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File:Briana Bowersock.jpg

Briana Bowersock is one of Jessica Lane's characters. She was born on July, 22nd 2009. She was 7 years old when she died. In 2012, she was diagnosed with DIPG. For anyone who is wondering what is DIPG, it's a childhood cancer. The diagnosis of DIPG is based on the clinical history and examination combined with findings on magnetic resonance imaging (MRI). Because DIPG grows in a diffusely infiltrative pattern, intermixing with healthy tissue, the margins of the tumor do not appear well-defined on MRI, like other types of brainstem tumors. DIPG characteristically involves a majority of the pons and does not enhance with MRI contrast agent. These findings on diagnostic imaging help to distinguish DIPG from other, less aggressive brainstem cancers.3 Surgical biopsy is not routinely obtained to confirm diagnosis in the United States. Undertaking the risks of the procedure is thought to be unwarranted, as neuroimaging is sufficient for diagnosis in typical cases of DIPG, and biopsy has no role in guiding therapeutic management at the present state of the field in 2014. The rarity of DIPG biopsies has contributed to the scarcity of tumor tissue available for experimental study. In France, however, biopsies are now routinely performed for DIPG.4Currently, international and multi-institutional efforts to share tumor tissue and resources resulting from these biopsies, as well as from a growing pool of early post-mortem autopsy tissue donations by patients and their families, have resulted in expanded possibilities to study the disease. This has given way to a better understanding of its biology in recent years. As researchers begin to learn more about DIPG molecular and genetic markers and how they may be associated with disease trajectory and prognosis, some now speculate that eventual development of disease stratification and targeted therapies may warrant revisiting the role of biopsy for DIPG patients in the future. Because DIPG grows diffusely and infiltrates healthy tissue in the critical structures of the brainstem, surgical treatment is not possible.  Radiation therapy has remained the mainstay of treatment for DIPG for the past three decades. At most treatment centers, the standard recommendation is conventionally fractionated local field radiotherapy with dose range of 54-60 Gy for a period of 6 weeks.5Radiotherapyprovides temporary improvement or stabilization of symptoms and extends overall survival by an average of 3 months; median survival is less than 5 months with no radiation treatment.6Hyperfractionated therapy (smaller, more frequent doses) did not improve survival in multiple prior studies and was associated with increased side effects.7-10Newer studies suggest that hypofractionated therapy (larger doses over a shorter period of 3 weeks) may offer comparable overall survival with reduced burden on the patient and family, who were able to spend an average of less than 10% of remaining survival time in the hospital receiving treatment.11-12 Many clinical trials over the years have explored the use of various chemotherapeutic agents for DIPG, employing conventional and high-dose strategies as well as targeted agents. Chemotherapy has been attempted at time points before, during and after radiation therapy. Despite all efforts, no improvement in survival has been demonstrated.13-18Historically, these trials were performed largely without guidance by preclinical experimental data, and were instead designed after therapeutic strategies used to treat adult high-grade glioma. Such a strategy is likely to be problematic, as emerging research suggests DIPG represents a distinct disease from its adult counterpart. Newer, ongoing efforts by the DIPG Preclinical Consortium, formed in 2011 as an international collaboration of DIPG researchers, will attempt to harness the emerging availability of DIPG cell lines and animal models to ascertain efficacy of potential drugs at the preclinical level, directing future clinical trials.19 The extent to which the failure of previous clinical trials is due to inherent resistance of the tumor cells is unclear.  Drug delivery to the pons, where DIPG is located, likely also poses a major therapeutic challenge. Because of the blood-brain barrier that naturally protects the brain and regulates its environment, drugs intended to treat DIPG often do not effectively reach their target. Convection Enhanced Delivery (CED) may be a promising approach to bypass the blood-brain barrier and provide localized drug delivery in higher concentrations without systemic side effects. A catheter is placed into the region of the tumor by stereotactic surgery, and an attached pump locally delivers the drug under positive pressure.20In a recent clinical trial, CED was recently demonstrated to feasibly deliver the drug topotecan to the brainstems of children with DIPG; however, this trial highlighted the need for further technical optimization.21A phase I safety trial of CED, designed to optimize technical parameters, is ongoing (clinicaltrials.gov ID NCT01502917). CED continues to gain attention as a promising area of development in the treatment of DIPG. She was at an amusement park when she died.

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