Prognostic factors for very early recurrence after neoadjuvant treatment and curative resection in pancreatic ductal adenocarcinoma.

Introduction: Very early recurrence in pancreatic ductal adenocarcinoma has been defined as recurrence ≤3 months after resection. Besides others, neoadjuvant treatment is delivered based on the assumption of preoperative eradication of micrometastasis as well as local downstaging. Prognostic factors of very early recurrence after neoadjuvant treatment remain largely unexplored.

B7-H3 and CSPG4-targeted CAR T cells as potent effectors in anaplastic thyroid cancer.

Background: Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy with poor survival and no available effective therapy. This unmet clinical need led us to investigate chimeric antigen receptor (CAR) T cells s as potential treatment option for this malignant disease. As target tumor antigens of our CAR T cell therapy, we selected the chondroitin sulfate proteoglycan 4 (CSPG4) and the B7-homolog 3 (B7-H3), as they are both highly and homogeneously expressed on different types of thyroid carcinoma cell lines and tissues, including ATC.

Association between opioid use and survival in advanced non small cell lung cancer patients treated with immune checkpoint inhibitors.

Cancer-related pain is a frequent challenge among non-small cell lung (NSCLC) cancer patients, particularly for those with advanced disease and/or bone metastases. Opioids are the mainstay of treatment for moderate to severe cancer-related pain. However, emerging lines of evidence suggest that concomitant opioid use may be associated with poor survival outcomes in advanced NSCLC patients treated with immune checkpoint inhibitors (ICIs).

Recurrent BEND2 Fusion Genes Identified by Whole Transcriptome Sequencing of Non-Functional Pancreatic Neuroendocrine Tumors Correlate with Poor Patient Prognosis.

Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogeneous clinical behavior, and a growing number of NF-PanNETs have been discovered incidentally. While chromatin remodeling and telomere maintenance gene alterations, such as ATRX and DAXX mutations, are well-established in the metastatic progression of PanNETs, many tumors lack known driver mutations. To identify additional prognostic biomarkers and alternative oncogenic mechanisms in primary non-functional pancreatic neuroendocrine tumors (NF-PanNETs), we employed whole transcriptome sequencing (WTS) on 73 non-syndromic NF-PanNETs with extended clinical follow-up (>4 years).

Overcoming resistance to immunotherapy by targeting CD38 in human tumor explants.

CD38, an ecto-enzyme involved in NAD catabolism, is highly expressed in exhausted CD8 T cells and has emerged as an attractive target to improve response to immune checkpoint blockade (ICB) by blunting T cell exhaustion. However, the precise role(s) and regulation of CD38 in exhausted T cells and the efficacy of CD38-directed therapeutic strategies in human cancer remain incompletely defined. Here, we show that CD38CD8 T cells are induced by chronic TCR activation and type I interferon stimulation and confirm their association with ICB resistance in human melanoma.

Epigenetic modifiers to enhance the efficacy of immune checkpoint inhibitors for the treatment of melanoma.

Immune checkpoint inhibitor (ICI)-based immunotherapy has significantly improved survival outcomes and radically changed the management of many different types of solid tumors, including melanoma. Almost half of advanced melanoma patients achieve a long-term clinical benefit from ICIs. Unfortunately, the other half of treated patients either rapidly progress or achieve a short-term clinical benefit due to the development of resistance.

Serum carbohydrate antigen 19-9 greater than 100 and risk of invasive carcinoma in pancreatic intraductal papillary mucinous neoplasms: Worrisome feature or high-risk stigmata?

Background: Elevated serum carbohydrate antigen 19-9 was incorporated as a worrisome feature in the International Association of Pancreatology 2017 Fukuoka guidelines and is associated with an increased risk of invasive carcinoma. We compared the independent predictive value of carbohydrate antigen 19-9 >100 U/mL with other worrisome feature and high-risk stigmata to better delineate its utility and importance.

Methods: We conducted a retrospective analysis of all patients who underwent pancreatic resection for intraductal papillary mucinous neoplasms at a high-volume tertiary center in the United States.

Generation of a Biliary Tract Cancer Cell Line Atlas Identifies Molecular Subtypes and Therapeutic Targets.

Unlabelled: Biliary tract cancers (BTC) are aggressive malignancies encompassing intrahepatic and extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinoma. Here, we report integrative analysis of 63 BTC cell lines via multi-omics and genome-scale CRISPR screens. We identify widespread EGFR dependency in BTC, alongside dependencies selective to anatomic subtypes.

Which technical difficulty score can best predict postoperative outcomes after minimally invasive liver resections?

Background: To assess technical difficulty scores for laparoscopic liver resections (LLR) in a large well-characterized cohort of low to high difficulty LLR.

Methods: Patients undergoing LLR and open liver resection (OLS) (2007-2022) at Massachusetts General Hospital were included. Patients were classified according to the technical difficulty scores Ban difficulty score, IWATE criteria, Hasegawa score, IMM score, and Southhampton score (SHH) and calibration of these scores in predicting postoperative outcome parameters was assessed.

TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids.

Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment of solid tumors. Multiple tumor microenvironmental factors are thought to contribute to resistance to CAR T-cell therapy in solid tumors, and appropriate model systems to identify and examine these factors using clinically relevant biospecimens are limited. In this study, we examined the activity of B7-H3-directed CAR T cells (B7-H3.

Clinicopathological Characteristics and Long-Term Outcomes of Cystic vs. Solid Pancreatic Neuroendocrine Tumors: A Multi-Institutional Experience with 1727 Patients.

Objective: To investigate the clinicopathological features and long-term outcomes of cystic and solid pancreatic neuroendocrine tumors (PanNETs).

Summary Background Data: PanNETs uncommonly present as cystic lesions. Whether cystic PanNETs represent a distinct clinical entity compared to solid PanNETs is controversial.

How to Predict Recurrence After Resection of Hepatocellular Carcinoma.

Background/aim: Predictors of recurrence following resection of hepatocellular carcinoma (HCC) are not fully established. This study investigated potential risk factors and prognostic scores for this situation.

Patients And Methods: In 297 patients undergoing resection of HCC between 2000 and 2021, risk scores and potential additional risk factors for intrahepatic and extrahepatic recurrence were assessed.

Best Practices for Delivering Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma.

Importance: Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.

Objective: To develop consensus best practices for delivering NT to patients with localized PDAC.

Dynamic Evolution of Fibroblasts Revealed by Single-Cell RNA Sequencing of Human Pancreatic Cancer.

Abstract: Cancer progression and response to therapy are inextricably reliant on the coevolution of a supportive tissue microenvironment. This is particularly evident in pancreatic ductal adenocarcinoma, a tumor type characterized by expansive and heterogeneous stroma. Herein, we employed single-cell RNA sequencing and spatial transcriptomics of normal, inflamed, and malignant pancreatic tissues to contextualize stromal dynamics associated with disease and treatment status, identifying temporal and spatial trajectories of fibroblast differentiation.

Impact of neoadjuvant chemoradiotherapy on pathologic response in pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Background: The impact of chemoradiotherapy on pathologic response, resection margin, and survival benefit is still debated. The aim of this study was to compare the rate of pathologic complete response (pCR) in surgical resection following neoadjuvant chemotherapy vs. chemoradiotherapy, and secondarily, to compare the rate of R0 resection and Overall Survival (OS).

HCC spatial transcriptomic profiling reveals significant and potentially targetable cancer-endothelial interactions.

Background: HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions.

Methods: We utilized computational deconvolution and cell-cell interaction analyses to cell type-specific (tumor-enriched and vessel-enriched) spatial transcriptomic data collected from 41 resected HCC tissue specimens.

Interobserver Variability in the International Study Group for Pancreatic Surgery (ISGPS)-Defined Complications After Pancreatoduodenectomy: An International Cross-Sectional Multicenter Study.

Objective: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others.

Background: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking.

Complexity and Experience Grading to Guide Patient Selection for Minimally Invasive Pancreatoduodenectomy: An International Study Group for Pancreatic Surgery (ISGPS) Consensus.

Objective: To develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally invasive pancreatoduodenectomy (MIPD).

Background: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis on appropriate patient selection according to adequate surgeon and center experience.

Generation of a biliary tract cancer cell line atlas reveals molecular subtypes and therapeutic targets.

Biliary tract cancers (BTCs) are a group of deadly malignancies encompassing intrahepatic and extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinoma. Here, we present the integrative analysis of 63 BTC cell lines via multi-omics clustering and genome- scale CRISPR screens, providing a platform to illuminate BTC biology and inform therapeutic development. We identify dependencies broadly enriched in BTC compared to other cancers as well as dependencies selective to the anatomic subtypes.

Lymph Node Yield is Associated with Improved Overall Survival and Increased Time to Recurrence in Node-Negative Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy.

Objective: To determine if lymph node yield (LNY) is associated with improved overall survival (OS) and time to recurrence (TTR) in patients with node-negative pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant therapy (NAT).

Background: Lymph node yield has been associated with survival in solid gastrointestinal cancers, including PDAC.

Methods: Patients with pathological T stage I-III, node-negative (N0), PDAC treated with NAT followed by pancreatoduodenectomy were identified in the Massachusetts General Hospital (MGH) pancreatectomy database and the National Cancer Database (NCDB).

Do Complications After Pancreatoduodenectomy Have an Impact on Long-Term Quality of Life and Functional Outcomes?

Objective: Our aim was to assess whether complications after pancreatoduodenectomy (PD) impact long-term quality of life (QoL) and functional outcomes.

Background: There is an increasing number of long-term post-PD survivors, but few studies have evaluated long-term QoL outcomes.

Methods: The EORTC QLQ-C30 and QLQ-PAN26 questionnaires were administered to patients who survived >5 years post-PD.