Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer.

Background And Objective: Trilaciclib is a cyclin-dependent kinase 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients with extensive-stage small-cell lung cancer. Trilaciclib is a substrate and time-dependent inhibitor of cytochrome P450 3A4 and an inhibitor of multidrug and toxin extrusion 1, multidrug and toxin extrusion 2-K, organic cation transporter 1, and organic cation transporter 2. Here, we investigate the pharmacokinetic drug-drug interaction potential of trilaciclib.

Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study.

Purpose: We report final antitumor efficacy results from a phase II study of trilaciclib, an intravenous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, administered prior to gemcitabine plus carboplatin (GCb) in patients with metastatic triple-negative breast cancer (NCT02978716).

Patients And Methods: Patients were randomized (1:1:1) to group 1 [GCb (days 1, 8); n = 34], group 2 [trilaciclib prior to GCb (days 1, 8); n = 33], or group 3 [trilaciclib (days 1, 8) and trilaciclib prior to GCb (days 2, 9); n = 35]. Subgroup analyses were performed according to CDK4/6 dependence, level of programmed death-ligand 1 (PD-L1) expression, and RNA-based immune signatures using proportional hazards regression.

Management of the Axilla in Early-Stage Breast Cancer: Ontario Health (Cancer Care Ontario) and ASCO Guideline.

Purpose: To provide recommendations on the best strategies for the management and on the best timing and treatment (surgical and radiotherapeutic) of the axilla for patients with early-stage breast cancer.

Methods: Ontario Health (Cancer Care Ontario) and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature.

Results: This guideline endorsed two recommendations of the ASCO 2017 guideline for the use of sentinel lymph node biopsy in patients with early-stage breast cancer and expanded on that guideline with recommendations for radiotherapy interventions, timing of staging after neoadjuvant chemotherapy (NAC), and mapping modalities.

Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer.

Chemotherapy-induced myelosuppression is an acute, dose-limiting toxicity of chemotherapy regimens used in the treatment of extensive-stage small cell lung cancer (ES-SCLC). Trilaciclib protects haematopoietic stem and progenitor cells from chemotherapy-induced damage (myeloprotection). To assess the totality of the myeloprotective benefits of trilaciclib, including analysis of several clinically relevant but low-frequency events, an exploratory composite endpoint comprising five major adverse haematological events (MAHE) was prospectively defined: all-cause hospitalisations, all-cause chemotherapy dose reductions, febrile neutropenia (FN), prolonged severe neutropenia (SN) and red blood cell (RBC) transfusions on/after Week 5.

Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial.

Importance: Stereotactic body radiotherapy (SBRT) for oligometastases is hypothesized to improve survival and is increasingly used. Little evidence supports its safe use to treat patients with multiple metastases.

Objective: To establish safety of SBRT dose schedules in patients with 3 to 4 metastases or 2 metastases in close proximity to each other.

Accuracy and efficiency of image-guided radiation therapy (IGRT) for preoperative partial breast radiosurgery.

Objective: To analyze and evaluate accuracy and efficiency of IGRT process for preoperative partial breast radiosurgery.

Methods: Patients were initially setup with skin marks and 5 steps were performed: (1) Initial orthogonal 2D kV images, (2) pre-treatment 3D CBCT images, (3) verification orthogonal 2D kV images, (4) treatment including mid-treatment 2D kV images (for the final 15 patients only), and (5) post-treatment orthogonal 2D kV or 3D CBCT images. Patient position was corrected at each step to align the biopsy clip and to verify surrounding soft tissue positioning.

Automatic Planning of Whole Breast Radiation Therapy Using Machine Learning Models.

To develop an automatic treatment planning system for whole breast radiation therapy (WBRT) based on two intensity-modulated tangential fields, enabling near-real-time planning. A total of 40 WBRT plans from a single institution were included in this study under IRB approval. Twenty WBRT plans, 10 with single energy (SE, 6MV) and 10 with mixed energy (ME, 6/15MV), were randomly selected as training dataset to develop the methodology for automatic planning.

Lessons Learned From Hurricane Maria in Puerto Rico: Practical Measures to Mitigate the Impact of a Catastrophic Natural Disaster on Radiation Oncology Patients.

Purpose: Although the wind, rain, and flooding of Hurricane Maria in Puerto Rico abated shortly after its landfall on September 20, 2017, the disruption of the electrical, communications, transportation, and medical infrastructure of the island was unprecedented in scope and caused lasting harm for many months afterward. A compilation of recommendations from radiation oncologists who were in Puerto Rico during the disaster, and from a panel of American Society for Radiation Oncology (ASTRO) cancer experts was created.

Methods And Materials: Radiation oncologists throughout Puerto Rico collaborated and improvised to continue treating patients in the immediate aftermath of the storm and as routine clinical operations were restored gradually.

Findings on Surveillance Imaging After Preoperative Partial Breast Irradiation for Early Stage Breast Cancer.

Purpose: To evaluate the mammographic sequelae of preoperative accelerated partial breast irradiation (APBI) delivered via either stereotactic radiosurgery or a conventionally fractionated regimen.

Methods And Materials: This multicenter, retrospective study evaluated surveillance mammograms from patients enrolled in 2 prospective, preoperative APBI clinical trials. At 1 site, 31 patients with cT1N0 invasive carcinomas or low- or intermediate-grade ductal carcinoma in situ (<2 cm) received preoperative stereotactic radiosurgery and had a total of 186 mammograms available for review.

Treatment constraints for single dose external beam preoperative partial breast irradiation in early-stage breast cancer.

Background: Following breast-conserving surgery and post-operative 3D-conformal accelerated partial breast irradiation (APBI), suboptimal cosmetic results have been reported. Preoperative radiation delivery to the intact tumor enables better target visualization and treatment volume reduction. Single dose preoperative APBI has the potential to improve toxicity profiles, reduce treatment burden and enable in vivo exploration of breast cancer radiogenomics.

Concurrent Veliparib With Chest Wall and Nodal Radiotherapy in Patients With Inflammatory or Locoregionally Recurrent Breast Cancer: The TBCRC 024 Phase I Multicenter Study.

Purpose Locoregional control for inflammatory breast cancers and chest wall recurrences is suboptimal, which has motivated interest in radiosensitization to intensify therapy. Preclinical studies have suggested a favorable therapeutic index when poly (ADP-ribose) polymerase inhibitors are used as radiosensitizers; clinical investigation is necessary to establish appropriate dosing and confirm safety. Patients and Methods We conducted a multi-institutional phase I study of veliparib and concurrent radiotherapy (RT) to the chest wall and regional lymph nodes in 30 patients with inflammatory or locally recurrent breast cancer after complete surgical resection.

Blocking Interleukin (IL)4- and IL13-Mediated Phosphorylation of STAT6 (Tyr641) Decreases M2 Polarization of Macrophages and Protects Against Macrophage-Mediated Radioresistance of Inflammatory Breast Cancer.

Purpose: To determine the role of macrophage polarization on the response of inflammatory breast cancer (IBC) cells to radiation and whether modulation of macrophage plasticity can alter radiation response.

Methods And Materials: The human THP-1 monocyte cell line and primary human monocytes isolated from peripheral blood mononuclear cells were differentiated into macrophages and polarized to either an "antitumor" (M1) or a "protumor" (M2) phenotype. These polarized macrophages were co-cultured with IBC cells (SUM149, KPL4, MDA-IBC3, or SUM190) without direct contact for 24 hours, then subjected to irradiation (0, 2, 4, or 6 Gy).

Breast Cancer Biology: Clinical Implications for Breast Radiation Therapy.

Historically, prognosis and treatment decision making for breast cancer patients have been dictated by the anatomic extent of tumor spread. However, in recent years, "breast cancer" has proven to be a collection of unique phenotypes with distinct prognoses, patterns of failure, and treatment responses. Recent advances in biologically based assays and targeted therapies designed to exploit these unique phenotypes have profoundly altered systemic therapy practice patterns and treatment outcomes.

Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.

Breast cancer is the most common malignancy diagnosed among women and represents a heterogeneous group of subtypes. Radiation therapy is a critical component of treatment for breast cancer patients. However, little is known about radiation response among these intrinsic subtypes.

Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer.

Introduction: Breast cancer treatment costs are rising, and identification of high-value oncology treatment strategies is increasingly needed. We sought to determine the potential cost savings associated with an evidence-based radiation treatment (RT) approach among women with early-stage breast cancer treated in the United States.

Patients And Methods: Using the National Cancer Database, we identified women with T1-T2 N0 invasive breast cancers treated with lumpectomy during 2011.

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma in Situ.

Purpose: Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation.

Methods And Materials: A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus.

Results: Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS.

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ.

Background Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT). Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. Results Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS.

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma In Situ.

Purpose: Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation.

Methods: A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7,883 patients and other published literature as the evidence base for consensus.

Results: Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS.

Intensified Local Resource Mobilization for the Polio Eradication Initiative: The Experience of World Health Organization in Nigeria During 2008-2015.

Background: Since the World Health Assembly (WHA) resolved in 1988 to eradicate poliovirus, several rounds of immunization campaigns have been conducted by member states. By 2000, with the support of the Global Polio Eradication Initiative (GPEI) partners, the number of polio cases decreased by 99%. Eradicating the remaining 1% proved to be more challenging.

Strategic Engagement of Technical Surge Capacity for Intensified Polio Eradication Initiative in Nigeria, 2012-2015.

Background: Following the 65th World Health Assembly (WHA) resolution on intensification of the Global Poliomyelitis Eradication Initiative (GPEI), the Nigerian government, with support from the World Health Organization (WHO) and other partners, implemented a number of innovative strategies to curb the transmission of wild poliovirus (WPV) in the country. One of the innovations successfully implemented since mid 2012 is the WHO's engagement of surge capacity personnel.

Methods: The WHO reorganized its functional structure, adopted a transparent recruitment and deployment process, provided focused technical and management training, and applied systematic accountability framework to successfully manage the surge capacity project in close collaboration with the national counterparts and partners.

FAS Death Receptor: A Breast Cancer Subtype-Specific Radiation Response Biomarker and Potential Therapeutic Target.

Although a standardized approach to radiotherapy has been used to treat breast cancer, regardless of subtype (e.g., luminal, basal), recent clinical data suggest that radiation response may vary significantly among subtypes.