PROSPECTS OF TWINNING CLIMATE CHANGE AND URBAN SUSTAINABILITY ISSUES THROUGH TRANSFORMATIVE ADAPTATION: LESSONS FOR AFRICAN CITIES

In most African cities, existing approaches to tackle climate change and sustainability issues have remained largelyweak, piecemeal and fragmented. For example, current adaptation practices are mainly focusing on ‘adapting to’climatic disturbances instead of ‘adapting with’ the vulnerable urban population. This approach views climate changeas the main source of vulnerability and focuses on protecting systems from weather and climatic events. It grosslyignores the social roots of vulnerability and misses out on opportunities such as those that emerge when climaticrisks are jointly treated with environmental sustainability concerns. To evade this problem, this paper proposes a shifttowards transformative adaptation, an approach that comprehensively attend to the entire urban socio-ecologicalsystem. The aim is to contribute to the discourse of inclusive cities by examining the prospects of simultaneouslyaddressing climate change alongside other urban development challenges. Drawing on growing literature and reportson climate change adaptation in cities, I argue that the adjustment approach does not comprehensively address theunderlying urban vulnerabilities and fail to match the severity of climate change impacts being experienced. On thecontrary, a transformative approach locates urban risk beyond the biophysical environment to the entire urban socialecologicalsystem.Thus,thisapproach is capable of jointlydealing withclimate change and other urban developmentchallengesasit holistically dealswith the underlying vulnerabilityrisksin urban settlementswhile addressingthe root causes of urban unsustainability. African cities can draw useful lessons from the benefits that come with atransformative adaptation trajectory

CAR-T Cell Therapy for Solid Tumors: Are we Still That Far? a Systematic Review of Literature

This systematic review aims to assess all the prospective studies published to date on the efficacy of CAR-T cell therapy in solid tumors. Databases searched were PubMed and Google Scholar from inception through May 1st 2021. Search query was (Chimeric antigen receptor) or (CAR-T) or (T-CAR). Twenty-nine prospective studies (265 patients) were included. Most published clinical trials are phase I. Clinical benefit was 100% in epithelial ovarian cancer, 70-82% in gastrointestinal tumors, 79% in mesothelioma, 63% in small-cell lung cancer, 24-67% in sarcoma, 50-62% in prostate cancer, and 45-50% in central nervous system tumors. No serious CAR-T cell specific serious toxicities were noted

Systematic review of neoadjuvant therapy by immune checkpoint inhibitors before radical cystectomy. Where do we stand?

INTRODUCTION: After demonstrating their efficacy in metastatic urothelial cancer (UC), immune checkpoint inhibitors (ICI) are currently being tested in the neoadjuvant setting before radical cystectomy. In this systematic review, we analyze current available data and ongoing trials exploring the efficacy and safety of ICI neoadjuvant therapy in UC. eViDeNce acQUiSiTioN: a systematic search was performed including the combination of the following words: ([“neoadjuvant” AND “immunotherapy”] AND [“bladder” AND “cancer”]). Three search engines (PubMed, Embase®, and Web of Science) were queried up to January 1, 2020. Study selection followed the PRISMA guidelines. After screening, 9 articles and abstracts fully compatible with the PicoS were included in the systematic review. EVIDENCE SYNTHESIS: The PURE-01 trial showed a 37% complete response (pT0) after neoadjuvant pembrolizumab. in the aBacUS trial, atezolizumab determined a complete response in 31% of patients. in both trials, an increased expression of PD-1 or PD-l1 was associated to an improved response to ici. Moreover, ici are well tolerated with grade iii-iV adverse events in 6% of cases. in the PUre-01 trial, radical cystectomy after neoadjuvant ici presents a similar complication rate compared to neoadjuvant chemotherapy, with fever (N.= 35, 52%) and ileus (N. = 21, 31%) being the most common postoperative complications. Numerous trials are currently recruiting to test ici in the neoadjuvant setting, either alone, in combination immunotherapy or with chemotherapy. coNclUSioNS: Pembrolizumab and atezolizumab single agent demonstrated favorable results for ici in the neoadjuvant setting. Patients with a higher tumor expression of PD-l1 appear to experience a higher response to ici, although the adequate biomarker remains to be identified. Radical cystectomy appears to be safe after ICI treatment. The results of the currently ongoing prospective trial are awaited with impatience by the uro-oncologic community

Immune checkpoint inhibitors for BCG-resistant NMIBC: The dawn of a new era

INTRODUCTION: High risk non-muscle invasive bladder cancer (NMIBC) is a recurring and potentially lethal disease. To date, with the exception of radical surgery, there are no validated strategies for patients not responding to intravesical BCG therapy. Immune checkpoint inhibitors (ICI) are currently being tested for BCG-resistant NMIBC. We report current available data and ongoing trials exploring the efficacy and safety of ICI in this setting.EVIDENCE ACQUISITION: A narrative search was performed including the combination of the following words: ("immunotherapy") AND ("BCG" AND "resistant" OR "non-muscle AND invasive") AND ("bladder AND "cancer"). Three search engines: PubMed, Embase and Web of Science were queried up to November 1, 2020. Congress abstracts reporting results and not only trials' design were also referenced. The US National Library of Medicine was queried via clinicaltrials.gov to explore ongoing trials on the subject.EVIDENCE SYNTHESIS: Pembrolizumab demonstrated a promising 40.6% (95% CI: 30.7-51.1) complete response within the KEYNOTE-057, with a median duration of response of 16.2 months. Preliminary data in the phase II SWOG S1605 trial with atezolizumab showed a 41.1% complete response at 3 months. Avelumab is being tested in the PREVERT phase II study exploring ICI with radiotherapy (60-66 Gy) of the whole bladder. CheckMate 9UT analyzes nivolumab monotherapy versus nivolumab + BMS-986205 (IDO-1 inhibitor) with or without BCG in patients with BCG-unresponsive, carcinoma in situ with or without papillary component. Finally, durvalumab is being studied in the BCG resistant space with radiotherapy in the ADAPT-BLADDER study. After proving its safety profile in the phase 1, the trial will randomize patients to durvalumab + BCG, durvalumab + radiation therapy (6Gy 3x) or BCG rechallenge.CONCLUSIONS: Pembrolizumab has received FDA approval in the treatment of BCG-resistant NMIBC. All five other ICI molecules are currently being extensively tested within clinical trials. The results of the currently ongoing studies are awaited with impatience by the uro-oncologic community and will probably open a new era in the treatment of BCG-resistant NMIBC

The Value of PD-L1 Expression as Predictive Biomarker in Metastatic Renal Cell Carcinoma Patients: A Meta-Analysis of Randomized Clinical Trials

Immune checkpoint inhibitors (ICIs) are soluble antibodies that have dramatically changed the outcomes including overall survival in a subset of kidney tumors, specifically in renal cell carcinoma (RCC). To date, there is no a single predictive biomarker approved to be used to select the patients that achieve benefit from ICIs targeting. It seems reasonable to analyze whether the programmed death-ligand 1 (PD-L1) expression could be useful. To assess the role of PD-L1 expression as a potential predictive biomarker for benefit of ICIs in RCC patients, we performed a search of randomized clinical trials (RCTs) comparing ICIs (monotherapy or in combination with other therapies) to standard of care in metastatic RCC patients according to PRISMA guidelines. Trials must have included subgroup analyses evaluating the selected outcomes (progression-free survival (PFS) and overall survival (OS)) in different subsets of patients according to PD-L1 expression on tumor samples. Hazard ratios with confidence intervals were used as the measure of efficacy between groups. A total of 4635 patients (six studies) were included (ICIs arm: 2367 patients; standard of care arm: 2268 patients). Globally, PFS and OS results favored ICIs. Differential expression of PD-L1 on tumor samples could select a subset of patients who could benefit more in terms of PFS (those with higher levels; p-value for difference between subgroups: <0.0001) but it did not seem to impact in OS results (p-value for difference: 0.63). As different methods to assess PD-L1 positivity were used among trials, this heterogeneity could have an influence on the results. PD-L1 could represent a biomarker to test PFS in clinical trials but its value for OS is less clear. In this meta-analysis, the usefulness of PD-L1 expression as a predictive biomarker to select treatment in metastatic RCC patients was not clearly shown

An update on the management of metastatic clear-cell renal cell carcinoma: the BSMO expert panel recommendations

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Incidence, Patterns, and Outcomes with Adjuvant Chemotherapy for Residual Disease After Neoadjuvant Chemotherapy in Muscle-invasive Urinary Tract Cancers.

Patients with residual muscle-invasive urinary tract cancer after neoadjuvant chemotherapy (NAC) have a high risk of recurrence. To retrospectively evaluate whether additional adjuvant chemotherapy (AC) improves outcomes compared with surveillance in patients with significant residual disease despite NAC. We identified 474 patients who received NAC from the Retrospective International Study of Cancers of the Urothelium database, of whom 129 had adverse residual disease (≥ypT3 and/or ypN &lt;sup&gt;+&lt;/sup&gt; ). Time to relapse (TTR) was the primary endpoint assessed starting from 2mo after surgery to minimize immortal time bias. Secondary endpoints included overall survival (OS), incidence of AC use, and chemotherapy patterns. Kaplan-Meier and Cox regression models estimated TTR, OS, and associations with AC, adjusting for the type of NAC, age, and pathological stage in multivariable analyses. A total of 106 patients underwent surveillance, while 23 received AC. Gemcitabine-cisplatin was the most frequent regimen employed in both settings (30.4%), and the majority (82.6%) of the patients switched to a different regimen. Median follow-up was 30mo. Over 50% of patients developed a recurrence. Median TTR was 16mo (range: &lt;1-108mo). Longer median TTR was observed with AC compared with surveillance (18 vs 10mo, p=0.06). Risk of relapse significantly decreased with AC when adjusted in multivariable analyses (p=0.01). The subgroup analyses of ypT4b/ypN &lt;sup&gt;+&lt;/sup&gt; patients (AC: 19; surveillance: 50) who received AC had significantly greater median TTR (20 vs 9mo; hazard ratio 0.43; 95% confidence interval: 0.21-0.89). No difference in OS was found. Limitations include the retrospective design. The utilization of AC after NAC in patients with high-risk residual disease is not frequent in clinical practice but might reduce the risk of recurrence. Further investigation is needed in this high-risk population to identify optimal therapy and to improve clinical outcomes such as the ongoing adjuvant immunotherapy trials. We found that administering additional chemotherapy in patients who had significant residual disease despite preoperative chemotherapy is not frequent in clinical practice. While it might reduce the risk of recurrence, it did not clearly increase overall survival. We encourage participation in the ongoing immunotherapy trials to see whether we can improve outcomes using a different type of therapy that stimulates the immune system