NRG Oncology International Consensus Contouring Atlas on Target Volumes and Dosing Strategies for Dose-Escalated Pancreatic Cancer Radiation Therapy.

Purpose: Dose-escalated radiation therapy is increasingly used in the treatment of pancreatic cancer; however, approaches to target delineation vary widely. We present the first North American cooperative group consensus contouring atlas for dose-escalated pancreatic cancer radiation therapy.

Methods And Materials: An expert international panel comprising 15 radiation oncologists, 2 surgeons, and 1 radiologist was recruited.

Stereotactic body radiotherapy plus rucosopasem in locally advanced or borderline resectable pancreatic cancer: GRECO-2 phase II study design.

Ablative doses of stereotactic body radiotherapy (SBRT) may improve pancreatic cancer outcomes but may carry greater potential for gastrointestinal toxicity. Rucosopasem, an investigational selective dismutase mimetic that converts superoxide to hydrogen peroxide, can potentially increase tumor control of SBRT without compromising safety. GRECO-2 is a phase II, multicenter, randomized, double-blind, placebo-controlled trial of rucosopasem in combination with SBRT in locally advanced or borderline resectable pancreatic cancer.

AXL/WRNIP1 Mediates Replication Stress Response and Promotes Therapy Resistance and Metachronous Metastasis in HER2+ Breast Cancer.

Unlabelled: Therapy resistance and metastatic progression are primary causes of cancer-related mortality. Disseminated tumor cells possess adaptive traits that enable them to reprogram their metabolism, maintain stemness, and resist cell death, facilitating their persistence to drive recurrence. The survival of disseminated tumor cells also depends on their ability to modulate replication stress in response to therapy while colonizing inhospitable microenvironments.

Delta Radiomic Features Predict Resection Margin Status and Overall Survival in Neoadjuvant-Treated Pancreatic Cancer Patients.

Background: Neoadjuvant therapy (NAT) emerged as the standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgery; however, surgery is morbid, and tools to predict resection margin status (RMS) and prognosis in the preoperative setting are needed. Radiomic models, specifically delta radiomic features (DRFs), may provide insight into treatment dynamics to improve preoperative predictions.

Methods: We retrospectively collected clinical, pathological, and surgical data (patients with resectable, borderline, locally advanced, and metastatic disease), and pre/post-NAT contrast-enhanced computed tomography (CT) scans from PDAC patients at the University of Texas Southwestern Medical Center (UTSW; discovery) and Humanitas Hospital (validation cohort).

Stereotactic body radiotherapy with or without selective dismutase mimetic in pancreatic adenocarcinoma: an adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial.

Background: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma.

Simultaneous selection of nanobodies for accessible epitopes on immune cells in the tumor microenvironment.

In the rapidly advancing field of synthetic biology, there exists a critical need for technology to discover targeting moieties for therapeutic biologics. Here we present INSPIRE-seq, an approach that utilizes a nanobody library and next-generation sequencing to identify nanobodies selected for complex environments. INSPIRE-seq enables the parallel enrichment of immune cell-binding nanobodies that penetrate the tumor microenvironment.

Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century.

The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g.

Ablative Radiation Therapy in Oligometastatic Pancreatic Cancer to Delay Polyprogression, Limit Chemotherapy, and Improve Outcomes.

Purpose: The oligometastatic state is observed in patients across many malignancies, with increased recognition regarding improved outcomes after local therapies. However, there is limited data specifically regarding pancreatic ductal adenocarcinoma. We hypothesized that an oligometastatic pancreatic ductal adenocarcinoma (OPanc) phenotype would benefit from stereotactic ablative radiation therapy (SABR) to all active metastatic sites.

Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) in Preclinical Models Enhances Single-Agent Immune Checkpoint Blockade.

Purpose: Harnessing the immune-stimulatory effects of radiation by combining it with immunotherapy is a promising new treatment strategy. However, more studies characterizing immunotherapy and radiation dose scheduling for the optimal therapeutic effect is essential for designing clinical trials.

Methods And Materials: A new ablative radiation dosing scheme, personalized ultrafractionated stereotactic adaptive radiation therapy (PULSAR), was tested in combination with α-PD-L1 therapy in immune-activated and resistant syngeneic immunocompetent mouse models of cancer.

Patterns of Dose Escalation Among Patients With Esophageal Cancer Undergoing Definitive Radiation Therapy: 2006-2016.

Purpose: Although single-institution series suggest potential benefit to dose escalation in definitive radiation therapy for esophageal cancer, randomized trials including intergroup-0123 and the recently presented A Randomized Trial of Dose Escalation in definitive Chemoradiotherapy for patients with Oesophageal cancer (ARTDECO) trial showed no improvement in outcomes with higher radiation therapy dose. As such, there may be significant variation in radiation dose for definitive treatment of esophageal cancer.

Methods And Materials: The National Cancer Database was used to identify patients who received a diagnosis of nonmetastatic T2+ esophageal cancer between 2006 and 2016 who did not receive definitive surgery and were treated with chemotherapy and radiation therapy doses between 41.

Trends and Factors Associated With Receipt of Upfront Surgery for Stage II to III Rectal Adenocarcinoma in the United States, 2006 to 2016.

Introduction: The German rectal study published in 2004 established neoadjuvant chemoradiation as a standard of care for locally advanced rectal cancer and current National Comprehensive Cancer Network guidelines endorse several preoperative regimens. Upfront surgery, however, is considered substandard care. In the era of evolving treatment paradigms for locally advanced rectal cancer, we sought to assess trends and predictors of receipt of upfront surgery for stage II to III rectal cancer.

Disparities in Characteristics, Access to Care, and Oncologic Outcomes in Young-Onset Colorectal Cancer at a Safety-Net Hospital.

Purpose: Young-onset colorectal cancer is an emerging cause of significant morbidity and mortality globally. Despite this, limited data exist regarding clinical characteristics and outcomes, particularly in safety-net populations where access to care is limited. We aimed to study disparities in clinical characteristics and outcomes in patients with young-onset colorectal cancer in the safety-net setting.

Long-Term Results of a Phase 1 Dose-Escalation Trial and Subsequent Institutional Experience of Single-Fraction Stereotactic Ablative Radiation Therapy for Liver Metastases.

Purpose: We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study.

Methods And Materials: Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive <9.

Targeting TAM to Tame Pancreatic Cancer.

Pancreatic cancer is expected to become the second leading cause of cancer-related death within the next few years. Current therapeutic strategies have limited effectiveness and therefore there is an urgency to develop novel effective therapies. The receptor tyrosine kinase subfamily TAM (Tyro3, Axl, MerTK) is directly implicated in the pathogenesis of the metastatic, chemoresistant, and immunosuppressive phenotype in pancreatic cancer.

Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016.

Background: When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC.

Cancer-Associated Fibroblasts: Versatile Players in the Tumor Microenvironment.

Cancer-associated fibroblasts (CAFs) are indispensable architects of the tumor microenvironment. They perform the essential functions of extracellular matrix deposition, stromal remodeling, tumor vasculature modulation, modification of tumor metabolism, and participation in crosstalk between cancer and immune cells. In this review, we discuss our current understanding of the principal differences between normal fibroblasts and CAFs, the origin of CAFs, their functions, and ultimately, highlight the intimate connection of CAFs to virtually all of the hallmarks of cancer.

Distinct Clinical Characteristics in Young-Onset Pancreatic Neuroendocrine Tumor.

Background: We aimed to study the effect of socioeconomic differences and molecular characteristics on survival in patients with young-onset pancreatic neuroendocrine tumors (YOPNET) and typical-onset PNET (TOPNET).

Methods: We identified the patients with YOPNET (<50 years) and TOPNET (≥50 years) who underwent definitive surgery diagnosed between 2004 and 2016 using the National Cancer Database. We evaluated overall survival (OS) using the Kaplan-Meier and Cox regression methods before and after propensity score matching.

Racial Disparities in Time to Treatment Initiation and Outcomes for Early Stage Anal Squamous Cell Carcinoma.

Objectives: Although cure rates for early stage anal squamous cell cancer (ASCC) are overall high, there may be racial disparities in receipt of treatment and outcome precluding favorable outcomes across all patient demographics. Therefore, the authors aimed to assess the time to treatment initiation and overall survival (OS) in Black and White patients receiving definitive chemoradiation for early stage ASCC.

Materials And Methods: The authors identified patients diagnosed with early stage (stage I-II) ASCC and treated with chemoradiation diagnosed between 2004 and 2016 in the National Cancer Database.

Feasibility and Outcome of Routine Use of Concurrent Chemoradiation in HIV-positive Patients With Squamous Cell Anal Cancer.

Objectives: Clinical concerns about hematologic toxicities in human immunodeficiency virus (HIV)+ patients with squamous cell anal cancer (SCAC) may lead to de-escalation of treatment intensity. The objective of this study is to evaluate clinical outcomes including toxicity following standard concurrent curative-intent chemoradiation for HIV+ and HIV- patients with SCAC.

Materials And Methods: Among 97 evaluable patients treated between 2009 and 2016 (median age 52.

Recent Trends and Overall Survival of Young Versus Older Adults With Stage II to III Rectal Cancer Treated With and Without Surgery in the United States, 2010-2015.

Background: The omission of surgery via nonoperative management (NOM) for rectal cancer may be increasing, and this strategy could be particularly attractive for younger patients, whose incidence of rectal cancer has been rising. We sought to assess trends in NOM in young (younger than 55 y) versus older adult (55 y and older) rectal cancer cohorts.

Methods: The National Cancer Database was used to identify patients diagnosed with stage II to III rectal cancer between 2010 and 2015.

Stage-specific Conditional Survival Among Young (Age Below 50 y) Versus Older (Age 50 y and Above) Adults With Colorectal Cancer in the United States.

Background: Conditional survival (CS) is a relevant prognostic measure and may be particularly important for young adult patients with colorectal cancer (CRC), whose incidence is rising. We sought to compare CS among young versus older adults with CRC.

Methods: Patients diagnosed with CRC between 2004 and 2010 were identified from the Surveillance, Epidemiology, and End Results registry.

Patterns of Care for Stage II-III Rectosigmoid Cancers in the United States, 2004-2015.

Objectives: Although current guidelines continue to recommend trimodality therapy for stage II to III rectal cancers, a lower incidence of local recurrence has been observed in patients with upper rectal tumors, including those in the rectosigmoid. In practice, patients with upper rectal tumors may not be receiving all 3 modalities of therapy. Patterns of care for patients with rectosigmoid cancers have not previously been described.

Induced Tumor Heterogeneity Reveals Factors Informing Radiation and Immunotherapy Combinations.

Purpose: To investigate how induced tumor heterogeneity influences immune responses to radiotherapy with different proportions of mixed immune-responsive and unresponsive tumor cells in a triple-negative breast cancer model. It is hypothesized that studying the immune environment of mixed tumors and responses to radiotherapy could nominate immune active therapies to enhance immune responses after radiotherapy.

Experimental Design: Evaluate efficacy and immune responses generated by radiotherapy in tumors with different proportions of immunologically responsive and unresponsive tumor cells.

Galectin-1-driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance.

Immune checkpoint inhibitors (ICIs), although promising, have variable benefit in head and neck cancer (HNC). We noted that tumor galectin-1 (Gal1) levels were inversely correlated with treatment response and survival in patients with HNC who were treated with ICIs. Using multiple HNC mouse models, we show that tumor-secreted Gal1 mediates immune evasion by preventing T cell migration into the tumor.

Sociodemographic Disparities in the Receipt of Adjuvant Chemotherapy Among Patients With Resected Stage I-III Pancreatic Adenocarcinoma.

Background: Adjuvant therapy for resected pancreatic adenocarcinoma was given a category 1 NCCN recommendation in 2000, yet many patients do not receive chemotherapy after definitive surgery. Whether sociodemographic disparities exist for receipt of adjuvant chemotherapy is poorly understood.

Methods: The National Cancer Database was used to identify patients diagnosed with nonmetastatic pancreatic adenocarcinoma who underwent definitive surgery from 2004 through 2015.