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.

Targeted radioimmunotherapy for embryonal tumor with multilayered rosettes.

PURPOSE: We explored the use of intraventricular 131I-Omburtamab targeting B7-H3 in patients with ETMR. METHODS: Patients were enrolled in an IRB approved, phase 1, 3 + 3 dose escalation trial. Patients with CNS disease expressing the antibody target antigen B7-H3 were eligible. We report on a cohort of three patients with ETMR who were enrolled on the study. Three symptomatic children (ages 14 months, 3 and 3.5 years) had large parietal masses confirmed to be B7-H3-reactive ETMR. Patients received 2 mCi 131I-Omburtamab as a tracer followed by one or two therapeutic 131I-Omburtamab injections. Dosimetry was based on serial CSF, blood samplings and region of interest (ROI) on nuclear scans. Brain and spine MRIs and CSF cytology were done at baseline, 5 weeks after 131I-Omburtamab, and approximately every 3 months thereafter. Acute toxicities and survival were noted. RESULTS: Patients received surgery, focal radiation, and high dose chemotherapy. Patients 1 and 2 received 131I-Omburtamab (80 and 53 mCi, respectively). Patient 3 had a local recurrence prior to 131I-Omburtamab treated with surgery, external beam radiation, chemotherapy, then 131I-Omburtamab (36 mCi). 131I-Omburtamab was well-tolerated. Mean dose delivered by 131I-Omburtamab was 68.4 cGy/mCi to CSF and 1.95 cGy/mCi to blood. Mean ROI doses were 230.4 (ventricular) and 58.2 (spinal) cGy/mCi. Patients 1 and 2 remain in remission 6.8 years and 2.3 years after diagnosis, respectively; patient 3 died of progressive disease 7 months after therapy (2 years after diagnosis). CONCLUSIONS: 131I-Omburtamab appears safe with favorable dosimetry therapeutic index. When used as consolidation following surgery and chemoradiation therapy, 131I-Omburtamab may have therapeutic benefit for patients with ETMR.

High-Dose Chemotherapy with Stem Cell Rescue in Desmoplastic Small Round Cell Tumor: A Single-Institution Experience and Review of the Literature.

PURPOSE: Desmoplastic small round cell tumor (DSRCT) is a rare cancer that predominantly affects males averaging 21 years of age at the time of diagnosis. We describe four cases from our institution and place them within the context of a comprehensive review of the literature. PATIENTS AND METHODS: Study population included any patient who received treatment at Children's Hospital at Montefiore (CHAM) with histologic diagnosis of DSRCT. A search of the electronic databases PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE for the terms "desmoplastic" AND "small" AND "round" AND "cell" AND "tumor" was performed. RESULTS: One CHAM patient died of disease at 39 months, one patient has relapsed disease at 40 months, and two patients have no evidence of disease at 60 and 91 months. In the literature review, the 3-year OS was 36% and 5-year OS was 13%. There was a statistically significant difference in OS between no transplant and SCT in remission (p=0.004); however, there was no difference between no transplant and SCT not in remission (p=0.23). CONCLUSION: Given the poor prognosis in DSRCT, this study supports further prospective research into the possible benefit of consolidation of autologous SCT in patients with DSRCT who are in remission, with the alternative inference that these patients in remission may fare well without SCT. Our retrospective review of the literature does not support SCT for patients who are not in remission.

Isoprostane: quantitation of renal ischemia and reperfusion injury after renal artery clamping in an animal model.

BACKGROUND AND PURPOSE: Laparoscopic and robotic partial nephrectomy involves temporary clamping of the renal artery, making the kidney susceptible to ischemic damage. Isoprostane represents one potential marker of oxidative injury. The objective was to determine if renal interstitial isoprostane levels can quantitate renal damage secondary to warm ischemia. A second goal is to investigate allopurinol for renoprotective abilities using this model. We chose to investigate potential renoprotection of allopurinol because previous studies have demonstrated transplant kidneys pretreated with allopurinol to have less damage from ischemia. MATERIALS AND METHODS: A microdialysis probe was inserted into the renal parenchyma of rats to allow continuous dialysis and collection of the effluent for isoprostane levels. After clamping of the renal vessels for predefined intervals of ischemia, the interstitial effluent from the probe was collected and subsequently analyzed for isoprostane levels with and without allopurinol pretreatment. RESULTS: Clamping of the renal artery and vein produced increases in isoprostane levels during the ischemic period and larger increases during reperfusion. There was a trend for increased postclamp isoprostane levels as clamp times increased. When comparing isoprostane levels in rats that did not receive allopurinol, there were significant differences between the clamp and postclamp levels of isoprostane, with allopurinol offering protection to the kidney from ischemic changes caused by clamping the renal hilum. CONCLUSIONS: Our data have demonstrated that isoprostane levels are a potential real-time marker of renal ischemia and reperfusion injury. We also found allopurinol administration demonstrated a trend toward renoprotective abilities in the hilar occluded kidney.