Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations.

BACKGROUND: Canine and human osteosarcoma are similar in clinical presentation and tumor genomics. Giant breed dogs experience elevated osteosarcoma incidence, and taller stature remains a consistent risk factor for human osteosarcoma. Whether evolutionarily conserved genes contribute to both human and canine osteosarcoma predisposition merits evaluation. METHODS: A multi-center sample of childhood osteosarcoma patients and controls underwent genome-wide genotyping and imputation. Ancestry-adjusted SNP associations were calculated within each dataset using logistic regression, then meta-analyzed across the three datasets, totaling 1091 patients and 3026 controls. Ten regions previously associated with canine osteosarcoma risk were mapped to the human genome, spanning ∼6 Mb. We prioritized association testing of 5985 human SNPs mapping to candidate osteosarcoma risk regions detected in Irish wolfhounds, the largest dog breed studied. Secondary analyses explored 6289 additional human SNPs mapping to candidate osteosarcoma risk regions identified in Rottweilers and greyhounds. RESULTS: Fourteen SNPs were associated with human osteosarcoma risk after adjustment for multiple comparisons, all within a 42 kb region of human Chromosome 7p12.1. The lead variant was rs17454681 (OR=1.25, 95 %CI: 1.12-1.39; P=4.1×10-5), and independent risk variants were not observed in conditional analyses. While the associated region spanned 2.1 Mb and contained eight genes in Irish wolfhounds, associations were localized to a 50-fold smaller region of the human genome and strongly implicate GRB10 (growth factor receptor-bound protein 10) in canine and human osteosarcoma predisposition. PheWAS analysis in UK Biobank data identified noteworthy associations of the rs17454681 risk allele with varied measures of height and pubertal timing. CONCLUSIONS: Our comparative oncology analysis identified a novel human osteosarcoma risk allele near GRB10, a growth inhibitor that suppresses activated receptor tyrosine kinases including IGF1R, PDGFRB, and EGFR. Epidemiologists may benefit from leveraging cross-species comparisons to identify haplotypes in highly susceptible but genetically homogenous populations of domesticated animals, then fine-mapping these associations in diverse human populations.

Audio-based event detection in the operating room.

PURPOSE: Even though workflow analysis in the operating room has come a long way, current systems are still limited to research. In the quest for a robust, universal setup, hardly any attention has been given to the dimension of audio despite its numerous advantages, such as low costs, location, and sight independence, or little required processing power. METHODOLOGY: We present an approach for audio-based event detection that solely relies on two microphones capturing the sound in the operating room. Therefore, a new data set was created with over 63 h of audio recorded and annotated at the University Hospital rechts der Isar. Sound files were labeled, preprocessed, augmented, and subsequently converted to log-mel-spectrograms that served as a visual input for an event classification using pretrained convolutional neural networks. RESULTS: Comparing multiple architectures, we were able to show that even lightweight models, such as MobileNet, can already provide promising results. Data augmentation additionally improved the classification of 11 defined classes, including inter alia different types of coagulation, operating table movements as well as an idle class. With the newly created audio data set, an overall accuracy of 90%, a precision of 91% and a F1-score of 91% were achieved, demonstrating the feasibility of an audio-based event recognition in the operating room. CONCLUSION: With this first proof of concept, we demonstrated that audio events can serve as a meaningful source of information that goes beyond spoken language and can easily be integrated into future workflow recognition pipelines using computational inexpensive architectures.

Model-based individual life-spanning documentation in visceral surgery: a proof of concept.

INTRODUCTION: Surgical documentation has many implications. However, its primary function is to transfer information about surgical procedures to other medical professionals. Thereby, written reports describing procedures in detail are the current standard, impeding comprehensive understanding of patient-individual life-spanning surgical course, especially if surgeries are performed at a timely distance and in diverse facilities. Therefore, we developed a novel model-based approach for documentation of visceral surgeries, denoted as 'Surgical Documentation Markup-Modeling' (SDM-M). MATERIAL AND METHODS: For scientific evaluation, we developed a web-based prototype software allowing for creating hierarchical anatomical models that can be modified by individual surgery-related markup information. Thus, a patient's cumulated 'surgical load' can be displayed on a timeline deploying interactive anatomical 3D models. To evaluate the possible impact on daily clinical routine, we performed an evaluation study with 24 surgeons and advanced medical students, elaborating on simulated complex surgical cases, once with classic written reports and once with our prototypical SDM-M software. RESULTS: Leveraging SDM-M in an experimental environment reduced the time needed for elaborating simulated complex surgical cases from 354 ± 85 s with the classic approach to 277 ± 128 s. (p = 0.00109) The perceived task load measured by the Raw NASA-TLX was reduced significantly (p = 0.00003) with decreased mental (p = 0.00004) and physical (p = 0.01403) demand. Also, time demand (p = 0.00041), performance (p = 0.00161), effort (p = 0.00024), and frustration (p = 0.00031) were improved significantly. DISCUSSION: Model-based approaches for life-spanning surgical documentation could improve the daily clinical elaboration and understanding of complex cases in visceral surgery. Besides reduced workload and time sparing, even a more structured assessment of individual surgical cases could foster improved planning of further surgeries, information transfer, and even scientific evaluation, considering the cumulative 'surgical load.' CONCLUSION: Life-spanning model-based documentation of visceral surgical cases could significantly improve surgery and workload.

Adoption as an Alternative Family-Building Strategy: Perceptions of Female, Young Adult Cancer Survivors Receiving Gonadotoxic Treatments.

Female survivors of young adult (YA) cancers are at risk of fertility impacts following cancer treatment. For these women, fertility-related distress is both prevalent and persistent. Yet there is little research regarding survivors' perspectives on alternative family-building options, particularly adoption. This exploratory secondary data analysis analyzed semistructured interviews and explored survivors' views of adoption. Overall, female YA survivors reported openness to adoption as a possible substitute for biological conception and an alternative to fertility preservation. It is imperative that this population receives support in decision-making around and consideration of the unique barriers to adoption for cancer survivors.

Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial.

Background: Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison between oral aprepitant and intravenous fosaprepitant in pediatric oncology patients. Methods: Our study was a double-parallel study, and the distribution ratio was 1:1. Children aged 2-12 years who were undergoing moderate or highly emetogenic chemotherapy (MEC or HEC) were randomly assigned to receive ondansetron and dexamethasone combined with either a single dose of intravenous fosaprepitant (arm A), or 3 days of oral aprepitant (arm B). The primary outcome measure was the rate of complete response (CR) of CINV within the acute phase, defined as from the start through 24 hours after the last chemotherapy dose. Response during the delayed phase, overall response, and use of rescue antiemetics were also assessed. Results: We prospectively evaluated 108 eligible patients, including 55 receiving fosaprepitant. Study observations were made during a single cycle for each patient. The occurrence of CR in the acute phase was statistically higher for patients receiving fosaprepitant (95% vs. 79%, P=0.018<0.05). Modest differences were seen in CR rates during the delayed phase (71% vs. 66%, P=0.586), and overall response rate (69% vs. 57%, P=0.179). The use of antiemetic rescue medicines was similar between arms A (11%) and B (7%). Conclusions: Fosaprepitant produced more CRs of CINV in the acute phase than did aprepitant, although there were no statistical differences in delayed phase response, overall response, or use of rescue antiemetics. This study confirms the safety, efficacy, and potential advantages of fosaprepitant in reducing CINV in pediatric oncology patients. Trial Registration: ClinicalTrials.gov identifier: NCT04873284.

Using Crowdfunding Campaigns to Examine Financial Toxicity and Logistical Burdens Facing Families of Children With Wilms Tumor.

INTRODUCTION: Treatment for pediatric solid tumors is often intense and multidisciplinary and can create a substantial financial burden for families. Assessing these burdens, termed the financial toxicity of treatment, can be difficult. Using Wilms tumor as an example, we evaluated crowdfunding campaigns in an attempt to better understand the impact of economic and logistic challenges associated with pediatric solid tumor care and identify features associated with successful fundraising with this method. METHODS: We used a webscraping algorithm to identify crowdfunding campaigns on GoFundMe.com for pediatric patients with Wilms tumor in the United States. We conducted a cross-sectional analysis to describe the patients and families seeking crowdfunding support for cancer care. After fundraizing information was extracted using the webscraping algorithm, each fundraiser was verified and examined by two independent reviewers to assess demographic, qualitative, disease, and treatment variables. Successful fundraisers, defined as those meeting stated financial goals, were compared to unsuccessful campaigns to identify variables associated with successful crowdfunding campaigns. RESULTS: We identified 603 children with Wilms tumor and an associated crowdfunding campaign. The median age was 4 y. The majority lived in two-parent households (68.5%). Patients mentioned siblings in 35.5% of fundraisers. While motivations for crowdfunding varied, hardships endured by families included loss of employment (52.2%), need for childcare for other children (9.8%), direct costs of care [co-payments, insurance, pharmaceuticals, out-of-pocket care costs, etc.] (80.9%), indirect costs associated with seeking care [transportation, parking, lodging, lost opportunity cost, etc.] (56.2%), and need for relocation to pursue complex cancer care (6.8%). Disease characteristics in this cohort were limited to self-reports by families. However, fundraisers mentioned disease characteristics, including tumor stage (47.6%), size (11.4%), positive nodal status (9.6%), metastatic disease (3.6%), pathology (11.8%), upstaging (4.6%), and disease recurrence (8.6%). No individually examined demographic, support, disease, or hardship-related factors varied significantly between successful and unsuccessful crowdfunding campaigns (all P > 0.05). However, successful campaigns requested less money ($11,783.25 successful versus $22,442.2 unsuccessful, <0.001), received more money ($16,409.5 successful vs 7427.4 unsuccessful, P < 0.001), and solicited larger donor numbers (170.3 successful versus 86.3 unsuccessful, P < 0.001). CONCLUSIONS: Families whose children undergo multimodal cancer care have significant expenses and burdens and can use crowdfunding to support their costs. Careful consideration of the financial and logistic strains associated with pediatric solid tumor treatment, including thorough analysis of crowdfunding sites, may support better understanding of nonclinical burdens, supporting therapeutic relationships and patient outcomes.

Pediatric renal malignancy diagnosis is associated with significant burden of care for families.

BACKGROUND AND OBJECTIVES: New childhood cancer diagnoses require timely, complex care coordination and cause considerable logistic burden for families. We used renal tumors as a model to examine healthcare utilization and cost following new solid tumor diagnosis. METHODS: Children (ages 0-21) with International Classification of Disease (ICD) codes for renal malignancy and subsequent nephrectomy were identified from North Carolina Medicaid claims data (2014-2020). We stratified patients by duration of follow-up, then quantified healthcare utilization and billing totals. RESULTS: Eighty-one children met study criteria. Median age at diagnosis was 3 years (interquartile range [IQR]: 1-5). Median family monthly earned income was $0. One month following diagnosis, children cumulatively spent a median of 16 days receiving medical care (IQR: 10-20), 28 days at 3 months (IQR: 21-43), and 50.5 days at 1 year (IQR: 35-94.5). Children cumulatively spent a median 12 days as inpatients during the first 3 months (IQR: 7-17) and 13.5 days at 1 year (IQR: 8.5-37). Children cumulatively completed a median 12 outpatient encounters at 3 months (IQR: 7-17) and 26 at 1 year (IQR: 12-36). At 1 year, median Medicaid claim reimbursements for children with renal malignancy was $50,041 (IQR: $36,670-$80,734). CONCLUSION: In examining healthcare utilization in children with renal tumor diagnoses, the substantial number of days spent in medical facilities greatly impacts the burden of care on families, especially for those with limited financial resources. Awareness of this logistic strain on families and careful planning to consolidate patient visits may improve the navigability of pediatric cancer regimens for families, particularly those with limited resources.

Versatile end effector for laparoscopic robotic scrub nurse.

PURPOSE: Integrating robotic scrub nurses in the operating room has the potential to help overcome staff shortages and limited use of available operating capacities in hospitals. Existing approaches of robotic scrub nurses are mainly focused on open surgical procedures, neglecting laparoscopic procedures. Laparoscopic interventions offer great potential for the context-sensitive integration of robotic systems due to possible standardization. However, the first step is to ensure the safe manipulation of laparoscopic instruments. METHODS: A robotic platform with a universal gripper system was designed to pick up and place laparoscopic as well as da Vinci[Formula: see text] instruments in an efficient workflow. The robustness of the gripper system was studied using a test protocol, which included a force absorption test to determine the operational safety limits of the design and a grip test to determine the system performance. RESULTS: The test protocol shows results regarding force and torque absorption capabilities of the end effector, which are essential when transferring an instrument to the surgeon to enable a robust handover. The grip tests show that the laparoscopic instruments can be safely picked up, manipulated and returned independent of unexpected positional deviations. The gripper system also enables the manipulation of da Vinci[Formula: see text] instruments, opening the door for robot-robot interaction. CONCLUSION: Our evaluation tests have shown that our robotic scrub nurse with the universal gripper system can safely and robustly manipulate laparoscopic and da Vinci[Formula: see text] instruments. The system design will continue with the integration of context-sensitive capabilities.

Risk of Surgical Intervention in Children with Diagnoses of Cancer and Preoperative Malnutrition: A National Analysis.

BACKGROUND: Perioperative nutrition is a critical component of appropriate healing and recovery after surgery. We sought to identify perioperative risk in children with cancer and low preoperative hypoalbuminemia undergoing surgical intervention. METHODS: We queried the 2015-2019 NSQIP-Peds datasets for children with a primary diagnosis of renal or hepatic malignancy undergoing surgical resection. Postoperative outcomes were evaluated for comparative risk between patients with low albumin (albumin<3.0 g/dL) and normal albumin within 30 days of their surgical procedure. Univariate analysis and multivariable logistic regression were conducted to identify perioperative risk in patients with hypoalbuminemia. RESULTS: We identified 360 children with primary diagnosis of hepatic malignancy and 896 children with renal malignancy undergoing surgical resection. Of these, 77 children had hypoalbuminemia. Patients with renal or hepatic malignancy diagnosis and low albumin levels were more likely to experience postoperative dehiscence, need for TPN at discharge, postoperative bleeding or transfusion, unplanned reoperation, and unplanned readmission, based on univariate analysis (all P > 0.05). Postoperative bleeding, need for nutritional support at discharge, and unplanned readmission were each associated with hypoalbuminemia. CONCLUSION: We demonstrate that low preoperative albumin is associated with significant perioperative risk. More attention should focus on perioperative nutritional status of children with cancer who are undergoing major resections.

Thyroid Nodules on Ultrasound in Children and Young Adults: Comparison of Diagnostic Performance of Radiologists' Impressions, ACR TI-RADS, and a Deep Learning Algorithm.

BACKGROUND. In current clinical practice, thyroid nodules in children are generally evaluated on the basis of radiologists' overall impressions of ultrasound images. OBJECTIVE. The purpose of this article is to compare the diagnostic performance of radiologists' overall impression, the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), and a deep learning algorithm in differentiating benign and malignant thyroid nodules on ultrasound in children and young adults. METHODS. This retrospective study included 139 patients (median age 17.5 years; 119 female patients, 20 male patients) evaluated from January 1, 2004, to September 18, 2020, who were 21 years old and younger with a thyroid nodule on ultrasound with definitive pathologic results from fine-needle aspiration and/or surgical excision to serve as the reference standard. A single nodule per patient was selected, and one transverse and one longitudinal image each of the nodules were extracted for further evaluation. Three radiologists independently characterized nodules on the basis of their overall impression (benign vs malignant) and ACR TI-RADS. A previously developed deep learning algorithm determined for each nodule a likelihood of malignancy, which was used to derive a risk level. Sensitivities and specificities for malignancy were calculated. Agreement was assessed using Cohen kappa coefficients. RESULTS. For radiologists' overall impression, sensitivity ranged from 32.1% to 75.0% (mean, 58.3%; 95% CI, 49.2-67.3%), and specificity ranged from 63.8% to 93.9% (mean, 79.9%; 95% CI, 73.8-85.7%). For ACR TI-RADS, sensitivity ranged from 82.1% to 87.5% (mean, 85.1%; 95% CI, 77.3-92.1%), and specificity ranged from 47.0% to 54.2% (mean, 50.6%; 95% CI, 41.4-59.8%). The deep learning algorithm had a sensitivity of 87.5% (95% CI, 78.3-95.5%) and specificity of 36.1% (95% CI, 25.6-46.8%). Interobserver agreement among pairwise combinations of readers, expressed as kappa, for overall impression was 0.227-0.472 and for ACR TI-RADS was 0.597-0.643. CONCLUSION. Both ACR TI-RADS and the deep learning algorithm had higher sensitivity albeit lower specificity compared with overall impressions. The deep learning algorithm had similar sensitivity but lower specificity than ACR TI-RADS. Interobserver agreement was higher for ACR TI-RADS than for overall impressions. CLINICAL IMPACT. ACR TI-RADS and the deep learning algorithm may serve as potential alternative strategies for guiding decisions to perform fine-needle aspiration of thyroid nodules in children.

In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues.

Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix-assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma.

Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry.

BACKGROUND: Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. METHODS: Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. RESULTS: Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. CONCLUSIONS: Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.

Accuracy of central neuro-imaging review of DIPG compared with histopathology in the International DIPG Registry.

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential. METHODS: Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, <50% pontine involvement, focally exophytic morphology, sharply defined margins, and/or marked diffusion restriction throughout. RESULTS: Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival. CONCLUSIONS: The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.

Characteristics of patients ≥10 years of age with diffuse intrinsic pontine glioma: a report from the International DIPG/DMG Registry.

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPG) generally occur in young school-age children, although can occur in adolescents and young adults. The purpose of this study was to describe clinical, radiological, pathologic, and molecular characteristics in patients ≥10 years of age with DIPG enrolled in the International DIPG Registry (IDIPGR). METHODS: Patients ≥10 years of age at diagnosis enrolled in the IDIPGR with imaging confirmed DIPG diagnosis were included. The primary outcome was overall survival (OS) categorized as long-term survivors (LTS) (≥24 months) or short-term survivors (STS) (<24 months). RESULTS: Among 1010 patients, 208 (21%) were ≥10 years of age at diagnosis; 152 were eligible with a median age of 12 years (range 10-26.8). Median OS was 13 (2-82) months. The 1-, 3-, and 5-year OS was 59.2%, 5.3%, and 3.3%, respectively. The 18/152 (11.8%) LTS were more likely to be older (P < .01) and present with longer symptom duration (P < .01). Biopsy and/or autopsy were performed in 50 (33%) patients; 77%, 61%, 33%, and 6% of patients tested had H3K27M (H3F3A or HIST1H3B), TP53, ATRX, and ACVR1 mutations/genome alterations, respectively. Two of 18 patients with IDH1 testing were IDH1-mutant and 1 was a LTS. The presence or absence of H3 alterations did not affect survival. CONCLUSION: Patients ≥10 years old with DIPG have a median survival of 13 months. LTS present with longer symptom duration and are likely to be older at presentation compared to STS. ATRX mutation rates were higher in this population than the general DIPG population.

Addressing Barriers to Fertility Preservation for Cancer Patients: The Role of Oncofertility Patient Navigation.

BACKGROUND: Infertility is a common late effect for cancer survivors. Whereas assisted reproductive technology has made it possible for survivors to take steps to preserve fertility before starting treatment, only a minority of patients proceed with preservation. Patient-, provider-, health system-, and societal-level barriers to fertility preservation (FP) exist. Oncofertility patient navigation is a valuable resource for addressing FP barriers. OBJECTIVES: To highlight the critical role of oncofertility patient navigation in addressing barriers to FP within an academic oncofertility program. METHODS: The role of the oncofertility patient navigator in reducing FP barriers, promoting informed decision-making, and ensuring program sustainability is described. Program metrics illustrating the impact of oncofertility patient navigation on referrals for FP counseling and access to FP in the last year also are provided. DISCUSSION: The oncofertility program at our academic adult and pediatric medical centers aims to facilitate rapid referral to fertility counseling and preservation services for postpubertal cancer patients. The patient navigator is integral to the success of the program. The navigator ensures that patients are: (1) well-informed about the potential impact of cancer on fertility and FP options, (2) aware of available resources (eg, financial) for pursuing FP, (3) able to access FP services if desired, and (4) well supported in making an informed FP decision. The inclusion of the patient navigator has led to an almost 2-fold increase in referrals for FP counseling in the past year over the historic annual average. CONCLUSIONS: Our institution's oncofertility program, with patient navigation at the core, provides a potential model for increasing patient access to oncofertility care and promoting program sustainability. Oncofertility patient navigation is a valuable resource for providing patients and families with education and support regarding FP decision-making, as well as addressing the multilevel barriers to FP.

Pursuing Precision: Receptor Tyrosine Kinase Inhibitors for Treatment of Pediatric Solid Tumors.

Receptor tyrosine kinases are critical for the growth and proliferation of many different cancers and therefore represent a potential vulnerability that can be therapeutically exploited with small molecule inhibitors. Over forty small molecule inhibitors are currently approved for the treatment of adult solid tumors. Their use has been more limited in pediatric solid tumors, although an increasing number of single-agent and combination studies are now being performed. These agents have been quite successful in certain clinical contexts, such as the treatment of pediatric tumors driven by kinase fusions or activating mutations. By contrast, only modest activity has been observed when inhibitors are used as single agents for solid tumors that do not have genetically defined alterations in the target genes. The absence of predictive biomarkers has limited the wider applicability of these drugs and much work remains to define the appropriate patient population and clinical situation in which receptor tyrosine kinase inhibitors are most beneficial. In this manuscript, we discuss these issues by highlighting past trials and identifying future strategies that may help add precision to the use of these agents for pediatric extracranial solid tumors.

Receptor tyrosine kinase inhibitors for the treatment of osteosarcoma and Ewing sarcoma.

Adjuvant chemotherapy for osteosarcoma and Ewing sarcoma consists of conventional cytotoxic regimens that have changed little over the past decades. There is an urgent need for agents that are more effective and have less long-term toxicity. Receptor tyrosine kinases regulate cell growth and proliferation of these tumors, and small-molecule inhibitors for many of these kinases are now available. In this article, we review published phase II trials for patients with recurrent disease and highlight the pathways targeted by available agents, as well as the toxicity and efficacy results seen to date. We also discuss the difficulties in identifying biomarkers to facilitate rational patient selection, as well as published and proposed strategies for how these inhibitors can be combined with conventional chemotherapy or other targeted agents. It is hoped future trials can capitalize on this growing experience to optimize the use of this exciting class of agents.

Imaging of childhood urologic cancers: current approaches and new advances.

Urologic tumors make up approximately 10% of all pediatric cancers, and include a variety of different histologies and imaging considerations. In this review, we discuss standard radiologic approaches for children with tumors arising in the genitourinary system, and identify important ways in which imaging affects the differential diagnosis, preoperative planning, and staging of these tumors. In addition, we provide an update on strategies to reduce the time of imaging, which may obviate the need for sedation in younger patients. Efforts to reduce a patient's overall radiation exposure and subsequent risk of second malignancy are also detailed, including recent work on surveillance imaging following completion of therapy. Finally, we highlight new techniques such as radiomics that are now being investigated for patients with these malignancies.

Phase II trial of gemcitabine and nab-paclitaxel in patients with recurrent Ewing sarcoma: A report from the National Pediatric Cancer Foundation.

BACKGROUND: The combination of gemcitabine and docetaxel is often used to treat patients with recurrent sarcoma. Nab-paclitaxel is a taxane modified to improve drug exposure and increase intratumoral accumulation and, in combination with gemcitabine, is standard therapy for pancreatic cancer. Applying the dosages and schedule used for pancreatic cancer, we performed a phase II trial to assess the response rate of gemcitabine and nab-paclitaxel in patients with relapsed Ewing sarcoma. PROCEDURE: Using a Simon's two-stage design to identify a response rate of ≥ 35%, patients received nab-paclitaxel 125 mg/m2 followed by gemcitabine 1000 mg/m2 i.v. on days 1, 8, and 15 of four-week cycles. Immunohistochemical analysis of archival tissue was performed to identify possible biomarkers of response. RESULTS: Eleven patients from four institutions enrolled, with a median age of 22 years (range, 14-27). Patients were heavily pretreated (median 3 prior regimens, range, 1-7). Thirty-five cycles were administered (median 2, range, 1-8). Accrual was stopped after 11 patients, due to only one confirmed partial response. Two other patients had partial responses after two cycles, but withdrew because of adverse effects or progression before confirmation of continued response. The predominant toxicity was myelosuppression, and four (36%) patients were removed due to hematologic toxicity despite pegfilgrastim and dose reductions. Expression of secreted protein, acidic and rich in cysteine (SPARC) and CAV-1 in archival tumors was not predictive of clinical benefit in this small cohort of patients. CONCLUSIONS: In patients with heavily pretreated Ewing sarcoma, the confirmed response rate of 9% was similar to multi-institutional studies of gemcitabine and docetaxel.