Inspiration Breath Hold Research Articles

Quantitative analysis of MRI-guided radiotherapy treatment process time for tumor real-time gating efficiency.

PurposeMagnetic Resonance‐guided radiotherapy (MRgRT) systems allow continuous monitoring of therapy volumes during treatment delivery and personalized respiratory gating approaches. Treatment length may therefore be significantly affected by patient’s compliance and breathing control. We quantitatively analyzed treatment process time efficiency (TE) using data obtained from real‐world patient treatment logs to optimize MRgRT delivery settings.MethodsData corresponding to the first 100 patients treated with a low T hybrid MRI‐Linac system, both in free breathing (FB) and in breath hold inspiration (BHI) were collected. TE has been computed as the percentage difference of the actual single fraction’s total treatment time and the predicted treatment process time, as computed by the TPS during plan optimization.Differences between the scheduled and actual treatment room occupancy time were also evaluated. Finally, possible correlations with planning, delivery and clinical parameters with TE were also investigated.ResultsNine hundred and nineteen treatment fractions were evaluated. TE difference between BHI and FB patients’ groups was statistically significant and the mean TE were 42.4%, and −0.5% respectively.No correlation was found with TE for BHI and FB groups. Planning, delivering and clinical parameters classified BHI and FB groups, but no correlation with TE was found.ConclusionThe use of BHI gating technique can increase the treatment process time significantly. BHI technique could be not always an adequate delivery technique to optimize the treatment process time. Further gating techniques should be considered to improve the use of MRgRT.

1675MO Screening of COVID-19 disease based on chest CT and PCR for cancer patients undergoing radiotherapy in a French coronavirus hotspot

The coronavirus disease (COVID-19) pandemic has caused 180,000 confirmed cases in France with more than 28, 000 deaths as of May 19. A large part of COVID-19 patients seem asymptomatic and cancer patients may be more vulnerable. We evaluated a screening strategy combining chest computed tomography (CT) and PCR for patients treated with radiotherapy (RT). A screening strategy was organized from March 18, in our RT department. An inspiratory breath hold chest acquisition was proposed during the CT simulation for RT. Images was reviewed by a radiologist according to the CO-RADS classification. A nasal swab with a polymerase chain reaction (PCR) assay was proposed by the radiation oncologist in case of evocative imaging or clinical context. For patients who were already undergoing RT at this time, a PCR was proposed in case of evocative symptoms and before concomitant chemotherapy. From March 18 to May 1, 2020, 507 CT simulation were performed for 449 patients, including 445 chest acquisition. 237 of the chest CT (53%) showed lung abnormalities, of which 34 (8%) were COVID-19 compatible (CO-RADS ≥ 3). 102 patients were tested by PCR after the chest CT. 24 of the 449 (5.3%) patients were considered as COVID-19 patients: 19 had positive PCR, and five were considered positive on the basis of imaging despite PCR-negative PCR. Four of the patients (17%) were diagnosed during RT: 3 on routine screening before chemoradiotherapy, and one on symptoms. Four patients needed several PCR for the diagnosis of COVID-19 with six confirmed false negative PCR (Sensitivity (Se)= 76 % (19/25)). Three PCR positive patients had no evocative lung images (Se = 84%). During this period, an additional 169 patients whose CT simulation was prior to March 18, were also undergoing RT. Among them, six patients (3.6%) were diagnosed with COVID-19 by PCR during RT, performed for symptoms in 4 cases and on screening for the other 2. Of the 30 COVID-19 patients, only 8 (27%) had symptoms at the time of diagnosis. Twelve patients (40%) reported no symptoms and benefited from screening. This study confirms the high proportion of asymptomatic patients with COVID-19 and suggests the value of screening by CT and PCR during COVID-19 pandemics.

Assessment of celiac artery compression using color-coded duplex sonography.

Median arcuate ligament syndrome (MALS) is a rare condition due to compression of the celiac artery (CA) by an anatomically abnormal median arcuate ligament. With ultrasonography (US) as first-line diagnostic modality in patients with unclear abdominal pain, there is limited data on its diagnostic performance in MALS. To investigate the value of CA peak systolic velocity (PSV) in the workup of patients with suspected MALS. Patients with diagnosis of MALS between 2009 and 2019 were referred by Department of Visceral Surgery after clinical and gastroenterological workup. Diagnosis was confirmed by surgery or further cross-sectional imaging. B-mode US findings and PSV in the CA during various respiratory states were compared between patients with a final MALS diagnosis and patients not meeting the diagnostic criteria. Patients with proven MALS (n = 10) had higher median CA PSV during normal inspiratory breath-hold (239 [IQR, 159-327] vs. 138 [IQR, 116-152] cm/s; p < #x003C;< #x200A;0.001), and expiratory breath-hold (287 [IQR, 191-412] vs. 133 [IQR, 115-194] cm/s; p < #x003C;< #x200A;0.001) compared to patients without MALS (n = 26). CA PSV in both inspiratory breath-hold (AUC 0.88, 95% CI 0.77-1.00) and expiratory breath-hold (AUC 0.89, 95% CI 0.78-1.00) was of diagnostic value for confirming MALS. The best diagnostic performance (100% sensitivity, 80% specificity) was found for the combination of CA PSVexpiration+2.4·PSVinspiration>550cm/s . Since results on optimal cutoff values are inconsistent, a combination of CA PSVs during breathing maneuvers may help to diagnose or rule out MALS.

Free breathing lung T1 mapping using image registration in patients with idiopathic pulmonary fibrosis.

To assess the use of image registration for correcting respiratory motion in free breathing lung T1 mapping acquisition in patients with idiopathic pulmonary fibrosis (IPF). The method presented used image registration to synthetic images during postprocessing to remove respiratory motion. Synthetic images were generated from a model of the inversion recovery signal of the acquired images that incorporated a periodic lung motion model. Ten healthy volunteers and 19 patients with IPF underwent 2D Look-Locker T1 mapping acquisition at 1.5T during inspiratory breath-hold and free breathing. Eight healthy volunteers and seven patients with IPF underwent T1 mapping acquisition during expiratory breath-hold. Fourteen patients had follow-up scanning at 6 months. Dice similarity coefficient (DSC) was used to evaluate registration efficacy. Image registration increased image DSC (P < .001) in the free breathing inversion recovery images. Lung T1 measured during a free breathing acquisition was lower in patients with IPF when compared with healthy controls (inspiration: P = .238; expiration: P = .261; free breathing: P = .021). Measured lung T1 was higher in expiration breath-hold than inspiration breath-hold in healthy volunteers (P < .001) but not in patients with IPF (P = .645). There were no other significant differences between lung T1 values within subject groups. The registration technique significantly reduced motion in the Look-Locker images acquired during free breathing and may improve the robustness of lung T1 mapping in patients who struggle to hold their breath. Lung T1 measured during a free breathing acquisition was significantly lower in patients with IPF when compared with healthy controls.

Dosimetric Correlation Between The Depth of Chest Wall Expansion and Heart Dose in Left Breast Cancer Irradiation Using Deep Inspiratory Breath Hold Technique

Introduction and Objective: In adjuvant radiotherapy for left breast cancer, a significant heart volume may be included in the radiation field leading to long-term cardiac toxicities. Deep inspiratory breath hold technique (DIBH) leads to chest wall separation away from the heart and thus can reduce the heart dose compared to free breathing technique. The aim of this study is to correlate dosimetrically the degree of chest wall expansion measured on planning 4D-CT scan to the heart dose in left breast cancer irradiation using DIBH technique. Materials and Methods: Thirty four patients with left breast cancer planned for adjuvant radiotherapy were included. All patients were scanned by Varian RPM (Real Time Position Managment) respiratory gating system using infrared reflecting markers and a video camera to detect the respiratory motion. IMRT or VMAT plans were done for all patients with a prescribed dose 50Gy/25fr/5w with or without operative bed boost dose 10Gy/5fr/1w. The degree of chest wall expansion was identified by measuring the amplitude of DIBH breathing curve from baseline in planning 4D-CT scan in centimeters. The depth of expansion was correlated dosimetrically with the heart V20, V30, and mean heartdose. Results: The mean distance of chest wall expansion was 2.9cm. The mean left lung dose was 8.6Gy. The mean left lung V20 was 13.8%. The mean heart dose was 1.8Gy. The mean heart V30 was 0.6%. A statistically significant reduction of the mean heart dose and V30 was observed with chest wall expansion of 1.4cm or higher (p&lt;0.05). Conclusion: In DIBH technique, the depth of chest wall expansion in 4DCT planning is dosimetrically correlated with the cardiac dose reduction during adjuvant irradiation of left breast cancer. Further clinical studies are needed to translate this dosimetric advantage into clinical benefit.

A Prospective Trial to Compare Deep Inspiratory Breath Hold With Prone Breast Irradiation

PurposeTo compare heart and lung doses for adjuvant whole breast irradiation (WBI) between radiation plans generated supine with deep inspiratory breath hold (S-DIBH) and prone with free-breathing (P-FB) and examine the effect of breast volume (BV) on dosimetric parameters. Methods and MaterialsPatients with left breast ductal carcinoma in situ or invasive cancer receiving adjuvant WBI were enrolled on a single-institutional prospective protocol. Patients were simulated S-DIBH and P-FB; plans were generated using both scans. Wilcoxon signed-rank and rank-sum tests were used to compare intrapatient differences between plans for the entire cohort and within BV groups defined by tertiles. ResultsForty patients were enrolled. Thirty-four patients are included in the analysis owing to patient withdrawal or inability to hold breath. With WBI dose of 4005 to 4256 cGy, mean heart dose (MHD) was 80 cGy in S-DIBH and 77 cGy in P-FB (P = .08). Mean ipsilateral lung dose (MLD) was 453 cGy in S-DIBH and 45 cGy in P-FB (P < .0001). Mean and max left anterior descending artery doses were 251 cGy and 551 cGy in S-DIBH, respectively (P = .1), and 324 cGy and 993 cGy in P-FB, respectively (P = .3). Hot spot and separation were 109% and 22 cm in S-DIBH, respectively, and 107% and 16 cm in P-FB, respectively (P < .0001). For patients with smallest BV, S-DIBH improved MHD and left anterior descending artery doses; for those with largest BV, P-FB improved cardiac dosimetry. With increasing BV, there was an increasing advantage of P-FB for MHD (P = .05), and max (P = .03) and mean (P = .02) left anterior descending artery doses, and the reduction in MLD, hot spot, and separation with P-FB increased (P < .05). ConclusionsMHD did not differ between P-FB and S-DIBH, whereas MLD was significantly lower with P-FB. Analysis according to breast volume revealed improved cardiac dosimetry with S-DIBH for women with smallest BV and improved cardiac dosimetry with P-FB for women with larger BV, thereby providing a dosimetric rationale for using breast size to help determine the optimal positioning for WBI.

Improvement in Cardiac Dosimetry by Optimizing Heart-Sparing Breast Radiotherapy

Darby et al. demonstrated that cardiac events after breast radiation therapy (RT) are associated with mean heart dose (MHD). MHD is dependent on treatment fields and can be reduced by various techniques, such as deep inspiratory breath hold (DIBH), prone positioning, and cardiac blocks. The purpose of this study was to assess changes in MHD with advancements in modern RT by technique and treatment fields. This retrospective study included breast cancer patients treated from 2010 to 2018 at a single institution in an IRB approved registry. MHD was analyzed with respect to clinical variables, including laterality, cardiac sparing technique, and treatment fields, including regional nodal irradiation (RNI) with or without internal mammary nodal irradiation (IMNI). 765 patients (431 left, 315 right, 19 bilateral) were included. The average MHD was 1.87 Gy (SD 1.36 Gy, median 1.43 Gy) for left sided cases vs. 0.71 Gy (SD 0.80 Gy, median 0.51 Gy) for right sided cases (p<0.0001). Of the 43 patients that had a MHD > 4 Gy, bilateral cases were at a highest risk (21.1%), vs. left sided (7.7%) and right sided cases (1.9%) (p<0.0001). For left sided cases, average MHD without RNI, RNI without IMNI, and RNI with IMNI were 1.40 Gy (SD 0.98 Gy, median 1.16 Gy), 2.01 Gy (SD 1.15 Gy, median 1.63 Gy), and 3.48 Gy (SD 2.17 Gy, median 3.21 Gy), respectively. Following the 2013 publication of Darby et al, the average MHD significantly decreased for left sided RT cases (2.02 vs 1.82 Gy, p= 0.039) due to institutional adoption of cardiac-sparing techniques. For left sided cases w/o RNI, use of cardiac sparing techniques reduced average MHD from 1.61 Gy (SD 1.09 Gy, median 1.36 Gy) to 1.22 Gy (SD 0.99 Gy, median 0.99 Gy) with DIBH and 1.02 Gy (SD 0.56 Gy, median 0.78 Gy) with prone positioning respectively (p<0.0001), with no difference between techniques (p = 0.42). For left sided cases with RNI, DIBH reduced average MHD from 2.4 Gy (SD 0.13 Gy, median 2.02 Gy) down to 2.1 Gy (SD 1.57 Gy, median 1.6 Gy), p= 0.046. For left sided cases of RNI with IMNI, average MHD was 3.09 Gy (SD 2.38 Gy, median 2.57 Gy) with partially wide tangents compared to 3.99 Gy (SD 1.82 Gy, median 3.79 Gy) with matched electron fields (p= 0.053). For left sided cases with IMNI, the MHD was 3.48 Gy (SD 2.31 Gy, median 3.21 Gy) with DIBH compared to 3.64 Gy ( SD 2.16 Gy, median 3.37 Gy) without DIBH (p=0.27). The MHD for left sided RT with reconstruction was 1.94 Gy (SD 1.21 Gy, median 1.53 Gy) and without reconstruction was 1.85 Gy (SD 1.42 Gy, median 1.39 Gy). Cardiac doses were lower following the publication of Darby et al. Overall the average MHD was <1 Gy and <2 Gy for right and left breast cancers, respectively, by increased utilization of cardiac sparing techniques such as DIBH and prone positioning.

Evaluating improvements in cardiac dosimetry in breast radiotherapy and comparison of cardiac sparing techniques

Data from Darby et al. demonstrated that cardiac dose in patients undergoing breast radiation therapy is associated with cardiac events. Cardiac dose is primarily dependent on treatment laterality and treatment fields. More recently, techniques such deep inspiratory breath hold (DIBH) and prone positioning have been used as cardiac sparing techniques. The purpose of this study is to assess changes in cardiac dosimetry with cardiac sparing techniques. This retrospective study included breast cancer patients treated from 2010 to 2018 at a single institution. Mean heart dose (MHD) was analyzed with respect to treatment era, laterality, cardiac sparing technique, and treatment fields, including regional nodal irradiation (RNI) and internal mammary nodal irradiation (IMNI). Seven hundred sixty-five patients were included in this study. Average MHD was 1.87 Gy for left-sided cases and 0.71 Gy for right-sided cases (p < 0.0001). For left-sided cases, the average MHD without RNI, RNI without IMNI, and RNI with IMNI was 1.40 Gy, 2.01 Gy, and 3.48 Gy respectively. For left-sided cases without RNI, the average MHD decreased from 1.61 to 1.22 Gy using DIBH (p < 0.0001), and to 1.02 Gy with prone positioning (p < 0.0001). There was no difference in MHD between DIBH and prone techniques (p = 0.44). For left-sided cases with RNI, DIBH reduced the average MHD from 2.4 to 2.1 Gy (p = 0.04). Following the 2013 publication of Darby et al., the average MHD significantly decreased for left-sided RT cases (2.02 vs. 1.83 Gy, p = 0.03) due to increased institutional adoption of cardiac-sparing techniques. Cardiac doses were lower following the 2013 publication of Darby et al. due to greater use of cardiac sparing techniques. Overall, the average MHD was < 1 Gy and < 2 Gy for right and left breast cancers, respectively, with lower doses achieved using DIBH and prone positioning as cardiac sparing techniques.

Proton Versus Photon Breath Hold Radiation for Left-Sided Breast Cancer after Breast-Conserving Surgery: A Dosimetric Comparison

Purpose Radiation to breast, chest wall, and/or regional nodes is an integral component of breast cancer management in many situations. Irradiating left-sided breast and/or regional nodes may be technically challenging because of cardiac tolerance and subsequent risk of long-term cardiac complications. Deep inspiratory breath-hold (DIBH) technique physically separates cardiac structures away from radiation target volume, thus reducing cardiac dose with either photon (Ph) or proton beam therapy (PBT). The utility of combining PBT with DIBH is less well understood. Methods and Materials We compared photon-DIBH (Ph-DIBH) versus proton DIBH (Pr-DIBH) for different planning parameters, including target coverage and organ at risk (OAR) sparing. Necessary ethical permission was obtained from the institutional review board. Ten previous patients with irradiated, intact, left-sided breast and Ph-DIBH were replanned with PBT for dosimetric comparison. Clinically relevant normal OARs were contoured, and Ph plans were generated with parallel, opposed tangent beams and direct fields for supraclavicular and/or axillae whenever required. For proton planning, all targets were delineated individually and best possible coverage of planning target volume was achieved. Dose-volume histogram was analyzed to determine the difference in doses received by different OARs. Minimum and maximum dose (Dmin and Dmax ) as well as dose received by a specific volume of OAR were compared. Each patient's initial plan (Ph-DIBH) was used as a control for comparing newly devised PBT plan (Pr-DIBH). Matched, paired t tests were applied to determine any significant differences between the 2 plans. Results Both the plans were adequate in target coverage. Dose to cardiac structure subunits and ipsilateral lung were significantly reduced with the proton breath-hold technique. Significant dose reduction with Pr-DIBH was observed in comparison to Ph-DIBH for mean dose (Dmean) to the heart (0.23 Gy versus 1.19 Gy; P < .001); Dmean to the left ventricle (0.25 Gy versus 1.7 Gy; P < .001); Dmean, Dmax, and the half-maximal dose to the left anterior descending artery (1.15 Gy versus 5.54 Gy; P < .003; 7.7 Gy versus 22.15 Gy; P < .007; 1.61 Gy versus 4.42 Gy, P < .049); Dmax of the left circumflex coronary artery (0.13 Gy versus 1.35 Gy; P < .001) and Dmean, the volume to the ipsilateral lung receiving 20 Gy and 5 Gy (2.28 Gy versus 8.04 Gy; P < .001; 2.36 Gy versus 15.54 Gy, P < .001; 13.9 Gy versus 30.28 Gy; P = .002). However, skin dose and contralateral breast dose were not significantly improved with proton. Conclusion This comparative dosimetric study showed significant benefit of Pr-DIBH technique compared with Ph-DIBH in terms of cardiopulmonary sparing and may be the area of future clinical research.

Deep Inspiratory Breath Hold Technique to Reduce Cardiotoxicity when Delivering Left Breast/Internal Mammary Chain Radical Radiotherapy: Obstacles to Compliance

Deep Inspiratory Breath Hold Technique to Reduce Cardiotoxicity when Delivering Left Breast/Internal Mammary Chain Radical Radiotherapy: Obstacles to Compliance

Inspiratory Breath-Hold - A Simple Clinical Intervention to Assess Risk Threshold for Suction Events in Stable LVAD Outpatients

Purpose HeartWare HVAD flow waveforms provide important clinical information on pump function and patient hemodynamics. We assessed changes in flow waveform during inspiratory breath-hold (IBH) maneuver and whether optimization in device speed and medical therapy improved waveform characteristics. Methods We studied HeartWare HVAD patients at consecutive follow-up visits. Characteristic changes in the HVAD monitor flow waveform with IBH were assessed and compared to baseline for reduced flow waveform pulsatility (RWP); flatline (FL); and suction (S). If suction was induced, management was changed by reduction in pump speed, diuretics or anti-hypertensives. Average flow, peak and trough pump flows, flow pulsatility (peak - trough), speed and power were recorded. Baseline pump parameters were compared between patients who required a change (C) vs no change (NC) in management. Patients in the C group were further assessed post-management change (PC) at next visit. Results Sixteen patients were included: 13 male (81.25%), median age 53.7 years (range 38.7-75.6), median support duration 254 days (range 21-2540). Suction was observed with IBH in 6 (37.5%, group C) vs no suction in n=10 (62.5%, group NC). There was no significant difference in any baseline pump parameter between C vs NC (Table). Of the 6 patients in group C who underwent management change, 4 had pump speed reduction and 2 decreased diuretic medications. Pump speed was significantly lower in the PC group (2533 ± 81.6 vs 2600 ± 63.2 respectively, p=0.025) at follow up. No other significant differences in pump parameters were noted (Table). At follow up (PC) there were significantly fewer waveform abnormalities (including RWP, FL, or S) 0.94 ± 0.90 vs 2.4 ± 0.5, p=0.034. Conclusion Pump parameters and flow waveform observation at rest do not reflect suction risk in stable HVAD outpatients. IBH is a simple clinical intervention to assess suction risk threshold and can be utilized to guide changes in management. HeartWare HVAD flow waveforms provide important clinical information on pump function and patient hemodynamics. We assessed changes in flow waveform during inspiratory breath-hold (IBH) maneuver and whether optimization in device speed and medical therapy improved waveform characteristics. We studied HeartWare HVAD patients at consecutive follow-up visits. Characteristic changes in the HVAD monitor flow waveform with IBH were assessed and compared to baseline for reduced flow waveform pulsatility (RWP); flatline (FL); and suction (S). If suction was induced, management was changed by reduction in pump speed, diuretics or anti-hypertensives. Average flow, peak and trough pump flows, flow pulsatility (peak - trough), speed and power were recorded. Baseline pump parameters were compared between patients who required a change (C) vs no change (NC) in management. Patients in the C group were further assessed post-management change (PC) at next visit. Sixteen patients were included: 13 male (81.25%), median age 53.7 years (range 38.7-75.6), median support duration 254 days (range 21-2540). Suction was observed with IBH in 6 (37.5%, group C) vs no suction in n=10 (62.5%, group NC). There was no significant difference in any baseline pump parameter between C vs NC (Table). Of the 6 patients in group C who underwent management change, 4 had pump speed reduction and 2 decreased diuretic medications. Pump speed was significantly lower in the PC group (2533 ± 81.6 vs 2600 ± 63.2 respectively, p=0.025) at follow up. No other significant differences in pump parameters were noted (Table). At follow up (PC) there were significantly fewer waveform abnormalities (including RWP, FL, or S) 0.94 ± 0.90 vs 2.4 ± 0.5, p=0.034. Pump parameters and flow waveform observation at rest do not reflect suction risk in stable HVAD outpatients. IBH is a simple clinical intervention to assess suction risk threshold and can be utilized to guide changes in management.

Abstract P3-12-10: Utilization patterns and temporal trends of internal mammary nodal irradiation (IMNI) at a tertiary cancer centre

Abstract Purpose: Despite data from multiple randomized trials, the role and uptake of internal mammary nodal irradiation (IMNI) is variable. This study was designed to quantify the rates and determinants of IMNI at a tertiary cancer centre. Methods: Treatment records of consecutively treated breast cancer (BC) patients receiving adjuvant locoregional (LR) radiotherapy (RT) from January 1, 2012 to October 31, 2017 was studied. LR-RT and use of IMNI as a function of clinicopathological factors, use of deep inspiratory breath-hold (DIBH) and dosimetric parameters were retrieved. Patients were divided into two groups:Group1 received LR-RT that included the IMN's, supraclavicular (SCLV) ± axillary regions,Group2 received LR-RT directed only to the SCLV±axillary areas. For the purpose of utilization analysis and temporal trends, early(2012-2015) and late(2016-2017) cohorts were examined based on the year of RT delivery. To determine if the use of IMNI was dependent on BC risk, we defined 3 risk categories:1) pT1/2, N0); 2)pT1/2, N1; and 3) pT3/4, N2/3 disease. Differences between the risk categories and groups were evaluated using chi-square/ Fisher's and Mann Whitney test for categorical and continuous variables, respectively. Univariable and multivariable logistic regression analysis was done to determine factors associated with the receipt of IMNI. Results:A total of 1566 patients met eligibility (Group 1=376; Group 2=1190). Of these patients, the percentage receiving LR-RT remained constant (17%) over the study period but the proportion of patients receiving IMNI increased significantly each year (p&amp;lt;0.0001), and was higher in the late vs. early treatment cohort (55% vs 8%, p&amp;lt;0.0001).On univariable analysis, younger age, LVI positivity, medial/central location, increasing stage, PR negativity, mastectomy, axillary dissection ,receipt of chemotherapy and increasing number of positive nodes had higher odds of receiving IMNI. Radiation oncologists with &amp;lt; or ≥5 years of practice was predictive of IMNI (31.3% vs 20.5%, p&amp;lt;0.0001),staff having &amp;lt;5years in practice being more likely to recommend IMNI. The distribution of patients in the different risk categories was similar between Groups 1 and 2 (p=0.097), and identified that the majority of patients receiving IMNI were in risk category 2(83%). Further comparison of risk categories suggested that the odds of receiving IMNI was lower in risk category 3 vs. category 1 (p=0.033). On multivariable analysis, decreasing age age (p=&amp;lt;0.001) , medial quadrant(p=0.0026),PR negative(p=0.0011), mastectomy(p=0.0055) , increasing nodal positivity (p&amp;lt;0.0001)and late RT cohort (p=0.001) had increased odds of IMNI. Overall use of DIBH was significantly higher in those receiving IMNI (45% vs 26%, p&amp;lt;0.0001). Mean heart (2.2vs1.7Gy, p&amp;lt;0.0001) and total lung doses (7.8vs6.6Gy,p&amp;lt;0.0001) were also significantly higher with IMNI. Conclusion: There was a significant increase in utilization of IMNI from 2012 to 2017. Younger age, medial location, PR negativity and increasing number of positive nodes predicted for receipt of IMNI. Staff with&amp;lt;5years in practice were more likely to recommend LR-RT that included the IMNs. The use of DIBH significantly increased with IMNI and allowed for acceptable dosimetric constraints. Citation Format: Misra S, Lee G, Maganti M, Koch CA. Utilization patterns and temporal trends of internal mammary nodal irradiation (IMNI) at a tertiary cancer centre [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-10.

Positive end-expiratory pressure improves elastic working pressure in anesthetized children

BackgroundPositive end-expiratory pressure (PEEP) has been demonstrated to decrease ventilator-induced lung injury in patients under mechanical ventilation (MV) for acute respiratory failure. Recently, some studies have proposed some beneficial effects of PEEP in ventilated patients without lung injury. The influence of PEEP on respiratory mechanics in children is not well known. Our aim was to determine the effects on respiratory mechanics of setting PEEP at 5 cmH2O in anesthetized healthy children.MethodsPatients younger than 15 years old without history of lung injury scheduled for elective surgery gave informed consent and were enrolled in the study. After usual care for general anesthesia, patients were placed on volume controlled MV. Two sets of respiratory mechanics studies were performed using inspiratory and expiratory breath hold, with PEEP 0 and 5 cmH2O. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory pressure (PIP), plateau pressure (PPL) and total PEEP (tPEEP) were measured. Respiratory system compliance (CRS), inspiratory and expiratory resistances (RawI and RawE) and time constants (KTI and KTE) were calculated. Data were expressed as median and interquartile range (IQR). Wilcoxon sign test and Spearman’s analysis were used. Significance was set at P < 0.05.ResultsWe included 30 patients, median age 39 (15–61.3) months old, 60% male. When PEEP increased, PIP increased from 12 (11,14) to 15.5 (14,18), and CRS increased from 0.9 (0.9,1.2) to 1.2 (0.9,1.4) mL·kg− 1·cmH2O− 1; additionally, when PEEP increased, driving pressure decreased from 6.8 (5.9,8.1) to 5.8 (4.7,7.1) cmH2O, and QE decreased from 13.8 (11.8,18.7) to 11.7 (9.1,13.5) L·min− 1 (all P < 0.01). There were no significant changes in resistance and QI.ConclusionsAnalysis of respiratory mechanics in anesthetized healthy children shows that PEEP at 5 cmH2O places the respiratory system in a better position in the P/V curve. A better understanding of lung mechanics may lead to changes in the traditional ventilatory approach, limiting injury associated with MV.

A Prospective Trial to Compare Deep Inspiratory Breath Hold (DIBH) with Prone Breast Irradiation

A Prospective Trial to Compare Deep Inspiratory Breath Hold (DIBH) with Prone Breast Irradiation

Metabolic Regression Velocity Post Lung SBRT - How Early Do We Get to See!

FDG PET-CT is a well-established cancer-imaging tool for diagnosis, staging, and response assessment. It is also well known that, post chemotherapy or radiotherapy, metabolic response precedes morphologic response based on size criteria. Normally PET-CT post SBRT is done at 3 months. However, earliest time needed when one would get maximum metabolic response following Lung SBRT was never known or assessed. Present study evaluates the metabolic regression velocity patterns post SBRT with serial FDG PET-CT scans in patients with oligo solitary lung metastases within first 3 months of the treatment. Five patients with oligometastatic lung tumors (Primaries: Colorectal cancer -2, Breast - 2 and Head and neck cancer- 1) were planned SBRT by Deep inspiratory breath hold technique using Active breath controller on 6 DOF C-arm Linac using body fix immobilization. A risk adapted multi-fractionated regimen (3-5 fractions) was used and doses delivered were in the range of 110-118gy BED. All patients underwent diagnostic pre- and post-treatment PET-CT scans. Post SBRT PET-CTs scans were timed serially at 48hrs, 10 days, 30 days and 60 and 90 days post treatment. PET-CT reports were reviewed in order to determine the pre- and post- treatment maximum standardized uptake value (m-SUV) of the lesion, including “complete resolution” of FDG-avidity. Corresponding Morphologic variations of the target lesions were studied on the CT images during the evaluation period (first 3 months). All 5 patients showed serial regression in metabolic activity, with maximum regression in metabolic activity occurring at 10 days post SBRT. The observed metabolic regression was between 40-54% (median – 50%) at 48 hours and 67-82% (median 80%) at 10 days post SBRT. 10 days after SBRT, there was no further decrease in metabolic activity. SUV thereupon remained constant ranging between 2.3 - 3.2 up to 3 months suggesting to fact that inflammation might have been initiated between 48hrs and 10 days. The earliest morphologic changes on CT in the form of ground glass appearance were detected at 60 days post SBRT scan uniformly in all patients. During the evaluation period (first 3 months) there was no significant change in size of the lesion. In cases of solitary lung oligomets the metabolic response precedes morphologic response with 50% median metabolic regression within 48hrs and 80% median metabolic regression by 10th day post SBRT. To the best of our knowledge, this is the first study reported in literature, which looked into the metabolic regression velocity patterns within the first 3 months post SBRT.

Bi-Institutional Report on Consolidative Proton Therapy after Initial Chemotherapy for Mediastinal Diffuse Large B-Cell and Primary Mediastinal Large B-Cell Lymphomas

Combined modality therapy with R-CHOP (rituximab, cyclophosphamide, vincristine, prednisone) and radiation is a standard treatment option for mediastinal aggressive non-Hodgkin lymphomas (MANHL), however very intense “radiation-free” chemotherapy is gaining in use, in part due to concern over radiation toxicity. We investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) in these pts with mediastinal lymphoma, a group of patients that have been shown to derive dosimetric benefit from PT compared to photon-based techniques. From 2011-2017, 24 adult patients with MANHL (either primary mediastinal large B cell lymphomas or mediastinal diffuse large B cell lymphoma) enrolled on either institutional review board-approved outcomes tracking protocols or registry studies received consolidative PT after first-line chemotherapy with R-CHOP (16 pts) or R-CHP-brentuximab vedotin (8 pts) at two academic institutions. Six cycles were given in 22 pts, and 4 cycles in 2 pts. Patients with relapsed disease at the time of PT were excluded. The majority were male (58%) with a median age of 36 [range 22-72]. Stage distribution included 10 stage I, 9 stage II, 3 stage III, and 2 Stage IV with 42% with B symptoms and 33% with extranodal involvement. The majority (87.5%) had disease that measured at least 7.5 cm before chemotherapy, with a median maximum dimension of 12 cm [range 4-23 cm]. Involved-site radiotherapy target volumes were used for all patients. Pts received a median dose of 30.6 Gy(RBE) [range 30–39.6 Gy(RBE)]. Pencil beam scanning was used in 33%, deep inspiratory breath hold was used in 33%, and both were used in 12.5%. Follow-up time was defined as time from start of PT to event or last follow-up. The median follow-up was 28 months (range, 1.2–76 months). The majority (75%) of pts were in complete metabolic response before PT with Deauville Score (DS) of 1 or 2, however 21% had DS4, none of whom relapsed. Of the 24 pts, there was only 1 local failure that occurred 19 months after PT within the high dose region in a pt with DS1. One patient relapsed below the diaphragm at 20 months. The one pt who had DS5 after chemotherapy died 11 months after PT with relapse in the hilum (out of field) and infradiaphragmatic. Consolidative PT was given 3 months after chemotherapy in this patient. The median mean lung dose was 6.7 Gy(RBE) [range 2.3-16.8], median lung V5 was 30% [range 12-59], median lung V20 was 16% [range 4-40]. The median mean heart dose was 10.9 Gy(RBE) [range 0.01-16.9]. None had grade 2 or higher radiation pneumonitis. Consolidative involved site PT following standard chemotherapy in aggressive mediastinal B cell lymphomas results in excellent local control (96%) with minimal toxicity in this bi-institutional early report.

Sparing of the Cardiac Valves and Left Ventricle using Proton Therapy with ECG-gated CT with Coronary Angiography for the Treatment of Mediastinal Lymphoma

ECG-gated CT with coronary angiography (E-CTA) enables accurate delineation of cardiac substructures in time and space. We compared IMRT and IMPT to assess doses to the cardiac valves and left ventricle for patients treated with mediastinal radiation for lymphoma. Patients were prospectively enrolled in an institutional review board-approved, observational study. During simulation, patients underwent a CT scan using deep inspiratory breath hold and an E-CTA. A study-specific, multidisciplinary-designed, cardiac substructure contouring atlas was used to delineate the cardiac substructures in systole and diastole, which were then combined into PRVs. Target volumes were delineated using involved site radiotherapy. IMRT and IMPT plans were generated and normalized for 95% coverage of the CTV. Absolute differences between IMRT and IMPT plans were determined for V5-30Gy in increments of 5Gy and mean doses. Due to expected dose differences based on adenopathy site, each cardiac structure was analyzed independently. A paired T-test was used to compare differences between mean doses to substructures by modality. Twelve patients aged 14-53 years with lymphoma involving the mediastinum underwent comparative planning. The median prescription dose was 30 Gy in 15 fractions (r, 21-30 Gy). The median mean heart dose was 9.4Gy and 4.7 Gy for IMRT vs IMPT. The average mean, V5Gy, and V15 Gy to the left ventricle were all significantly less with IMPT. The average V25Gy was nearly significant as well (5.2 vs 2.8%, p=0.06). No individual patient had an increase in the dose to the LV with IMPT. The pulmonic valve was the only valve with a significant reduction in V30 Gy (27.2 vs 15.0%, p = 0.05). The majority of patients did not have any V30 Gy to the mitral or tricuspid valve with either modality. One patient did have an increase in the aortic valve V30 Gy by 10.6% with IMPT, and no significant benefit for the other valves with IMPT. The average mean dose to all valves was significantly lower IMPT. For patients with mediastinal lymphomas, IMPT reduced average doses to the left ventricle and cardiac valves when using E-CTA for cardiac substructure delineation.Abstract MO_20_2648; Table 1Substructure ParameterIMRT Mean (range)IMPT Mean (range)Paired T-TestLeft Ventricle Mean Dose [Gy]6.4 (0.6 – 14.6)2.1 (0.0 – 7.9)< 0.01 V5Gy [%]41.2 (0.0 – 91.9)10.8 (0.0 – 35.4)0.01 V15Gy [%]10.9 (0.0 – 32.3)5.2 (0.0 – 24.0)0.01 V25Gy [%]5.2 (0.0 - 26.1)2.8 (0.0 – 16.1)0.06Aortic Valve Mean Dose [Gy]16.1 (5.7 – 25.8)8.6 (0.8 – 17.2)<0.01 V30Gy [%]7.9 (0.0 – 36.9)3.6 (0.0 – 15.8)0.22Mitral Valve Mean Dose [Gy]10.5 (2.2 – 21.1)3.7 (0.0 – 10.6)< 0.01 V30Gy [%]3.1 (0.0 – 27.9)1.21 (0.0 – 12.2)0.20Pulmonic Valve Mean Dose [Gy]19.3 (8.0 – 30.1)14.1 (2.1 – 29.2)< 0.01 V30Gy [%]27.2 (0.0 – 71.5)15.0 (0.0-68.5)0.05Tricuspid Valve Mean Dose [Gy]8.6 (0.7 – 28.9)3.1 (0.0 – 20.2)< 0.01 V30Gy [%]6.5 (0.0 – 49.9)3.9 (0.0 – 39.0)0.18 Open table in a new tab

Radiologic Quantification and Predictors of Lung Fibrosis after Stereotactic Ablative Radiation Therapy(SABR)

Stereotactic ablative radiotherapy (SABR) to lung cancer lesions may result in acute or chronic fibrotic changes to lung parenchyma. These changes exist along a continuum ranging from mild scarring to marked inflammatory responses. Systematic methods to quantity SABR-induced lung fibrosis may assist in the evaluation of radiation related lung toxicity. We sought to develop a method to radiologically quantify SABR-induced lung fibrosis and conducted an exploratory analysis to identify pre-treatment radiologic features associated with fibrotic change. We evaluated 30 patients with non-small cell lung cancer (NSCLC) treated with lung SABR using 25Gy in 1 fraction from 2012-2017. All patients had a baseline inspiratory breath hold simulation CT scan. GTV was recorded. Peri-tumor region was defined as a 2cm expansion around, but not including, GTV, respecting the lung borders and excluding large vessels and mediastinal structures. Mean and standard deviation (STD) HU and the percentage of values below -950HU (B950) for baseline ipsilateral lung and peri-tumor region were calculated. All 30 patients had a follow up scan 2-4 months post-treatment. Twenty-eight patients had a follow up scan 5-9 months post-treatment. For subjective assessment of lung fibrosis, tumor-adjacent regions were assigned a severity score of 0-4, based on a published method (Dahele et al., J Thorac Oncol 2011). For quantification of lung fibrosis, the region of fibrotic change (RFC) was determined by contouring fibrotic regions within the vicinity of the treated lesion and measuring the volume exceeding -135HU. Higher subjective fibrosis scores were associated with higher quantitative measurements of fibrosis. Mean RFC of the patient cohort increase from 2.98cc to 5.37cc from 1st to 2nd follow up scan (p=0.0854). GTV was positively correlated with RFC on 2nd follow up scan (R2=0.465, p=<0.0001). Higher GTV was associated with higher subjective fibrosis scores on 2nd follow up scan. Baseline peri-tumor mean and STD HU were positively correlated with RFC on 2nd follow up scan (R2=0.1582, p=0.0361; R2=0.1826, p=0.0233). Lower baseline peri-tumor mean and STD HU were associated with lower subjective fibrosis scores on 2nd follow up scan. Baseline ipsilateral lung mean and STD HU and ipsilateral lung B950 and peri-tumor B950 were not significantly correlated with RFC on follow up scans. Radiologic quantification of lung fibrosis is an effective method to evaluate SABR-induced changes and may enable more rapid and systematic assessment compared to subjective scoring. GTV and baseline peri-tumor mean and STD HU positively correlate with radiologic lung fibrosis post-SABR. These pre-treatment radiologic features may serve as predictive imaging biomarkers of SABR-induced lung injury if validated in larger prospective studies.

Intrafraction esophageal motion in patients with clinical T1N0 esophageal cancer.

To investigate the intrafraction movement of the esophagus using fiducial markers. Studies on intrafraction esophageal motion using the fiducial markers are scarce. We retrospectively analyzed patients with clinical T1N0 esophageal cancer who had received fiducial markers at our hospital between July 2007 and December 2013. Real-Time Position Management System to track the patient's respiration was used, and each patient underwent three-dimensional computed tomography of the resting expiratory and inspiratory level. We used the center of the marker to calculate the distance between the expiratory and inspiratory breath-holds, which were measured with the radiotherapy treatment planning system in three directions: left-right (LR), superior-inferior (SI), and anterior-posterior (AP). The movements at each site were compared with the Kruskal-Wallis analysis and Wilcoxon rank sum test with a Bonferroni correction. A total of 101 patients with 201 fiducial markers were included. The upper, middle and lower thoracic positions had 40, 77, and 84 markers, respectively. The mean absolute magnitudes of the shifts (standard deviation) were 0.18 (0.19) cm, 0.68 (0.46) cm, and 0.24 (0.24) cm in the LR, SI, and AP directions, respectively. From the cumulative frequency distribution, we assumed that 0.35 cm LR, 0.8 cm SI, and 0.3 cm AP in the upper; 0.5 cm LR, 1.55 cm SI, and 0.55 cm AP in the middle; and 0.75 cm LR, 1.9 cm SI, and 0.95 cm AP in the lower thoracic esophagus covered 95% of the cases. The internal margin based on the site of esophagus was estimated.

Preliminary toxicity results using partial breast 3D-CRT with once daily hypo-fractionation and deep inspiratory breath hold

BackgroundTo evaluate the clinical outcomes of patients treated with 3D conformal Hypo-fractionated, deep Inspiratory breath-hold (DIBH), Partial breast radiotherapy, termed “HIP.” HIP was implemented to merge the schedule of once-daily breast hypofractionation with partial breast treatment.MethodsWe identified 38 breast cancers in 37 patients from 2013 to 2014 treated at our institution with HIP following lumpectomy for early stage breast cancer. Patients received a hypo-fractionated course (≤ 20 fractions) of once daily radiation to the partial breast (lumpectomy cavity + margin) utilizing DIBH regardless of laterality. Clinical and treatment-related characteristics were obtained, including target volume and organ at risk (OAR) dosimetric characteristics. Patients were followed clinically and with at least yearly mammograms for up to 36 months (range 5–36 months). Acute and late toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.ResultsPatients received a median dose of 42.56 Gy in 16 Fractions (Fx) (range 40.05–53.2 Gy; and 15–20 Fx). OAR doses were low, with a mean heart dose of 0.37 Gy, an ipsilateral lung V20 mean of 4%, and a contralateral lung V5 of 1%. Acute toxicity (≤ grade 2) was present in 79% (n = 30) of the cases, with dermatitis being the most common finding (63%). Late grade 1–2 toxicity was present in 42% (n = 16) of the cases, with hyperpigmentation being the most common finding (n = 9). There were no severe acute or late toxicities (≥ grade 3). At a median follow up of 21 months, there were no local, regional, or distant failures.ConclusionsWe report limited toxicity in this low risk cohort of patients with early stage breast cancer treated with HIP, a unique and logical combination of 3-D conformal external beam radiotherapy, moderate hypo-fractionation, and DIBH.