The Dutch-Belgian Registry of Stereotactic Body Radiation Therapy for Liver Metastases: Clinical Outcomes of 515 Patients and 668 Metastases.

PURPOSE: Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. METHODS AND MATERIALS: A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03). RESULTS: Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients. CONCLUSIONS: This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases.

Treatment Toxicity: Radiation.

Intentional and unintentional radiation exposures have a powerful impact on normal tissue function and can induce short-term and long-term injury to all cell systems. Radiation effects can lead to lifetime-defining health issues for a patient and can produce complications to all organ systems. Providers need to understand acute and late effects of radiation treatment and how the fingerprints of therapy can have an impact on health care in later life. This article reviews current knowledge concerning normal tissue tolerance with therapy.

The Lens Opacities Classification System III Grading in Irradiated Uveal Melanomas to Characterize Proton Therapy-Induced Cataracts.

PURPOSE: To evaluate the use of the Lens Opacities Classification System III grading (LOCS III) for the characterization of radiation-induced cataract, and to correlate the proton beam projection onto the lens with cataract location and grade as defined by the LOCS III. DESIGN: Prospective, interventional case series. METHODS: Fifty-two consecutive patients with cataract following proton therapy were included. All cataracts were graded using LOCS III. Relationships between proton beam and cataract subtypes, as well as between dose, proportion of lens irradiated, and extent of cataracts, were assessed. RESULTS: Tumor diameter, volume, stage, and equatorial tumor location were associated with extent of posterior subcapsular cataracts (PSC) that were diagnosed at a median (interquartile range) 36 months (22;83) after treatment. In multivariate analysis, the tumor volume (P < .01) and an equatorial tumor location (P = .01) were risk factors for extensive PSC. Lens irradiation was avoided in 10 patients. In the remaining 42 patients (81%), the extent of PSC significantly correlated with the dose to the lens receiving 10, 26, and 47 Gy (P = .03, P = .03, and P = .04, respectively), the dose to the lens periphery receiving 10 and 26 Gy (P = .02 and P = .02, respectively), and the dose to the ciliary body receiving 10 and 26 Gy (P = .03 and P = .02, respectively). Nuclear color significantly correlated with the dose to the ciliary body receiving 10 Gy (P = .03) and 26 Gy (P = .02). After adjustment of the results on tumor volume and tumor location, the volume of lens receiving 10 Gy (P = .04) and 26 Gy (P = .03) remained significantly associated with the extent of PSC. CONCLUSIONS: Proton dose correlated with the occurrence of PSC and nuclear color cataracts as defined by LOCS III grading. Better characterization of cataracts with the LOCS III after irradiation may help to further fill gaps in the current understanding of the mechanisms of radiation-induced cataracts.

Classification of chronic radiation-induced ulcers in the chest wall after surgery in breast cancers.

BACKGROUND AND PURPOSE: To explore the methods of clinical classification in chronic radiation-induced ulcers in the chest wall (CRUCWs). MATERIALS AND METHODS: A total of 64 patients with CRUCWs were treated. We divided the cases into 3 types (mild, moderate, or severe) according to their clinical manifestations. Conservative treatments, axial-pattern myocutaneous or local flaps, or filleted flaps were applied correspondingly. RESULTS: The cases were divided as follows: mild (n = 11), moderate (n = 45), and severe (n = 8). Eight cases were cured by conservative surgical therapy. One case had a recurrence 6 months after conservative therapy and was cured by a latissimus dorsi myocutaneous flap. The transferred flaps all survived, including 26 transverse rectus abdominis myocutaneous flaps, 8 longitudinal rectus abdominis myocutaneous flaps, 6 latissimus dorsi myocutaneous flaps, 3 contralateral breast flaps, 5 lateral thoracic rotation flaps, and 7 filleted flaps. In 2 transverse rectus abdominis myocutaneous flaps and 2 latissimus dorsi myocutaneous flaps, distal necrosis appeared in small areas. The resulting wounds were salvaged with skin graft and full healing was achieved. CONCLUSION: CRUCWs can be divided into three types. Surgical methods should vary with distinguished classifications. The effective classification of CRUCWs has definite instructive significance on the selection of surgical approaches.

Identifying and acting on potentially inappropriate care? Inadequacy of current hospital coding for this task.

INTRODUCTION: Recent Australian attempts to facilitate disinvestment in healthcare, by identifying instances of 'inappropriate' care from large Government datasets, are subject to significant methodological flaws. Amongst other criticisms has been the fact that the Government datasets utilized for this purpose correlate poorly with datasets collected by relevant professional bodies. Government data derive from official hospital coding, collected retrospectively by clerical personnel, whilst professional body data derive from unit-specific databases, collected contemporaneously with care by clinical personnel. AIM: Assessment of accuracy of official hospital coding data for hyperbaric services in a tertiary referral hospital. METHODS: All official hyperbaric-relevant coding data submitted to the relevant Australian Government agencies by the Royal Hobart Hospital, Tasmania, Australia for financial year 2010-2011 were reviewed and compared against actual hyperbaric unit activity as determined by reference to original source documents. RESULTS: Hospital coding data contained one or more errors in diagnoses and/or procedures in 70% of patients treated with hyperbaric oxygen that year. Multiple discrete error types were identified, including (but not limited to): missing patients; missing treatments; 'additional' treatments; 'additional' patients; incorrect procedure codes and incorrect diagnostic codes. Incidental observations of errors in surgical, anaesthetic and intensive care coding within this cohort suggest that the problems are not restricted to the specialty of hyperbaric medicine alone. Publications from other centres indicate that these problems are not unique to this institution or State. CONCLUSIONS: Current Government datasets are irretrievably compromised and not fit for purpose. Attempting to inform the healthcare policy debate by reference to these datasets is inappropriate. Urgent clinical engagement with hospital coding departments is warranted.

[Plastic reconstruction of radiation injuries]. / Plastische Rekonstruktion von Strahlenfolgen.

In addition to surgical and drug therapy, radiotherapy (or radiation therapy) is one of the three mainstays of modern oncological therapy regimes. It uses ionizing radiation to control tumors by damaging the DNA of cancerous tissue leading to cellular death. Although advances have been made in recent years resulting in a reduced dosage to the surrounding tissues, radiation injuries and tissue-related side effects cannot be completely avoided. Knowledge of the pathophysiology, treatment modalities and interdisciplinary treatment approaches are essential for effective therapy whilst limiting side effects. Surgery within the irradiated area is technically demanding due to tissue alterations and unpredictable wound healing. The plastic reconstructive surgeon either faces the challenge of delayed wound healing following neoadjuvant radiation or chronic radiation-linked changes following previous radiotherapy, which can also occur after a latency period of many years. Reconstructive interventions can be essential to repair deficits of a functional and/or aesthetic nature in order to maintain a high quality of life for oncology patients. This can also be of benefit to patients in a palliative oncological setting to improve daily functions and quality of life.

Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity.

PURPOSE: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases. METHODS AND MATERIALS: Immunofluorescence experiments were performed on a collection of skin fibroblasts from 12 radioresistant, 5 hyperradiosensitive, and 100 OR patients irradiated at 2 Gy. The numbers of micronuclei, γH2AX, and pATM foci that reflect different steps of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation and plotted against the severity grades established by the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group. RESULTS: OR patients did not necessarily show a gross DSB repair defect but a systematic delay in the nucleoshuttling of the ATM protein required for complete DSB recognition. Among the radiobiological factors, the maximal number of pATM foci provided the best discrimination among OR patients and a significant correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions. CONCLUSIONS: Our results are consistent with a general classification of human radiosensitivity based on 3 groups: radioresistance (group I); moderate radiosensitivity caused by delay of nucleoshuttling of ATM, which includes OR patients (group II); and hyperradiosensitivity caused by a gross DSB repair defect, which includes fatal cases (group III).

Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

BACKGROUND: PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. METHODS: Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. RESULTS: 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = -0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported "no problems" responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. CONCLUSIONS: Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. TRIAL REGISTRATION: NCT Clinicaltrials.gov identifier: NCT02158637.

HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). METHODS: Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information about current and past sunlight exposure, former occupation type, subdivided in indoor working and outdoor working, and iris color were obtained by standardized interviewer-assisted questionnaires. Associations between environmental factors adjusted for age, gender, and smoking and early and late AMD were performed by multivariate regression analysis. RESULTS: Current sunlight exposure showed no association with early AMD or late AMD, but past sunlight exposure (≥8 hours outside daily) was significantly associated with early AMD (odds ratio: 5.54, 95% confidence interval 1.25-24.58, P = 0.02) and late AMD (odds ratio: 2.77, 95% confidence interval 1.25-6.16, P = 0.01). Outside working was found to be associated with late AMD (odds ratio: 2.57, 95% confidence interval 1.89-3.48, P = 1.58 × 10). No association was observed between iris color and early or late AMD. CONCLUSION: Sunlight exposure during working life is an important risk factor for AMD, whereas sunlight exposure after retirement seems to have less influence on the disease development. Therefore, preventive measures, for example, wearing sunglasses to minimize sunlight exposure, should start early to prevent development of AMD later in life.

Glaucoma after chemical burns and radiation.

Glaucoma after chemical burns represents a posttraumatic glaucoma, usually open-angle glaucoma. It is a frequent complication of chemical burns, especially with alkali and it can appear in the acute stage or as a late complication. Because of the complications and scars, the treatment is very difficult. Topical treatment is based on AC inhibitors, ß-blockers, α2-agonists. Trabeculectomy, shunts, cyclophotocoagulation, and cryotherapy are the solutions in the late stages. Glaucoma after irradiation is a closing-angle secondary glaucoma. The risk factors such as the radiation dose and the volume of the radiated structure are important in the appearance and evolution of this type of glaucoma. Topical treatment is usually ineffective, the preferable options being laser and surgical treatments. Although it is not a frequently seen pathology, it is important to know how to diagnose and treat this type of glaucoma. There are various options available for treatment, but choosing one is difficult because of the possible complications.

[The morbidity and mortality of residents of Kazakhstan exposed to radiation impact and their posterity].

The most part of population exposed to radiation and their offspring residing in territories bordering upon the Semipalatinsk nuclear testing area represent objects of studying aged 40 years and older because the age is the factor decreasing health indices at the expense of natural gerontological processes. In these conditions, additional radiation exposition, besides radiological biological effects, plays the role ofpotentiation of common biological and environmental risk factors. From the archives of research institute of radiation medicine and ecology the primary medical documents were retrieved containing information about established diagnoses of individuals included into elaboration of epidemiological statistical analysis of dynamics of morbidity of persons in 2008-2012. Within the same period, the acts-certificates of causes of death of specific persons included into study groups were retrieved. It is established that in 8 classes of diseases in the main group and in 5 classes of diseases in comparison group significant exceeding of average annual indices of prevalence of diseases as compared with control group was established. The common prevalence of diseases in the main group comprised 3147.5 cases, in the comparison group - 2615.6 cases and in control group - 2203.8 cases per 1000 of population (RR=1.42;1.19; p<0.05;0.05). The indices of total mortality in the main group comprised 1887.3 cases, in the comparison group - 1531.2 cases and in control group - 1155.1 cases per 100 000 of population (RR=1.58;1.36; p<0.05;0.05). Among persons in the main group in 7 classes of diseases and in the comparison group in 5 classes of diseases significant exceeding of indices of mortality was registered over same indices in control group was registered as causes of death.

NONINVASIVE GRADING OF RADIATION RETINOPATHY: The Use of Optical Coherence Tomography Angiography.

PURPOSE: Previous studies have shown that spectral domain optical coherence tomography can diagnose radiation retinopathy (RR) before ophthalmoscopic findings. Recently, optical coherence tomography angiography (OCT-A) has been helpful in seeing vascular findings undetected by spectral domain optical coherence tomography. The authors wish to demonstrate the OCT-A grading at varying levels of RR. METHODS: The OCT-A, spectral domain optical coherence tomography, and ophthalmoscopic findings on 7 patients from December 2014 to March 2015 with varying levels of RR are demonstrated. RESULTS: Findings on OCT-A could be demonstrated before spectral domain optical coherence tomography findings. Patients can be graded on a scale of increasing severity from 0 to 5, based on positive or negative clinical findings of RR between OCT-A. Optical coherence tomography increased central macular thickness, optical coherence tomography evident cysts, and ophthalmoscopy (Grade 0: -,-,-,-; Grade 1: +,-,-,-; Grade 2: +,+,-,-; Grade 3: +,+,+,-; Grade 4: ++,+,+,+; Grade 5: unreadable,++,++,+). CONCLUSION: The use of OCT-A allows for earlier detection of RR; thus, existing grading systems should be modified to include OCT-A.

Validity and Reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

IMPORTANCE: To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). OBJECTIVE: To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items. DESIGN, SETTING, AND PARTICIPANTS: A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit. MAIN OUTCOMES AND MEASURES: Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30). RESULTS: A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median [range] r=0.43 [0.10-.56]; all P≤.006). CONCLUSIONS AND RELEVANCE: Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.

Classification and Reporting of Late Radiographic Changes After Lung Stereotactic Body Radiotherapy: Proposing a New System.

UNLABELLED: Radiation-induced parenchymal lung changes after stereotactic body radiotherapy are common, and can obscure the primary tumor site. In this study we propose a structured radiographic reporting tool for characterization of these changes, pilot its feasibility in a group of radiation oncologists, and test the interrater agreement. We could demonstrate the applicability of the scale, with a fair to moderate agreement. BACKGROUND: The purpose of the study was to design and pilot a synoptic scale for characterization of late radiographic changes after lung stereotactic body radiotherapy (SBRT). PATIENTS AND METHODS: A participatory design process involving 6 radiation oncologists and 2 thoracic radiologists was used in the scale's design. Seventy-seven early-stage non-small-cell lung cancer patients who were treated with SBRT were included, and after treatment their serial computed tomography (CT) images were scored by 6 radiation oncologists. Gwet's First-order Agreement Coefficient (AC1) and a leave-one-out (LOO) analysis was used to assess interrater reliability and variability among raters, respectively. RESULTS: The scale reports on 5 independent categories including "tumor in primary site," "tumor in involved lobe," "consolidation," "volume loss," and "ground-glass or interstitial changes." At each time point, each category is reported as "increased," "stable," "decreased," "obscured," or "not present," compared with the previous. The total number of rated images for the pilot ranged from 450 at 6 months to 84 at 48 months. The primary tumor site was scored as obscured in 38% to 40% of ratings from 12 months onward; 3% to 5% of primary tumors were scored as "increased." Consolidation, volume loss, and ground-glass or interstitial changes were increasingly marked as "stable" with time. At 24 months, AC1 was 0.28 (LOO, 0.22-0.42), 0.47 (LOO, 0.39-0.72), 0.45 (LOO, 0.42-0.50), 0.21 (LOO, 0.15-0.26), and 0.25 (LOO, 0.20-0.38) for the 5 categories listed, respectively. CONCLUSION: In a population of clinicians, this scale could be implemented to characterize evolving lung changes after SBRT, and had fair to moderate interrater agreement. Obscured tumor site is a common challenge of follow-up CT imaging, and new imaging techniques should be explored. This scale provides a tool for communicating changes after SBRT.

An ontology design for visualizing implicit knowledge of the radiotherapy risk.

Knowledge sharing of radiotherapy risk contributes to keep the safety practice between the oncologists, medical physicists, and therapists. But the mechanisms of risks tend to complex because of its diversities. Recently, an ontological analysis is tried to share knowledge in the various domains. Therefore, the aim of this study is to construct Radiotherapy Risk Ontology (RRO) and clarify the implicit structures of risks towards knowledge sharing. The method of this study is below. First, the classes and relations were extracted from the risk categorization of the publications. Second, these classes and relationships were connecting and mapping by the ontology editor. Third, the total relationships of classes were verified using paired comparison chart. This paper distinguishes between publication-oriented relationships and the other relationships. And these relationships was defined the explicit and implicit relationships. RRO was constructed 789 classes and 14 types of the explicit relationships. The 22 types of the implicit relationships were clarified using paired comparison. RRO provided the conceptual mapping and the implicit knowledge. The result of this study assisted the knowledge sharing.

Radiation-induced craniofacial deformities: a new classification and management algorithm.

Little is written about the spectrum of late radiation-induced craniofacial abnormalities and the guidelines for treating these abnormalities. The clinical records of 13 patients (eight males and five females) who received childhood craniofacial radiation between birth and 11 years of age and who subsequently had reconstructive surgery were reviewed. Eleven patients had their irradiation at the age from 1 to 5 years. The other two patients received their treatment at a relatively older age (9 and 11 years). Their deformities ranged from isolated soft-tissue deficiency with no or minimal bony deficiency to cases having osseous deformities with or without soft-tissue deficiency but still the normal or near-normal craniofacial form can be obtained with surgical intervention and the outermost extreme of the deformity is the patients whose normal or near-normal craniofacial form and function cannot be regained even with much sophisticated surgeries. Our new classification is based on two factors: the tissue component of the deformity and the possibility of regaining a normal or near-normal craniofacial form and function with the planned surgical intervention. Based on this classification, a new treatment algorithm was created.