Chromatic bleaching and fractionation effects on optically stimulated luminescent dosimeter reuse.

BACKGROUND: Optically stimulated luminescent dosimeters (OSLDs) can be bleached and reused, but questions remain about the effects of repeated bleaching and fractionation schedules on OSLD performance. PURPOSE: The aim of this study was to investigate how light sources with different wavelengths and different fractionation schemes affect the performance of reused OSLDs. METHODS: OSLDs (N = 240) were irradiated on a cobalt-60 beam in different step sizes until they reached an accumulated dose of 50 Gy. Between irradiations they were bleached using light sources of different wavelengths: the Imaging and Radiation Oncology Core (IROC) bleaching system (our control); monochromatic red, green, yellow, and blue lights; and a polychromatic white light. Sensitivity and linearity-based correction factors were determined as a function of dose step-size. The rate of signal removal from different light sources was characterized by sampling these OSLDs at various time points during their bleaching process. Relative doses were calculated according to the American Association of Physicists in Medicine Task Group-191. Signal repopulation was investigated by irradiating OSLDs (N = 300) to various delivered doses of 2, 10, 20, 30, 40, and 50 Gy in a single fraction, bleached with one of the colors, and read over time. Fractionation effects were evaluated by irradiating OSLDs up to 30 Gy in different size steps. After reading, the OSLDs were bleached following IROC protocol. OSLDs (N = 40) received irradiations in 5, 10, 15, 30 Gy fractions until they had an accumulated dose of 30 Gy; The sensitivity response of these OSLDs was compared with reference OSLDs that had no accumulated dose. RESULTS: Light sources with polychromatic spectrums (IROC and white) bleached OSLDs faster than did sources with monochromatic spectra. Polychromatic light sources (white light and IROC system) provided the greatest dose stability for OSLDs that had larger amounts of accumulated dose. Signal repopulation was related to the choice of bleaching light source, timing of bleaching, and amount of accumulated dose. Changes to relative dosimetry were more pronounced in OSLDs that received larger fractions. At 5-Gy fractions and above, all OSLDs had heightened sensitivity, with OSLDs exposed to 30-Gy fractions being 6.4% more sensitive than reference dosimeters. CONCLUSIONS: The choice of bleaching light plays a role in how fast an OSLD is bleached and how much accumulated dose an OSLD can be exposed to while maintaining stable signal sensitivity. We have expanded upon investigations into signal repopulation to show that bleaching light plays a role in the migration of deep traps to dosimetric traps after bleaching. Our research concludes that the bleaching light source and fractionation need to be considered when reusing OSLD.

Radiation Therapy Technology Advances and Mitigation of Subsequent Neoplasms in Childhood Cancer Survivors.

PURPOSE: In this Pediatric Normal Tissue Effects in the Clinic (PENTEC) vision paper, challenges and opportunities in the assessment of subsequent neoplasms (SNs) from radiation therapy (RT) are presented and discussed in the context of technology advancement. METHODS AND MATERIALS: The paper discusses the current knowledge of SN risks associated with historic, contemporary, and future RT technologies. Opportunities for research and SN mitigation strategies in pediatric patients with cancer are reviewed. RESULTS: Present experience with radiation carcinogenesis is from populations exposed during widely different scenarios. Knowledge gaps exist within clinical cohorts and follow-up; dose-response and volume effects; dose-rate and fractionation effects; radiation quality and proton/particle therapy; age considerations; susceptibility of specific tissues; and risks related to genetic predisposition. The biological mechanisms associated with local and patient-level risks are largely unknown. CONCLUSIONS: Future cancer care is expected to involve several available RT technologies, necessitating evidence and strategies to assess the performance of competing treatments. It is essential to maximize the utilization of existing follow-up while planning for prospective data collection, including standardized registration of individual treatment information with linkage across patient databases.

Technical note: Radiological clinical equivalence for phantom materials in carbon ion therapy.

PURPOSE: As carbon ion radiotherapy increases in use, there are limited phantom materials for heterogeneous or anthropomorphic phantom measurements. This work characterized the radiological clinical equivalence of several phantom materials in a therapeutic carbon ion beam. METHODS: Eight materials were tested for radiological material-equivalence in a carbon ion beam. The materials were computed tomography (CT)-scanned to obtain Hounsfield unit (HU) values, then irradiated in a monoenergetic carbon ion beam to determine relative linear stopping power (RLSP). The corresponding HU and RLSP for each phantom material were compared to clinical carbon ion calibration curves. For absorbed dose comparison, ion chamber measurements were made in the center of a carbon ion spread-out Bragg peak (SOBP) in water and in the phantom material, evaluating whether the material perturbed the absorbed dose measurement beyond what was predicted by the HU-RLSP relationship. RESULTS: Polyethylene, solid water (Gammex and Sun Nuclear), Blue Water (Standard Imaging), and Techtron HPV had measured RLSP values that agreed within ±4.2% of RLSP values predicted by the clinical calibration curve. Measured RLSP for acrylic was 7.2% different from predicted. The agreement for balsa wood and cork varied between samples. Ion chamber measurements in the phantom materials were within 0.1% of ion chamber measurements in water for most materials (solid water, Blue Water, polyethylene, and acrylic), and within 1.9% for the rest of the materials (balsa wood, cork, and Techtron HPV). CONCLUSIONS: Several phantom materials (Blue Water, polyethylene, solid water [Gammex and Sun Nuclear], and Techtron HPV) are suitable for heterogeneous phantom measurements for carbon ion therapy. Low density materials should be carefully characterized due to inconsistencies between samples.

OSLD nanoDot characterization for carbon radiotherapy dosimetry.

Objective. This study characterized optically-stimulated luminescent dosimeter (OSLD) nanoDots for use in a therapeutic carbon beam using the Imaging and Radiation Oncology Core (IROC) framework for remote output verification.Approach. The absorbed dose correction factors for OSLD (fading, linearity, beam quality, angularity, and depletion), as defined by AAPM TG 191, were characterized for carbon beams. For the various correction factors, the effect of linear energy transfer (LET) was examined by characterizing in both a low and high LET setting.Main results. Fading was not statistically different between reference photons and carbon, nor between low and high LET beams; thus, the standard IROC-defined exponential function could be used to characterize fading. Dose linearity was characterized with a linear fit; while low and high LET carbon linearity was different, these differences were small and could be rolled into the uncertainty budget if using a single linearity correction. A linear fit between beam quality and dose-averaged LET was determined. The OSLD response at various angles of incidence was not statistically different, thus a correction factor need not be applied. There was a difference in depletion between low and high LET irradiations in a primary carbon beam, but this difference was small over the standard five readings. The largest uncertainty associated with the use of OSLDs in carbon was because of thekQcorrection factor, with an uncertainty of 6.0%. The overall uncertainty budget was 6.3% for standard irradiation conditions.Significance. OSLD nanoDot response was characterized in a therapeutic carbon beam. The uncertainty was larger than for traditional photon applications. These findings enable the use of OSLDs for carbon absorbed dose measurements, but with less accuracy than conventional OSLD audit programs.

Mortality After Major Cardiovascular Events in Survivors of Childhood Cancer.

BACKGROUND: Adult survivors of childhood cancer are at risk for cardiovascular events. OBJECTIVES: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations. METHODS: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical factors. RESULTS: Among 25,658 childhood cancer survivors (median age at diagnosis 7 years, median age at follow-up or death 38 years) and 5,051 siblings, 1,780 survivors and 91 siblings had a cardiovascular event. After HF, CAD, and stroke, 10-year all-cause mortalities were 30% (95% CI: 26%-33%), 36% (95% CI: 31%-40%), and 29% (95% CI: 24%-33%), respectively, among survivors vs 14% (95% CI: 0%-25%), 14% (95% CI: 2%-25%), and 4% (95% CI: 0%-11%) among siblings. All-cause mortality risks among childhood cancer survivors were increased after HF (HR: 7.32; 95% CI: 2.56-20.89), CAD (HR: 5.54; 95% CI: 2.37-12.93), and stroke (HR: 3.57; 95% CI: 1.12-11.37). CAD-specific mortality risk was increased (HR: 3.70; 95% CI: 1.05-13.02). Among 5,114 CARDIA participants, 345 had a major event. Although CARDIA participants were on average decades older at events (median age 57 years vs 31 years), mortality risks were similar, except that all-cause mortality after CAD was significantly increased among childhood cancer survivors (HR: 1.85; 95% CI: 1.16-2.95). CONCLUSIONS: Survivors of childhood cancer represent a population at high risk for mortality after major cardiovascular events.

Neurocognitive outcomes and functional independence in adult survivors of childhood medulloblastoma diagnosed over three decades.

BACKGROUND: Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown. METHODS: Adult survivors of childhood medulloblastoma (n=505; median[minimum-maximum] age, 29[18-46] years) and sibling controls (n=727; 32[18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI]≥30 Gy, no chemotherapy), standard-risk (CSI>0 to <30 Gy +chemotherapy) and high-risk (CSI≥30 Gy +chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver's license, marital/partner status. Multivariable models estimated risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence. RESULTS: Survivors in each treatment exposure group had 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval [CI] 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems and seizures were associated with 33%-34%, 25-26% and 21%-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with non-independence. CONCLUSIONS: Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.

Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors.

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), female breast cancer (OR = 1.42, 95% CI = 1.27-1.58), thyroid cancer (OR = 1.48, 95% CI = 1.31-1.67), squamous cell carcinoma (OR = 1.20, 95% CI = 1.00-1.44) and melanoma (OR = 1.60, 95% CI = 1.31-1.96); however, the association for colorectal cancer was not significant (OR = 1.19, 95% CI = 0.94-1.52). An investigation of joint associations between PRSs and radiotherapy found more than additive increased risks of basal cell carcinoma, and breast and thyroid cancers. For survivors with radiotherapy exposure, the cumulative incidence of subsequent cancer by age 50 years was increased for those with high versus low PRS. These findings suggest a degree of shared genetic etiology for these malignancy types in the general population and survivors, which remains evident in the context of strong radiotherapy-related risk.

Impact of risk-based therapy on late morbidity and mortality in neuroblastoma survivors: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described. METHODS: Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals for CHC compared with 1029 CCSS siblings. RESULTS: Among survivors (49.8% male; median age = 21 years, range = 7-42; median follow-up = 19.3 years, range = 5-29.9), 80% with low-risk disease were treated with surgery alone, whereas 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh = 27.7 [21.4-35.8]; SMRintermediate = 3.3 [1.7-6.5]; SMRlow = 2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh = 28.0 [18.5-42.3]; SIRintermediate = 3.7 [1.2-11.3]) but did not differ from the US population for survivors of low-risk disease. Compared with siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh = 16.1 [11.2-23.2]; HRintermediate = 6.3 [3.8-10.5]; HRlow = 1.8 [1.1-3.1]). CONCLUSION: Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multimorbidity, whereas survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes.