FDA Approval Summary: Nadofaragene firadenovec-vncg for bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer.

On December 16, 2022, the FDA approved the adenoviral vector-based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector-based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months.

Preoperative prediction of lymphovascular space invasion in endometrioid adenocarcinoma: an MRI-based radiomics nomogram with consideration of the peritumoral region.

Background: Lymphovascular space invasion (LVSI) of endometrial cancer (EC) is a postoperative histological index, which is associated with lymph node metastases. A preoperative acknowledgement of LVSI status might aid in treatment decision-making.

Purpose: To explore the utility of multiparameter magnetic resonance imaging (MRI) and radiomic features obtained from intratumoral and peritumoral regions for predicting LVSI in endometrioid adenocarcinoma (EEA).

Pathological prognosis classification of patients with neuroblastoma using computational pathology analysis.

Neuroblastoma is the most common extracranial solid tumor in early childhood. International Neuroblastoma Pathology Classification (INPC) is a commonly used classification system that provides clinicians with a reference for treatment stratification. However, given the complex and subjective assessment of the INPC, there will be inconsistencies in the analysis of the same patient by multiple pathologists.

Impact of perineural invasion on survival in node negative colon cancer.

Perineural invasion (PNI) has been implicated as a poor prognostic indicator in many cancers. The National Comprehensive Cancer Network recommends consideration of observation or adjuvant therapy in the presence of PNI in early colon cancer. These recommendations are based on single institutional studies that fail to evaluate PNI within the context of adjuvant chemotherapy.

Next-Generation Sequencing of Pulmonary Sarcomatoid Carcinoma Reveals High Frequency of Actionable MET Gene Mutations.

Purpose: To further understand the molecular pathogenesis of pulmonary sarcomatoid carcinoma (PSC) and develop new therapeutic strategies in this treatment-refractory disease.

Materials And Methods: Whole-exome sequencing in a discovery set (n = 10) as well as targeted MET mutation screening in an independent validation set (n = 26) of PSC were performed. Reverse transcriptase polymerase chain reaction and Western blotting were performed to validate MET exon 14 skipping.

Pharmacogenetics in neuroendocrine tumors of the pancreas.

Neuroendocrine tumors (NETs) arise from cells distributed throughout the endocrine system. Although, NETs are heterogeneous in their behavior, they tend to be more aggressive when arising in the pancreas. Pancreatic NET (panNET) represents three percent of all primary pancreatic neoplasms.

Successful treatment of a patient with Li-Fraumeni syndrome and metastatic lung adenocarcinoma harboring synchronous EGFR L858R and ERBB2 extracellular domain S310F mutations with the pan-HER inhibitor afatinib.

We report the case of a young, never-smoker woman with Li-Fraumeni syndrome and advanced lung adenocarcinoma refractory to multiple lines of conventional chemotherapy and negative for actionable alterations by routine testing. Comprehensive genomic profiling by clinical-grade next generation sequencing was performed on 3320 exons of 184 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer. The tumor was found to harbor both EGFR L858R and ERBB2 S310F alterations and also tested positive for a known TP53 germline mutation.

Updates on first-line therapy for metastatic pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is the 10th most common malignancy in the United States but is responsible for the 4th most cancer related deaths. This disease can only be potentially cured through early discovery and complete surgical resection. Unfortunately, nearly half of patients have metastatic spread at presentation.

A Phase I study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer.

Introduction: This study aimed to assess the safety and tolerability of the multitargeted tyrosine kinase inhibitor, vandetanib (V), in combination with two chemotherapeutic agents, oxaliplatin (O) and docetaxel (D) in advanced gastroesophageal (GE) cancer.

Methods: This was a Phase I study (NCT00732745) with a standard 3+3 dose escalation design. The primary aim was to determine the optimal dose of the combination of vandetanib and OD chemotherapy.

Management of borderline resectable pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is the fourth most common cause of cancer-related death among U.S. men and women.

Polyradiculopathies from schwannomatosis.

We describe a case of schwannomatosis presenting as radicular pain and numbness in multiple radicular nerve distributions. There were multiple peripheral nerve tumors detected by magnetic resonance imaging (MRI) at the left vestibular nerve, cauda equina, right radial nerve, thoracic paraspinal nerve, and brachial plexi. Several resected tumors have features of schwannomas, including hypercellular Antoni A areas, hypocellular Antoni B areas, Verocay bodies, and hyalinized blood vessels.

Risk of skin rash associated with erlotinib in cancer patients: a meta-analysis.

Skin rash is a major side effect of erlotinib, an inhibitor of the epidermal growth factor receptor widely used in cancer treatment and clinical trials.This study aims to evaluate the risk of skin toxicity with erlotinib through a systematic review and meta-analysis of randomized controlled clinical trials (RCTs). Eligible studies included prospective RCTs in which erlotinib was compared with controls at the starting dose of 150 mg daily.

Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma.

Matrix metalloproteinase-9 (MMP-9) is hypothesized to facilitate leukocyte extravasation and extracellular remodeling in asthmatic airways. Careful descriptive studies have shown that MMP-9 levels are higher in the sputum of asthmatics; however, the consequence of increased MMP-9 activity has not been determined in this disease. We induced asthma in transgenic mice that express human MMP-9 in the murine lung tissue macrophage to determine the direct effect of human MMP-9 expression on airway inflammation.

Risk of high-grade skin rash in cancer patients treated with cetuximab--an antibody against epidermal growth factor receptor: systemic review and meta-analysis.

Background: Cetuximab, a chimeric antibody against epidermal growth factor receptor has emerged as an effective therapy for advanced colorectal cancer (CRC) and head-neck cancer. However, severe skin toxicity may limit its use. Its efficacy in the treatment of other cancers is also undergoing extensive investigation.

Increased risk of high-grade dermatologic toxicities with radiation plus epidermal growth factor receptor inhibitor therapy.

Background: The addition of epidermal growth factor receptor (EGFR) inhibitors to radiotherapy has produced increased locoregional control and has reduced mortality from various solid tumors with few additional toxicities. Although anecdotal reports have suggested increased radiation dermatitis, the overall effect of these regimens on dermatologic toxicities has not been ascertained.

Methods: Dermatologic toxicity data were analyzed from abstracts presented at the annual meetings of the American Society of Clinical Oncology, the American Society of Therapeutic Radiology and Oncology, Cochrane Collaboration, MEDLINE, and EMBASE databases.

Superoxide dismutase expression attenuates cigarette smoke- or elastase-generated emphysema in mice.

Rationale: Oxidants are believed to play a major role in the development of emphysema.

Objectives: This study aimed to determine if the expression of human copper-zinc superoxide dismutase (CuZnSOD) within the lungs of mice protects against the development of emphysema.

Methods: Transgenic CuZnSOD and littermate mice were exposed to cigarette smoke (6 h/d, 5 d/wk, for 1 yr) and compared with nonexposed mice.

Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats.

Many possible treatments for pulmonary fibrosis have been investigated, but except for some current clinical trials, none have succeeded in clinical trials. On the basis of the antioxidant action of bilirubin (BIL), we examined the effects of hyperbilirubinemia on the development of bleomycin (BLM)-induced pulmonary fibrosis in rats. The animals' plasma BIL level was kept within 3 and 10 mg/dl by repeated intravenous infusion of a high dose of BIL.