Inspiration Breath Research Articles

Dosimetric Analysis of Proton Beam Therapy vs. Photon Radiotherapy for Cardiac Tumors with or without Deep Inspiratory Breath Holding: A Case Report

Proton beam therapy (PBT) has been demonstrated to deliver equivalent dosimetric radiation with the benefit of improved sparing of organs at risk (OAR). Deep inspiration breath holding (DIBH) is a commonly used method for reducing the radiation dose to the heart and lungs. However, few studies have ever reported the usage of DIBH combined with proton beam therapy in cardiac tumors. The purpose of this case report is to compare the dosimetric differences between photon radiotherapy and proton radiation therapy (PBT) with or without deep inspiration breath holding. A 66-year-old female patient with cardiac tumors was recruited, and the prescribed dose of radiotherapy for cardiac tumors was 95%PGTV 50Gy/2.5Gy/20f. Two simulation CT scans were collected during free breath (FB) and DIBH. And the target area was delineated on deep inspiratory breath holding image (DIBH-CT) and free breathing image (FB-CT). The target area of FB-CT was modified by referring to the ten-time phases of 4D-CT. Finally, IMRT, VMAT and PBT plans (DIBH-IMRT, DIBH-VAMT, DIBH-PBT, FB-IMRT, FB-VAMT, FB-PBT) were generated on the above images, and the organs at risk were limited as follows: lungs V20 ≤20%, lungs mean ≤11 Gy, heart V30 ≤40%, coronary artery mean ≤26 Gy, spinal cord ≤30 Gy, and left breast mean ≤5 Gy. All of the six plans satisfied most of the treatment planning goals. DIBH resulted in a dose reduction in all organs at risk including the heart, lungs, coronary artery (CA), spinal cord and breasts, when compared with FB using IMRT, VMAT, or PBT. Compared with the FB, DIBH provided a significant reduction in the mean dose of coronary artery (CA mean for DIBH-IMRT vs FB-IMRT = 28.32 Gy vs 42.66 Gy, CA mean for DIBH-VMAT vs FB-VAMT = 26.44Gy vs 40.85Gy, CA mean for DIBH-PBT vs FB-PBT = 27.71Gy vs 39.51Gy). Similarly, when compared with IMRT or VMAT in either FB or DIBH, PBT reduced radiation doses for all of the OAR. In comparison, the difference was less significant between IMRT and VMAT technique. Pitmen compared with IMRT and VMAT, reduced significantly the max dose of spinal cord, lungs V5, breast-L/R mean. Totally, DIBH-PBT was observed sufficient dose coverage and better sparing of organs at risk. PBT combined with DIBH technique gained an advantage in the sparing of OAR for cardiac tumors, especially in coronary protection. The possibility of broader application of PBT with DIBH in clinical practice is currently being evaluated and further studies are needed.

Radiation Induced Lung Injury in Rats after Pre-Oxygenation Radiotherapy

Deep inspiratory breath holding (DIBH) has been widely used during the radiotherapy of thoracic tumors. The main disadvantage of voluntary DIBH is the short duration of each breath hold. The hypocapnia induced by hyperoxia (oxygen concentration > 50%) pre-oxygenation (PreO2) combined with mechanical hyperventilation has been reported to prolong the duration of single breath hold, but its safety remains controversial, especially the sensitivity of lung tissue to radiation damage under hyperoxia exposure has not been elucidated. In this study, we aim to investigate the changes of radiation induced lung injury in rats after PreO2 radiation. We evaluated the lung tissue of rats at different time points (48h, 2w, 4w, 8w, 12w) after thoracic radiation (15Gy single fraction to the right lung), and sequenced the transcriptome of lung tissue at 48 hours after irradiation. Rat cohorts (n = 7/group): 1. Control (Con); 2. Radiation group (RT); 3. Pre-oxygenation (oxygen concentration > 90%) for 8 hours before thoracic radiation (PreO2). The inflammatory exudation emerged in the pulmonary interstitium at 48 hours, and reached the most serious alveolitis after four weeks of irradiation (the comparison of alveolitis scores in RT4w vs Con4w and PreO2(4w) vs Con4w, P<0.001) on hematoxylin-eosin staining. While the alveolitis scores in RT group and PreO2 group were not statistically different at each time point. Masson staining showed that the pulmonary fibrosis in the RT group and the PreO2 group reached an obvious pathological change at 12 weeks after irradiation, but the difference between the two groups was not significant. Transcriptome sequencing showed that the number of differential genes in PreO2 vs Con was 559 (302 up-regulated genes and 257 down-regulated genes). The GO enrichment analysis indicated that chromosome segregation was the most significant functional item with P value in the comparative analysis, and the KEGG enrichment analysis suggested that cell division was the most significant enrichment pathway of these differential genes. While there was a small quantity of differential genes in PreO2 vs RT group (3 up-regulated genes and 12 down-regulated genes). Pentose and glucuronate conversions were the most significant enrichment pathway of these differential genes. This study demonstrated that PreO2 radiotherapy did not increase the severity of radiation induced lung injury in rats compared to conventional radiotherapy. Further study should be conducted to confirm these results and to investigate the regulatory mechanism of pneumonia caused by PreO2 radiotherapy.

Variation in Left Anterior Descending Coronary Artery Accumulated Dose Estimates during Breast Cancer Radiotherapy

Left anterior descending (LAD) coronary artery RT dose has been associated with the risk of coronary ischemic events in patients with breast cancer treated with radiotherapy (RT). However, consensus dose constraints commonly utilize mean heart dose, which has been shown to be an inadequate surrogate for LAD dose. Given the LAD is adjacent to the steep dose gradients of the left breast/chest wall, we hypothesize that variations in patient positioning or depth of breath hold may contribute to significant deviations in daily LAD dose exposure compared to predicted. Our objective was to investigate variations in accumulated LAD dose in patients with left-sided breast cancer treated with RT. Retrospective analysis of 10 consecutive patients with left-sided breast cancer treated between 2019-2022 with volumetric modulated arc therapy (VMAT) in the supine position. RT was delivered using daily cone beam computed tomography (CBCT) image guidance with deep-inspiratory breath hold technique and an optical surface monitoring system. Daily CBCT scans were individually registered to each planning CT based on daily positional changes. The LAD was manually segmented and transformed to each CBCT. Daily fractional dose was calculated (mean, volume receiving 15 Gy [V15 Gy], V30 Gy, and max) and summed to produce an accumulated dose which was compared to the predicted dose. Significant deviations in accumulated dose were defined as at least ±15% from predicted. The RT targets included breast/chest wall only (n = 1), supraclavicular nodes (n = 8), and/or internal mammary chain (n = 5). All plans were prescribed to 50 Gy in 25 fractions. The median predicted mean heart dose was 5.1 Gy. Overall, there were no significant differences between the median predicted vs. accumulated LAD doses: mean 10.4 vs. 10.2 Gy, V15 Gy 21% vs. 25%, V30 Gy 0% vs. 1%, max 24.5 vs 25.7 Gy (all p>.05). However, there was a subset of patients (n = 5, 50%) with significant deviations in accumulated vs. predicted dose (at least ±15%). For LAD mean, n = 2 had higher accumulated vs. predicted doses (16.6 vs. 11.6 Gy; 14.6 vs. 12.8 Gy), while n = 3 had lower (21.8 vs. 26.5 Gy; 2.7 vs. 4.2 Gy; 13.9 vs. 16.5 Gy). For LAD V15 Gy, n = 3 had higher accumulated vs. predicted doses (43 vs. 35%; 51% vs. 25%; 14% vs. 9%), while n = 2 had lower (49% vs. 61%; 37% vs. 56%). For LAD V30 Gy, n = 4 had higher accumulated vs. predicted doses (12% vs. 5%; 5% vs. 0%; 4% vs. 0%; 4% vs. 2%), while n = 1 had lower (32% vs. 44%). Daily setup differences, including the extent of inspiratory breath hold, may contribute to deviations in accumulated LAD dose (more than 15% of predicted) in approximately half of patients and were more pronounced in V15 and V30 Gy metrics. The potential for significant LAD dose uncertainty in a clinically meaningful subset of patients should be recognized and warrants further analysis in an expanded cohort.

Selective transduction and photoinhibition of pre-Bötzinger neurons that project to the facial nucleus in rats affect the nasofacial activity.

The preBötzinger Complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases.

Capnometry after an inspiratory breath hold, PLAT CO2 , as a surrogate for in mild to moderate pediatric acute respiratory distress syndrome: A feasibility study.

Accurate and reliable noninvasive methods to estimate gas exchange are necessary to guide clinical decisions to avoid frequent blood samples in children with pediatric acute respiratory distress syndrome (PARDS). We aimed to investigate the correlation and agreement between end-tidal measured immediately after a 3-s inspiratory-hold (PLAT CO2 ) by capnometry and measured by arterial blood gases (ABG) in PARDS. Prospective cohort study. Seven-bed Pediatric Intensive Care Unit, Hospital El Carmen de Maipú, Chile. Thirteen mechanically ventilated patients aged ≤15 years old undergoing neuromuscular blockade as part of management for PARDS. None. All patients were in volume-controlled ventilation mode. The regular end-tidal (without the inspiratory hold) was registered immediately after the ABG sample. An inspiratory-hold of 3 s was performed for lung mechanics measurements, recording in the breath following the inspiratory-hold. (PLAT CO2 ). End-tidal alveolar dead space fraction (AVDSf) was calculated as and its surrogate (S)AVDSf as . Measurements of were considered the gold standard. We performed concordance correlation coefficient (ρc), Spearman's correlation (rho), and Bland-Altmann's analysis (mean difference ± SD [limits of agreement, LoA]). Eleven patients were included, with a median (interquartile range) age of 5 (2-11) months. Tidal volume was 5.8 (5.7-6.3) mL/kg, PEEP 8 (6-8), driving pressure 10 (8-11), and plateau pressure 17 (17-19) cm H2 O. Forty-one paired measurements were analyzed. was higher than (52 mmHg [48-54] vs. 42 mmHg [38-45], p < 0.01), and there were no significant differences with PLAT CO2 (50 mmHg [46-55], p > 0.99). The concordance correlation coefficient and Spearman's correlation between and PLAT CO2 were robust (ρc = 0.80 [95% confidence interval [CI]: 0.67-0.90]; and rho = 0.80, p < 0.001.), and for were weak and strong (ρc = 0.27 [95% CI: 0.15-0.38]; and rho = 0.63, p < 0.01). The bias between PLAT CO2 and was -0.4 ± 3.5 mmHg (LoA -7.2 to 6.4), and between and was -8.5 ± 4.1 mmHg (LoA -16.6 to -0.5). The correlation between AVDSf and (S)AVDSf was moderate (rho = 0.55, p < 0.01), and the mean difference was -0.5 ± 5.6% (LoA -11.5 to 10.5). This pilot study showed the feasibility of measuring end-tidal CO2 after a 3-s end-inspiratory breath hole in pediatric patients undergoing controlled ventilation for ARDS. Encouraging preliminary results warrant further study of this technique.

Stereotactic Magnetic Resonance–guided Adaptive Radiation Therapy for Localized Kidney Cancer: Early Outcomes from a Prospective Phase 1 Trial and Supplemental Cohort

Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13–20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration rate was –1.8 ml/min/1.73 m2 (95% confidence interval or CI [–6.6 to 3.1 ml/min/1.73 m2]), and the mean decrease in tumor diameter was –0.20 cm (95% CI [–0.6 to 0.2 cm]) at the last follow-up. Anterior location and overlap of the 25 or 28 Gy isodose line with gastrointestinal organs at risk were predictive of the benefit from online adaptive planning. Kidney SMART is feasible and, at the early time point evaluated in this study, was well tolerated with minimal decline in renal function. More studies are warranted to further evaluate the safety and efficacy of this technique. Patient summaryFor patients with localized renal cell carcinoma who are not surgical candidates, stereotactic magnetic resonance-–guided adaptive radiotherapy is a feasible and safe noninvasive treatment option that results in minimal impact on kidney function.

Cardiac exposure in left-sided breast cancer patients undergoing deep inspiratory breath hold radiation therapy.

Left-sided breast cancer (BC) patients undergoing post-operative radiation therapy (PRT) may have higher risk of late cardiovascular toxicity, which may be reduced by hearth-sparing RT techniques. This study evaluated dosimetric parameters of the deep inspiration breath hold (DIBH) compared to free breathing (FB) RT. We analysed factors impacting on doses to the heart and cardiac substructures and sought anatomic factors allowing patient selection for DIBH. The study group included 67 left-sided BC patients who underwent RT after breast-conserving surgery or mastectomy. Patients treated with DIBH were trained to hold their breath. Computed tomography (CT) scans were performed in both FB and DIBH patients. Plans were generated using 3-dimensional (3D) conformal RT. The dosimetric variables were obtained from dose-volume histograms, and the anatomical variables were derived from the CT scans. The variables in the two groups were compared by t-test, the U test, and the chi-squared test. Correlation analysis was performed using Pearson's correlation coefficient. Receiver operating characteristic curves were used to analyze the efficacy of the predictors. Compared to the FB, DIBH allowed for a mean dose reduction to the heart, left anterior descending coronary artery (LAD), left ventricle (LV), and right ventricle (RV) by 30.0%, 38.7%, 39.3%, and 34.7%, respectively. DIBH markedly increased the heart height (HH), heart chest wall distance (HCWD), the mean distance between the ipsilateral lung and breast (DBIB), and decreased the heart-chest wall length (HCWL) (P<0.05). The different value of HH, DBIB, HCWL, and HCWD between DIBH and FB were 1.31, 1.95, -0.67, and 0.22 cm, respectively (all P<0.05). ΔHH was an independent predictor of the mean dose to the heart, LAD, LV, and RV, with the area under the curve values of 0.818, 0.725, 0.821, and 0.820, respectively. DIBH significantly reduced the dose to the entire heart and its substructures in left-sided BC patients undergoing post-operative RT. ΔHH predicts the mean dose to the heart and its substructures. These results may inform patient selection for DIBH.

Reproducibility of non-contrast enhanced multi breath-hold ultrashort echo time functional lung MRI

PurposeTo evaluate the intraindividual reproducibility of functional lung imaging using non-contrast enhanced multi breath-hold 3D-UTE MRI. MethodsTen healthy volunteers underwent non-contrast enhanced 3D-UTE MRI at three time points for same-day and different-day measurements employing a stack-of-spirals trajectory at 3 T. At each time point, inspiratory and expiratory breathing states were acquired for tidal and deep breathing, each within a single breath-hold. For functional image analysis, fractional ventilation (FV) was calculated pixelwise after image registration from the MR signal change. To decouple FV from breathing depth, the individual lung volume was used for volume adjustment (rFV). Reproducibility evaluation was performed in eight lung segments. Statistical analyses included two way mixed intraclass correlation (ICC), sign-test, Friedman-test and modified Bland-Altman analyses. ResultsFV from tidal breathing showed an ICC of 0.81, a bias of 1.3% and an interval of confidence (CI) ranging from −67.1 to 69.6%. FV from deep breathing was higher reproducible with an ICC of 0.92 (bias, −0.2%; CI, −34.2 to 33.7%). Following volume adjustment, reproducibility of rFV for tidal breathing improved (ICC, 0,86; bias, 2.0%; CI, −34.3 to 38.3%), whereas it did not bear significant benefits for deep breathing (ICC, 0.89; bias, 2.8%; CI, −24.9 to 30.5%). Reproducibility was independent from the examination day. ConclusionNon-contrast-enhanced multi breath-hold 3D-UTE MRI allows for highly reproducible ventilation imaging.

Gated radiation therapy for patients with breast cancer to reduce the dose to the lung and heart: A comparative cross-sectional study

ABSTRACT JOURNAL/crsat/04.03/02201859-202306020-00005/figure1/v/2023-08-03T140821Z/r/image-tiff Background: Deep inspiratory breath hold (DIBH) is an established technique to treat left breast cancer with fewer side-effects to the surrounding organs at risk (OARs). However, studies assessing DIBH in resource-poor settings, especially in a government setup, are scarce. Objectives: Our primary objective was to assess and compare the dosimetric changes in the DIBH technique compared to the free breathing technique among patients with left-sided breast cancer undergoing radiation therapy. Materials and Methods: This was a comparative cross-sectional study conducted in the Department of Radiation Oncology, Kidwai Memorial Institute of Oncology (Bengaluru, India), over a period of 24 months. A total of 65 patients were treated with the three-dimensional conformal radiation therapy (3D-CRT) technique either using DIBH or free breathing as per the standard protocol. The dosimetric comparisons for the surrounding OARs, in terms of mean percentage volume receiving 15 Gy (V15Gy) and 20 Gy (V20Gy) in the left lung, V25Gy, V30Gy, V5Gy in the heart the mean dose in Gy received by 25% (V25%) and 40% (V40%) of the heart, V10% and V30% of the left anterior descending artery (LAD) and mean values of Dmean dose (Gy) received by the left lung, heart, and LAD artery were compared between both the techniques. Results: Among 65 patients, 25 (38.4%) were treated by the free breathing technique and 40 (61.6%) by DIBH. Various dosimetric parameters that were significantly lower in the DIBH compared to free breathing techniques included the mean percentage volume of left lung receiving 20 Gy (V20 Gy) (29.5% vs. 23.5%), heart receiving 25 Gy (V25Gy) (6.7% vs. 2.9%) and 30 Gy (12.8% vs. 2.0%), mean values of Dmean received by the heart (7.8 Gy vs. 4.5 Gy) and LAD artery (31.3 Gy vs. 16.9 Gy), mean dose received by 10% volume of LAD (V10%) (36.3 Gy vs. 29.0 Gy) and 30% of LAD artery (V30%) (34.3 Gy vs. 22.2 Gy) (P &lt; 0.001). Conclusion: DIBH significantly decreases the radiation dose delivered to the heart, left lung, and LAD artery. Thus, in patients with left-sided breast cancer, DIBH leads to a lower radiation dose to the OARs, leading to potentially less side-effects.

A Dosimetric Study Comparing Different Radiotherapy Planning Techniques With and Without Deep Inspiratory Breath Hold for Breast Cancer.

To analyze whether deep inspiratory breath hold (DIBH) would be dosimetrically beneficial irrespective of radiotherapy planning techniques for patients with left breast cancers requiring adjuvant radiotherapy. Planning CT scans were taken in free-breathing (FB) as well as deep-inspiration breath hold (DIBH) for patients requiring adjuvant radiotherapy for left breast cancers. After registration, three radiotherapy plans - 3D-conformal radiotherapy (3DCRT), intensity modulated RT (IMRT), and volumetric modulated arc-therapy (VMAT) - were generated for both FB and DIBH scans for each patient. The dose-volume parameters were collected from the dose-volume histogram and analyzed. A paired t-test is used for statistical analysis of the parameters. The study was conducted on thirteen patients. The mean dose of the left lung was reduced with DIBH by 32%, 24%, and 6% (8.6 Gy, 6.6 Gy, and 6.4 Gy) with 3DCRT, IMRT, and VMAT, respectively. The mean heart dose was reduced by 3.3 Gy (2.2 vs 5.5 Gy), 2.2 Gy (7.5 vs 9.7 Gy), and 1.2 Gy (5.8 vs 7 Gy) with 3DCRT, IMRT, and VMAT with DIBH. Similarly, the left anterior descending artery (LAD) mean dose was relatively reduced by 80%, 34%, and 20% when compared with the FB scans for 3DCRT, IMRT, and VMAT respectively, with max dose in the 3DCRT plan. DIBH appears to have maximum benefit in achieving a better sparing of organs-at-risk for patients being considered for 3DCRT, and to a lesser extent with even IMRT and VMAT techniques.

Sex differences in blood pressure and inactive limb blood flow responses during dynamic leg exercise with increased inspiratory muscle work.

We hypothesized that, compared with young males, young females have a smaller decrease in blood flow to the inactive limb, accompanied by a smaller increase in arterial blood pressure, during dynamic exercise with increased inspiratory muscle work. Young males and females performed dynamic knee-extension and -flexion exercises for 10 min (spontaneous breathing for 5 min and voluntary hyperpnoea with or without inspiratory resistance for 5 min). Mean arterial blood pressure (MAP) and mean blood flow (MBF) in the brachial artery were continuously measured by means of finger photoplethysmography and Doppler ultrasound, respectively. No sex differences were found in the ΔMAP and ΔMBF (Δ: from baseline) during exercise without inspiratory resistance. In contrast, the ΔMAP during exercise with inspiratory resistive breathing was greater (P < 0.05) in males (+31.3 ± 2.1 mmHg, mean ± SE) than females (+18.9 ± 3.2 mmHg). The MBF during exercise with inspiratory resistance did not change in males (-4.4 ± 10.6 mL/min), whereas it significantly increased in females (+25.2 ± 15.4 mL/min). These results suggest that an attenuated inspiratory muscle-induced metaboreflex in young females affects blood flow distribution during submaximal dynamic leg exercise.

19P Cardiac and lung sparing radiotherapy in breast and chest wall irradiation with surface guided radiotherapy using deep inspiratory breath hold technique

Breast cancer is the commonest cancer among women requires multimodality treatment including adjuvant radiotherapy for better loco regional control. Long term toxicity to heart and lung following chemotherapy especially anthracyclines and Trastuzumab.Deep inspiratory breath-hold technique is a state of art technique for reducing heart doses without compromising target coverage or other organ-at-risk. The technique is based upon the observation that during inspiration, the flattening of the diaphragm and expansion of the lungs pulls the heart away from the chest wall.

Comparison of Short Term Clinical and Dosimetric Outcomes of Fast Forward vs. Hypofractionated Radiotherapy for Early Breast Cancer – A Single Center Experience

<h3>Purpose/Objective(s)</h3> To share the experience of planning, dosimetric evaluation and delivery of ultra-hypofractionated (fast forward-FF) versus hypofractionated (HF) radiotherapy in breast cancers treated at our center. <h3>Materials/Methods</h3> 60 patients (average age 44 years- range 32-65 years) of early [T1, T2N0] breast cancer (BC) treated between October 2020 and October 2021 were included. Plans of 15 patients of left BC by FF, left BC by HF, right BC by FF and right BC by HF were evaluated in terms of coverage and organs at risk (OAR) constraints. Patients were planned by field within field [FIF] planning for phase I (42.5 Gy/16# for HF and 26 Gy/5# for FF). Boost plans were generated by FIF/electron/conformal planning to a dose of 10-16 Gy @ 2 Gy/fraction. Deep inspiratory breath hold (DIBH) was used for left sided BC patients who were able to hold breath. PTV coverage goal was V95 more than or equal to 95%, V105 <7%, V107 < 2%. Constraints for FF were – lung V8<15%, heart V1.5<30%, V7<5%. Constraints for HF plans were – lung V20<20%, heart avg <3 Gy. 15 right sided BC patients were treated with FF and 15 by HF plans. For left sided BC, plans were generated for dosimetric comparison between FF and HF plans, but all patients were treated by HF plans. <h3>Results</h3> For left sided BC cases, high heart dose was seen in those with more heart volume, precordial location of boost volume and patients unable to do DIBH. All patients treated by FF had grade I skin reaction and 1/15 had wet desquamation in inframammary fold. Among patients treated by HF, majority patients had dry desquamation, 3/45 had wet desquamation in folds. Edema developed in FF by 2-3^rd fraction and by 7-9^th fraction in HF. Edema was milder in HF. The edema and skin changes resolved in 2-3 weeks. At 3 and 6 months, mild skin discoloration and minimal induration at post op site was seen which was similar in those treated by FF and HF. <h3>Conclusion</h3> Adequate coverage and OAR constraints can be met for FF as for HF plans. Radiation dermatitis is milder in FF arm and the edema is milder in the HF arm. Radiation of early breast cancer by FF is executable at independent centers with diligent planning with tight constraints and precise delivery.

Radiation-Induced Acute Cardiotoxicity in Women with Left Sided Breast Cancer: Results from a Phase II Prospective Clinical Trial

<h3>Purpose/Objective(s)</h3> Women with left sided breast cancer (BC) who receive adjuvant radiotherapy (RT) have increased risk of subsequent cardiac events, which may be mitigated by maintaining mean heart dose (MHD) below a threshold of 3 Gy. We hypothesized that early MRI evaluation of cardiac functional changes can identify acute cardiac insult and predict for the risk of long-term cardiac complications. Here we report the findings of a phase II prospective clinical trial evaluating RT-related LV structure and function using cardiac MRI in women with left sided BC treated with adjuvant RT. <h3>Materials/Methods</h3> Patients with left sided BC were enrolled into a single institutional phase II study. After informed consent, patients were allocated for breast RT with free breathing (FB) or with deep inspiratory breath hold (DIBH) delivery, if the predicted MHD was ≤3 Gy (≤ 5 Gy, if also regional nodal RT) or > 3 Gy (> 5 Gy, if regional nodal RT), respectively, on initial FB planning. Cardiac MRI was performed at baseline (pre-RT), and at 16 and 52 weeks. Cardiac toxicity was defined as change in the indexed LV end diastolic volume (LVEDVi), LV ejection fraction (LVEF), indexed LV end systolic volume (LVESVi) and indexed LV mass (LV MASSi). Estimation of multiple serum cardiac biomarkers were also done at the three time points. Continuous variables were expressed as mean ± standard deviation, and ANOVA analysis was used to identify correlation between changes in cardiac parameters from baseline to 16 and 52 weeks, when compared to cardiac radiation dosimetric data. <h3>Results</h3> Of the 69 participants, 25 received RT with FB technique. 44 received RT with DIBH, of which 23 also had received adjuvant chemotherapy (CT) prior to RT. For the FB, DIBH (no CT), and DIBH (with CT) cohorts, MHD was 1.70 ± 0.93 Gy, 1.93 ± 1.30 Gy, and 2.26 ± 1.15 Gy and mean LV dose was 2.47 ± 1.48 Gy, 3.18 ± 1.93 Gy, and 3.23 ± 1.82 Gy, respectively. Evaluation of LVEDVi, LVEF, LVESVi, and LV MASSi showed no statistical difference between the 3 treatment arms. No statistical correlation was noted between LVEF changes (≥ 5% and ≥ 10% from baseline) and the cardiac dosimetric data; all p values > 0.1. Prior CT did not measurably impact cardiac function. <h3>Conclusion</h3> In this prospective study, no significant post-RT cardiac events were demonstrable by functional imaging. This supports the significance of maintaining MHD ≤ 3 Gy to minimize or prevent RT related cardiac toxicity in women with left sided BC. Our observation warrants further investigation in a large prospective setting to evaluate late cardiac events. Analysis of serum cardiac biomarkers is currently ongoing.

Inspiratory and leg muscle blood flows during inspiratory muscle metaboreflex activation in heart failure with preserved ejection fraction.

The purpose of this study was to determine the cardiovascular consequences elicited by activation of the inspiratory muscle metaboreflex in patients with heart failure with preserved ejection fraction (HFpEF) and controls. Patients with HFpEF (n = 15; 69 ± 10 yr; 33 ± 4 kg/m2) and controls (n = 14; 70 ± 8 yr; 28 ± 4 kg/m2) performed an inspiratory loading trial at 60% maximal inspiratory pressure (PIMAX) until task failure. Mean arterial pressure (MAP) was measured continuously. Near-infrared spectroscopy and bolus injections of indocyanine green dye were used to determine the percent change in blood flow index (%ΔBFI) from baseline to the final minute of inspiratory loading in the vastus lateralis and sternocleidomastoid muscles. Vascular resistance index (VRI) was calculated. Time to task failure was shorter in HFpEF than in controls (339 ± 197 s vs. 626 ± 403 s; P = 0.02). Compared with controls, patients with HFpEF had a greater increase from baseline in MAP (16 ± 7 vs. 10 ± 6 mmHg) and vastus lateralis VRI (76 ± 45 vs. 32 ± 19%) as well as a greater decrease in vastus lateralis %ΔBFI (-32 ± 14 vs. -17 ± 9%) (all, P < 0.05). Sternocleidomastoid %ΔBFI normalized to absolute inspiratory pressure was higher in HFpEF compared with controls (8.0 ± 5.0 vs. 4.0 ± 1.9% per cmH2O·s; P = 0.03). These data indicate that patients with HFpEF exhibit exaggerated cardiovascular responses with inspiratory muscle metaboreflex activation compared with controls.NEW & NOTEWORTHY Respiratory muscle dysfunction is thought to contribute to exercise intolerance in heart failure with preserved ejection fraction (HFpEF); however, the underlying mechanisms are unknown. In the present study, patients with HFpEF had greater increases in leg muscle vascular resistance index and greater decreases in leg muscle blood flow index compared with controls during inspiratory resistive breathing (to activate the metaboreflex). Furthermore, respiratory muscle blood flow index responses normalized to pressure generation during inspiratory resistive breathing were exaggerated in HFpEF compared with controls.

Frequency and Risk Factors for Air Embolism in Computed Tomography Fluoroscopy-Guided Biopsy of Lung Tumor With the Use of Noncoaxial Automatic Needle.

The aim of the study is to analyze incidence and risk factors for air embolism during computed tomography (CT) fluoroscopy-guided lung biopsies using noncoaxial automatic needle. Between February 2014 and December 2019, 204 CT fluoroscopy-guided lung biopsies (127 men; mean age, 70.6 years) using noncoaxial automatic needle under inspiratory breath holding were performed. We retrospectively evaluated the incidence of air embolism as presence of air in the systemic circulation on whole-chest CT images obtained immediately after biopsy. Risk factors of the patient, tumor and procedural factors (size, location and type of nodule, distance from the pleura, the level of the lesion relative to the left atrium, emphysema, patient position, penetration of a pulmonary vein, etc) were analyzed. The technical success rate was 97.1%. Air embolism was radiologically identified in 8 cases (3.92%, 7 males; size, 21.6 ± 18.2 mm; distance to pleura, 11.9 ± 14.5 mm). Two patients showed overt symptoms and the others were asymptomatic. Independent risk factors were needle penetration of the pulmonary vein ( P = 0.0478) and higher location relative to left atrium ( P = 0.0353). Size, location and type of nodule, distance from the pleura, emphysema, patient position, and other variables were not significant risk factors. As other complications, pneumothorax and alveolar hemorrhage were observed in 57.4% and 77.5%, respectively. In CT fluoroscopy-guided lung biopsy using the noncoaxial automatic needles, radiological incidence of air embolism was 3.92%. Given the frequency of air embolism, it is necessary to incorporate this into postprocedure imaging and clinical evaluation.

Considering Lumpectomy Cavity PTV Expansions: Characterization of Intrafraction Lumpectomy Cavity Motion

PurposeAccelerated partial breast irradiation and lumpectomy cavity boost radiation therapy plans generally use volumetric expansions from the lumpectomy cavity clinical target volume to the planning target volume (PTV) of 1 to 1.5 cm, substantially increasing the volume of irradiated breast tissue. The purpose of this study was to quantify intrafraction lumpectomy cavity motion during external beam radiation therapy to inform the indicated clinical target volume to PTV expansion. Methods and MaterialsForty-four patients were treated with a whole breast irradiation using traditional linear accelerator-based radiation therapy followed by lumpectomy cavity boost using magnetic resonance (MR)-guided radiation therapy on a prospective registry study. Two-dimensional cine-MR images through the center of the surgical cavity were acquired during each boost treatment to define the treatment position of the lumpectomy cavity. This was compared with the reference position to quantify intrafraction cavity motion. Free-breathing technique was used during treatment. Clinical outcomes including toxicity, cosmesis, and rates of local control were additionally analyzed. ResultsThe mean maximum displacement per fraction in the anterior-posterior (AP) direction was 1.4 mm. Per frame, AP motion was <5 mm in 92% of frames. The mean maximum displacement per fraction in the superior-inferior (SI) direction was 1.2 mm. Per frame, SI motion was <5 mm in 94% of frames. Composite motion was <5 mm in 89% of frames. Three-year local control was 97%. Eight women (18%) developed acute G2 radiation dermatitis. With a median follow-up of 32.4 months, cosmetic outcomes were excellent (22/44, 50%), good (19/44, 43%), and fair (2/44, 5%). ConclusionsIn approximately 90% of analyzed frames, intrafraction displacement of the lumpectomy cavity was <5 mm, with even less motion expected with deep inspiratory breath hold. Our results suggest reduced PTV expansions of 5 mm would be sufficient to account for lumpectomy cavity position, which may accordingly reduce late toxicity and improve cosmetic outcomes.

Changes In Splanchnic Blood Flow And Blood Pressure During Inspiratory Resistive Breathing

PURPOSE: The hyperpnea during whole-body heavy exercise leads to an increase in respiratory muscle work, which is associated with cardiovascular regulations during exercise (i.e., respiratory muscle metaboreflex). In resting condition, blood flow to inactive limbs is reduced with inspiratory resistive breathing. Furthermore, increasing the work of breathing during dynamic exercise influences inactive limb blood flow. Therefore, it is conceivable that the respiratory muscle-induced metaboreflex is associated with blood flow redistribution during exercise. Redistribution of blood flow is also associated with splanchnic blood flow as well as inactive blood flow. However, influence of respiratory muscle metaboreflex on splanchnic blood flow in humans remains unknown. We hypothesized that blood flow to splanchnic organs would reduce via respiratory muscle-induced metaboreflex. METHODS: Ten healthy young men (20.2 ± 0.4 yrs, mean ± SE) performed two voluntary hyperventilation tests (tidal volume of 40% of vital capacity, a breathing frequency of 40 breaths/min and inspiratory duty cycle of 50%). One trial was voluntary hyperventilation with inspiratory resistance (about 40% of maximal inspiratory pressure), and the trial was terminated when the subject could not maintain the target ventilation (the resistance trial), and the other one was voluntary hyperventilation without inspiratory resistance until the same time as the resistance trial (the non-resistance trial). During trials, mean arterial blood pressure (MAP) was measured using finger photoplethysmography, and celiac artery blood flow was recorded by Doppler ultrasonography. RESULTS: MAP increased progressively and was higher (P < 0.05) in the resistance trial (100.5 ± 4.4 mmHg) than in the non-resistance trial (92.8 ± 2.0 mmHg) at the end of trial. Celiac artery blood flow decreased gradually from baseline value in the resistance trial (469.3 ± 47.6 mL/min), whereas did not change in the non-resistance trial (605.7 ± 56.2 mL/min). Celiac artery vascular conductance was lower in the resistance trial (4.8 ± 0.6 mL/min/mmHg) than in the non-resistance trial (6.6 ± 0.6 mL/min/mmHg, P < 0.05). CONCLUSIONS: These results suggest that increasing work of breathing affects the splanchnic circulation, via respiratory muscle-induced metaboreflex.

Deep inspiratory breath hold assisted by continuous positive airway pressure ventilation for lung stereotactic body radiotherapy

PurposeContinuous positive airway pressure (CPAP) ventilation hyperinflates the lungs and reduces diaphragmatic motion. We hypothesized that CPAP could be safely combined with deep inspiratory breath hold (CPAP-DIBH) during lung stereotactic radiotherapy (SBRT). Material and methodsPatients with stage-1 lung cancer or lung metastasis treated with CPAP-DIBH SBRT between 3/2017–5/2021 were analyzed retrospectively. Patient characteristics, treatment parameters, duration of breath holds in all sessions and tolerance to CPAP-DIBH were recorded. Local control (LC) was assessed from CT or PET-CT imaging. The distances between the tumor and mediastinal organs at risk (OAR) in centrally located tumors using either free breathing (FB) or CPAP-DIBH were compared. Toxicity was graded retrospectively. ResultsForty-five patients with 71 lesions were treated with CPAP-DIBH SBRT. Indications for CPAP-DIBH were prior radiation (35/71, 65%), lower lobe location (34/71, 48%), multiple lesions (26/71, 36.6%) and proximity to mediastinal OAR (7/71, 10%). Patient characteristics were: F:M 43%: 57%; mean gross tumor volume 4.5cm3 (SD 7.9), mean planning target volume 20cm3 (SD 27), primary: metastatic lesions (7%:93%). Mean radiation dose was 52.5 Gray (SD3.5). Mean lung volume was 5292cm3 (SD 1106). Mean duration of CPAP-DIBH was 41.3s (IQR 31–46.8). LC at 2 years was 89.5% (95% CI 76–95.5). In patients with central lesions, the distance between the tumor and mediastinal OAR increased from 0.84cm (SD 0.65) with FB to 1.23cm (SD 0.8) with CPAP-DIBH (p=0.002). Most patients tolerated CPAP well and completed all treatments after starting therapy. Three patients did not receive treatment: 2 were unable to tolerate CPAP and 1 had syncope (pre-existing). Toxicity was grade 2 in 4/65 (6%) and grade 3 in 1/65 (1.5%). There was no grade 2 or higher esophageal or tracheal toxicities. ConclusionCPAP-DIBH assisted lung SBRT was tolerated well and was associated with minimal toxicity and favorable LC. This technique may be considered when treating multiple lung lesions, lesions located in the lower lobes or adjacent to mediastinal OAR.

A Delphi Survey of Canadian Respiratory Therapists' Practice Statements on Pediatric Mechanical Ventilation.

Pediatric mechanical ventilation practice guidelines are not well established; therefore, the European Society for Paediatric and Neonatal Intensive Care (ESPNIC) developed consensus recommendations on pediatric mechanical ventilation management in 2017. However, the guideline's applicability in different health care settings is unknown. This study aimed to determine the consensus on pediatric mechanical ventilation practices from Canadian respiratory therapists' (RTs) perspectives and consensually validate aspects of the ESPNIC guideline. A 3-round modified electronic Delphi survey was conducted; contents were guided by ESPNIC. Participants were RTs with at least 5 years of experience working in standalone pediatric ICUs or units with dedicated pediatric intensive care beds across Canada. Round 1 collected open-text feedback, and subsequent rounds gathered feedback using a 6-point Likert scale. Consensus was defined as ≥ 75% agreement; if consensus was unmet, statements were revised for re-ranking in the subsequent round. Fifty-two RTs from 14 different pediatric facilities participated in at least one of the 3 rounds. Rounds 1, 2, and 3 had a response rate of 80%, 93%, and 96%, respectively. A total of 59 practice statements achieved consensus by the end of round 3, categorized into 10 sections: (1) noninvasive ventilation and high-flow oxygen therapy, (2) tidal volume and inspiratory pressures, (3) breathing frequency and inspiratory times, (4) PEEP and FIO2 , (5) advanced modes of ventilation, (6) weaning, (7) physiological targets, (8) monitoring, (9) general, and (10) equipment adjuncts. Cumulative text feedback guided the formation of the clinical remarks to supplement these practice statements. This was the first study to survey RTs for their perspectives on the general practice of pediatric mechanical ventilation management in Canada, generally aligning with the ESPNIC guideline. These practice statements considered information from health organizations and institutes, supplemented with clinical remarks. Future studies are necessary to verify and understand these practices' effectiveness.