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.

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.

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.

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.

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.

Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma.

Objectives: To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC).

Methods: 51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31 and CD105.

Assessment of Treatment Response With Diffusion-Weighted MRI and Dynamic Contrast-Enhanced MRI in Patients With Early-Stage Breast Cancer Treated With Single-Dose Preoperative Radiotherapy: Initial Results.

Single-dose preoperative stereotactic body radiotherapy is a novel radiotherapy technique for the early-stage breast cancer, and the treatment response pattern of this technique needs to be investigated on a quantitative basis. In this work, dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted magnetic resonance imaging were used to study the treatment response pattern in a unique cohort of patients with early-stage breast cancer treated with preoperative radiation. Fifteen female qualified patients received single-dose preoperative radiotherapy with 1 of the 3 prescription doses: 15 Gy, 18 Gy, and 21 Gy.

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers.

Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available.

A phase 1 trial of preoperative partial breast radiation therapy: Patient selection, target delineation, and dose delivery.

Purpose: Diffusion of accelerated partial breast irradiation into clinical practice is limited by the need for specialized equipment and training. The accessible external beam technique yields unacceptable complication rates, likely from large postoperative target volumes. We designed a phase 1 trial evaluating preoperative radiation therapy to the intact tumor using widely available technology.

Genomic profiling in locally advanced and inflammatory breast cancer and its link to DCE-MRI and overall survival.

Purpose: We have previously reported that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns obtained from locally advanced breast cancer (LABC) patients prior to neoadjuvant therapy predicted pathologic clinical response. Genomic analyses were also independently conducted on the same patient population. This retrospective study was performed to test two hypotheses: (1) gene expression profiles are associated with DCE-MRI perfusion patterns, and (2) association between long-term overall survival data and gene expression profiles can lead to the identification of novel predictive biomarkers.

Exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy.

Purpose: Radiation therapy is associated with acute treatment-related complications that can lead to decreased quality of life (QOL). Exercise has been shown in other cancer treatment settings to improve negative outcomes. We conducted a prospective pilot study to explore the association between exercise, patient-reported outcomes, and acute radiation therapy toxicities.

Dosimetric comparison of preoperative single-fraction partial breast radiotherapy techniques: 3D CRT, noncoplanar IMRT, coplanar IMRT, and VMAT.

The purpose of this study was to compare dosimetric parameters of treatment plans among four techniques for preoperative single-fraction partial breast radiotherapy in order to select an optimal treatment technique. The techniques evaluated were noncoplanar 3D conformal radiation therapy (3D CRT), noncoplanar intensity-modulated radiation therapy (IMRTNC), coplanar IMRT (IMRTCO), and volumetric-modulated arc therapy (VMAT). The planning CT scans of 16 patients in the prone position were used in this study, with the single-fraction prescription doses of 15 Gy for the first eight patients and 18 Gy for the remaining eight patients.

The use of adjuvant radiotherapy in elderly patients with early-stage breast cancer: changes in practice patterns after publication of Cancer and Leukemia Group B 9343.

Background: The Cancer and Leukemia Group B (CALGB) 9343 randomized phase 3 trial established lumpectomy and adjuvant therapy with tamoxifen alone, rather than both radiotherapy and tamoxifen, as a reasonable treatment course for women aged >70 years with clinical stage I (AJCC 7th edition), estrogen receptor-positive breast cancer. An analysis of the Surveillance, Epidemiology, and End Results (SEER) registry was undertaken to assess practice patterns before and after the publication of this landmark study.

Methods: The SEER database from 2000 to 2009 was used to identify 40,583 women aged ≥70 years who were treated with breast-conserving surgery for clinical stage I, estrogen receptor-positive and/or progesterone receptor-positive breast cancer.