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\"[This book] follows Morel, a Frenchman who survives the Holocaust--a survival he credits to imagining elephants roaming the wilderness. Once free, he travels to French Equatorial Africa with the aim of saving his beloved elephants from being hunted and killed for meat and ivory. Realizing his more conventional tactics are not eliciting a response, however, he turns militant, and the story takes a dark turn. This novel examines the corrosive force of human desensitization, and it is one of the first classic ecological novels of our time\" -- Provided by publisher

PurposeWe aimed to evaluate if imaging biomarkers on FDG PET are associated with clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).MethodsIn this retrospective monocentric study, we included 109 patients with advanced NSCLC who underwent baseline FDG PET/CT before ICI initiation between July 2013 and September 2018. Clinical, biological (including dNLR = neutrophils/[leukocytes minus neutrophils]), pathological and PET parameters (tumor SUVmax, total metabolic tumor volume [TMTV]) were evaluated. A multivariate prediction model was developed using Cox models for progression-free survival (PFS) and overall survival (OS). The association between biomarkers on FDG PET/CT and disease clinical benefit (DCB) was tested using logistic regression.ResultsEighty patients were eligible. Median follow-up was 11.6 months (95%CI 7.7–15.5). Sixty-four and 52 patients experienced progression and death, respectively. DCB was 40%. In multivariate analyses, TMTV > 75 cm3 and dNLR > 3 were associated with shorter OS (HR 2.5, 95%CI 1.3–4.7 and HR 3.3, 95%CI 1.6–6.4) and absence of DCB (OR 0.3, 95%CI 0.1–0.9 and OR 0.4, 95%CI 0.2–0.9). Unlike TMTV, dNLR was a significant prognostic factor for PFS (HR 1.9, 95%CI 1.1–3.3) along with anemia (HR 1.9, 95%CI 1.2–3.8). No association was observed between tumor SUVmax and PFS or OS.ConclusionBaseline tumor burden (TMTV) on FDG PET/CT scans and inflammatory status (dNLR) were associated with poor OS and absence of DCB for ICI treatment in advanced NSCLC patients, unlike tumor SUVmax, and may be used together to improve the selection of appropriate candidates.

PurposeAn imaging-based stratification tool is needed to identify melanoma patients who will benefit from anti Programmed Death-1 antibody (anti-PD1). We aimed at identifying biomarkers for survival and response evaluated in lymphoid tissue metabolism in spleen and bone marrow before initiation of therapy.MethodsThis retrospective study included 55 patients from two institutions who underwent 18F-FDG PET/CT before anti-PD1. Parameters extracted were SUVmax, SUVmean, HISUV (SUV-based Heterogeneity Index), TMTV (total metabolic tumor volume), TLG (total lesion glycolysis), BLR (Bone marrow-to-Liver SUVmax ratio), and SLR (Spleen-to-Liver SUVmax ratio). Each parameter was dichotomized using the median as a threshold. Association with survival, best overall response (BOR), and transcriptomic analyses (NanoString assay) were evaluated using Cox prediction models, Wilcoxon tests, and Spearman’s correlation, respectively.ResultsAt 20.7 months median follow-up, 33 patients had responded, and 29 patients died. Median PFS and OS were 11.4 (95%CI 2.7–20.2) and 28.5 (95%CI 13.4–43.8) months. TMTV (>25cm3), SLR (>0.77), and BLR (>0.79) correlated with shorter survival. High TMTV (>25 cm3), SLR (>0.77), and BLR (>0.79) correlated with shorter survival, with TMTV (HR PFS 2.2, p = 0.02, and HR OS 2.5, p = 0.02) and BLR (HR OS 2.3, p = 0.04) remaining significant in a multivariable analysis. Low TMTV and TLG correlated with BOR (p = 0.03). Increased glucose metabolism in bone marrow (BLR) was associated with transcriptomic profiles including regulatory T cell markers (p < 0.05).ConclusionLow tumor burden correlates with survival and objective response while hematopoietic tissue metabolism correlates inversely with survival. These biomarkers should be further evaluated for potential clinical application.

PurposeTo compare the prognostic value of imaging biomarkers derived from a quantitative analysis of baseline 18F-FDG-PET/CT in patients with mucosal melanoma (Muc-M) or cutaneous melanoma (Cut-M) treated with immune checkpoint inhibitors (ICIs).MethodsIn this retrospective monocentric study, we included 56 patients with non-resectable Muc-M (n = 24) or Cut-M (n = 32) who underwent baseline 18F-FDG-PET/CT before treatment with ICIs between 2011 and 2017. Parameters were extracted from (i) tumoral tissues: SUVmax, SUVmean, TMTV (total metabolic tumor volume), and TLG (total lesion glycolysis) and (ii) lymphoid tissues: BLR (bone marrow-to-liver SUVmax ratio) and SLR (spleen-to-liver SUVmax ratio). Association with survival and response was evaluated using Cox prediction models, Student’s t tests, and Spearman’s correlation respectively. p < 0.05 was considered significant.ResultsMajority of ICIs were anti-PD1 (92.9%, n = 52/56). All 18F-FDG-PET/CT were positive. Overall (Muc-M to Cut-M), ORR was 33%:42%, DCR was 56%:69%, median follow-up was 25.0:28.9 months, median PFS was 4.7:10.7 months, and median OS was 23.9:28.3 months. In Muc-M, increased tumor SUVmax was associated with shorter OS while it was not correlated with PFS, ORR, or DCR. In Cut-M, increased TMTV and increased BLR were independently associated with shorter OS, shorter PFS, and lower response (ORR, DCR).ConclusionWhile all Muc-M and Cut-M were FDG avid, prognostic imaging biomarkers differed. For Muc-M patients treated with ICI, the only prognostic imaging biomarker was a high baseline maximal glycolytic activity (SUVmax), whereas for Cut-M patients, baseline metabolic tumor burden or bone marrow metabolism was negatively correlated to ICI response duration.

PurposeWe evaluated whether biomarkers on baseline [18F]-FDG PET/CT are associated with recurrence after surgery in patients with invasive breast cancer of no special type (NST).MethodsIn this retrospective single-center study, we included consecutive patients with non-metastatic breast cancer of NST who underwent [18F]-FDG PET/CT before treatment, including surgery, between 2011 and 2016. Clinicopathological data were collected. Tumor SUVmax, total metabolic tumor volume (TMTV), and spleen- and bone marrow-to-liver SUVmax ratios (SLR, BLR) were measured from the PET images. Cut-off values were determined using predictiveness curves to predict 5-year recurrence-free survival (5y-RFS). A multivariable prediction model was developed using Cox regression. The association with stromal tumor-infiltrating lymphocytes (TILs) levels (low if <50%) was studied by logistic regression.ResultsThree hundred and three women were eligible, including 93 (31%) with triple-negative breast carcinoma. After a median follow-up of 6.2 years, 56 and 35 patients experienced recurrence and death, respectively. The 5y-RFS rate was 86%. In multivariable analyses, high TMTV (>20 cm3) and high SLR (>0.76) were associated with shorter 5y-RFS (HR 2.4, 95%CI 1.3–4.5, and HR 1.9, 95%CI 1.0–3.6). In logistic regression, high SLR was the only independent factor associated with low stromal TILs (OR 2.8, 95%CI 1.4–5.7).ConclusionHigh total metabolic tumor volume and high spleen glucose metabolism on baseline [18F]-FDG PET/CT were associated with poor 5y-RFS after surgical resection in patients with breast cancer of NST. Spleen metabolism was inversely correlated with stromal TILs and might be a surrogate for an immunosuppressive tumor microenvironment.

PurposeTo determine if pretreatment [18F]FDG PET/CT could contribute to predicting complete pathological complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy with or without pembrolizumab.MethodsIn this retrospective bicentric study, we included TNBC patients who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy (NAC) or chemo-immunotherapy (NACI) between March 2017 and August 2022. Clinical, biological, and pathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from the PET images. Cut-off values were determined using ROC curves and a multivariable model was developed using logistic regression to predict pCR.ResultsN = 191 patients were included. pCR rates were 53 and 70% in patients treated with NAC (N = 91) and NACI (N = 100), respectively (p < 0.01). In univariable analysis, high Ki67, high tumor SUVmax (> 12.3), and low TMTV (≤ 3.0 cm3) were predictors of pCR in the NAC cohort while tumor staging classification (< T3), BRCA1/2 germline mutation, high tumor SUVmax (> 17.2), and low TMTV (≤ 7.3 cm3) correlated with pCR in the NACI cohort. In multivariable analysis, only high tumor SUVmax (NAC: OR 8.8, p < 0.01; NACI: OR 3.7, p = 0.02) and low TMTV (NAC: OR 6.6, p < 0.01; NACI: OR 3.5, p = 0.03) were independent factors for pCR in both cohorts, albeit at different thresholds.ConclusionHigh tumor metabolism (SUVmax) and low tumor burden (TMTV) could predict pCR after NAC regardless of the addition of pembrolizumab. Further studies are warranted to validate such findings and determine how these biomarkers could be used to guide neoadjuvant therapy in TNBC patients.

Although it has been well-documented that pain intensity alone is not sufficient to assess chronic pain, the objective pain surface encapsulated in a digital tool might present a major interest in the objective assessment of pain. This study aims to determine the potential added value of pain surface measurement by determining the correlation between pain surface and pain intensity in chronic pain patients. Two databases from observational prospective and retrospective longitudinal studies including patients with chronic pain were used in this research. Pain intensity was assessed by the Numeric Pain Rating Scale. Pain surface (cm²) and pain typology (neuropathic vs mechanical components) were measured by a specific pain mapping digital tool (PRISMap, Poitiers University Hospital). Patients were asked to draw their pain surface on a computerized tactile interface in a predetermined body (adapted from the patient's BMI). A color code was used to represent pain intensity (very intense, intense, moderate, and low). Simple linear regression was used to assess the proportion of variance in pain surface explained by pain intensity. The final analysis included 637 patients with chronic pain. The percentage of variance of the pain surface explained by pain intensity was 1.24% (R²=0.0124; 95% CI 0.11%-6.3%). In addition, 424 (66.6%) patients used more than 1 intensity or color, among whom 218 (34.2%) used 2 intensities or colors, 155 (24.3%) used 3 intensities or colors, and 51 (8%) used 4 intensities or colors. This study showed that pain intensity and pain surface provide complementary and distinct information that would help to improve pain assessment. Two-thirds of the cohort used 2 or more intensities to describe their pain. Combining pain intensity and pain surface should be strongly considered as a means of improving daily practice assessment of patients with chronic pain in primary and secondary care. ClinicalTrials.gov NCT02964130; https://clinicaltrials.gov/study/NCT02964130?term=PREDIBACK&rank=2.

Environmental challenges are rarely confined to national, disciplinary, or linguistic domains. Convergent solutions require international collaboration and equitable access to new technologies and practices. The ability of international, multidisciplinary and multilingual research teams to work effectively can be challenging. A major impediment to innovation in diverse teams often stems from different understandings of the terminology used. These can vary greatly according to the cultural and disciplinary backgrounds of the team members. In this paper we take an empirical approach to examine sources of terminological confusion and their effect in a technically innovative, multidisciplinary, multinational, and multilingual research project, adhering to Open Science principles. We use guided reflection of participant experience in two contrasting teams—one applying Deep Learning (Artificial Intelligence) techniques, the other developing guidance for Open Science practices—to identify and classify the terminological obstacles encountered and reflect on their impact. Several types of terminological incongruities were identified, including fuzziness in language, disciplinary differences and multiple terms for a single meaning. A novel or technical term did not always exist in all domains, or if known, was not fully understood or adopted. Practical matters of international data collection and comparison included an unanticipated need to incorporate different types of data labels from country to country, authority to authority. Sometimes these incongruities could be solved quickly, sometimes they stopped the workflow. Active collaboration and mutual trust across the team enhanced workflows, as incompatibilities were resolved more speedily than otherwise. Based on the research experience described in this paper, we make six recommendations accompanied by suggestions for their implementation to improve the success of similar multinational, multilingual and multidisciplinary projects. These recommendations are conceptual drawing on a singular experience and remain to be sources for discussion and testing by others embarking on their research journey.