Beyond the rare: a case of pseudomyogenic hemangioendothelioma treated sequentially with everolimus, denosumab, and pazopanib.

Pseudomyogenic hemangioendothelioma is an ultra-rare vascular sarcoma that most commonly affects young adults, with a male predominance. It is diagnosed using a combination of imaging studies, histopathological examinations, and immunohistochemical staining. Surgical excision is the mainstay of treatment for pseudomyogenic hemangioendothelioma, with the goal of achieving a wide local excision and reducing the risk of recurrence.

Microsatellite Instability and Clinical Use in Sarcomas: Systematic Review and Illustrative Case Report.

Sarcomas, a diverse group of malignancies, exhibit substantial heterogeneity in both biological behavior and microenvironment, influencing their response to immunotherapy. Although pembrolizumab is approved for deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) tumors regardless of histology, there is a paucity of data to support its effectiveness in dMMR/MSI-H sarcomas. This study presents a case of a metastatic undifferentiated pleomorphic sarcoma of the retroperitoneum with dMMR status demonstrating a sustained complete response to pembrolizumab.

Challenges and opportunities for sarcoma care and research in Latin America: a position paper from the LACOG sarcoma group.

As a developing region, Latin America faces unique cancer control and prevention challenges, which are intensified when considering rare cancers, including sarcomas. Sarcomas are a group of malignancies that arise in the connective tissues of the body-such as muscle, fat, nerves, blood vessels, and bones-accounting for a diverse range of tumours that, although rare, require specialized attention. Sarcoma care and research in Latin America require a comprehensive approach that includes deeper epidemiologic knowledge, diagnostic capacity building, access to innovative treatments, increased patient advocacy, and strengthening of clinical research capacity.

Analysis of histology-agnostic targets among soft tissue and bone sarcomas in the AACR GENIE database.

Background: The development of novel therapies for patients with sarcoma is challenging due to the rarity and diversity of these mesenchymal neoplasms. Hence, histology-agnostic approvals can be of particular interest for the treatment of patients with soft tissue and bone sarcoma.

Methods: We queried the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database Cohort v12.

Antibody-Drug Conjugates and Tissue-Agnostic Drug Development: An Update.

Antibody-drug conjugates (ADCs) deliver effective medications to tumor cells that express specific antigens, maximizing efficacy and reducing adverse effects. Because ado-trastuzumab emtansine was approved in 2013, 5 ADCs received US Food and Drug Administration approval for solid tumor treatment. Technical advancements in the development of each component of ADCs allowed novel monoclonal antibodies, linkers, and payloads to increase drug transport to malignant cells and drug activity even in cancers with heterogeneous antigen expression.

Basket Trials: Review of Current Practice and Innovations for Future Trials.

Advances in biology and immunology have elucidated genetic and immunologic origins of cancer. Innovations in sequencing technologies revealed that distinct cancer histologies shared common genetic and immune phenotypic traits. Pharmacologic developments made it possible to target these alterations, yielding novel classes of targeted agents whose therapeutic potential span multiple tumor types.

Precision Medicine Targeting Genomic Alterations in Advanced Cholangiocarcinoma: Current State and Future Perspectives.

Although a relatively uncommon tumor, cholangiocarcinoma is on the rise globally. Of note, most patients are diagnosed with metastatic disease, and the prognosis is poor with cytotoxic chemotherapy. Strategies targeting specific genomic alterations have demonstrated promising activity in recent years and could represent a new therapeutic avenue for these patients.

Impact of tissue-agnostic approvals for patients with sarcoma.

Tissue-agnostic drug development is a major step forward in offering treatment options for rare tumors. Sarcomas are heterogeneous rare malignancies with more than 100 subtypes. Recent failure of Phase III trials, nonbiomarker-driven clinical trials, and rarity hamper developmental therapeutics in sarcomas.

Discovery of targeted expression data for novel antibody-based and chimeric antigen receptor-based therapeutics in soft tissue sarcomas using RNA-sequencing: clinical implications.

Recent failure of phase 3 trials and paucity of druggable oncogenic drivers hamper developmental therapeutics in sarcomas. Antibody-based therapeutics, like antibody-drug conjugates (ADCs) and chimeric antigen receptor (CAR)-based therapeutics, have emerged as promising strategies for anticancer drug delivery. The efficacy of these novel therapies is highly dependent on expression of the antibody target.

Hepatocellular Carcinoma Immunotherapy.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third leading cause of cancer-related death worldwide. Single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in early-phase trials, a finding that was not confirmed in phase III studies. The combination of atezolizumab (an anti-PD-L1 ICI) with bevacizumab (an anti-VEGF antibody) was approved as first-line therapy in 2020, however, with significant improvement in response rate, progression-free survival, and overall survival in comparison with the previous standard of care, sorafenib.

Moving Beyond 3+3: The Future of Clinical Trial Design.

Misgivings have been raised about the operating characteristics of the canonical 3+3 dose-escalation phase I clinical trial design. Yet, the traditional 3+3 design is still the most commonly used. Although it has been implied that adhering to this design is due to a stubborn reluctance to adopt change despite other designs performing better in hypothetical computer-generated simulation models, the continued adherence to 3+3 dose-escalation phase I strategies is more likely because these designs perform the best in the real world, pinpointing the correct dose and important side effects with an acceptable degree of precision.

Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib.

Background: Sorafenib was the first systemic therapy approved for the treatment of Child-Turcotte-Pugh (CTP) class A patients with advanced hepatocellular carcinoma (HCC). However, there are no biomarkers to predict survival and treatment outcomes and guide HCC systemic therapy. Type 1 insulin-like growth factor (IGF-1)/CTP composite score has emerged as a potential hepatic reserve assessment tool.

Systemic Options for Malignant Peripheral Nerve Sheath Tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal neoplasms that represent a profound therapeutic challenge due to their high proclivity for recurrence and metastasis and relatively poor response to systemic therapy regimens. While our understanding of the pathophysiology of MPNST is growing, including loss of the tumor suppressor gene neurofibromin and subsequent activation of the Ras pathway, targeted therapy to modify the poor prognosis seen in MPNST patients has thus far been without success. Correspondingly, MPNST patients are treated as per soft tissue sarcoma treatment algorithms with anthracycline-based therapy as the front-line therapy of choice for patients with unresectable, locally advanced, or metastatic MPNST.

Histology-agnostic drug development - considering issues beyond the tissue.

With advances in tumour biology and immunology that continue to refine our understanding of cancer, therapies are now being developed to treat cancers on the basis of specific molecular alterations and markers of immune phenotypes that transcend specific tumour histologies. With the landmark approvals of pembrolizumab for the treatment of patients whose tumours have high microsatellite instability and larotrectinib and entrectinib for those harbouring NTRK fusions, a regulatory pathway has been created to facilitate the approval of histology-agnostic indications. Negative results presented in the past few years, however, highlight the intrinsic complexities faced by drug developers pursuing histology-agnostic therapeutic agents.

Origin and role of hepatic myofibroblasts in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the second leading cause of cancer-related death worldwide. Fibrosis and cirrhosis are important risk factors for the development of HCC. Hepatic myofibroblasts are the cells responsible for extracellular matrix deposition, which is the hallmark of liver fibrosis.

Budd-Chiari Syndrome after Bilateral Nephrectomy for Polycystic Kidney Disease in a Kidney Transplant Recipient.

We report a rare case of Budd-Chiari syndrome (BCS) as a postoperative complication after bilateral nephrectomy in a kidney transplant recipient with polycystic liver and kidneys. Contrast-enhanced computed tomography of the abdomen showed a narrowed inferior vena cava, compressed by the polycystic liver that moved downwards after nephrectomy. A stenting angioplasty was performed, resulting in remarkable clinical improvement.

Response rates and survival to systemic therapy after immune checkpoint inhibitor failure in recurrent/metastatic head and neck squamous cell carcinoma.

Objectives: Prior reports have demonstrated a potential enhancement in overall response rate (ORR) to chemotherapy after exposure to immunotherapy. The goal of this study was to evaluate the ORR and survival to chemotherapy and/or targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients who progressed on immune checkpoint inhibitors (ICI).

Materials And Methods: We retrospectively collected clinical and pathologic data from patients with recurrent/metastatic HNSCC who progressed on ICI and subsequently received chemotherapy or targeted therapy.

Immunotherapy response evaluation with magnetic resonance elastography (MRE) in advanced HCC.

Background: Currently, there are no imaging predictors of immunotherapy outcome in hepatocellular carcinoma (HCC). The study aim was to determine if stiffness changes measured by magnetic resonance elastography (MRE) can be a predictor of immunotherapy response in patients with advanced HCC.

Materials And Methods: This was a prospective study of 15 patients with biopsy proven-advanced HCC treated with Pembrolizumab.

Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA.

Purpose: Molecular profiling has been used to select patients for targeted therapy and determine prognosis. Noninvasive strategies are critical to hepatocellular carcinoma (HCC) given the challenge of obtaining liver tissue biopsies.

Experimental Design: We analyzed blood samples from 206 patients with HCC using comprehensive genomic testing (Guardant Health) of circulating tumor DNA (ctDNA).

Immunologic Correlates of Pathologic Complete Response to Preoperative Immunotherapy in Hepatocellular Carcinoma.

In hepatocellular carcinoma (HCC), surgical resection is associated with high recurrence rate, and no effective adjuvant therapy currently exists. We initiated a pilot randomized trial of perioperative immunotherapy with nivolumab and ipilimumab for resectable HCC. Here, we provide an illustrative report of a case that achieved a complete response and report immunologic correlates of this complete pathologic response to perioperative immunotherapy.

Clinical and prognostic significance of circulating levels of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma.

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) play critical roles in angiogenesis in hepatocellular carcinoma (HCC). In addition, recent data suggest that Ang-1/Ang-2 are involved in regulating the immune response. The aim of our study was to explore the clinical prognostic significance of plasma Ang-1 and Ang-2 in HCC.

Changes in the Care Setting of First Consults to Palliative and Supportive Care Over a Seven-Year Period.

Context: Optimal benefits from palliative care (PC) are achieved when first consults (PC1) occur early, in the outpatient setting. Late PC1, like those in the intensive care unit (ICU), limit these benefits.

Objectives: The objective of this study was to determine the proportion of PC1 over time in the outpatient, ICU, and inpatient non-ICU settings.

Prognostic Factors in Patients with Metastatic Breast Cancer with Bone-Only Metastases.

Background: Patients with metastatic breast cancer with bone-only metastases (BOM) are a unique patient population without consensus regarding high-risk characteristics, which we sought to establish.

Methods: We identified 1,445 patients with BOM followed for at least 6 months at MD Anderson Cancer Center from January 1, 1997, to December 31, 2015.

Results: Seventy-one percent ( = 936) of the 1,325 patients with BOM with available pain characterization were symptomatic at time of BOM diagnosis.