(Pre)treatment risk factors for late fatigue and fatigue trajectories following radiotherapy for breast cancer.

Fatigue is common in breast-cancer survivors. Our study assessed fatigue longitudinally in breast cancer patients receiving adjuvant radiotherapy (RT) and aimed to identify risk factors associated with long-term fatigue and underlying fatigue trajectories. Fatigue was measured in a prospective multicenter cohort (REQUITE) using the Multidimensional Fatigue Inventory (MFI-20) and analyzed using mixed models. Multivariable logistic models identified factors associated with fatigue dimensions at 2 years post-RT and latent class growth analysis identified individual fatigue trajectories. A total of 1443, 1302, 1203 and 1098 patients completed the MFI-20 at baseline, end of RT, after 1 and 2 years. Overall, levels of fatigue significantly increased from baseline to end of RT for all fatigue dimensions (P < .05) and returned to baseline levels after 2 years. A quarter of patients were assigned to latent trajectory high (23.7%) and moderate (24.8%) fatigue classes, while 46.3% and 5.2% to the low and decreasing fatigue classes, respectively. Factors associated with multiple fatigue dimensions at 2 years include age, BMI, global health status, insomnia, pain, dyspnea and depression. Fatigue present at baseline was consistently associated with all five MFI-20 fatigue dimensions (ORGeneralFatigue = 3.81, P < .001). From latent trajectory analysis, patients with a combination of factors such as pain, insomnia, depression, younger age and endocrine therapy had a particularly high risk of developing early and persistent high fatigue years after treatment. Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered.

Research involving the recently deceased: ethics questions that must be answered.

Research involving recently deceased humans that are physiologically maintained following declaration of death by neurologic criteria-or 'research involving the recently deceased'-can fill a translational research gap while reducing harm to animals and living human subjects. It also creates new challenges for honouring the donor's legacy, respecting the rights of donor loved ones, resource allocation and public health. As this research model gains traction, new empirical ethics questions must be answered to preserve public trust in all forms of tissue donation and in the practice of medicine while respecting the legacy of the deceased and the rights of donor loved ones. This article suggests several topics for immediate investigation to understand the attitudes and experiences of researchers, clinical collaborators, donor loved ones and the public to ensure research involving the recently deceased advances ethically.

Penalized least-squares for imaging with hypertelescopes.

Practical considerations such as cost constrain the aperture size of conventional telescopes, which, combined with atmospheric turbulence effects, even in the presence of adaptive optics, limit achievable angular resolution. Sparse aperture telescopes represent a viable alternative for achieving improved angular resolution by combining light collected from small apertures distributed over a wide spatial area either using amplitude interferometry or a direct imaging approach to beam-combining. The so-called densified hypertelescope imaging concept in particular provides a methodology for direct image formation from large sparse aperture arrays. The densification system suppresses wide-angle side lobes and concentrates that energy in the center of the focal plane, significantly improving the signal-to-noise ratio of the measurement. Even with densification, an inevitable consequence of sparse aperture sampling is that the point-spread function associated with the direct image contains an additional structure not present in full aperture imaging systems. Postdetection image reconstruction is performed here to compute a high-fidelity estimate of the measured object in the presence of noise. In this paper, we describe a penalized least-squares object-estimation approach and compare the results with the classical Richardson-Lucy deconvolution algorithm as it is applied to hypertelescope image formation. The parameters of the algorithm are selected based on a comprehensive simulation study using the structure similarity metric to assess reconstruction performance. We find that the penalized least-squares formulation with optimized parameters provides significantly improved reconstructions compared with the conventional Richardson-Lucy algorithm.

Atmospheric turbulence characterization through multiframe blind deconvolution.

Characterization of turbulence in the atmosphere and mitigation of its effects in optical systems are important capabilities in both commercial and military applications. We present an image processing approach that jointly characterizes the magnitude of turbulence in the atmosphere and mitigates the adverse effects imposed on optical imaging systems. The magnitude of turbulence is measured indirectly through a series of image frames in terms of the atmospheric coherence length. We believe the results demonstrate the utility of the approach on both simulated and experimental data.

The health sphere beyond borders: Coverage portability and justice in a global space.

Medical coverage often stops at borders, for both travellers and long-term migrants. Such patchiness imposes a de facto limit on free movement. This article considers this phenomenon not as a mere policy choice or technical matter, but as a form of territorial discrimination that is incoherent and even unjust. This legacy of nationally bounded social citizenship rests on a mistaken version of solidarity. Moreover, with growing mobility and rising expectations of medical coverage around the world, the fragmenting of safety nets by the political honeycomb of statehood will become a vexing problem in coming decades. A proper understanding of the health sphere not only can justify incremental reforms that lessen territorial discrimination, without impairing either solidarity or sustainability. It also foreshadows a radically different vision of how social provision might work in a future global space beyond the nation-state.

The sputum microbiome is distinct between COPD and health, independent of smoking history.

BACKGROUND: Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD). However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD. METHODS: We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium. RESULTS: In healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera. Haemophilus formed only 3% of the healthy microbiome. In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively. There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history. Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001). CONCLUSION: The healthy and COPD sputum microbiomes are distinct and independent of smoking history. Our results underline the important role for Gammaproteobacteria in COPD.

Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study.

BACKGROUND: Recent studies suggest that lung microbiome dysbiosis, the disease associated disruption of the lung microbial community, might play a key role in chronic obstructive pulmonary disease (COPD) exacerbations. However, characterising temporal variability of the microbiome from large longitudinal COPD cohorts is needed to better understand this phenomenon. METHODS: We performed a 16S ribosomal RNA survey of microbiome on 716 sputum samples collected longitudinally at baseline and exacerbations from 281 subjects with COPD at three UK clinical centres as part of the COPDMAP consortium. RESULTS: The microbiome composition was similar among centres and between stable and exacerbations except for a small significant decrease of Veillonella at exacerbations. The abundance of Moraxella was negatively associated with bacterial alpha diversity. Microbiomes were distinct between exacerbations associated with bacteria versus eosinophilic airway inflammation. Dysbiosis at exacerbations, measured as significant within subject deviation of microbial composition relative to baseline, was present in 41% of exacerbations. Dysbiosis was associated with increased exacerbation severity indicated by a greater fall in forced expiratory volume in one second, forced vital capacity and a greater increase in CAT score, particularly in exacerbations with concurrent eosinophilic inflammation. There was a significant difference of temporal variability of microbial alpha and beta diversity among centres. The variation of beta diversity significantly decreased in those subjects with frequent historical exacerbations. CONCLUSIONS: Microbial dysbiosis is a feature of some exacerbations and its presence, especially in concert with eosinophilic inflammation, is associated with more severe exacerbations indicated by a greater fall in lung function. TRIAL REGISTRATION NUMBER: Results, NCT01620645.

Target Localization and Tracking by Fusing Doppler Differentials from Cellular Emanations with a Multi-Spectral Video Tracker.

We present an algorithm for fusing data from a constellation of RF sensors detecting cellular emanations with the output of a multi-spectral video tracker to localize and track a target with a specific cell phone. The RF sensors measure the Doppler shift caused by the moving cellular emanation and then Doppler differentials between all sensor pairs are calculated. The multi-spectral video tracker uses a Gaussian mixture model to detect foreground targets and SIFT features to track targets through the video sequence. The data is fused by associating the Doppler differential from the RF sensors with the theoretical Doppler differential computed from the multi-spectral tracker output. The absolute difference and the root-mean-square difference are computed to associate the Doppler differentials from the two sensor systems. Performance of the algorithm was evaluated using synthetically generated datasets of an urban scene with multiple moving vehicles. The presented fusion algorithm correctly associates the cellular emanation with the corresponding video target for low measurement uncertainty and in the presence of favorable motion patterns. For nearly all objects the fusion algorithm has high confidence in associating the emanation with the correct multi-spectral target from the most probable background target.

Blood and sputum eosinophils in COPD; relationship with bacterial load.

BACKGROUND: Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients. Bacterial infection causes increased airway neutrophilic inflammation. The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain. We tested the hypothesis that bacterial load and eosinophil counts are inversely related. METHODS: COPD patients were seen at stable state and exacerbation onset. Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae. PPM positive was defined as total load ≥1 × 104copies/ml. Sputum and whole blood were analysed for differential cell counts. RESULTS: At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs. 1.25% respectively, p = 0.01). Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs. 0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples. CONCLUSIONS: These findings indicate an inverse relationship between bacterial infection and eosinophil counts. Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.

Characteristics and longitudinal progression of chronic obstructive pulmonary disease in GOLD B patients.

BACKGROUND: The characteristics and natural history of GOLD B COPD patients are not well described. The clinical characteristics and natural history of GOLD B patients over 1 year in a multicentre cohort of COPD patients in the COPDMAP study were assessed. We aimed to identify the subgroup of patients who progressed to GOLD D (unstable GOLD B patients) and identify characteristics associated with progression. METHODS: Three hundred seventy COPD patients were assessed at baseline and 12 months thereafter. Demographics, lung function, health status, 6 min walk tests and levels of systemic inflammation were assessed. Students t tests and Mann Whitney-U tests were used. RESULTS: One hundred seven (28.9%) of patients were categorised as GOLD B at baseline. These GOLD B patients had similar FEV1 to GOLD A patients (66% predicted). More GOLD B patients were current smokers (p = 0.031), had chronic bronchitis (p = 0.0003) and cardiovascular comorbidities (p = 0.019) compared to GOLD A. At 12 months, 25.3% of GOLD B patients progressed to GOLD D. These patients who progressed (unstable patients) had worse health status and symptoms (SGRQ-C Total, 50.0 v 41.1, p = 0.019 and CAT, 21.0 v 14.0, p = 0.006) and lower FEV1 (60% v 69% p = 0.014) at baseline compared to stable patients who remained in GOLD B. CONCLUSIONS: Unstable GOLD B patients who progressed to GOLD D had a higher level of symptoms at baseline. A high symptom burden may predict an increased likelihood of disease progression in GOLD B patients.

Pharmacokinetic and Other Considerations for Drug Therapy During Targeted Temperature Management.

OBJECTIVE: To synthesize an emerging body of literature describing pharmacokinetic alterations and related pharmacodynamic implications affecting drugs commonly used in patients receiving targeted temperature management following cardiac arrest. DATA SOURCES: Peer-reviewed articles indexed in PubMed. STUDY SELECTION: A systematic search of the PubMed database for relevant preclinical studies and clinical and observational trials of physiologic changes and drug pharmacokinetic and pharmacodynamic alterations, especially during targeted temperature management/therapeutic hypothermia, but also from cardiac surgery and acute stroke hypothermia models. DATA EXTRACTION: Detailed review of information contained in published scientific work. DATA SYNTHESIS: Physiologic changes during targeted temperature management significantly alter both the pharmacokinetic and the pharmacodynamic parameters of medications. Current literature describes these alterations and provides practical considerations for management of medications. Medication selection should center on the pharmacokinetics and pharmacodynamics of agents in an attempt to ameliorate potential adverse effects. CONCLUSIONS: This review provides an overview of physiologic changes associated with targeted temperature management and practical considerations for the management of medications. Clinicians should understand and anticipate potential drug-therapy interactions of targeted temperature management and mitigate adverse outcomes by appropriate medication selection, dosing, and monitoring. We discuss complications of hypothermia including shivering, electrolyte abnormalities, hemodynamic changes, arrhythmias, and seizures. We review management of these complications as well as considerations for sedation, analgesia, anticoagulation, and prognostication. Approach to interpretation of the clinical significance of drug interactions during targeted temperature management therapy is also addressed.

Navigating the infodemic: A qualitative study of university students' information strategies during the COVID-19 pandemic.

Objectives: We aimed to study the strategies which university students developed for vetting information during the COVID-19 pandemic and associated infodemic. Methods: We conducted semi-structured interviews with 34 students, using a piloted topic guide which explored several areas of pandemic experiences, including students' use of media. Transcripts were analysed inductively following the thematic approach. Higher order themes were finalised following a coding exercise undertaken by two of the authors. Results: Participants were acutely aware of misinformation during the pandemic. They rated legacy news media (print and broadcast media with pre-Internet origins) higher than social media for reliable information about the pandemic. However, strikingly, not all legacy media were automatically trusted and not all social media were uniformly distrusted. Participants identified a set of mechanisms for establishing whether a piece of information was truthful and accurate. These mechanisms had four main focal points: (1) the source, (2) the message, (3) individual media literacy and (4) the trustworthiness of others. Despite possessing a critical awareness of misinformation, participants avoided posting anything in relation to the pandemic for fear of becoming the target of online abuse. Conclusions: In addition to underscoring the role of media literacy, our research foregrounds the need to attend to the importance of fostering media confidence. We define media confidence as the ability of digital media users to challenge and interrogate questionable or inaccurate information safe in the knowledge that there are adequate regulatory mechanisms in place to curb abuse, trolling and intimidation.

What to Expect? Use of Supplemental Fixation With a Concomitant Dorsal Spanning Plate for Complex Intraarticular Distal Radius Fractures.

BACKGROUND: The dorsal spanning plate (DSP) is a versatile implant suitable for bridging severely comminuted intraarticular distal radius fractures [AO (Arbeitsgemeinschaft für Osteosynthesefragen) 23-C.1-C.3]. It may be used alone or with supplemental fixation such as a volar locking plate (VLP) or fragment-specific fixation (FSF). Outcomes following DSP fixation with additional implants have not been specifically evaluated. METHODS: We retrospectively reviewed consecutive patients who underwent internal fixation of a distal radius fracture by a single surgeon from 2017 to 2021. Patients were grouped according to implants used: DSP only, DSP + FSF, and DSP + VLP. Preoperative variables, treatment times, and wrist range of motion (ROM) were assessed. Functional wrist ROM was defined as minimum 80° combined flexion and extension. RESULTS: One hundred fifty-two patients underwent surgery for wrist fracture, 33 of them were treated with a DSP: 8 DSP only, 6 DSP + VLP, and 19 DSP + FSF. Falls from height greater than 10 ft accounted for 52% of injuries, most of which were treated with a DSP + FSF. Treatment times and ROM were similar between subgroups. Wrist ROM did not improve significantly beyond 4 weeks following DSP removal. Overall, DSP patients recovered a mean wrist ROM of 85° (range 0°-130°) within a median 26 weeks total treatment period (range 12-68 weeks). CONCLUSION: Regardless of the construct used, if the distal radius articular surface is well reduced and other principles of fracture fixation are applied, most patients treated with a DSP can expect to regain functional wrist ROM. LEVEL OF EVIDENCE: Level IV-Retrospective review of prospectively collected data.

Endoscopic Rhizotomy for Facetogenic Back Pain: A Review of the History, Financial Considerations, Patient Selection Criteria, and Clinical Outcomes.

BACKGROUND: Chronic back pain (CBP) is a condition that places a considerable burden on society, with several million people affected in the United States alone. Treatment options to address this problem and relieve CBP are constantly evolving, and one of the most promising treatment modalities for CBP that is refractory to conservative treatment options is endoscopic rhizotomy (ER). METHODS: A thorough search of the PubMed (MEDLINE) database was conducted to assess the full progression of ER from its earliest uses to present day in a historical narrative review of ER, with treatment of facetogenic pain as a model pathology. RESULTS: ER allows for direct visualization and ablation of sensory branches of the dorsal ramus to provide pain relief in up to 80% of patients faced with refractory CBP. This technique has been built upon since the early 20th century, and the novel endoscopic approach continues to gain popularity among physicians. Benefits of ER include superior postoperative median pain-free duration compared with traditional percutaneous radiofrequency ablation, as well as direct visualization of regional anatomy. Patient selection criteria for the procedure and a modest list of contraindications allow the use of ER as a viable treatment option for a significant population of patients suffering from CBP. Potential barriers to ER include high cost of the procedure, longer intraoperative time, and expensive proprietary equipment. CONCLUSIONS: ER is an effective treatment for refractory CBP with notable advantages. As the technology and popularity of this procedure progress, improvements in the cost, training, and intraoperative time may make it a favorable alternative to the current standard of care.

Contouring variation affects estimates of normal tissue complication probability for breast fibrosis after radiotherapy.

BACKGROUND: Normal tissue complication probability (NTCP) models can be useful to estimate the risk of fibrosis after breast-conserving surgery (BCS) and radiotherapy (RT) to the breast. However, they are subject to uncertainties. We present the impact of contouring variation on the prediction of fibrosis. MATERIALS AND METHODS: 280 breast cancer patients treated BCS-RT were included. Nine Clinical Target Volume (CTV) contours were created for each patient: i) CTV_crop (reference), cropped 5 mm from the skin and ii) CTV_skin, uncropped and including the skin, iii) segmenting the 95% isodose (Iso95%) and iv) 3 different auto-contouring atlases generating uncropped and cropped contours (Atlas_skin/Atlas_crop). To illustrate the impact of contour variation on NTCP estimates, we applied two equations predicting fibrosis grade ≥ 2 at 5 years, based on Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) models, respectively, to each contour. Differences were evaluated using repeated-measures ANOVA. For completeness, the association between observed fibrosis events and NTCP estimates was also evaluated using logistic regression. RESULTS: There were minimal differences between contours when the same contouring approach was followed (cropped and uncropped). CTV_skin and Atlas_skin contours had lower NTCP estimates (-3.92%, IQR 4.00, p < 0.05) compared to CTV_crop. No significant difference was observed for Atlas_crop and Iso95% contours compared to CTV_crop. For the whole cohort, NTCP estimates varied between 5.3% and 49.5% (LKB) or 2.2% and 49.6% (RS) depending on the choice of contours. NTCP estimates for individual patients varied by up to a factor of 4. Estimates from "skin" contours showed higher agreement with observed events. CONCLUSION: Contour variations can lead to significantly different NTCP estimates for breast fibrosis, highlighting the importance of standardising breast contours before developing and/or applying NTCP models.

Comparing symptom reporting by prostate cancer patients and healthcare professionals in the international multicentre REQUITE study.

INTRODUCTION: Previous studies showed that healthcare professionals and patients had only moderate to low agreement on their assessment of treatment-related symptoms. We aimed to determine the levels of agreement in a large cohort of prostate cancer patients. METHODS: Analyses were made of data from 1,756 prostate cancer patients treated with external beam radiotherapy (RT) and/or brachytherapy in Europe and the USA and recruited into the prospective multicentre observational REQUITE study. Eleven pelvic symptoms at the end of RT were compared after translating patient-reported outcomes (PROs) into CTCAE-based healthcare professional ratings. Gwet's AC2 agreement coefficient and 95% confidence intervals were calculated for each symptom. To compare severity of grading between patients and healthcare professionals, percent agreement and deviations for each symptom were graphically depicted. Stratified and sensitivity analyses were conducted to identify potential influencing factors and to assess heterogeneity and robustness of results. RESULTS: The agreement for the 11 pelvic symptoms varied from very good (AC2 > 0.8: haematuria, rectal bleeding, management of sphincter control) to poor agreement (AC2 ≤ 0.2: proctitis and urinary urgency). Fatigue had a negative impact on the agreement. Patients tended to grade symptoms more severely than healthcare professionals. Information on sexual dysfunction was missing more frequently in healthcare professional assessment than PROs. CONCLUSION: Agreement was better for observable than subjective symptoms, with patients usually grading symptoms more severely than healthcare professionals. Our findings emphasize that PROs should complement symptom assessment by healthcare professionals and be taken into consideration for clinical decision-making to incorporate the patient perspective.

Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy. MATERIALS AND METHODS: A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited across 18 European and US centres into the prospective REQUITE cohort study. Toxicity data (CTCAE v4.0) were collected at baseline, end of radiotherapy, and annual follow-up. A total of 7,097,340 SNPs were tested for association with the residuals of toxicity endpoints, adjusted for clinical, treatment co-variates and population substructure. RESULTS: Quantile-quantile plots showed more associations with toxicity above the p < 5 × 10-5 level than expected by chance. Eight SNPs reached genome-wide significance. Nipple retraction grade ≥ 2 was associated with the rs188287402 variant (p = 2.80 × 10-8), breast oedema grade ≥ 2 with rs12657177 (p = 1.12 × 10-10), rs75912034 (p = 1.12 × 10-10), rs145328458 (p = 1.06 × 10-9) and rs61966612 (p = 1.23 × 10-9), induration grade ≥ 2 with rs77311050 (p = 2.54 × 10-8) and rs34063419 (p = 1.21 × 10-8), and arm lymphoedema grade ≥ 1 with rs643644 (p = 3.54 × 10-8). Heritability estimates across significant endpoints ranged from 25% to 39%. Our study did not replicate previously reported SNPs associated with breast radiation toxicity at the pre-specified significance level. CONCLUSIONS: This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints.

Large-scale meta-genome-wide association study reveals common genetic factors linked to radiation-induced acute toxicities across cancer types.

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung). METHODS: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV-formerly SNP)-based heritability of rSTATacute in all patients and for each cancer type. RESULTS: Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was higher for prostate (17%, SE = 0.07), head and neck (27%, SE = 0.09), and breast (16%, SE = 0.09) cancers. We identified 130 suggestive associated SNVs with rSTATacute (5.0 × 10‒8 < P < 1.0 × 10‒5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size ‒0.17; P = 1.7 × 10‒7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 × 10‒6, P = .079 corrected) as the top gene set associated with rSTATacute among all patients. In silico gene expression analysis showed that the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed P = .004 corrected; sun exposed P = .026 corrected). CONCLUSIONS: There is shared SNV-based heritability for acute radiation-induced toxicity across and within individual cancer sites. Future meta-genome-wide association studies among large radiation therapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.