Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.

v-SYMPHONY career development series: A collaboration to enhance professional awareness for pediatric hematology oncology trainees.

BACKGROUND: A recent survey of pediatric hematology oncology (PHO) physicians identified that a majority believe fellows are struggling to find jobs that align with their goals. Career development for trainees has historically been home institution-specific, limiting fellows' exposures to career path possibilities. The "virtual-Symposium of Pediatric Hematology/Oncology of New York (v-SYMPHONY)" instituted a tristate Career Development Series for PHO trainees to better address their needs and increase awareness of the variety of PHO career opportunities. PROCEDURE: The v-SYMPHONY Career Development Series incorporated three sessions: (a) institutional perspective, (b) individual perspectives, and (c) nuts and bolts of job search. Pre- and post-series surveys were administered to participants to measure impact. RESULTS: Forty-one fellows registered for the series and completed a pre-survey. Over half (54%) were in their third or later year of fellowship. Careers with a clinical focus were the most commonly desired career path (59%). Most had received career development advice only from faculty within their institutions (90%). Post-surveys were completed by 11 PHO fellows. Overall, 100% of respondents reported benefiting from the career sessions and recommended the series should be repeated annually. Over 90% learned new information to prepare for the job search. CONCLUSIONS: The v-SYMPHONY Career Development Series for PHO fellows across multiple institutions was established and was extremely well received by its participants. PHO fellows agreed that these sessions were beneficial in helping prepare them for the job search process. An annual regional Career Development Series is feasible and is strongly suggested to support PHO fellows.

Pneumatosis intestinalis in the pediatric oncology population: An 11-year retrospective review at Memorial Sloan Kettering Cancer Center.

BACKGROUND: Pneumatosis intestinalis (PI) is characterized by the presence of intramural gas in the gastrointestinal (GI) tract. The overall aim of this study was to review risk factors and outcome of pediatric oncology patients at our institution who developed PI. PROCEDURE: Patients diagnosed with PI between 2007 and 2018 were identified from ICD-10 coding of radiology reports at Memorial Sloan Kettering Kids, a tertiary pediatric oncology center. Outcomes of interest were (a) resolution and time to resolution of PI, (b) surgical intervention within 2 weeks of diagnosis of PI, or (c) death secondary to PI. To capture the resolution of PI, we defined the "time to recovery (TTR)" as the time elapsed between date of PI diagnosis and the date of recovery. RESULTS: Forty-two patients were identified. Within 30 days of diagnosis of PI, three patients had surgical intervention for PI (7%) and two patients died (5%) due to non-PI causes. Median TTR of PI was 4.5 days (95% CI: 3-7 days). In univariable and multivariable analyses, only steroid use in the prior 30 days was significantly associated with a faster TTR of PI (HR = 2.27 [95% CI: 1.17-4.41], p = .02). CONCLUSIONS: This is the largest case series of patients with PI in the pediatric oncology population, which reveals significantly lower surgical and mortality rates than other published PI series. For the majority of patients, conservative medical management is indicated. A prospective study is warranted to define diagnosis and management guidelines for PI in the pediatric oncology population in a cooperative group setting.

Pediatric rhabdomyosarcoma with bone marrow metastasis.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of adolescence and childhood. Although most patients with localized RMS are cured, outcome of those with metastatic disease remains unsatisfactory. RMS with bone marrow (BM) metastasis accounts for approximately 6% of all cases with RMS and has a 3-year event-free survival of 14%. Our study aims to describe our institution's experience of patients with metastatic RMS with BM involvement. METHODS: This was a single-institution retrospective study from Memorial Sloan Kettering Kids, a tertiary pediatric oncology center. Patients with RMS who were diagnosed with BM metastasis between 1998 and 2018 were identified from pathology reports. RESULTS: For patients with RMS and BM positivity at diagnosis (N = 27), the median survival was 1.5 years. The 1-, 2-, and 3-year overall survival (OS) were 81%, 32%, and 20%, respectively. There is one long-term (defined as >4 year) survivor who is still alive 14.9 years after diagnosis despite two metastatic recurrences. An Oberlin status of 4 that included BM metastasis portended a 3-year OS of 0%. CONCLUSIONS: Although most patients will respond to initial therapy, BM metastasis at the time of diagnosis lends a near-fatal diagnosis in pediatric patients with RMS. Novel therapies are desperately needed to consolidate their initial remission.