Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma.

Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16).

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer.

Introduction: Advanced unresectable gastroesophageal cancers continue to confer a dismal patient prognosis. Limited options remain once the cancer is refractory to cytotoxics/biologics (like irinotecan, taxane, and ramucirumab). Recently, anti-programmed death-1 (anti-PD-1) inhibitors have been used with limited efficacy in select patients with adenocarcinoma.

Bayesian non-parametric survival regression for optimizing precision dosing of intravenous busulfan in allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (allo-SCT) is now part of standard of care for acute leukemia (AL). To reduce toxicity of the pre-transplant conditioning regimen, intravenous busulfan is usually used as a preparative regimen for AL patients undergoing allo-SCT. Systemic busulfan exposure, characterized by the area under the plasma concentration versus time curve (AUC), is strongly associated with clinical outcome.

Pharmacotherapeutic considerations for elderly patients with colorectal cancer.

: Oncology care in the elderly presents a dilemma. The majority of cancer cases are diagnosed in the elderly yet they are underrepresented in clinical trials. In addition to limited evidence-based medicine, the elderly is a heterogeneous population filled with pharmacotherapeutic challenges and barriers.

Magnetic Resonance Imaging and Bioluminescence Imaging for Evaluating Tumor Burden in Orthotopic Colon Cancer.

Quantifying tumor burden is important for following the natural history of orthotopic colon cancer and therapeutic efficacy. Bioluminescence imaging (BLI) is commonly used for such assessment and has both advantages and limitations. We compared BLI and magnetic resonance imaging (MRI) for quantifying orthotopic tumors in a mouse model of colon cancer.

English Translation of M. Bérard: Tumeur Embryonnaire Du Muscle Strié. [Embryonal Tumor of Striated Muscle]. Lyon Med 1894; 77: 52.

We have chosen to translate what we believe to be the first publication of a well-documented case of a young patient with embryonal rhabdomyosarcoma. The author, M. Léon Bérard, was a hospital fellow working in the department of M.

Systemic therapy for unresectable, mixed hepatocellular-cholangiocarcinoma: treatment of a rare malignancy.

Background: Combined hepatocellular-cholangiocarcinoma (HCC-CC) has a reported incidence of less than 5% of primary hepatic malignancies. The treatment approach to this malignancy is undefined. Our objective of this case series is to provide some insight into chemotherapy and/or targeted therapy in this setting.

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma.

Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.

Context: Recent whole genome mRNA expression profiling studies revealed that bladder cancers can be grouped into molecular subtypes, some of which share clinical properties and gene expression patterns with the intrinsic subtypes of breast cancer and the molecular subtypes found in other solid tumors. The molecular subtypes in other solid tumors are enriched with specific mutations and copy number aberrations that are thought to underlie their distinct progression patterns, and biological and clinical properties.

Objective: The availability of comprehensive genomic data from The Cancer Genome Atlas (TCGA) and other large projects made it possible to correlate the presence of DNA alterations with tumor molecular subtype membership.

Ubiquitination and regulation of AURKA identifies a hypoxia-independent E3 ligase activity of VHL.

The hypoxia-regulated tumor-suppressor von Hippel-Lindau (VHL) is an E3 ligase that recognizes its substrates as part of an oxygen-dependent prolyl hydroxylase (PHD) reaction, with hypoxia-inducible factor α (HIFα) being its most notable substrate. Here we report that VHL has an equally important function distinct from its hypoxia-regulated activity. We find that Aurora kinase A (AURKA) is a novel, hypoxia-independent target for VHL ubiquitination.

Early learners as health coaches for older adults preparing for surgery.

Background: Few opportunities exist for early learners to engage in authentic roles on health care teams. In a geriatric optimization clinic for frail high-risk surgical patients, first-year medical and nurse practitioner students were integrated into an interprofessional team as health coaches.

Materials And Methods: Frail surgical patients with planned operations were referred to a new preoperative optimization clinic to see a geriatrician, occupational, and physical therapists and a nutritionist.

Multimodal Magnetic Resonance and Near-Infrared-Fluorescent Imaging of Intraperitoneal Ovarian Cancer Using a Dual-Mode-Dual-Gadolinium Liposomal Contrast Agent.

The degree of tumor removal at surgery is a major factor in predicting outcome for ovarian cancer. A single multimodality agent that can be used with magnetic resonance (MR) for staging and pre-surgical planning, and with optical imaging to aid surgical removal of tumors, would present a new paradigm for ovarian cancer. We assessed whether a dual-mode, dual-Gadolinium (DM-Dual-Gd-ICG) contrast agent can be used to visualize ovarian tumors in the peritoneal cavity by multimodal MR and near infra-red imaging (NIR).

Co-morbidities Rather than Age Impact Outcomes in Patients Receiving Preoperative Therapy for Gastroesophageal Adenocarcinoma.

Background: Older patients with localized gastric adenocarcinoma (LGAC) have substantial postoperative morbidity and mortality; however, postoperative outcomes of the patients who receive preoperative chemotherapy and/or chemoradiation have not been reported. We examined the impact of age at baseline on potential predictors of postoperative outcomes.

Methods: Patients with LGAC who were treated with chemotherapy and/or chemoradiation followed by surgery (n = 203) formed two groups: (1) ≥65 years old (n = 70) and (2) <65 years old (n = 133).

Challenges in the Diagnosis of Urothelial Carcinoma Variants: Can Emerging Molecular Data Complement Pathology Review?

Urothelial carcinoma can exhibit a wide variety of histopathologic phenotypes or variant morphologies, classifications of which have recently been revised in the 2016 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs. Many of these variants not only present diagnostic challenges, but also have clinical implications that affect patient prognosis and treatment strategies. This review will discuss these variant morphologies and their relationship to current understanding of the underlying biology of urothelial carcinoma and molecular classification paradigms.

Intrinsic subtypes and bladder cancer metastasis.

Recent studies demonstrated that bladder cancers can be grouped into basal and luminal molecular subtypes that possess distinct biological and clinical characteristics. Basal bladder cancers express biomarkers characteristic of cancer stem cells and epithelial-to-mesenchymal transition (EMT). Patients with basal cancers tend have more advanced stage and metastatic disease at presentation.

Bladder Cancer Molecular Taxonomy: Summary from a Consensus Meeting.

The advent of Omics technologies has been key to the molecular subclassification of urothelial bladder cancer. Several groups have used different strategies to this aim, with partially overlapping findings. The meeting at the Spanish National Cancer Research Center-CNIO was held to discuss such classifications and reach consensus where appropriate.

Epidermal growth factor receptor inhibition in metastatic anal cancer.

Metastatic squamous cell carcinoma (SCCA) anal cancer is relatively rare. With limited data, cisplatin plus 5-fluorouracil has traditionally been utilized in the first-line setting. Treatment beyond front-line cisplatin progression is not well defined.

Inotuzumab ozogamicin in the treatment of acute lymphoblastic leukemia.

Over 90% of leukemic blasts in patients with acute lymphoblastic leukemia express the marker CD22. Inotuzumab ozogamicin (INO) is a CD22-directed humanized monoclonal antibody conjugated to the potent cytotoxin, calicheamicin, via an acid labile linker. INO has shown high rates of response in the treatment of relapsed and refractory (R/R) ALL in single-agent studies, with fewer adverse effects than traditional cytotoxic chemotherapy.

NDN is an imprinted tumor suppressor gene that is downregulated in ovarian cancers through genetic and epigenetic mechanisms.

NDN is a maternally imprinted gene consistently expressed in normal ovarian epithelium, is dramatically downregulated in the majority of ovarian cancers. Little or no NDN expression could be detected in 73% of 351 epithelial ovarian cancers. NDN was also downregulated in 10 ovarian cancer cell lines with total loss in 6 of 10.

Predictive Value of Serum miR-10b, miR-29c, and miR-205 as Promising Biomarkers in Esophageal Squamous Cell Carcinoma Screening.

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide. The high mortality of ESCC is mainly due to late diagnosis. Current detection methods have their own weakness, including high costs and invasive procedures.

Cetuximab in combination with cisplatin and 5-Fluorouracil induces dramatic response in metastatic refractory squamous cell carcinoma of the anal canal.

Metastatic squamous cell carcinoma (SCC) of the anal canal is rare with limited data regarding treatment. Epidermal growth factor receptor (EGFR) expression has been observed in SCC of the anal canal and Kristen rat sarcoma vial oncogene (KRAS) mutations are rare. EGFR monoclonal antibodies, cetuximab and panitumumab, represent a potential option in this patient population.

Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia.

Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10(-8)) are, however, still of interest for identifying causal associations.

A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naïve Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in Urothelial Cancer.

Background: Gene expression profiling (GEP) suggests there are three subtypes of muscle-invasive urothelial cancer (UC): basal, which has the worst prognosis; p53-like; and luminal. We hypothesized that GEP of transurethral resection (TUR) and cystectomy specimens would predict subtypes that could benefit from chemotherapy.

Objective: To explore clinical outcomes for patients treated with dose-dense (DD) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and bevacizumab (B) and the impact of UC subtype.

Association of OPN overexpression with tumor stage, differentiation, metastasis and tumor progression in human laryngeal squamous cell carcinoma.

Background: Osteopontin (OPN) is overexpressed in many human tumors and involved in promotion of cancer cells by regulating various facets of tumor progression such as cell proliferation, invasion and metastasis. To understand roles of OPN in tumor progression of laryngeal squamous cell carcinoma (LSCC) or develop molecular marker for prognosis and treatment of LSCC, we thus explore biological function of OPN and correlation with p53 in LSCC.

Methods: The expression of OPN and p53 in tumor tissues of LSCC was determined immunohistochemically in both LSCC and adjacent normal tissues.