The interplay of future solar energy, land cover change, and their projected impacts on natural lands and croplands in the US.

Projections for deep decarbonization require large amounts of solar energy, which may compete with other land uses such as agriculture, urbanization, and conservation of natural lands. Existing capacity expansion models do not integrate land use land cover change (LULC) dynamics into projections. We explored the interaction between projected LULC, solar photovoltaic (PV) deployment, and solar impacts on natural lands and croplands by integrating projections of LULC with a model that can project future deployment of solar PV with high spatial resolution for the conterminous United States. We used scenarios of LULC projections from the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios from 2010 to 2050 and two electricity grid scenarios to model future PV deployment and compared those results against a baseline that held 2010 land cover constant through 2050. Though solar PV's overall technical potential was minimally impacted by LULC scenarios, deployed PV varied by -16.5 to 11.6 % in 2050 from the baseline scenario. Total land requirements for projected PV were similar to other studies, but measures of PV impacts on natural systems depended on the underlying land change dynamics occurring in a scenario. The solar PV deployed through 2050 resulted in 1.1 %-2.4 % of croplands and 0.3 %-0.7 % of natural lands being converted to PV. However, the deepest understanding of PV impacts and interactions with land cover emerged when the complete net gains and losses from all land cover change dynamics, including PV, were integrated. For example, one of the four LULC projections allows for high solar development and a net gain in natural lands, even though PV drives a larger percentage of natural land conversion. This paper shows that integrating land cover change dynamics with energy expansion models generates new insights into trade offs between decarbonization, impacts of renewables, and ongoing land cover change.

Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT).

INTRODUCTION: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023. RESULTS: BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAFV600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team.

Prediction of Adjuvant Gemcitabine Sensitivity in Resectable Pancreatic Adenocarcinoma Using the GemPred RNA Signature: An Ancillary Study of the PRODIGE-24/CCTG PA6 Clinical Trial.

PURPOSE: GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population. PATIENTS AND METHODS: Routine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level. RESULTS: Eighty-nine patients' tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred- patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P < .001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P < .001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS (P = .008) and CSS (P = .004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P = .001). CONCLUSION: This ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events.

Unexpected Differences in the Speed of Non-Malignant versus Malignant Cell Migration Reveal Differential Basal Intracellular ATP Levels.

Cellular locomotion is required for survival, fertility, proper embryonic development, regeneration, and wound healing. Cell migration is a major component of metastasis, which accounts for two-thirds of all solid tumor deaths. While many studies have demonstrated increased energy requirements, metabolic rates, and migration of cancer cells compared with normal cells, few have systematically compared normal and cancer cell migration as well as energy requirements side by side. Thus, we investigated how non-malignant and malignant cells migrate, utilizing several cell lines from the breast and lung. Initial screening was performed in an unbiased high-throughput manner for the ability to migrate/invade on collagen and/or Matrigel. We unexpectedly observed that all the non-malignant lung cells moved significantly faster than cells derived from lung tumors regardless of the growth media used. Given the paradigm-shifting nature of our discovery, we pursued the mechanisms that could be responsible. Neither mass, cell doubling, nor volume accounted for the individual speed and track length of the normal cells. Non-malignant cells had higher levels of intracellular ATP at premigratory-wound induction stages. Meanwhile, cancer cells also increased intracellular ATP at premigratory-wound induction, but not to the levels of the normal cells, indicating the possibility for further therapeutic investigation.

Exploring the evidence of Middle Amazonian aquifer sedimentary outburst residues in a Martian chaotic terrain.

The quest for past Martian life hinges on locating surface formations linked to ancient habitability. While Mars' surface is considered to have become cryogenic ~3.7 Ga, stable subsurface aquifers persisted long after this transition. Their extensive collapse triggered megafloods ~3.4 Ga, and the resulting outflow channel excavation generated voluminous sediment eroded from the highlands. These materials are considered to have extensively covered the northern lowlands. Here, we show evidence that a lacustrine sedimentary residue within Hydraotes Chaos formed due to regional aquifer upwelling and ponding into an interior basin. Unlike the northern lowland counterparts, its sedimentary makeup likely consists of aquifer-expelled materials, offering a potential window into the nature of Mars' subsurface habitability. Furthermore, the lake's residue's estimated age is ~1.1 Ga (~3.2 Ga post-peak aquifer drainage during the Late Hesperian), enhancing the prospects for organic matter preservation. This deposit's inferred fine-grained composition, coupled with the presence of coexisting mud volcanoes and diapirs, suggest that its source aquifer existed within abundant subsurface mudstones, water ice, and evaporites, forming part of the region's extremely ancient (~ 4 Ga) highland stratigraphy. Our numerical models suggest that magmatically induced phase segregation within these materials generated enormous water-filled chambers. The meltwater, originating from varying thermally affected mudstone depths, could have potentially harbored diverse biosignatures, which could have become concentrated within the lake's sedimentary residue. Thus, we propose that Hydraotes Chaos merits priority consideration in future missions aiming to detect Martian biosignatures.

Atezolizumab plus bevacizumab in advanced hepatocellular carcinoma after treatment failure with multikinase inhibitors.

BACKGROUND AND AIMS: Data on the effectiveness of atezolizumab plus bevacizumab (atezo-bev) after failure of multikinase inhibitor (MKI) therapy in patients with advanced hepatocellular carcinoma are scarce. METHODS: This retrospective multicentre study included all consecutive patients treated with atezo-bev after failing one or more MKI treatments in the setting of an early access program. The primary endpoint was the objective response rate (ORR) by investigator assessment (using Response Evaluation Criteria in Solid Tumors v1.1). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan‒Meier method. RESULTS: Fifty patients were included in this analysis. Atezo-bev was started between April 2020 and November 2021 (median follow-up, 18.21 months). The investigator-assessed ORR was 14% (95% CI 5.37-22.63%), with 7 patients displaying a tumour response, and the disease control rate was 56% (95% CI 51.21-60.8%). After starting atezo-bev, the median OS was 17.1 months (95% CI 10.58-22.01), and the median PFS was 7.99 months (95% CI 4.78-10.50). Treatment-related adverse events led to treatment discontinuation in 7 patients. CONCLUSIONS: Atezo-bev every three weeks showed clinical benefit for a proportion of patients previously treated with one or multiple lines of MKIs.

Evidence of an oceanic impact and megatsunami sedimentation in Chryse Planitia, Mars.

In 1976, NASA's Viking 1 Lander (V1L) was the first spacecraft to operate successfully on the Martian surface. The V1L landed near the terminus of an enormous catastrophic flood channel, Maja Valles. However, instead of the expected megaflood record, its cameras imaged a boulder-strewn surface of elusive origin. We identified a 110-km-diameter impact crater (Pohl) ~ 900 km northeast of the landing site, stratigraphically positioned (a) above catastrophic flood-eroded surfaces formed ~ 3.4 Ga during a period of northern plains oceanic inundation and (b) below the younger of two previously hypothesized megatsunami deposits. These stratigraphic relationships suggest that a marine impact likely formed the crater. Our simulated impact-generated megatsunami run-ups closely match the mapped older megatsunami deposit's margins and predict fronts reaching the V1L site. The site's location along a highland-facing lobe aligned to erosional grooves supports a megatsunami origin. Our mapping also shows that Pohl's knobby rim regionally represents a broader history of megatsunami modification involving circum-oceanic glaciation and sedimentary extrusions extending beyond the recorded megatsunami emplacement in Chryse Planitia. Our findings allow that rocks and soil salts at the landing site are of marine origin, inviting the scientific reconsideration of information gathered from the first in-situ measurements on Mars.

Feasibility and acceptability of incorporating social network visualizations into a culturally centered motivational network intervention to prevent substance use among urban Native American emerging adults: a qualitative study.

BACKGROUND: Coupling social network visualizations with Motivational Interviewing in substance use interventions has been shown to be acceptable and feasible in several pilot tests, and has been associated with changes in participants' substance use and social networks. The objective of this study was to assess acceptability and feasibility of an adaptation of this behavior change approach into a culturally centered behavior change intervention for American Indian/Alaska Native (AI/AN) emerging adults living in urban areas. AI/AN populations experience high rates of health disparities and substance use. Although 70% of AI/AN people live outside of tribal lands, there are few culturally tailored health interventions for these AI/AN populations. Social networks can both increase and discourage substance use. Leveraging healthy social networks and increasing protective factors among urban AI/AN emerging adults may help increase resilience. METHODS: We conducted thirteen focus groups with 91 male and female participants (32 urban AI/AN emerging adults ages 18-25, 26 parents, and 33 providers) and one pilot test of the three workshop sessions with 15 AI/AN emerging adults. Focus group participants provided feedback on a proposed workshop-based intervention curriculum that combined group Motivational Interviewing (MI) and social network visualizations. Pilot workshop participants viewed their own social networks during group MI sessions focused on substance use and traditional practices and discussed their reactions to viewing and discussing their networks during these sessions. We used a combination of open coding of focus group and workshop session transcripts to identify themes across the group sessions and content analysis of comments entered into an online social network interview platform to assess the extent that participants had an intuitive understanding of the information conveyed through network diagrams. RESULTS: Focus group and pilot test participants reacted positively to the intervention content and approach and provided constructive feedback on components that should be changed. Themes that emerged included feasibility, acceptability, relevance, understandability, and usefulness of viewing personal network visualizations and discussing social networks during group MI workshops. Workshop participants demonstrated an intuitive understanding of network concepts (network composition and structure) when viewing their diagrams for the first time. CONCLUSIONS: Social network visualizations are a promising tool for increasing awareness of social challenges and sources of resilience for urban AI/AN emerging adults. Coupled with Motivational Interviewing in a group context, social network visualizations may enhance discussions of network influences on substance use and engagement in traditional practices. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04617938. Registered October 26, 2020.

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial.

Importance: Early results at 3 years from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial showed survival benefits with adjuvant treatment with modified FOLFIRINOX vs gemcitabine in patients with resected pancreatic ductal adenocarcinoma; mature data are now available. Objective: To report 5-year outcomes and explore prognostic factors for overall survival. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial was conducted at 77 hospitals in France and Canada and included patients aged 18 to 79 years with histologically confirmed pancreatic ductal adenocarcinoma who had undergone complete macroscopic (R0/R1) resection within 3 to 12 weeks before randomization. Patients were included from April 16, 2012, through October 3, 2016. The cutoff date for this analysis was June 28, 2021. Interventions: A total of 493 patients were randomized (1:1) to receive treatment with modified FOLFIRINOX (oxaliplatin, 85 mg/m2 of body surface area; irinotecan, 150-180 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 2400 mg/m2, every 2 weeks) or gemcitabine (1000 mg/m2, days 1, 8, and 15, every 4 weeks) as adjuvant therapy for 24 weeks. Main Outcomes and Measures: Primary end point was disease-free survival. Secondary end points included overall survival, metastasis-free survival, and cancer-specific survival. Prognostic factors for overall survival were determined. Results: Of the 493 patients, 216 (43.8%) were women, and the mean (SD) age was 62.0 (8.9) years. At a median of 69.7 months' follow-up, 367 disease-free survival events were observed. In patients receiving chemotherapy with modified FOLFIRINOX vs gemcitabine, median disease-free survival was 21.4 months (95% CI, 17.5-26.7) vs 12.8 months (95% CI, 11.6-15.2) (hazard ratio [HR], 0.66; 95% CI, 0.54-0.82; P < .001) and 5-year disease-free survival was 26.1% vs 19.0%; median overall survival was 53.5 months (95% CI, 43.5-58.4) vs 35.5 months (95% CI, 30.1-40.3) (HR, 0.68; 95% CI, 0.54-0.85; P = .001), and 5-year overall survival was 43.2% vs 31.4%; median metastasis-free survival was 29.4 months (95% CI, 21.4-40.1) vs 17.7 months (95% CI, 14.0-21.2) (HR, 0.64; 95% CI, 0.52-0.80; P < .001); and median cancer-specific survival was 54.7 months (95% CI, 45.8-68.4) vs 36.3 months (95% CI, 30.5-43.9) (HR, 0.65; 95% CI, 0.51-0.82; P < .001). Multivariable analysis identified modified FOLFIRINOX, age, tumor grade, tumor staging, and larger-volume center as significant favorable prognostic factors for overall survival. Shorter relapse delay was an adverse prognostic factor. Conclusions and Relevance: The final 5-year results from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial indicate that adjuvant treatment with modified FOLFIRINOX yields significantly longer survival than gemcitabine in patients with resected pancreatic ductal adenocarcinoma. Trial Registration: EudraCT: 2011-002026-52; ClinicalTrials.gov Identifier: NCT01526135.

Triggering Receptors Expressed on Myeloid Cells 1 : Our New Partner in Human Oncology?

Inflammation is recognized as one of the hallmarks of cancer. Indeed, strong evidence indicates that chronic inflammation plays a major role in oncogenesis, promoting genome instability, epigenetic alterations, proliferation and dissemination of cancer cells. Mononuclear phagocytes (MPs) have been identified as key contributors of the inflammatory infiltrate in several solid human neoplasia, promoting angiogenesis and cancer progression. One of the most described amplifiers of MPs pro-inflammatory innate immune response is the triggering receptors expressed on myeloid cells 1 (TREM-1). Growing evidence suggests TREM-1 involvement in oncogenesis through cancer related inflammation and the surrounding tumor microenvironment. In human oncology, high levels of TREM-1 and/or its soluble form have been associated with poorer survival data in several solid malignancies, especially in hepatocellular carcinoma and lung cancer. TREM-1 should be considered as a potential biomarker in human oncology and could be used as a new therapeutic target of interest in human oncology (TREM-1 inhibitors, TREM-1 agonists). More clinical studies are urgently needed to confirm TREM-1 (and TREM family) roles in the prognosis and the treatment of human solid cancers.

Impact of G-CSF Prophylaxis on Chemotherapy Dose-Intensity, Link Between Dose-Intensity and Survival in Patients with Metastatic Pancreatic Adenocarcinoma.

BACKGROUND: In metastatic pancreatic adenocarcinoma, few data are available on the use of granulocyte-colony stimulating factor (G-CSF) prophylaxis and its impact on dose-intensity (DI), or the link between DI and progression-free survival (PFS). This study assessed the impact of G-CSF prophylaxis on the DI received by patients and the relationship between full DI and PFS according to chemotherapy regimens. PATIENTS AND METHODS: Patients from three first-line randomized phase II clinical trials were included in this retrospective cohort. G-CSF prophylaxis groups were identified and balanced according to baseline characteristics using a propensity score. Patients were classified into 2 treatment groups (FOLFIRINOX vs FOLFIRI/nab-paclitaxel (NAB)). DI was a binary variable (full/reduced). Adverse events were defined using NCI-CTCAE v4.0. RESULTS: Of the 498 patients, 154 (31%) were in "prophylaxis" group; 179 (36%) were treated by FOLFIRINOX and 319 (64%) by FOLFIRI/NAB. In FOLFIRINOX group, G-CSF prophylaxis was significantly associated with a higher rate of full DI (OR, 5.07; 95% CI, 1.52-16.90; P < .01) while in FOLFIRI/NAB group, it was significantly associated with a lower rate of full DI (OR, 0.23; 95% CI, 0.06-0.83; P = .03). Full DI was associated with a non-significant increase in PFS (FOLFIRINOX group: HR 0.83; 95% CI, 0.59-1.16; P = .27; FOLFIRI/NAB group: HR 0.84; 95% CI, 0.63-1.11; P = .22). CONCLUSION: Granulocyte-colony stimulating factor prophylaxis was associated with a higher rate of full DI with FOLFIRINOX. Full DI was associated with a non-significant increase in PFS. These results need to be confirmed prospectively.

Impact of the COVID-19 pandemic on disease stage and treatment for patients with pancreatic adenocarcinoma: A French comprehensive multicentre ambispective observational cohort study (CAPANCOVID).

BACKGROUND: The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) - from diagnosis to treatment - of the reorganisation of the health care system during the first lockdown. METHODS: This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1, 2019 and October 31, 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 to May 11, 2020) and after lockdown. RESULTS: During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p = 0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p = 0.97). The number of borderline tumours increased (13.6%-21.7%), whereas the rate of metastatic diseases rate dropped (47.1%-40.3%) (p = 0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7%-32.6%) compared with upfront surgery (13%-7.8%) (p = 0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9%-69%; p = 0.044). After lockdown, the number of borderline tumours decreased (21.7%-9.6%) and advanced diseases increased (59.7%-69.8%) (p = 0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%). CONCLUSION: This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up. TRIAL REGISTRATION: Clinicaltrials.gov NCT04406571.

The Immune Landscape of Human Pancreatic Ductal Carcinoma: Key Players, Clinical Implications, and Challenges.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancer worldwide with an overall survival rate, all stages combined, of still <10% at 5 years. The poor prognosis is attributed to challenges in early detection, a low opportunity for radical resection, limited response to chemotherapy, radiotherapy, and resistance to immune therapy. Moreover, pancreatic tumoral cells are surrounded by an abundant desmoplastic stroma, which is responsible for creating a mechanical barrier, preventing appropriate vascularization and leading to poor immune cell infiltration. Accumulated evidence suggests that PDAC is impaired with multiple "immune defects", including a lack of high-quality effector cells (CD4, CD8 T cells, dendritic cells), barriers to effector cell infiltration due to that desmoplastic reaction, and a dominance of immune cells such as regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages, resulting in an immunosuppressive tumor microenvironment (TME). Although recent studies have brought new insights into PDAC immune TME, its understanding remains not fully elucidated. Further studies are required for a better understanding of human PDAC immune TME, which might help to develop potent new therapeutic strategies by correcting these immune defects with the hope to unlock the resistance to (immune) therapy. In this review, we describe the main effector immune cells and immunosuppressive actors involved in human PDAC TME, as well as their implications as potential biomarkers and therapeutic targets.

2-Hydroxyglutarate destabilizes chromatin regulatory landscape and lineage fidelity to promote cellular heterogeneity.

The epigenome delineates lineage-specific transcriptional programs and restricts cell plasticity to prevent non-physiological cell fate transitions. Although cell diversification fosters tumor evolution and therapy resistance, upstream mechanisms that regulate the stability and plasticity of the cancer epigenome remain elusive. Here we show that 2-hydroxyglutarate (2HG) not only suppresses DNA repair but also mediates the high-plasticity chromatin landscape. A combination of single-cell epigenomics and multi-omics approaches demonstrates that 2HG disarranges otherwise well-preserved stable nucleosome positioning and promotes cell-to-cell variability. 2HG induces loss of motif accessibility to the luminal-defining transcriptional factors FOXA1, FOXP1, and GATA3 and a shift from luminal to basal-like gene expression. Breast tumors with high 2HG exhibit enhanced heterogeneity with undifferentiated epigenomic signatures linked to adverse prognosis. Further, ascorbate-2-phosphate (A2P) eradicates heterogeneity and impairs growth of high 2HG-producing breast cancer cells. These findings suggest 2HG as a key determinant of cancer plasticity and provide a rational strategy to counteract tumor cell evolution.

Testing for SARS-CoV-2 in Symptomatic Vaccinated and Unvaccinated Health Care Workers During the Delta Variant Surge.

BACKGROUND: Infection with SARS- CoV- 2 in health care workers (HCWs) challenges employee health services. METHODS: We analyzed telephone Coronavirus Disease 2019 (COVID-19) hotline data over 8 weeks in 2021 during SARS- CoV- 2 Delta variant surge. We calculated COVID-19 case rates among persons-under-investigation (PUIs) for illness at two health care centers (HCs). RESULTS: There were 41 COVID-19 cases among the 285 PUIs (14.4%) at the study HC and 549 (16.9%) of 3244 at the comparison HC. At the study HC, 11.7% of vaccinated PUIs versus 36.6% of unvaccinated PUIs were COVID-19 positive. The COVID-19 positivity rates among vaccinated and unvaccinated PUIs at the comparison HC were 16.1% and 33.3%, respectively. DISCUSSION: In the SARS-CoV-2 Delta variant surge, COVID-19 test positivity rates among unvaccinated symptomatic HCWs are dramatically elevated. Aggressive testing of HCW PUIs is particularly critical during periods of disease upsurge.

Gemcitabine/Nab-Paclitaxel versus FOLFIRINOX in Locally Advanced Pancreatic Cancer: A European Multicenter Study.

BACKGROUND: Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX (FFX) are two standard first-line therapies for metastatic pancreatic cancer (PC) but have rarely been compared, especially in patients with locally advanced PC (LAPC). METHODS: This is a retrospective European multicenter study including patients with LAPC treated with either GN or FFX as the first-line therapy between 2010 and 2019. Coprimary objectives were progression-free survival (PFS) and overall survival (OS), both estimated using the Kaplan-Meier method. RESULTS: A total of 147 patients (GN: n = 60; FFX: n = 87) were included. Tumor resection rates were similar between the two groups (16.7% vs. 16.1%; p = 1), with similar R0 resection rates (88.9%). Median PFS rates were not statistically different: 9 months (95% CI: 8-13.5) vs. 12.1 months (95% CI: 10.1-14.6; p = 0.8), respectively. Median OS rates were 15.7 months (95% CI: 12.6-20.2) and 16.7 months (95% CI: 14.8-20.4; p = 0.7), respectively. Abdominal pain at the baseline (HR = 2.03, p = 0.03), tumors located in the tail of the pancreas (HR = 4.35, p = 0.01), CA19-9 > 200 UI/L (HR = 2.03, p = 0.004) and tumor resection (HR = 0.37, p = 0.007) were independent prognostic factors for PFS, similarly to OS. CA19-9 ≤ 200 UI/L (OR = 2.6, p = 0.047) was predictive of the tumor response. Consolidation chemoradiotherapy, more often used in the FFX group (11.7% vs. 50.6%; p < 0.001), was not predictive. CONCLUSION: This retrospective study did not show any difference between GN and FFX as the first-line treatment in patients with LAPC.

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.

Hepatitis B reactivation and immune check point inhibitors.

BACKGROUND: Liver toxicity during immune checkpoint inhibitor treatment is mostly due to immune mediated hepatitis. Viral hepatitis, as well as auto-immune or metabolic hepatitis, are considered as exclusion criteria for ICI induced immune hepatitis diagnosis. However, considering the high prevalence of viral hepatitis B infection and the increasing prescription of immune checkpoint inhibitors, their use in patients with HBV chronic viral infection may be common, even more if patients are treated for hepatocellular carcinoma. Few clinical studies directly deal with the risk of HBV reactivation during ICI therapy and real-life data is currently based on five reported cases of HBV reactivation, one with fatal outcome. In this review, we summarize the current available clinical information about HBV reactivation risk during ICI treatment, its hypothetic mechanism, and propose practical recommendations about verifying and monitoring HBV status throughout the treatment.