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Background: Over recent years, immune checkpoint inhibitors (ICIs) have changed the clinical management and prognosis for most cancers. However, data on older patients in clinical trials are scarce. Objective: We performed a systematic review and pooled analysis of real-life studies to explore the efficacy and toxicity of ICIs in unselected older individuals in multiple tumor settings treated outside of clinical trials. Patients and Methods: We searched articles, including prospective cohort studies, observational or retrospective series, or expanded access programs, published in English from 2010 to October 2020 in PubMed, MEDLINE, the Cochrane Library, and EMBASE. We excluded hematological malignancies. Results: Forty-eight studies met the predefined criteria and were eligible for inclusion in the systematic review. We included 5524 patients. The pooled median overall survival was 8.9 (95% CI 7.3–10.5) and 14.3 (95% CI 11.3–17) months for non-small cell lung cancer (NSCLC: n = 17 studies; 95% in pretreated setting) and melanoma, respectively (n = 3). Median progression-free survival was 3.2 (95% CI 2.7–3.8) and 7.9 (95% CI 6.05–9.78) months for NSCLC and melanoma cohorts. Pooled rates of Grade 1–5 hepatitis, pneumonitis, hypothyroidism, and diarrhea were 5.3% (95% CI 3.7–7.6), 6% (95% CI 3.8–9.4), 8.3% (95% CI 5.4–12.5) and 7.6% (95% CI 5.7–10), respectively. Conclusions: Our findings suggest that ICIs could be safely administered in older individuals with comparable survival outcomes with respect to younger individuals. Future studies should include some form of geriatric assessment to improve patient stratification. [ABSTRACT FROM AUTHOR]

In this article, we problematize the implementation of smart urban experiments in the resource-rich, Arctic periphery. Our case study is the so-called Norrbotten Technological Megasystem in Sweden, with a specific focus on the mining towns of Malmberget/Gällivare and Kiruna. Kiruna in particular is a well know case study as its urban centre is being relocated due to subsidence caused by underground mining. The new town centre is being developed as a testbed for smart urbanism. We argue that if we look at the nexus between resource extraction and urbanization in Kiruna and Malmberget, we find smart city thinking more aligned to the bottom line of the resource extraction industry rather than being an innovative project to make economic development compatible with broader climate and societal challenges. Methodologically, we use historic analysis and assemblage thinking to look at the territorialization and de-territorialization of resource-extraction in Norrbotten over the last 100 years. [ABSTRACT FROM AUTHOR]

Rockfall protection net fences are key protection systems in mountainous areas worldwide to ensure the safety of infrastructures, roads and urban areas. Maintenance of these products is fundamental for public administrations in order to guarantee risk mitigation. This paper deals with the assessment of the installation problems and damages induced by ageing of rockfall protection net fences, using numerical modelling in order to evaluate the influence of these issues on their behavior. A percentage of the residual efficiency is assessed as a useful tool for risk analysis and maintenance planning. [ABSTRACT FROM AUTHOR]

This paper reports the results of three innovative laboratory tests implemented during winter 2013 in the framework of the Climate for Culture European Project (2009–2014). Thermal analysis was used to assess the heating efficiency of some heaters with different power consumption, geometric shape and dimensions. Experimental laboratory results were obtained under natural indoor environmental conditions and the outcomes were applied to a real case study of two churches on the Italian Alps during the Friendly Heating project. Results provide useful information to help final users and/or conservators to exploit at the best the heating efficiency of some heaters on the basis of the geometric characteristics of the elements and represent helpful advices for their installation, considering both the optimal position for the maximum comfort performance and the need for not exceeding specific risk thresholds for artwork preservation. [ABSTRACT FROM AUTHOR]

• Vitamin D modulates the systemic inflammatory response through interaction with immune system. • We systematically reviewed studies about vitamin D3 and risk and mortality for COVID-19 infection. • Reduced vitamin D values resulted in a higher infection risk, mortality and severity COVID-19 infection. Vitamin D modulates the systemic inflammatory response through interaction with immune system. As such, it has a possible protective role against the risk of respiratory tract infections and other diseases. It may be useful in particular, during COVID-19 pandemic. PubMed, the Cochrane Library, and EMBASE were searched from inception until January 31, 2021, for observational or clinical studies reporting the prognosis (and therapeutic effect) of COVID-19 infection in patients with deficient vitamin D levels. The infection rate, severity, and death from COVID-19 infection were pooled to provide an odds ratio with a 95 % confidence interval (OR 95 % CI). An OR > 1 was associated with the worst outcome in deficient compared with nondeficient patients. We assessed the association between vitamin D and risk, severity, and mortality for COVID-19 infection, through a review of 43 observational studies. Among subjects with deficient vitamin D values, risk of COVID-19 infection was higher compared to those with replete values (OR = 1.26; 95 % CI, 1.19–1.34; P <.01). Vitamin D deficiency was also associated with worse severity and higher mortality than in nondeficient patients (OR = 2.6; 95 % CI, 1.84–3.67; P <.01 and OR = 1.22; 95 % CI, 1.04–1.43; P <.01, respectively). Reduced vitamin D values resulted in a higher infection risk, mortality and severity COVID-19 infection. Supplementation may be considered as preventive and therapeutic measure. [ABSTRACT FROM AUTHOR]

• Plasticizer loss is the main phenomenon affecting the durability of PVC membranes. • A device for accelerated ageing tests on PVC membranes has been developed. • Mechanical tests are performed to study the time-dependent properties of membranes. • Plasticizer loss with time has been modelled from plasticizer absorption tests data. • The end-of-life time of the two commercial PVC membranes is evaluated. Waterproofing heavily influences the operation and maintenance costs of underground structures. Currently, the most commonly used technology for tunnel waterproofing is plasticized polyvinyl chloride (PVC-P) geomembranes. However, not much is known about the long-term durability of these geomembranes, especially in relation to the long expected lifespan of new tunnels (i.e. 100–150 years). Therefore, in this paper, the durability of two commercially available PVC-P geomembranes is studied with the help of a specifically designed accelerated ageing device in addition to mechanical and absorption tests. The degradation resulting from plasticizer loss is extrapolated to the long term, and a threshold value for the end-of-life of the PVC-P geomembrane is estimated from the mechanical tests. [ABSTRACT FROM AUTHOR]

• EPB conditioning is critical in high-cobble content soils. • Cobble segregation in bulk chamber may lead to major problems. • Slump test is suitable for soils with maximum particle diameter of 40 mm. • The interaction between the conditioned matrix and cobbles is important. • Tilt Slidind Test evaluates the interaxtion of cobbles with the matrix. Many cities are built on alluvial soils and the excavation for services and tunnels become more important as the surface becomes more congested. Today EPB shields excavation is the leading technology for tunnel excavation in urban context due to the limited space on the surface, the noise, vibration and safety requirements. In cases with high cobbles content optimization of the conditioning is necessary in order to allow a homogeneous flow of cobbles in the pressure chamber and along the screw conveyor. This should be assessed through a test that evaluates the reduction of the gravitational separation of the larger elements in the chamber and the risks of face instability, tool breakage and water inflow through the screw conveyor. This paper presents a new test to evaluate the homogeneity of flow of cobbles in the excavated mass. The development of the test is described along two test campaigns and the improvements achieved in the second campaign are explained. Two indexes are proposed to assess the suitability of conditioning. [ABSTRACT FROM AUTHOR]

Objective: The causative and prognostic roles of human papillomavirus (HPV) in non-oropharyngeal squamous cell carcinoma of the head and neck are uncertain. This umbrella review assessed the strength and quality of evidence and graded the evidence derived from published meta-analyses on this subject. Data sources: MEDLINE, Embase, and the Cochrane Library were searched. Meta-analyses of observational studies and randomized trials were included. Review methods: Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: 15 meta-analyses were evaluated. The association with HPV was highly suggestive of oral (OR = 2.40, [1.87–3.07], P < 0.00001) and nasopharyngeal cancers (OR = 17.82 [11.20–28.35], P < 0.00001). Improved survival emerged only in hypopharyngeal carcinoma and was confirmed in studies in which only p16 + cancers were considered. Conclusion: HPV infection may increase the risk of oral cavity and nasopharyngeal cancer. However, the prognosis was not influenced, except in hypopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or without chemotherapy (CT), being acceptable in intermediate and locally advanced diseases, there is uncertainty regarding the best treatment option for these patients. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different treatments for HPV+ oropharyngeal carcinoma. Material and methods: Randomized clinical trials that enrolled adults with non-metastatic HPV+ oropharynx cancer and provided data about overall survival (OS) and/or progression-free survival (PFS) and/or locoregional control and distant metastases (LRC and DM) were included. Fixed- or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (CrIs). The primary outcome was OS. Results: A total of 844 citations were screened; 11 randomized clinical trials were included (HPV+ stage III–IV cancer, mainly oropharynx carcinomas). Nine treatment arms were compared. Radiotherapy (altered or standard fractionation) + triweekly cisplatin (HR 3.8; 95% CrIs 0.29–65 and 0.3; 95% CrIs 0.03–2.51) was superior to RT in term of OS (P score = 0.42 and 0.16). Radiotherapy with low and high cisplatin doses appeared similar (HR 1.57; 95% CrIs 0.19–12.72). Altered fractionation or standard RT + 3-weekly cisplatin are the 2 highest-ranked options in terms of PFS (P score = 0.35 and 0.34). Conclusions: This meta-analysis confirms the role of cisplatin added to RT as the best option for HPV+ oropharyngeal carcinoma. RT+ 3-weekly cisplatin is likely to be the best radical treatment in terms of OS and PFS. [ABSTRACT FROM AUTHOR]

Simple Summary: The coronavirus disease (COVID-19) pandemic has increased morbidity and mortality in the general population. Patients with cancer have immune dysfunction due to the use of immunosuppressive agents, poor nutritional status, or the direct effects of the tumor on the reactivity of the immune system, making oncological patients more susceptible to severe disease and death. In this systematic review and meta-analysis, we evaluated whether lung cancer increases the risk of severe COVID-19 and the risk of dying from the disease. We found that mortality in patients with lung cancer was significantly higher than that in control patients (HR = 2.00 [95%CI 1.52, 2.63], p < 0.01) or with other malignancies (HR = 1.91 [95%CI 1.53, 2.39], p < 0.01). In addition, we also observed a higher risk of severe infection in patients with lung cancer (HR = 1.47 [95%CI 1.06, 2.03], p = 0.02). We suggest that, in this setting, vaccine use may be considered a useful and mandatory measure to save lives. Introduction: The outbreak of COVID-19 poses an unprecedented challenge to global public health. Patients with cancer are at a higher risk during the SARS-CoV-2 pandemic. Patients with lung cancer and COVID-19 were compared to those without cancer and those with other malignancies for the main outcome of this study. The aim of this study was to evaluate the differences in susceptibility, disease severity, and mortality between lung cancer patients and the general population. Methods: Using PRISMA reporting guidelines, we conducted a systematic review and meta-analysis of the published literature. The Cochrane Library database, PubMed, EMBASE, and PubMed Central were comprehensively searched for published papers until 31 May 2022. A pooled risk ratio (OR) with 95% CI was presented as the result of this meta-analysis. Results: We included 29 studies involved 21,257 patients with lung cancer and SARS-CoV-2 infection. Analysis data showed that mortality in patients with lung cancer was significantly higher than that in patients without cancer (HR = 2.00 [95%CI 1.52, 2.63], p < 0.01) or with other malignancies (HR = 1.91 [95%CI 1.53, 2.39], p < 0.01). In addition, we also observed a higher risk of severe infection in terms of life-threatening or required ICU admission/mechanical ventilation for lung cancer patients (HR = 1.47 [95%CI 1.06, 2.03], p = 0.02) than for patients with no cancer or other malignancies. Regarding lung cancer as a risk factor for acquiring SARS-CoV-2 infection, we could not reach statistical significance (hazard ratio [HR] =2.73 [95%CI 0.84, 8.94], p = 0.1). Conclusion: Lung cancer represents an important comorbidity and modifies COVID-19 prognosis in terms of disease severity and mortality. More patients experience severe or even fatal events. Considering their inherent fragility, patients with lung cancer, and generally all oncological populations, should be treated more carefully during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

In the last decade, immunotherapy with immune checkpoint inhibitors (ICIs) has changed the therapeutic algorithm of cancer patients. ICIs combined with other therapeutic options, such as chemo- and targeted therapies, generate impressive results in cancer patients. Locoregional treatments (LRTs) play an important role in the management of various solid tumors (e.g., hepatocellular carcinoma (HCC), neuroendocrine tumors, etc.), and this therapeutic approach may enhance the activity of the immune response to tumor cells destroying primary tumors and leading to the release of several soluble molecules. This systematic review was performed to identify studies reporting objective response rate (ORR) and survival information in patients with solid tumors treated with ICIs plus LRTs. In the present work, fourteen studies were included, and the majority of them (five studies) enrolled patients with hepatocellular carcinoma (HCC), whereas the others included patients with different diseases. The highest ORRs were seen in HCC (67%, Y-90 RE plus ipilimumab and nivolumab) and melanoma (38%, dendritic cells with mRNA p lus ipilimumab) patients. ORRs were not observed in liver metastases from melanoma and colorectal cancer. These data suggest that combination of ICIs and LRTs is feasible and more active in primary tumors (particularly HCC) than metastases with a synergistic effect on antitumor immunity. However, further studies are needed to better select patients, schedules, and setting of treatments. • Assessment to evaluate clinical trials that tested immuno- and locoregional therapies in cancer patients with solid tumors. • Preclinical studies have shown a synergistic effect between these two therapeutic options. • This analysis showed the highest objective response rate in hepatocarcinoma and melanoma. • Objective response rate was not observed in liver metastases from melanoma and colorectal cancer. [ABSTRACT FROM AUTHOR]

Introduction: Currently, the standard treatment for gastric and gastroesophageal junction (GEJ) adenocarcinoma, including distal esophagus, consists of perioperative chemotherapy (CT) according to FLOT schedule (5FU/leucovorin/oxaliplatin and docetaxel), or of concomitant chemoradiotherapy (CTRT) based on CROSS regimen. However, due to the relatively lack of direct comparisons between perioperative CT and neoadjuvant CTRT, the effectiveness of these new combinations is unknown. Therefore, we performed a network meta-analysis (NMA) to compare the efficacy of different neoadjuvant treatments for gastric and GEJ adenocarcinoma in terms of overall and disease-free survival (OS and DFS). Materials and methods: We searched MEDLINE, Embase, and Cochrane from database inception until February 1st 2022 for randomized clinical trials that enrolled adults with gastric and GEJ carcinomas and provided data about OS and/or DFS. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank (SUCRA) curve plots were produced. The primary outcome was OS, secondary endpoint DFS. Results: A total of 1247 citations were screened; 14 randomized clinical trials were included. In Bayesian comparisons, FLOT-based CT ranked as one of the better regimens with a probability of 41%, both with induction CT followed by CTRT (P = 0.45). For DFS analysis, the FLOT regimen was the preferred option (P = 0.62). Conclusions: In conclusion, this NMA adds further evidence to the optimization of treatment strategies for gastric and GEJ adenocarcinomas and confirms that incorporation of perioperative triplet-based CT improved both OS and DFS compared to surgery alone and other preoperative strategies. [ABSTRACT FROM AUTHOR]

Objectives: To prospectively assess prevalence/characteristics of clinically unsuspected pulmonary embolism (PE) in cancer patients undergoing follow-up chest MDCT and investigate MDCT protocol.Methods: We evaluated 1013 oncologic patients. MDCT images at 5 and 1.25 mm thickness were independently evaluated. Pulmonary artery opacification degree was assessed. Presence, level, and site of PE were reported. Type of malignancy and metastases were reported for PE-positive patients.Results: After excluding 1.4% (14/1013) of examinations due to inadequate vessel opacification, 999 patients (572 male; mean age:68 ± 12 years; range:26-93 years) entered the study. Prevalence of PE was 5%. There was significant improvement in the sensitivity for both readers in the evaluation of 1.25 mm compared to 5 mm images (46-50% to 82-92%). 30% (15/51) PE were not described by the radiologist in the prospectively issued report; 53 % (27/51) of PE were segmental, 72.5% (37/51) unilateral. The right lower lobe was the most involved (59%). 27% patients had colon cancer, 18% lung cancer. Among PE-positive patients (25 male; mean age 70 ± 10 years; range:44-87 years), 25% (13/51) had lung cancer, 15% (8/51) colon cancer.Conclusions: Thin reconstructions are essential for PE diagnosis, regardless of reader experience. Regarding oncologic patients, incidental PE diagnosis influences anticoagulation therapy.Key Points: • CT pulmonary angiography is the gold standard for PE diagnosis. • Cancer and oncological treatments are risk factors for PE. • The prevalence of unsuspected PE was 5%. • Thin reconstructions are essential for PE diagnosis regardless of reader experience. • In oncologic patients, PE diagnosis influences anticoagulation therapy. [ABSTRACT FROM AUTHOR]

Renewable energy infrastructures are becoming increasingly present in our environments, inevitably shaping the urban experiences of the everyday person as they move through the city. The profound impact these infrastructures have on social worlds has yet to be explored, with contemporary renewable energy discourse primarily focussing on the techno-economic. We argue for the everyday aestheticisation of renewable energy infrastructures, and how design thinking might offer a way forward in co-creating future meaningful experiences with renewable energy. We offer a collaborative design thinking workshop on the speculative experimentation of energy futures as a case study. The findings provide multi-scalar insights on exploring urban energy futures with citizen-designers – with aesthetics and lived experiences as central. • Everyday aesthetics in design thinking promotes the inclusion of citizen-designers. • Collaborative design thinking offers opportunities for creative serendipity. • Aesthetic emergence occurs through embeddedness within a local context. • Lived experiences influence the everyday aestheticisation of renewable energy. • Design thinking complements the governance and planning of renewable energy. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) is useful for staging non-small cell lung cancer (NSCLC), decide the appropriate initial management, and evaluate the response to therapy. Metastatic spreading is very common during the course of NSCLC and principal localization sites include: regional and mediastinal lymph nodes and organs such as the contralateral lung parenchyma, bone, brain, adrenal gland, pleura, and liver. Myocardial localizations are very rare, often asymptomatic, and difficult to diagnose. For this reason, only a few cases are reported in the literature. Here, we report a case of an asymptomatic patient affected by locally advanced NSCLC and high metabolic lesion of the interventricular septum. [ABSTRACT FROM AUTHOR]

Clinical observations have demonstrated that microsatellite instability-high (MSI-H) and/or deficient MMR (dMMR) status are associated with favorable prognosis and no benefit from 5-Fluorouracil (5-FU)-based adjuvant chemotherapy in patients with resected stage II colorectal cancer (CRC). This study represents a systematic review and meta-analysis exploring the predictive role of MSI-H status in stage III CRC undergoing or not adjuvant chemotherapy. Published articles that evaluated the role of adjuvant chemotherapy in resected stage III CRC from inception to September 2020 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. The random-effects model was conducted to estimate the pooled effect size of OS and DFS. The primary outcome of interest was OS. 21,590 patients with MSI-H/dMMR stage III CRC, from n = 17 retrospective studies, were analyzed. Overall, OS was improved with any adjuvant chemotherapy vs. any control arm (single-agent 5-FU or surgery alone): HR 0.42, 95% CI 0.26–0.66; P < 0.01. Conversely, DFS was not significantly improved (HR 0.7, 95% CI 0.45–1.09; P = 0.11). In patients with stage III MSI-H/dMMR CRC, adjuvant chemotherapy is associated with a significant OS improvement. Thus, MSI-H/dMMR status does represent a predictive factor for postoperative chemotherapy benefit in stage III CRC beyond its prognostic role. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is exceptionally responsive to chemotherapy and radiotherapy. In relapsed patients, particularly in resistant/refractory cases, the progression of disease occurs rapidly with second-line agents. Topotecan (TOPO), a camptothecin analog, is the only agent able to increase overall survival (OS) compared with the best supportive care alone. However, the efficacy of platinum-based chemotherapy rechallenge or other agents has not been systematically explored. In the present review, published articles, which evaluated outcome and toxicity associated with TOPO or non-TOPO-based chemotherapy in patients with SCLC from inception to September 2020 were systematically searched and identified by searching the PubMed, EMBASE and Cochrane Library databases. The primary outcome of interest was the risk of death (OS), and the secondary endpoints were risk of progression progression-free survival (PFS), overall response rate (ORR) and G3-4 hematological toxicities. A total of nine studies were included in quantitative synthesis for a total of 1,689 patients. They included platinum-based rechallenge, anthracycline-based combinations or camptothecin analogs. TOPO did not improve OS with respect to other therapies [hazard ratio (HR), 0.92; 95% confidence interval (95% CI), 0.78-1.09; P=0.33]. Similarly, PFS was similar in the two arms (HR, 1.1; 95% CI, 0.72-1.67; P=0.66). The ORR was not statistically higher with non-TOPO agents (relative risk, 1.53; 95% CI, 0.95-2.48). In subgroup analysis, combination chemotherapy was associated with an improved PFS but not OS or ORR compared with TOPO alone (HR, 1.85; 95% CI, 1.52-2.24; P<0.01). The rates of G3-4 anemia, febrile neutropenia and neutropenia were similar. In conclusion, in patients with relapsed SCLC, TOPO was associated with a similar survival, PFS and ORR as other agents. However, polychemotherapy was associated with improved PFS. [ABSTRACT FROM AUTHOR]

Objective: The human papillomavirus (HPV) is implicated in the pathogenesis of several cancers among humans. The role of HPV as one of the etiological agents in esophageal carcinogenesis is partially unknown. We assessed whether the available evidence supports the association of HPV with risk and prognosis in patients with esophageal squamous cell carcinomas (ESCCs). Design: For this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and SCOPUS were searched up to February 2021. The included studies were prospective or retrospective studies that evaluated the incidence, risk, and prognosis of HPV-16/18–related ESCCs in adult subjects. The primary outcome was the incidence rate of ESCC in HPV-16/18 carriers. Secondary outcomes included the risk of ESCCs compared with healthy HPV-16/18 carriers (expressed as odds ratios [ORs] with 95% confidence intervals [CIs]) and the survival of HPV + versus HPV- ESCCs. Results: The search identified 1649 unique citations, of which 145 met the inclusion criteria and were included in the pooled analysis (16,484 patients). The pooled HPV prevalence in ESCCs was 18.2% (95% CI 15.2–21.6%; P < 0.001). A significantly increased ESCC risk was associated with HPV infection (OR = 3.81; 95% CI 2.84–5.11; P < 0.001). Main limitation were methods of HPV detection (DNA only), race of populations included (mainly Asiatic countries) and lack of adjustment for other prognostic factors. Conclusions: The findings suggest that HPV-16/18 is detectable in about 1 on 5 cases of ESCC with different prevalences across the world. It is moderately but significantly associated with a diagnosis of ESCC. Further epidemiological studies are needed to confirm and increase the current knowledge of the subject. [ABSTRACT FROM AUTHOR]

Steroids are commonly used in patients with solid tumours for supportive therapy. In other cases, they are an essential part of cancer treatment such as prostate cancer. Some preclinical observations lead to the notion that glucocorticoids may modulate growth factors' pathways and may induce the progression of cancers. Glucocorticoids are associated with several side-effects on many organ systems (e.g. serious infections, diabetes, sepsis and thrombosis). We have performed a systematic review and meta-analysis to evaluate the outcome of cancer patients that assume or not steroids. Published articles that evaluated survival associated with steroids use in cancer patients from inception to June 2020 were identified by searching the PubMed, EMBASE and Cochrane Library databases. The primary outcome of interest was the risk of death, and the secondary end-point was the risk of progression in steroid versus non-steroid users. Seventy-six studies were in quantitative synthesis for a total of 83,614 patients. Use of steroids was associated with a reduced survival (hazard ratios (HR) = 1.18, 95% confidence interval (CI): 1.1–1.26; P <.01). Progression-free survival was also decreased in steroid versus non-steroid users (HR = 1.13, 95% CI: 1.01–1.26; P =.03). In patients with lung cancer, advanced disease and supportive care indications were settings where the use of steroids increased the risk of death. In patients with advanced cancers, use of steroids should be reduced and, at best, avoided because it may reduce survival, in particular, for patients with lung cancer and for palliative/supportive care purposes. • Steroids are commonly used in patients with solid tumors for supportive therapy. • We evaluated the outcome of cancer patients that assume or not steroids. • Use of steroids was associated with a reduced survival (HR = 1.18, 95%CI 1.1–1.26; P<.01). • Use of steroid should be reduced and at best avoided because it may reduce survival. [ABSTRACT FROM AUTHOR]

• European Cancer Organisation essential requirements for quality cancer care (ERQCC) are position papers on delivering high-quality care. • Each paper focuses on a cancer type, in this case lung cancer. • Lung cancer is a great societal burden and is challenging to treat. • High-quality care can only be a carried out in specialised units or centres. • The essential, multidisciplinary details for such centres are set out by the European Cancer Organisation expert group. European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give patients, health professionals, managers and policymakers a guide to essential care throughout the patient journey. Lung cancer is the leading cause of cancer mortality and has a wide variation in treatment and outcomes in Europe. It is a major healthcare burden and has complex diagnosis and treatment challenges. Care must only be carried out in lung cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals detailed here. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship. [ABSTRACT FROM AUTHOR]

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population. [ABSTRACT FROM AUTHOR]

The application of full‐face mechanized tunnelling, mainly with EPB shielded machines, has widely increased in the last years and today it can be considered the key technology when tunnelling in soils above and below the water table. The applicability range of EPB machines has widened thanks on one side to the technological and mechanical progresses and on the other side to the quality and effectiveness of the conditioning products. No recognized standards are available for laboratory testing of conditioned soil and each research centre has developed its own procedures and methods. In this paper, an overview of the most frequently used procedures is presented and discussed briefly. [ABSTRACT FROM AUTHOR]

• Adding cisplatin to single-agent chemotherapy does not prolong OS in elderly NSCLC. • This paper reports that cisplatin does not improve quality of life. • A significant worsening of some toxicity-related scales was found. To evaluate the effect on quality of life (QOL) of the addition of cisplatin to single-agent chemotherapy in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC) enrolled in two parallel phase 3 trials, MILES-3 and MILES-4. Advanced NSCLC pts, >70 years old, performance status (PS) 0–1, were eligible. Patients were randomly assigned to chemotherapy without or with cisplatin. EORTC QLQ C30 and LC13 questionnaires were planned at baseline, end of cycle 1 and end of cycle 2 in both trials and were used for joint QOL analysis. Trial-specific data including questionnaires at non-shared time-points were used for additional analyses. Intention-to-treat strategy was applied. Analyses were adjusted for baseline QOL, stage, performance status, gender, age, size of centre, trial, histotype and non-platinum companion drug. Overall, 458/531 pts (86%) answered baseline questionnaire and missing rates over treatment were slightly higher among patients receiving cisplatin. Mean change in sore mouth after cycle 2 was worse with cisplatin (P = 0.02). The size of differences between arms was in the small-medium range for peripheral neuropathy and alopecia (0.25 and 0.31 after one and 0.28 and 0.36 after two cycles, respectively) and for nausea/vomiting, sore mouth and dysphagia after two cycles (0.26, 0.38 and 0.25, respectively) always in the direction of worsening with cisplatin. Using a 10% change from baseline as clinically relevant threshold to categorize response, there was no significant difference between the arms. Time to deterioration of sore mouth and alopecia, with progression/death as competitive risk, was shorter with cisplatin (HR 1.72 95%CI 1.02–2.89, P = 0.04 and HR 1.84 95%CI 1.09–3.10, P = 0.02, respectively). The addition of cisplatin to single agent chemotherapy worsens sore mouth and alopecia and does not improve any QOL items in elderly patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: Frailty increases the risk of adverse health outcomes and/or dying when exposed to a stressor, and routine frailty assessment is recommended to guide treatment decision. The Balducci frailty criteria (BFC) and Fried frailty criteria (FFC) are commonly used, but these are time consuming. Vulnerable Elders Survey-13 (VES-13) score of ≥7, a simple and resource conserving function-based scoring system, may be used instead. This prospective study evaluates the performance of VES-13 in parallel with BFC and FFC, to identify frailty in elderly patients with early-stage cancer.Methods: Patients aged ≥70 years with early-stage solid tumors were classified as frail/nonfrail based on BFC (≥1 criteria), FFC (≥3 criteria), and VES-13 (score ≥ 7). All patients were assessed for functional decline and death.Results: We evaluated 185 patients. FFC had a 17% frailty rate, whereas BFC and VES-13 both had 25%, with poor concordance seen between the three geriatric tools. FFC (hazard ratio = 1.99, p = .003) and VES-13 (hazard ratio = 2.81, p < .001) strongly discriminated for functional decline, whereas BFC (hazard ratio = 3.29, p < .001) had the highest discriminatory rate for deaths. BFC and VES-13 remained prognostic for overall survival in multivariate analysis correcting for age, tumor type, stage, and systemic treatment.Conclusions: A VES-13 score of ≥7 is a valuable discriminating tool for predicting functional decline or death and can be used as a frailty-screening tool among older cancer patients in centers with limited resources to conduct a comprehensive geriatric assessment. [ABSTRACT FROM AUTHOR]

One of the historical standard of care for locally advanced rectal adenocarcinoma (LARC) is neoadjuvant fluoropyrimidine-based chemoradiotherapy (FP-based CTRT) followed 6–8 weeks later by surgery. The incorporation of further chemotherapy cycles (CT) before or after CTRT (total neoadjuvant therapy) resulted in better outcomes than CTRT alone. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different neoadjuvant treatments for LARC. Fixed-or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) or risk ratios (RRs) with 95 % credible intervals (95 % CrIs). A total of 23 randomized clinical trials were included. In Bayesian comparisons. FOLFIRINOX followed by capecitabine-based CTRT resulted in better OS than other regimens, including the previous standard, and ranked as the best regimen with a probability of 87 %. This NMA confirms that adopting total neoadjuvant therapy improves outcome compared to other preoperative strategies, including FP-based CTRT. [Display omitted] • This network meta-analysis found that induction FOLFIRINOX ranked as the best option in terms of overall survival for LARC. • Chemotherapy doublets following CTRT resulted as the best treatment both in terms of disease-free survival. • FOLFIRINOX followed by CTRT and (CT)RT + oxaliplatin-based CT resulted as the preferred options for LARC. • Incorporation of total neoadjuvant therapy into the LARC management is emerging as the new standard of care. [ABSTRACT FROM AUTHOR]

• This systematic review and meta-analysis of 103 studies comprising 948 217 patients found that NAFLD is associated with a significantly higher risk of HCC as compared to no NAFLD. • In addition, NAFLD nonsignificantly increased the risk of HCC-related mortality but not of recurrence or overall mortality. • Given the higher risk of HCC in patients with NAFLD, general health interventions and screening should be implemented for high-risk cases (eg, those with steatohepatitis and fibrosis). Hepatic steatosis of nonalcoholic etiology (nonalcoholic fatty liver disease; NAFLD) is an emergent condition that may lead to hepatic cirrhosis and finally to liver cancer. We evaluate the risk of developing hepatocellular carcinoma (HCC) and quantify the prognosis in terms of recurrence (DFS) as well as HCC-specific and overall survival (CSS and OS) of patients with and without NAFLD. We searched published articles that evaluated the risk and outcomes of HCC in patients with steatosis/steatohepatitis from inception to July 2021 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. Prospective cohort, case-control, or retrospective studies were selected that were published in English and provided incidence and survival rates of HCC patients with NAFLD. A random-effects model was created to estimate the pooled effect size. The primary outcome of interest was HCC incidence. The secondary endpoints were DFS, CSS, and OS. In total, 948 217 patients with NAFLD were analyzed, from n = 103 observational studies. NAFLD significantly increased the risk of HCC (HR = 1.88 [95% CI, 1.46-2.42]; P <.01] but not risk of recurrence (HR = 0.99 [95% CI, 0.85-1.15]; P =.9) or overall mortality (HR = 1.04 [95% CI, 0.88-1.24]; P = 0.64). Conversely, NAFLD increased HCC-related mortality risk (HR = 2.16 [95% CI, 0.85-5.5]; P =.1). Risk of HCC was increased in Western countries but not in Asian countries. Patients with NAFLD have an increased risk of HCC as compared to patients without NAFLD. NAFLD also increases liver cancer (HCC) mortality. These results justify applying general measures to patients with proven NAFLD and monitoring patients with NASH and fibrosis. [ABSTRACT FROM AUTHOR]

Epithelial-to-mesenchymal transition (EMT) is a core process underlying cell movement during embryonic development and morphogenesis. Cancer cells hijack this developmental program to execute a multi-step cascade, leading to tumorigenesis and metastasis. CD133 (PROM1), a marker of cancer stem cells, has been shown to facilitate EMTin various cancers, but the regulatory networks controlling CD133 gene expression and function in cancer remain incompletely delineated. In this study, we show that a ribonucleoprotein complex including the long noncoding RNA MALAT1 and the RNA-binding protein HuR (ELAVL1) binds the CD133 promoter region to regulate its expression. In luminal nonmetastatic MCF-7 breast cancer cells, HuR silencing was sufficient to upregulate N-cadherin (CDH2) and CD133 along with a migratory and mesenchymal-like phenotype. Furthermore, we found that in the basal-like metastatic cell line MDAMB- 231 and primary triple-negative breast cancer tumor cells, the repressor complex was absent from the CD133-regulatory region, but was present in the MCF-7 and primary ER+ tumor cells. The absence of the complex from basal-like cells was attributed to diminished expression of MALAT1, which, when overexpressed, dampened CD133 levels. In conclusion, our findings suggest that the failure of a repressive complex to form or stabilize in breast cancer promotes CD133 upregulation and an EMT-like program, providing new mechanistic insights underlying the control of prometastatic processes. Cancer Res; 76(9); 2626-36. [ABSTRACT FROM AUTHOR]

miR-296-5p is a central regulator of signalling pathways affecting development, stem cell differentiation and cancer. We hypothesized that miR-296-5p is involved in breast cancer onset and progression possibly through regulation of its target SCRIB (Scribble), a polarity protein recently implicated in the acquisition of cancer stem cell traits and in cell motility. We found that miR-296-5p levels were consistently reduced in human breast cancer tissues compared with non-neoplastic mammary parenchyma, and low expression of this miRNA predicted shorter disease-free survival independently of classic clinicopathological parameters. Further, reduced miR-296-5p levels were significantly correlated with an earlier spread of cancer in the overall series and with distant metastases in the subset. In contrast with its regulator, SCRIB was overexpressed and mislocalized in primary breast cancers or locoregional or distant metastatic lesions compared with normal parenchyma. Notably, SCRIB mislocalization was associated with overall survival, metastatic spread and organ tropism in patients with breast cancer. Finally, direct injection of a precursor miR-296-5p into tumours of a breast cancer xenograft model significantly decreased tumour growth. Our results show that the miR-296-5p/SCRIB axis plays a role in breast carcinogenesis and an miR-296-5p-based therapeutic approach hampers breast cancer tumour growth in vivo. Modulation of miR-296-5p may represent a new therapeutic option for patients with breast cancer. [ABSTRACT FROM AUTHOR]

Background: Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer. Methods: We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan-Meier method. Results: Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco regionalor metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%. Conclusions: The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Rechallenge ICI is an active and feasible strategy. • Rechallenge ICI could be considered on an individual basis. • Prospective studies are needed to clarify the role of rechallenge ICI. The role of immune checkpoint inhibitors (ICI) rechallenge in cancer patients is not defined. When ICIs are discontinued due to treatment completion or toxicity, another course of ICIs is feasible in clinical practice, but the amount of data is still quite limited to draw definitive conclusions. Here we report the results of a meta-analysis evaluating efficacy and safety of ICI rechallenge. PubMed, Embase, and Cochrane library were searched for studies reporting efficacy and safety of ICI rechallenge. Pooled analysis of response rate (ORR), median progression-free survival (mPFS) and median overall survival (mOS) were calculated. A total of 49 studies were included in qualitative and quantitative pooled analysis Overall response rate, mPFS and mOS were 21.8 % (range 0–70 %), 4.9 months (range 0–19.1 months) and 15.6 months (range 5.1–39 months), respectively. Incidence of any grade and grade 3−4 adverse events were 52.2 % (range 4–100 %) and 21.5 % (range 0–97.8 %), respectively. In the subgroup of patients who had previously discontinued ICI because of disease progression ORR, mPFS and mOS were 15.2 %, 2.9 and 7.9 months. Patients who had previously discontinued ICI because of toxicity achieved an ORR of 44 % and a mPFS of 13.2 months with the rechallenge. Our results suggest that rechallenge ICI is an active and feasible strategy, and it could be considered on an individual basis. However, this analysis is based on non-randomized studies. Prospective studies are needed to clarify the role of rechallenge after disease progression or adverse events. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer patients show an increased vulnerability to SARS-CoV-2 infection and may experience severe COVID-19 complications. AIOM-L Corona aimed to assess the prognostic factors associated with outcomes in 231 cancer patients infected by SARS-CoV-2 between March and September 2020 in Lombardy, the most extensively affected Italian region. A total of 93 events occurred. Known risk factors for mortality in COVID-19 remained significant in the study population. Specifically, age ≥60 years, metastases, dyspnea, desaturation, and interstitial pneumonia were all associated with mortality. Notably, metastatic patients receiving systemic active therapy were less likely to die as compared to untreated counterparts, even after adjusting for other confounding variables (Odds Ratio 0.23, 95%CI 0.11–0.51, p < 0.001). While large data sets are needed to confirm these findings, for now, during the COVID-19 pandemic, cancer patients should avoid exposure or increase their protection to SARS-CoV-2 while treatment adjustments and prioritizing vaccination should adequately be considered. Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years; 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12–218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32–2.15); however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11–0.51, p < 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations. [ABSTRACT FROM AUTHOR]

probiotics and prebiotics can exert several beneficial effects in the gastrointestinal tract, such as anti-tumor activity; many studies have been conducted to analyze this activity and its mechanisms. However, their mode of action is not yet well understood. Recent data show the relationship between colon cancer and intestinal bacterial flora. We reviewed the evidence from, different studies in order to prove these beneficial effects on the host. [ABSTRACT FROM AUTHOR]