Despite limitations in the breadth and depth of data available, there is evidence that ketamine may be a viable option for treatment-refractory cancer pain.

Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.

Most drugs cannot penetrate the blood–brain barrier (BBB), greatly limiting the use of anti-cancer agents for brain cancer therapy. Temperature sensitive liposomes (TSL) are nanoparticles that rapidly release the contained drug in response to hyperthermia (>40 °C). Since hyperthermia also transiently opens the BBB, we hypothesized that localized hyperthermia can achieve drug delivery across the BBB when combined with TSL. TSL-encapsulated doxorubicin (TSL-Dox) was infused intravenously over 30 min at a dose of 0.94 mg/kg in anesthetized beagles (age ∼17 months). Following, a hyperthermia probe was placed 5–10 mm deep through one of four 3-mm skull burr holes. Hyperthermia was performed randomized for 15 or 30 min, at either 45 or 50 °C. Blood was drawn every 30 min to measure TSL-Dox pharmacokinetics. Nonsurvival studies were performed in four dogs, where brain tissue at the hyperthermia location was extracted following treatment to quantify doxorubicin uptake via high-performance liquid chromatography (HPLC) and to visualize cellular uptake via fluorescence microscopy. Survival studies for 6 weeks were performed in five dogs treated by a single hyperthermia application. Local doxorubicin delivery correlated with hyperthermia duration and ranged from 0.11 to 0.74 μg/g of brain tissue at the hyperthermia locations, with undetectable drug uptake in unheated tissue. Fluorescence microscopy demonstrated doxorubicin delivery across the BBB. Histopathology in Haematoxylin & Eosin (H&E) stained samples demonstrated localized damage near the probe. No animals in the survival group demonstrated significant neurological deficits. This study demonstrates that localized doxorubicin delivery to the brain can be facilitated by TSL-Dox with localized hyperthermia with no significant neurological deficits.

Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as delivery techniques that address the difficulty in crossing the blood brain barrier (BBB) are developed. Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanoparticle delivery system for treatment of the uniformly fatal pediatric disease of DIPG.