Behrooz Hakimian

Wedge Resection and Brachytherapy for Lung Cancer in Patients With Poor Pulmonary Function

BACKGROUND Although lobectomy is the standard for lung cancer because a wedge resection has a 3 to 5 times greater incidence of local recurrence, poor pulmonary function may preclude lobectomy. For these patients, low-dose-rate brachytherapy has recently been used to decrease local recurrence after sublobar resection. Current techniques expose operating room personnel and patient contacts to unnecessary radioactivity risks. We present our technique of sublobar resection combined with afterload catheters for high-dose-rate brachytherapy for patient benefit with minimal risk to others. METHODS Forty-eight patients (25 women, 23 men) underwent wedge resection, node dissection, and brachytherapy. A remote-afterloading high-dose-rate unit for radiation produced a median dose of 2450 cGy (350 cGy per fraction over 7 fractions twice daily for 4 days). The dose was prescribed to 1 cm deep to the stapled line. Biologically, this dose is approximately 5000 cGy and above (180 cGy/d equivalent) at the depth of 5 mm in reference to the resection margin. RESULTS Two patients died. The length of mean stay was 5.5 days (median, 5 days). Complications included prolonged air leak in 5 patients, atrial fibrillation in 5, pneumonia in 3, trapped lung in 2, and 1 each with empyema, bleeding, and recurrent laryngeal nerve injury. Three patients required a blood transfusion. Within the follow-up of 1 to 27 months, there were four recurrences. CONCLUSIONS Wedge resection and brachytherapy appears to be a reasonable treatment for patients with lung cancer and pulmonary function that prohibits a lobectomy.

Intracranial Activity of Cabozantinib in MET Exon 14–Positive NSCLC with Brain Metastases

Introduction: A significant portion of NSCLCs with MET proto‐oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping alterations are sensitive to small‐molecule mesenchymal‐epithelial transition tyrosine kinase inhibitors. However, the incidence and management of brain metastases in this molecular subset is unknown and represents an unmet clinical need. Methods: Hybrid capture–based comprehensive genomic profiling identified a patient with a MET exon 14 skipping alteration, and serial magnetic resonance imaging was utilized to follow intracranial disease during crizotinib and subsequent cabozantinib therapy. Results: Intracranial progression developed in the context of ongoing extracranial disease control during crizotinib therapy. Rapid intracranial response was observed after change to cabozantinib. Conclusions: This report provides the first detailed description of brain metastases in MET exon 14–positive NSCLC and provides preliminary support for the intracranial activity of cabozantinib. Prospective study is warranted and needed to refine the management of intracranial disease in MET exon 14–positive NSCLC.

Clinical experience using a video‐guided spirometry system for deep inhalation breath‐hold radiotherapy of left‐sided breast cancer

The purpose was to report clinical experience of a video‐guided spirometry system in applying deep inhalation breath‐hold (DIBH) radiotherapy for left‐sided breast cancer, and to study the systematic and random uncertainties, intra‐ and interfraction motion and impact on cardiac dose associated with DIBH. The data from 28 left‐sided breast cancer patients treated with spirometer‐guided DIBH radiation were studied. Dosimetric comparisons between free‐breathing (FB) and DIBH plans were performed. The distance between the heart and chest wall measured on the digitally reconstructed radiographs (DRR) and MV portal images, dDRR(DIBH) and dport(DIBH), respectively, was compared as a measure of DIBH setup uncertainty. The difference (Δd) between dDRR(DIBH) and dport(DIBH) was defined as the systematic uncertainty. The standard deviation of Δd for each patient was defined as the random uncertainty. MV cine images during radiation were acquired. Affine registrations of the cine images acquired during one fraction and multiple fractions were performed to study the intra‐ and interfraction motion of the chest wall. The median chest wall motion was used as the metric for intra‐ and interfraction analysis. Breast motions in superior–inferior (SI) direction and “AP” (defined on the DRR or MV portal image as the direction perpendicular to the SI direction) are reported. Systematic and random uncertainties of 3.8 mm and 2 mm, respectively, were found for this spirometer‐guided DIBH treatment. MV cine analysis showed that intrafraction chest wall motions during DIBH were 0.3 mm in “AP” and 0.6 mm in SI. The interfraction chest wall motions were 3.6 mm in “AP” and 3.4 mm in SI. Utilization of DIBH with this spirometry system led to a statistically significant reduction of cardiac dose relative to FB treatment. The DIBH using video‐guided spirometry provided reproducible cardiac sparing with minimal intra‐ and interfraction chest wall motion, and thus is a valuable adjunct to modern breast treatment techniques. PACS number: 87.55.kh, 87.55.ne, 87.55.tg

TU‐F‐17A‐06: Motion Stability and Dosimetric Impact of Spirometer‐Based DIBH‐RT of Left‐Sided Breast Cancer

PURPOSE Patients undergoing radiotherapy (RT) for left-sided breast cancer have increased risk of coronary artery disease. Deep Inhalation Breath Hold assisted RT (DIBH-RT) is shown to increase the geometric separation of the target area and heart, reducing cardiac radiation dose. The purposes of this study are to use Cine MV portal images to determine the stability of spirometer-guided DIBH-RT and examine the dosimetric cardiopulmonary impact of this technique. METHODS Twenty consecutive patients with left-sided breast cancer were recruited to the IRB-approved study. Free-breathing (FB) and DIBH-CTs were acquired at simulation. Rigid registration of the FB-CT and DIBH-CT was performed using primarily breast tissue. Treatment plans were created for each FB-CT and DIBH-CT using identical paired tangent fields with field-in-field or electronic compensation techniques. Dosimetric evaluation included mean and maximum (Dmax) doses for the left anterior descending artery (LAD), mean heart dose, and left lung V20. Cine MV portal images were acquired for medial and lateral fields during treatment. Analysis of Cine images involved chest wall segmentation using an algorithm developed in-house. Intra- and inter-fractional chest wall motion were determined through affine registration to the first frame of each Cine. RESULTS Dose to each cardiac structure evaluated was significantly (p<0.001) reduced with the DIBH plans. Mean heart dose decreased from 2.9(0.9-6.6) to 1.6(0.6-5.3) Gy; mean LAD dose from 16.6(3-43.6) to 7.4(1.7-32.7) Gy; and LAD Dmax from 35.4 (6.1-53) to 18.4(2.5-51.2) Gy. No statistically significant reduction was found for the left lung V20. Average AP and SI median chest wall motion (intrafractional) was 0.1 (SD=0.9) and 0.5 (SD=1.1) mm, respectively. Average AP inter-fractional chest wall motion was 2.0 (SD=1.4) mm. CONCLUSION Spirometer-based DIBH treatments of the left breast are reproducible both inter- and intra-fractionally, and provide a statistically and potentially clinically useful dosimetric advantage to cardiac structures.

MO-FG-CAMPUS-JeP2-01: 4D-MRI with 3D Radial Sampling and Self-Gating-Based K-Space Sorting: Image Quality Improvement by Slab-Selective Excitation

PURPOSE A recent 4D MRI technique based on 3D radial sampling and self-gating-based K-space sorting has shown promising results in characterizing respiratory motion. However due to continuous acquisition and potentially drastic k-space undersampling resultant images could suffer from low blood-to-tissue contrast and streaking artifacts. In this study 3D radial sampling with slab-selective excitation (SS) was proposed in attempt to enhance blood-to-tissue contrast by exploiting the in-flow effect and to suppress the excess signal from the peripheral structures particularly in the superior-inferior direction. The feasibility of improving image quality by using this approach was investigated through a comparison with the previously developed non-selective excitation (NS) approach. METHODS Two excitation approaches SS and NS were compared in 5 cancer patients (1 lung 1 liver 2 pancreas and 1 esophagus) at 3Tesla. Image artifact was assessed in all patients on a 4-point scale (0: poor; 3: excellent). Signal-tonoise ratio (SNR) of the blood vessel (aorta) at the center of field-of-view and its nearby tissue were measured in 3 of the 5 patients (1 liver 2 pancreas) and blood-to-tissue contrast-to-noise ratio (CNR) were then determined. RESULTS Compared with NS the image quality of SS was visually improved with overall higher signal in all patients (2.6±0.55 vs. 3.4±0.55). SS showed an approximately 2-fold increase of SNR in the blood (aorta: 16.39±1.95 vs. 32.19±7.93) and slight increase in the surrounding tissue (liver/pancreas: 16.91±1.82 vs. 22.31±3.03). As a result the blood-totissue CNR was dramatically higher in the SS method (1.20±1.20 vs. 9.87±6.67). CONCLUSION The proposed 3D radial sampling with slabselective excitation allows for reduced image artifact and improved blood SNR and blood-to-tissue CNR. The success of this technique could potentially benefit patients with cancerous tumors that have invaded the surrounding blood vessels where radiation therapy is needed to remove tumor from those regions prior to surgical resection. This work is partially supported by NIH R03CA173273; and CTSI core voucher award.

TH-EF-BRA-07: Evaluation of Internal Target Volume Derived From a Prototype 4D-MRI Sequence with 3D Radial Stack-Of-Stars Trajectory and K-Space Self-Gating

PURPOSE 4D-MRI based on resorting of 2D-cine-MRI images shows great potential to assess tumor motion more accurately compared to 4D-CT, however, it suffers from low through-plane resolution and stitching artifacts. 4D-MRI based on 3D acquisition results in stitching-artifact-free images with high in-plane and through-plane resolutions. In this study, we report our early clinical experience of a prototype 4D-MRI sequence with 3D stack-of-stars (SOS) trajectory for internal target volume (ITV) definition. METHODS Ten patients with 13 total lesions (7 pancreatic, 1 lung with 2 lesions, 1 liver with 3 lesions and 1 esophagus) were recruited. 4D-MRI used in-plane radial and through-plane Cartesian sampling. Two imaging orientations, i.e. axial slab (A) and coronal slab (B), were compared. ITVs were derived from 3-bin (ITV3), 5-bin (ITV5) and 10-bin (ITV10) reconstruction protocols. ITV5 was set as standard and minimum expansion of ITV3 needed to encompass ITV5 was derived. Similarity index was calculated from ITV3 and ITV5 (SI3/5), and ITV10 and ITV5 (SI10/5). Imaging noise was calculated for both method A and B. Wilcoxon-rank-sum test was performed with a p value <0.05 deemed as significant. RESULTS No significant difference (p=0.34) was observed from method A and B, indicating a uniform imaging noise distribution from 3D acquisition. Imaging noise and artifacts were visually different from different binning protocols, with more bins resulting in more noise, more artifacts and larger ITV. On average, ITV differs by 7% (1%-19%) comparing ITV3 with ITV5 for the patient cohort. For the pancreas sub-group, ITV differs by 4% (1%-6%). An average of 2.3mm (2mm-3mm) expansion was needed for ITV3 to encompass ITV5. SI10/5 was 0.93±0.03 (mean±σ) and SI3/5 was 0.95±0.03. CONCLUSION 4D-MRI with 3D SOS trajectory was evaluated on 10 patients. Significant difference in ITV was observed with different binning protocols. Imaging noise was similar irrespective of the imaging orientations. This work is partially supported by NIH R03CA173273 and CTSI core voucher award.

SU‐E‐J‐151: An Off‐Line QA Tool for Evaluating Reproducibility of Deep Inhalation Breath‐Hold Treatment for Breast Radiotherapy

Purpose: To develop an off‐line QA tool for evaluating reproducibility of deep inhalation breath hold (DIBH) breast treatment using a spirometer‐based breathing control system with video guidance. Methods: Tangential beam plans (open medial field; lateral IMRT field) used for whole breast radiation with DIBH‐guided by a spirometer‐based breathing control system have been studied. An imaging sequence was set‐up at the treatment machine to acquire multiple (>15) EPID image frames during beam‐on with source‐to‐imager distance 150cm. Images were exported from the EPID and imported into an off‐line QA tool developed in‐house for evaluation of intra‐and inter‐fractional uncertainties for DIBH treatments. The user defines a region of interest (ROI) (e.g., expander, clip(s), chestwall) on the first (reference) image. A rectangular imaging template is created from the ROI with a defined expansion (e.g., 1cm). The template is then matched to each of the following image frames using cross‐correlation. Template movement is used to estimate breast motion during one or multiple breath‐hold sessions. The breath‐hold lung volume information is extracted from the spirometer and compared to the corresponding motion curve estimated from the EPID images. Results: Motions of different regions of the breast can be visualized and shown to be constant within 1mm at the imager (∼.7mm in the breast) for some patients. Both drifting and random motions can be identified on individual patients on specific days. Off‐line analysis of these data may provide a useful tool to assure that individual patients are adequately performing the DIBH technique, and to identify patients who require new margins or planning strategies. Conclusion: An off‐line QA motion evaluation tool has been designed for DIBH breast treatment, and is an effective method for evaluation of DIBH reproducibility both intra‐and inter‐fraction.