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Background: The Children's Oncology Group (COG) adopted cisplatin, 5‐flourouracil, and vincristine (C5V) as standard therapy after the INT‐0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease. Methods: In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5‐flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility. Results: One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%‐97%) for cisplatin, 96% (95% CI, 94%‐97%) for 5‐fluorouracil, 95% (95% CI, 93%‐97%) for doxorubicin, and 90% (95% CI, 87%‐93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5‐year event‐free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%‐93%) and 95% (95% CI, 87%‐98%), respectively. Conclusions: The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials. The addition of doxorubicin to the previous standard regimen of cisplatin, 5‐flourouracil, and vincristine is a feasible, tolerable, and efficacious novel treatment regimen (cisplatin, 5‐flourouracil, vincristine, and doxorubicin). This regimen is a reasonable option for future clinical trials, especially those including patients with unresectable disease at diagnosis. [ABSTRACT FROM AUTHOR]

Background: The prognosis for children with recurrent solid tumors generally is poor. Targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor A with everolimus and bevacizumab, respectively, synergistically improves progression-free survival and is well tolerated in adults with solid tumors.Methods: In the current phase 1 study, a total of 15 children with recurrent or refractory solid tumors were treated with bevacizumab and everolimus to establish the maximum tolerated dose, toxicity, and preliminary antitumor response (ClinicalTrials.gov identifier NCT00756340). The authors also evaluated everolimus-mediated inhibition of the mTOR pathway in the peripheral blood mononuclear cells of treated patients.Results: Tumors predominantly were soft tissue and/or bone sarcomas (8 cases) and brain tumors (5 cases). The first 2 patients enrolled at dose level 1 (10 mg/kg of bevacizumab and 4 mg/m2 of everolimus) experienced dose-limiting toxicities (DLTs). The next 5 patients were enrolled at dose level 0 (8 mg/kg of bevacizumab and 4 mg/m2 of everolimus), and DLTs occurred in 2 patients. The authors then modified the protocol to permit expansion of dose 0, and 8 additional patients were added, with no DLTs reported. Of all the patients, stable disease occurred in 4 patients (30.8%; median, 2 courses), and progressive disease occurred in 9 patients (69.2%). Overall survival was 0.59 years (95% CI, 0.24-1.05 years). The mTOR biomarker phospho-4EBP1 Thr/37/46 significantly decreased from baseline to day 27 in peripheral blood mononuclear cells (P = .045). Phospho-AKT levels also decreased from those at baseline.Conclusions: The maximum tolerated dose of cotreatment with bevacizumab and everolimus was 8 mg/kg of bevacizumab and 4 mg/m2 of everolimus in a 4-week cycle for children with recurrent solid tumors. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to characterize chronic disease, health-related quality of life (HRQOL), emotional distress, and social attainment among long-term survivors of neuroblastoma.Methods: Chronic health conditions among 136 ≥10-year neuroblastoma survivors (median age, 31.9 years; range, 20.2-54.6 years) and 272 community controls (median age, 34.7 years; range, 18.3-59.6 years) were graded with a modified version of the Common Terminology Criteria for Adverse Events (version 4.03). HRQOL and emotional distress were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey and the Brief Symptom Inventory-18. Log-binomial regression and logistic regression were used to compare the prevalence of chronic conditions and the frequency of reduced HRQOL, distress, and social attainment between survivors and controls. The cumulative burden approach was used to estimate multimorbidity.Results: By the age of 35 years, survivors had experienced, on average, 8.5 grade 1 to 5 conditions (95% confidence interval [CI], 7.6-9.3), which was higher than the average for controls (3.3; 95% CI, 2.9-3.7). Compared with controls, survivors had a higher prevalence of any pulmonary (P = .003), auditory (P < .001), gastrointestinal (P < .001), neurological (P = .003), or renal condition (P < .001); were more likely to report poor physical HRQOL (P = .01) and symptoms of anxiety (P = .01) and somatization (P = .01); and were less likely to live independently (P = .01) or marry (P = .01). In analyses limited to survivors, those with 1 or more grade 3 to 5 conditions were more likely to report reduced general health (odds ratio [OR], 6.6; 95% CI, 1.6-26.9), greater bodily pain (OR, 4.2; 95% CI, 1.0-17.0), and unemployment (OR, 3.2; 95% CI, 1.2-8.5).Conclusions: Because of the high burden of chronic diseases and the associations of these morbidities with reduced HRQOL and social attainment, screening and interventions that provide opportunities to optimize health are important among neuroblastoma survivors. [ABSTRACT FROM AUTHOR]

Background: It is possible that the relative lack of progress in treatment outcomes among adolescent and young adult (AYA) patients with cancer is caused by a difference in disease biology compared with the corresponding diseases in younger and older individuals. There is evidence that colon cancer is more aggressive and has a poorer prognosis in AYA patients than in older adult patients.Methods: To further understand the molecular basis for this difference, whole-exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2 pediatric colon cancers.Results: A statistically significant difference in mutational frequency was observed between AYA and adult samples in 43 genes, including ROBO1, MYC binding protein 2 (MYCBP2), breast cancer 2 (early onset) (BRCA2), MAP3K3, MCPH1, RASGRP3, PTCH1, RAD9B, CTNND1, ATM, NF1; KIT, PTEN, and FBXW7. Many of these mutations were nonsynonymous, missense, stop-gain, or frameshift mutations that were damaging. Next, RNA sequencing was performed on a subset of the samples to confirm the mutations identified by exome sequencing. This confirmation study verified the presence of a significantly greater frequency of damaging mutations in AYA compared with adult colon cancers for 5 of the 43 genes (MYCBP2, BRCA2, PHLPP1, TOPORS, and ATR).Conclusions: The current results provide the rationale for a more comprehensive study with a larger sample set and experimental validation of the functional impact of the identified variants along with their contribution to the biologic and clinical characteristics of AYA colon cancer. Cancer 2018;124:1070-82. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The identification of new therapies for high-risk (HR) hepatoblastoma is challenging. Children's Oncology Group study AHEP0731 included a HR stratum to explore the efficacy of novel agents. Herein, the authors report the response rate to the combination of vincristine (V) and irinotecan (I) and the outcome of patients with high-risk hepatoblastoma.Methods: Patients with newly diagnosed metastatic hepatoblastoma or those with a serum α-fetoprotein (AFP) level <100 ng/mL were eligible. Patients received 2 cycles of V at a dose of 1.5 mg/m2 /day intravenously on days 1 and 8 and I at a dose of 50 mg/m2 /day intravenously on days 1 to 5. Patients were defined as responders if they had either a 30% decrease in tumor burden according to Response Evaluation Criteria In Solid Tumors (RECIST) or a 90% (>1 log10 ) decline in their AFP level. Responders were to receive 2 additional cycles of VI intermixed with 6 cycles of the combination of cisplatin, doxorubicin, 5-fluorouracil, and vincristine (C5VD). Nonresponders were to receive 6 cycles of C5VD alone.Results: A total of 32 patients with a median age at diagnosis of 26 months (range, 11-159 months) were enrolled between September 2009 and February 2012. Fourteen of 30 evaluable patients were responders (RECIST and AFP in 6 patients, RECIST only in 3 patients, and AFP only in 5 patients). The median AFP decline after 2 cycles of VI for the entire group was 345,565 ng/mL (85% of the initial AFP). The 3-year event-free and overall survival rates were 49% (95% confidence interval, 30%-65%) and 62% (95% confidence interval, 42%-77%), respectively.Conclusions: The VI combination appears to have substantial activity against HR hepatoblastoma. The ultimate impact of this regimen in improving the outcomes of children with HR hepatoblastoma remains to be determined. Cancer 2017;123:2360-2367. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article presents a study assessing the oxaliplatin and irinotecan toxicities in children with solid tumors. The study was performed through an oral cephalosporin and administration of oxaliplatin with irinotecan. Results of the study show different variations in the response of patients and an indication of antitumor activity.

The article presents a prospective study which evaluates the toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric solid tumors. Image guided RFA was performed to patients included in the study, and the toxicity and imaging response was assessed at one month and three months prospectively. The results observed from the study indicate that RFA toxicity was limited and it may offer a local tumor control alternative in selected cases.

The article focuses on a study conducted to estimate the maximum tolerated dose (MTD) of an oxaliplatin and etoposide regimen in children with recurrent solid tumors. During the study, 16 patients received a total of 63 courses. In the study, Neutropenia was found to be of the dose-limiting toxicity. The study also showed that calcium and magnesium infusions did not allow escalation of the oxaliplatin dose.

The article focuses on the study which explores the disease control intervals in high-risk neuroblastoma. Results show that patients with longer initial disease control have postrecurrence survival advantage. Previous disease control interval must be considered in stratification schemes for future testing in the treatment of neuroblastoma. Study must take into account the current patterns of recurrence or progression of neuroblastoma for the optimal evaluation of new treatment strategies.

Background: The presence of a mediastinal mass in a child poses significant anesthesia-related risks including death. To optimize outcome clinicians must be able to predict which patients are at highest risk of anesthetic complications. Methods: We conducted a retrospective review of 118 pediatric patients who presented with mediastinal masses. We investigated their medical records for clinical symptoms and signs at presentation and reviewed their chest radiographs, computed tomography scans, and echocardiograms and electrocardiograms when available. We then conducted analyses to identify clinical and diagnostic imaging features associated with anesthesia-related complications. Results: Eleven of 117 [9.4%, 95% confidence interval (CI) 4.1–14.7%] patients experienced an anesthesia-related complication. Four preoperative features were significantly associated with anesthetic complications: orthopnea ( P = 0.033, odds ratio (OR) 5.31, 95% CI, 1.15–24.56), upper body edema ( P = 0.035, OR 8.00, 95% CI, 1.16–55.07), great vessel compression ( P = 0.037, OR 5.41, 95% CI, 1.11–26.49), and main-stem bronchus compression ( P = 0.044, OR 5.11, 95% CI, 1.05–24.92). The presence of pleural effusion ( P = 0.060, OR 4.53, 95% CI, 0.94–21.96) or tracheal compression ( P = 0.061, OR 5.09, 95% CI, 0.93–27.81) also appeared to be risk factors. Although the rate of anesthesia-related complications detected in our cohort was comparable with that found in earlier studies, the events were less severe. Conclusions: Patients who present with orthopnea, upper body edema, great vessel compression and main stem bronchus compression are at risk of anesthesia-related complications. The low severity of complications in our series may reflect a combination of factors: use of the least invasive method such as interventional radiology to obtain tissue for diagnosis, completion of a thorough preoperative assessment and minimal anesthesia intervention. [ABSTRACT FROM AUTHOR]