.0, and 69.5% (P=0.053) in Phases I, II, and III, respectively. The late complication (LAC, ≥G2) rates were 33.8, 26.7, and 15.9%, respectively (P=0.012), and the serious LAC (≥G3) rates were 4.5, 4.2, and 0%, respectively, in Phases I, II, and III.ConclusionConcurrent chemo-EBRT combined with individualized 252Cf neutron ICBT protected by IPIA shows promising efficacy and safety in treating low-lying T2 and T3 rectal adenocarcinoma patients without surgery opportunity or willing.

Abstract 11597: Characterization of Epinephrine Use During Extracorporeal Cardiopulmonary Resuscitation

Introduction: Guidelines recommend dosing Epinephrine (Epi) at regular intervals during pediatric cardiac arrest, including patients requiring extracorporeal membrane oxygenation (ECMO). The impact of Epi-induced vasoconstriction on systemic afterload and veno-arterial ECMO support is poorly understood. Hypothesis: Higher total dose of Epi and shorter interval between Epi dose and ECMO flow during cardiac arrest will increase systemic afterload and interfere with ECMO support. Methods: This is an ancillary study to a single-center, retrospective observational study of patients 0-18 years old who required ECMO cannulation during resuscitation over a six-year period. Patients were excluded if ECMO was initiated prior to arrest or if the resuscitation record was incomplete. The primary exposure was time from last dose of Epi to initiation of ECMO flows; secondary exposures included cumulative Epi dose delivered and indexed to arrest time. Mean arterial pressure (MAP) and systemic vasodilator therapy were used as surrogates for systemic afterload; ECMO pump speed and vasoactive-inotrope score (VIS) were used as measures of ECMO support. Results: A total 92 events in 87 patients analyzed. The patient cohort was 53% female with median (IQR) age of 122 (30-478) days, weight 4.4 (3.3 - 8.7) kg, and 43% single ventricle physiology. On average, Epi was given 7 (4 - 10) times during a 35 (27 - 44) min arrest, for a total dose of 65 (37 - 101) mcg/kg; the last dose was given 6 (2 -16) min prior to the initiation of ECMO flows. In the 6 hours following initiation of ECMO, MAP increased from 42 (36 - 56) mmHg to 57 (47 - 70) mmHg, (p<0.0001). Shorter interval between last Epi dose and ECMO initiation trended with higher MAP after 1 hour of support (estimate -0.43, p=0.06) and associated with increased of vasodilators within 6 hours of ECMO (vasodilators used (1 - 6) vs not used 9 (3 - 16) min, p=0.05). No other associations were found between Epi delivery, MAP, vasodilator use, pump speed or VIS. Conclusion: There is limited evidence to support that regular dosing of Epi throughout a cardiac arrest is associated with clinically significant increases in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

The Impact of Age in Allogeneic Stem Cell Transplantation with Thiotepa Busulfan and Fludarabine (TBF) for Myelofibrosis : A Retrospective Analysis

Allogeneic hematopoietic stem-cell transplantation (HSCT) currently remains the only curative therapy for intermediate or high risk disease.myelofibrosis (MF). We are reporting 56 patients (pts) who underwent an allogeneic HSCT in our Centre between 2016 and 2020, and assessed factors predictive of outcome. The median age was 59 years (36-72). Most patients (72%) were JAK2+ and had int2-high DIPSS (92%). The conditioning regimen consisted of thiotepa, busulfan , fludarabine (TBF). All pts received thiotepa 10 mg/kg and fludarabine 150 mg/m^2. The dose of busulfan was adjusted considering the age and the comorbidity score. One pt received 3 days of busulfan (total dose 9.6 mg/kg); 47 received 2 days (total dose 6.4 mg/kg) and 8 received one day of busulfan iv (3.2 mg/kg). Donor was an identical sibling in 13 pt, haploidentical in 18, matched unrelated donor (UD) in 18 and a mismatchedUD in 7. Thus we had 31 HLA matched and 25 HLA mismatched grafts. Fortytwo patients received post-transplant cyclophosphamide (PTCy)-based GVHD (Graft versus host disease ) prophylaxis with cyclosporine and mycophenolate mofetil , and 14 patients received a standard GvHD prophylaxis (CSA+MTX+ATG). The 2 year survival (OS) was 73 % and disease free survival (DFS) was 66 % and the cumulative incidence (CI) of TRM was 23% and of relapse 11%. The incidence of acute GvHD grade II-IV was 22% in HLA matched and 50% in HLA mismatched pts (p=0.022), grade III-IV was 6% and 25% respectively (p=0.042) . The incidence of moderate-severe chronic GvHD was 25% in HLA matched and 36% in HLA mismatched grafts (p=0.36). HLA had a major impact on survival : 85% vs 49% survival for matched vs mismatched patients (p=0.01). Patients age &gt;60 years had a major impact on outcome, with a 2 year survival of 51% vs 88% in patients over (n=24) or under 60 years of age (n=32) (p=0.007; the DFS was 46 % and 80% respectively and the CI of TRM was 42% vs 9% (p=0.003). As to the total dose of busulfan, we found 26% TRM in patients receiving busulfan for 2 days (total doe 6.4 mg/kg) (n=47) and 0% in older patients receiving 1 day only (total dose 3.2 mg/kg) (n=8) ; relapse rate was 10% and 20% respectively. In multivariate cox analysis including age, spleen size ,DIPSS score, number of transfusion received and donor type, only HLA matching influenced the incidence of acute GvHD; transfusion burden and age plays a role in NRM and OS; DIPSS predicts relapse . In conclusion: older patients with MF have a high NRM and need to be prepared with a milder conditioning regimen. Disclosures Laurenti: Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

ArthroRad trial: multicentric prospective and randomized single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis depending on the dose—results after 3 months’ follow-up

Purpose Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime Patients and methods Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. Results A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. Conclusion We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.

Prospective superficial EPR in-vivo dosimetry study during hypofractionated radiotherapy of breast cancer patients treated with helical tomotherapy

Background In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). Methods In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient’s skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. Results Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. Conclusion Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.

Pain as the evaluation criterion for bone metastasis radiosensitivity. Comparative efficacy of radiation therapy in patients with bone metastases of various primary tumors.

Purpose: Assessment of the comparative radiosensitivity of bone metastases of various nature and histogenesis. Material/methods: As part of a randomized study, 810 courses of 3D-conformal or IMRT / VIMAT radiotherapy were performed for bone metastases of various origins and localization with persistent pain syndrome. Radiotherapy protocol included hypofractionation regimes of 2, 3 or 4 fractions of 6,5 Gy with total dose of 13-26 Gy or standard fractionation regime with total dose of 46 Gy. Results: The overall effectiveness (сomplete and partial pain relief) of radiotherapy was 96.2%, complete response rate (CRR) – 56.2%, partial response rate – 40.0%. Pain relapse rate was 8.6%, on average after 9.5 months after irradiation. The independent predictors of the CRR were: the initial pain intensity [hazard ratio (RR): 0.48, confidence interval (CI): 0.40-0.58; p = 0.0001], dose/number of fractions (RR: 1.26, CI: 1.07-1.50; p = 0.0059) and primary tumor site (RR: 0.95, CI: 0.92-0,99; p = 0.0053). We constructed a scale of comparative radiosensitivity of bone metastases of various primary tumors, taking into account the complete response rate and the probability of surviving without pain relapse for 6, 12 and 24 months after radiotherapy. The radiosensitive group included metastases from breast and prostate cancer, melanoma, bladder and PNET (CRR 60% or more), and relatively radioresistant group - metastases from unknown origin, colon, stomach and kidney cancer (CRR 40% or less). Conclusion: More than 95% overall effectiveness of radiotherapy for bone metastases, with pain relapse rate of less than 10% of cases, allows us to consider widefield irradiation in doses of 19.5-26 Gy, in 3-4 fractions of 6.5 Gy, the preferred treatment for multifocal lesions. Dose escalation in patients with bone metastases of kidney, colon, lung cancer and metastases from unknown origin seems to be justified in the cases with a life expectancy of more than a year.