skip to main content

Explore Research Products in the NSF-PAR

Title: Asparaginase formulation impacts hypertriglyceridemia during therapy for acute lymphoblastic leukemia
Abstract Background

Glucocorticoids and asparaginase, used to treat acute lymphoblastic leukemia (ALL), can cause hypertriglyceridemia. We compared triglyceride levels, risk factors, and associated toxicities in two ALL trials at St. Jude Children's Research Hospital with identical glucocorticoid regimens, but different asparaginase formulations. In Total XV (TXV), nativeEscherichia colil‐asparaginase was front‐line therapy versus the pegylated formulation (PEG‐asparaginase) in Total XVI (TXVI).

 Procedure

Patients enrolled on TXV (n = 498) and TXVI (n = 598) were assigned to low‐risk (LR) or standard/high‐risk (SHR) treatment arms (ClinicalTrials.gov identifiers: NCT00137111 and NCT00549848). Triglycerides were measured four times and were evaluable in 925 patients (TXV:n = 362; TXVI:n = 563). The genetic contribution was assessed using a triglyceride polygenic risk score (triglyceride‐PRS). Osteonecrosis, thrombosis, and pancreatitis were prospectively graded.

 Results

The largest increase in triglycerides occurred in TXVI SHR patients treated with dexamethasone and PEG‐asparaginase (4.5‐fold increase;P <1 × 10−15). SHR patients treated with PEG‐asparaginase (TXVI) had more severe hypertriglyceridemia (>1000 mg/dL) compared to nativel‐asparaginase (TXV): 10.5% versus 5.5%, respectively (P = .007). At week 7, triglycerides did not increase with dexamethasone treatment alone (LR patients) but did increase with dexamethasone plus asparaginase (SHR patients). The variability in triglycerides explained by the triglyceride‐PRS was highest at baseline and declined with therapy. Hypertriglyceridemia was associated with osteonecrosis (P = .0006) and thrombosis (P = .005), but not pancreatitis (P = .4).

 Conclusion

Triglycerides were affected more by PEG‐asparaginase than nativel‐asparaginase, by asparaginase more than dexamethasone, and by drug effects more than genetics. It is not clear whether triglycerides contribute to thrombosis and osteonecrosis or are biomarkers of the toxicities.

  more » « less
NSF-PAR ID:
10459212
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Pediatric Blood & Cancer
Volume:
67
Issue:
1
ISSN:
1545-5009
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ; ; ( , Journal of Neuroendocrinology)
    Abstract Background

    The optimal duration of capecitabine combined with temozolomide (CapTem) for metastatic pancreatic neuroendocrine tumours (PanNETs) remains controversial. The present study aimed to assess the activity and safety of prolonged CapTem and Cap maintenance therapy in patients with metastatic PanNETs.

     Methods

    Retrospective real‐world data of 94 patients with metastatic PanNETs were obtained from one cancer centre. Fifteen patients were treated with Cap maintenance therapy after fixed 12–13 cycles of CapTem (group I), 44 patients were treated with prolonged CapTem until disease progression (group II), and 35 patients were treated with fixed 12–13 cycles of CapTem (group III).

     Results

    The mean ± SE follow‐up period was 41.79 ± 26.31 months. The median CapTem treatment duration was 12 months in group I and 14 months in group II. The median time to best partial response was 12 months both in groups I and group II. The objective response rates of groups I and II were significantly higher than those of group III (73.3%, 41.9%, and 20%, respectively,p = .002). The median progression‐free survival (mPFS) of group I and group II was significantly higher than that of group III (35 months, 26 months vs. 19 months,p < .001). Safety analysis of the three groups indicated rare events of grade 3–4 toxicities, with nausea, vomiting, fatigue, and anaemia being the most common adverse effects.

     Conclusions

    Patients with PanNETs who responded well to CapTem treatment may benefit from prolonged CapTem and Cap maintenance therapy after fixed cycles. Prospective studies are encouraged to further explore the prolonged CapTem treatment and maintenance therapy.

     
    more » « less
  2. ; ; ; ; ; ; ; ; ; ; et al ( , Head & Neck)
    Abstract Background

    Recurrent head and neck cancer has poor prognosis. Stereotactic body radiotherapy (SBRT) may improve outcomes by delivering ablative radiation doses.

     Methods

    We reviewed patients who received definitive‐intent SBRT reirradiation at our institution from 2013 to 2020. Patterns of failure, overall survival (OS), and toxicities were analyzed.

     Results

    One hundred and thirty‐seven patients were evaluated. The median OS was 44.3 months. The median SBRT dose was 45 Gy and median target volume 16.9 cc. The 1‐year local, regional, and distant control was 78%, 66%, and 83%, respectively. Systemic therapy improved regional (p = 0.004) and distant control (p = 0.04) in nonmetastatic patients. Grade 3+ toxicities were more common at mucosal sites (p = 0.001) and with concurrent systemic therapy (p = 0.02).

     Conclusions

    In a large cohort of SBRT reirradiation for recurrent, small volume head and neck cancers, a median OS of 44.3 months was observed. Systemic therapy improved regional and distant control. Toxicities were modulated by anatomic site and systemic therapy.

     
    more » « less
  3. ; ; ; ; ; ; ; ; ; ; et al ( , Journal of Applied Clinical Medical Physics)
    Abstract Purpose

    To determine the optimal dose‐volume constraint for laryngeal sparing using three commonly employed intensity modulated radiation therapy (IMRT) approaches in patients with oropharyngeal cancer treated to the bilateral neck.

     Materials and methods

    Thirty patients with stage II‐IVA oropharynx cancers received definitive radiotherapy with split‐field IMRT (SF‐IMRT) to the bilateral neck between 2008 and 2013. Each case was re‐planned using whole‐field IMRT (WF‐IMRT) and volumetric modulated arc therapy (VMAT) and plan quality metrics and dose to laryngeal structures was evaluated. Two larynx volumes were defined and compared on the current study: the Radiation Therapy Oncology Group (RTOG) larynx as defined per the RTOG 1016 protocol and the MDACC larynx defined as the components of the larynx bounded by the superior and inferior extent of the thyroid cartilage.

     Results

    Target coverage, conformity, and heterogeneity indices were similar in all techniques. The RTOG larynx mean dose was lower with WF‐IMRT than SF‐IMRT (22.1 vs 25.8 Gy;P < 0.01). The MDACC larynx mean dose was 17.5 Gy ± 5.4 Gy with no differences between the 3 techniques. WF‐IMRT and VMAT plans were associated with lower mean doses to the supraglottic larynx (42.1 vs 41.2 vs 54.8 Gy;P < 0.01) and esophagus (18.1 vs 18.2 vs 36 Gy;P < 0.01).

     Conclusions

    Modern whole field techniques can provide effective laryngeal sparing in patients receiving radiotherapy to the bilateral neck for advanced oropharyngeal cancers.

     Summary

    We evaluated laryngeal dose in patients with locally advanced oropharyngeal cancer treated to the bilateral neck using split‐field IMRT (SF‐IMRT), whole‐field IMRT (WF‐IMRT) and volumetric arc therapy (VMAT). All three techniques provided good sparing of laryngeal structures and were able to achieve a mean larynx dose < 33 Gy. There were no significant differences in dose to target structures or non‐laryngeal organs at risk among techniques.

     
    more » « less
  4. ; ; ; ; ; ; ; ; ; ; et al ( , The Laryngoscope)
    Objectives

    We aim to report oncologic outcomes after conventional radiotherapy (ConRT) using opposed lateral beams and intensity‐modulated radiation therapy (IMRT) for tumor (T)1 nodal (N)0 T1 N0 glottic squamous cell carcinoma.

     Study Design

    Retrospective case‐control study.

     Methods

    We retrospectively reviewed demographic, disease, and treatment characteristics for patients treated at our institution during 2000 to 2013.

     Results

    One hundred fifty‐three patients (71%) were treated using ConRT and 62 (29%) using IMRT. The median follow‐up for all patients was 68 months. There was no statistically significant difference in 5‐year local control between patients with T1a versus T1b disease (94% vs. 89%, respectively,P= 0.5). Three‐year locoregional control for patients treated with ConRT was 94% compared to 97% with IMRT (P= 0.4). Three‐year overall survival (OS) for patients treated with ConRT was 92.5% compared with 100% with IMRT (P= 0.1). Twelve of 14 patients with local recurrence underwent salvage surgery with 5‐year ultimate locoregional control of 98.5% and 97.1% in the ConRT and IMRT cohorts, respectively (P= 0.7). Multivariate analysis showed age < 60 years (P< 0.0001) and pretreatment Eastern Cooperative Oncology Group performance status <2 (P= 0.0022) to be independent correlates of improved OS. Postradiation cerebrovascular events were in four patients in the ConRT cohort (3%), whereas no patients in the IMRT cohort suffered any events.

     Conclusion

    Because the oncologic outcomes for patients treated with IMRT were excellent and IMRT allows for carotid sparing, we have transitioned to IMRT as our standard for most patients with T1 glottic cancer.

     Level of Evidence

    3bLaryngoscope, 130:146–153, 2020

     
    more » « less
  5. ; ; ; ; ; ; ( , Journal of Magnetic Resonance Imaging)
    Background

    Carotid webs (CaWs) are fibromuscular projections in the internal carotid artery (ICA) that cause mild luminal narrowing (<50%), but may be causative in up to one‐third of seemingly cryptogenic strokes. Understanding hemodynamic alterations caused by CaWs is imperative to assessing stroke risk. Time‐Average Wall Shear Stress (TAWSS) and Oscillatory Shear Index (OSI) are hemodynamic parameters linked to vascular dysfunction and thrombosis.

     Purpose

    To test the hypothesis: “CaWs are associated with lower TAWSS and higher OSI than mild atherosclerosis or healthy carotid bifurcation.”

     Study Type

    Prospective study.

     Population

    A total of 35 subjects (N = 14 bifurcations with CaW, 11F, age: 49 ± 10, 10 mild atherosclerosis 6F, age: 72 ± 9, 11 healthy 9F, age: 42 ± 13).

     Field Strength/Sequence

    4D flow/STAR‐MATCH/3D TOF/3T MRI, CTA.

     Assessment

    4D Flow velocity data were analyzed in two ways: 1) 3D ROI in the ICA bulbar segment (complex flow patterns are expected) was used to quantify the regions with low TAWSS and high OSI. 2) 2D planes were placed perpendicular to the centerline of the carotid bifurcation for detailed analysis of TAWSS and OSI.

     Statistical Tests

    Independent‐samples Kruskal–Wallis‐H test with 0.05 used for statistical significance.

     Results

    The percent surface area where low TAWSS was present in the ICA bulb was 12.3 ± 8.0% (95% CI: 7.6–16.9) in CaW subjects, 1.6 ± 1.9% (95% CI: 0.2–2.9) in atherosclerosis, and 8.5 ± 7.7% (95% CI: 3.6–13.4) in healthy subjects, all differences were statistically significant (ƞ2 = 0.3 [95% CI: 0.05–0.5],P‐value CaW vs. healthy = 0.2). OSI had similar values in the CCA between groups (ƞ2 = 0.07 [95% CI: 0.0–0.2],P‐value = 0.5), but OSI was significantly higher downstream of the bifurcation in CaW subjects compared to atherosclerosis and normal subjects. OSI returned to similar values between groups 1.5 diameters distal to the bifurcation (ƞ2 = 0.03 [95% CI: 0.0–0.2],P‐value = 0.7).

     Conclusion

    Lower TAWSS and higher OSI are present in the ICA bulb in patients with CaW when compared to patients with atherosclerotic or healthy subjects.

     Evidence Level

    2

     Technical Efficacy

    Stage 2

     
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email