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Background: Post‐mastectomy radiation therapy (PMRT) in women with pathologic stage T1‐2N1M0 breast cancer is controversial. Methods: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1‐2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing‐risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM). Results: A total of 3532 patients were included for analysis with a median follow‐up time among survivors of 6.8 years (interquartile range [IQR], 4.5–9.5 years). The 2154 (61%) patients who received PMRT had significantly more adverse risk factors than those patients not receiving PMRT: younger age, larger tumors, more positive lymph nodes, lymphovascular invasion, extracapsular extension, and positive margins (p <.05 for all). On competing risk regression analysis, receipt of PMRT was significantly associated with a decreased risk of LRR (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.14–0.31; p <.001) and OR (HR, 0.76; 95% CI, 0.62–0.94; p =.011). Model performance metrics for each end point showed good discrimination and calibration. An online prediction model to estimate predicted risks for each outcome based on individual patient and tumor characteristics was created from the model. Conclusions: In a large multi‐institutional cohort of patients, PMRT for T1‐2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision‐making regarding PMRT in this population. In a large multi‐institutional cohort of patients, post‐mastectomy radiation therapy (PMRT) for T1‐2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision‐making regarding PMRT in this population. [ABSTRACT FROM AUTHOR]

Background: The trial assigning individualized options for treatment (Rx) (TAILORx) confirmed the predictive value of the 21-gene recurrence score (RS) assay in hormone receptor (HR)-positive, HER2-negative, node-negative breast cancer and established thresholds for chemotherapy benefit in younger and older patients. Real-world chemotherapy use and RS-guided treatment costs in British Columbia post-TAILORx were examined.Methods: The authors assembled 3 cohorts of HR-positive, HER2-negative, node-negative patients with breast cancer defined by diagnosis: before RS funding (cohort 1 [C1]: January 2013-December 2013), after introduction of public RS funding (cohort 2 [C2]: July 2015-June 2016), and after TAILORx results (cohort 3 [C3]: July 2018-June 2019). Chemotherapy use was compared between cohorts by age and RS. Budgetary impacts of RS testing on chemotherapy costs were evaluated pre- and post-TAILORx.Results: Among the 2066 patients included, chemotherapy use declined by 19% after RS funding was introduced and by an additional 23% after TAILORx publication (P = .001). Reduction in chemotherapy use was significant for RS 11-20 tumors (C3 vs C2, P = .004). There was no significant change in chemotherapy use in patients >50 years old (C2:12% vs C3:10%, P = .22). RS testing was associated with higher cost savings post-TAILORx, except in patients 70 to 80 years old, where testing led to excess costs when adjusting for the low rate of RS-concordant chemotherapy prescribed.Conclusions: TAILORx has had population-based impacts on chemotherapy prescribing in intermediate RS tumors and patients ≤50 years old. The lower clinical use of RS and increased spending in patients 70-80 years old highlights the importance of careful selection of older candidates for high-cost genomic testing.Lay Summary: The 21-gene recurrence score (RS) test helps predict whether patients with hormone-positive, HER2-negative, lymph node-negative breast cancer are likely to benefit from chemotherapy. The recent trial assigning individualized options for treatment (Rx) (TAILORx) found that patients with intermediate RS tumors did not benefit from chemotherapy. The authors assessed whether TAILORx results translated to real-world changes in chemotherapy prescribing patterns. In this study, chemotherapy use decreased by 23% after TAILORx, with the greatest reductions seen among intermediate RS tumors and younger patients. In contrast, RS testing had lower clinical value and increased treatment costs in elderly patients, which requires further study to ensure optimal care for this age group. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine whether new systemic therapy regimens have resulted in improved survival and increased time on first- and second-line hormonal treatment for patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) over time.Methods: Patients diagnosed with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative MBC were identified across 3 time cohorts (2003-2005, 2007-2009, and 2011-2013). Data were prospectively collected. Cases with previous, synchronous, or subsequent contralateral breast cancer were excluded. The types of first- and second-line therapies, the times on first- and second-line hormonal treatment, and the median survival times were compared across the cohorts.Results: Within the time period analyzed, 9 new adjuvant systemic therapies (with or without neoadjuvant therapy) and 2 metastatic systemic therapies were approved at BC Cancer for the treatment of HR-positive, HER2-negative MBC. In the 3 time cohorts, 3953 patients diagnosed with MBC were identified. Among the 2432 patients (62%) who had HR-positive/HER2-negative disease, 2197 (90%) received at least 1 line of systemic therapy after the diagnosis of MBC, and 80% of these patients (1752 of 2197) received first- and/or second-line hormonal treatment. The median duration on hormonal treatment was 9.0 months for the first line and 6.1 months for the second line. The durations were similar across the time cohorts (range for the first line, 8.9-9.0 months; range for the second line, 6.0-6.1 months). The median survival for the entire study population was 2.0 years (95% confidence interval, 1.8-2.1 years), and there was no significant difference between the cohorts (range, 1.9-2.0 years).Conclusions: Even though more adjuvant and metastatic systemic therapies have been approved since 2003, population-level gains in survival and the time on hormonal treatment for patients with HR-positive, HER2-negative MBC have not been made over the course of a decade. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the accuracy and the sensitivity to contour variation and model size of a finite element model-based deformable registration algorithm for the prostate. Methods and materials: Two magnetic resonance images (MRIs) were obtained for 21 prostate patients with three implanted markers. A single observer contoured the prostate and markers and performed blinded recontouring of the first MRI. A biomechanical-model based deformable registration algorithm, MORFEUS, was applied to each dataset pair, deforming the second image (B) to the first image (A). The residual error was calculated by comparing the center of mass (COM) of the markers with the predicted COM. Sensitivity to contour variation was calculated by deforming B to the repeat contour of A (A2). The sensitivity to the model size was calculated by reducing the number of nodes (B′, A′, A2′) and repeating the analysis. Results: The average residual error of the registration for B to A and B to A2 was 0.22 cm (SD: 0.08 cm) and 0.24 cm (SD: 0.09 cm), respectively. The average residual error of the registration of B′ to A′ and B′ to A2′ was 0.22 cm (SD: 0.10 cm) and 0.25 cm (SD: 0.10 cm), respectively. The average time to run MORFEUS on the standard and reduced model was 3606 s (SD: 7788 s) and 56 s (SD: 16 s), respectively. Conclusions: The accuracy of the algorithm, equal to the image voxel size, is not affected by intraobserver contour variability or model size. Reducing the model size significantly increases algorithm efficiency. [ABSTRACT FROM AUTHOR]

This paper is the first investigation of using direct aperture optimization (DAO) for online adaptive radiation therapy (ART). A geometrical model representing the anatomy of a typical prostate case was created. To simulate interfractional deformations, four different anatomical deformations were created by systematically deforming the original anatomy by various amounts (0.25, 0.50, 0.75, and 1.00 cm). We describe a series of techniques where the original treatment plan was adapted in order to correct for the deterioration of dose distribution quality caused by the anatomical deformations. We found that the average time needed to adapt the original plan to arrive at a clinically acceptable plan is roughly half of the time needed for a complete plan regeneration, for all four anatomical deformations. Furthermore, through modification of the DAO algorithm the optimization search space was reduced and the plan adaptation was significantly accelerated. For the first anatomical deformation (0.25 cm), the plan adaptation was six times more efficient than the complete plan regeneration. For the 0.50 and 0.75 cm deformations, the optimization efficiency was increased by a factor of roughly 3 compared to the complete plan regeneration. However, for the anatomical deformation of 1.00 cm, the reduction of the optimization search space during plan adaptation did not result in any efficiency improvement over the original (nonmodified) plan adaptation. The anatomical deformation of 1.00 cm demonstrates the limit of this approach. We propose an innovative approach to online ART in which the plan adaptation and radiation delivery are merged together and performed concurrently—adaptive radiation delivery (ARD). A fundamental advantage of ARD is the fact that radiation delivery can start almost immediately after image acquisition and evaluation. Most of the original plan adaptation is done during the radiation delivery, so the time spent adapting the original plan does not increase the overall time the patient has to spend on the treatment couch. As a consequence, the effective time allotted for plan adaptation is drastically reduced. For the 0.25, 0.5, and 0.75 cm anatomical deformations, the treatment time was increased by only 2, 4, and 6 s, respectively, as compared to no plan adaptation. For the anatomical deformation of 1.0 cm the time increase was substantially larger. The anatomical deformation of 1.0 cm represents an extreme case, which is rarely observed for the prostate, and again demonstrates the limit of this approach. ARD shows great potential for an online adaptive method with minimal extension of treatment time. [ABSTRACT FROM AUTHOR]