Search

The addition of CDK4/6 inhibitors to endocrine therapy in advanced hormone receptor-positive HER2-negative breast cancer has led to practice-changing improvements in overall survival. However, data concerning the safety of CDK4/6i combination with radiotherapy (RT) are conflicting. A retrospective evaluation of 288 advanced breast cancer patients (pts) treated with CDK4/6i was performed, and 100 pts also received RT. Forty-six pts received 63 RT courses concurrently and fifty-four sequentially before CDK4/6i initiation (76 RT courses). Neutropenia was common (79%) and more frequent during and after concurrent RT than sequential RT (86% vs. 76%); however, CDK4/6i dose reduction rates were similar. In patients treated with CDK4/6i alone, the dose reduction rate was 42% (79 pts) versus 38% with combined therapy, and 5% discontinued treatment due to toxicity in the combined group. The risk of CDK4/6i dose reduction was correlated with neutropenia grade, RT performed within the first two CDK4/6i cycles, and more than one concurrent RT; a tendency was observed in concurrent bone irradiation. However, on multivariate regression analysis, only ECOG 1 performance status and severe neutropenia at the beginning of the second cycle were found to be associated with a higher risk of CDK4/6i dose reduction. This largest single-center experience published to date confirmed the acceptable safety profile of the CDK4/6i and RT combination without a significantly increased toxicity compared with CDK4/6i alone. However, one might delay RT for the first two CDK4/6i cycles, when myelotoxic AE are most common.

Cardiac stereotactic body radiotherapy is an emerging treatment method for recurrent ventricular tachycardia refractory to invasive treatment methods. The single-fraction delivery of 25 Gy was assumed to produce fibrosis, similar to a post-radiofrequency ablation scar. However, the dynamics of clinical response and recent preclinical findings suggest a possible different mechanism. The data on histopathological presentation of post-radiotherapy hearts is scarce, and the authors provide significantly different conclusions. In this article, we present unique data on histopathological examination of a heart explanted from a patient who had a persistent anti-arrhythmic response that lasted almost a year, until a heart failure exacerbation caused a necessity of a heart transplant. Despite a complete treatment response, there was no homogenous transmural fibrosis in the irradiated region, and the overall presentation of the heart was similar to other transplanted hearts of patients with advanced heart failure. In conclusion, our findings support the theorem of functional changes as a source of the anti-arrhythmic mechanism of radiotherapy and show that durable treatment response can be achieved in absence of transmural fibrosis of the irradiated myocardium., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miszczyk, Sajdok, Nożyński, Cybulska, Bednarek, Jadczyk, Latusek, Kurzelowski, Dolla, Wojakowski, Dyla, Zembala, Drzewiecka, Kaminiów, Kozub, Chmielik, Grza̧dziel, Bekman, Gołba and Blamek.)

Background: Stereotactic Arrhythmia Radioablation (STAR) is an emerging treatment modality for patients with sustained ventricular tachycardia (VT) and refractory to treatment with drugs and radiofrequency catheter ablation (RFA). It is believed that up to 12-17% of patients experience recurrence of VT within 1 year of follow-up; thus, novel therapeutic options are needed. The aim of this article is to present initial experience within a novel treatment modality for VT., Case Summary: Two patients with a medical history of coronary artery disease and heart failure with reduced left ventricle (LV) ejection fraction, after implantation of cardioverter-defibrillator (ICD) and previous unsuccessful RFAs owing to sustained VT were admitted to the cardiology department due to recurrence of sustained VT episodes. With electroanatomical mapping (EAM), the VT substrate in LV has been confirmed and specified. In order to determine the target volume for radioablation, contrast-enhanced computed tomography was performed and the arrhythmia substrate was contoured using EAM data. Using the Volumetric Modulated Arc Therapy technique and three 6 MeV flattening filter-free photon beam fields, a single dose of 25 Gy was delivered to the target volume structure located in the apex and anterior apical segments of LV in the first patient and in the apex, anterolateral and inferior apical segments of the second patient. In both cases, volumes of the target structures were comparable. Interrogation of the implanted ICD at follow-up visits throughout 6 months after the treatment revealed no VT episodes in the first patient and sudden periprocedural increase in VT burden with a subsequent gradual decrease of ventricular arrhythmia to only two non-sustained episodes at the end of the follow-up period in case of the second patient. A significant reduction in premature ventricular contractions burden was observed compared to the pre-treatment period. No noticeable deterioration in LV function was noted, nor any adverse effects of radiosurgery associated with the implanted device., Conclusion: The early response to STAR can be unpredictable and probably does not reflect the final outcome of irradiation. Close monitoring of patients, especially in the early period after irradiation is crucial to properly handle potentially harmful early reactions to STAR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kurzelowski, Latusek, Miszczyk, Jadczyk, Bednarek, Sajdok, Gołba, Wojakowski, Wita, Gardas, Dolla, Bekman, Grza̧dziel and Blamek.)

State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33-35 fractions). During the 28-month (median) follow-up 27 patients (28%) developed RIHT. For each patient, we extracted 1316 radiomic features from original and transformed images using manually contoured thyroid masks. Creating models based on clinical, radiomic features or a combination thereof, we considered 3 variants of data preprocessing. Based on their performance metrics (sensitivity, specificity), we picked best models for each variant ((0.8, 0.96), (0.9, 0.93), (0.9, 0.89) variant-wise) and compared them with external NTCP models ((0.82, 0.88), (0.82, 0.88), (0.76, 0.91)). We showed that radiomic-based models did not outperform state-of-art NTCP models ( p > 0.05). The potential benefit of radiomic-based approach is that it is dose-independent, and models can be used prior to treatment planning allowing faster selection of susceptible population.

We aimed to externally validate five normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RIHT) in a prospectively recruited cohort of 108 patients with oropharyngeal cancer (OPC). NTCP scores were calculated using original published formulas. Plasma thyrotropin (TSH) level was additionally assessed in the short-term after RT. After a median of 28 months of follow-up, thirty one (28.7%) patients developed RIHT. Thyroid mean dose and thyroid volume were significant predictors of RIHT: odds ratio equal to 1.11 (95% CI 1.03-1.19) for mean thyroid dose and 0.87 (95%CI 0.81-0.93) for thyroid volume in univariate analyses. Two of the evaluated NTCP models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance with accuracies of 0.87 (95%CI 0.79-0.93) and 0.84 (95%CI: 0.76-0.91), respectively. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse, overestimating the risk of RIHT in this patient cohort. A short-term TSH level change relative to baseline was not indicative of RIHT development in the follow-up (OR 0.96, 95%CI: 0.65-1.42, p = 0.825). In conclusion, the models by Rønjom et al. and by Boomsma et al. demonstrated external validity and feasibility for long-term prediction of RIHT in survivors of OPC treated with Intensity-Modulated Radiation Therapy (IMRT).

Objectives: No experimental study has shown that the myocardium of a remotely preconditioned patient is more resistant to a standardized ischaemic/hypoxic insult., Methods: This was a single-centre randomized (1:1), double-blinded, sham-controlled, parallel-group study. Patients referred for elective coronary bypass surgery were allocated to either remote ischaemic preconditioning (3 cycles of 5-min ischaemia/5-min reperfusion of the right arm using a blood pressure cuff inflated to 200 mmHg) or sham intervention. One hundred and thirty-four patients were recruited, of whom 10 dropped out, and 4 were excluded from the per-protocol analysis. The right atrial trabecula harvested on cannulation for cardiopulmonary bypass was subjected to 60 min of simulated ischaemia and 120 min of reoxygenation in an isolated organ experiment. Postoperative troponin T release and haemodynamics were assessed in an in vivo study., Results: The atrial trabeculae obtained from remotely preconditioned patients recovered 41.9% (36.3-48.3) of the initial contraction force, whereas those from non-preconditioned patients recovered 45.9% (39.1-53.7) (P = 0.399). Overall, the content of cleaved poly (ADP ribose) polymerase in the right atrial muscle increased from 9.4% (6.0-13.5) to 19.1% (13.2-23.8) (P < 0.001) after 1 h of ischaemia and 2 h of reperfusion in vitro. The amount of activated Caspase 3 and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells also significantly increased. No difference was observed between the remotely preconditioned and sham-treated myocardium. In the in vivo trial, the area under the curve for postoperative concentration of troponin T over 72 h was 16.4 ng⋅h/ml (95% confidence interval 14.2-18.9) for the remote ischaemic preconditioning and 15.5 ng⋅h/ml (13.4-17.9) for the control group in the intention-to-treat analysis. This translated into an area under the curve ratio of 1.06 (0.86-1.30; P = 0.586)., Conclusions: Remote ischaemic preconditioning with 3 cycles of 5-min ischaemia/reperfusion of the upper limb before cardiac surgery does not make human myocardium more resistant to ischaemia/reperfusion injury., Clinical Trial Registration Number: NCT01994707., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)