Histology-Specific Clinical Trial of Lenvatinib and Pembrolizumab in Patients with Sarcoma.

Purpose: Survival of patients with metastatic sarcoma remains poor, and there is a pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multireceptor tyrosine kinase inhibitor targeting tumor vasculature, has an immunomodulatory activity that contributes to its antitumor effects.

Baseline MRI predictors of successful organ preservation in the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial.

Background: Prospective randomized trials have not yet identified baseline features predictive of organ preservation in locally advanced rectal cancers treated with total neoadjuvant therapy and a selective watch-and-wait strategy.

Methods: This was a secondary analysis of the OPRA trial, which randomized patients with stage II-III rectal adenocarcinoma to receive either induction or consolidation total neoadjuvant therapy. Patients were recommended for total mesorectal excision, or watch and wait based on clinical response at 8 ± 4 weeks after completing treatment.

Optimizing Sample Size for Supervised Machine Learning with Bulk Transcriptomic Sequencing: A Learning Curve Approach.

Accurate sample classification using transcriptomics data is crucial for advancing personalized medicine. Achieving this goal necessitates determining a suitable sample size that ensures adequate statistical power without undue resource allocation. Current sample size calculation methods rely on assumptions and algorithms that may not align with supervised machine learning techniques for sample classification.

MRI Predicts Residual Disease and Outcomes in Watch-and-Wait Patients with Rectal Cancer.

Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT.

Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: Pooled analysis of the CAO/ARO/AIO-12 and the OPRA randomized phase 2 trials.

Background: Total neoadjuvant therapy (TNT) has been used for patients with locally advanced rectal cancer. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy (CT) is a matter of debate.

Methods: We performed a pooled analysis of the CAO/ARO/AIO-12 and OPRA multicenter, randomized phase 2 trials to identify patient subsets that could benefit from one TNT sequence over the other regarding disease-free survival (DFS).

: An End-to-End Pipeline for Implementing Mixture Cure Models With an Application to Liposarcoma Data.

Purpose: Cure models are a useful alternative to Cox proportional hazards models in oncology studies when there is a subpopulation of patients who will not experience the event of interest. Although software is available to fit cure models, there are limited tools to evaluate, report, and visualize model results. This article introduces the R package, an end-to-end pipeline for building mixture cure models, and demonstrates its use in a data set of patients with primary extremity and truncal liposarcoma.

Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy.

Objective: Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer.

Background: Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate.

Methods: A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management.

Endoscopic Predictors of Residual Tumor After Total Neoadjuvant Therapy: A Post Hoc Analysis From the Organ Preservation in Rectal Adenocarcinoma Trial.

Background: Restaging endoscopy plays a critical role in selecting patients with locally advanced rectal cancer who respond to neoadjuvant therapy for nonoperative management.

Objective: This study evaluated the restaging endoscopic features that best predict the presence of residual tumor in the bowel wall.

Design: This was a post hoc analysis of a prospective randomized trial.

PDGFRβ Signaling Cooperates with β-Catenin to Modulate c-Abl and Biologic Behavior of Desmoid-Type Fibromatosis.

Purpose: This study sought to identify β-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRβ), affect these targets to alter natural history or treatment response in patients.

Immune-related Adverse Events after Immune Checkpoint Blockade-based Therapy Are Associated with Improved Survival in Advanced Sarcomas.

Unlabelled: The association between immune-related AEs (irAE) and outcome in patients with sarcoma is not known. We retrospectively reviewed a cohort of patients with advanced sarcoma treated with immune checkpoint blockade (ICB)-based therapy. Association of irAEs with survival was assessed using a Cox regression model that incorporated irAE occurrence as a time-dependent covariate.

Compliance and Toxicity of Total Neoadjuvant Therapy for Rectal Cancer: A Secondary Analysis of the OPRA Trial.

Purpose: Patients with locally advanced rectal cancer treated with total neoadjuvant therapy (TNT) may achieve organ preservation without a compromise to oncologic outcomes. However, reports on patient compliance with TNT and with treatment-related toxicities are limited.

Methods And Materials: The OPRA trial assessed organ preservation rates and oncologic outcomes in patients with clinical stage II/III rectal adenocarcinoma randomized to induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT).

BatMan: Mitigating Batch Effects Via Stratification for Survival Outcome Prediction.

Reproducible translation of transcriptomics data has been hampered by the ubiquitous presence of batch effects. Statistical methods for managing batch effects were initially developed in the setting of sample group comparison and later borrowed for other settings such as survival outcome prediction. The most notable such method is ComBat, which adjusts for batches by including it as a covariate alongside sample groups in a linear regression.

A Phase II Study of Epacadostat and Pembrolizumab in Patients with Advanced Sarcoma.

Purpose: Epacadostat, an indole 2,3 dioxygenase 1 (IDO1) inhibitor, proposed to shift the tumor microenvironment toward an immune-stimulated state, showed early promise in melanoma but has not been studied in sarcoma. This study combined epacadostat with pembrolizumab, which has modest activity in select sarcoma subtypes.

Patients And Methods: This phase II study enrolled patients with advanced sarcoma into five cohorts including (i) undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma, (ii) liposarcoma (LPS), (iii) leiomyosarcoma (LMS), (iv) vascular sarcoma, including angiosarcoma and epithelioid hemangioendothelioma (EHE), and (v) other subtypes.

On data normalization and batch-effect correction for tumor subtyping with microRNA data.

The discovery of new tumor subtypes has been aided by transcriptomics profiling. However, some new subtypes can be irreproducible due to data artifacts that arise from disparate experimental handling. To deal with these artifacts, methods for data normalization and batch-effect correction have been utilized before performing sample clustering for disease subtyping, despite that these methods were primarily developed for group comparison.

Histology-Specific Prognostication for Radiation-Associated Soft Tissue Sarcoma.

Purpose: Radiation-associated sarcomas (RAS) are rare but aggressive malignancies. We sought to characterize the histology-specific presentation and behavior of soft tissue RAS to improve individualized prognostication.

Methods: A single-institutional prospectively maintained database was queried for all patients with primary, nonmetastatic RAS treated with surgical resection from 1982 to 2019.

A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery.

Background: Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy.

: An R Package for Benchmarking microRNA Array Data Normalization in the Context of Sample Classification.

We present a new R package for assessing the performance of data normalization methods in connection with methods for sample classification. It includes two microRNA microarray datasets for the same set of tumor samples: a re-sampling-based algorithm for simulating additional paired datasets under various designs of sample-to-array assignment and levels of signal-to-noise ratios and a collection of numerical and graphical tools for method performance assessment. The package allows users to specify their own methods for normalization and classification, in addition to implementing three methods for training data normalization, seven methods for test data normalization, seven methods for classifier training, and two methods for classifier validation.

Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma.

PD-1 blockade (nivolumab) efficacy remains modest for metastatic sarcoma. In this paper, we present an open-label, non-randomized, non-comparative pilot study of bempegaldesleukin, a CD122-preferential interleukin-2 pathway agonist, with nivolumab in refractory sarcoma at Memorial Sloan Kettering/MD Anderson Cancer Centers (NCT03282344). We report on the primary outcome of objective response rate (ORR) and secondary endpoints of toxicity, clinical benefit, progression-free survival, overall survival, and durations of response/treatment.

Depth normalization of small RNA sequencing: using data and biology to select a suitable method.

Deep sequencing has become one of the most popular tools for transcriptome profiling in biomedical studies. While an abundance of computational methods exists for 'normalizing' sequencing data to remove unwanted between-sample variations due to experimental handling, there is no consensus on which normalization is the most suitable for a given data set. To address this problem, we developed 'DANA'-an approach for assessing the performance of normalization methods for microRNA sequencing data based on biology-motivated and data-driven metrics.

PRECISION.seq: An R Package for Benchmarking Depth Normalization in microRNA Sequencing.

We present a new R package for assessing the performance of depth normalization in microRNA sequencing data. It provides a pair of microRNA sequencing data sets for the same set of tumor samples, additional pairs of data sets simulated by re-sampling under various patterns of differential expression, and a collection of numerical and graphical tools for assessing the performance of normalization methods. Users can easily assess their chosen normalization method and compare its performance to nine methods already included in the package.