•Infants treated with proton therapy have similar disease control to their older counterparts.•Young age may not be an adverse prognostic factor if patients receive standard radiation ...doses.•Rhabdomyosarcoma of the nasal ala in infants may signify a distinctly poor prognosis.•Toxicity data suggest evidence of hypoplasia among survivors.
In infants with rhabdomyosarcoma, young age is considered an adverse prognostic factor and treatment is often attenuated to reduce side effects. Proton therapy may improve the therapeutic ratio in these patients. We report outcomes in infants with rhabdomyosarcoma treated with proton therapy.
Between 2009 and 2019, 37 infants <24 months old with non-metastatic rhabdomyosarcoma received proton therapy. Local control (LC), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan–Meier product limit. The log-rank test assessed significance between selected prognostic factors. Toxicity was graded per CTCAEv5.0.
Median follow-up was 5.1 years. Overall, 76% of patients had an unfavorable primary site. Median dose was 50.4GyRBE. At 5 years, LC, PFS, and OS rates were 83%, 78%, and 83%. On univariate analysis, 5-year LC and OS were inferior for favorable versus unfavorable disease sites (67% vs 89%, 67% vs 89%, respectively; p < .05) and 5-year OS was superior in stage 3 versus stage 1–2 disease (91% vs 69%; p = .05), owing to inclusion of nasal ala patients among stage 1. Of 9 recurrences, 7 were in-field, 4 occurring in infants with nasal ala primaries. Recategorizing nasal ala as an unfavorable site resulted in 100% 5-year LC and OS for favorable sites.
Six infants experienced late grade 3 toxicity. None developed grade 4 or 5 late toxicity.
Young age alone may not be an adverse prognostic factor provided infants receive local therapy similar to older children. Consideration should be given to classifying nasal ala primaries as an unfavorable site.
Bradfield shares his thoughts on writing short stories, and the limited market for them in contemporary society. Publishing short stories was once a writer's prelude to getting a novel published, but ...that career path is disappearing.
Purpose
Despite the dosimetric advantages of proton therapy, little data exist on patients who receive proton therapy for Ewing sarcoma of the cranium and skull base. This study reports local disease ...control and toxicity in such patients.
Materials/methods
We reviewed 25 patients (≤21 years old) with nonmetastatic Ewing sarcoma of the cranium and skull base treated between 2008 and 2018. Treatment toxicity was graded per the Common Terminology Criteria for Adverse Events v4.0. The Kaplan‐Meier product limit method provided estimates of disease control and survival.
Results
Median patient age was 5.9 years (range, 1–21.7). Tumor subsites included the skull base (48%), non‐skull‐base calvarial bones (28%), paranasal sinuses (20%), and nasal cavity (4%). All patients underwent multiagent alkylator‐ and anthracycline‐based chemotherapy; 16% underwent gross total resection (GTR) before radiation. Clinical target volume (CTV) 1 received 45 GyRBE and CTV2 received 50.4 GyRBE following GTR or 54–55.8 GyRBE following biopsy or subtotal resection. Median follow‐up was 3.7 years (range, 0.26–8.3); no patients were lost. The 4‐year local control, disease‐free survival, and overall survival rates were 96%, 86%, and 92%, respectively. Two patients experienced in‐field recurrences. One patient experienced bilateral conductive hearing loss requiring aids, two patients developed intracranial vasculopathy, and 6 patients required hormone replacement therapy for neuroendocrine deficits. None developed a secondary malignancy.
Conclusion
Proton therapy is associated with a favorable therapeutic ratio in children with large Ewing tumors of the cranium and skull base. Despite its high conformality, we observed excellent local control and no marginal recurrences. Treatment dosimetry predicts limited long‐term neurocognitive and neuroendocrine side effects.
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.
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.
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.
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.
Since the original description of pathogenic germline
DICER1
variation underlying PPB, the spectrum of extrapulmonary neoplasms known to be associated with
DICER1
has continued to expand and now ...includes tumors of the ovary, thyroid, kidney, eye and brain among other sites. This report documents our experience with another manifestation: a primitive sarcoma that resembles PPB and
DICER1
-associated sarcoma of the kidney. These tumors are distinguished by their unusual location in the peritoneal cavity, associated with visceral and/or parietal mesothelium. A total of seven cases were identified through pathology review in children presenting at a median age of 13 years (range 3 to 14 years). Primary sites of origin included the Fallopian tube (4 cases), serosal surface of the colon (one case), and pelvic sidewall (2 cases). One case had pathologic features of type I PPB, another type Ir (regressed) PPB and the remaining 5 had features of type II or III PPB with a mixed primitive sarcomatous pattern with or without cystic elements. All had a pathogenic
DICER1
variation identified in germline and/or tumor DNA. PPB-like peritoneal tumors represent a newly described manifestation of
DICER1
pathogenic variation whose pathologic features are also recapitulated in
DICER1
-related renal sarcoma, cervical embryonal rhabdomyosarcoma, and some Sertoli-Leydig cell tumors with heterologous elements. Tumors arising from the Fallopian tube or elsewhere in the abdomen/pelvis, especially those with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation, should prompt consideration of germline and tumor
DICER1
testing.
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.
Purpose: Despite widespread concerns of radiotherapy toxicity in children with head and neck tumors, recent Children's Oncology Group (COG) findings suggest that the use of 45 Gy results in an ...unacceptably high rate of local recurrences in patients with low-risk orbital rhabdomyosarcoma. We therefore evaluated outcomes in our pediatric patients who received 45 GyRBE using proton therapy.
Material and methods: To assess disease control and toxicity, we reviewed the medical records of 30 children (≤21 years old) with COG stage 1, group III embryonal orbital rhabdomyosarcoma enrolled on a prospective outcome study and treated with proton therapy between 2007 and 2018.
Results: Median age at the time of radiation was 4.8 years old. Twenty-one and nine patients received ifosfamide- and cyclophosphamide-based chemotherapy according to their respective cooperative group regimens. Median duration between the start of induction chemotherapy and radiation was 12 weeks. Two patients had a complete response to induction chemotherapy and two had stable disease. Twenty-six patients had a partial response to induction chemotherapy, with a median volume reduction of 66%. With a median follow-up of 4.0 years (range, 0.5-9.5 years), we observed 1 local failure 6 months following treatment in a patient who had a partial response to cyclosphophomide-based induction chemotherapy. The 5-year local control, progression-free survival, and overall survival rates were 97%, 97%, and 100%, respectively. Serious late toxicities included 18 patients with cataracts, 4 with exposure keratoconjunctivitis resulting in permanently reduced visual acuity, and 1 with chronic sinusitis.
Conclusion: 45 GyRBE offers effective local control for most patients with group III orbital rhabdomyosarcoma. The delivery of proton therapy to the postinduction tumor volume plus a small margin can mitigate early- and intermediate-term toxicity, but side effects still occur and long-term data are needed to demonstrate the dosimetric advantage of proton therapy.
Background The Florida Association of Pediatric Tumor Programs (FAPTP) has used the Statewide Patient Information Reporting System (SPIRS) since 1981 to track all new cases of pediatric cancer. We ...reviewed the last 40 years of data to see how pediatric cancer care has evolved. Methods We retrospectively analyzed SPIRS data from 1981 through 2020 in five-year increments, looking at numbers of new diagnoses, care delivery sites, and trial enrollment in Children's Oncology Group (COG) studies. Results From 1981-2020 Florida's population increased almost 88% while the pediatric population only grew 61%. New pediatric cancer diagnoses increased 326% to over 1,000 new cases/year. The percentage of patients treated at FAPTP centers grew from 30% to 57% with an annual percentage change (APC) of 10.3% (95% Confidence Interval CI of 0.6 to 20.9%). The rate of COG clinical trial enrollment decreased from 32% in 1981-1985 to 20% in 2016-2020, for an APC of 8.91% (95% CI of -13.3 to -4.3%). Conclusions The striking increase in pediatric cancer cases in Florida over the last 40 years was out of proportion to the population growth. More patients received care at FAPTP centers, but a lower percentage were enrolled on COG trials.
The release of engineered nanoparticles (ENPs) into the environment has raised concerns about the potential risks to food safety and human health. There is a particular need to determine the extent ...of ENP uptake into plant foods. Belowground vegetables growing in direct contact with the growth substrate are likely to accumulate the highest concentration of ENPs. Carrot (
Daucus carota
) was grown in sand amended with ZnO, CuO, or CeO
2
NPs or the same concentrations of Zn
2+
, Cu
2+
, or Ce
4+
. Treatment with ZnO or Zn
2+
produced a concentration-dependent decrease in root and total biomass. Ionic Cu
2+
and Ce
4+
caused a greater reduction in shoot biomass as compared to the corresponding ENP treatments. Accumulation of Zn, Cu, or Ce in the taproot was restricted to the taproot periderm. Metal concentrations in the taproot periderm were higher for the ionic treatments than for the ENP treatments. Radial penetration of the metals into the taproot and subsequent translocation to shoots were also generally greater for plants receiving the ionic treatment than those receiving the ENP treatment. The distribution of the metals from the ENP treatments across the periderm, taproot, and shoots differed from that observed for the ionic treatments. Overall, the ENPs were no more toxic than the ionic treatments and showed reduced accumulation in the edible tissues of carrot. The results demonstrate that the understanding of ionic metal transport in plants may not accurately predict ENP transport and that an additional comparative study is needed for this and other crop plants.
The ionic forms of Zn, Cu, and Ce are transported into carrot taproots, while nanomaterial forms of ZnO, CuO, and CeO
2
were largely screened by the taproot outer periderm layer.
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