A pilot study of cardiac MRI in breast cancer survivors after cardiotoxic chemotherapy and three-dimensional conformal radiotherapy

Purpose/Objectives: Node-positive breast cancer patients often receive chemotherapy and regional nodal irradiation. The cardiotoxic effects of these treatments, however, may offset some of the survival benefit. Cardiac magnetic resonance (CMR) is an emerging modality to assess cardiac injury. This is a pilot trial assessing cardiac damage using CMR in patients who received anthracycline-based chemotherapy and three-dimensional conformal radiotherapy (3DCRT) regional nodal irradiation using heart constraints. Materials and Methods: Node-positive breast cancer patients (2000-2008) treated with anthracycline-based chemotherapy and 3DCRT regional nodal irradiation (including the internal mammary chain nodes) with heart ventricular constraints (V25 \u3c 10%) were invited to participate. Cardiac tissues were contoured and analyzed separately for whole heart (pericardium) and for combined ventricles and left atrium (myocardium). CMR obtained ventricular function/dimensions, late gadolinium enhancement (LGE), global longitudinal strain (GLS), and extracellular volume fraction (ECV) as measures of cardiac injury and/or early fibrosis. CMR parameters were correlated with dose-volume constraints using Spearman correlations. Results: Fifteen left-sided and five right-sided patients underwent CMR. Median diagnosis age was 50 (32-77). No patients had baseline cardiac disease before regional nodal irradiation. Median time after 3DCRT was 8.3 years (5.2-14.4). Median left-sided mean heart dose (MHD) was 4.8 Gy (1.1-11.2) and V25 was 5.7% (0-12%). Median left ventricular ejection fraction (LVEF) was 63%. No abnormal LGE was observed. No correlations were seen between whole heart doses and LVEF, LV mass, GLS, or LV dimensions. Increasing ECV did not correlate with increased heart or ventricular doses. However, correlations between higher LV mass and ventricular mean dose, V10, and V25 were seen. Conclusion: At a median follow-up of 8.3 years, this cohort of node-positive breast cancer patients who received anthracycline-based chemotherapy and regional nodal irradiation had no clinically abnormal CMR findings. However, correlations between ventricular mean dose, V10, and V25 and LV mass were seen. Larger corroborating studies that include advanced techniques for measuring regional heart mechanics are warranted

Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. EXPOSURES: Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. MAIN OUTCOMES AND MEASURES: The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. RESULTS: The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07). CONCLUSIONS AND RELEVANCE: Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes

Love a Mother: Reducing Maternal Mortality in South Sudan

South Sudan has the highest maternal mortality rate in the world, with a 1 in 7 chance that a woman will die during childbirth. The biggest cause for maternal mortality is postpartum hemorrhaging 8 . By surveying and educating people in and around the city of Juba about blood donation, more South Sudanese people will donate blood. Therefore, more mothers’ lives will be saved

Definitive Chemoradiation Associated with Improved Survival Outcomes in Patients with Synchronous Oligometastatic Esophageal Cancer

Background: The study of oligometastatic esophageal cancer (EC) is relatively new. Preliminary data suggests that more aggressive treatment regimens in select patients may improve survival rates in oligometastatic EC. However, the consensus recommends palliative treatment. We hypothesized that oligometastatic esophageal cancer patients treated with a definitive approach (chemoradiotherapy [CRT]) would have improved overall survival (OS) compared to those treated with a purely palliative intent and historical controls. Methods: Patients diagnosed with synchronous oligometastatic (any histology, ≤5 metastatic foci) esophageal cancer treated in a single academic hospital were retrospectively analyzed and divided into definitive and palliative treatment groups. Definitive CRT was defined as radiation therapy to the primary site with ≥40 Gy and ≥2 cycles of chemotherapy. Results: Of 78 Stage IVB (AJCC 8th ed.) patients, 36 met the pre-specified oligometastatic definition. Of these, 19 received definitive CRT, and 17 received palliative treatment. With a median follow-up of 16.5 months (Range: 2.3–95.0 months), median OS for definitive CRT and palliative groups were 90.2 and 8.1 months (p < 0.01), translating into 5-year OS of 50.5% (95%CI: 32.0–79.8%) vs. 7.5% (95%CI: 1.7–48.9%), respectively. Conclusions: Oligometastatic EC patients treated with definitive CRT benefited from that approach with survival rates (50.5%) that vastly exceeded historical standards of 5% at 5 years for metastatic EC. Oligometastatic EC patients treated with definitive CRT had significantly improved OS compared to those treated with palliative-only intent within our cohort. Notably, definitively treated patients were generally younger and with better performance status versus those palliatively treated. Further prospective evaluation of definitive CRT for oligometastatic EC is warranted

Development of a comprehensive cardiac atlas on a 1.5 Tesla Magnetic Resonance Linear Accelerator

Background and purpose: The 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL) provides an innovative modality for improved cardiac imaging when planning radiation treatment. No MRL based cardiac atlases currently exist, thus, we sought to comprehensively characterize cardiac substructures, including the conduction system, from cardiac images acquired using a 1.5 T MRL and provide contouring guidelines. Materials and methods: Five volunteers were enrolled in a prospective protocol (NCT03500081) and were imaged on the 1.5 T MRL with Half Fourier Single-Shot Turbo Spin-Echo (HASTE) and 3D Balanced Steady-State Free Precession (bSSFP) sequences in axial, short axis, and vertical long axis. Cardiac anatomy was contoured by (AS) and confirmed by a board certified cardiologist (JR) with expertise in cardiac MR imaging. Results: A total of five volunteers had images acquired with the HASTE sequence, with 21 contours created on each image. One of these volunteers had additional images obtained with 3D bSSFP sequences in the axial plane and additional images obtained with HASTE sequences in the key cardiac planes. Contouring guidelines were created and outlined. 15-16 contours were made for the short axis and vertical long axis. The cardiac conduction system was demonstrated with eleven representative contours. There was reasonable variation of contour volume across volunteers, with structures more clearly delineated on the 3D bSSFP sequence. Conclusions: We present a comprehensive cardiac atlas using novel images acquired prospectively on a 1.5 T MRL. This cardiac atlas provides a novel resource for radiation oncologists in delineating cardiac structures for treatment with radiotherapy, with special focus on the cardiac conduction system

Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis

Axonal degeneration is an important determinant of progressive neurological disability in multiple sclerosis (MS). Thus, therapeutic approaches promoting neuroprotection could aid the treatment of progressive MS. Here, we used what we believe is a novel water-soluble fullerene derivative (ABS-75) attached to an NMDA receptor antagonist, which combines antioxidant and anti-excitotoxic properties, to block axonal damage and reduce disease progression in a chronic progressive EAE model. Fullerene ABS-75 treatment initiated after disease onset reduced the clinical progression of chronic EAE in NOD mice immunized with myelin-oligodendrocyte glycoprotein (MOG). Reduced disease progression in ABS-75–treated mice was associated with reduced axonal loss and demyelination in the spinal cord. Fullerene ABS-75 halted oxidative injury, CD11b+ infiltration, and CCL2 expression in the spinal cord of mice without interfering with antigen-specific T cell responses. In vitro, fullerene ABS-75 protected neurons from oxidative and glutamate-induced injury and restored glutamine synthetase and glutamate transporter expression in astrocytes under inflammatory insult. Glutamine synthetase expression was also increased in the white matter of fullerene ABS-75–treated animals. Our data demonstrate the neuroprotective effect of treatment with a fullerene compound combined with a NMDA receptor antagonist, which may be useful in the treatment of progressive MS and other neurodegenerative diseases

Consensus Quality Measures and Dose Constraints for Lung Cancer from the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology (ASTRO) Expert Panel

INTRODUCTION: For patients with lung cancer, it is critical to provide evidence-based radiation therapy to ensure high quality care. The VA National Radiation Oncology Program (VA NROP) partnered with the American Society for Radiation Oncology (ASTRO) as part of the VA Radiation Oncology Quality Surveillance (VA ROQS) to develop lung cancer quality metrics and assess quality of care as a pilot program in 2016. Herein, we present recently updated consensus quality measures and dose-volume histogram (DVH) constraints. METHODS: A series of measures and performance standards were reviewed and developed by a Blue-Ribbon Panel of lung cancer experts in conjunction with ASTRO in 2022. As part of this initiative, quality, surveillance, and aspirational metrics were developed for a) Initial Consultation and Work Up, b) Simulation, Treatment Planning, and Treatment Delivery, and c) Follow Up. DVH metrics for target and organ at risk treatment planning dose constraints were also reviewed and defined. RESULTS: Altogether, a total of 19 lung cancer quality metrics were developed. There were 121 DVH constraints developed for various fractionation regimens including ultrahypofractionated (1,3,4,5 fraction[s]), hypofractionated (10 and 15 fractionations), and conventional fractionation (30-35 fractions). CONCLUSIONS: The devised measures will be implemented for quality surveillance for Veterans both inside and outside of the VA system, as well as provide a resource for lung cancer specific quality metrics. The recommended DVH constraints serve as a unique, comprehensive resource for evidence and expert-consensus based constraints across multiple fractionation schemas

Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Quality Measures Initiative

INTRODUCTION: Ensuring high quality, evidence-based radiation therapy for patients is of the upmost importance. As a part of the largest integrated health system in America, the Department of Veterans Affairs National Radiation Oncology Program (VA-NROP) established a quality surveillance initiative to address the challenge and necessity of providing the highest quality of care for veterans treated for cancer. METHODS: As part of this initiative, the VA-NROP contracted with the American Society for Radiation Oncology (ASTRO) to commission five Blue-Ribbon Panels for lung, prostate, rectal, breast, and head & neck cancers experts. This group worked collaboratively with the VA-NROP to develop consensus quality measures. In addition to the site-specific measures, an additional Blue-Ribbon Panel comprised of the chairs and other members of the disease sites was formed to create 18 harmonized quality measures for all five sites (13 quality, 4 surveillance, and 1 aspirational). CONCLUSION: The VA-NROP and ASTRO collaboration have created quality measures spanning five disease sites to help improve patient outcomes. These will be used for the ongoing quality surveillance of veterans receiving radiation therapy through the VA and its community partners. ETHICS BOARD APPROVAL: N/A - No human subjects were required