Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.

Body composition as a novel biomarker of recurrence risk in patients with triple-negative breast cancer.

Background And Hypothesis: Triple-negative breast cancer (TNBC) patients are at increased risk for recurrence compared to other subtypes of breast cancer. Previous evidence showed that adiposity may contribute to worsened cancer control. Current measures of obesity, such as body-mass index (BMI), are poor surrogates of adiposity, while visceral-to-subcutaneous adiposity ratio (VSR), which can be measured from routine computed tomography (CT) imaging, is a direct adiposity measure.

Feasibility and Tolerability of Adjuvant Capecitabine-Based Chemoradiation in Patients With Breast Cancer and Residual Disease After Neoadjuvant Chemotherapy: A Prospective Clinical Trial.

Purpose: Addition of adjuvant capecitabine improves overall survival for patients with breast cancer lacking pathologic complete response to standard-of-care neoadjuvant chemotherapy. Combining radiosensitizing capecitabine concurrent with radiation may further improve disease control, although the feasibility and tolerability of chemoradiation in this setting is unknown. This study aimed to determine the feasibility of this combination.

Robust biomarker discovery through multiplatform multiplex image analysis of breast cancer clinical cohorts.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and enable development of spatial biomarkers to predict patient response to immunotherapy and other therapeutics. However, spatial biomarker discovery is often carried out on a single patient cohort or imaging technology, limiting statistical power and increasing the likelihood of technical artifacts. In order to analyze multiple patient cohorts profiled on different platforms, we developed methods for comparative data analysis from three disparate multiplex imaging technologies: 1) cyclic immunofluorescence data we generated from 102 breast cancer patients with clinical follow-up, in addition to publicly available 2) imaging mass cytometry and 3) multiplex ion-beam imaging data.

Variation in Treatment Patterns of Patients with Early-Onset Gastric Cancer.

Background: Early-onset gastric cancer (EOGC), or gastric cancer in patients younger than 45 years old, is poorly understood and relatively uncommon. Similar to other gastrointestinal malignancies, the incidence of EOGC is rising in Western countries. It is unclear which populations experience a disproportionate burden of EOGC and what factors influence how patients with EOGC are treated.

ECOG-ACRIN Guideline for Contouring and Treatment of Early Stage Anal Cancer Using IMRT/IGRT.

Purpose: Previous anal cancer guidelines delineate target volumes similarly for all patients with squamous cell carcinoma of the anal canal and/or perianal skin (SCCA), regardless of disease stage. The purpose of this guideline is to provide customized radiation treatment recommendations for early stage (T1-2 N0 M0) anal cancer treated with intensity modulated and image guided radiation therapy (RT).

Methods And Materials: A contouring atlas and radiation treatment recommendations for the ongoing, randomized phase II trial of deintensified chemoradiation for early stage SCCA (EA2182) was created by an expert panel of radiation oncologists.

Trends in the Incidence and Treatment of Early-Onset Pancreatic Cancer.

Background: Early-onset pancreatic cancer (EOPC) is relatively uncommon. It is unclear if the incidence of EOPC is evolving and how these patients are treated.

Methods: We conducted a retrospective, population-based study using SEER 2004-2016.

Initial analysis of the dosimetric benefit and clinical resource cost of CBCT-based online adaptive radiotherapy for patients with cancers of the cervix or rectum.

Purpose: This provides a benchmark of dosimetric benefit and clinical cost of cone-beam CT-based online adaptive radiotherapy (ART) technology for cervical and rectal cancer patients.

Methods: An emulator of a CBCT-based online ART system was used to simulate more than 300 treatments for 13 cervical and 15 rectal cancer patients. CBCT images were used to generate adaptive replans.

Safety considerations with new treatment regimens for anal cancer.

: Anal cancer is a rare malignancy, but incidence rates are rising. Primary chemoradiation is the standard of care for early disease with surgery reserved for salvage. Despite success in terms of survival, patients suffer significant morbidity.

Early detection of SARS-CoV-2 from staging PET-CT.

Objective: SARS-CoV-2 infection may manifest with minimal or no clinical symptoms. However, signs of infection may appear on routine imaging obtained in the care of patients with cancer. The management of patients planned for chemoradiation with asymptomatic or mildly symptomatic SARS-CoV-2 infection is uncertain.

MRI-cytometry: Mapping nonparametric cell size distributions using diffusion MRI.

Purpose: This report introduces and validates a new diffusion MRI-based method, termed MRI-cytometry, which can noninvasively map intravoxel, nonparametric cell size distributions in tissues.

Methods: MRI was used to acquire diffusion MRI signals with a range of diffusion times and gradient factors, and a model was fit to these data to derive estimates of cell size distributions. We implemented a 2-step fitting method to avoid noise-induced artificial peaks and provide reliable estimates of tumor cell size distributions.

Quantitative Comparison of Prone and Supine PERCIST Measurements in Breast Cancer.

Positron emission tomography (PET) is typically performed in the supine position. However, breast magnetic resonance imaging (MRI) is performed in prone, as this improves visibility of deep breast tissues. With the emergence of hybrid scanners that integrate molecular information from PET and functional information from MRI, it is of great interest to determine if the prognostic utility of prone PET is equivalent to supine.

Combining Adjuvant Radiotherapy With Capecitabine in Chemotherapy-resistant Breast Cancer: Feasibility, Safety, and Toxicity.

Background: In a randomized trial (CREATE-X), patients with residual disease after standard neoadjuvant chemotherapy had improved survival with the addition of adjuvant capecitabine. For patients who required radiotherapy (RT), capecitabine was given sequentially. Concurrent capecitabine-RT might be more efficacious.

Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that does not respond to endocrine therapy or human epidermal growth factor receptor 2 (HER2)-targeted therapies. Individuals with TNBC experience higher rates of relapse and shorter overall survival compared to patients with receptor-positive breast cancer subtypes. Preclinical discoveries are needed to identify, develop, and advance new drug targets to improve outcomes for patients with TNBC.

Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204).

Background: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum.

Subjects, Materials, And Methods: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled.

Systemic Inflammation After Radiation Predicts Locoregional Recurrence, Progression, and Mortality in Stage II-III Triple-Negative Breast Cancer.

Purpose: Patients with triple-negative breast cancer experience high rates of recurrence after radiation, which may be facilitated by the recruitment of circulating tumor cells to proinflammatory microenvironments in the absence of lymphocytes. We hypothesized that patients with lymphopenia and elevated inflammatory hematologic markers after radiation therapy would have an increased risk of locoregional failure.

Methods And Materials: With approval, we retrospectively studied a cohort of women treated with adjuvant radiation therapy for stage II-III triple-negative breast cancer.

Magnetic resonance imaging of mean cell size in human breast tumors.

Purpose: Cell size is a fundamental characteristic of all tissues, and changes in cell size in cancer reflect tumor status and response to treatments, such as apoptosis and cell-cycle arrest. Unfortunately, cell size can currently be obtained only by pathological evaluation of tumor tissue samples obtained invasively. Previous imaging approaches are limited to preclinical MRI scanners or require relatively long acquisition times that are impractical for clinical imaging.

Pooled Analysis of external-beam RADiotherapy parameters in phase II and phase III trials in radiochemotherapy in Anal Cancer (PARADAC).

Purpose: Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer.

Materials And Methods: Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated.

National Cancer Institute (NCI) state of the science: Targeted radiosensitizers in colorectal cancer.

Colorectal cancer (CRC) represents a major public health problem as the second leading cause of cancer-related mortality in the United States. Of an estimated 140,000 newly diagnosed CRC cases in 2018, roughly one-third of these patients will have a primary tumor located in the distal large bowel or rectum. The current standard-of-care approach includes curative-intent surgery, often after preoperative (neoadjuvant) radiotherapy (RT), to increase rates of tumor down-staging, clinical and pathologic response, as well as improving surgical resection quality.

The Importance of Imaging in Radiation Oncology for National Clinical Trials Network Protocols.

Imaging is essential in successfully executing radiation therapy (RT) in oncology clinical trials. As technically sophisticated diagnostic imaging and RT were incorporated into trials, quality assurance in the National Clinical Trials Network groups entered a new era promoting image acquisition and review. Most trials involving RT require pre- and post-therapy imaging for target validation and outcome assessment.

IL-6 variant is associated with metastasis in breast cancer patients.

Introduction: Although tumor metastases remain significant drivers of mortality, the genetic factors that increase the risks of metastases are not fully identified. Interleukin 6 (IL-6) has emerged as an important factor in breast cancer progression with IL-6 single nucleotide polymorphism (SNP) variants shown to affect survival. We hypothesized that SNPs of the IL-6 promoter at rs1800795 in breast cancer patients are associated with distant metastases.

Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial.

Importance: The role of epidermal growth factor receptor (EGFR) inhibition in chemoradiation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain.

Objective: To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma.

Design, Setting, And Participants: A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus.

A phase I trial of concurrent sorafenib and stereotactic radiosurgery for patients with brain metastases.

We hypothesized that sorafenib (BAY 43-9006), an oral multi-kinase inhibitor, used in combination with SRS will improve overall intracranial control. This Phase I study assesses the safety, tolerability, and maximal tolerated dose of sorafenib administered with SRS to treat 1-4 brain metastases. This was an open label phase I dose escalation study with an expansion cohort.

A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy.

Triple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival.