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Owing to adjacent critical organs, the aggressive multimodality local therapy necessary for Ewing sarcoma of the chest wall is a challenge. Our previous review of historical outcomes at our institution revealed suboptimal disease control and a high incidence of grade ≥3 toxic effects in patients treated before 2006. The purpose of this study was to evaluate changes during the past decade since the introduction of proton therapy.Thirty-nine consecutive pediatric patients with a chest wall Ewing sarcoma treated between 2006 and 2020 at the University of Florida were identified. The median maximum tumor diameter was 10 cm (range, 4-28 cm). At diagnosis, 19 patients had local disease and the others had a pleural effusion (11), pleural nodules (5), or pulmonary metastases (4). Patients were treated with chemotherapy regimens according to contemporary North American and European protocols: 7 were treated with preoperative, 18 with postoperative, and 14 with definitive radiation. Preceding primary site treatment, 15 patients required hemithorax radiation and 4 patients underwent whole-lung irradiation using photon techniques. The total median radiation dose to the primary tumor was 52.8 GyRBE [relative biological effectiveness] (range, 44.4-55.8 GyRBE).With a median follow-up of 4 years (range, 0.7-14.7 years), the 5-year local control, progression-free survival, and overall survival rates were 97.2%, 74.4%, and 81.6%, respectively, for the whole cohort. For the 19 patients with nonmetastatic disease, the 5-year local control, progression-free survival, and overall survival rates were 100%, 78.9%, and 78.9%, respectively. No patients developed grade ≥4 toxic effects. Two patients (5%) experienced grade 3 toxic effects related to multimodality treatment; both were patients who required surgery to correct scoliosis. Two patients (5%) developed grade 2 pneumonitis.Compared with our prior published institutional experience, our data suggest improvements in disease control and multimodality toxic effects since the introduction of proton therapy. This should be confirmed with a larger sample size and longer follow-up.

In 2010, we published a comprehensive review of our institutional outcomes about treating children with spinal and paraspinal Ewing sarcoma using photon therapy. Multimodality therapy was associated with fair disease control but also with serious toxicity, including a 37% rate of grade 3 or greater toxicity. We therefore sought to assess our more recent experience about treating children with more modern technology and treatment regimens.Between 2010 and 2021, 32 pediatric patients with nonmetastatic spinal and paraspinal Ewing sarcoma were treated at University of Florida and enrolled in a retrospective outcome study. Median age at diagnosis was 9.8 years (range, 2.1-21.8 years). Within the cervical, thoracic, and lumbar spine regions, 3, 22, and 7 tumors arose, respectively. Median maximum tumor diameter was 5 cm (range, 3-19 cm). At diagnosis, 28 of 32 patients had motor, bowel, or bladder deficits. Chemotherapy was delivered according to contemporary North American and European interval-compressed regimens. Before radiation therapy, 14 patients underwent gross total resection, whereas 18 underwent a biopsy or subtotal resection with cord decompression. All patients were treated with proton therapy; 6 with hardware stabilization also received a component of intensity modulated photon therapy. Median prescription dose was 50.4 gray relative biological effectiveness (GyRBE; range, 45-55.8 GyRBE). Median maximum dose to the spinal cord was 50.2 GyRBE (range, 0-54.9 GyRBE).With a median follow-up of 4.1 years (range, 0.7-9.4 years), the 5-year local control, progression-free survival, and overall survival rates were 92%, 79%, and 85%, respectively. Ten of 30 living patients have residual motor, bowel, or bladder deficits. Overall, 22% of patients experienced Common Terminology Criteria for Adverse Events grade 3 late toxicity related to multimodality treatment: kyphosis (n = 4), esophagitis (n = 2), and chronic kidney disease (n = 1). No patients developed grade 4 or greater toxicity, new neurologic deficits, or second malignancy.Modern treatment advances may offer an improved therapeutic ratio for pediatric patients with spinal and paraspinal Ewing sarcoma. With appropriate management, most patients can be cured with recovery of long-term neurologic function and modest side effects.

Children with relapsed/refractory central nervous system (CNS) tumors require novel combinations of therapies. Irinotecan and temozolomide (IT) is a frequently used therapy with an established toxicity profile. Bevacizumab is an anti-VEGF monoclonal antibody with demonstrated activity in CNS tumors. Therefore, the combination of these agents has therapeutic potential in CNS tumors. The objective of this study was to determine the maximum tolerated dose (MTD) of escalating dose IT combined with a fixed dose of bevacizumab (BIT) in children with relapsed/refractory CNS tumors.A phase I trial was performed in a 3 + 3 design. Therapy toxicities and radiologic responses to treatment were described.One hundred eighty cycles of therapy were administered to 26 patients. The MTD of BIT was dose level 1, (bevacizumab 10 mg/kg on days 1 and 15, irinotecan 125 mg/mAt the MTD, BIT therapy was well tolerated, and prolonged treatment courses of up to 24 cycles were feasible, with radiographic responses observed. Further evaluation is needed for efficacy in a phase II trial (NCT00876993, registered April 7, 2009, www.gov ).

Posaconazole is a lipophilic triazole antifungal that exhibits variable absorption when administered orally. It possesses a broad spectrum of activity against various fungi, such as Aspergillus and traditionally resistant molds such as Rhizopus and Mucor, which carry a poor prognosis. Unfortunately, the tablet and suspension formulations of posaconazole are Food and Drug Administration approved for treatment of fungal diseases only in patients older than 13 years of age. Furthermore, the approval of the IV formulation is exclusively for adult patients. Nevertheless, the extended spectrum of activity and available dosage forms make it an attractive option for pediatric use. The data that exist to guide dosing of posaconazole in young pediatric patients are limited primarily to case series and case reports. Thus, we recommend therapeutic drug monitoring to ensure both safety and efficacy in pediatric patients. Herein we describe our experience with both oral and IV posaconazole in the salvage therapy of a 5-year-old female with extensive cutaneous Mucor. In contrast to previous reports, which show larger doses may be necessary to obtain therapeutic concentrations in pediatric patients as compared with adults, our patient reached targeted concentrations with weight-based dosing.

Voriconazole pharmacokinetics are not well characterized in children despite prior studies. To assess the appropriate pediatric dosing, a study was conducted in 40 immunocompromised children aged 2 to 0–12 ) was calculated using the noncompartmental method and compared to that for adults receiving approved dosing regimens (6→4 mg/kg IV q12h, 200 mg PO q12h). On average, the AUC 0–12 in children receiving 7 mg/kg IV q12h on day 1 and at IV steady state were 7.85 and 21.4 μg·h/ml, respectively, and approximately 44% and 40% lower, respectively, than those for adults at 6→4 mg/kg IV q12h. Large intersubject variability was observed. At steady state during oral treatment (200 mg q12h), children had higher average exposure than adults, with much larger intersubject variability. The exposure achieved with oral dosing in children tended to decrease as weight and age increased. The most common treatment-related adverse events were transient elevated liver function tests. No clear threshold of voriconazole exposure was identified that would predict the occurrence of treatment-related hepatic events. Overall, voriconazole IV doses higher than 7 mg/kg are needed in children to closely match adult exposures, and a weight-based oral dose may be more appropriate for children than a fixed dose. Safety of voriconazole in children was consistent with the known safety profile of voriconazole.

BACKGROUND The optimal administration of radiotherapy for patients with high-risk neuroblastoma (NB) currently is undefined in the context of modern therapy using myeloablative chemotherapy with autologous stem cell rescue (hematopoietic stem cell transplantation [HSCT]). METHODS The authors conducted a retrospective review of the records of 21 consecutive patients with high-risk NB to assess local control and toxicity of external beam radiotherapy (XRT). Therapy included multiagent induction chemotherapy and delayed surgical resection, consolidation of HSCT and local XRT, and 13-cis-retinoic acid maintenance therapy. XRT was delivered to the primary site, using postchemotherapy volumes, and to initial metastatic sites with 1–2 cm margins to 2100 centigrays (cGy) using 14 fractions administered once daily. RESULTS Four of 21 patients did not receive XRT due to toxic death (n = 2), disease progression before XRT (n = 1), or parental refusal (n = 1). The median time to XRT post-HSCT was 54 days. Thirteen patients received a second peripheral blood stem cell infusion after completing XRT. Twelve of the 14 patients who received XRT post-HSCT and for whom toxicity data were available had Grade 3–4 acute toxicities, including gastrointestinal toxicity (n = 8), hematologic toxicity (n = 9), and infection (n = 1). Nonrecurrent long-term toxicities included prolonged nutritional deficiency (n = 9) and leg-length discrepancy (n = 1). Tumors recurred in 7 of 21 patients (5 of 17 patients who received radiotherapy), either within a radiation field (n = 1) or at distant nonirradiated sites (n = 6). The estimated local failure rate was 7% (95% confidence interval [95% CI], 0–14%), with a 2-year event-free survival rate of 48% (95% CI, 26–70%). CONCLUSIONS Post-HSCT, fractionated XRT to 2100 cGy was a tolerable and effective treatment for patients with high-risk NB, and minimal recurrences were observed at designated XRT sites. Cancer 2004. © 2004 American Cancer Society.

Purpose To perform a retrospective review of the authors' experience with invasive aspergillosis (IA) in a pediatric population treated with conventional chemotherapy. Case series of IA in the pediatric oncology population are limited but generally report poor overall survival. Methods Medical records were reviewed of all patients receiving conventional chemotherapy for malignant disease who developed IA at Children's Hospital and Regional Medical Center, Seattle, Washington, between January 1, 1995, and January 1, 2002. Results During the study period there were 11 cases of IA in pediatric cancer patients treated with conventional chemotherapy. All patients had pulmonary IA; two also had evidence of disseminated disease. All patients underwent diagnostic tissue biopsy. Sixty-four percent required further surgery to excise bulky disease. Medical therapy varied with disease presentation and the overall clinical picture, although prolonged treatment with amphotericin B and itraconazole was the mainstay of therapy. Resolution of clinical disease was seen in 91% of patients. Seventy-three percent received further chemotherapy. The 3-year estimated survival was 82%, with a median follow-up of 32.5 months. Conclusions Early diagnosis and aggressive intervention improve long-term survival from IA in immunocompromised pediatric oncology patients. Aggressive surgical resection, prolonged medical therapy after gross resolution of disease, and chemoprophylaxis during subsequent chemotherapy decrease the likelihood of recurrent IA despite subsequent cytotoxic therapy. The ability to proceed with intensive chemotherapy despite a history of IA may improve long-term survival.