Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers.

Background: Breast and prostate tumors are known to be less responsive to immune checkpoint inhibitors (ICIs). Tissue-based tumor mutation burden (tTMB) has emerged as a predictive biomarker of response to ICIs, including in these "cold tumors". In clinical practice, when tTMB is not available, blood-based TMB score (bTMB) can be used to consider treatment with ICIs.

Machine Vision-Detected Peritumoral Lymphocytic Aggregates Are Associated With Disease-Free Survival in Patients With Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer, with a disease recurrence rate of around 20%. Lymphoid formations, which occur in nonlymphoid tissues during chronic inflammatory, infectious, and immune responses, have been linked with tumor suppression. Lymphoid aggregates potentially enhance the body's antitumor response, offering an avenue for attracting tumor-infiltrating lymphocytes and fostering their coordination.

A novel computational pathology approach for identifying gene signatures prognostic of disease-free survival for papillary thyroid carcinomas.

Introduction: Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer, with the classical and follicular variants representing most cases. Despite generally favorable prognoses, approximately 10% of patients experience recurrence post-surgery and radioactive iodine therapy. Attempts to stratify risk of recurrence have relied on gene expression-based prognostic and predictive signatures with a focus on mutations of well-known driver genes, while hallmarks of tumor morphology have been ignored.

Image analysis Uncovers associations between immune landscape, collagen structure, and neoadjuvant chemotherapy in high-grade serous ovarian carcinomas.

Background: The changes in the tumor microenvironment of high-grade serous ovarian carcinomas following neoadjuvant chemotherapy are a complex area of study. Previous research underscores the importance of investigating the immune and collagen components within the tumor microenvironment for prognostic implications.

Methods: In this study, we utilized computational pathology techniques with Hematoxylin and Eosin-stained images to quantitatively characterize the immune and collagen architecture within the tumor microenvironment of patients with high-grade serous ovarian carcinoma.

A Pilot Trial of Proton-Based Cardiac Sparing Accelerated Fractionated Radiation Therapy in Unresectable Non-small Cell Lung Cancer With Extended Durvalumab Therapy (PARTICLE-D).

Purpose: Concurrent chemoradiation therapy is the current nonsurgical standard of care for locally advanced non-small cell lung cancer. However, this is a difficult regimen to tolerate, especially for those who are elderly, have multiple comorbidities, or have poor performance status. Alternative treatment regimens are needed for this vulnerable population.

A prognostic and predictive computational pathology immune signature for ductal carcinoma in situ: retrospective results from a cohort within the UK/ANZ DCIS trial.

Background: The density of tumour-infiltrating lymphocytes (TILs) could be prognostic in ductal carcinoma in situ (DCIS). However, manual TIL quantification is time-consuming and suffers from interobserver and intraobserver variability. In this study, we developed a TIL-based computational pathology biomarker and evaluated its association with the risk of recurrence and benefit of adjuvant treatment in a clinical trial cohort.

Haplo-cord transplant. Realizing the potential of umbilical cord blood grafts. - A review of techniques and analysis of outcomes.

The combination of cord blood transplant with progenitor cells from partially HLA-matched adult donors has been used over the past two decades. In Europe and the US the adult donor graft is CD34 selected and provides early hematopoiesis, but durable engraftment derives from the cord blood graft . Neutrophil recovery is prompt and rates of acute and chronic GVHD are low.

Outcomes of initial therapy for synchronous brain metastases from small cell lung cancer: a single-institution retrospective analysis.

Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases at the time of initial SCLC diagnosis. A total of 107 SCLC patients with synchronous brain metastases treated at a single institution were included in this retrospective analysis.

Deep learning reveals lung shape differences on baseline chest CT between mild and severe COVID-19: A multi-site retrospective study.

Severe COVID-19 can lead to extensive lung disease causing lung architectural distortion. In this study we employed machine learning and statistical atlas-based approaches to explore possible changes in lung shape among COVID-19 patients and evaluated whether the extent of these changes was associated with COVID-19 severity. On a large multi-institutional dataset (N = 3443), three different populations were defined; a) healthy (no COVID-19), b) mild COVID-19 (no ventilator required), c) severe COVID-19 (ventilator required), and the presence of lung shape differences between them were explored using baseline chest CT.

Computational Pathology Assessments of Cardiac Stromal Remodeling: Clinical Correlates and Prognostic Implications in Heart Transplantation.

Both overt and indolent inflammatory insults in heart transplantation can accelerate pathologic cardiac remodeling, but there are few tools for monitoring the speed and severity of remodeling over time. To address this need, we developed an automated computational pathology system to measure pathologic remodeling in transplant biopsy samples in a large, retrospective cohort of n=2167 digitized heart transplant biopsy slides. Biopsy images were analyzed to identify the pathologic stromal changes associated with future allograft loss or advanced allograft vasculopathy.

Interpretable deep learning insights: Unveiling the role of 1 Gy volume on lymphopenia after radiotherapy in breast cancer.

Background: Lymphopenia is known for its significance on poor survivals in breast cancer patients. Considering full dosimetric data, this study aimed to develop and validate predictive models for lymphopenia after radiotherapy (RT) in breast cancer.

Material And Methods: Patients with breast cancer treated with adjuvant RT were eligible in this multicenter study.

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics.

Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density).

Patients on Antithrombotic Agents with Small Bowel Bleeding -Yield of Small Bowel Capsule Endoscopy and Subsequent Management.

Background And Aims: Small bowel gastrointestinal bleeding (GIB) is associated with multiple blood transfusions, prolonged and/or multiple hospital admissions, utilization of significant healthcare resources, and negative effects on patient quality of life. There is a well-recognized association between antithrombotic medications and small bowel GIB. We aimed to identify the diagnostic yield of small bowel capsule endoscopy (SBCE) in patients on antithrombotic medications and the impact of SBCE on treatment course.

Neoadjuvant Dual Checkpoint Inhibitors vs Anti-PD1 Therapy in High-Risk Resectable Melanoma: A Pooled Analysis.

Importance: Despite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known.

Objective: To compare the safety and efficacy of dual checkpoint inhibitors with anti-programmed cell death protein-1 (anti-PD1) therapy in a neoadjuvant setting among patients with HRRM.

Design, Setting, And Participants: In this pooled analysis of clinical trials, studies were selected provided they investigated immune checkpoint inhibitor treatment, were published between January 2018 and March 2023, and were phase 1, 2, or 3 clinical trials.

Failing to Make the Grade: Conventional Cardiac Allograft Rejection Grading Criteria Are Inadequate for Predicting Rejection Severity.

Background: Cardiac allograft rejection is the leading cause of early graft failure and is a major focus of postheart transplant patient care. While histological grading of endomyocardial biopsy samples remains the diagnostic standard for acute rejection, this standard has limited diagnostic accuracy. Discordance between biopsy rejection grade and patient clinical trajectory frequently leads to both overtreatment of indolent processes and delayed treatment of aggressive ones, spurring the need to investigate the adequacy of the current histological criteria for assessing clinically important rejection outcomes.

Impact of Visceral Obesity on Clinical Outcome and Quality of Life for Patients with Multiple Myeloma: A Secondary Data Analysis of STaMINA (BMT CTN 0702) Trial.

Obesity is a common health problem in patients with multiple myeloma (MM) that has been linked to poor clinical outcomes and quality of life (QoL). We conducted a secondary analysis of the BMT CTN 0702, a randomized, controlled trial comparing outcomes of 3 treatment interventions after a single hematopoietic cell transplantation (HCT) (n = 758), to investigate the impact of visceral obesity, as measured by waist-to-hip ratio (WHR), on clinical outcomes and QoL in MM patients. A total of 549 MM patients, median age 55.

Computational Image and Molecular Analysis Reveal Unique Prognostic Features of Immune Architecture in African Versus European American Women with Endometrial Cancer.

Endometrial cancer (EC) disproportionately affects African American (AA) women in terms of progression and death. In our study, we sought to employ computerized image and bioinformatic analysis to tease out morphologic and molecular differences in EC between AA and European-American (EA) populations. We identified the differences in immune cell spatial patterns between AA and EA populations with markers of tumor biology, including histologic and molecular subtypes.

Rank acquisition impact on radiomics estimation (AсquIRE) in chest CT imaging: A retrospective multi-site, multi-use-case study.

Background: Radiomics is a method within medical image analysis that involves the extraction of quantitative data from radiologic scans, often in conjunction with machine learning algorithms to phenotype disease appearance, prognosticate disease outcome, and predict treatment response. However, variance in CT scanner acquisition parameters, such as convolution kernels or pixel spacing, can impact radiomics texture feature values.

Purpose: The extent to which the parameters influence radiomics features continues to be an active area of investigation.

Computational pathology identifies immune-mediated collagen disruption to predict clinical outcomes in gynecologic malignancies.

Background: The role of immune cells in collagen degradation within the tumor microenvironment (TME) is unclear. Immune cells, particularly tumor-infiltrating lymphocytes (TILs), are known to alter the extracellular matrix, affecting cancer progression and patient survival. However, the quantitative evaluation of the immune modulatory impact on collagen architecture within the TME remains limited.

A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia.

The curative potential of allogeneic hematopoietic transplantation (allo-HCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin, which has significant activity against ALL. We hypothesized that low-dose INO would be safe and feasible after allo-HCT.

Dosimetric Effect of Thymus and Thoracic Duct on Radiation-Induced Lymphopenia in Patients With Primary Lung Cancer Who Received Thoracic Radiation.

Purpose: Radiation-induced lymphopenia is a well-recognized factor for tumor control and survival in patients with cancer. This study aimed to determine the role of radiation dose to the thymus and thoracic duct on radiation-induced lymphopenia.

Methods And Materials: Patients with primary lung cancer treated with thoracic radiation therapy between May 2015 and February 2020 with whole blood count data were eligible.

The Impact of Prophylactic Cranial Irradiation and Consolidative Thoracic Radiation Therapy for Extensive Stage Small-Cell Lung Cancer in the Transition to the Chemo-Immunotherapy Era: A Single Institution Series.

Introduction: Extensive-stage small-cell lung cancer (ES-SCLC) continues to have poor survival due to its aggressive behavior, despite improvements with incorporation of immunotherapy with standard chemotherapy. Controversy exists regarding the role of consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) in ES-SCLC due to high recurrence rates. We report our institutional result of the benefit of PCI and TRT in ES-SCLC.

Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer.

Purpose: A single arm, phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple-negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, overall survival (OS), and identify pathologic and transcriptomic correlates of response to therapy.

Patients And Methods: Patients with ≤2 prior therapies for metastatic disease were treated with CNP regardless of tumor programmed cell death-ligand 1 status. Core tissue biopsies were obtained prior to treatment initiation.

Impact of Visceral Obesity on Clinical Outcome and Quality of Life for Patients with Multiple Myeloma: A Secondary Data Analysis of STaMINA (BMT CTN 0702) Trial.

Obesity is a common health problem among multiple myeloma (MM) patients, and it has been linked to poor clinical outcomes and quality of life (QOL). We conducted a secondary analysis of the BMT CTN 0702, a randomized, controlled trial comparing outcomes of three treatment interventions after a single hematopoietic cell transplant (HCT), to investigate the impact of visceral obesity, as measured by waist-to-hip ratio (WHR), on clinical outcomes and QOL in MM patients. 549 MM patients, median age 55.

Outcomes of Antineoplastic Immunotherapy at a Large Healthcare Organization: Impact of Provider, Race and Socioeconomic Status.

Purpose: Disparities in cancer care delivery remain a pressing health-care crisis within the United States (US). The use of immune checkpoint inhibitors (ICIs) and their management may be a disparity generator that impacts survival. This retrospective study assessed disparities in a cohort of patients with a variety of solid tumors treated with ICIs within a single health-care organization focusing on the impact of race, socioeconomic status (SES) and site of care delivery on survival and the development of severe immune-related adverse events (irAEs).