Association between treatment-related lymphopenia and survival in glioblastoma patients following postoperative chemoradiotherapy.

PURPOSE: Our study investigated the association between treatment-related lymphopenia and overall survival (OS) in a series of glioblastoma (GBM) patients. We also explored clinical and dosimetric predictors of lymphocytes depletion. METHODS: Between 2015 and 2019, 64 patients were treated at the same institution with postoperative chemoradiotherapy. Peripheral lymphocyte count (PLC) data and dose-volume histogram parameters were collected. Radiotherapy (RT) schedule consisted in standard total dose of 60 Gy in 30 daily fractions, with concomitant and adjuvant temozolomide (TMZ). Posttreatment acute absolute lymphopenia (nadir AAL) was calculated as a PLC lower than 1.0â€¯× 103/mm3. Acute relative lymphopenia (ARL) was expressed by the nadir-PLC/baseline-PLC ratio < 0.5. Nadir-PLC was the lowest PLC registered between the end of RT and the first month of follow-up. Survival rates were estimated with Kaplan-Meier curves. Clinical and dosimetric variables related to AAL/ARL and OS were identified by univariate and multivariate analyses. RESULTS: A total of 57 patients were eligible and included in the analyses. The median PLC was significantly decreased following chemoradiotherapy (2180/mm3 vs 900/mm3). Median OS was 16 months (range 5-55 months), with no significant difference between patients who developed nadir AAL and those who did not (16 months vs 16.5 months; p = 0.304). When considering ARL vs non-ARL, median OS was 14 months vs 26 months (p = 0.013), respectively. In multivariate Cox regression only age, sex, extent of surgery, access to adjuvant chemotherapy and brain D98% were independently associated with OS. CONCLUSION: Although iatrogenic immunosuppression could be associated with inferior clinical outcomes, our data show that treatment-related lymphopenia does not adversely affect GBM survival. Prospective studies are required to confirm these findings.

A Systematic Review and a Meta-analysis of Randomized Controlled Trials' Control Groups in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

PURPOSE OF REVIEW: Determining the risk for progression or survival after standard androgen deprivation treatment (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) is essential for stratifying patients according to expected outcomes in future studies of treatment combination. This systematic review and meta-analysis aims to estimate the progression-free survival (PFS) and overall survival (OS) probabilities in the control group of randomized controlled trials (RCTs) of different regimens of standard androgen deprivation treatment (ADT) in mHSPC and to identify possible predictors of outcomes. RECENT FINDINGS: Studies reporting time-dependent outcomes (progression or death) after standard ADT treatment of mHSPC were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through June 2021. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of disease progression and survival. Fifteen studies met the inclusion criteria. The pooled estimate of the actuarial PFS rate was 35.2% at two years. The pooled actuarial OS rate was 62.5% at three years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, high-volume disease and the presence of visceral metastases were associated with shorter survival. Our findings show that PFS and OS are highly variable in patients with mHSPC treated with ADT, providing a helpful benchmark for indirect comparisons of the benefits of the combination of chemotherapy and second-generation hormonotherapy.

Stereotactic radiotherapy for liver oligometastases.

The liver is the first metastatic site in 15-25% of colorectal cancer patients and one of the first metastatic sites for lung and breast cancer patients. A computed tomography (CT ) scan with contrast medium is a standard procedure for assessing liver lesions but magnetic resonance imaging (MRI) characterizes small lesions better thanks to its high soft-tissue contrast. Positron emission tomography with computed tomography (PET-CT ) plays a complementary role in the diagnosis of liver metastases. Triphasic (arterial, venous and time-delayed) acquisition of contrast-medium CT images is the first step in treatment planning. Since the liver exhibits a relatively wide mobility due to respiratory movements and bowel filling, appropriate techniques are needed for target identification and motion management. Contouring requires precise recognition of target lesion edges. Information from contrast MRI and/or PET-CT is crucial as they best visualize metastatic disease in the parenchyma. Even though different fractionation schedules were reported, doses and fractionation schedules for liver stereotactic radiotherapy (SRT ) have not yet been established. The best local control rates were obtained with BED10 values over 100 Gy. Local control rates from most retrospective studies, which were limited by short follow-ups and included different primary tumors with intrinsic heterogeneity, ranged from 60% to 90% at 1 and 2 years. The most common SRT-related toxicities are increases in liver enzymes, hyperbilirubinemia and hypoalbuminemia. Overall, late toxicity is mild even in long-term follow-ups.

Integrating stereotactic radiotherapy and systemic therapies.

This paper focuses on stereotactic radiotherapy (SRT ) interactions with targeted therapies and immune system modulating agents because SRT inevitably interacts with them in the treatment of oligometastatic patients. Radiation oncologists need to be aware of the advantages and risks of these interactions which can, on one hand, enhance the effect of therapy or, on the other, potentiate reciprocal toxicities. To date, few prospective studies have evaluated the interactions of SRT with new-generation drugs and data are mainly based on retrospective experiences, which are often related to small sample sizes.

Radiotherapy role in non-seminomatous germ cell tumors, radiobiological and technical issues of an unexplored scenario.

Historically, non-seminomatous germ cell tumor (NSGCT) has been considered a radio-resistant disease, excluding radiotherapy (RT) from curative strategies. However, case series exploring the use of radiation treatment in this setting are often outdated, and prospective ongoing studies testing new radiotherapeutic approaches in NSGCT are lacking. Considering that tremendous advances in radiotherapy technology have enabled improved precision in RT delivery as well as dose escalation while decreasing treatment-related morbidity, we overviewed the currently available literature to explore the radiobiological basis, the technical issues, and potential strategies for implementation of RT in the management of this clinical entity. The purpose of the present overview is to provide insight for future research in this unexplored scenario. In summary, the biological rationale for RT use and potential implementation with systemic therapies exist, especially considering the advantage of new technologies, which were unavailable in the era of early literature reports. The NSGCT radioresistance paradigm could be based only on the fact that effective treatment schedules were simply undeliverable with older RT techniques due to toxicity issues, but the availability of actual techniques may prompt further exploration to offer treatment alternatives to these patients. Ongoing trials on this issue are lacking, but potential areas of research are platinum-refractory disease and consolidation therapy for residual masses after PST.

PROACTA: a survey on the actual attitude of the Italian radiation oncologists in the management and prescription of hormonal therapy in prostate cancer patients.

AIM: To investigate the actual attitude of Radiation Oncologists in the prescription of hormonal therapy in prostate cancer (PC) with or without Radiation Therapy (RT). MATERIALS AND METHODS: In 2019, a survey named Prescription of Radiation Oncologists ACtual Attitude including 18 items was sent to all Italian Radiation Oncologists of the Italian Association of Radiotherapy and Clinical Oncology. The first 4 items were about the Radiation Oncology Centers characteristics and years of practice of the respondents. The remaining 14 items concerned the setting in which hormone therapy was prescribed in PC patients (radical, postprostatectomy/oligometastatic state), the kind of drug, the choice modality (Multidisciplinary Group/autonomy decision) and other factors. RESULTS: A total of 127 questionnaires were returned, mainly by Northern Italy Radiation Oncology Centres (44.9%), and by experienced Radiation Oncologists (78%), who declared to prescribe independently hormone therapy in 85.8% of cases. The Androgen deprivation therapy (ADT) prescription in castration naive PC was made independently by 56.7% of respondents and associated with radical RT, postoperative or salvage RT according to various risk factors. In castration-sensitive oligorecurrent PC, the majority (51.2%) administered ADT only if local ablative treatment was not feasible, while in metastatic castration resistant disease novel hormone therapy use was established in almost half of cases within multidisciplinary board. Radiation Oncologists could prescribe these drugs independently in 64% of cases. CONCLUSION: Our survey established the prescription attitude of ADT and new hormonal agents (abiraterone, enzalutamide, apalutamide) by Italian Radiation Oncologists and highlighted the importance of expertise in global PC management.

Sequential chemo-hypofractionated RT versus concurrent standard CRT for locally advanced NSCLC: GRADE recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

INTRODUCTION: Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach. AIMS: A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC MATERIALS AND METHODS: The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3-G4 toxicity, late pulmonary toxicity G3-G4, and acute esophageal toxicity G3-G4. RESULTS: The probability of OS and G3-G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms. CONCLUSIONS: The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients.

Safety culture to improve accidental event reporting in radiotherapy.

BACKGROUND AND PURPOSE: The potential for unintended and adverse radiation exposure in radiotherapy (RT) is real and should be studied because RT is a highly complex, multistep process, which requires input from numerous individuals from different areas and steps of the RT workflow. The 'Incident' (I) is an event the consequence of which is not negligible from the point of view of protection or safety. A 'near miss' (NM) is defined as an event that is highly likely to happen but did not occur. The purpose of this work is to show that through systematic reporting and analysis of these adverse events, their occurrence can be reduced. MATERIALS AND METHODS: Staff were trained to report every type of unintended and adverse radiation exposure and to provide a full description of it. RESULTS: By 2018, 110 worksheets had been collected, with an average of 6.1 adverse events per year (with 780 patients treated per year, meaning an average incident rate of 0.78%). In 2001-2009, 37 events were registered (13 I and 24 NM), the majority of them were in the decision phase (12/37), while in 2010-2013, there were 42 (1 I and 41 NM) in both the dose-calculation and transfer phase (19/42). In 2014-2018, 31 events (1 I and 30 NM) were equally distributed across the phases of the RT process. In 9/15 cases of I, some checkpoint was introduced. CONCLUSION: The complexity of the RT workflow is prone to errors, and this must be taken into account by encouraging a safety culture. The aim of this paper is to present the collected incidents and near misses and to show how organization and practice were modified by the acquired knowledge.

Molecular analysis of carnivore Protoparvovirus detected in white blood cells of naturally infected cats.

BACKGROUND: Cats are susceptible to feline panleukopenia virus (FPV) and canine parvovirus (CPV) variants 2a, 2b and 2c. Detection of FPV and CPV variants in apparently healthy cats and their persistence in white blood cells (WBC) and other tissues when neutralising antibodies are simultaneously present, suggest that parvovirus may persist long-term in the tissues of cats post-infection without causing clinical signs. The aim of this study was to screen a population of 54 cats from Sardinia (Italy) for the presence of both FPV and CPV DNA within buffy coat samples using polymerase chain reaction (PCR). The DNA viral load, genetic diversity, phylogeny and antibody titres against parvoviruses were investigated in the positive cats. RESULTS: Carnivore protoparvovirus 1 DNA was detected in nine cats (16.7%). Viral DNA was reassembled to FPV in four cats and to CPV (CPV-2b and 2c) in four cats; one subject showed an unusually high genetic complexity with mixed infection involving FPV and CPV-2c. Antibodies against parvovirus were detected in all subjects which tested positive to DNA parvoviruses. CONCLUSIONS: The identification of FPV and CPV DNA in the WBC of asymptomatic cats, despite the presence of specific antibodies against parvoviruses, and the high genetic heterogeneity detected in one sample, confirmed the relevant epidemiological role of cats in parvovirus infection.

Re-irradiation with curative intent in patients with squamous cell carcinoma of the head and neck: a national survey of usual practice on behalf of the Italian Association of Radiation Oncology (AIRO).

OBJECTIVE: To report the results of a national survey investigating the pattern of practice of curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head and neck. METHODS: In March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings. RESULTS: Overall, 77 centers completed the survey. The majority (50/77, 64.9%) of participating radiation oncologists were senior consultants (> 10 years of experience). Of the responding centers, 63 (81.8%) performed curative ReRT, while 14 (18.1%) did not, mainly (5/14, 35.7%) due to the avoidance of severe toxicity. The use of adjuvant ReRT was reported by less than half of the interviewed radiation oncologists (36/77, 46.7%). In case of unresectable local recurrence, definitive ReRT was claimed to be adopted in 55/77 (71.4%) for non-nasopharyngeal and 47/77 (61%) for nasopharyngeal cancer. The preferred treatment technique was Intensity Modulated Radiation Therapy (IMRT) followed by Stereotactic Body Radiation Therapy (SBRT). When IMRT was applied, the most common (19/55 responders, 34.5%) selection of treatment volume consisted of the Gross Tumor Volume (GTV) + 0.5 cm margin to account for microscopic disease. CONCLUSION: Despite the absence of definitive evidence-based recommendations, a possible consideration for ReRT in case of unresectable recurrent head and neck cancer was reported by over 80% of radiation oncologists taking part in the national survey.

GUROPA survey: genito-urinary radiation oncology prescription attitudes.

AIMS: To investigate the role of Radiation Oncology in the management of genito-urinary (GU) cancer excluding prostate and penile cancer. METHODS: The questionnaire was focused on the evaluation of the degree of involvement of radiation oncologists in the work-up of bladder, renal cell carcinoma and testicular cancer (TC). RESULTS: Eighty-eight radiation oncologists completed the survey. The majority (85.4%) of participating radiation oncologists were senior consultants (> 5 years of experience). Sixty-four (73.6%) carried out a multidisciplinary tumor board discussion of GU cases, while 23 (26.4%) did not. Seventy-five percent of responders reported that, every year, visited < 50 GU patients (pts), 18.1% visited 50-100 pts and 6.9% visited > 100 pts. Bladder cancer, curative radiotherapy (RT) as part of trimodality approach was claimed to be adopted in less than 10 cases per year. Regarding renal cell carcinoma (RCC) patients, primary tumor directed RT was adopted only in 8 cases (9.4%) in at least 10 pts per year. Palliative RT was more frequent in RCC (48.2%) in over than 10 pts per year. In case of TC, the prescription of RT was limited (< 10 patients per year) due to the low incidence of disease and recent shift to surveillance as a first option in stage I seminoma. CONCLUSIONS: Our survey showed that radiation oncologists are rarely involved in the decision making strategy of GU cancer, despite many clinical trials support RT use. These patients probably deserve a more uniform approach based on updated, detailed and evidence-based recommendations.

Retreatment for prostate cancer with stereotactic body radiation therapy (SBRT): Feasible or foolhardy?

The most popular therapeutic option in the management of radio-recurrent prostatic carcinoma is represented by the androgen deprivation therapy, that however should be considered only palliative and hampered by potential adverse effects of testosterone suppression. Local therapies such as surgery, cryoablation or brachytherapy might be curative choices for patients in good conditions and with a long-life expectancy, but at cost of significant risk of failure and severe toxicity. The administration of stereotactic body radiation therapy (SBRT) in this setting have come about because of tremendous technologic advances in image guidance and treatment delivery techniques that enable the delivery of large doses to tumor with reduced margins and high gradients outside the target, thereby reducing the volume of rectum which already received significant doses from primary radiotherapy. So far, very modest data are available to support its employment. Rationale, clinical experience, and challenges are herein reviewed and discussed.

Fast and sensitive method for the diagnosis and follow-up of anticoagulant rodenticides poisoning in animal whole blood.

Rodent control strategies are primarily based on the use of anticoagulant rodenticides (ARs), making them widely used worldwide. However, due to their high toxicity and availability, ARs are among the leading causes of animal poisoning in Europe. They are the primary agents involved in intoxication in cats and the second in dogs. Additionally, their long persistence in the body can lead to secondary exposure, particularly in wild predators. The laboratory findings and clinical signs of intoxication can range from increased clotting time (prolonged prothrombin time and activated partial thromboplastin time) to severe bleeding and death. Despite the prevalence and severity of this intoxication, only a few methods are available for the identification and quantification of ARs in animals, and most of them are suitable only for post-mortem diagnosis. In this study, we present the validation of a rapid and sensitive method for the identification and quantification of ARs in animal whole blood, using a small sample volume. The developed LC-MS/MS method demonstrated high accuracy and precision at the limit of quantification (LOQ), as well as at low, medium, and high concentrations. It exhibited higher sensitivity (LOQ 0.1 - 0.3 ng/mL) compared to previously published methods. After validation, the method was successfully applied to real cases of suspected poisoning events, resulting in the identification of several positive samples. The examples presented in this study highlight the utility of this method for diagnosis and follow-up, emphasizing the importance of method sensitivity in order to avoid misclassifying truly positive samples as negative.

Toxicity profile and Patient-Reported outcomes following salvage Stereotactic Ablative Radiation Therapy to the prostate Bed: The POPART multicentric prospective study.

Background: While SBRT to the prostate has become a valuable option as a radical treatment, limited data support its use in the postoperative setting. Here, we report the updated results of the multicentric Post-Prostatectomy Ablative Radiation Therapy (POPART) trial, investigating possible predictors of toxicities and patient-reported outcomes. Methods: Patients with PSA levels between 0.1-2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD21.5 = 74.3 Gy). Late toxicity was assessed using CTCAE v.5 scale, while EPIC-CP, ICIQ-SF, IIEF 5 questionnaires and PSA levels measured quality of life and biochemical control. Pre- and post-treatment scores were compared using a paired t-test, with MID established at > 0.5 pooled SD from the baseline. A logistic regression analysis was performed to evaluate potential associations between specific patient/tumor/treatment factors and outcome deterioration. Results: From April 2021 to April 2023 a total of 50 pts were enrolled and treated. Median follow-up was 12.2 (3-27) months. No late ≥ G2 GI or GU toxicity was registered. Late G1 urinary and rectal toxicities occurred in 46 % and 4 % of patients, respectively. Among 47 patients completing all EPIC-CP domains, four (9 %) showed worsened QoL, and eleven (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032). At Multivariate analysis bladder wall D10cc independently correlated with late G1 GU toxicity (P = 0.034). Median post-treatment PSA nadir was 0.04 ng/mL (0.00 - 0.84). At the last follow-up, six patients presented with biochemical failure, including two nodal relapses. Conclusions: Our findings show that post-prostatectomy SBRT did not result in increased toxicity nor a significant decline in QoL measures, thus showing that it can be safely extended to the postoperative setting. Long-term follow-up and randomized comparisons with different RT schedules are needed to validate this approach.

Lexicographic optimization-based planning for stereotactic radiosurgery of brain metastases.

AIM: To validate a fully-automated lexicographic optimization-planning system (mCycle, Elekta) for single-(SL) and multiple-(ML, up to 4 metastases) lesions in intracranial stereotactic radiosurgery (SRS, 21 Gy, single fraction). METHODS: A pre-determined priority list, Wish-List (WL), represents a dialogue between planner and clinician, establishing strict constraints and pursuing objectives. In order to satisfy the clinical protocol without manual intervention, four patients were required to tweak and fine-tune each WL (SLp, MLp) for coplanar arcs. Thirty-five testing plans (20 SLp, 15 MLp) were automatically re-planned (mCP). Automatic and manual plans were compared including dose constraints, conformality, modulation complexity score (MCS), delivery time, and local gamma analysis (2%/2 mm). To ensure plan clinical acceptability, two radiation oncologists conducted an independent blind plan choice. RESULTS: Each WL-tuning took 3 days. Estimated median manual plans and mCP calculation time were 8 and 3 h, respectively. Significant increases in SLp and MLp target coverage and conformity were registered. mCP showed a not significant and clinically acceptable higher median brain V12Gy. SLp registered a -5.8% MU decrease with comparable median delivery time (MP 2.0 min, mCP 1.9 min) while MLp showed a +9.8% MU increase and longer delivery time (MP 3.5 min, mCP 4.4 min). mCP MCS resulted significantly higher without affecting gamma passing rates. At blind choice, mCP were preferred in the majority of cases. CONCLUSIONS: Lexicographic optimization produced acceptable SRS plans with coplanar arcs significantly reducing the overall planning time in cases with up to 4 brain metastases. These planning improvements suggest further investigations by setting high-quality non-coplanar arc plans as a reference.

Management of patients with extensive small-cell lung cancer in the immunotherapy era: An Italian consensus through a Delphi approach.

BACKGROUND: Immunotherapy represented a turning point for treating extensive small-cell lung cancer (ES-SCLC). Although, many issues remain debated. METHODS: A group of Italian medical and radiation oncologists with expertise in managing patients with ES-SCLC developed a list of statements divided in six areas of interest. The Delphi method was used to assess the consensus on the defined list of statements. RESULTS: 32 statements were included in the final list to be voted by the Delphi panel, and 26 reached a consensus on the agreement. A prompt involvement of a multidisciplinary team is a priority to provide an integrated treatment strategy. First-line recommended treatment is immunotherapy in combination with platinum-based chemotherapy and etoposide for four cycles followed by maintenance immunotherapy. CONCLUSIONS: While awaiting new data from clinical trials and real-world studies, these recommendations can represent a useful tool to guide the management of ES-SCLC patients in daily practice.

Treatment Optimization in Linac-Based SBRT for Localized Prostate Cancer: A Single-Arc versus Dual-Arc Plan Comparison.

This study aimed to comprehensively present data on treatment optimization in linac-based SBRT for localized prostate cancer at a single institution. Moreover, the dosimetric quality and treatment efficiency of single-arc (SA) versus dual-arc (DA) VMAT planning and delivery approaches were compared. Re-optimization was performed on twenty low-to-intermediate-risk- (36.25 Gy in 5 fractions) and twenty high-risk (42.7 Gy in 7 fractions) prostate plans initially administered with the DA FFF-VMAT technique in 2021. An SA approach was adopted, incorporating new optimization parameters based on increased planning and clinical experience. Analysis included target coverage, organ-at-risk (OAR) sparing, treatment delivery time, and the pre-treatment verification's gamma analysis-passing ratio. The SA optimization technique has consistently produced superior plans. Rectum and bladder mean doses were significantly reduced, and comparable target coverage and homogeneity were achieved in order to maintain a urethra protection strategy. The mean SA treatment delivery time was reduced by 22%; the mean monitor units increased due to higher plan complexity; and dose measurements demonstrated optimal agreement with calculations. The substantial reduction in treatment delivery time decreased the probability of prostate motion beyond the applied margins, suggesting potential decrease in treatment-related toxicity and improved target coverage in prostate SBRT. Further investigations are warranted to assess the long-term clinical outcomes.

Analysis of Metaldehyde in Animal Whole Blood and Serum by Gas Chromatography-Mass Spectrometry.

Metaldehyde, a widely used molluscicide, is the third cause of intoxication by pesticides in domestic animals in Europe. Most mammalian species are susceptible, and its exposure may lead to death within a few hours. While metaldehyde intoxication diagnosis is in most cases presumptive, based on the symptomatology or from "postmortem" analysis, few analytical methods are currently available for live animals. The aim of this work was to describe a fast analytical method for the specific and quantitative determination of metaldehyde in animal whole blood and serum at concentrations of toxicological significance. A liquid-liquid extraction with chloroform and gas chromatography-mass spectrometry quantification are proposed. The method limit of quantification (LOQ) was 0.04 µg/mL in serum and whole blood. The method was linear in the range from 0.04 to 200 µg/mL. The recovery was between 93% and 102% for LOQ, low, medium and high spike concentrations. Intra- and inter-assay relative standard deviation was <12% in all spike concentrations in both serum and whole blood, apart from one of the experiments at LOQ in whole blood, which accounted for 17.7%. The method was applied to real intoxication cases, and the concentration found in positive samples was between 29 and 69 µg/mL. The proposed method provides high sensitivity, accuracy and precision and can be used to assist in the diagnosis of metaldehyde poisoning.

Dosimetric Impact of Intrafraction Prostate Motion and Interfraction Anatomical Changes in Dose-Escalated Linac-Based SBRT.

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient's original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient's CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were -3.0% [-18.5-2.8] for CTV D99% and -2.6% [-17.8-1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments.