S.J. Chmura

Assessment of interfractional variation of the breast surface following conventional patient positioning for whole-breast radiotherapy

The purpose of this study was to quantify the variability of the breast surface position when aligning whole‐breast patients to bony landmarks based on MV portal films or skin marks alone. Surface imaging was used to assess the breast surface position of 11 whole‐breast radiotherapy patients, but was not used for patient positioning. On filmed fractions, AlignRT v5.0 was used to capture the patients surface after initial positioning based on skin marks (28 “preshifts” surfaces), and after treatment couch shifts based on MV films (41 “postshifts” surfaces). Translations and rotations based on surface captures were recorded, as well as couch shifts based on MV films. For nonfilmed treatments, “daily” surface images were captured following positioning to skin marks alone. Group mean and systematic and random errors were calculated for all datasets. Pearson correlation coefficients, setup margins, and 95% limits of agreement (LOA) were calculated for preshifts translations and MV film shifts. LOA between postshifts surfaces and the filmed treatment positions were also computed. All the surface captures collected were retrospectively compared to both a DICOM reference surface created from the planning CT and to an AlignRT reference surface. All statistical analyses were performed using the DICOM reference surface dataset. AlignRT reference surface data was only used to calculate the LOA with the DICOM reference data. This helped assess any outcome differences between both reference surfaces. Setup margins for preshifts surfaces and MV films range between 8.3–12.0 mm and 5.4–13.4 mm, respectively. The largest margin is along the left–right (LR) direction for preshift surfaces, and along craniocaudal (CC) for films. LOA ranges between the preshifts surfaces and MV film shifts are large (12.6–21.9 mm); these decrease for postshifts surfaces (9.8–18.4 mm), but still show significant disagreements between the two modalities due to their focus on different anatomical landmarks (patients topography versus bony anatomy). Pearsons correlation coefficients further support this by showing low to moderate correlations in the anterior–posterior (AP) and LR directions (0.47–0.69) and no correlation along CC(<0.15). The use of an AlignRT reference surface compared to the DICOM reference surface does not significantly affect the LOA. Alignment of breast patients based solely on bony alignment may lead to interfractional inconsistencies in the breast surface position. The use of surface imaging tools highlights these discrepancies, and allows the radiation oncology team to better assess the possible effects on treatment quality. PACS number: 87

SU‐FF‐T‐02: In Vitro Validation of Temporal Optimization Effects On Cell Survival for a Single Fraction of Radiation

Purpose: To experimentally validate how temporal modification of the applied dose pattern within a single fraction of radiation therapy affects cell survival. Method and Materials: The linear quadratic (LQ) repair‐time model predicts that, for a single fraction of dose, the degree of cell kill is dependent on the pattern of dose applied over a period of irradiation. Previously, we demonstrated that: (1) maximum cell kill is achieved using a “triangular” temporal dose pattern (delivering the highest doses during the middle of a fraction and the lowest at the beginning and end), and (2) minimum cell kill is achieved with a “V‐shaped” pattern (delivering the lowest doses at the middle of a fraction and the highest at the beginning and end). Furthermore, the model also predicted that cells with low α/β values will have a larger difference in survival based on the applied pattern of dose. Two cells lines with low α/β values (PC‐3, WiDr) and one with a high α/β value (SQ‐20b) were chosen for this study. For each cell line, one group of cells in a six‐well plate received 9 Gy in a triangular dose pattern, and the same dose was delivered to a second plate using a V‐shaped pattern. The delivery time for each dose pattern was 20 min. Cell survival was assessed using a clonogenic assay. Results: For the SQ‐20b cells, irradiation with both dose patterns resulted in only a 4.5% relative difference in cell survival (p>0.25). However, the triangle and V‐shaped patterns resulted in relative cell survival differences of 15.2% and 18.6% for both the PC‐3 (p<0.025) and WiDr (p<0.01) cell lines, respectively. Conclusion: These results verify the assertions of the modeling study in vitro, and imply that the temporal pattern of applied dose is another variable to be considered in treatment planning and delivery.

SU-F-J-19: Robust Region-Of-Interest (ROI) for Consistent Registration On Deteriorated Surface Images

PURPOSE For African-American patients receiving breast radiotherapy with a bolus, skin darkening can affect the surface visualization when using optical imaging for daily positioning and gating at deep-inspiration breath holds (DIBH). Our goal is to identify a region-of-interest (ROI) that is robust against deteriorating surface image quality due to skin darkening. METHODS We study four patients whose post-mastectomy surfaces are imaged daily with AlignRT (VisionRT, UK) for DIBH radiotherapy and whose surface image quality is degraded toward the end of treatment. To simulate the effects of skin darkening, surfaces from the first ten fractions of each patient are systematically degraded by 25-35%, 40-50% and 65-75% of the total area of the clinically used ROI_ipsilateral-chestwall. The degraded surfaces are registered to the reference surface in six degrees-of-freedom. To identify a robust ROI, three additional reference ROIs - ROI_chest+abdomen, ROI_bilateral-chest and ROI_extended-ipsilateral-chestwall are created and registered to the degraded surfaces. Differences in registration using these ROIs are compared to that using ROI_ipsilateral-chestwall. RESULTS For three patients, the deviations in the registrations to ROI_ipsilateral-chestwall are > 2.0, 3.1 and 7.9mm on average for 25-35%, 40-50% and 65-75% degraded surfaces, respectively. Rotational deviations reach 11.1° in pitch. For the last patient, registration is consistent to within 2.6mm even on the 65-75% degraded surfaces, possibly because the surface topography has more distinct features. For ROI_bilateral-chest and ROI_extended-ipsilateral-chest registrations deviate in a similar pattern. However, registration on ROI_chest+abdomen is robust to deteriorating image qualities to within 4.2mm for all four patients. CONCLUSION Registration deviations using ROI_ipsilateral-chestwall can reach 9.8mm on the 40-50% degraded surfaces. Caution is required when using AlignRT for patients experiencing skin darkening since the accuracy of AlignRT registration deteriorates. To avoid this inaccuracy, we recommend use of ROI_chest+abdomen, on which registration is consistent within 4.2mm even for highly degraded surfaces.

SU-F-J-123: CT-Based Determination of DIBH Variability and Its Dosimetric Impact On Post-Mastectomy Plus Regional Nodal Radiation Therapy

PURPOSE Breast cancer radiotherapy delivered using voluntary deep inspiration breath-hold (DIBH) requires reproducible breath holds, particularly when matching supraclavicular fields to tangential fields. We studied the impact of variation in DIBHs on CTV and OAR dose metrics by comparing the dose distribution computed on two DIBH CT scans taken at the time of simulation. METHODS Ten patients receiving 50Gy in 25 fractions to the left chestwall and regional lymph nodes were studied. Two simulation CT scans were taken during separate DIBHs along with a free-breathing (FB) scan. The treatment was planned using one DIBH CT. The dose was recomputed on the other two scans using adaptive planning (Pinnacle 9.10) in which the scans are registered using a cross-correlation algorithm. The chestwall, lymph nodes and OARs were contoured on the scans following the RTOG consensus guidelines. The overall translational and rotational variation between the DIBH scans was used to estimate positional variation between breath-holds. Dose metrics between plans were compared using paired t-tests (p < 0.05) and means and standard deviations were reported. RESULTS The registration parameters were sub-millimeter and sub-degree. Although DIBH significantly reduced mean heart dose by 2.4Gy compared to FB (p < 0.01), no significant changes in dose were observed for targets or OARs between the two DIBH scans. Nodal coverage as assessed by V90% was 90%±8% and 89%±8% for supraclavicular and 99%±2% and 97%±22% for IM nodes. Though a significant decrease (10.5%±12.4%) in lung volume in the second DIBH CT was observed, the lung V20Gy was unchanged (14±2% and 14±3%) between the two DIBH scans. CONCLUSION While the lung volume often varied between DIBHs, the CTV and OAR dose metrics were largely unchanged. This indicates that manual DIBH has the potential to provide consistent dose delivery to the chestwall and regional nodes targets when using matched fields.

Abstract OT3-03-04: NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer

Background: The current standard of care for metastatic breast cancer patients (pts) is to deliver palliative chemotherapy, biologic &/or hormonal therapy when appropriate, with radiation &/or surgery reserved for the management of symptomatic or non-responsive (mets). For selected pts with limited metastatic (met) disease, mets-directed ablative therapy, with either surgical resection or high dose conformal radiotherapy (in addition to standard systemic therapies) to lung, liver, CNS adrenal, & multiple organs has been shown to result in long-term disease control numerically superior to systemic therapy alone. NRG-BR002 is a randomized Phase II trial to evaluate stereotactic body radiotherapy (SBRT) &/or surgical resection (SR) of all met sites in newly oligometastatic breast cancer in addition to standard systemic therapy. Trial Design & Eligibility For the Ph IIR, eligible breast cancer pts who have received up to 6 months of first line systemic therapy without progression will be randomized to receive either standard systemic therapy with mets directed therapy as needed ( control arm) versus ablative therapy of all met sites with either body SBRT &/or surgical resection (SR) ( per the treating physician discretion) to determine if there is an improvement median progression free survival (PFS). If this aim is met the trial continues as a Ph III to evaluate if SBRT/SR improves 5 year overall survival. Secondary aims include local control in the met site, new distant met rate, & technical quality. The primary translational endpoint tests whether Women with pathologically confirmed met breast cancer to Statistics: For the Ph IIR portion to detect a signal for improved median PFS from 10.5 months to 19 months with 95% power & accounting for ineligible/lost pts, 146 pts will be required. For the Ph III, an additional 246, for a total of 402 pts will be required to definitively determine if ablative therapy improves 5-year overall survival from 28% to 42.5% (HR=0.67), with 85% power & a 1-sided type I error of 0.025. For the translational research, the number of pts accrued in the Ph IIR & Ph III portions will provide sufficient power ≥ 91% to detect whether Present Accrual & Target Accrual NRG BR002 activated 12/24/2014 with a target accrual of 146 pts for the Ph II component & 256 additional for the Ph III. Contact Information: Protocol: CTSU member web site https://www.ctsu.org. Enrollment: OPEN at https://open.ctsu.org. Support: Supported by NRG Oncology grants U10CA180868 & U10CA180822 from the National Cancer Institute (NCI). Citation Format: Chmura SJ, Winter KA, Salama JK, Woodward WA, Borges VF, Al-Hallaq H, Matuszak M, Jaskowiak NT, Milano MT, Bandos H, White JR. NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-03-04.

Abstract 1369: Mouse models of clinical oligo- and poly-metastatic progression

We previously proposed a metastatic state defined by a limited number of metastases, termed oligometastasis(es). These limited metastases may be cured by metastasis-directed treatments in contrast to widespread metastatic disease. While many animal models of polymetastases exist, an oligometastasis(es) model is lacking. Here, we report the first mouse xenograft model of oligometastasis(es) employing the MDA-MB-435 human tumor that maintains a stable oligometastatic phenotype in vivo. We also developed an MDA-MB-435 polymetastatic progression model in which the pattern of dissemination induced poly-foci in the lung, or to multiple anatomic sites including lung, heart, muscle, pleura, bone and peritoneal cavity. We performed microRNA expression profiling from distinct lung metastases of oligometastatic and polymetastatic animals. MicroRNA expression distinguished oligometastatic cell lines from those of polymetastatic, and accurately identified oligometastatic patients from a prior clinical study who failed to develop widespread metastases (p=0.005). These findings form the basis for investigating mechanisms underlying the specific metastatic pattern of individual cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1369. doi:1538-7445.AM2012-1369

SU‐E‐T‐228: Correlation of 3D Surface Matching with AlignRT and MV Imaging for Whole‐Breast Radiotherapy (WBRT)

Purpose: Surface matching provides quantitative shifts for patient positioning of superficial treatment sites such as breast. We investigated the reliability of 3D surface matching using AlignRT compared to positioning using skin marks followed by MV portal imaging for WBRT. Methods: Five patients receiving two‐field WBRT without respiratory gating were positioned daily on a breastboard (n=2) or custom alphacradle (n=3). For each treatment fraction guided by MV (n=23), the 3D surface captured using AlignRT (v4.5) was compared to the surface generated from CT simulation data. The AlignRT registration algorithm outputs 3D rotations plus translations to optimize matching between surfaces in user‐defined ROIs. The correlation of AlignRT and MV shifts in 4 degree‐of‐freedom (3D translations and table rotation) was studied for two ROIs: the entire surface (‘all’) and the treated breast (‘Breast’). Two surfaces were re‐captured in the treatment position to compare residual registration errors. Parametric statistical tests were considered significant at p 0.9) although residual 3D distances according to AlignRT remained high for ‘all’ (5.0±4.7mm) and ‘Breast’ (4.7±4.2mm). Furthermore, absolute table rotations calculated by AlignRT for consecutively acquired surfaces exhibited fluctuations that were significantly larger for registrations of ‘Breast’ (0.62±0.58 degrees) than ‘all’ (0.27±0.18 degrees). Conclusion: Breast surface matching using AlignRT depends upon the registered ROI. A large ROI showed higher correlation with MV shifts and increased stability when calculating table rotations. Registrations exhibited a large baseline offset for all ROIs, indicating that quantitative table shifts from AlignRT overestimate those determined from MV imaging by expert physicians for WBRT.

SU‐GG‐T‐400: Dosimetric Characterization and Biological Validation of a Phantom for Three Dimensional IMRT‐Based In Vitro Experiments

Purpose: To characterize the dosimetry of a previously described cylindrical phantom for use in 3‐dimensional intensity modulated radiation therapy (IMRT)‐based in vitro cell experiments and validate the phantom by comparing its performance in vitro to a standard experimental setup. Method and Materials: The phantom was loaded with a stack of three 6‐well tissue‐culture plates. An IMRT plan with a single PTV encompassing all plates was created and delivered in the phantom. Calculated doses were compared to those measured using both an array of thermoluminescencedosimeters(TLDs) and film placed in the phantom. In vitro validation was performed by delivering an array of doses from 0–10 Gy to two human cancer cell lines (A549 and SCC116) using both the phantom and a standard experimental setup employing a single open field. Percentage of viable cells post‐irradiation (%Via) was compared for both setups using the diphenylamine (DPA) assay. Results: The percent differences between TLD measurements and corresponding points in the treatment plan ranged from −1.3%–2.9% (p>0.05 for all cases). Average point‐by‐point percent dose difference (%Ddiff) between each film and the corresponding calculated dose plane ranged from 1.6%–3.1%, while the %Ddiff at which 95% of the film points agreed to ⩽3.0% ranged from 2.8%–4.1%. These results show good general agreement between measured and predicted dose. Comparison of the two experimental setups revealed average differences in %Via of 1.28% and 3.26% for SCC116 and A549, respectively (p>0.05 for all cases). Conclusion: Good general agreement between calculated and TLD and film measured dose within the phantom under experimental conditions, along with strong agreement in cell response when using the phantom versus a standard experimental setup show that the phantom is a useful, efficient, and dynamic tool for 3‐dimensional in vitro cell experiments. Conflict of Interest: Supported by a grant from MedImmune.