Long-term Effects Of Radiation Research Articles

Absorbed radiation doses in the thyroid as estimated by UNSCEAR and subsequent risk of childhood thyroid cancer following the Great East Japan Earthquake.

The identification of thyroid cancers among children after the Chernobyl nuclear power plant accident propelled concerns regarding long-term radiation effects on thyroid cancer in children affected by the Fukushima Daiichi nuclear power plant accident in Fukushima, Japan. Herein we consider the potential association between absorbed dose in the thyroid and the risk of developing thyroid cancer as detected by ultrasonography on 300 473 children and adolescents aged 0–18 years in Fukushima. The absorbed dose mentioned in the present study indicates the sum of that from external exposure and that from internally deposited radionuclides. We grouped participants according to estimated absorbed doses in each of 59 municipalities in Fukushima Prefecture, based on The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2013 report. The 59 municipalities were assigned to quartiles by dose. We limited our analyses to participants aged ≥6 years because only one case of thyroid cancer was observed in participants aged ≤5 years; 164 299 participants were included in the final analysis. Compared with the lowest dose quartile, the age- and sex-adjusted rate ratios (95% confidence intervals) for the low-middle, high-middle and highest quartiles were 2.00 (0.84–4.80), 1.34 (0.50–3.59) and 1.42 (0.55–3.67) for the 6–14-year-old groups and 1.99 (0.70–5.70), 0.54 (0.13–2.31) and 0.51 (0.12–2.15) for the >15-year-old group, respectively. No dose-dependent pattern emerged from the geographical distribution of absorbed doses by municipality, as estimated by UNSCEAR, and the detection of thyroid cancer among participants within 4–6 years after the accident. Ongoing surveillance might further clarify the effects of low-dose radiation exposure on thyroid cancer in Fukushima.

RADIATION DAMAGE OF THE NERVOUS SYSTEM AND ENDOCANABINOIDS.

The review analyzes the change of the existing paradigm of high radioresistance of the nervous system according tothe results of the study of neuropsychiatric disorders in in the aftermath of the Chornobyl accident in both earlyand remote post-accident period. The participation of the endocannabinoid system in ensuring homeostasis andpathology formation, potential possibilities of using cannabis drugs, agonists and antagonists of endocannabinoidreceptors for the treatment of early and long-term effects of radiation are considered.

LATE RADIATION TOXICITY AFTER RADICAL RADIOTHERAPY FOR GENITAL CANCER.

Radiation therapy for malignant tumors of the female genital area, even with the use of modern radiotherapy equipment and dosimetric planning, causes the development of local radiation changes. An approach involving methodsof general and local exposure is used in their treatment. One of the most promising directions is the creation of optimal combinations of medicines (in the form of ointments, gels, aerosols, suppositories, etc.), which have a therapeutic effect on the inflammatory process. The article reflects the clinical course and stage of occurrence of late radiation reactions of the skin, vaginal/cervix mucosa, bladder, and intestines, as well as the features of their treatment.Literary data and own practical experience in the treatment of radiation complications are presented. Whenreviewing the topic under study, it could be concluded that the leading cause of the development of local radiationdamage is the errors in the planning and implementation of radiation therapy, when high absorbed doses thatexceed the tolerance of healthy tissues are used. Another reason for this is the poor accounting for dose distribution of ionizing radiation in tissues, the presence of concomitant diseases in patients, and the underestimation ofthe long-term effects of radiation.

The age-dependent effect of high-dose X-ray radiation on NFκB signaling, structure, and mechanical behavior of the intervertebral disc

ABSTRACTPurpose: Ionizing radiation damages tissue and provokes inflammatory responses in multiple organ systems. We investigated the effects of high-dose X-ray radiation on the molecular inflammation and mechanical function of the intervertebral disc (IVD).Methods: Functional spine units (FSUs) containing the vertebrae-IVDs-vertebrae structure extracted from 1-month, 6-month, and 16-month-old NFκB-luciferase reporter mice and from 6-month-old myeloid differentiation factor 88 (MyD88)-null mice. After a preconditioning period in culture, the FSUs were subjected a single dose of ionizing X-ray radiation at 20 Gys, and then NFκB expression was monitored. The IVDs were then subjected to mechanical testing using dynamic compression, glycosaminoglycan (GAG) quantification, and histological analyses.Results: In the 1-month-old FSUs, the NFκB-driven luciferase activity was significantly elevated for 1 day following the exposure to radiation. The 6-month-old FSUs showed increased NFκB activity for 3 days, while the 16-month-old FSUs sustained elevated levels of NFκB activity throughout the 10-day culture period. All irradiated groups showed significant loss of disc height, GAG content, mechanical function and changes in structure. Ablation of MyD88 blunted the radiation-mediated NFκB signaling, and preserved GAG content, and the IVDs’ structure and mechanical performance.Conclusions: These results suggest that high-dose radiation affects the IVDs’ NFκB-dependent inflammatory processes that subsequently lead to functional deterioration. Blocking the transactivation potential of NFκB via MyD88 ablation preserved the structure and mechanical function of the FSUs. The long-term effects of radiation on IVD homeostasis should be considered in individuals susceptible to occupational and medical exposure.

First Insights into the Effect of Low-Dose X-Ray Irradiation in Adipose-Derived Stem Cells.

(1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno- nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1–2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine.

1975P - The tumor static exposure (TSE) concept & utility: Application to combination treatment of radiation and radiosensitizing agent in tumor xenograft experiments

BackgroundWe present a pharmacodynamic model that describes the tumor volume evolution during and after treatment with radiation and in combination with a radiosensitizing agent. A key contribution is the inclusion of a long-term radiation effect, which allows the model to describe distinct tumor behaviors including tumor eradication and tumor regrowth with different growth rates. Additionally, we introduce the concept of TSE (Tumor Static Exposure), the exposures of one or multiple compounds that result in tumor stasis and provide an example of its utility for optimizing drug combinations in oncology. MethodsThe model was challenged with data from four treatment groups (Vehicle, radiation, radiation + radiosensitizer 25 or 100mg/kg) in xenograft study using a clinically-relevant administration schedule (6 weeks treatment, 5 days on/2 days off) and a mixed-effects approach was used for model-fitting. The model incorporated a permanent inhibition of the natural growth rate. This step was required to capture the complete tumor eradication and the observed tumor regrowth with different rates with animals having slower regrowth compared to control animals. The presence of a radiosensitizer will lead to the same tumor evolution as if a higher dose of radiation had been administered. The model was applied to predict exposure combinations that result in tumor eradication using the TSE. ResultsThe developed model captured experimental data from all treatment groups adequately, with the parameter estimates taking biologically reasonable values. Model simulation showed that tumor eradication is observed at total radiation dose of 110Gy, which is reduced to 80 or 30Gy with co-administration of 25 or 100mg/kg of a radiosensitizer. ConclusionsThe new model can describe different tumor dynamics including tumor eradication and tumor regrowth with different rates. The proposed model can be expanded for radiation in combination with chemical interventions or immunotherapy. The model and TSE can be applied to generate treatment predictions for different dosing schedules or determining drug synergies. The translational utility of the TSE concept is currently under investigation. Legal entity responsible for the studyMerck Healthcare KGaA. FundingTim Cardilin was supported by an education Grant from Merck Healthcare KGaA, Darmstadt, Germany. This work was also partially funded by the Swedish Foundation for Strategic Research (Grant no. AM13-0046). DisclosureS. El Bawab: Full / Part-time employment: Merck Healthcare KGaA. A. Zimmermann: Full / Part-time employment: Merck Healthcare KGaA. F. Lignet: Full / Part-time employment: Merck Healthcare KGaA. All authors have declared no conflicts of interest.

Heavy-ion induced radiation effects in 50 nm NAND floating gate flash memories

Using the 86Kr, 129Xe and 209Bi ions provided by the Heavy Ion Research Facility in Lanzhou (HIRFL), the short-term and long-term radiation effects induced by heavy ions induced in 50 nm NAND floating gate (FG) flash memories are investigated. The linear energy transfer (LET) value covers the range from 20.7 to 99.8 MeV·cm2/mg. Only upset errors in FG cells are observed due to that the flash memories are powered off and the peripheral circuitries are shielded during heavy ion irradiation. The errors in FG cells irradiated with ions of different LET values are decreasing with time under room temperature condition. After the reprogramming of flash memories, retention errors in FG cells are observed in some flash memories, which are irradiated by heavy ions with LET values greater than 37.6 MeV·cm2/mg. The dependence of single event upset, annealing of errors and retention errors in FG cells on the ion LET value is analysed and the underlying mechanisms are discussed.

Long-term effects of electromagnetic radiation of the mobile phone frequency on the morphofunctional state of the reproductive system of rats and males and their offspring

The experiment established the long-term effects of low-intensity electromagnetic radiation from a mobile phone (EMR MP 1745 MHz, xpd = 7.5 ± 0.3 μW/cm2) in the offspring of male rats from parents, one of which was either subjected to a prolonged exposure of the investigated factor. A change in the sex ratio of the born offspring and a decrease in their body weight have been established. The analysis of the reproductive system of the offspring of males when they reached the age of 2 and 4 months, revealed significant impairments, with the most pronounced changes found in the offspring obtained from both the irradiated parents or when only the male was irradiated. These changes are manifested in the disruption of the normal functioning of the spermatogenic epithelium, namely, an intensification of the initial stage of spermatogenesis is noted, with a significant inhibition at the stage of spermatid transformation. A decrease in the number of mature germ cells – spermatozoa and a pronounced deterioration of their viability, as well as an increase in testosterone secretion is established. The revealed violations in the morphofunctional state of the reproductive system of the offspring suggest that the trans-generation effect of EMR exposure generated by cellular sources can be considered as a factor affecting the decline in the male fertility.

What is the best therapeutic approach to a pediatric patient with a deep-seated brain AVM?

Although brain arteriovenous malformations (bAVMs) account for a very small proportion of cerebral pathologies in the pediatric population, they are the cause of roughly 50% of spontaneous intracranial hemorrhages. Pediatric bAVMs tend to rupture more frequently and seem to have higher recurrence rates than bAVMs in adults. Thus, the management of pediatric bAVMs is particularly challenging. In general, the treatment options are conservative treatment, microsurgery, endovascular therapy (EVT), gamma knife radiosurgery (GKRS), proton-beam stereotactic radiosurgery (PSRS), or a combination of the above. In order to identify the best approach to deep-seated pediatric bAVMs, we performed a systematic review, according to the PRISMA guidelines. None of the options seem to offer a clear advantage over the others when used alone. Microsurgery provides the highest obliteration rate, but has higher incidence of neurological complications. EVT may play a role when used as adjuvant therapy, but as a stand-alone therapy, the efficacy is low and the long-term side effects of radiation from the multiple sessions required in deep-seated pediatric bAVMs are still unknown. GKRS has a low risk of complication, but the obliteration rates still leave much to be desired. Finally, PSRS offers promising results with a more accurate radiation that avoids the surrounding tissue, but data is limited due to its recent introduction. Overall, a multi-modal approach, or even an active surveillance, might be the most suitable when facing deep-seated bAVM, considering the difficulty of their management and the high risk of complications in the pediatric population.

Radiation-induced genomic instability in breast carcinomas of the Swedish hemangioma cohort.

Radiation-induced genomic instability (GI) is hypothesized to persist after exposure and ultimately promote carcinogenesis. Based on the absorbed dose to the breast, an increased risk of developing breast cancer was shown in the Swedish hemangioma cohort that was treated with radium-226 for skin hemangioma as infants. Here, we screened 31 primary breast carcinomas for genetic alterations using the OncoScan CNV Plus Assay to assess GI and chromothripsis-like patterns associated with the absorbed dose to the breast. Higher absorbed doses were associated with increased numbers of copy number alterations in the tumor genome and thus a more unstable genome. Hence, the observed dose-dependent GI in the tumor genome is a measurable manifestation of the long-term effects of irradiation. We developed a highly predictive Cox regression model for overall survival based on the interaction between absorbed dose and GI. The Swedish hemangioma cohort is a valuable cohort to investigate the biological relationship between absorbed dose and GI in irradiated humans. This work gives a biological basis for improved risk assessment to minimize carcinogenesis as a secondary disease after radiation therapy.

PECULIARITIES OF RADIATION NORMALIZATION IN THE USSR (RUSSIA) AND THE USA CONCERNING TO LONG-TERM PILOTABLE SPACE FLIGHTS

Retrospectively, from the 60s of the last century to the present time, coordinated approaches have been considered in our country and in the United States in addressing the issues of ensuring radiation safety and radiation rating of short-term space flights and establishing the maximum radiation exposure levels for cosmonauts and astronauts. At the same time, for long space flights some basic differences in the choice of radiation hazard criteria for a complex (in contrast to terrestrial) character of the radiation impact of cosmic radiation are shown. Differences in models of the formation of the radiation hazard to the organism are also noted taking into account the recovery and compensatory processes. A thorough experimental and model substantiation of not only the risk of immediate effects, but also the main and unfavorable long-term effects of cosmic radiation on cosmonauts, have been carried out. To solve problems of rationing in Russia and establish the dose limits for cosmonauts, the results of unique experiments are presented and quantitative approaches to the determination of the state of the leading regulatory systems, body reserves, the total radiation risk throughout the life of cosmonauts, as well as the possible reduction of the average life expectancy.

Long-term immune effects of high-level natural radiation on Yangjiang inhabitants in China

Purpose: Low dose radiation was found to perturb immune function or inflammatory reactions, which required further study. This study aimed to evaluate the health effects following long-term low dose radiation by detecting levels of peripheral blood lymphocyte subsets and serum cytokines of residents living in the Yangjiang High Background Radiation Area (HBRA).Materials and methods: Flow cytometry was used to detect peripheral blood T lymphocytes and its subsets (CD4+ T, CD8+ T lymphocyte) in 100 healthy female residents selected from HBRA and a Control Area (CA), respectively. Thirty cytokines or receptors and CRP levels were measured using antibody arrays in the 40 subjects described above. Subjects were chosen based on an age and BMI match between the two groups. Cytokine expression levels were then verified using ELISA methods.Result: In comparison to CA, CD8+ T lymphocyte numbers were significantly increased with cumulative dose following adjustment to age and BMI. Of the 30 selected targets, 22 indexes were measurable and inflammatory cytokines such as IFN-γ, IL-α, MCP-1, sIL-6R, EGFR, and CRP levels were observed to be significantly up-regulated with cumulative doses. ELISA results confirmed the cytokine array results and found CRP, MCP-1, and sIL-6R levels are linear with cumulative dose following adjustment to age and BMI.Conclusion: Immune function was found to be affected in humans exposed to long-term low dose radiation. Specifically, we observed an increase in CD8+T lymphocyte numbers and an up-regulation of inflammatory biomarkers, including IFN-γ, MCP-1, sIL-6R, EGFR, CRP.

Abstract P1-12-13: Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer

Abstract Objectives: Upper extremity dysfunction (UED) is a known side effect of breast cancer treatment. It is unclear, however, to what degree radiation contributes to this morbidity. We aimed to characterize the level of UED using patient-reported outcomes (PROs) prior to, during, and after treatment with radiation for breast cancer. Our secondary aims were to evaluate the association of UED with pain scores. Methods: This is a single-institution, prospective, longitudinal cohort study of patients treated with radiation for breast cancer. The validated patient-reported outcome measure, Quick Disabilities of the Arm, Shoulder and Hand (QD) was used to capture UED prior to radiation, at the end of radiation, and 1 month following the completion of radiation. Pain scores were also collected at these intervals using the numeric pain reporting scale (NPRS) from 0 (no pain) to 10 (worst pain). Results: Forty-four patients were enrolled on this study and 43 (97.7%) had completed radiation at the time of analysis. Thirteen patients (29.5%) were treated with mastectomy, axillary lymph node dissection and regional nodal irradiation in the supine position. The other 31 (70.5%) patients underwent lumpectomy and sentinel lymph node biopsy. Of these patients, 26 (83.9%) were treated in the prone position and 30 (96.8%) received whole breast irradiation. Median time from surgery to radiation was 69 days (range 35 – 212 days), 76 days for mastectomy and 68 days for lumpectomy. Median time from start to end of radiation was 38 days for mastectomy and 28 days for lumpectomy. Pre-treatment median QD score prior to radiation was 12.5 (11.4 for lumpectomy, 15.9 for mastectomy), 9.1 at the end of radiation (9.1 for lumpectomy, 18.2 for mastectomy), and 2.4 at 1 month after radiation (2.3 for lumpectomy, 2.5 for mastectomy). Median NPRS scores at pre-treatment, post-treatment and 1 month follow-up were 1, 1, and 1 for lumpectomy and 0, 1, 0 for mastectomy patients, respectively. Conclusion: In this initial pilot study with 1 month of follow up, patient-reported UED as demonstrated by QD scores were higher pre-radiation and decreased by one month after. This likely reflects recuperation after surgical procedure. Median average pain scores were low at all time points. Further evaluation of UED over time to characterize the long-term effect of radiation and correlation with quality of life and other clinical factors is planned. Citation Format: Healy E, Pan X, Beyer S, Washington I, Bazan J, White J. Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-13.

Long-term radiation effects in GaAs microwave devices exposed to pulsed ionizing radiation

The investigation results of the GaAs microwave devices characteristics under pulse irradiation are presented. The study covers the field effect transistor with Schottky barrier, pseudomorphic high-electron mobility transistors and resonant tunnelling diodes implemented in GaAs technology processes. It has been demonstrated that GaAs MESFET, pHEMT and RTDs may show the long-term parameter recovery undo pulsed ionizing exposure.

Long-term transient radiation effects in high-speed signal switches implemented in 0.1 um E/D pHEMT process

The transient radiation effects in 0.1 μm E/D pHEMT high-speed signal switches have been investigated. It was shown that a signal switch transient recovery time caused by pulsed irradiation can exceed 100 ms due to a switch control driver’s functional upset.

Gamma Knife Radiosurgery of Arteriovenous Malformations: Long-Term Outcomes and Late Effects.

Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVM) is an accepted treatment option that has been performed for more than 40 years. The goal of AVM GKRS is nidus obliteration to eliminate the risk of intracranial hemorrhage while minimizing the risk of short- and long-term adverse radiation effects (ARE). Nidus obliteration typically occurs between 1 and 5 years after GKRS. The most important factor associated with nidus obliteration is the prescribed radiation dose. The chance of obliteration ranges from 60 to 70% for margin doses of 15-16 Gy to 90% or more for margin doses of 20-25 Gy. Neurologic decline after GKRS can occur from either hemorrhage or ARE. Numerous studies have shown that the risk of AVM bleeding is either unchanged or decreased following GKRS. Advances in neuroimaging and dose-planning software have reduced the incidence of early ARE to <4%. Volume-staged procedures can be safely performed for large-volume AVM that were previously considered too large for GKRS. Late ARE (generally cyst formation) are common in patients who develop early MRI imaging changes (areas of high T2 signal) after GKRS, but most cases can be managed with either observation or resection of the thrombosed AVM.

Long-term Tumor Adaptation after Radiotherapy: Therapeutic Implications for Targeting Integrins in Prostate Cancer.

Adaptation of tumor cells to radiotherapy induces changes that are actionable by molecular targeted agents and immunotherapy. This report demonstrates that radiation-induced changes in integrin expression can be targeted 2 months later. Integrins are transmembrane cell adhesion molecules that are essential for cancer cell survival and proliferation. To analyze the short- and long-term effects of radiation on the integrin expression, prostate cancer cells (DU145, PC3, and LNCaP) were cultured in a 3D extracellular matrix and irradiated with either a single dose of radiation (2-10 Gy) or a multifractionated regimen (2-10 fractions of 1 Gy). Whole human genome microarrays, immunoblotting, immunoprecipitation assays, and immunofluorescence staining of integrins were performed. The results were confirmed in a prostate cancer xenograft model system. Interestingly, β1 and β4 integrins (ITGB1 and ITGB4) were upregulated after radiation in vitro and in vivo. This overexpression lasted for more than 2 months and was dose dependent. Moreover, radiation-induced upregulation of β1 and β4 integrin resulted in significantly increased tumor cell death after treatment with inhibitory antibodies. Combined, these findings indicate that long-term tumor adaptation to radiation can result in an increased susceptibility of surviving cancer cells to molecular targeted therapy due to a radiation-induced overexpression of the target. IMPLICATIONS: Radiation induces dose- and schedule-dependent adaptive changes that are targetable for an extended time; thus suggesting radiotherapy as a unique strategy to orchestrate molecular processes, thereby providing new radiation-drug treatment options within precision cancer medicine.

Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors : Asystematic analysis of 102 cases.

Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT. We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded. 102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after amedian of 17 (3-54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4-80) Gy in patients with PHC versus 14.2 (1.8-61.7) Gy in those without PHC (p = 0.028). Adose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36months; p = 0.571). iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.

Long-Term Supratentorial Radiologic Effects of Surgery and Local Radiation in Children with Infratentorial Ependymoma

Current standard of care for children with infratentorial ependymoma includes maximal safe resection and local radiation of 54-59 Gray. High-dose local radiation has been associated with declines in multiple cognitive domains. The anatomic and physiologic correlates of this cognitive decline remain undefined, and there have been no radiographic studies on the long-term effects of this treatment paradigm. A comprehensive database of pediatric brain tumor patients treated at Stanford Children's from 2004-2016 was queried. Seven patients with posterior fossa ependymoma who were treated with surgery and local radiation alone, who had no evidence of recurrent disease, and had imaging suitable for analysis were identified. Diffusion-weighted magnetic resonance imaging datasets were used to calculate apparent diffusion coefficient maps for each subject, while arterial spin labeling datasets were used to calculate maps of cerebral blood flow. Diffusion-weighted imaging and arterial spin labeling datasets of 52 age-matched healthy children were analyzed in the same fashion to enable group comparisons. Several statistically significant differences were detected between the 2 groups. Cerebral blood flow was lower in the caudate and pallidum and higher in the nucleus accumbens in the ependymoma cohort compared with controls. Apparent diffusion coefficient was increased in the thalamus and trended toward decreased in the amygdala. Surgery and local radiation for posterior fossa ependymoma are associated with supratentorial apparent diffusion coefficient and cerebral blood flow alterations, which may represent an anatomic and physiologic correlate to the previously published decline in neurocognitive outcomes in this population.

Early outcomes of breast cancer patients treated with post-mastectomy uniform scanning proton therapy

BackgroundPostmastectomy proton radiotherapy improves normal tissue sparing in comparison to photon-based approaches. Several studies have reported dosimetry comparison and tolerable acute toxicity profile with limited follow-up. We report our institutional experience of postmastectomy proton radiation including clinical efficacy and toxicities. MethodsFrom December 2013 to February 2015, 42 consecutive patients who received mastectomy for non-metastatic breast cancer were treated with adjuvant chest wall and regional nodal proton therapy at a single proton center. 3D conformal uniform scanning with en face matching fields was used. ResultsThe median follow-up among patients was 35 months (range 1–55 months). There was one local failure, zero regional nodal failure, and six distant failures. The 3-year rate of locoregional disease-free survival was 96.3%, metastasis-free survival was 84.1%, and overall survival was 97.2%. The only local failure event occurred on the chest wall within the radiation field, approximately 2.5 years after the completion of radiation. Skin dermatitis, fatigue, and esophagitis were the most common acute toxicity. All patients developed grade 1 or 2 acute skin toxicity and there was no grade 3 or 4 acute skin toxicity. Proton radiation is able to achieve excellent target coverage with median PTV V95 over 95% and heart sparing with median mean heart dose less than 1 Gy (RBE). ConclusionWith close to three years of median follow-up, post-mastectomy proton radiation has shown excellent locoregional control rates and favorable toxicity profile. Long-term adverse effect of heart-sparing radiation will require longer follow-up time and randomized clinical trials.