Radiation-Induced Dyspnea in Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

In this study, we investigated the prognostic factors for radiation-induced dyspnea after hypo-fractionated radiation therapy (RT) in 106 patients treated with Stereotactic Body RT for Non-Small-Cell Lung Cancer (NSCLC). The median prescription dose was 50 Gy (range: 40–54 Gy), delivered in a median of four fractions (range: 3–12). Dyspnea within six months after SBRT was scored according to CTCAE v.4.0. Biologically Effective Dose (α/β = 3 Gy) volume histograms for lungs and heart were extracted. Dosimetric parameters along with patient-specific and treatment-related factors were analyzed, multivariable logistic regression method with Leave-One-Out (LOO) internal validation applied. Model performance was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot parameters. Fifty-seven patients (53.8%) out of 106 developed dyspnea of any grade after SBRT (25/57 grade ≥ 2 cases). A three-variable predictive model including patient comorbidity (COPD), heart volume and the relative lungs volume receiving more than 15 Gy was selected. The model displays an encouraging performance given by a training ROC-AUC = 0.71 [95%CI 0.61–0.80] and a LOO-ROC-AUC = 0.64 [95%CI 0.53–0.74]. Further modeling efforts are needed for dyspnea prediction in hypo-fractionated treatments in order to identify patients at high risk for developing lung toxicity more accurately.

An Innovative VMAT Technique for Left-sided Breast Cancer Patients With Postmastectomy Radiotherapy (PMRT) Evaluated by Ratio of Heart Volume in Tangent Line (RHVTL)

For patients with left-sided breast cancer (LBC), postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival and many advanced planning techniques was adopted in PMRT. We aim to use an innovative VMAT technique to enhance the conformity of PTV and reduce the scattering dose of surrounding OARs, thereby reducing the long-term toxicity of the heart as well as ipsilateral lung (IL). The study further analyzes the more appropriate treatment planning techniques for personalized LBC patients with PMRT. 35 LBC patients were retrospectively selected undergoing PMRT. The PTV included lymph nodes, chest walls, excluding internal mammary nodes, where 95% of PTV receiving the prescription dose of 50Gy (2Gy/fraction) with three different techniques, VMAT, IMRT, Hybrid VMAT. Furthermore, the ratio of Heart Volume in Tangent line and heart volume (RHVTL) was proposed to evaluate the relative antonymy position between patient's heart and PTV, which hypothetically represents the complexity of treatment planning. The data from this study showed that for LBC patients undergoing PMRT, the CI from VMAT was 0.85 (IMRT and H-VMAT were 0.77 and 0.83), the heart D mean was 502.9cGy (IMRT and H-VMAT were 675.6cGy and 687cGy) and the V20 of IL was 21.3 as the lowest of the three techniques, but the dose of the contralateral breast (CB) and contralateral lung increased noticeably. In H-VMAT and IMRT, the mean heart dose was significantly related to RHVTL, with R-values of 0.911 and 0.892 respectively, while the values in VMAT was 0.613, thus the VMAT technique was relatively unaffected by the difficulty of treatment plan. For RHVTL values exceed than 0.06, the mean heart dose under VMAT technique raised by 98.7cGy compared to the RHVTL value of less than 0.06, but H-VMAT and IMRT increased by 233cGy and 261.58cGy individually. This study illustrates that separated fields and adjacent fields in VMAT technique obtained the optimal conformality and lowest doses of heart in three techniques for LBC with PMRT. Thus, based on the results of our preliminary study, the VMAT technique is highly recommended when RHVTL is exceeded 0.06.

Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer

Background We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC). Materials and methods Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy). Results Following re-optimization, mean MDHeart, VHeart-50-Gy and VLAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gy and VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeart values exceeded the median value in a published series, the average MDHeart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeart values. Conclusions Cardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeart levels, for whom larger reductions in heart doses can be achieved.

Effect of Exercise-Induced Reductions in Blood Volume on Cardiac Output and Oxygen Transport Capacity

We wanted to demonstrate the relationship between blood volume, cardiac size, cardiac output and maximum oxygen uptake (V.O2max) and to quantify blood volume shifts during exercise and their impact on oxygen transport. Twenty-four healthy, non-smoking, heterogeneously trained male participants (27 ± 4.6 years) performed incremental cycle ergometer tests to determine V.O2max and changes in blood volume and cardiac output. Cardiac output was determined by an inert gas rebreathing procedure. Heart dimensions were determined by 3D echocardiography. Blood volume and hemoglobin mass were determined by using the optimized CO-rebreathing method. The V.O2max ranged between 47.5 and 74.1 mL⋅kg–1⋅min–1. Heart volume ranged between 7.7 and 17.9 mL⋅kg–1 and maximum cardiac output ranged between 252 and 434 mL⋅kg–1⋅min–1. The mean blood volume decreased by 8% (567 ± 187 mL, p = 0.001) until maximum exercise, leading to an increase in [Hb] by 1.3 ± 0.4 g⋅dL–1 while peripheral oxygen saturation decreased by 6.1 ± 2.4%. There were close correlations between resting blood volume and heart volume (r = 0.73, p = 0.002), maximum blood volume and maximum cardiac output (r = 0.68, p = 0.001), and maximum cardiac output and V.O2max (r = 0.76, p < 0.001). An increase in maximum blood volume by 1,000 mL was associated with an increase in maximum stroke volume by 25 mL and in maximum cardiac output by 3.5 L⋅min–1. In conclusion, blood volume markedly decreased until maximal exhaustion, potentially affecting the stroke volume response during exercise. Simultaneously, hemoconcentrations maintained the arterial oxygen content and compensated for the potential loss in maximum cardiac output. Therefore, a large blood volume at rest is an important factor for achieving a high cardiac output during exercise and blood volume shifts compensate for the decrease in peripheral oxygen saturation, thereby maintaining a high arteriovenous oxygen difference.

Evaluation and Implementation of Otsu and Active Contour Segmentation in Contrast-Enhanced Cardiac CT Images

The CT cardiac acquisition process is usually conducted by using an additional image with contrast medium that is injected inside the body and reconstructed by a radiologist using an integrated CT Scan software with the aim to find the morphology and volume dimension of the heart and coronary arteries. In fact, the data obtained from the hospital are raw data without segmented contour from a radiologist. For the purpose of automation, dataset is needed to be used as input data for further program development. This study is focused on the evaluation of the segmentation results of CT cardiac images using Otsu threshold and active contour algorithm with the aim to make a dataset for the heart volume quantification that can be used interactively as an alternative to integrated CT scan software. 2D contrast enhanced cardiac CT from 6 patients using image processing techniques was run on Matlab software. Of the 689 slices that was used, as many as (73.75 ± 19.41)%of CT cardiac slices have been segmented properly, (19.15 ± 19.61)%of the slices that were segmented included the spine bone, (1.36 ± 0.98)%of the slices did not include all region of the heart, (16.58 ± 15.26)%of the slices included other organs with the consistency from the measurement proven from inter-observer variability to produce r = 0,9941.The result is due to the geometry influence from the diameter of the patient’s body thickness that tends to be thin.

Evaluation of dosimetric implications of Pareto and constrained mode of optimization for Monaco TPS generated VMAT plans in post operated carcinoma of the left breast

Intensity-modulated radiotherapy (IMRT) is being practiced for the last several years with a special approach for radiation therapy in post-mastectomy breast cancer patients. Meeting the cardiac dose constraints has always been a challenge during radiotherapy planning by both IMRT and VMAT (volumetric modulated arc therapy) of post-mastectomy left breast patients. With the advancement in IMRT planning techniques, it has been modified to VMAT with more degrees of freedom for modulation and is being utilised more frequently. This helps in obtaining a suitable plan for achieving both the dose homogeneity in target volume and dose constraints to Organ at Risk (OAR). 10 Patients with carcinoma of the left breast (post-mastectomy) were selected for this study. VMAT treatment plans for these patients were generated for 6 MV photons on the Monaco treatment planning system (TPS) using two types of optimization modes i.e. Pareto and Constrained mode available in Monaco TPS. For comparative dosimetric evaluation of the efficacy of these two types of optimization modes similar calculation algorithms, calculation grids, arcs, and beam sequencing parameters were used for generating treatment plans. The dosimetric quantities such as volume receiving more than 95% of the prescribed dose (V95), volume receiving more than 107% of the prescribed dose (V107) and Maximum dose (Dmax) for target volume, mean dose (Dmean) for heart, volume receiving more than 30 Gy (V30) volume receiving more than 20 Gy (V20) volume receiving more than 5 Gy (V5) for ipsilateral lung and total monitor units delivered were analysed for both optimization modes. A judicious mix of multiple planning parameters and variables using these two modes of optimization was applied and recorded. Both optimization modes yielded similar outcomes. However, Pareto mode has shown better coverage for planning target volume (PTV) with comparable doses to OARs.

Breath Hold Breast Radiotherapy In The Era of Precision Medicine: Appropriate Selection for Left Descending Artery Sparing

Background and purpose To identify anatomical and/or preplanning characteristics correlated with left descending artery (LAD) dose and therefore provide guidance in the selection of patients with left-breast cancer that could benefit the most from the use of deep inspiration breath hold radiotherapy (DIBH-RT). Materials and methods We retrospectively identified patients with left-sided breast cancer who underwent whole breast radiotherapy in DIBH and extracted data from treatment plans in free-breathing (FB) and DIBH. The following anatomical parameters were obtained from the planning CTs in FB: lung volume, heart volume, breast separation, minimum distance from LAD to tangent open field. Receiving operating characteristics was also performed to define the cut-off point of parameters to use in LAD dosimetry prediction. Areas under the curve (AUCs) were calculated for all variables. Post-test probability has been calculated to evaluate advantage for parameters combination. Results One hundred ninety-seven patients were identified. The strongest predictor at FB CT scan of LAD maximum dose > 10 Gy and a LAD mean dose > 4 Gy was the minimum distance of LAD from tangent open fields. Adding consecutively other preplanning anatomic parameters, the positive predictive value (PPV) to identify patients at risk of higher dose to LAD was > 90%. Conclusions The dosimetric benefit of DIBH is valid for all patients and DIBH should be preferred for all left sided patients; however we can identify a subgroup of patients who benefit the least from DIBH. This is the group with favorable anatomy: limited breast separation, well expanded lungs, LAD distant from open tangent fields.

Brain natriuretic peptide and atrial septal defect size in children

Background Atrial septal defect (ASD) is one of the most common forms of congenital heart disease (CHD). Brain natriuretic peptide (BNP) is a heart marker released into the circulation during pressure overload, heart volume expansion, and increased stress on +the myocardial wall. Objective To assess for a possible association between atrial septal defect size and BNP level in pediatric patients. Methods This cross sectional study on children with ASD was done from March to December 2018 in pediatric outpatients and inpatients at Dr. Wahidin Sudirohusodo Hospital, Makassar, South Sulawesi. Measurement of ASD defect was conducted using echocardiography and categorized as small defect (<3 mm), medium defect (3-8 mm), and large defect (>8 mm). Brain natriuretic peptide was measured using radioimmunoassay and immunoradiometricassay. Nutritional status was categorized using WHO if the patients aged younger than 5 years and NCHS for patients aged equal or more than 5-year-old. Results Mean BNP levels were 65.5 pg/mL in the small ASD group, 273.2 pg/mL in the moderate ASD group, and in 654.5 pg/mL in the large ASD group, with significant differences among ASD groups. We found a significant positive correlation between BNP levels and ASD diameter (r=0.829; P=0.001), with Y regression equation of: (BNP level) =2.624 + 0.009X (ASD diameter in mm). Conclusion Brain natriuretic peptide levels have significant positive correlation with ASD size. Hence, BNP measurements can be used to predict septal defect size in children with ASD. Acyanotic CHD patients with suspected ASD and high BNP levels may have moderate-to-large ASDs.