The emerging landscape of neo/adjuvant immunotherapy in renal cell carcinoma.

Adjuvant and neoadjuvant therapies that reduce the risk of renal cell carcinoma (RCC) recurrence remain an area of unmet need. Advances have been made in metastatic RCC recently by leveraging PD-1/PD-L1 immune checkpoint inhibitors (ICIs). These agents are currently being investigated in the adjuvant and neoadjuvant settings to determine if intervention early in the disease trajectory offers a clinically meaningful benefit. While a disease-free survival benefit has been demonstrated with pembrolizumab, results from other ICI studies have not been positive to date. More mature data from these studies are needed to determine whether there is a survival benefit to ICIs in the curative-intent setting. The success of ICIs has also ushered a new wave of studies combining ICIs with other agents such as targeted therapies and vaccines, which are in early stages of investigation. We review the current state of adjuvant/neoadjuvant therapy in RCC and highlight opportunities for ongoing study.

The emerging treatment landscape of advanced urothelial carcinoma.

PURPOSE OF REVIEW: Urothelial carcinoma (UC) is one of the most common malignancies in the Western world. Historically, patients with advanced disease have had a poor prognosis and progress within months of completing upfront platinum-based chemotherapy. In the last two years, the treatment landscape for metastatic UC (mUC) has significantly shifted with the emergence of contemporary immunotherapy and targeted agents. The purpose of this review is to highlight the current and emerging systemic treatment options for mUC of the bladder. RECENT FINDINGS: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the postplatinum and platinum-ineligible settings. Additionally, they have become a standard maintenance treatment option after avelumab demonstrated increased overall survival in patients with stable disease or better after first line platinum-based chemotherapy. Novel targeted therapies and antibody-drug conjugates (ADCs) have been granted Food and Drug Administration approval for subsequent line therapy based on promising results in phase II and III trials. SUMMARY: There has been a considerable increase in the variety of effective therapies for mUC, including the utility of ICIs, novel targeted agents, and ADCs. Platinum-based chemotherapy remains an effective first-line option. As the role of novel therapies continues to shift toward earlier in the disease course, there remains an important need to develop feasible, globally accessible predictive biomarkers that can aid in patient selection and inform sequencing of therapeutic options.

Wait times in the management of non-small cell lung carcinoma before, during and after regionalization of lung cancer care: a high-resolution analysis.

Background: Timeliness can have a substantial effect on treatment outcomes, prognosis and quality of life for patients with lung cancer. We sought to evaluate changes in wait times for patients with non-small cell lung carcinoma (NSCLC) and to identify bottlenecks in cancer care. Methods: We included patients who received treatment with curative intent or palliative treatment for NSCLC, diagnosed through mediastinal staging by a thoracic surgeon. Data were collected from 3 cohorts over 3 time periods: before the regionalization of lung cancer care (2005-2007, C1), immediately postregionalization (2011-2013, C2) and 5 years after regionalization (2016-2017, C3). Total wait time and delays along treatment pathways were compared across cohorts using multivariate Cox proportionality models. Results: Our total sample size was 299 patients. Overall, there was no significant difference in total wait time among the 3 cohorts. However, wait time from symptom onset to first physician visit significantly increased in C3 compared with C2 (hazard ratio [HR] 0.41, p < 0.01) and C1 (HR 0.43, p < 0.01). Time from first physician visit to computed tomography (CT) scan significantly decreased in C3 compared with C2 (HR 1.54, p < 0.01). Time from abnormal CT scan to first surgeon visit also significantly decreased in C2 (HR 1.43, p < 0.01) and C3 (HR 4.47, p < 0.01) compared with C1, and between C3 and C2 (HR 2.67, p < 0.01). In contrast, time from first surgeon visit to completion of staging significantly increased in C2 (HR 0.36, p < 0.01) and C3 (HR 0.24, p < 0.01) compared with C1, as well as between C3 and C2 (HR 0.60, p < 0.01). Time to first treatment after completion of staging was significantly shorter for C3 than C1 (HR 1.58, p < 0.01). Conclusion: Trends toward a reduction in wait time are evident 5 years after the regionalization of lung cancer care, primarily led by shorter wait times for CT scans and thoracic surgeon consults. However, wait times can further be reduced by addressing delays in staging completion and patient and provider education to identify the early signs of NSCLC.

Contexte: La rapidité d'intervention peut avoir un effet considérable sur l'issue du traitement, le pronostic et la qualité de vie des patients atteints d'un cancer du poumon. Nous avons voulu évaluer les changements des temps d'attente des patients ayant un carcinome pulmonaire non à petites cellules et recenser les obstacles aux soins oncologiques. Méthodes: Nous avons inclus des patients ayant reçu un traitement curatif ou palliatif pour un carcinome pulmonaire non à petites cellules diagnostiqué par stadification de lésions médiastinales par un chirurgien thoracique. Les données ont été recueillies auprès de 3 cohortes, à 3 moments : avant la régionalisation des soins oncologiques (2005­2007; C1), immédiatement après la régionalisation (2011­2013; C2) et 5 ans après la régionalisation (2016­2017; C3). Le temps d'attente total et les délais au cours du processus de traitement des cohortes ont été comparés au moyen de modèles à risques proportionnels de Cox multivariés. Résultats: Au total, l'échantillon comptait 299 patients. Dans l'ensemble, aucune différence statistiquement significative n'a été observée entre les 3 cohortes pour ce qui est du temps d'attente total. Cependant, la C3 présentait un temps d'attente entre l'apparition des symptômes et la première consultation médicale significativement plus long que la C2 (rapport de risque [RR] 0,41; p < 0,01) et que la C1 (RR 0,43; p < 0,01). Le temps d'attente entre la première consultation médicale et la tomodensitométrie (TDM) était par contre significativement plus court dans la C3 que dans la C2 (RR 1,54; p < 0,01). Le délai entre l'obtention d'un résultat anormal à la TDM et la première consultation chirurgicale était également significativement moindre dans la C2 (RR 1,43; p < 0,01) et dans la C3 (RR 4,47; p < 0,01) que dans la C1, mais aussi entre la C3 et la C2 (RR 2,67; p < 0,01). À l'inverse, le temps écoulé entre la première consultation chirurgicale et la fin de la stadification était significativement plus long dans la C2 (RR 0,36; p < 0,01) et la C3 (RR 0,24; p < 0,01) que dans la C1; il en était également ainsi entre la C3 et la C2 (RR 0,60; p < 0,01). Enfin, le délai entre le premier traitement et la fin de la stadification était significativement plus court dans la C3 que dans la C1 (RR 1,58; p < 0,01). Conclusion: Cinq ans après la régionalisation des soins oncologiques, on peut observer une réduction des temps d'attente, principalement une diminution du temps d'attente pour une TDM ou une consultation chirurgicale. Les temps d'attente pourraient être davantage raccourcis par une réduction des délais dans la stadification, ainsi que par la sensibilisation des patients et des fournisseurs de soins à l'égard de la reconnaissance des signes précoces de carcinome pulmonaire non à petites cellules.

ST-elevation in ethylene glycol toxicity mimicking myocardial infarction.

Electrocardiographic changes due to ethylene glycol toxicity are described in a 37-year-old woman who presented with intentional overdose. She received prompt treatment with dialysis and fomepizole, which reversed profound metabolic acidosis. ST-elevation in leads I, aVL, and aVR were observed 87 h after admission along with diffuse repolarization abnormalities. Coronary angiography found no evidence of coronary artery disease, and echocardiogram revealed normal left ventricle size and a mildly hypokinetic basal inferior wall. Diffuse repolarization abnormalities persisted for several days. Review of literature supports the diagnosis of myocarditis induced by toxic metabolites of ethylene glycol in context of hepatic and renal failure.

Role of neural precursor cells in promoting repair following stroke.

Stem cell-based therapies for the treatment of stroke have received considerable attention. Two broad approaches to stem cell-based therapies have been taken: the transplantation of exogenous stem cells, and the activation of endogenous neural stem and progenitor cells (together termed neural precursors). Studies examining the transplantation of exogenous cells have demonstrated that neural stem and progenitor cells lead to the most clinically promising results. Endogenous activation of neural precursors has also been explored based on the fact that resident precursor cells have the inherent capacity to proliferate, migrate and differentiate into mature neurons in the uninjured adult brain. Studies have revealed that these neural precursor cell behaviours can be activated following stroke, whereby neural precursors will expand in number, migrate to the infarct site and differentiate into neurons. However, this innate response is insufficient to lead to functional recovery, making it necessary to enhance the activation of endogenous precursors to promote tissue repair and functional recovery. Herein we will discuss the current state of the stem cell-based approaches with a focus on endogenous repair to treat the stroke injured brain.