Wenyong Tan

Dosimetric comparison of intensity-modulated radiotherapy plans, with or without anterior myocardial territory and left ventricle as organs at risk, in early-stage left-sided breast cancer patients.

PURPOSE We evaluated heart sparing using an intensity-modulated radiotherapy (IMRT) plan with the left ventricle (LV) and/or the anterior myocardial territory (AMT) as additional organs at risk (OARs). METHODS AND MATERIALS A total of 10 patients with left-sided breast cancer were selected for dosimetric planning. Both lungs, the right breast, heart, LV, and AMT were defined as OARs. We generated one tangential field plan and four IMRT plans for each patient. We examined the dose-volume histogram parameters of the planning target volume and OARs. RESULTS Compared with the tangential field plan, the mean dose to the heart in the IMRT plans did not show significant differences; however, the dose to the AMT and LV decreased by 18.7-45.4% and 10.8-37.4%, respectively. The maximal dose to the heart decreased by 18.6-35.3%, to the AMT by 22.0-45.1%, and to the LV by 23.5-45.0%, And the relative volumes of the heart (V≥12), AMT (V>11) and LV (V>10) decreased significantly with different levels, respectively. The volume of the heart, AMT, LV, both lungs, and right breast receiving≥5 Gy showed a significant increase. Compared with the IMRT (H) plan, the mean dose to the heart, AMT, and LV decreased by 17.5-21.5%, 25.2-29.8%, and 22.8-29.8% and the maximal dose by 13.6-20.6%, 23.1-29.6%, and 17.3-29.1%, respectively. The IMRT plans for both lungs and the right breast showed no significant differences. CONCLUSIONS The IMRT plans with the addition of the AMT and/or LV as OARs considerably increased heart sparing. We recommend including the LV as an additional OAR in such plans.

Anterior Myocardial Territory May Replace the Heart as Organ at Risk in Intensity-Modulated Radiotherapy for Left-Sided Breast Cancer

PURPOSE We investigated whether the heart could be replaced by the anterior myocardial territory (AMT) as the organ at risk (OAR) in intensity-modulated radiotherapy (IMRT) of the breast for patients with left-sided breast cancer. METHODS AND MATERIALS Twenty-three patients with left-sided breast cancer who received postoperative radiation after breast-conserving surgery were studied. For each patient, we generated five IMRT plans including heart (H), left ventricle (LV), AMT, LV+AMT, and H+LV as the primary OARs, respectively, except both lungs and right breast, which corresponded to IMRT(H), IMRT(LV), IMRT(AMT), IMRT(LV+AMT), and IMRT(H+LV). For the planning target volumes and OARs, the parameters of dose-volume histograms were compared. RESULTS The homogeneity index, conformity index, and coverage index were not compromised significantly in IMRT(AMT), IMRT(LV) and IMRT(LV+ AMT), respectively, when compared with IMRT(H). The mean dose to the heart, LV, and AMT decreased 5.3-21.5% (p < 0.05), 19.9-29.5% (p < 0.05), and 13.3-24.5% (p < 0.05), respectively. Similarly, the low (e.g., V5%), middle (e.g., V20%), and high (e.g., V30%) dose-volume of the heart, LV, and AMT decreased with different levels. The mean dose and V10% of the right lung increased by 9.2% (p < 0.05) and 27.6% (p < 0.05), respectively, in IMRT(LV), and the mean dose and V5% of the right breast decreased significantly in IMRT(AMT) and IMRT(LV+AMT). IMRT(AMT) was the preferred plan and was then compared with IMRT(H+LV); the majority of dose-volume histogram parameters of OARs including the heart, LV, AMT, both lungs, and the right breast were not statistically different. However, the low dose-volume of LV increased and the middle dose-volume decreased significantly (p < 0.05) in IMRT(AMT). Also, those of the right lung (V10%, V15%) and right breast (V5%, V10%) decreased significantly (p < 0.05). CONCLUSIONS The AMT may replace the heart as the OAR in left-sided breast IMRT after breast-conserving surgery to decrease the radiation dose to the heart.

A retrospective analysis in patients with EGFR-mutant lung adenocarcinoma: is EGFR mutation associated with a higher incidence of brain metastasis?

Lung adenocarcinomas are more commonly associated with brain metastases (BM). Epidermal growth factor receptor (EGFR) mutations have been demonstrated to be both predictive and prognostic for patients with lung adenocarcinoma. We aimed to explore the potential association between EGFR mutation and the risk of BM in pulmonary adenocarcinoma patients. Data of 234 patients from 2007 to 2014 were retrospectively reviewed. A total of 108 patients had EGFR mutations in the entire cohort. Among them, 76 patients developed BM during their disease course. The incidence of BM was statistically higher in patients with EGFR mutations both at initial diagnosis (P=0.014) and at last follow-up (P<0.001). Multivariate logistic regression analysis revealed that EGFR mutation significantly increased the risk of BM at initial diagnosis (OR=2.515, P=0.022). In patients without BM at initial diagnosis, the accumulative rate of subsequent BM was significantly higher with EGFR mutations (P=0.001). Multivariate Cox regression analysis identified EGFR mutation as the only independent risk factor for subsequent BM (HR=3.036, P=0.001). Patients with EGFR mutations demonstrated longer overall survival (OS) after BM diagnosis than patients with wild-type EGFR (P=0.028). Our data suggest that EGFR mutation is an independent predictive and prognostic risk factor for BM and a positive predictive factor for OS in patients with BM.

Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs.

Estimation of the displacement of cardiac substructures and the motion of the coronary arteries using electrocardiographic gating

Purpose The aim of this study was to quantify the displacement of cardiac substructures, including the anterior myocardial territory (AMT), left ventricle, and coronary arteries during a normal cardiac cycle. Materials and methods Computed tomography (CT) images with retrospective electrocardiographic gating of 17 eligible patients were obtained. All images were reconstructed automatically for the end-diastolic and end-systolic phases. CT scanning without contrast at a random phase and a selected vertebral body were used as references to measure three-dimensionaldisplacements of the cardiac substructures. Results The displacement between the end-diastolic and end-systolic phases (Dd-s) was greater than that between the end-systolic and random phases and between the end-diastolic and random cardiac phases. The largest displacements for the heart were in the left, posterior, and inferior directions with an average Dd-s of approximately 4–6 mm. The average Dd-s for the AMT and left ventricle was 1.2–2.7 mm in the anterior and right directions, 4.3–7.8 mm in left and posterior directions, and 4.9–6.3 mm in superior and inferior directions. For the coronary arteries, the average Dd-s was 2.8–5.9 mm in the anterior-posterior direction, 3.5–6.6 mm in left-right direction, and 3.8–5.3 mm in the superior-inferior direction. Inter-observer agreement was excellent for the heart, AMT, and left ventricle (kappa coefficient, >0.75 for all) and good for most coronary arteries in three dimensions (kappa coefficient, 0.511–0.687). The Dd-s did not differ significantly between men and women. Conclusion Most average displacements of the cardiac substructures and coronary arteries were 3–8 mm in three dimensions. These findings will be useful to accurately estimate the radiation dose to cardiac substructures during thoracic radiation and to evaluate the risk of radiation-related heart disease.

Target volume and position variations during intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma.

Purpose Considerable anatomical changes occur during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to quantify volumetric and positional variations of the target volume during IMRT. Materials and methods Twenty patients with locally advanced NPC who received concurrent (13 patients) or sequential (seven patients) chemoradiotherapy were prospectively recruited and underwent planning computed tomography (CT) and six repeat CTs (every five fractions). Each repeat CT was rigidly registered to the planning CT. Gross tumor volume (GTV) and elective clinical target volume (CTV) were manually delineated on each axial CT image. CTVs of the primary tumor and lymph nodes were expanded with 5 mm margins to corresponding GTVs, with necessary modifications. Volume loss, system and random errors, and the mean and three-dimensional vector displacements were calculated and compared statistically. Results Volumes of the primary tumor and small (>1 cm, ≤3 cm) and large (>3 cm) positive neck lymph nodes decreased at a rate of 2.6%, 3.7%, and 3.9% per treatment day, respectively. CTVs of the primary tumor, lymph nodes, and elective region decreased 1.5%, 2.3%, and 0.3% per treatment day, respectively. Average displacements of the GTVs and CTVs were <1.3 mm in all directions. GTVs and CTVs of the large and small lymph nodes shifted medially by 0.8–1.3 and 0.6–1.2 mm, respectively, on average. Average three-dimensional displacements of the GTVs and CTVs were 3.4–4.3 mm and 2.5–3.7 mm, respectively. Volume loss and displacements in most directions were significantly larger in patients receiving concurrent chemoradiotherapy than in those receiving sequential therapy. Volume loss and displacements of the GTV of large nodes and elective CTV were significantly larger in male than in female patients. Conclusion Volumetric and positional changes of the target volume were considerable, and volume loss increased as treatment time elapsed during IMRT for NPC.

Sparing functional anatomical structures during intensity-modulated radiotherapy: an old problem, a new solution.

During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect to radiation response are not taken into consideration. However, advances in imaging and radiation techniques as well as an improved understanding of the radiobiological response of organs have raised the possibility of sparing the critical functional structures within various organs at risk during intensity-modulated radiotherapy. Here, we discuss these structures, which include the critical brain structure, or neural nuclei, and the nerve fiber tracts in the CNS, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional structures in the heart and lung. We suggest that these structures can be used as potential surrogate organs at risk in order to minimize their radiation dose and/or irradiated volume without compromising the dose coverage of the target volume during radiation treatment.

Target Volume and Position Variations During Intensity Modulated Radiation Therapy for Patients With Locally-Advanced Nasopharyngeal Carcinoma

Purpose/Objective(s): Dysphagia following radiation therapy for head and neck cancer is usually a late effect caused by the occasional formation of a benign stricture and changes in pharyngoesophageal motility. Besides oropharyngeal dysfunction, narrowing of the UES has been reported to contribute to post-radiation therapy dysphagia. The purpose of this study is to evaluate the swallowing function of patients post-radiation therapy who underwent both swallowing therapy and UES dilatation. Materials/Methods: Twenty-one male patients diagnosed with oropharyngeal SCCA six months post-surgery and radiation therapy participated in the study. Nine of the patients were placed on swallowing therapy alone and twelve were enrolled in both swallowing therapy and a home esophageal dilatation program using a Maloney dilator. The Functional Oral Intake Scale (FOIS) and results from the radiographic swallowing study were collected prior to and following the 5 weeks of swallowing rehabilitation. Oropharyngeal and UES pressures were measured on 3 of the patients who received both swallowing therapy and UES dilatation at the completion of the study. Hyolaryngeal excursion, penetration and aspiration as well as UES opening were measured on the lateral view during the radiographic swallowing study. Results: The FOIS scores of all patients were increased following swallowing rehabilitation. Statistical significance was shown between the swallowing therapy only group and the combination of swallowing therapy and UESdilatation group (p< 0.03).Hyolaryngeal excursion and penetration and aspiration showed improvement following rehabilitation, however, no statistical significancewas found between the swallowing therapy only group or the combination group. The UES on the lateral view of the swallowing study revealed an increased opening especially for the dilatation group (p < 0.027) after rehabilitation. All three patients who were measured for oropharyngeal and UES pressures demonstrated a decrease in UES pressure. Conclusions: Our results indicate that dysphagia caused by a benign stricture and changes in motility are the result of muscle changes secondary to the impact of radiation therapy. These changes can be improved by swallowing rehabilitation which should include a multimodality approach. Home dilatation should be considered as a factor in swallowing rehabilitation in patients who suffer dysphagia following radiation therapy. Author Disclosure: B. Capobres Villegas: None. Y. Zu: None. L. Ouyoung: None. U.K. Sinha: None.