Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.

Can 18 F-FDG-Positron Emission Tomography be a Prognostic Tool in Children With Rhabdomyosarcoma Treated With Definitive Radiotherapy?

Background: Persisting residual masses at treatment completion are known in rhabdomyosarcoma (RMS) treated with definitive radiotherapy (RT) to the primary site, but their prognostic significance is uncertain. Tumor response as assessed by anatomic imaging is not prognostic and studies based on 18 F-FDG-PET response are limited. We report the prognostic significance of persistent FDG-avidity in residual masses, assessed 3-month postdefinitive RT, in pediatric RMS.

A prospective, open-label, randomised, parallel design study of 4 generic formulations of intramuscular L-asparaginase in childhood precursor B-cell acute lymphoblastic leukaemia (ALL).

Aims: L-asparaginase is an essential medicine for childhood ALL. The quality of generic L-asparaginase available in India is a matter of concern. We compared four commonly used generic formulations of L-asparaginase in India.

Enrollment of adolescent and young adult patients newly diagnosed with cancer in NCI CTEP-sponsored clinical trials before and after launch of the NCI National Clinical Trials Network.

Background: Participation of adolescents and young adults (AYAs) in oncology clinical trials is important to ensure adequate opportunities for AYA patients to contribute to, and benefit from, advances in cancer treatment.

Methods: Accrual data for National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) cooperative group-led treatment trials were examined to assess enrollment of newly diagnosed AYA patients (15-39 years) during the period 2004-2019, with particular interest in comparing enrollment before launch of the NCI National Clinical Trials Network (NCTN) to after. All phase 2, 2/3, and 3 trials activated during the period between January 1, 2004, and December 31, 2019, were identified (n = 1568) and reduced to a set of 304 that met predetermined criteria to focus on cooperative group-led trials that involved therapy for newly diagnosed cancer and had age eligibility overlapping the AYA range.

Clinical trials for chimeric antigen receptor T-cell therapy: lessons learned and future directions.

Purpose Of Review: The purpose of this review is to summarize the status and utilization of chimeric antigen receptor T-cell (CAR-T) therapy based on the most recent clinical trials in patients with leukemia and lymphoma. Additionally, this review will highlight limitations in current strategies, discuss efforts in toxicity mitigation, and outline future directions for investigation.

Recent Findings: CD19 targeted CAR-T-cell therapy (CD19-CAR) is highly effective in patients with relapsed/refractory (r/r) B-cell hematologic malignancies.

Pharmacogenomics of in vitro response of the NCI-60 cancer cell line panel to Indian natural products.

Background: Indian natural products have been anecdotally used for cancer treatment but with limited efficacy. To better understand their mechanism, we examined the publicly available data for the activity of Indian natural products in the NCI-60 cell line panel.

Methods: We examined associations of molecular genomic features in the well-characterized NCI-60 cancer cell line panel with in vitro response to treatment with 75 compounds derived from Indian plant-based natural products.

Advances in the management of alveolar soft part sarcoma.

Alveolar Soft Part Sarcoma is one of the less commonly diagnosed soft tissue sarcoma subtypes, an infrequent subtype within the already rare category of human malignancy of sarcoma. In this article we will summarize the histopathological features, natural history and distinct molecular and biological features that have become increasingly appreciated with newer technologies and precision oncology. We will discuss the contemporary management of this disease as well as emerging treatment options.

Molecular genomic features associated with in vitro response of the NCI-60 cancer cell line panel to natural products.

Natural products remain a significant source of anticancer chemotherapeutics. The search for targeted drugs for cancer treatment includes consideration of natural products, which may provide new opportunities for antitumor cytotoxicity as single agents or in combination therapy. We examined the association of molecular genomic features in the well-characterized NCI-60 cancer cell line panel with in vitro response to treatment with 1302 small molecules which included natural products, semisynthetic natural product derivatives, and synthetic compounds based on a natural product pharmacophore from the Developmental Therapeutics Program of the US National Cancer Institute's database.

Increased toxicities in children with Burkitt lymphoma treated with rituximab: Experience from a tertiary cancer center in India.

Background: Even though rituximab has emerged as standard of care for the management of high-risk pediatric Burkitt lymphoma (BL), its safety in children from the low-middle-income countries (LMICs) remains to be proven. We herein report our experience of using rituximab in children with BL.

Methods: All patients diagnosed with BL between January 2015 and December 2017 were treated in a risk-stratified manner with either the modified MCP-842 or modified LMB protocol.

Outcomes with nondose-dense chemotherapy for Ewing sarcoma: A practical approach for the developing world.

Background: The current multidisciplinary approach in the treatment of Ewing sarcoma has improved cure rates, with contemporary dose-dense chemotherapy attaining 5-year event-free survival (EFS) of 73% in localized cases. Dose-intense and dose-dense chemotherapy is difficult in the majority of resource-limited settings with limited access to optimal supportive care. We report on patients with Ewing sarcoma treated on EFT-2001, a nondose-dense chemotherapy protocol.

A comparison of asparaginase activity in generic formulations of E.coli derived L- asparaginase: In-vitro study and retrospective analysis of asparaginase monitoring in pediatric patients with leukemia.

Aims: L-asparaginase is an essential medicine in the treatment of pediatric acute lymphoblastic leukemia (ALL) and the quality of generic formulations is an area of concern. We compared nine generic formulations of L-asparaginase available in India with the innovator.

Methods: The quality of formulations was assessed by measuring 72-hour trough asparaginase activity in children with ALL during induction following administration of 10,000 IU/m of L-asparaginase.

Clinical profile and outcome of classical Hodgkin lymphoma treated with a risk-adapted approach in a tertiary cancer center in India.

Background: Classical Hodgkin lymphoma (cHL) has excellent survival rates, but late effects are an issue and dictate modern approaches. We analyzed the clinical profile and outcome of cHL treated on a risk-adapted approach aimed at reducing late effects while improving historical outcomes at our center.

Procedure: Children (≤15 years) consecutively treated for cHL from January 2013 through December 2016 were retrospectively analyzed.

Holistic support coupled with prospective tracking reduces abandonment in childhood cancers: A report from India.

Background: High cure rates of over 80% in childhood cancers reported from high-income countries (HICs) are not replicated in low- and middle-income countries (LMICs). Treatment abandonment (TxA) is an important reason for this poorer outcome. We assessed the effect of a holistic support group approach coupled with prospective tracking on TxA in children with cancer in a limited-resources environment.

The Role of Childhood Infections and Immunizations on Childhood Rhabdomyosarcoma: A Report From the Children's Oncology Group.

Background: Rhabdomyosarcoma (RMS) is a rare, highly malignant tumor arising from primitive mesenchymal cells that differentiate into skeletal muscle. Relatively little is known about RMS susceptibility. Based on growing evidence regarding the role of early immunologic challenges on RMS development, we evaluated the role of infections and immunizations on this clinically significant pediatric malignancy.

Effect of caloric content and composition of a liquid meal on gastric emptying in the rat.

We examined the effect of caloric content and substrate composition on gastric emptying in conscious Sprague-Dawley rats using gastric radioscintigraphy. Three-milliliter volumes of normal saline, glucose, casein hydrolysate, or intralipid containing 0, 1, 2, 3, or 6 kcal labeled with 99mTc-diethylenetriaminepentaacetic acid were given intragastrically. Gamma-camera imaging and computer analysis allowed construction of gastric emptying curves constructed over many time points for each emptying study.

Induction of malnutrition in chronic alcoholism: role of gastric emptying.

Epidemiological studies reveal that chronic alcoholics exhibiting liver disease are generally malnourished. Experimental studies unequivocally demonstrate that incidence of malnutrition cannot be avoided in animals fed liquid diets containing high concentrations of alcohol. Furthermore, ingestion of additional amounts of macronutrients by such chronically alcoholic animals prevents or regresses alcohol-induced adverse effects despite a continuous intake of high amounts of alcohol.

Unsaturated fat and low energy intake induce whereas an increment in energy intake ameliorates fatty liver during prolonged alcohol consumption by rats.

Two groups of rats were fed liquid diets containing 35% of energy as fat and either 36 or 26% of energy as alcohol to examine the effect of fat and energy intake on alcoholic fatty liver production. After 4 wk, five rats in each group were killed for analysis of liver triglyceride concentration, and then the alcohol diets fed to remaining rats were switched. All remaining rats were killed for hepatic triglyceride determination after another 4 wk.

Carbohydrate intake determines pancreatic acinar amylase activity and release despite chronic alcoholemia in rats.

Adverse effects observed in alcoholic rats are often attributed to alcohol per se. Alcoholic liver damage, however, can be avoided by modulating nutritional factors despite high blood alcohol concentrations. Hence, we examined the effect of blood alcohol concentration on pancreatic enzyme activity and release.

Regulation of pancreatic amylase by dietary carbohydrate in chronic alcoholic rats.

The nutritional adequacy of dietary ingredients is essential for optimal food consumption and growth of animals. Dietary carbohydrate levels regulate pancreatic amylase synthesis. Ethanol diets with 36% of total calories from ethanol and 11% from carbohydrate are nutritionally inadequate, whereas a 26% ethanol diet made isocaloric to the 36% alcohol diet by the addition of maltose-dextrins provides all nutrients in amounts recommended for normal growth.

Reversal by glucose of pancreatic amylase insufficiency in chronic alcoholic rats.

Carbohydrate consumption regulates pancreatic amylase synthesis in rats. The Lieber-DeCarli 36% alcohol diet employed in chronic alcohol studies and the isocaloric control diet contain 11 and 47% of total calories from carbohydrates, respectively. Young rats fed ad libitum the 36% ethanol diet for 2 weeks obtained 1.