PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

Purpose: To assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer.

Materials And Methods: A phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC).

Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis.

Background & Aims: The liver is a common site of cancer metastasis, most commonly from colorectal cancer, and primary liver cancers that have metastasized are associated with poor outcomes. The underlying mechanisms by which the liver defends against these processes are largely unknown. Prohibitin 1 (PHB1) and methionine adenosyltransferase 1A (MAT1A) are highly expressed in the liver.

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial.

Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes.

Association of x-ray velocimetry (XV) ventilation analysis compared to spirometry.

Introduction: X-ray Velocimetry (XV) ventilation analysis is a 4-dimensional imaging-based method for quantifying regional ventilation, aiding in the assessment of lung function. We examined the performance characteristics of XV ventilation analysis by examining correlation to spirometry and measurement repeatability.

Methods: XV analysis was assessed in 27 patients receiving thoracic radiotherapy for non-lung cancer malignancies.

Updates on radiotherapy-immunotherapy combinations: Proceedings of 6 annual ImmunoRad conference.

Focal radiation therapy (RT) has attracted considerable attention as a combinatorial partner for immunotherapy (IT), largely reflecting a well-defined, predictable safety profile and at least some potential for immunostimulation. However, only a few RT-IT combinations have been tested successfully in patients with cancer, highlighting the urgent need for an improved understanding of the interaction between RT and IT in both preclinical and clinical scenarios. Every year since 2016, ImmunoRad gathers experts working at the interface between RT and IT to provide a forum for education and discussion, with the ultimate goal of fostering progress in the field at both preclinical and clinical levels.

Chronic antigen in solid tumors drives a distinct program of T cell residence.

Analyses of healthy tissue reveal signatures that identify resident memory CD8 T cells (T), which survey tissues without recirculating. The density of T phenotype cells within solid tumors correlates favorably with prognosis, suggesting that intratumoral residents control cancer. However, residence has not been directly tested, and intratumoral T phenotype cells could instead reflect aspects of the microenvironment that correlate with prognosis.

Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.

Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control.

Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases.

Design, Setting, And Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups.

A Single-Institution Retrospective Study of Three-Fraction HDR Accelerated Partial Breast Irradiation.

Purpose: Accelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy is a standard of care treatment typically delivered over 10 fractions. The TRIUMPH-T multi-institutional study recently demonstrated promising results using a shorter three fraction regimen, however there are limited additional published series using this regimen. Here, we report our experience and outcomes for patients treated as per the TRIUMPH-T regimen.

Activated T cell therapy targeting glioblastoma cancer stem cells.

Naïve T cells become effector T cells following stimulation by antigen-loaded dendritic cells (DCs) and sequential cytokine activation. We aimed to develop procedures to efficiently activate T cells with tumor-associated antigens (TAAs) to glioblastoma (GBM) stem cells. To remove antigen presentation outside of the immunosuppressive tumor milieu, three different glioma stem cell (GSC) specific antigen sources to load DCs were compared in their ability to stimulate lymphocytes.

miR766-3p and miR124-3p Dictate Drug Resistance and Clinical Outcome in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with poor prognosis, which is mainly due to drug resistance. The biology determining the response to chemo-radiotherapy in HNSCC is poorly understood. Using clinical samples, we found that miR124-3p and miR766-3p are overexpressed in chemo-radiotherapy-resistant (non-responder) HNSCC, as compared to responder tumors.

Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity.

The standard of care is unsuccessful to treat recurrent and aggressive soft-tissue sarcomas. Interventions aimed at targeting components of the tumor microenvironment have shown promise for many solid tumors yet have been only marginally tested for sarcoma, partly because knowledge of the sarcoma microenvironment composition is limited. We employ single-cell RNA sequencing to characterize the immune composition of an undifferentiated pleiomorphic sarcoma mouse model, showing that macrophages in the sarcoma mass exhibit distinct activation states.

Quantitative Nodal Burden and Mortality Across Solid Cancers.

Background: Nodal staging systems vary substantially across solid tumors, implying heterogeneity in the behavior of nodal variables in various contexts. We hypothesized, in contradiction to this, that metastatic lymph node (LN) number is a universal and dominant predictor of outcome across solid tumors.

Methods: We performed a retrospective cohort analysis of 1 304 498 patients in the National Cancer Database undergoing surgery between 2004 and 2015 across 16 solid cancer sites.

Novel potent azetidine-based compounds irreversibly inhibit Stat3 activation and induce antitumor response against human breast tumor growth in vivo.

Signal transducer and activator of transcription (Stat)3 is a valid anticancer therapeutic target. We have discovered a highly potent chemotype that amplifies the Stat3-inhibitory activity of lead compounds to levels previously unseen. The azetidine-based compounds, including H172 (9f) and H182, irreversibly bind to Stat3 and selectively inhibit Stat3 activity (IC 0.

A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma.

Purpose: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line.

Patients And Methods: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts.

Comparative Proteomic Analysis of HPV(+) Oropharyngeal Squamous Cell Carcinoma Recurrence.

Deintensification therapy for human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV(+) OPSCC) is under active investigation. An adaptive treatment approach based on molecular stratification could identify high-risk patients predisposed to recurrence and better select for appropriate treatment regimens. Collectively, 40 HPV(+) OPSCC FFPE samples (20 disease-free, 20 recurrent) were surveyed using mass spectrometry-based proteomic analysis via data-independent acquisition to obtain fold change and false discovery differences.

Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy.

Studies suggest that the efficacy of cancer chemotherapy and immunotherapy is influenced by intestinal bacteria. However, the influence of the microbiome on radiation therapy is not as well understood, and the microbiome comprises more than bacteria. Here, we find that intestinal fungi regulate antitumor immune responses following radiation in mouse models of breast cancer and melanoma and that fungi and bacteria have opposite influences on these responses.

HER2 Activation and Endocrine Treatment Resistance in HER2-negative Breast Cancer.

The lethality of estrogen receptor alpha positive (ER+) breast cancer, which is often considered to have better prognosis than other subtypes, is defined by resistance to the standard of care endocrine treatment. Relapse and metastasis are inevitable in almost every patient whose cancer is resistant to endocrine treatment. Therefore, understanding the underlying causes of treatment resistance remains an important biological and clinical focus of research in this area.

A chemokine regulatory loop induces cholesterol synthesis in lung-colonizing triple-negative breast cancer cells to fuel metastatic growth.

Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites.

Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose?

Recent evidence indicates that ionizing radiation can enhance immune responses to tumors. Advances in radiation delivery techniques allow hypofractionated delivery of conformal radiotherapy. Hypofractionation or other modifications of standard fractionation may improve radiation's ability to promote immune responses to tumors.

Advances in Combining Radiation and Immunotherapy in Breast Cancer.

Breast irradiation has long been utilized in the adjuvant or metastatic setting to eliminate microscopic disease or to palliate existing disease, respectively. However, preclinical data have demonstrated that radiation can also alter the tumor microenvironment and induce antitumor immune responses. As a result, multiple clinical studies have been undertaken and have reported synergy between radiation and immune checkpoint blockade across various cancer types.

Five-dimensional quantitative low-dose Multitasking dynamic contrast- enhanced MRI: Preliminary study on breast cancer.

Purpose: To develop a low-dose Multitasking DCE technique (LD-MT-DCE) for breast imaging, enabling dynamic T mapping-based quantitative characterization of tumor blood flow and vascular properties with whole-breast coverage, a spatial resolution of 0.9 × 0.9 × 1.

Variations in the association of grade with survival across the head and neck cancer landscape.

Background: Although pathologic tumor grade is a well-established prognostic risk factor that impacts staging and treatment decisions across multiple cancer types, its role in head and neck squamous cell carcinoma (HNSCC) is less certain.

Methods: HNSCC patients diagnosed from 2010 to 2015 and undergoing primary surgery in the National Cancer Data Base were identified. Propensity score matching and multivariable Cox regression were performed.

Comparison of Survival After Transoral Robotic Surgery vs Nonrobotic Surgery in Patients With Early-Stage Oropharyngeal Squamous Cell Carcinoma.

Importance: Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data.

Objective: To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer.

Design, Setting, And Participants: A retrospective cohort comparative effectiveness analysis was performed of patients in the National Cancer Database with clinical T1 and T2 oropharyngeal squamous cell carcinoma diagnosed between January 1, 2010, and December 31, 2015, who underwent definitive robotic and nonrobotic surgery.