J.F. Wilson

SU-FF-J-125: Thoracic Organ Motion as Assessed by 4D CT: Prone Versus Supine

Purpose: Radiotherapy is sometimes carried out with the patient in prone position. The purpose of this work is to study the changes of respiratory organ motion for patients in prone versus in supine position. Method and Materials: We obtained 4D CT datasets for 15 patients, 5 in prone and 10 in supine position, using a GE LightSpeed 4D CT scanner. Patients in both positions were immobilized by Alpha cradle. Lung movement (the change in lung spatial dimensions between maximum and minimum inspiration) in the superior-inferior (S/I) direction was measured on the 4D CT, as well as in the anterior-posterior (A/P) and left-right (L/R) directions in two transverse CT images near the diaphragm and near T4. We also measured the movement of the anterior chest wall with respect to the table top on the T4 transverse CT image as well as on the transverse image defined by the nipple. Results: Average lung movement changes from supine to prone position were: in 17.8 to 11.5 mm in S/I direction changes, and 1.6 to 0.5 mm in the A/P direction on the T4 image. In the transverse image defined by the nipple, we observed chest wall average movement of 0.1±0.4 mm in prone position versus 1.9±0.4 mm in supine position. Similarly, at the level of T4, the chest wall moved 0.3±0.3 mm in prone setup and 2.0±0.7 mm in supine position. Conclusion: Respiratory organ motions in thorax are generally reduced when patient position is changed from supine to prone. We have found a significant reduction in anterior chest wall movement for the prone position, an advantage of treating breast cancer in the prone position.

P3-13-05: Analysis of Heart Dose-Volume Parameters and Cardiac Events among Node Positive Breast Cancer (NPBC) Patients Treated with Three-Dimensional Conformal Radiation Therapy (3D-CRT).

Background For NPBC patients the use of regional nodal irradiation (RNI) to the supraclavicular, axillary, internal mammary lymph nodes (IMN) in addition to the chest wall and/or breast can maximize locoregional control and improve overall survival. However, comprehensive RNI for breast cancers located on the left side has been linked to late cardiac morbidity, potentially lessening the therapeutic benefit of treatment. The optimal radiation dose-volume constraints for the heart in this setting are not fully understood. We examined NPBC patients treated with RNI using 3D-CT based radiation therapy (RT) to evaluate cardiac dose and incidence of cardiac events. Methods: Between 2000 and 2007, 150 NPBC patients were treated with RNI following lumpectomy or mastectomy using 3D-CRT. In all cases, treatment target and normal tissue volumes were delineated on treatment CT scans. The heart contour included the ventricles and the left atrium. The dose-volume histogram of the cardiac doses delivered and the incidence of cardiac events is reported. Results: Median follow-up of surviving patients is 7 (1-10.6) years. Median patient age is 50 (27-91). 52.35% are premenopausal, 75.7% estrogen receptor positive, 66.3% progesterone receptor positive and 15.92% HER-2 positive. Mean positive lymph nodes is 5 (1-29). Extracapsular extension is present in 47.31%. Mean microscopic tumor size is 3.73 (0.1-21) cm. The IMN receive > 40 Gy in 65.5%. 94% had chemotherapy, and in 82.3% it was anthracycline-based. At the time of RT, 12.2% smoked, 9.5% had diabetes, 32.4% with hypertension, and 4.7% with a history of coronary artery disease. There was 1 (0.7%) right sided patient with cardiac events and 4 (2.7%) left sided experiencing cardiac events (p = 0.121, Fisher9s Exact test). A total of 10 cardiac diagnoses were experienced among the 5 patients: coronary artery disease with myocardial infarction (3), congestive heart failure (2), cardiomyopathy (2), and arrhythmia (3). The median time interval to onset of the events is 2.5 years (0-4.3 years). The cardiac doses among 150 patients are as follows: mean V25 is 5.7, (0.0 - 20.0%), V25 is Conclusions: The cardiac event rate among these NPBC patients treated with RNI and anthracycline-based chemotherapy is low. However, those patients with cardiac events have a higher mean V45. No other dose-volume relationships are discernible. Additional analysis using 3DCRT volumes are important to validate these findings and better define the dose-volume parameters for cardiac toxicity. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-05.

TH‐C‐224C‐07: EUD‐Assessed Impacts of Respiratory Motion On Breast Irradiation

Purpose:Respiration results in intrafractional motion and anatomic changes for both target and normal structures (e.g., lung,heart) during the radiation treatment for breast cancer. The purpose of this work is to quantify the dosimetric and radiobiological impacts using the concept of equivalent uniform dose (EUD). Method and Materials: Intrafractional variations were assessed based on 4DCT datasets acquired using a GE LightSpeed‐RT scanner and Varian RPM‐respiratory‐gating system. The 4DCT datasets along with the conventional 3DCT images for 10 patients were analyzed retrospectively. Each set of 4DCT consisted of 10 CT image sets at a phase between 0–90% during one respiration cycle. For each case, a 3D dosimetric plan of two tangential beams irradiating the whole breast was generated based on the 3DCT images using Xio (CMS) planning system. The parameters for this dosimetric plan (e.g., energy, beam angles, beam shape, wedge, weighting, isocenter location) were copied to each phase image set of the 4DCT to generated 3D dose distribution. DVHs for each phase image set were generated and were used for EUD calculation based on LQ model for breast tumor and Lyman model for lung.Results: 4DCT showed breast position/shape and lung position/shape/volume are changed with respiration. For example, lung volume changed up to 20% for the cases studied. These changes result in significant intrafractional variations in dose distributions/DVHs. Our calculations show that, compared to the planned EUD (based on the 3DCT), the breast EUD was lowered by an average of 5% (when including all 10 breathing phases) and up to 10% (at a particular phase). Lung EUD varied by ±3% during respiration.Conclusion: Respiratory motion in breast radiation treatment can potentially result in decreased target coverage and normal structure sparing. This effect that can be assessed using EUD, and decreased EUD may be an indicator for gated breast irradiation.

Abstract 3727: Influence of patient, physician, and hospital characteristics on the receipt of guideline-concordant care for inflammatory breast cancer

Introduction: Inflammatory breast cancer (IBC) is an aggressive and lethal form of locally advanced breast cancer that makes up 1-6% of all breast cancers and has a median overall survival of less than 4 years. Physically, IBC is characterized by erythema, edema, and fine dimpling, so treatment can be delayed due to misdiagnosis as mastitis or dermatitis. Therapy for IBC tends to vary since no treatments are highly effective. Because IBC is such a rare subtype, studies have been challenged to demonstrate patterns of IBC treatment and analyze factors affecting differences in treatment. In this study we examined factors affecting the receipt of guideline-concordant care and survival for IBC patients. Methods: Patients diagnosed with non-metastatic IBC in 2004 were identified from the Breast and Prostate Cancer Data Quality and Patterns of Care Study, containing information from cancer registry reports in seven states supplemented through medical record re-abstraction and physician verification. Variation in guideline-concordant care for IBC, based on 2003 National Comprehensive Cancer Network (NCCN) guidelines, was assessed according to patient, physician, and hospital characteristics. Additionally, survival based on receipt of guideline-concordant care was analyzed using Kaplan-Meier curves and log-rank tests. Results: Of the 107 IBC patients in the study, only 25.8% of them received treatment that was fully concordant with guidelines. The majority of patients received guideline-concordant surgery (90.4%), with percentages lower for chemotherapy (51.9%), radiation (40.7%), and hormone therapy (78.0%). Guideline-concordant care was less common among patients with extreme categories of patient age (under 40 or over 80 years; P = 0.19), non-white race (P = 0.03), lower body mass index (BMI Results suggested that IBC patients experienced longer breast cancer-specific survival if they received guideline-concordant treatment based on 2003 (P = 0.06) and 2013 (P = 0.06) NCCN guidelines. Conclusion: Targeting factors associated with receipt of care that is not guideline-concordant may reduce survival disparities in IBC patients. Further research is needed to identify approaches to ensure that physicians are adhering to NCCN guidelines for IBC cases and to identify reasons for non-adherence to guidelines. Citation Format: Ryan A. Denu, John M. Hampton, Adam Currey, Roger T. Anderson, Rosemary D. Cress, Steven T. Fleming, Joseph Lipscomb, Susan A. Sabatino, Xiao-Cheng Wu, J F. Wilson, Amy Trentham-Dietz. Influence of patient, physician, and hospital characteristics on the receipt of guideline-concordant care for inflammatory breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3727. doi:10.1158/1538-7445.AM2015-3727

SU‐E‐T‐277: Modeling Normal Tissue Complication Probability Based On Compiled Clinical Data From Skin Cancer Radiotherapy

PURPOSE Our objective is to model normal tissue complication probability (NTCP) based on published clinical data of head/face non-melanoma skin cancers to determine optimum treatment schemes using advanced radiotherapy (RT) technologies. METHODS Reports citing crude estimates of erythema, desquamation and telangiectasia for primary basal and squamous cell carcinoma (BCC & SCC, resp) of the head/face were used in model development. The models had the form: NTCP = 1/(1+exp(-(BED + BEDprolif x T - TD50)/k), where BED is the LQ model based biological effective dose. Uncomplicated tumor control functions (UCTCs) were created using NTCP models together with our own separately published TCP models. Values of BED maximizing UCTC were calculated and compared with 5 × 7.2 Gy in one week and 15 × 3 Gy in 3 weeks treatment schedules (BED 14 = 54.5 & 54.6 Gy, respectively). RESULTS Literature search yield six reports useful in the development of a TCP model for BCC/SCC. The reported a median total dose of 39.0 Gy (range: 23.9-52.4 Gy), dose per fraction of 3.3 Gy/fx (range: 1.7-7.3 Gy/fx), & total treatment time of 28.7 days (range: 12-40 days). Three NTCP and 12 UTCP models were generated for treatments with tumors of size < 2cm and > 2cm. Maximum UCTC occurred at biological effective doses (BEDs) ranging from 36.25-52.25 Gy to the BCC/SCC tumors < 2 cm and 55.0-61.4 Gy to the BCC/SCC tumors > 2 cm in size. CONCLUSION Three NTCP models for endpoints observed in skin cancer RT were developed based on published data, which can depend on the size of irradiated skin area (future work will explore the area-NTCP relationship further). BED values for single and multiple fraction treatments were identified to maximize UCTC for tumors > 2 cm in size, though smaller tumors may benefit from treatment schedules with lower BED.

SU-E-T-597: Online Adaptive Replanning for Sequential Boost After Whole Breast Irradiation

PURPOSE For whole breast irradiation (WBI) followed by sequential boost of the lumpectomy cavity (LC), the LC shape and volume can change significantly after WBI. Consequently, the boost plan, normally generated together with WBI plan before the start of treatment, may not be optimal. Here we propose the use of online adaptive replanning at the time of boost to account for the LC change. METHODS Daily diagnostic-quality CT sets acquired during IGRT using an in-room CT (CTVision, Siemens) for 19 breast cancer patients treated with WBI with sequential boost in prone position were used. Contours of LC, treated breast, ipsilateral lung, and heart were generated by deformably registering the planning CT with the fraction CT acquired on the first boost fraction using an auto-segmentation tool (ABAS, Elekta) with manual editing, if necessary. Three plans were generated based on the daily CT: (1) repositioning plan by applying the original boost plan with the shift, (2) adaptive plan by quickly modifying the original plan using a tool (RealArt, Prowess), and (3) reoptimization plan by a fully-blown optimization. RESULTS Significant changes were observed in the LC volume and shape. The LC volume on the first day of boost changes in the range of 30% and 130% from that on planning CT. The plan quality of the adaptive plans and the re-optimization plans were comparable. Compared to the repositioning plans, the adaptive plans generally lead to improvement in target coverage and normal tissue sparing, with an average increase in LC V95 of 2.3% and decrease in breast tissue V50 of 3.0%. CONCLUSION Significant changes in LC shape and volume at the time of boost from the original plan for WBI with sequential boost can be addressed by the online replanning at the first boost fraction.

SU‐C‐213CD‐03: Significant Inter‐Fractional Variations of Lumpectomy Cavity in Partial Breast Irradiation

Purpose: Inter‐fractional variation in partial breast irradiation (PBI) using external beams is a significant issue. Image guided RT(IGRT), by imaging and repositioning the patient prior to the delivery based on rigid‐body registration, has been introduced to reduce inter‐fractional setup and translational variations. However, IGRT is not capable of addressing organ deformation and rotation. The purpose of this work is to quantitatively characterize those variations in PBI in supine position. Methods: A total of 100 diagnostic‐quality CT sets acquired using an in‐room CT during IGRT at each fraction for 10 breast cancer patients treated with PBI in supine position were analyzed. Targets and organs at risk, including the lumpectomy cavity,treated breast, lung and heart, were delineated by populating the contours from the planning CT to each fraction CT using an auto‐segmentation tool (ABAS, CMS/Elekta) with manual editing. Various parameters, including volume, maximum overlap rate (MOR), dices coefficient, and distance between centers of mass (COM) were calculated to quantify the inter‐fractional variations. Results: The shape and volume of the lumpectomy cavity in the fractional CTs, particularly in the first fraction CT, change significantly from those in the planning CT. On average, the volume of the lumpectomy cavity decreases by 23%. The MOR varies from 50% to 90% with the mean value of 72%. The dices coefficient is shown in a similar range. The variation of the treated breast is relatively small. The changes in the distances between the COMs of the lumpectomy cavity and the heart and of the lumpectomy cavity and the treated breast are up to 3 mm. Conclusions: The inter‐fractional lumpectomy cavity deformation is significant during PBI. Strategies that can address not only the translational motion but also the deformation, such as adaptive RT, should be explored for PBI.

Plan Quality of Proton Versus Photon IG-IMRT

Results: Median biological effective dose (BED) at an a/b ratio of 10 as the prescribed dose was 84.5GyE10 (range, 60-96.8GyE10). Eleven (40%) patients developed acute Grade 1, 12 (45%) patients Grade 2, and 4(15%) patients Grade 3 acute dermatitis. In uni-variate analysis, factors associated with onset of Grade 2 or higher acute dermatitis included BED (GyE10) as prescription dose (p Z 0.030), skin dose parameter (V45-70GyE10) (p Z 0.044, 0.039, 0.031, 0.015, 0.010, and 0.022, respectively), and gradient dose index (GDI65GyE and 70GyE) (p Z 0.031, and 0.048, respectively). When plotting the p value of the logistic regression analysis between the variables, V65 GyE10 of skin surface area show the strongest statistical significance (p & 0.01). Conclusions: High incidence of severe (Grade 2 or higher) radiation dermatitis (60% of entire cohort) was observed during clinical use of PBT in HNC patients. The entrance portal area to skin irradiated volume with 45-70GyE10 was possible predictor for acute skin toxicity and higher dose volume of superficial regions over 65GyE10 should be considered in the treatment planning as sensitive organ volume in PBT. Author Disclosure: H. Inokuchi: None. T. Nakamura: None. T. Tomoda: None. A. Takada: None. K. Takayama: None. C. Makita: None. M. Shiomi: None. T. Kato: None. N. Fuwa: None.

SU‐GG‐J‐49: Interfractional Breast Shape Variation and Dosimetric Consequences in Whole Breast Irradiation

Purpose: This work aims to quantify interfractional variations in breast shape and their dosimetric consequences for conformal whole breast irradiation (WBI). Materials/Methods: Daily CT data acquired for 10 breast cancer patients during IGRT were analyzed. Patients were setup supine and daily pre‐treatment CTs were acquired using CT‐on‐Rails (CTVision, Siemens). Contours of breast and critical structures on daily CTs were generated using a tool (ABAS, CMS) based on deformable image registration. Interfractional changes of breast shape and volume were measured by using Dices Coefficient. For each patient, two commonly‐used WBI plans with tangential beams based on the planning CT, one using wedges and another using field‐in‐field (FiF) technique, were developed. Each daily CT was registered with corresponding planning CT to obtain repositioning shifts. Plans were applied to the daily CTs. Dosimetric variations were measured by a series of dose‐volume parameters. Results: Breast volume variations were generally small. Interfractional shifts can be significant and breast shape varies modestly. The average overlap between planning and daily breast volumes was 88–93%. The daily values of D95 and D50 (dose received by 95% and 50% of treated breast volume) varied by 1–2% from their planning values for both plans. For D98, the variation was upto 5%. These variations were not significantly different between the wedge and FIF plans. Daily global maximum was on average increased by 2–4% for the FiF plans as compared to the wedge plans. The interfractional variation of V52.5 (volume receiving 52.5 Gy) was significantly higher for FiF plans compared to the corresponding wedge plans. Conclusion: Interfractional variations in patient positioning result in modest breast shape changes which can lead to dosimetric variations during the course of treatment and cannot be fully corrected for by patient repositioning. FiF plans are more sensitive to the breast shape change than wedge plans.

SU‐GG‐T‐21: Dosimetry Benefits of Online Adaptive Replanning for Whole Breast Irradiation

Purpose: Interfraction breast shape change (deformation) can be substantial (e.g., large or pendulous breasts in supine position), which, in turn, can degrade dose uniformity in breast. This change cannot be fully corrected for by patient repositioning. We have previously developed an online adaptive replanning technique to address interfraction variations. This work aims to demonstrate that this online replanning scheme can effectively account for the daily variation including setup errors and anatomic changes in whole breast irradiation (WBI). Method and Materials: Daily CT scans collected during IGRT for representative breast cancer patients treated in supine position using a CT‐on‐Rails (CTVision, Siemens) were analyzed. For each patient, a WBI IMRT plan with tangential 6MV beams was generated based on the planning CT using a planning system (Prowess Inc.). An adaptive plan was generated based on each daily CT using the system (RealART, Prowess Inc) with the online replanning algorithms implemented. For comparison, the plan (repositioning plan) with the patient repositioned based on the registration between the daily CT and the planning CT was reconstructed by copying the original plan over to the daily CT with shifts considered. A total of 20 adaptive plans and 20 repositioning plans were generated and compared. Results: DVH comparison shows that the adaptive plans, which are similar to the original plans, are generally superior than the repositioning plan in term of target coverage and/or critical structure sparing. Repositioning plans suffer from reduced target coverage. For example, values of V45Gy (breast volume covered by 45 Gy) and V50Gy are reduced by 10% and 6% respectively, for repositioning plans, while no changes in these values for adaptive plans. Conclusion: Interfractional variations in whole breast irradiation cause dosimetry degradation which cannot be accounted for by patient repositioning, but can be corrected by the online adaptive replanning.