The potential release of metal oxide engineered nanoparticles (ENP) into agricultural systems has created the need to evaluate the impact of these materials on crop yield and food safety. The study ...here grew sweet potato (Ipomoea batatas) to maturity in field microcosms using substrate amended with three concentrations (100, 500 or 1000 mg kg DW−1) of either nZnO, nCuO, or nCeO2 or equivalent amounts of Zn2+, Cu2+, or Ce4+. Adverse effects on tuber biomass were observed only for the highest concentration of Zn or Cu applied. Exposure to both forms of Ce had no adverse effect on yield and a slight positive benefit at higher concentrations on tuber diameter. The three metals accumulated in both the peel and flesh of the sweet potato tubers, with concentrations higher in the peel than the flesh for each element. For Zn, >70% of the metal was in the flesh and for Cu >50%. The peels retained 75–95% of Ce in the tubers. The projected dietary intake of each metal by seven age-mass classes from child to adult only exceeded the oral reference dose for chronic toxicity in a scenario where children consumed tubers grown at the highest metal concentration. The results throughout were generally not different between the ENP- and ionic-treatments, suggesting that the added ENPs underwent dissolution to release their component ions prior to accumulation. The results offer insight into the fate and impact of these ENPs in soils.
•Reduced sweet potato biomass yield was observed with Zn or Cu at 1000 mg kg−1 soil.•Metals accumulated more in sweet potato peels that in the tuber flesh.•Little risk from consumption was projected for dietary intake of Zn, Cu, or Ce.•No consistent differences occurred between the nanoparticle and ionic forms.•Results suggested dissolution of the nanoparticles in the microcosms to ionic form.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Socioeconomic disparities exist in pediatric patients with hematologic malignancies, leading to suboptimal survival rates. Social determinants of health impact health outcomes, and in children, they ...may not only lead to worse survival outcomes but carry over into late effects in adult life. The social deprivation index (SDI) is a composite score using geographic county data to measure social determinants of health. Using the SDI, the purpose of the present study is to stratify survival outcomes in pediatric patients with hematologic malignancies based on area deprivation.
A retrospective cohort study was performed using the national Surveillance, Epidemiology, and End Results oncology registry in the USA from 1975 to 2016 based on county-level data. Pediatric patients (≤18 y old) with a diagnosis of leukemia or lymphoma based on the International Classification for Oncology, third edition (ICD-O-3) were used for inclusion criteria. Patients were grouped by cancer subtype for leukemia into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia while for lymphoma into non-Hodgkin's lymphoma and Hodgkin's lymphoma. SDI scores were calculated for each patient and divided into quartiles, with Q1 being the lowest area of deprivation and Q4 being the highest, respectively.
A total of 38,318 leukemia and lymphoma patients were included. Quartile data demonstrated stratification in survival based on area deprivation for ALL, with no survival differences in the other cancer subtypes. Patients with ALL from the most deprived area had a roughly 3% difference in both overall and cancer-specific morality at 5 years compared with the least deprived area.
Disparities in pediatric patients with ALL represent a significant area for quality improvement. Social programs may have value in improving survival outcomes and could rely on metrics such as SDI.
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 sub(2) NPs or the same concentrations of Zn super(2+), Cu super(2+), or Ce super(4+). Treatment with ZnO or Zn super(2+) produced a concentration-dependent decrease in root and total biomass. Ionic Cu super(2+) and Ce super(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.
Purpose
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.
Methods
A phase I trial was performed in a 3 + 3 design. Therapy toxicities and radiologic responses to treatment were described.
Results
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/m
2
on days 1 and 15, and temozolomide 125 mg/m
2
on days 1–5 of 28-day cycles). The regimen was well tolerated with primarily hematologic toxicity, which was not dose limiting. Among 22 response-evaluable patients, there was 1 complete response (CR), 6 partial responses (PR), and 10 stable diseases (SD) with an overall response rate (ORR: CR + PR) of 31.8%.
Conclusion
At 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.clinicaltrials.gov
).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, PRFLJ, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ewing sarcoma of the pelvis is associated with inferior local control compared with those arising from other primary sites. Despite its increased use, outcome data for treatment with proton therapy ...remain limited. We report 3-year disease control and toxicity in pediatric patients treated with proton therapy.
Thirty-five patients aged ≤21 years (median, 14 years) with nonmetastatic pelvic Ewing sarcoma received proton therapy and chemotherapy between 2010 and 2018. Overall survival and tumor control rates were calculated using the Kaplan-Meier method. A log-rank test assessed significance between strata of prognostic factors. Significant toxicity was reported per the Common Terminology Criteria for Adverse Events, version 4.0.
Most patients received definitive radiation (n = 26; median dose 55.8 Gy relative biological effectiveness RBE; range, 54.0-64.8), 7 received preoperative radiation (50.4 Gy RBE), and 2 received postoperative radiation (45 Gy RBE and 54 Gy RBE). The median primary tumor size was 10.5 cm. With a median follow-up of 3 years (range, 0.3-9.0 years), the 3-year overall survival, progression-free survival, and local control rates were 83% (95% confidence interval CI, 65%-93%), 64% (95% CI, 45%-79%), and 92% (95% CI, 74%-98%), respectively. There was no association between local control, progression-free survival, or overall survival and tumor size, patient age, radiation dose, or definitive versus pre-/postoperative radiation therapy. Median time to progression was 1 year (range, 0.1-1.9 years). All patients with large tumors (≥8 cm) who underwent definitive proton therapy with a higher dose (≥59.4 Gy RBE) remained free from tumor recurrence (n = 5). Five patients experienced grade ≥2 subacute/late toxicity, all of whom were treated with combined surgery and radiation.
Definitive proton therapy offers local control comparable to photon therapy in pediatric patients with pelvic Ewing sarcoma. These data lend preliminary support to radiation dose escalation without significant toxicity, which may contribute to the favorable outcomes. Combined surgery and radiation therapy, particularly preoperative radiation, is associated with postoperative complications, but not survival, compared with radiation alone.
There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions ...related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions.
Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications.
Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection.
Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes.
clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
The expanding production and use of engineered nanomaterials (ENMs) have raised concerns about the potential risk of those materials to food safety and human health. In a prior study, the ...accumulation of Zn, Cu, and Ce from ZnO, CuO, or CeO2, respectively, was examined in carrot (Daucus carota L.) grown in sand culture in comparison to accumulation from exposure to equivalent concentrations of ionic Zn(2+), Cu(2+), or Ce(4+). The fresh weight concentration data for peeled and unpeeled carrots were used to project dietary intake of each metal by seven age-mass classes from child to adult based on consumption of a single serving of carrot. Dietary intake was compared to the oral reference dose (oral RfD) for chronic toxicity for Zn or Cu and estimated mean and median oral RfD values for Ce based on nine other rare earth elements. Reverse dietary intake calculations were also conducted to estimate the number of servings of carrot, the mass of carrot consumed, or the tissue concentration of Zn, Cu, or Ce that would cause the oral RfD to be exceeded upon consumption. The projections indicated for Zn and Cu, the oral RfD would be exceeded in only a few highly unrealistic scenarios of exceedingly high Zn or Cu concentrations in the substrate from ZnO or CuO or consumption of excessive amounts of unpeeled carrot. The implications associated with the presence of Ce in the carrot tissues depended upon whether the mean or median oral RfD value from the rare earth elements was used as a basis for comparison. The calculations further indicated that peeling carrots reduced the projected dietary intake by one to two orders of magnitude for both ENM- and ionic-treated carrots. Overall in terms of total metal concentration, the results suggested no specific impact of the ENM form on dietary intake. The effort here provided a conservative view of the potential dietary intake of these three metals that might result from consumption of carrots exposed to nanomaterials (NMs) and how peeling mitigated that dietary intake. The results also demonstrate the potential utility of dietary intake projections for examining potential risks of NM exposure from agricultural foods.
Studies reporting on the impact of social determinants of health on childhood cancer are limited. The current study aimed to examine the relationship between health disparities, as measured by the ...social deprivation index, and mortality in paediatric oncology patients using a population-based national database.
In this cohort study of children across all paediatric cancers, survival rates were determined using the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. The social deprivation index was used to measure and assess healthcare disparities and specifically the impact on both overall and cancer-specific survival. Hazard ratios were used to assess the association of area deprivation.
The study cohort was composed of 99,542 patients with paediatric cancer. Patients had a median age of 10 years old (IQR: 3–16) with 46,109 (46.3%) of female sex. Based on race, 79,984 (80.4%) of patients were identified as white while 10,801 (10.9%) were identified as Black. Patients from socially deprived areas had significantly higher hazard of death overall for both non-metastatic 1.27 (95% CI: 1.19–1.36) and metastatic presentations 1.09 (95% CI: 1.05–1.15) compared to in more socially affluent areas.
Patients from the most socially deprived areas had lower rates of overall and cancer-specific survival compared to patients from socially affluent areas. With an increase in childhood cancer survivors, implementation of social determinant indices, such as the social deprivation index, might aid improvement in healthcare outcomes for the most vulnerable patients.
There was no study sponsor or extramural funding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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