Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are increasingly recognized as having diverse biology. With the development of tyrosine kinase inhibitors molecularly matched to oncogenic KIT and PDGFRA mutations, GISTs have become a quintessential model for precision oncology. However, about 5-10% of GIST lack these driver mutations and are deficient in succinate dehydrogenase (SDH), an enzyme that converts succinate to fumarate. SDH deficiency leads to accumulation of succinate, an oncometabolite that promotes tumorigenesis. SDH-deficient GISTs are clinically unique in that they generally affect younger patients and are associated with GIST-paraganglioma hereditary syndrome, also known as Carney-Stratakis Syndrome. SDH-deficient GISTs are generally resistant to tyrosine-kinase inhibitors, the standard treatment for advanced or metastatic GIST. Thus, surgical resection is the mainstay of treatment for localized disease, but recurrence is common. Clinical trials are currently underway investigating systemic agents for treatment of advanced SDH-deficient GIST. However, further studies are warranted to improve our understanding of SDH-deficient GIST disease biology, natural history, surgical approaches, and novel therapeutics.

Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma.

Neuroblastoma is a neural crest-derived childhood tumor of the peripheral nervous system in which MycN amplification is a hallmark of poor prognosis. Here we show that MycN is expressed together with phosphorylation-stabilizing factor CIP2A in regions of the neural plate destined to form the CNS, but MycN is excluded from the neighboring neural crest stem cell domain. Interestingly, ectopic expression of MycN or CIP2A in the neural crest domain biases cells toward CNS-like neural stem cells that express Sox2. Consistent with this, some forms of neuroblastoma have been shown to share transcriptional resemblance with CNS neural stem cells. As high MycN/CIP2A levels correlate with poor prognosis, we posit that a MycN/CIP2A-mediated cell-fate bias may reflect a possible mechanism underlying early priming of some aggressive forms of neuroblastoma. In contrast to MycN, its paralogue cMyc is normally expressed in the neural crest stem cell domain and typically is associated with better overall survival in clinical neuroblastoma, perhaps reflecting a more "normal" neural crest-like state. These data suggest that priming for some forms of aggressive neuroblastoma may occur before neural crest emigration from the CNS and well before sympathoadrenal specification.

An interactive contouring module improves engagement and interest in radiation oncology among preclinical medical students: Results of a randomized trial.

PURPOSE: Studies have shown significant gaps in knowledge of radiation therapy among medical students and primary care providers. The goal of this study was to evaluate the effect of an interactive contouring module on knowledge and interest in radiation oncology among preclinical medical students. METHODS AND MATERIALS: Second-year medical students at the University of California, San Diego were randomized to participate in an interactive contouring exercise or watch a traditional didactic lecture on radiation oncology. Participants completed knowledge tests and surveys at baseline, immediately following the exercise, and 3 months later. Statistical analysis included Wilcoxon signed-rank test for pre- and posttest comparisons and Wilcoxon rank sum test for comparison between groups. RESULTS: Forty-three medical students participated in the trial (21 in the didactic group; 22 in the contouring group). Students completing the contouring module demonstrated similar overall knowledge improvement compared with the traditional didactic group (+8.6% vs +6.6%, not significant) but endorsed greater engagement on a 5-point Likert-type scale (3.10 vs 3.76, P = .02). At 3-month follow-up, there was a nonsignificant trend toward improved overall knowledge in the contouring group (43% vs 51%, P = .10), with a significance difference in a subset of questions on knowledge of the process of radiation therapy as well as side effects (51% vs 75%, P = .002). Students in the contouring group demonstrated more interest in pursuing a clinical radiation oncology rotation (2.52 vs 3.27, P = .01). CONCLUSIONS: Use of an interactive contouring module was an effective method to teach preclinical medical students about radiation oncology, with no significant difference in knowledge gained compared with a traditional didactic lecture; however, higher engagement among students completing the contouring module led to improved retention of knowledge of radiation side effects and greater interest in radiation oncology. These data suggest a potential benefit of integrating an interactive radiation oncology module into the preclinical medical school curriculum.

Multi-institutional Randomized Trial Testing the Utility of an Interactive Three-dimensional Contouring Atlas Among Radiation Oncology Residents.

PURPOSE: The delivery of safe and effective radiation therapy relies on accurate target delineation, particularly in the era of highly conformal treatment techniques. Current contouring resources are fragmented and can be cumbersome to use. The present study reports on the efficacy and usability of a web-based contouring atlas compared with those of existing contouring resources in a randomized trial. METHODS AND MATERIALS: We enrolled radiation oncology residents into a 2-phase contouring study. All residents contoured a T1N1 nasopharyngeal cancer case using the currently available resources. The participants were then randomized to recontour the case with access to existing resources or an interactive web-based contouring atlas (eContour.org). Contour analysis was performed using conformation number and simultaneous truth and performance level estimation. At completion of the second contouring session, the residents completed a multiple choice question knowledge test and a 10-item System Usability Scale. RESULTS: Twenty-four residents from 5 institutions completed the study. Compared with the residents using currently available resources, the residents using eContour had improved contour agreement with both the consensus (0.63 vs 0.52; P=.02) and the expert (0.58 vs 0.50; P=.01) contours for the high-risk clinical target volume and greater agreement with the expert contour for the contralateral parotid gland (0.44 ± 0.12 vs 0.56 ± 0.08; P=.003). The residents using eContour demonstrated greater knowledge of contour delineation and radiographic anatomy on a multiple-choice knowledge-based test (89% vs 77%; P=.03). Usability (89 vs 66; P<.0001) and satisfaction (4.1 vs 3.0; P=.002) were greater for eContour than for the existing resources. CONCLUSIONS: This study demonstrates the capacity of an interactive 3-dimensional contouring atlas to improve quality of resident target delineation in radiation oncology. Further research is needed to define the utility of easily accessible interactive educational reference tool to improve adherence to contouring-based guidelines and quality of care in routine clinical practice.