Radiation Exposure of Cardiac Conduction Nodes During Breast Proton Therapy.

Purpose: The exposition of cardiac conduction system during breast radiation therapy has never been studied, despite the increasing use of intensity-modulated radiation therapy, which exposes larger volume to low-dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arc therapy and estimated the potential dosimetric benefit with intensity-modulated proton therapy. Materials and Methods: Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation computed tomography scans of 12 breast cancer patients having undergone conserving surgery and adjuvant locoregional volumetric modulated arc therapy. Intensity-modulated proton therapy treatment was replanned on the simulation computed tomography scans for all breast cancer patients. Mean and maximum doses delivered to the SAN and the AVN were retrieved and compared. Correlation coefficients were calculated between doses to the SAN or the AVN and the whole heart. Results: Average mean doses delivered to the SAN and AVN were 2.8 and 2.3 Gy, respectively, for left-sided irradiation and 9.6 and 3.6 Gy, respectively, for right-sided irradiation. Average maximum doses to the SAN and AVN were 3.5 Gy and 2.8 Gy, respectively, for left-sided irradiation and 13.1 and 4.6 Gy, respectively, for right-sided irradiation. Intensity-modulated proton therapy significantly reduced mean and maximum doses to the SAN and AVN. Correlations between doses to the SAN or AVN and whole heart were usually significant. Conclusion: SAN and AVN can be substantially exposed during breast volumetric modulated arc therapy, especially for right-sided irradiation. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac-sparing techniques, such as respiratory techniques or proton therapy, which could benefit patients with underlying rhythmic or conduction disorders.

Development of Simplified Auto-Segmentable Functional Cardiac Atlas.

PURPOSE: There is increasing evidence that radiation doses to cardiac substructures are associated with cardiac adverse events. Manual delineation of cardiac substructures is time-consuming, and auto-segmentation of cardiac substructure atlases has consequently been evaluated. However, proper automatic delineation of small substructures, such as the left anterior descending coronary artery, is challenging, and auto-segmentation of cardiac conduction system substructures has never been evaluated, despite multiple reports of radiation-induced arrhythmia after thoracic irradiations. The aim of this study was to propose and evaluate a simplified auto-segmentable functional cardiac atlas. METHODS AND MATERIALS: We created a cardiac substructure atlas based on 20 computed tomography scans from patients with breast cancer comprising the 4 cardiac cavities, a high-risk cardiac zone as a left anterior descending coronary artery surrogate, and the 2 cardiac conduction nodes. Automatic delineation of this atlas by an atlas-based auto-segmentation algorithm was evaluated on a validation data set, consisting of 20 additional computed tomography scans. Dice similarity coefficients were used to evaluate the concordance level between the manual and the automatic contours; a dosimetric comparison between mean and maximum doses to the manual and to the auto-segmented substructures was additionally performed, based on intensity modulated radiation therapy treatment plans of the patients of the validation set. RESULTS: Average dice similarity coefficient values were 0.78 for the 4 cardiac cavities, 0.65 for the high-risk cardiac zones, 0.56 for the sinoatrial node, and 0.15 for the atrioventricular node. Compared with manual contours, auto-segmented substructures were slightly smaller but the dosimetric parameters were similar. CONCLUSIONS: We proposed a simplified functional cardiac atlas that included the cardiac conduction system and circumvented coronary delineation difficulties by using a surrogate high-risk cardiac zone. Most cardiac substructures were associated with acceptable atlas-based auto-segmentation properties. Such an atlas could be used for epidemiologic studies and for clinical practice.

A Radiation Therapy Contouring Atlas for Cardiac Conduction Node Delineation.

PURPOSE: The heart is a complex organ at risk. Currently, radiation therapy cardiac delineation atlases do not include conduction system substructures, which exposure may clinically translate into arrhythmia and conduction disorders. We present a method to reproducibly delineate conduction nodes on noncontrast simulation computed tomography scans. METHODS AND MATERIALS: Localization and dimensioning of the sinoatrial and atrioventricular nodes volumes on noncontrast simulation computed tomography scans were proposed based on radio-anatomic and histologic considerations and agreed upon by a multidisciplinary staff. RESULTS: The proposed atlas enables the dosimetric evaluation of the sinoatrial and atrioventricular nodes exposure, and both contours correspond to 2-cm diameter spheres. CONCLUSIONS: This delineation atlas should facilitate the delineation of cardiac conduction nodes in clinical research and daily practice.

Cardiotoxicity in breast cancer patients treated with radiation therapy: From evidences to controversies.

Radiation therapy has a prime importance for breast cancer management. However, first-generation techniques delivered significant radiation dose to the heart, which substantially increased cardiac mortality. Breast radiation therapy has fortunately evolved, and state-of-the-art radiation therapy techniques currently efficiently spare the heart without altering local control or overall survival. However, at the present time, potential cardiotoxicity risk is still a matter of concern and controversies exist concerning how to precisely evaluate cardiac radiation exposure, how to predict radiation-induced cardiac adverse events and which dosimetric constraints are clinically relevant. Based on current literature, this paper aims to review the present understanding of cardiotoxicity associated with breast cancer irradiation and to discuss controversies and perspectives about cardiac sparing improvement.

Role of nutritional status in the early postoperative prognosis of patients operated for retroperitoneal liposarcoma (RLS): A single center experience.

PURPOSE: To assess the nutritional status and its role in the outcome of patients operated for retroperitoneal liposarcoma (RLS). MATERIAL AND METHODS: Retrospective study on consecutive patients operated with en bloc compartment resection for primary or local recurrence of RLS between 2016 and 2017. Preoperative nutritional and laboratory assessment comprising serum albumin, serum transthyretin, orosomucoid, and CRP was systematically performed. The following preoperative parameters were analysed: weight, body mass index (BMI), significant weight loss (>5% in one month and/or >10% in 6 months), serum albumin, transthyretin, CRP, orosomucoid. PINI (prognostic inflammatory and nutritional index) was calculated. RESULTS: There were 40 patients operated for RLS: 22 women and 18 men with a median age of 61 years (34-90). Median tumour was 280 mm (80-530). Median preoperative BMI was 24.8 (18-42) and median postoperative BMI was 23 (17.8-44). Twenty-one patients (52.5%) were considered to be malnourished: 3 with biological signs of malnutrition and 18 with weight loss. Eleven (47.6%) in the group of malnourished patients and 4 (26.3%) in the group with satisfactory nutritional status developed postoperative complications (p = 0.042). A PINI score>1 was related to significantly longer hospitalisation time 21.8 days (10-58) in comparison with 14.9 [9-30] in patients with PINI < 1, p = 0.003. CONCLUSIONS: The malnourished patients with RLS experienced more postoperative complications and longer hospitalisation. Nutritional status and biological markers contribute to the global management of RLS with improved postoperative behaviour including fewer complications and shorter hospitalisation. A prospective larger study with longer follow-up is necessary to refine these results.

Effects of an opioid on respiratory movements and expiratory activity in humans during isoflurane anaesthesia.

Opioids increase abdominal muscle activity during anaesthesia. We proposed that opioid activity during anaesthesia would change chest wall size and movement, and contribute to ventilation. Using an optical system to measure chest wall volume, we studied 10 patients during isoflurane anaesthesia, first under the influence of an opioid and then after reversal with naloxone. Measurements were made during quiet breathing and with carbon dioxide stimulation. Airway occlusion pressure was measured to assess inspiratory and expiratory muscle activity. Chest wall volume decreased with the onset of spontaneous breathing, and decreased further when breathing was stimulated by carbon dioxide. Reversal of opioid activity increased chest wall volume. Breathing movements were predominantly abdominal. Opioid action affected the timing and amplitude of breathing but the pattern of abdominal movement was not affected. Since opioids augment abdominal muscle action during expiration, the unchanged pattern of movement can be attributed to both diaphragm and abdominal activity displacing the abdominal wall reciprocally, in the inspiratory and expiratory phases of the respiratory cycle, respectively.

Case study thoracic radiotherapy in an elderly patient with pacemaker: the issue of pacing leads.

To assess clinical outcome of patients with pacemaker treated with thoracic radiation therapy for T8-T9 paravertebral chloroma. A 92-year-old male patient with chloroma presenting as paravertebral painful and compressive (T8-T9) mass was referred for radiotherapy in the Department of Radiation Oncology, Institut Curie. The patient presented with cardiac dysfunction and a permanent pacemaker that had been implanted prior. The decision of Multidisciplinary Meeting was to deliver 30 Gy in 10 fractions for reducing the symptoms and controlling the tumor growth. The patient received a total dose of 30 Gy in 10 fractions using 4-field conformal radiotherapy with 20-MV photons. The dose to pacemaker was 0.1 Gy but a part of the pacing leads was in the irradiation fields. The patient was treated the first time in the presence of his radiation oncologist and an intensive care unit doctor. Moreover, the function of his pacemaker was monitored during the entire radiotherapy course. No change in pacemaker function was observed during any of the radiotherapy fractions. The radiotherapy was very well tolerated without any side effects. The function of the pacemaker was checked before and after the radiotherapy treatment by the cardiologist and no pacemaker dysfunction was observed. Although updated guidelines are needed with acceptable dose criteria for implantable cardiac devices, it is possible to treat patients with these devices and parts encroaching on the radiation field. This case report shows we were able to safely treat our patient through a multidisciplinary approach, monitoring the patient during each step of the treatment.

Wound healing and catheter thrombosis after implantable venous access device placement in 266 breast cancers treated with bevacizumab therapy.

The aim of this study was to determine, in a population with metastatic breast cancer treated with bevacizumab therapy, the incidence of wound dehiscence after placement of an implantable venous access device (VAD) and to study the risk of catheter thrombosis. This study enrolled all VADs placed by 14 anesthetists between 1 January 2007 and 31 December 2009: 273 VADs in patients treated with bevacizumab therapy and 4196 VADs in patients not treated with bevacizumab therapy. In the bevacizumab therapy group, 13 cases of wound dehiscence occurred in 12 patients requiring removal of the VAD (4.76%). All cases of dehiscence occurred when bevacizumab therapy was initiated less than 7 days after VAD placement. Bevacizumab therapy was initiated less than 7 days after VAD placement in 150 cases (13 of 150: 8.6%). The risk of dehiscence was the same from 0 to 7 days. In parallel, the VAD wound dehiscence rate in patients not receiving bevacizumab therapy was eight of 4197 cases (0.19%) (Fisher's test significant, P<0.001). No risk factors of dehiscence were identified: anesthetists, learning curves, and irradiated patients. VAD thrombosis occurred in four patients (1.5%). In parallel, VAD thrombosis occurred in 51 of 4197 patients (1.2%) not receiving bevacizumab therapy (Fisher's test not significant; P=0.43). Bevacizumab therapy was permanently discontinued in five patients related to wound dehiscence and in one patient due to extensive skin necrosis. These data suggest the need to observe an interval of at least 7 days between VAD placement and initiation of bevacizumab therapy to avoid the risk of a wound dehiscence requiring chest wall port explant. The risk of VAD thrombosis does not require any particular primary prevention.

Cardiac toxicity in breast cancer patients: from a fractional point of view to a global assessment.

When focusing on heart disease, most available studies split the two different parts of the adjuvant treatment, i.e., systemic therapies and radiation therapy, making it difficult to implement efficient strategies for preventing treatment-induced cardiac toxicity. This paper reviews the current understanding of treatments-induced cardiac toxicity in a global approach. Many factors should be considered when assessing the cardiac hazard. Treatment-related risk factors include heart dose exposure, chemotherapy, targeted agents such as HER2 inhibitors, but also endocrine agents, or anesthetic procedure. Patients' characteristics should also be taken into account. Age, menopausal status, stress, previous history of cardiac disease, genetic profile, and body mass index could all impact on cardiac function after adjuvant therapies. Cardiac toxicity should not be analyzed as the consequence of a specific therapy, but should be considered as the result of additive or supra-additive toxicities. By this way, it will be possible to implement new strategies for preventing treatment-induced cardiac toxicity.

Potentiation of mivacurium blockade by low dose of pancuronium: a pharmacokinetic study.

BACKGROUND: Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium. METHODS: After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 microg/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography. RESULTS: Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P < 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml. min-1. kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml. min-1. kg-1; P < 0.05). CONCLUSIONS: A subparalyzing dose of pancuronium decreased plasma cholinesterase activity and the clearance of the two most active isomers of mivacurium. Pancuronium potentiates mivacurium more than other neuromuscular blocking agents because, in addition to its occupancy of postsynaptic acetylcholine receptors, it slows down the hydrolysis of mivacurium.