Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared. RESULTS: Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707). CONCLUSIONS: Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era.

[Economic development, urbanization, and urban concentration: an attempt at a synthesis]. / Developpement economique, urbanisation et concentration urbaine: essai de synthese.

The relationship between economic development and urbanization in developing countries is reviewed. The authors conclude that urbanization is a necessary but not in itself a sufficient condition of development. They note that policies designed to either encourage or discourage urbanization have proved ineffective. Problems encountered are primarily due to the fact that, although urbanization is not occurring in developing countries at the same rate as it did previously in today's developed ones, the overall rate of population growth is much higher. "The degree of concentration of urban systems reflects a moving equilibrium between economies of agglomeration (centripetal), and diseconomies (centrifugal) and distance costs. Big city environmental costs are externalities not reflected in market prices, and which public authorities are called upon to manage. The choice of public investment in infrastructures can influence, marginally, the patterns of urban systems." (SUMMARY IN ENG)

[The location of employment in developing countries. Models of urbanization and comparative analyses of the Canadian and Mexican urban systems]. / La localizacion del empleo en los paises en desarrollo. Modelos de urbanizacion y analisis comparativos de los sistemas urbanos canadiense y mexicano.

PIP: The rapid urban growth and increasing number of megacities in Latin America and other developing countries are fundamentally different phenomena than those observed at the time that location theory was developed. To examine whether existing location theory applies to developing countries, an econometric analysis of the relationship between urbanization, city size, and development was first conducted. The relationship between urbanization and development was expressed in the form of a series of regression analyses applied to World Bank data for 96 developing and developed countries. After logarithmic transformation, a simple equation associating total and total urban population of the country and per capita gross national product was able to explain 93% of the variance in total urban population. This result demonstrates that it is not possible to regard urbanization as abnormal. As to the size of particular cities, deviations from the "normal" trajectory of urbanization apparently originate in particular institutional features of some countries. Manifestations of overurbanization in Latin America demonstrate that urbanization is a necessary, but not sufficient, condition of development. A comparative study of spatial location of employment in different economic sectors in Canada and Mexico was next conducted. For this analysis, cities of over 25,000 population in Canada and Mexico were classified into 32 economic activity sectors, which were regrouped into 18 for the analysis. Two matrixes of ten city types and 18 and 32 employment groups were constructed for each country, with the corresponding number of employees noted. The employment information was transformed into quotients of location, with a quotient above 100 signifying concentration of employment. The results did not suggest that factors of localization of employment are different in developing countries. Models of localization of economic activities adopt analogous characteristics imposed by geography and technological conditions. In Canada as in Mexico, economies of scale and distance are the principle variable explaining models of localization.^ieng