TPS601 Background: This phase III post-NC trial evaluates if CWRNRT post-Mx or whole breast irradiation (WBI) with RNRT after BCS significantly reduces the IBCR-FI rate in pts with PAx nodes that are negative after NC. Secondary aims are OS, LRR-FI, DR-FI, DFS-DCIS, second primary cancer, and comparison of RT effect on cosmesis in reconstructed Mx pts. Correlative science examines RT effect by tumor subtype, molecular outcome predictors for residual disease pts, and predictors for the degree of reduction in locoregional recurrence. Methods: Clinical T1-3, N1 IBC PAx nodes (FNA or core needle biopsy) pts complete ≥8 weeks of NC (anthracycline and/or taxane). HER2+ pts receive anti-HER2 therapy. Following NC, BCS or Mx, sentinel node biopsy (≥2 nodes) and/or Ax dissection with histologically negative nodes is performed. ER/PR and HER-2neu status before NC is required. Pts receive appropriate adjuvant systemic therapy. Radiation credentialing with a facility questionnaire/case benchmark is required. Random assignment for Mx pts is to no CWRNRT or CWRNRT and for BCS pts to WBI or WBI+RNRT. Statistics: 1636 pts to be enrolled over 5 yrs (definitive analysis at 7.5 yrs). Study is powered at 80% to test that RT reduces the annual hazard rate of events for IBCR-FI by 35% for an absolute risk reduction of 4.6% (5-yr cumulative rate). Intent-to-treat analysis with 3 interim analyses (43, 86, and 129 events) and a 4th/final analysis at 172 events. Pt-reported outcomes focusing on RT effect will be provided by 736 pts before random assignment and at 3, 6, 12, and 24 mos. Accrual as of 1-23-18 is 848 (51.83%). Contacts: Protocol: CTSU member website https://www.ctsu.org. Questions: NRG Oncology Pgh Clin Coord Dpt: 1-800-477-7227 or ccd@nsabp.org. Pt entry: OPEN at https://open.ctsu.org or the OPEN tab on CTSU member website. Support: U10 CA-2166; -180868, -180822; 189867; Elekta Clinical trial information: NCT01872975.
Purpose: Radiation therapy (RT) of left sided breast cancers with deep‐inspiratory breathhold (DIBH) can reduce the dose to heart. The purpose of this study is to develop and test a new laser‐based tool to improve ease of RT delivery using DIBH. Methods: A laser sensor together with breathing monitor device (Anzai Inc., Japan) was used to record the surface breathing motion of phantom/volunteers. The device projects a laser beam to the chestwall and the reflected light creates a focal spot on a light detecting element. The position change of the focal spot correlates with the patient's breathing motion and is measured through the change of current in the light detecting element. The signal is amplified and displayed on a computer screen, which is used to trigger radiation gating. The laser sensor can be easily mounted to the simulation/treatment couch with a fixing plate and a magnet base, and has a sensitivity range of 10 to 40 cm from the patient. The correlation of breathing signals detected by laser sensor and visionRT is also investigated. Results: It is found that the measured breathing signal from the laser sensor is stable and reproducible and has no noticeable delay. It correlates well with the VisionRT surface imaging system. The DIBH reference level does not change with movement of the couch because the laser sensor and couch move together. Conclusion: The Anzai laser sensor provides a cost‐effective way to improve beam gating with DIBH for treating left breast cancer. It can be used alone or together with VisionRT to determine the correct DIBH level during the radiation treatment of left breast cancer with DIBH.
Abstract Background: The benefit of adjuvant regional nodal irradiation including the chest wall after mastectomy (CWI+RNI) and with whole breast irradiation (WBI+RNI) after breast conserving surgery (BCS) is well established in pts with pathologically positive axillary nodes (pN+). Pts who present with axillary node involvement (cN+), receive neoadjuvant chemotherapy (NC), and are found to be pathologically node-negative at surgery (ypN0), have lower loco-regional recurrence (LRR) rates compared to those who remain pathologically node-positive (ypN+). This phase III, randomized trial aimed to evaluate whether CWI+RNI after mastectomy or addition of RNI to WBI after BCS significantly improves invasive breast cancer recurrence-free interval (IBC-RFI) in cN+ pts found to be ypN0 after NC. Methods: Eligible pts had clinical cT1-3, N1, M0 invasive breast cancer (biopsy-proven N+ by FNA/core needle bx), completed ≥8 wks of NC (and anti-HER2 therapy if HER2+), and were ypN0 after mastectomy or BCS and sentinel node biopsy (SLNB, ≥2 nodes), axillary lymph node dissection (ALND), or both. Pts were randomized to “No RNI” (i.e., observation after mastectomy or WBI after BCS) vs. “RNI” (i.e., CWI+RNI after mastectomy or WBI+RNI after BCS). Primary endpoint was IBC-RFI. Secondary endpoints reported here: LRR-free interval (LRRFI), distant recurrence-free interval (DRFI), disease-free survival (DFS), and overall survival (OS). Study was designed to have 80% power to detect 35% reduction in annual rate of IBC-RFI for an absolute risk reduction of 4.6% (5-yr cumulative rate). Per protocol, final analysis was to occur after 172 events or 10 yrs after study initiation.Here we report the time-driven analysis prespecified in the protocol. Results: From 9/13-12/20, 1,641 pts were enrolled; 1,556 pts were available for primary event analysis; median f/u time 59.5 mos (IQR 40.7-74.1). Pt/tumor characteristics were well balanced between groups. Median age 52 yrs (range 21-84); 31% non-white; 21% cT1, 60% cT2, 19% cT3; 23% triple-negative, 21% HR+/HER2-, 56% HER2+; 58% BCS; 55% SLNB, 45% ALND+/-SLNB; and 78% had breast pathologic complete response. At the time of the analysis, 109 IBC-RFI events (63% of the planned 172) were confirmed (“No RNI”: 59, “RNI”: 50). There was no statistically significant difference between groups for IBC-RFI (HR=0.88, 95%CI 0.60-1.29; p=0.51), 5-yr point estimates: 91.8% for “No RNI” and 92.7% for “RNI.” There were no statistically significant differences between the treatment groups for secondary endpoints. There were no study-related deaths and no unexpected toxicities.Grade 4 toxicity was rare (0.1% with “No RNI”, 0.5% with “RNI”); 6.5% of pts developed grade 3 toxicity in “No RNI” and 10% in “RNI” group. Most common grade 3 toxicity was radiation dermatitis (3.3% in “No RNI,” 5.7% in “RNI”). Conclusion: In pts who present with biopsy-proven axillary node involvement and convert their axillary nodes to ypN0 after NC, CWI+RNI after mastectomy, or WBI+RNI after BCS, did not significantly improve IBC-RFI, LRRFI, DRFI, DFS, or OS. These findings suggest that downstaging involved axillary nodes with NC can result in optimization of adjuvant radiotherapy without adversely affecting oncologic outcomes. Follow-up of pts for long-term outcomes continues. NCT01872975 *EPM and JW are co-first authors. Table 1 Citation Format: Eleftherios Mamounas, Hanna Bandos, Julia White, Thomas Julian, Atif Khan, Simona Shaitelman, Mylin Torres, Frank Vicini, Patricia Ganz, Susan McCloskey, Nilendu Gupta, X. Allen Li, Peter Lucas, Nadeem Abu-Rustum, Saumil Gandhi, Rahul Tendulkar, Robert Coleman, Keiichi Fujiwara, Samantha Seaward, William Irvin, Kristin Higgins, Robert Mutter, Jean-Francois Boileau, Andrew Muskovitz, Reshma Jagsi, Anna Weiss, Curran Walter Jr., Norman Wolmark. Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-07.
Real-time motion monitoring (RTMM) is necessary for accurate motion management of intrafraction motions during radiation therapy (RT).Building upon a previous study, this work develops and tests an improved RTMM technique based on real-time orthogonal cine magnetic resonance imaging (MRI) acquired during magnetic resonance-guided adaptive RT (MRgART) for abdominal tumors on MR-Linac.A motion monitoring research package (MMRP) was developed and tested for RTMM based on template rigid registration between beam-on real-time orthogonal cine MRI and pre-beam daily reference 3D-MRI (baseline). The MRI data acquired under free-breathing during the routine MRgART on a 1.5T MR-Linac for 18 patients with abdominal malignancies of 8 liver, 4 adrenal glands (renal fossa), and 6 pancreas cases were used to evaluate the MMRP package. For each patient, a 3D mid-position image derived from an in-house daily 4D-MRI was used to define a target mask or a surrogate sub-region encompassing the target. Additionally, an exploratory case reviewed for an MRI dataset of a healthy volunteer acquired under both free-breathing and deep inspiration breath-hold (DIBH) was used to test how effectively the RTMM using the MMRP can address through-plane motion (TPM). For all cases, the 2D T2/T1-weighted cine MRIs were captured with a temporal resolution of 200 ms interleaved between coronal and sagittal orientations. Manually delineated contours on the cine frames were used as the ground-truth motion. Common visible vessels and segments of target boundaries in proximity to the target were used as anatomical landmarks for reproducible delineations on both the 3D and the cine MRI images. Standard deviation of the error (SDE) between the ground-truth and the measured target motion from the MMRP package were analyzed to evaluate the RTMM accuracy. The maximum target motion (MTM) was measured on the 4D-MRI for all cases during free-breathing.The mean (range) centroid motions for the 13 abdominal tumor cases were 7.69 (4.71-11.15), 1.73 (0.81-3.05), and 2.71 (1.45-3.93) mm with an overall accuracy of <2 mm in the superior-inferior (SI), the left-right (LR), and the anterior-posterior (AP) directions, respectively. The mean (range) of the MTM from the 4D-MRI was 7.38 (2-11) mm in the SI direction, smaller than the monitored motion of centroid, demonstrating the importance of the real-time motion capture. For the remaining patient cases, the ground-truth delineation was challenging under free-breathing due to the target deformation and the large TPM in the AP direction, the implant-induced image artifacts, and/or the suboptimal image plane selection. These cases were evaluated based on visual assessment. For the healthy volunteer, the TPM of the target was significant under free-breathing which degraded the RTMM accuracy. RTMM accuracy of <2 mm was achieved under DIBH, indicating DIBH is an effective method to address large TPM.We have successfully developed and tested the use of a template-based registration method for an accurate RTMM of abdominal targets during MRgART on a 1.5T MR-Linac without using injected contrast agents or radio-opaque implants. DIBH may be used to effectively reduce or eliminate TPM of abdominal targets during RTMM.
The EGS4 Monte Carlo radiation transport code was used to systematically study the dose perturbation near planar and cylindrical air cavities in a water medium irradiated by megavoltage x‐ray beams. The variables of the problem included x‐ray energy, cavity shape and dimension, and depth of the cavity in water. The Monte Carlo code was initially validated against published measurements and its results were found to agree within 2% with the published measurements. The study results indicate that the dose perturbation is strongly dependent on x‐ray energy, field size, depth, and size of cavity in water. For example, the Monte Carlo calculations show dose reductions of 42% and 18% at 0.05 and 2 mm, respectively, beyond the air–water interface distal to the radiation source for a 3 cm thick air slab irradiated by a single 5×5 cm 2 15 MV beam. The dose reductions are smaller for a parallel‐opposed pair of 5×5 cm 2 15 MV x‐ray beams, being 21% and 11% for the same depths. The combined set of Monte Carlo calculations showed that the dose reduction near an air cavity is greater for: (a) Smaller x‐ray field size, (b) higher x‐ray energy, (c) larger air‐cavity size, and (d) smaller depth in water where the air cavity is situated. A potential clinical application of these results to the treatment of prostate cancer is discussed.
Full Monte Carlo radiation transport simulations of accelerator heads are impractical for routine treatment planning because of the excessive computational burden and memory requirements. To improve the accuracy and efficiency of treatment plans for helical tomotherapy, we have developed a dual-source model to characterize the radiation emitted from the head of a commercial helical tomotherapy accelerator. Percentage depth dose (PDD) and beam profiles computed using the dual-source model with the EGS/BEAMnrc Monte Carlo package agree within 2% of measurements for a wide range of field sizes, which suggests that the proposed dual-source model provides an adequate representation of the tomotherapy head for dose calculations in routine treatment planning.
An inverse optimization package which is capable of generating nonuniform dose distribution with subregional dose escalation is developed to achieve maximum equivalent uniform dose (EUD) for target while keeping the critical structure doses as low as possible. Relative cerebral blood volume (rCBV) maps obtained with a dynamic susceptibility contrast‐enhanced MRI technique were used to delineate spatial radiosensitivity distributions. The voxel rCBV was converted to voxel radiosensitivity parameters (e.g., and ) based on previously reported correlations between rCBV, tumor grade, and radiosensitivity. A software package, DOSEPAINT , developed using MATLAB , optimizes the beamlet weights to achieve maximum EUD for target while limiting doses to critical structures. Using DOSEPAINT , we have generated nonuniform 3D‐dose distributions for selected patient cases. Depending on the variation of the pixel radiosensitivity, the subregional dose escalation can be as high as 35% of the uniform dose as planned conventionally. The target dose escalation comes from both the inhomogeneous radiosensitivities and the elimination of integral target dose constraint. The target EUDs are found to be higher than those for the uniform dose planned ignoring the spatial inhomogeneous radiosensitivity. The EUDs for organs at risk are found to be approximately equal to or lower than those for the uniform dose plans. In conclusion, we have developed a package that is capable of generating nonuniform dose distributions optimized for spatially inhomogeneous radiosensitivity. Subregional dose escalation may lead to increased treatment effectiveness as indicated by higher EUDs. The current development will impact biological image guided radiotherapy.
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