Highlights d Proteomic profiles of extracellular vesicles and particles (EVPs) from 426 human samples d Identification of pan-EVP markers d Characterization of tumor-derived EVP markers in human tissues and plasma d EVP proteins can be useful for cancer detection and determining cancer type

BRAF hyperactivates ERK and signals as a RAF inhibitor-sensitive monomer. Although RAF inhibitors can produce impressive clinical responses in patients with mutant tumors, the mechanisms of resistance to these drugs are incompletely characterized. Here, we report a complete response followed by clinical progression in a patient with a-mutant brain tumor treated with dabrafenib. Whole-exome sequencing revealed a secondary mutation at progression that was not present in the pretreatment tumor. Expressing BRAF induces ERK signaling, promotes RAF dimer formation, and is sufficient to confer resistance to dabrafenib. Newer RAF dimer inhibitors and an ERK inhibitor are effective against BRAF-mediated resistance. Collectively, our results validate a novel biochemical mechanism of RAF inhibitor resistance mediated by a secondary mutation, emphasizing that, like driver mutations in cancer, the spectrum of mutations that drive resistance to targeted therapy are heterogeneous and perhaps emerge with a lineage-specific prevalence. In contrast to receptor tyrosine kinases, in which secondary mutations are often responsible for acquired resistance, second-site mutations in have not been validated in clinically acquired resistance to RAF inhibitors. We demonstrate a secondary mutation in (V600E/L514V) following progression on dabrafenib and confirm functionally that this mutation is responsible for resistance. .

AbstractObjectivesRetinoblastoma is the most common primary intraocular tumor of childhood with >95% survival rates in the US. Traditional therapy for retinoblastoma often included enucleation (removal of the eye). While much is known about the visual, physical, and cognitive ramifications of enucleation, data are lacking about survivors' perception of how this treatment impacts overall quality of life.MethodsQualitative analysis of an open-ended response describing how much the removal of an eye had affected retinoblastoma survivors' lives and in what ways in free text, narrative form.ResultsFour hundred and four retinoblastoma survivors who had undergone enucleation (bilateral disease = 214; 52% female; mean age = 44, SD = 11) completed the survey. Survivors reported physical problems (n = 205, 50.7%), intrapersonal problems (n = 77, 19.1%), social and relational problems (n = 98, 24.3%), and affective problems (n = 34, 8.4%) at a mean of 42 years after diagnosis. Three key themes emerged from survivors' responses; specifically, they (1) continue to report physical and intrapersonal struggles with appearance and related self-consciousness due to appearance; (2) have multiple social and relational problems, with teasing and bullying being prominent problems; and (3) reported utilization of active coping strategies, including developing more acceptance and learning compensatory skills around activities of daily living.Significance of resultsThis study suggests that adult retinoblastoma survivors treated with enucleation continue to struggle with a unique set of psychosocial problems. Future interventions can be designed to teach survivors more active coping skills (e.g., for appearance-related issues, vision-related issues, and teasing/bullying) to optimize survivors' long-term quality of life.

Brain tumors represent the most common solid tumors in childhood, accounting for almost 25% of all childhood cancer, second only to leukemia. Childhood CNS tumors encompass a wide variety of diagnoses, from benign to malignant. Any brain tumor can be associated with significant morbidity, even when low grade, and mortality from childhood CNS tumors is disproportionately high compared to other childhood malignancies. Management of children with CNS tumors requires knowledge of the unique aspects of care associated with this particular patient population, beyond general oncology care. Pediatric brain tumor patients have unique needs during treatment, as cancer survivors, and at end of life. A multidisciplinary team approach, including advanced practice nurses with a specialty in neuro-oncology, allows for better supportive care. Knowledge of the unique aspects of care for children with brain tumors, and the appropriate interventions required, allows for improved quality of life.

Background Ophthalmic Artery Chemosurgery (OAC) is associated with grade 3 and 4 neutropenia, however the effect on T-cell number and function is unknown. The purpose of this retrospective review was to confirm that patients treated with OAC do not develop immunosuppression warranting PCP prophylaxis. Procedure IRB approval was obtained for a single center retrospective review of immune function tests in retinoblastoma patients who received OAC. Results Twenty-three patients received ≥ 3 cycles of OAC and had immune function testing (absolute CD4 count) performed at a median of 34 days post-completion of therapy (range 15-63 days). Only one patient had a low absolute CD4 count of 189 cells/mL (normal 359-1570 cells/mL) two and a half months after IV carboplatin and 28 days after their third dose of OAC. This patient was found to have co-existing hypogammaglobulinemia. Repeat immune function testing normalized through continued OAC treatment. Conclusion Clinically significant immune suppression appears rare following OAC alone, but patients previously treated with IV chemotherapy may be immunosuppressed and may benefit from pneumocystis pneumonia prophylaxis until the CD4 count recovers.