Reirradiation of bone metastasis: A narrative review of the literature.

Patients with bone metastasis are prevalent among those receiving palliative radiotherapy (RT), with approximately 20 % requiring reirradiation (reirradiation). The goal of bone reirradiation may be local control (oligoreoccurrence or oligoprogression of a previously treated lesion or in a previous treatment field) or symptomatic (threatening or painful progression). Published data on bone reirradiation indicate almost two-thirds of overall pain response. The primary organ at risk (especially for spine treatment) is the spinal cord. The risk of radiation myelitis is<1 % for cumulative doses of<50Gy. Intensity-modulated RT (IMRT) and stereotactic RT (SRT) appear to be safer than three-dimensional RT (3DRT), although randomized trials comparing these techniques in reirradiation are lacking. Reirradiation requires multidisciplinary assessment. Alternative treatments for bone metastases (surgery, interventional radiology, etc.) must be considered. Patients should have a performance status≤2, with at least a 1-month interval between treatments. The planning process involves reviewing previous RT plans, cautious dose adjustments, and precise target delineation and dose distribution to minimize toxicity. Cumulative dosimetry, patient consent, and vigilant post-treatment monitoring and dose reporting are crucial.

[Update of guidelines of the AFSOS, SFRO, SFH, SFNCM, SFCE, GFRP for the management of radio-induced nausea and vomiting]. / Actualisation du référentiel AFSOS, SFRO, SFH, SFNCM, SFCE, GFRP : nausées et vomissements radio-induits.

BACKGROUND: Radiation-induced nausea and vomiting have mutiple clinical consequences: delay or refusal of irradiation (decreased antineoplastic efficacy of irradiation), altered quality of life, dehydration, malnutrition, interruption of treatment, decompensation of comorbidities and aspiration. These guidelines aim at defining good clinical practices for management of radiation-induced nausea and vomiting (RINV). METHODS: AFSOS, SFRO, SFH, SFNEP, SFCE and GFRP applied an expert consensus methodology to propose updated guidelines. RESULTS: RINV are underdiagnosed and undertreated. Assessment of the emetogenic risk depends on two main factors: 1) the irradiated anatomical localization and 2) the associated concomitant chemotherapy. In case of exclusive radiotherapy, primary antiemetic prophylaxis depends on the emetogenic risk of irradiated anatomical localization. Primary antiemetic prophylaxis is initiated at the onset of irradiation and continues until 24h after the end of the irradiation. In the case of concomitant radiochemotherapy, the emetogenic risk is generally higher for chemotherapy and the primary antiemetic prophylaxis corresponds to that of chemo-induced nausea and vomiting. In the case of persistence of these symptoms, subject to a well-conducted treatment, a rigorous diagnostic procedure must be carried out before being attributed to radiotherapy and precise evaluation of their impact. Remedial treatments are less well codified. CONCLUSION: It is essential to know and good management practices for radiation-induced nausea and vomiting.

Combined cardiovascular effects of ovariectomy and high-intensity interval training in female spontaneously hypertensive rats.

Hypertensive postmenopausal women are more likely to develop adverse cardiac remodeling and respond less effectively to drug treatment than men. High-intensity interval exercise (HIIE) is a nonpharmacological strategy for the treatment of hypertension; however, the effectiveness in women remains uncertain. This study was designed to evaluate 1) the effects of HIIE training upon morphological and functional markers of cardiovascular health in female SHR and 2) to determine whether the hormonal shift induced by ovariectomy could influence cardiovascular responses to HIIE. Thirty-six SHR were randomly assigned to four groups: ovariectomized sedentary, ovariectomized trained, sham-operated sedentary, and sham-operated trained. The trained rats performed HIIE 5 days/wk for 8 wk. Blood pressure and echocardiographic measurements were performed before and after training in animals. Cardiac response to ß-adrenergic stimulation and the expression of calcium regulatory proteins and estrogen receptors in heart samples were assessed. Endothelium-dependent vasorelaxation in response to acetylcholine was evaluated in aortic rings as well as the expression of nitric oxide synthase isoforms (eNOS and P-eNOS) by Western blotting. In both groups of trained SHR, HIIE induced eccentric cardiac remodeling with greater inotropic and chronotropic effects, as well as an increase in SERCA and ß1AR expression. However, although the trained rats showed improved endothelial function and expression of eNOS and P-eNOS in the aorta, there was no demonstrated effect on blood pressure. In addition, the responses to HIIE training were not affected by ovariectomy. This work highlights the importance of assessing the cardiovascular efficacy and safety of different exercise modalities in women.NEW & NOTEWORTHY This study reports the effects of high-intensity interval exercise (HIIE) training on cardiac and endothelial function in female hypertensive rats. Despite a lack of effect on blood pressure (BP), HIIE training induces eccentric cardiac remodeling with greater functionals effects. Furthermore, training has beneficial effects on endothelial function. However, ovarian hormones do not seem to modulate cardiac and aortic adaptations to this training modality. All this underlines the need to consider training modalities on the cardiovascular system in women.

Recommendations for Post-Operative RadioTherapy After Complete Resection of Thymoma-a French DELPHI Consensus Initiative.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT. METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement. RESULTS: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years. CONCLUSION: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

CyberKnife® stereotactic radiation therapy for stage I lung cancer and pulmonary oligometastases: is fiducial implantation still relevant?-a cohort study.

Background: Few studies have investigated whether there is a difference in local control or overall survival rates following treatment with robotic stereotactic body radiation therapy (SBRT) with or without prior fiducial marker implantation. Our study aimed to investigate this in patients with primary or secondary lung tumors. Methods: A retrospective study was conducted at the Institut de Cancérologie de Lorraine of patients treated for primary lung cancer or pulmonary oligometastases with SBRT from January 2013 to July 2016. We included patients at least 18 years old who had stage I non-small cell lung cancer (NSCLC) or lung metastases and a follow-up of at least 1 month. Results: A total of 294 patients were included. Tumors included 122 lung metastases, 89 stage I NSCLC, and 83 non-histologically confirmed lung lesions. The tracking methods were Synchrony® in 191 cases (119 gold seeds and 72 coils) and Xsight® Spine with 4D computed tomography in 103 cases. Median follow-up was 31.6 months [interquartile range (IQR), 18.1-50.2 months]. The two- and five-year probability of local control were respectively 92.22% [95% confidence interval (CI): 0.89-0.95] and 85.35% (95% CI: 0.79-0.99). The two- and five-year probability of overall survival were respectively 87.46% and 72.77% (P=0.586). Local control rates did not significantly differ between techniques at 2 and 5 years (P=0.685) (gold seeds, coils or Xsight® Spine) within tumors grouped by location, gross tumor volume (GTV) (respectively P=0.9, P=0.7, and P=0.4), planning target volume (PTV) (respectively P=0.4, P=0.9, and P=0.7), or PTV/GTV ratio (respectively P=0.6, P=0.6, and P=0.5). Metastasis-free survival and Overall survival rates did not significantly differ between techniques at 2 and 5 years (P=0.664 and P=0.586, respectively). There were no grade 4 or 5 toxicities and only one grade 3 pneumonitis and one grade 3 pneumothorax. Conclusions: Fiducial-less SBRT using Xsight® Spine is a safe alternative to Synchrony® using gold seeds or coils, with comparable local control and overall survival rates and a similar toxicity profile.

Ultra-high resolution CT imaging of interstitial lung disease: impact of photon-counting CT in 112 patients.

OBJECTIVES: To compare lung parenchyma analysis on ultra-high resolution (UHR) images of a photon-counting CT (PCCT) scanner with that of high-resolution (HR) images of an energy-integrating detector CT (EID-CT). METHODS: A total of 112 patients with stable interstitial lung disease (ILD) were investigated (a) at T0 with HRCT on a 3rd-generation dual-source CT scanner; (b) at T1 with UHR on a PCCT scanner; (c) with a comparison of 1-mm-thick lung images. RESULTS: Despite a higher level of objective noise at T1 (74.1 ± 14.1 UH vs 38.1 ± 8.7 UH; p < 0.0001), higher qualitative scores were observed at T1 with (a) visualization of more distal bronchial divisions (median order; Q1-Q3) (T1: 10th division [9-10]; T0: 9th division [8-9]; p < 0.0001); (b) greater scores of sharpness of bronchial walls (p < 0.0001) and right major fissure (p < 0.0001). The scores of visualization of CT features of ILD were significantly superior at T1 (micronodules: p = 0.03; linear opacities, intralobular reticulation, bronchiectasis, bronchiolectasis, and honeycombing: p < 0.0001), leading to the reclassification of 4 patients with non-fibrotic ILD at T0, recognized with fibrotic ILD at T1. At T1, the mean (± SD) radiation dose (CTDI vol: 2.7 ± 0.5 mGy; DLP: 88.5 ± 21 mGy.cm) was significantly lower than that delivered at T0 (CTDI vol: 3.6 ± 0.9 mGy; DLP: 129.8 ± 31.7 mGy.cm) (p < 0.0001), corresponding to a mean reduction of 27% and 32% for the CTDIvol and DLP, respectively. CONCLUSIONS: The UHR scanning mode of PCCT allowed a more precise depiction of CT features of ILDs and reclassification of ILD patterns with significant radiation dose reduction. CLINICAL RELEVANCE STATEMENT: Evaluation of lung parenchymal structures with ultra-high-resolution makes subtle changes at the level of the secondary pulmonary lobules and lung microcirculation becoming visually accessible, opening new options for synergistic collaborations between highly-detailed morphology and artificial intelligence. KEY POINTS: • Photon-counting CT (PCCT) provides a more precise analysis of lung parenchymal structures and CT features of interstitial lung diseases (ILDs). • The UHR mode ensures a more precise delineation of fine fibrotic abnormalities with the potential of modifying the categorization of ILD patterns. • Better image quality at a lower radiation dose with PCCT opens new horizons for further dose reduction in noncontrast UHR examinations.

Prognostic factors of local control and progression-free survival in AJCC stages T1 and T2 cervical cancer patients treated with adjuvant brachytherapy after chemoradiotherapy.

Purpose: We assessed prognostic factors of local control and progression-free survival (PFS) of patients treated for AJCC stages T1 and T2 cervical cancer using utero-vaginal brachytherapy after chemoradiotherapy. Material and methods: This retrospective single-institution analysis included patients who underwent brachytherapy after radiochemotherapy between 2005 and 2015 at the Institut de Cancérologie de Lorraine. Adjuvant hysterectomy was optional. A multivariate analysis of prognostic factors was carried out. Results: Of 218 patients, 81 (37.2%) were AJCC stage T1, and 137 (62.8%) were AJCC stage T2. 167 (76.6%) patients had squamous cell carcinoma, 97 (44.5%) patients had pelvic nodal disease, and 30 (13.8%) patients had para-aortic nodal disease. One hundred eighty-four patients (84.4%) underwent concomitant chemotherapy, while adjuvant surgery was performed in 91 patients (41.9%) and 42 (46.2%) patients had pathological complete response. Median follow-up was 4.2 years, and local control was reported in 87.8% (95% CI: 83.0-91.8) and 87.2% (95% CI: 82.3-91.3) of patients at 2 and 5 years, respectively. In multivariate analysis, T stage (hazard ratio [HR] = 3.65, 95% CI: 1.27-10.46, p = 0.016) was associated with local control. PFS was reported in 67.6% (95% CI: 60.9-73.4) and 57.4% (95% CI: 49.3-64.2) of patients at 2 and 5 years, respectively. In multivariate analysis, para-aortic nodal disease (HR = 2.03, 95% CI: 1.16-3.54, p = 0.012), pathological complete response (HR = 0.33, 95% CI: 0.15-0.73, p = 0.006), and intermediate-risk clinical tumor volume of > 60 cc (HR = 1.90, 95% CI: 1.22-2.98, p = 0.005) were associated with PFS. Conclusions: Lower dose brachytherapy may benefit AJCC stages T1 and T2 tumors, whereas higher doses are required for larger tumors and para-aortic nodal disease involvement, respectively. Pathological complete response should be associated with better local control and not surgery.

Ultra-High-Resolution Photon-Counting CT Imaging of the Chest: A New Era for Morphology and Function.

ABSTRACT: After a decade of preclinical testing, photon-counting computed tomography (PCCT) has now entered daily routine, enabling radiologists to start investigating thoracic disorders in unprecedented conditions. The improved spatial resolution of the ultra-high-resolution (UHR) scanning mode is a major step for the analysis of bronchopulmonary disorders, making abnormalities at the level of small anatomical structures such as secondary pulmonary lobules accessible to radiologists. Distal divisions of pulmonary and systemic vessels also benefit from UHR protocols as alterations of lung microcirculation were previously excluded from confident analysis with energy-integrating detector CT. Although noncontrast chest CT examinations were the initial target of UHR protocols, the clinical value of this mode is also applicable to chest CT angiographic examinations with improved morphological evaluation and higher-quality lung perfusion imaging. The clinical benefits of UHR have been evaluated in initial studies, allowing radiologists to foresee the field of future applications, all combining high diagnostic value and radiation dose reduction. The purpose of this article is to highlight the technological information relevant to daily practice and to review the current clinical applications in the field of chest imaging.

Pro-inflammatory cytokine secretion induced by amyloid transthyretin in human cardiac fibroblasts.

Extracellular aggregates of wild-type human transthyretin are associated with heart diseases such as wild-type transthyretin (TTR)-derived amyloidosis (ATTR-wt). Due to their strategic location, cardiac fibroblasts act as sentinel cells that sense injury and activate the inflammasome. No studies of the effects of TTR amyloid aggregation on the secretion of inflammatory factors by primary human cardiac fibroblasts (hCFs) have been reported yet. The intracellular internalization of TTR aggregates, which correspond to the early stage of ATTR-wt, were determined using immunofluorescence and Western blotting of cell lysates. A further objective of this study was to analyze the secretion of inflammatory factors by hCFs after analysis of TTR amyloid aggregation using X-MAP® Luminex Assay techniques. We show that TTR aggregates are internalized in hCFs and induce the secretion of both Brain Natriuretic Peptide (BNP) and N-terminal pro B-type Natriuretic Peptide(NT-proBNP). Also, pro-inflammatory mediators such as interleukin-6 (IL-6) and IL-8 are secreted without significant changes in the levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). In conclusion, these findings suggest that IL-6 and IL-8 play important roles in the development of ATTR-wt, and indicate that IL-6 in particular could be a potentially important therapeutic target in patients with ATTR-wt.

Acute skin toxicity of conventional fractionated versus hypofractionated radiotherapy in breast cancer patients receiving regional node irradiation: the real-life prospective multicenter HYPOBREAST cohort.

BACKGROUND: Large-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data. METHODS: We conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity. RESULTS: Between November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall). CONCLUSION: Using real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life.

Molecular and functional characterization of the mouse intrinsic cardiac nervous system.

BACKGROUND: The intrinsic cardiac nervous system (ICNS) refers to clusters of neurons, located within the heart, that participate in the neuronal regulation of cardiac functions and that are involved in the initiation of cardiac arrhythmias. Therefore, deciphering its role in cardiac physiology and physiopathology is mandatory. OBJECTIVE: The aim of this study was to provide a phenotypic, electrophysiological, and pharmacological characterization of the mouse ICNS, which is still poorly characterized. METHODS: Global cardiac innervation and phenotypic diversity were investigated using immunohistochemistry on cleared murine hearts and on tissue sections. The patch clamp technique was used for the electrophysiological and pharmacological characterization of isolated mouse intracardiac neurons. RESULTS: We have identified the expression of 7 distinct neuronal markers within the mouse ICNS, thus proving the neurochemical diversity of this network. Of note, it was the first time that the existence of neurons expressing the calcium-binding protein calbindin, neuropeptide Y, and cocaine and amphetamine regulated transcript peptide was described in the mouse. Electrophysiology studies also revealed the existence of 4 different neuronal populations on the basis of their electrical behavior. Finally, we showed that these neurons can be modulated by several neuromodulators. CONCLUSION: This study showed that the mouse ICNS presents a molecular and functional complexity similar to other species and is therefore a suitable model to decipher the role of individual neuronal subtypes regarding the modulation of cardiac function and the initiation of cardiac arrhythmias.

Dual-energy CT lung perfusion characteristics in pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH): preliminary experience in 63 patients.

BACKGROUND: In the stratification of potential causes of PH, current guidelines recommend performing V/Q lung scintigraphy to screen for CTEPH. The recognition of CTEPH is based on the identification of lung segments or sub-segments without perfusion but preserved ventilation. The presence of mismatched perfusion defects has also been described in a small proportion of idiopathic pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH). Dual-energy CT lung perfusion changes have not been specifically investigated in these two entities. PURPOSE: To compare dual-energy CT (DECT) perfusion characteristics in PAH and PVOD/PCH, with specific interest in PE-type perfusion defects. MATERIALS AND METHODS: Sixty-three patients with idiopathic or heritable PAH (group A; n = 51) and PVOD/PCH (group B; n = 12) were investigated with DECT angiography with reconstruction of morphologic and perfusion images. RESULTS: The number of patients with abnormal perfusion did not differ between group A (35/51; 68.6%) and group B (6/12; 50%) (p = 0.31) nor did the mean number of segments with abnormal perfusion per patient (group A: 17.9 ± 4.9; group B: 18.3 ± 4.1; p = 0.91). The most frequent finding was the presence of patchy defects in group A (15/35; 42.9%) and a variable association of perfusion abnormalities in group B (4/6; 66.7%). The median percentage of segments with PE-type defects per patient was significantly higher in group B than in group A (p = 0.041). Two types of PE-type defects were depicted in 8 patients (group A: 5/51; 9.8%; group B: 3/12; 25%), superimposed on PH-related lung abnormalities (7/8) or normal lung (1/8). The iodine concentration was significantly lower in patients with abnormal perfusion (p < 0.001) but did not differ between groups. CONCLUSION: Perfusion abnormalities did not differ between the two groups at the exception of a higher median percentage of segments with PE-type defects in patients with PVOD/PCH. KEY POINTS: • Patchy perfusion defect was the most frequent pattern in PAH. • A variable association of perfusion abnormalities was seen in PVOD/PCH. • Lobular and PE-type perfusion defects larger than a sub-segment were depicted in both PAH and PVOD/PCH patients.

Dual-Energy CT Perfusion of Invasive Tumor Front in Non-Small Cell Lung Cancers.

Background Active endothelial cell proliferation occurs at the tumor edge, known as the invading-tumor front. This study focused on perfusion analysis of non-small cell lung cancers. Purpose To analyze dual-phase, dual-energy CT perfusion according to the degree of tumor hypoxia. Materials and Methods This prospective study was performed 2016-2017. A two-phase dual-energy CT protocol was obtained for consecutive participants with operable non-small cell lung cancer. The first pass and delayed iodine concentration within the tumor and normalized iodine uptake, corresponding to the iodine concentration within the tumor normalized to iodine concentration within the aorta, were calculated for the entire tumor and within three peripheral layers automatically segmented (ie, 2-mm-thick concentric subvolumes). The expression of the membranous carbonic anhydrase (mCA) IX, a marker of tumor hypoxia, was assessed in tumor specimens. Comparative analyses according to the histologic subtypes, type of resected tumors, and mCA IX expression were performed. Results There were 33 mCA IX-positive tumors and 16 mCA IX-negative tumors. In the entire tumor, the mean normalized iodine uptake was higher on delayed than on first-pass acquisitions (0.35 ± 0.17 vs 0.13 ± 0.15, respectively; P < .001). A single layer, located at the edge of the tumor, showed higher values of the iodine concentration (median, 0.53 mg/mL vs 0.21 mg/mL, respectively; P = .03) and normalized iodine uptake (0.04 vs 0.02, respectively; P = .03) at first pass in mCA IX-positive versus mCA IX-negative tumors. Within this layer, a functional profile of neovascularization was found in 23 of 33 (70%) of mCA IX-positive tumors, and the median mCA IX score of these tumors was higher than in tumors with a nonfunctional profile of neovascularization (median mCA IX score, 20 vs 2, respectively; P = .03). Conclusion A two-phase dual-energy CT examination depicted higher perfusion between the tumor edge and lung parenchyma in hypoxic tumors. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Murphy and Ryan in this issue.

Evaluation Of a New Reconstruction Technique for Dual-Energy (DECT) Lung Perfusion: Preliminary Experience In 58 Patients.

PURPOSE: To compare dual-energy (DE) lung perfused blood volume generated by subtraction of virtual monoenergetic images (Lung Mono) with images obtained by three-compartment decomposition (Lung PBV). MATERIAL AND METHODS: The study included 58 patients (28 patients with and 30 patients without PE) with reconstruction of Lung PBV images (i.e., the reference standard) and Lung Mono images. The inter-technique comparison was undertaken at a patient and segment level. RESULTS: The distribution of scores of subjective image noise (patient level) significantly differed between the two reconstructions (p<0.0001), with mild noise in 58.6% (34/58) of Lung Mono images vs 25.9% (15/58) of Lung PBV images. Detection of perfusion defects (segment level) was concordant in 1104 segments (no defect: n=968; defects present: n=138) and discordant in 2 segments with a PE-related defect only depicted on Lung Mono images. Among the 28 PE patients, the distribution of gradient of attenuation between perfused areas and defects was significantly higher on Lung Mono images compared to Lung PBV (median= 73.5 HU (QI=65.0; Q3=86.0) vs 24.5 HU (22.0; 30.0); p<0.0001). In all patients, fissures were precisely identified in 77.6% of patients (45/58) on Lung Mono images while blurred (30/58; 51.7%) or not detectable (28/58; 48.3%) on Lung PBV images. CONCLUSION: Lung Mono perfusion imaging allows significant improvement in the overall image quality and improved detectability of PE-type perfusion defects.

Outcomes of anus squamous cell carcinoma. Management of anus squamous cell carcinoma and recurrences.

BACKGROUND: Little is known about the management of squamous cell carcinoma of the anal canal and its recurrence at a population level. The aim of this study was to draw a picture of management, recurrence and survival in squamous cell carcinoma of the anal canal. MATERIAL AND METHODS: The 5-year probability of recurrences was estimated using the cumulative incidence function to consider competing risks of death. Net survival was estimated and a multivariate survival analysis was performed. The study was conducted using data of the Burgundy Digestive Cancer Registry. Overall, 273 squamous cell carcinomas of the anal canal registered between 1998 and 2014 were considered. RESULTS: Overall, 80% of patients were treated with curative intent. Of these, 61% received chemoradiotherapy, 35% received radiotherapy and 4% received abdominoperineal resection alone. After these treatments, for cure the 5-year cumulative recurrence rate was 27% overall; it was 20% after chemoradiotherapy and 38% after radiotherapy. Five-year net survival was 71% overall; it was 81% after chemoradiotherapy and 55% after radiotherapy. CONCLUSIONS AND RELEVANCE: Chemoradiotherapy was highly effective in routine practice. We confirm that it is difficult to distinguish between persistent active disease and local inflammation due to radiotherapy. Squamous cell carcinoma of the anal canal recurrences remains a substantial problem, highlighting the interest of prolonged surveillance. Aggressive management of recurrences may be beneficial.

Impact of Neck Dissection in Head and Neck Squamous Cell Carcinomas of Unknown Primary.

PURPOSE: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP. METHODS: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage. RESULTS: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. CONCLUSION: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage.

Unraveling the interplay of image formation, data representation and learning in CT-based COPD phenotyping automation: The need for a meta-strategy.

PURPOSE: In the literature on automated phenotyping of chronic obstructive pulmonary disease (COPD), there is a multitude of isolated classical machine learning and deep learning techniques, mostly investigating individual phenotypes, with small study cohorts and heterogeneous meta-parameters, e.g., different scan protocols or segmented regions. The objective is to compare the impact of different experimental setups, i.e., varying meta-parameters related to image formation and data representation, with the impact of the learning technique for subtyping automation for a variety of phenotypes. The identified associations of these parameters with automation performance and their interactions might be a first step towards a determination of optimal meta-parameters, i.e., a meta-strategy. METHODS: A clinical cohort of 981 patients (53.8 ± 15.1 years, 554 male) was examined. The inspiratory CT images were analyzed to automate the diagnosis of 13 COPD phenotypes given by two radiologists. A benchmark feature set that integrates many quantitative criteria was extracted from the lung and trained a variety of learning algorithms on the first 654 patients (two thirds) and the respective algorithm retrospectively assessed the remaining 327 patients (one third). The automation performance was evaluated by the area under the receiver operating characteristic curve (AUC). 1717 experiments were conducted with varying meta-parameters such as reconstruction kernel, segmented regions and input dimensionality, i.e., number of extracted features. The association of the meta-parameters with the automation performance was analyzed by multivariable general linear model decomposition of the automation performance in the contributions of meta-parameters and the learning technique. RESULTS: The automation performance varied strongly for varying meta-parameters. For emphysema-predominant phenotypes, an AUC of 93%-95% could be achieved for the best meta-configuration. The airways-predominant phenotypes led to a lower performance of 65%-85%, while smooth kernel configurations on average were unexpectedly superior to those with sharp kernels. The performance impact of meta-parameters, even that of often neglected ones like the missing-data imputation, was in general larger than that of the learning technique. Advanced learning techniques like 3D deep learning or automated machine learning yielded inferior automation performance for non-optimal meta-configurations in comparison to simple techniques with suitable meta-configurations. The best automation performance was achieved by a combination of modern learning techniques and a suitable meta-configuration. CONCLUSIONS: Our results indicate that for COPD phenotype automation, study design parameters such as reconstruction kernel and the model input dimensionality should be adapted to the learning technique and may be more important than the technique itself. To achieve optimal automation and prediction results, the interaction between input those meta-parameters and the learning technique should be considered. This might be particularly relevant for the development of specific scan protocols for novel learning algorithms, and towards an understanding of good study design for automated phenotyping.

Assessment of pulmonary arterial circulation 3 months after hospitalization for SARS-CoV-2 pneumonia: Dual-energy CT (DECT) angiographic study in 55 patients.

BACKGROUND: During COVID-19, the main manifestations of the disease are not only pneumonia but also coagulation disorders. The purpose of this study was to evaluate pulmonary vascular abnormalities 3 months after hospitalization for SARS-CoV-2 pneumonia in patients with persistent respiratory symptoms. METHODS: Among the 320 patients who participated in a systematic follow-up 3 months after hospitalization, 76 patients had residual symptoms justifying a specialized follow-up in the department of pulmonology. Among them, dual-energy CT angiography (DECTA) was obtained in 55 patients. FINDINGS: The 55 patients had partial (n = 40; 72.7%) or complete (n = 15; 27.3%) resolution of COVID-19 lung infiltration. DECTA was normal in 52 patients (52/55; 94.6%) and showed endoluminal filling defects in 3 patients (3/55; 5.4%) at the level of one (n = 1) and two (n = 1) segmental arteries of a single lobe and within central and peripheral arteries (n = 1). DECT lung perfusion was rated as non-interpretable (n = 2;3.6%), normal (n = 17; 30.9%) and abnormal (n = 36; 65.5%), the latter group comprising 32 patients with residual COVID-19 opacities (32/36; 89%) and 4 patients with normal lung parenchyma (4/36; 11%). Perfusion abnormalities consisted of (a) patchy defects (30/36; 83%), (b) PE-type defects (6/36; 16.6%) with (n = 1) or without proximal thrombosis (n = 5); and (c) focal areas of hypoperfusion (2/36; 5.5%). Increased perfusion was seen in 15 patients, always matching GGOs, bands and/or vascular tree-in- bud patterns. INTERPRETATION: DECT depicted proximal arterial thrombosis in 5.4% of patients and perfusion abnormalities suggestive of widespread microangiopathy in 65.5% of patients. Lung microcirculation was abnormal in 4 patients with normal lung parenchyma.

Polyunsaturated Phospholipids Increase Cell Resilience to Mechanical Constraints.

If polyunsaturated fatty acids (PUFAs) are generally accepted to be good for health, the mechanisms of their bona fide benefits still remain elusive. Membrane phospholipids (PLs) of the cardiovascular system and skeletal muscles are particularly enriched in PUFAs. The fatty acid composition of PLs is known to regulate crucial membrane properties, including elasticity and plasticity. Since muscle cells undergo repeated cycles of elongation and relaxation, we postulated in the present study that PUFA-containing PLs could be central players for muscle cell adaptation to mechanical constraints. By a combination of in cellulo and in silico approaches, we show that PUFAs, and particularly the ω-3 docosahexaenoic acid (DHA), regulate important properties of the plasma membrane that improve muscle cell resilience to mechanical constraints. Thanks to their unique property to contortionate within the bilayer plane, they facilitate the formation of vacuole-like dilation (VLD), which, in turn, avoid cell breakage under mechanical constraints.

An ecological niche shift for Neanderthal populations in Western Europe 70,000 years ago.

Middle Paleolithic Neanderthal populations occupied Eurasia for at least 250,000 years prior to the arrival of anatomically modern humans. While a considerable body of archaeological research has focused on Neanderthal material culture and subsistence strategies, little attention has been paid to the relationship between regionally specific cultural trajectories and their associated existing fundamental ecological niches, nor to how the latter varied across periods of climatic variability. We examine the Middle Paleolithic archaeological record of a naturally constrained region of Western Europe between 82,000 and 60,000 years ago using ecological niche modeling methods. Evaluations of ecological niche estimations, in both geographic and environmental dimensions, indicate that 70,000 years ago the range of suitable habitats exploited by these Neanderthal populations contracted and shifted. These ecological niche dynamics are the result of groups continuing to occupy habitual territories that were characterized by new environmental conditions during Marine Isotope Stage 4. The development of original cultural adaptations permitted this territorial stability.