Purpose Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of anticancer therapy, longitudinal reports of SNHL in childhood cancer survivors treated with contemporary RT are limited. We report the incidence, onset, severity, and long-term trajectory of SNHL among children receiving RT. Potential risk factors for SNHL were also identified. Patients and Methods Serial audiologic testing was conducted on 235 pediatric patients who were treated with conformal or intensity-modulated RT as part of an institutional phase II trial for localized primary brain tumors, including craniopharyngioma, ependymoma, and juvenile pilocytic astrocytoma. All but one patient had measurable cochlear radiation dose (CRD) greater than 0 Gy. The median follow-up from RT initiation to latest audiogram was 9 years with a median of 11 post-RT audiograms per patient. Audiograms were classified by the Chang Ototoxicity Grading Scale. Progression was defined by an increase in Chang grade from SNHL onset to the most recent evaluation. Results At last evaluation, SNHL was prevalent in 14% of patients: 2.1% had mild and 11.9% had significant SNHL requiring hearing aids. Median time from RT to SNHL onset was 3.6 years (range, 0.4 to 13.2 years). Among 29 patients with follow-up evaluations after SNHL onset, 65.5% experienced continued decline in hearing sensitivity in either ear and 34.5% had no change. Younger age at RT initiation (hazard ratio [HR], 2.32; 95% CI, 1.21 to 4.46), higher CRD (HR, 1.07; 95% CI, 1.03 to 1.11), and cerebrospinal fluid shunting (HR, 2.02; 95% CI, 1.07 to 3.78) were associated with SNHL. Conclusion SNHL is a late effect of RT that likely worsens over time. Long-term audiologic follow-up for a minimum of 10 years post-RT is recommended.
Objective Carboplatin is a common chemotherapy agent with potential ototoxic side effects that is used to treat a variety of pediatric cancers, including retinoblastoma. Retinoblastoma is a malignant tumor of the retina that is usually diagnosed in young children. Distortion-product otoacoustic emission tests offer an effective method of monitoring for ototoxicity in young children. This study was designed to compare measurements of distortion-product otoacoustic emissions obtained before and after several courses of carboplatin chemotherapy in order to examine if (a) mean distortion-product otoacoustic emission levels were significantly different; and (b) if criterion reductions in distortion-product otoacoustic emission levels were observed in individual children. Methods A prospective repeated measures study. Ten children with a median age of 7.6 months (range, 3–72 months) diagnosed with unilateral or bilateral retinoblastoma were examined. Distortion-product otoacoustic emissions were acquired from both ears of the children with 65/55 dB SPL primary tones (f2= 793–7996 Hz) and a frequency resolution of 3 points/octave. Distortion-product otoacoustic emission levels in dB SPL were measured before chemotherapy treatment (baseline measurement) and after 3–4 courses of chemotherapy (interim measurement). Comparisons were made between baseline and interim distortion-product otoacoustic emission levels (collapsed across ears). Evidence of ototoxicity was based on criterion reductions (≥ 6 dB) in distortion-product otoacoustic emission levels. Results Significant differences between baseline and interim mean distortion-product otoacoustic emission levels were only observed at f2=7996 Hz. Four children exhibited criterion reductions in distortion-product otoacoustic emission levels. Conclusions Mean distortion-product otoacoustic emission levels at most frequencies were not changed following 3–4 courses of carboplatin chemotherapy in children with retinoblastoma. However, on an individual basis, children receiving higher doses of carboplatin exhibited criterion reductions in distortion-product otoacoustic emission level at several frequencies. These findings suggest that higher doses of carboplatin affect outer hair cell function, and distortion-product otoacoustic emission tests can provide useful information when monitoring children at risk of developing carboplatin ototoxicity.
6507 Background: Randomized trials have proven that screening high-risk patients with LDCT of chest reduces lung cancer mortality compared to screening with chest x-ray. Under-served patients lack access to this test due to geographic and socio-economic factors. We hypothesized that a mobile screening unit would improve access and increase survival in this group, which is most at risk of lung cancer deaths. Methods: We installed a BodyTom portable 32 slice low-dose CT scanner (Samsung Inc) into a 35 foot coach (Frazier Inc), reinforced to avoid equipment damage during road travel. It includes waiting area, high speed wireless internet connection for rapid image transfer, and electronic tablets to deliver smoking cessation and health education programs and shared decision-making video aids. We used LUNG RADS approach to lesion classification, yielding high sensitivity and specificity in assessment. All films were reviewed by a central panel. This is certified as a lung cancer screening Center of Excellence by the Lung Cancer Alliance. Protocol was approved by Advarra IRB. Medicare pts excluded as insurance covered them for LDCT, although this reduced potential number of cases diagnosed as this is highest risk population. Results: We screened 1200 uninsured or under-insured subjects, mean age 61 years (range 55-64), with average pack year history of 47.8 (30-150); 61% male; 18% Black, 3% Hispanic/Latino; 78% rural. We found 97 pts with LUNG RADS 4 lesions, 30 lung cancers (2.5%), including 15 at stage I-II treated with curative intent; 5 incidental non-lung cancers (renal CA 2, head & neck CA 1, pancreas CA 2); more than 50% with cardiovascular disease or COPD seen on LDCT. Of eligible first-screen subjects (J. Clin. Oncol., 2019, 37, 383S), 440 attended Year 1 repeat LDCT and 161 attended Year 2 LDCT. Only one pt with surgically resected CA lung has relapsed to date. Conclusions: Mobile LDCT yields higher screening rate for under-served pts than prior international studies, with strong protocol adherence and paucity of early cancer deaths in high-risk population with traditionally poor compliance.
Application of the prostate-specific antigen (PSA) test, which measures PSA levels in blood, is standard in prostate cancer (PCa) screening. However, because PSA levels may be elevated for reasons other than PCa, it leads to high rates of misdiagnosis and overtreatment. Recently, alteration in the Nglycan sialylation of PSA, specifically increased levels of α2-3-linked N-acetylneuraminic acid (α2-3-Neu5Ac or α2-3-sialic acid), was identified as a potential biomarker for clinically significant PCa. Here, we introduce a robust top-down native mass spectrometry (MS) approach, performed using a combination of α2-3-Neu5Acspecific and nonspecific neuraminidases and employing center-ofmass monitoring (CoMMon), for quantifying the levels of α2-3-Neu5Ac as a fraction of total N-linked Neu5Ac present on PSA extracted from blood serum. To illustrate the potential of the assay for clinical diagnosis and disease staging of PCa, the percentages of α2-3-Neu5Ac on PSA (%α23PSA) in the serum of low-grade (International Society of Urological Pathology Grade Group/GG1), intermediate-grade (GG2), and high-grade (GG3,4,5) PCa individuals were measured. We observed a high sensitivity (85.5%) and specificity (84.6%) for discrimination of GG1 from clinically significant GG2−5 patients when using a %α23PSA test cut-off of 28.0%. Our results establish that the %α23PSA in blood serum PSA, which can be precisely measured in a non-invasive manner with our dual neuraminidase native MS/CoMMon assay, can discriminate between clinically significant PCa (GG2−5) and low-grade PCa (GG1). Such discrimination has not been previously achieved and represents an important clinical need. This assay could greatly improve the standard PSA test and serve as a valuable PCa diagnostic tool.
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