Contralateral Lung Research Articles

Prospective Observation Study for Primary Spontaneous Pneumothorax: Incidence of and Risk Factors for Postoperative Neogenesis of Bullae.

Details of the neogenesis of bullae (NOB), which causes recurrent primary spontaneous pneumothorax (PSP) following bullectomy, have not been reported and risk factors for NOB remain unclear. We aimed to clarify the details of NOB. We conducted a prospective study using three computed tomography (CT) examinations performed 6, 12, and 24 months after bullectomy to identify the incidence of and risk factors for NOB. We enrolled 50 patients who underwent bullectomy for PSP. After excluding 11 patients who canceled the postoperative CT examination at 6 months after bullectomy, only 39 patients were analyzed. The incidence of NOB at 6, 12, and 24 months after bullectomy was 38.5%, 55.2%, and 71.2%, respectively. The rate of NOB in the operated lung was almost 2 times higher than that in the contralateral nonoperative lung. Male sex, multiple bullae on preoperative CT, long stapling line (≥7 cm), deep stapling depth (≥1.5 cm), and heavier resected sample (≥5 g) were suggested to be risk factors for NOB. We recognized a high incidence of postoperative NOB in PSP patients. Bullectomy itself seems to promote NOB. Postoperative NOB occurs frequently, especially in patients who require a large-volume lung resection with a long staple line.

Radiomics-Assisted Computed Tomography-Based Analysis to Evaluate Lung Morphology Characteristics after Congenital Diaphragmatic Hernia.

Purpose: Children with congenital diaphragmatic hernia suffer from long-term morbidity, including lung function impairment. Our study aims to analyze lung morphology characteristics via radiomic-assisted extraction of lung features in patients after congenital diaphragmatic hernia repair. Materials and Methods: 72 patients were retrospectively analyzed after approval by the local research ethics committee. All the image data were acquired using a third-generation dual-source CT (SOMATOM Force, Siemens Healthineers, Erlangen, Germany). Dedicated software was used for image analysis, segmentation, and processing. Results: Radiomics analysis of pediatric chest CTs of patients with status after CDH was possible. Between the ipsilateral (side of the defect) and contralateral lung, three shape features and two higher-order texture features were considered statistically significant. Contralateral lungs in patients with and without ECMO treatment showed significant differences in two shape features. Between the ipsilateral lungs in patients with and without the need for ECMO 1, a higher-order texture feature was depicted as statistically significant. Conclusions: By adding quantitative information to the visual assessment of the radiologist, radiomics-assisted feature analysis could become an additional tool in the future to assess the degree of lung hypoplasia in order to further improve the therapy and outcome of CDH patients.

One-lung ventilation with a bronchial blocker in thoracic patients

BackgroundLung isolation is a technique used in a multitude of surgeries to ensure single-lung ventilation with collapse of the contralateral lung, as to achieve improved access and visualization of relevant anatomical structures. Despite being accepted and having favorable outcomes, bronchial blockers (BBs) are not to this day the main device of choice among anaesthesiologists.MethodsIn this retrospective and descriptive study, we analyzed the safety and efficacy of a BB in all types of thoracic surgeries in our centre between 2015 and 2022, excluding patients with massive hemoptysis or empyema, or who had undergone a prior pneumonectomy.ResultsOne hundred and thirty-four patients were intervened due to lung cancer (67.9%), respiratory disease (23.9%), and non-respiratory disease (8.2%) undergoing lung surgeries (65.7%), pleural and mediastinal surgeries (29.9%), chest wall surgeries (3.0%) and other surgeries (1.5%). In most cases, lung collapse was considered excellent (63.9%) or good (33.1%) with only 4 cases (3.0%) of poor lung collapse. More than 90% of patients did not present intraoperative or immediate postoperative complications. No statistically significant differences were found between lung collapse and the demographic, clinical or BB-related variables (p > 0.05). However, we found a significatively higher proportion of excellent lung collapses in VATS surgeries and lateral decubitus positioning, as well as a significatively less proportion of poor lung collapses (p < 0.05). Moreover, there was a significantly higher proportion of excellent lung collapses when the BB was placed in the left bronchus (p < 0.05).ConclusionsWith these results, in our experience BBs constitute an effective alternative, capable of achieving pulmonary collapse in all kinds of thoracic procedures with satisfactory safety rates due to their minimal complications.

Assessing vaccine-mediated protection in an ultra-low dose Mycobacterium tuberculosis murine model.

Despite widespread immunization with Bacille-Calmette-Guerin (BCG), the only currently licensed tuberculosis (TB) vaccine, TB remains a leading cause of mortality globally. There are many TB vaccine candidates in the developmental pipeline, but the lack of a robust animal model to assess vaccine efficacy has hindered our ability to prioritize candidates for human clinical trials. Here we use a murine ultra-low dose (ULD) Mycobacterium tuberculosis (Mtb) challenge model to assess protection conferred by BCG vaccination. We show that BCG confers a reduction in lung bacterial burdens that is more durable than that observed after conventional dose challenge, curbs Mtb dissemination to the contralateral lung, and, in a small percentage of mice, prevents detectable infection. These findings are consistent with the ability of human BCG vaccination to mediate protection, particularly against disseminated disease, in specific human populations and clinical settings. Overall, our findings demonstrate that the ultra-low dose Mtb infection model can measure distinct parameters of immune protection that cannot be assessed in conventional dose murine infection models and could provide an improved platform for TB vaccine testing.

Chest Computed Tomography Findings in Unilateral Pulmonary Fibrosis Secondary to Chronic Hypoperfusion.

Unilateral lung fibrosis is uncommon and few cases secondary to parenchymal hypoperfusion have been reported, requiring further understanding of this entity. This study aims to report the chest computed tomography (CT) findings of patients with unilateral lung fibrosis related to parenchymal hypoperfusion observed in our institution. Patients with a chest CT between 2004 and 2022 showing a condition causing hypoperfusion of either lung and ipsilateral unilateral lung fibrosis were retrospectively identified. Clinical and scintigraphic data were collected. Pattern and distribution of fibrosis were recorded, and its progression was evaluated when follow-up was available. In adequate CTs, fibrosis was quantified using data-driven textural analysis (DTA). Affected and contralateral lungs and baseline and follow-up data were compared using the Wilcoxon signed-rank test. Thirteen patients (male: 7, female: 6, median age: 61 y) were included; 5 with congenital unilateral absence of a pulmonary artery and 8 with fibrosing mediastinitis. The mean scintigraphic perfusion of affected lungs was 3.3% ± 1.1 compared with 96.7% ± 1.1 contralaterally (n = 7, P = 0.017). Fibrosis had a UIP pattern in one case, indeterminate in the others, and was most commonly diffuse craniocaudally and peripheral or central axially. DTA in 12 patients showed a mean fibrotic score of 32% ± 24.6 compared with 0.5% ± 0.4 in the contralateral lungs ( P = 0.002). Median follow-up was 4.5 years (minimum to maximum: 1 to 13 y). Of 10 patients, fibrosis was progressive in 60%. DTA of 5 follow-up CTs showed increased reticulations ( P = 0.043). In patients with lung hypoperfusion, the possible complication of lung fibrosis should be considered.

Functional lung imaging of 2-year-old children after congenital diaphragmatic hernia repair using dynamic mode decomposition MRI

ObjectivesTo investigate the feasibility of non-contrast-enhanced functional lung imaging in 2-year-old children after congenital diaphragmatic hernia (CDH) repair.MethodsFifteen patients after CDH repair were examined using non-contrast-enhanced dynamic magnetic resonance imaging (MRI). For imaging two protocols were used during free-breathing: Protocol A with high temporal resolution and Protocol B with high spatial resolution. The dynamic images were then analysed through a recently developed post-processing method called dynamic mode decomposition (DMD) to obtain ventilation and perfusion maps. The ventilation ratios (VRatio) and perfusion ratios (QRatio) of ipsilateral to contralateral lung were compared to evaluate functional differences. Lastly, DMD MRI-based perfusion results were compared with perfusion parameters obtained using dynamic contrast-enhanced (DCE) MRI to assess agreement between methods.ResultsBoth imaging protocols successfully generated pulmonary ventilation (V) and perfusion (Q) maps in all patients. Overall, the VRatio and QRatio values were 0.84 ± 0.19 and 0.70 ± 0.24 for Protocol A, and 0.88 ± 0.18 and 0.72 ± 0.23 for Protocol B, indicating reduced ventilation (p<0.05\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$p<0.05$$\\end{document}) and perfusion (p<0.01\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$p<0.01$$\\end{document}) on the ipsilateral side. Moreover, there is a very strong positive correlation (r>0.89,p<0.01\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$r>0.89,p<0.01$$\\end{document}) and close agreement between DMD MRI-based perfusion values and DCE MRI-based perfusion parameters.ConclusionsDMD MRI can obtain pulmonary functional information in 2-year-old CDH patients. The results obtained with DMD MRI correlate with DCE MRI, without the need for ionising radiation or exposure to contrast agents. While further studies with larger cohorts are warranted, DMD MRI is a promising option for functional lung imaging in CDH patients.Clinical relevance statementWe demonstrate that pulmonary ventilation and perfusion information can be obtained in 2-year-old patients after CDH repair, without the need for ionising radiation or contrast agents by utilising non-contrast-enhanced MRI acquisitions together with dynamic mode decomposition analysis.Key Points• Non-contrast-enhanced functional MR imaging is a promising option for functional lung imaging in 2-year-old children after congenital diaphragmatic hernia.• DMD MRI can generate pulmonary ventilation and perfusion maps from free-breathing dynamic acquisitions without the need for ionising radiation or contrast agents.• Lung perfusion parameters obtained with DMD MRI correlate with perfusion parameters obtained using dynamic contrast-enhanced MRI.

Unique Cardiopulmonary Interactions in Congenital Diaphragmatic Hernia: Physiology and Therapeutic Implications.

Congenital diaphragmatic hernia (CDH) results in abdominal contents entering the thoracic cavity, affecting both cardiac and pulmonary development. Maldevelopment of the pulmonary vasculature occurs within both the ipsilateral lung and the contralateral lung. The resultant bilateral pulmonary hypoplasia and associated pulmonary hypertension are important components of the pathophysiology of this disease that affect outcomes. Despite prenatal referral to specialized high-volume centers, advanced ventilation strategies, pulmonary hypertension management, and the option of extracorporeal membrane oxygenation, overall CDH mortality remains between 25% and 30%. With increasing recognition that cardiac dysfunction plays a large role in morbidity and mortality in patients with CDH, it becomes imperative to understand the different clinical phenotypes, thus allowing for individual patient-directed therapies. Further research into therapeutic interventions that address the cardiopulmonary interactions in patients with CDH may lead to improved morbidity and mortality outcomes.

Risk of developing subsequent primary lung cancer after receiving radiation for breast cancer

BackgroundRadiotherapy (RT) is integral to breast cancer treatment, especially in the current era that emphasizes breast conservation. The aim of our study was to determine the incidence of subsequent primary lung cancer after RT exposure for breast cancer over a time span of 3 decades to quantify this risk over time as modern oncologic treatment continues to evolve. MethodsThe SEER (Surveillance, Epidemiology, and End Results) database was queried from 1988 to 2014 for patients diagnosed with nonmetastatic breast cancer. Patients who subsequently developed primary lung cancer were identified. Multivariable regression modeling was performed to identify independent factors associated with the development of lung cancer stratified by follow up intervals of 5 to 9 years, 10 to 15 years, and >15 years after breast cancer diagnosis. ResultsOf the 612,746 patients who met our inclusion criteria, 319,014 (52%) were irradiated. primary lung cancer developed in 5556 patients (1.74%) in the RT group versus 4935 patients (1.68%) in the non-RT group. In a multivariable model stratified by follow-up duration, the overall HR of developing subsequent ipsilateral lung cancer in the RT group was 1.14 (P = .036) after 5 to 9 years of follow-up, 1.28 (P = .002) after 10 to 15 years of follow-up, and 1.30 (P = .014) after >15 years of follow-up. The HR of contralateral lung cancer was not increased at any time interval. ConclusionsThe increased risk of developing a primary lung cancer secondary to RT exposure for breast cancer is much lower than previously published. Modern RT techniques may have contributed to the improved risk profile, and this updated study is important for counseling and surveillance of breast cancer patients.

Case report of non-tracheal intubation—an alternative for postpneumonectomy patients undergoing contralateral pulmonary resection

BackgroundSurgery on the contralateral or other lungs after pneumonectomy on one side is highly challenging and complex. It is critical to creating conditions for fluent surgical maneuvers while ensuring adequate ventilation for a patient during such an operation in the same chest cavity that appears incompatible.Case presentationWe have reported herein the case of a patient who, following a left pneumonectomy, underwent a right upper pulmonary nodule wedge resection via video-assisted thoracoscopic surgery without requiring endotracheal intubation. We managed ventilation with a laryngeal mask airway under general anesthesia combined with a thoracic epidural block. The diseased lobe collapsed well for the surgical procedure during VATS without hypoxia, after which the resection was safely performed.ConclusionsNon-tracheal intubation anesthesia can be a potentially attractive alternative for patients undergoing contralateral pulmonary resection after pneumonectomy.

Locoregional breast radiotherapy including IMN: optimizing the dose distribution using an automated non-coplanar VMAT-technique

Background Volumetric Modulated Arc Therapy (VMAT) offers better conformity, homogeneity and sparing of the heart and ipsilateral lung for locoregional radiotherapy in left-sided breast cancer compared to three-dimensional conformal radiotherapy (3D-CRT). However, conventional coplanar VMAT (cVMAT) can result in higher doses to the normal tissue on the contralateral side. This study investigates a non-coplanar VMAT-technique (ncVMAT) to mitigate this issue. Material and methods CT series of 20 left sided breast cancer patients were included for planning of locoregional breast radiotherapy including internal mammary nodes (IMN). Three treatment plans; 3D-CRT, cVMAT and ncVMAT, were generated for each patient with a prescription dose of 40.05 Gy in 15 fractions. Both VMAT-techniques consisted of a single arc in the axial plane, while ncVMAT included an additional arc in the sagittal plane. All plans were optimized to cover the clinical target volume (CTV) by 38.05 Gy for the breast and 36.05 Gy for lymph nodes, with as low as possible dose to organs at risk. Results Full CTV coverage was achieved for all plans. Both cVMAT and ncVMAT delivered more conformal and homogeneous target doses than 3D-CRT. Doses to the heart and ipsilateral lung were significantly lower with ncVMAT compared to both cVMAT and 3D-CRT. ncVMAT reduced doses to both the contralateral breast and lung compared to cVMAT and achieved levels similar to 3D-CRT for the contralateral breast and moderately higher doses for the contralateral lung. Delivery of high doses (>30 Gy) to the contralateral side was completely avoided with ncVMAT, contrary to the results for cVMAT and 3D-CRT. Conclusion ncVMAT reduced doses to the heart and ipsilateral lung as compared to both cVMAT and 3D-CRT. All contralateral dose metrics were reduced with the novel ncVMAT technique compared to cVMAT, and the mean contralateral breast doses were similar to 3D-CRT.

Comparative analysis of dose calculation algorithms for CyberKnife-based stereotactic radiotherapy in lung cancer.

The accuracy of dose calculation is the prerequisite for CyberKnife (CK) to implement precise stereotactic body radiotherapy (SBRT). In this study, CK-MLC treatment planning for early-stage non-small cell lung cancer (NSCLC) were compared using finite-size pencil beam (FSPB) algorithm, FSPB with lateral scaling option (FSPB_LS) and Monte Carlo (MC) algorithms, respectively. We concentrated on the enhancement of accuracy with the FSPB_LS algorithm over the conventional FSPB algorithm and the dose consistency with the MC algorithm. In this study, 54 cases of NSCLC were subdivided into central lung cancer (CLC, n=26) and ultra-central lung cancer (UCLC, n=28). For each patient, we used the FSPB algorithm to generate a treatment plan. Then the dose was recalculated using FSPB_LS and MC dose algorithms based on the plans computed using the FSPB algorithm. The resultant plans were assessed by calculating the mean value of pertinent comparative parameters, including PTV prescription isodose, conformity index (CI), homogeneity index (HI), and dose-volume statistics of organs at risk (OARs). In this study, most dose parameters of PTV and OARs demonstrated a trend of MC > FSPB_LS > FSPB. The FSPB_LS algorithm aligns better with the dose parameters of the target compared to the MC algorithm, which is particularly evident in UCLC. However, the FSPB algorithm significantly underestimated the does of the target. Regarding the OARs in CLC, differences in dose parameters were observed between FSPB and FSPB_LS for V10 of the contralateral lung, as well as between FSPB and MC for mean dose (Dmean) of the contralateral lung and maximum dose (Dmax) of the aorta, exhibiting statistical differences. There were no statistically significant differences observed between FSPB_LS and MC for the OARs. However, the average dose deviation between FSPB_LS and MC algorithms for OARs ranged from 2.79% to 11.93%. No significant dose differences were observed among the three algorithms in UCLC. For CLC, the FSPB_LS algorithm exhibited good consistency with the MC algorithm in PTV and demonstrated a significant improvement in accuracy when compared to the traditional FSPB algorithm. However, the FSPB_LS algorithm and the MC algorithm showed a significant dose deviation in OARs of CLC. In the case of UCLC, FSPB_LS showed better consistency with the MC algorithm than observed in CLC. Notwithstanding, UCLC's OARs were highly sensitive to radiation dose and could result in potentially serious adverse reactions. Consequently, it is advisable to use the MC algorithm for dose calculation in both CLC and UCLC, while the application of FSPB_LS algorithm should be carefully considered.

Interpretable Machine Learning for Predicting Symptomatic Pneumonitis in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Immune Checkpoint Inhibitor Consolidation.

The rate of grade 2 and higher pneumonitis has increased with the use of immune checkpoint inhibitors (ICI) following chemoradiotherapy (CRT) for lung cancer, which may alter previously established dose-volume constraints (DVC). In this study, we used an interpretable machine learning model with clinical and dosimetric features to predict grade 2+ pneumonitis and determine DVC associated with pneumonitis for locally advanced non-small cell lung cancer (LA-NSCLC) radiotherapy (RT). Between October 2017 and December 2021, 223 consecutively treated patients with LANSCLC treated with CRT and ICI were retrospectively reviewed. The dataset was split into training and test sets (n = 144/79). Clinical features included age, sex, smoking status, pack-years, BMI, ECOG PS, COPD, tumor location, delivered dose, RT technique, chemotherapy agent and volume of GTVp/GTVn. A total of 228 dosimetric features from the heart, contralateral/ipsilateral lung and lungs-IGTV were extracted, including the minimum/mean dose to the hottest x% volume (Dx%[Gy]/MOHx%[Gy]; x was 5-95 in 5% increments) and minimum/mean/maximum dose and percent volume receiving at least xGy (VxGy [%]; x was 5-60 in 5Gy increments), as well as the overlapping volume of each structure with PTV and the distance from each structure to GTVp/GTVn. Feature selection was performed using Boruta, followed by collinearity removal based on the variance inflation factor. The explainable boosting machine (EBM) was trained on the selected features. The performance of EBM on the test set was evaluated using the area under the receiver operating characteristic curve (AUC) and compared with that of blackbox (BB) models, including extreme gradient boosting (XGB), random forest (RF), and supporting vector machine (SVM). The global explanation of each feature's contribution to the predictions provided by the EBM was used to determine DVC. Shapley additive explanations (SHAP) were used to explain BB predictions. Selected features, ranked in order of EBM's overall feature importance, were V25Gy [%] and MOH65%[Gy] in the ipsilateral lung, the maximum dose in the heart, MOH30%[Gy] in the contralateral lung, and BMI. No dosimetric features in the lungs-IGTV were selected. The SHAP values of three BB models showed similar trends to the feature importance of the EBM. The global explanations of the EBM suggested that to mitigate the risk of pneumonitis, the ipsilateral lung should have V25Gy [%] < 36.8% and MOH65%[Gy] < 39.5Gy, and the heart should have D0.03cc [Gy] < 66.0Gy. Furthermore, an increased risk of pneumonitis was indicated with an increase in BMI, and, surprisingly, a decrease in MOH30%[Gy] in the contralateral lung. The EBM showed the best performance for predicting grade 2+ pneumonitis (AUC = 0.739), followed by RF, SVM, and XGB (AUC = 0.735, 0.733, and 0.717). EBM has the potential to predict grade 2+ pneumonitis in LA-NSCLC patients treated with CRT and ICI, while providing guidance on DVC.

Konjenital Diyafragma Hernisi Tanılı Fetüslerde Prognostik Marker Olarak Mide Pozisyonu

Aim: To examine the relationship between stomach position and neonatal survival in congenital diaphragmatic hernia (CDH). &#x0D; Materials and Method: A total of 36 pregnant women with a diagnosis of fetal CDH, aged between 18-45 years and 22-39 weeks of gestation, who applied Ankara City Hospital Perinatology clinic between December 2019 and December 2022, were analyzed retrospectively. Pregnancies were classified into two categories based on neonatal survival. Demographic characteristics, clinical features and contralateral lung size/head circumference (LHR) ratio, stomach position, and other prognostic indicators were evaluated among the survivor (n=8) and non-survivor (n=22) groups. &#x0D; Results: The mean maternal age was 29.30 ± 1.02 (range 17-40), and 36% (13/36) of the patients were primigravid. The median gestational week at diagnosis was 25.10 (13.5-37.6). There was no statistically significant difference between the survivor and non-survivor groups in terms of CDH type, liver position, gestational week at diagnosis, and median LHR. Grade 2 stomach position was found to be statistically significantly higher in the survivor group (p=0.01). Operation rate and 1st-5th minute Apgar scores were higher than in the non-survivor group (p=0.02, p=0.01, and p=0.00, respectively). &#x0D; Conclusion: Stomach position grading in CDH is a practical and applicable method associated with neonatal survival, and grade 2 stomach position may be a marker associated with increased survival in fetuses with CDH regardless of LHR. It may be useful in assessing neonatal prognosis and planning perinatal management, such as maternal transfer to a tertiary center where fetal interventions are available.

The Impact of Deep Inspiration Breath Hold (DIBH) Implementation on the Hybrid Technique in Left-Sided Whole Breast Irradiation: A Dosimetric Characteristic Study of 3D-CRT Hybrid VMAT in DIBH and Free Breathing Conditions, and VMAT in Free Breathing Conditions.

To investigate the impact of DIBH for heart sparing effect on left sided breast postoperative whole breast irradiation by comparing the dosimetric characteristics of 3D-CRT hybrid VMAT and pure VMAT treatment planning under DIBH condition. The primary CT data sets from previously treated left sided early breast cancer were used for pure volumetric arc therapy (VMAT) technique re-planning for the dosimetric characteristics comparison. A treatment plan of 3D-CRT hybrid VMAT technique was re-planned on the free breath (FB) condition for the investigation of the dosimetric characteristics comparison on DIBH condition. The prescribed dose for all the treatment plans was 42.5Gy in 16 fractions. All plans were optimized to cover 100% of the PTV by 95% of prescribed dose. The dosimetric differences among the 3 treatment plans for the 20 patients were analyzed using Wilcoxon signed-rank test, with p value<0.05 considered statistically significant. 3D-CRT hybrid VMAT using DIBH technique yielded the best results on the conformity index (CI) and homogeneity index (HI). By comparing this 3D-CRT hybrid VMAT technique using FB and DIBH technique, the mean heart dose (MHD) was reduced from 5.38Gy to 1.65Gy, respectively (p =0.001) and the left anterior descending coronary artery (LAD)0.03cc dose was reduced from 27.87Gy to 9.41Gy, respectively (p =0.001). 3D-CRT hybrid VMAT using DIBH technique significantly reduced the V5, V20 and D mean of the ipsilateral lung and D mean of the contralateral lung. The D5 of right breast was significantly reduced by 3D-CRT hybrid VMAT compared with VMAT using DIBH technique. The incorporation of DIBH into 3D-CRT hybrid VMAT technique provides the best benefits for the heart and the OAR with respect to the radiation dose-sparing effect without compromising the target conformity and homogeneity in the treatment planning.

Comparison of photon intensity modulated, hybrid and volumetric modulated arc radiation treatment techniques in locally advanced non-small cell lung cancer

Background and purposeThere is no consensus on the best photon radiation technique for non-small cell lung cancer (NSCLC). This study quantified the differences between commonly used treatment techniques in NSCLC to find the optimal technique. Materials and methodsTreatment plans were retrospectively generated according to clinical guidelines for 26 stage III NSCLC patients using intensity modulated radiation therapy (IMRT), hybrid, and volumetric modulated arc therapy (VMATC, and VMATV5 optimized for lower lung and heart dose). Plans were evaluated for target coverage, organs at risk dose (including heart substructures) and normal tissue complication probabilities (NTCP). ResultsThe comparison showed significant and largest median differences (>1 Gy or >5%) in favor of IMRT for the mediastinal envelope and heart (maximum dose), in favor of the hybrid technique for the lungs (V5Gy of the total lungs and V5Gy of the contralateral lung) and in favor of VMATC for the heart (Dmean), most of the substructures of the heart, and the spinal cord (maximum dose). The VMATV5 technique had significantly lower heart dose compared to the hybrid technique and significantly lower lung dose compared to the VMATC, combining both advantages in one technique. The mean ΔNTCP did not exceed the 2 percent point (pp) for grade 5 (mortality), and 10 pp for grade ≥2 toxicities (radiation pneumonitis and acute esophageal toxicity), but ΔNTCP was mostly in favor of VMATC/V5 for individual patients. ConclusionThis planning study showed that VMATV5 was preferred as it achieved low lung and heart doses, as well as low NTCPs, simultaneously.

Comparison of Hybrid Techniques with 3D-Conformal Radiotherapy in Patients with Lung Cancer

Purpose: It’s postulated that hybrid techniques (HT) with lower weighting of IMRT/VMAT component would improve lung dose-volume parameters despite some disadvantage in PTV homogeneity index (HI) and target coverage (TC). &#x0D; Material and Methods: Conformal plans were prepared using 6-10-15 MV-X photon energies while IMRT/VMAT plans of HTs were prepared using 6MV-X. Four HTs were developed having two different ratios (10% and 50%) of IMRT/VMAT component (h-IMRT1, h-IMRT2 and h-VMAT1, h-VMAT2, respectively). HTs were compared with 3D-CRT in terms of HI and TC for PTV, and total lung (TL) and contralateral lung (CL) V5Gy, V10Gy, V20Gy and mean lung dose (MLD). &#x0D; Results: All HTs were advantageous for HI and TC, while disadvantageous for TL and CL-V5Gy. H-IMRT2 provided better TC than h-IMRT1, and so did h-VMAT2 compared to h-VMAT1. Lower weighting of IMRT/VMAT decreased TL and CL-V5Gy in HTs. In addition, h-IMRT1 decreased TL and CL-MLD and CL-V20Gy compared to h-IMRT2, while h-VMAT2 decreased TL-V20Gy and CL-MLD compared to h-VMAT2. &#x0D; Conclusion: In the RT of lung tumors close to vertebra, it may be appropriate to suggest a ratio of IMRT/VMAT component about 10% in order to decrease the low and intermediate dose-wash lung volume, if HI and TC values are acceptable.

Multi-Criteria Optimization and RapidPlan for Improved Organs at Risk Sparing in Treatment Planning of Malignant Pleural Mesothelioma

Treatment planning for malignant pleural mesothelioma is complex and time-consuming owing to the large volume of the target as well as its overlap and proximity to critical organs. Knowledge-based planning (KBP) model using RapidPlan (RP) was previously developed and clinically tested at our institution for treatment planning of these cases that had undergone pleurectomy-decortication, and therefore had two intact-lungs. The aim of this work is to investigate if multi-criteria optimization (MCO) can further improve the RP model with respect to organ at risk (OAR) sparing without compromising target coverage. The RP model was trained with clinically accepted plans of 57 patients that used Volumetric Modulated Arc Therapy (VMAT) with 2 partial arcs and 6 MV photons. The dose volume histogram (DVH) estimation model was trained to estimate doses to the heart, ipsilateral lung, total lung, contralateral lung, stomach, esophagus, kidneys and liver. Clinical treatment plans for 12 patients were re-planned using RP as well as a combination of RP and MCO. Application of MCO was after RP and used tradeoff exploration to navigate to the improved dose distribution on a Pareto surface. Selection of a plan that further improved OAR sparing while maintaining coverage constraints of PTV D95 and V95 ≥ 94% was made. Dosimetric parameters for clinical plans (CP), plans using RP as well as plans generated with RP and MCO were all compared for 12 new validation cases. Wilcoxon sign-rank test was used for statistical significance testing. The mean heart dose was reduced from 20.9 Gy ± 3.2 Gy for CP to 17.1 Gy ± 4.2 Gy with RP and further to 13.8 Gy ± 3.3 Gy with RP and MCO. The heart V30 Gy was reduced from 23.7% ± 8% to 18.2% ± 9.4% with RP and further to 13.6% ± 5.7% with RP and MCO. The corresponding results for contralateral lung V5 Gy were 68.6% ± 14.1% with CP, 50% ± 26.3% with RP and 45.3% ± 22.8% with RP and MCO, while the mean esophagus dose was reduced from 26.5 Gy ± 3.1 Gy to 21.5 Gy ± 4.7 Gy with RP and further to 19.1 Gy ± 4.2 Gy with RP and MCO. All these dosimetric improvements were statistically significant (p<0.001). However, improvements with RP and MCO for the total lung mean and V20 Gy, liver mean, stomach mean and kidney V18 Gy were marginal over the RP. Sparing of ipsilateral lung V20 Gy was maintained at ≥ 50 cc on average for all plans. PTV D95 and V95 were both normalized at 94%. Combination of RP and MCO significantly improved sparing of the OARs, especially the heart, contralateral lung and esophagus without compromising coverage or doses to other structures. Since doses to the heart, and contralateral lung are known to correlate with incidence of radiation pneumonitis, it would be prudent to consider planning with both RP and MCO to help determine the optimal treatment plan for the individual patient's anatomy.

Quality Assurance of Protocol Compliance in a Multicenter Randomized Trial Investigating the Role of Hypofractionated Comprehensive Reginal Nodal Irradiation in Node-Positive Breast Cancer (HARVEST)

The HARVEST trial (NCT03829553) is a phase III, multicenter, randomized clinical trial to explore efficacy and safety of hypofractionated irradiation (HFI) involving regional nodal irradiation (RNI, including internal mammary nodes, IMN) in N+ breast cancer patients treated with mastectomy or breast conserving surgery (BCS). Current study aims to analyze the dosimetric quality assurance so as to evaluate the compliance to the trial protocol. Eligible patients were randomly assigned (1:1) to receive conventional fractionated irradiation (CFI: 50 Gy/25Fx) or HFI (40.05 Gy/15Fx), which is delivered to ipsilateral chest wall or whole breast (CW/WB) with tumor bed boost (HFI: 10.68 Gy/4Fx; CFI: 10 Gy/5Fx) and comprehensive RNI (supra/infraclavicular nodes and IMN in each patient, lower axilla if indicated) by using IMRT technique. The plan quality was evaluated based on dose distribution, dose volume histogram (DVH) and field parameters. The target coverage, including planning target volume of CW/WB (PTV1) and tumor bed (PTV2) and doses of the organs at risk (OARs) were evaluated. The LQ model was used to convert doses of OARs in HFI group using α/β = 3 Gy (EQD23) for comparison. Between Feb 21, 2019 and Feb 14, 2022, 801 patients were enrolled at 8 centers with 401 and 400 in CFI and HFI group, respectively. There were 182 patients received BCS and 387 patients were with more than three positive lymph nodes. In the CFI group, the D90 and V45 of PTV1 reached the prescribed dose in 70.6% and 96.0% of the patients, respectively. In the HFI group, the D90 and V36 of PTV1 reached the prescribed dose in 87.8% and 95.5% of the patients, respectively. When the tumor bed was irradiated, the D90 of PTV2 reached the prescribed dose in 95.6% in the CFI group and 100% in the HFI group, respectively. The mean D90 of PTV1 and PTV2 were 50.09±0.65 Gy and 60.63±0.91 Gy in CFI group while 40.11±0.56 Gy and 50.79±2.03 Gy in HFI group. For OARs constraints, protocol compliance was all above 95% (heart: 95.3%; ipsilateral lung: 95.5%; contralateral lung: 97.1%; humeral head: 98.2% and spinal cord: 100%) with no significant difference between CFI and HFI groups. For patients with left-sided breast cancer, the Dmean of the heart was 5.10±1.75 Gy vs. 4.59±1.86 Gy (EQD23) in CFI and HFI groups (p = 0.51), respectively. No significant differences in Dmean of the heart (1.45±0.71 Gy vs. 1.33±0.77 Gy (EQD23), p = 0.40) was found either between two groups in right-sided patients. The differences were significant in the Dmean of the ipsilateral lung (13.37±1.99 Gy vs. 11.17±3.50 Gy (EQD23), p<0.01), contralateral lung (0.88±0.73 Gy vs. 0.74±0.61 Gy (EQD23), p<0.01) and the ipsilateral humeral head (15.27±7.62 Gy vs. 13.05±6.19 Gy (EQD23), p<0.01) and the Dmax of spinal cord (21.40±8.82 Gy vs. 19.47±7.99 Gy (EQD23), p = 0.05) between CFI and HFI groups. A high degree of compliance with protocol dose constraints was found for treatment plans in the HARVEST trial and doses to the most of OARs decreased in HFI group.

Dosimetric Comparison of Adaptive Radiotherapy Modalities for Stereotactic Partial Breast Irradiation

An increase in the availability of adaptive radiotherapy (ART) platforms have proven to be effective in the treatment of a variety of sites. In this study, we aim to evaluate the effectiveness of non-adaptive RT and 3 different ART platforms: (1) CBCT-based, (2) CT-based, and (3) MRI-based for stereotactic partial breast irradiation (SPBI). Data were collected from 32 patients (16 left and 16 right breast) treated at a single institution. 16 patients (8 left and 8 right) treated using the non-ART platform were re-planned onto two different ART platforms, CBCT- and MRI-based. The remaining 16 patients treated using CT-based adaptive platform were not re-planned due to the prone patient treatment position (others systems supine). All cases were planned to 30 Gy in 5 fractions. Plan quality was evaluated based on pre-defined planning goals to the OARS: ipsilateral and contralateral lungs (Dmean, Dmax, V20 Gy, V9 Gy), ipsilateral (V15 Gy, V30 Gy) and contralateral breasts (Dmax), heart (Dmean, Dmax, V3 Gy, V1.5 Gy), skin (Dmax, V36.5 Gy), and rib (Dmax, V30 Gy). Target goals were defined by Dmax, Dmin, gradient index, and paddock conformality index. Re-planned cases were compared within the cohort using a paired t-test and a 2-sided t-test was used comparing to the CT-based platform. Comparing the left and right breast cohort across all platforms, the CT-based ART system showed a signification dose reduction in Dmean (p<0.001 for all platforms), Dmax (p<0.001 for left breast, p<0.03 for right breast) and V9 Gy (p<0.004 for left breast, p<0.001 for right breast) to the ipsilateral lung, V15 Gy (p<0.004 for left breast cohort) to the ipsilateral breast, and Dmax to the contralateral breast (p<0.001) and ribs (p = 0.01, p<0.001, p = 0.01 for CBCT-ART, MRI-ART, and non-ART for left breast cohort only). On average, the MR-Linac platform showed the least degree of OAR sparing across nearly all dosimetric parameters evaluated when compared to all modalities, especially for contralateral lung Dmean and Dmax (p<0.05 for all dosimetric parameters for all platforms) and contralateral breast Dmax (p<0.003 for all platforms). The CBCT-based platform showed superior dose reduction in contralateral lung mean (p<0.03 for all platforms) and heart Dmean (p = 0.065, p<0.001, p = 0.045 for non-adaptive, MRI-ART, and CT-ART for left breast and p<0.008 for right breast). PTV coverage was comparable across all platforms, averaging at approximately 95%. The CT-based ART platform showed a significantly reduced gradient index relative to the CBCT- and MRI-based platforms (p<0.001). For SPBI treatments, the CT-based ART platforms displayed a higher degree of OAR sparing for many of the dosimetric parameters recorded relative to the other ART and non-ART platforms presented. The MRI-based system typically showed less reduced OAR sparing; however, the advantage of the system is shown if soft tissue contrast is needed. PTV coverage remained comparable across all platforms.

Phase I-II Study of Prone Hypofractionated Accelerated Breast and Nodal Intensity Modulated Radiation Therapy

In patients (pts) with breast cancer, prone radiation therapy (RT) has been shown to reduce heart and lung dose which may decrease late toxicity. Routinely used for whole breast irradiation, its use to treat regional lymph nodes (LNs) is not widespread. In this phase I-II study, pts treated with partial mastectomy or mastectomy with 1-5 pathologically involved LNs underwent whole breast or post-mastectomy RT plus regional nodal irradiation using IMRT to the supraclavicular and level III axillary LNs. Pts who underwent sentinel LN biopsy (SLNB) alone (no axillary dissection) had the level I and II axillary LNs included in the RT field. 40.5Gy in 15 daily 2.7Gy fractions with daily concomitant 0.5Gy tumor bed boost was prescribed. Normal tissue dose constraints included heart V5Gy<5%, ipsilateral lung V10Gy<20%, contralateral lung V5Gy<15%, ipsilateral brachial plexus (BP) maximal dose (Dmax)<43Gy, spinal cord Dmax≤37.5Gy, spinal cord + 0.5cm Dmax<41Gy, thyroid contralateral lobe Dmax<16Gy, esophagus V30Gy<50% and Dmax≤40.5Gy. The primary endpoints were dosimetric feasibility and incidence of >grade 2 acute toxicity according to CTCAE, v3.0. The secondary endpoint was late toxicity. Exploratory outcomes were local recurrence, disease free survival (DFS), and overall survival (OS). Between January 2011 to December 2016, 97 pts with stage IB-IIA breast cancer were enrolled. 66 pts underwent partial mastectomy and 31 pts underwent mastectomy. 16 pts had SLNB alone. 33% (95% CI: 23.8%, 43.3%) met all protocol dose constraints. Heart, contralateral lung, spinal cord and esophagus V30Gy constraints were met by all pts. The ipsilateral lung constraint was met in 95% (95% CI: 88.6%, 98.4%) of plans with a mean V10Gy of 9.44% (SD: 6.08). The BP Dmax constraint was exceeded in 31.6% (95% CI: 22.4%, 41.9%) of plans with a mean increase of 2.86 Gy (SD: 7.92 Gy) over target. The esophageal Dmax<40.5Gy constraint was exceeded in 6 plans with an increase in 0.74 Gy (SD: 0.46 Gy) over target. There were no grade 3 acute toxicities meeting the primary toxicity endpoint. Common acute low-grade toxicities by pt included fatigue (grade 1: 54 [56%]; grade 2: 2 [2%]), esophagitis (grade 1: 8 [8%]; grade 2: 2 [2%]), dermatitis (grade 1: 81 [84%]; grade 2: 6 [6%]). At median and maximum follow up of 8.02 (IQR: 3.31) and 13.3 years, respectively, there were 2 local recurrences (2.1%). DFS and OS were 86.6% (95% CI: 78.2%, 92.7%) and 90.7% (95% CI: 83.1%, 95.7%), respectively. The incidence of pts with maximum grade 1, 2 and 3 late toxicities were 39 (40%), 14 (14%), and 2 (2%), respectively. The maximum grade late toxicities included 1 grade 3 retraction and 2 grade 3 asymmetries. There was no brachial plexopathy or pneumonitis. Patients treated with prone hypofractionated hybrid breast/chest wall tangents and IMRT to the regional LNs demonstrate excellent dosimetry to the heart, lungs and spinal cord, minimal acute and late toxicity and excellent clinical outcomes. PMID: 26723552.