Multicentre Investigation of Prognostic Factors Incorporating p16 and Tumour Infiltrating Lymphocytes for Anal Cancer After Chemoradiotherapy

Aims Anal squamous cell carcinomas (ASCC) are strongly associated with human papillomaviruses. Standard of care is chemoradiotherapy at uniform doses with no treatment stratification. Immunohistochemical staining for p16INK4A (p16), a surrogate for human papillomaviruses, is prognostic for outcomes. We investigated this alongside clinical-pathological factors, including tumour infiltrating lymphocyte (TIL) scores. Materials and methods Using an independent, multicentre cohort of 257 ASCC treated with chemoradiotherapy, pretreatment biopsies were stained and scored for p16 and TIL. Kaplan–Meier curves were derived for outcomes (disease-free survival [DFS], overall survival and cancer-specific survival), by stage, p16 and TIL scores and Log-rank tests were carried out to investigate prognostic effect. A multivariate analysis was carried out using Cox regression. Results Stage, sex, p16 and TILs were independently prognostic. Hazard ratios for death (overall survival) were 2.51 (95% confidence interval 1.36–4.63) for p16 negative versus p16 positive, 2.17 (1.34–3.5) for T3/4 versus T1/2, 2.42 (1.52–3.8) for males versus females and 3.30 (1.52–7.14) for TIL1 versus TIL3 (all P < 0.05). Conclusions We have refined prognostic factors in ASCC. p16 adds to stratification by stage with respect to DFS in early disease and overall survival/DFS in locally advanced cancers. Our data support the role of the host immune response in mediating outcomes. These factors will be prospectively evaluated in PLATO (ISRCTN88455282)

Essays On Risk and Time with applications in insurance and finance

The predictions of theoretical models of human decision-making should agree with empir- ical and experimental evidence. In that respect, some fields of economics have embraced more plausible representations of preferences than others. For example, while standard in finance, temporally risk-averse preferences are still uncommon in the life-cycle literature, although they greatly improve its predictions. Chapter I introduces the issues that this dissertation touches on regarding the modeling of intertemporal preferences under uncertainty Chapter II discusses the allocation of aggregate longevity risk within a pension system when insurance markets are perfect. For a given expected budget, temporally risk-averse individuals prefer contributions and benefits to depend on the evolution of aggregate mor- tality rates rather than being fixed. The optimal allocation therefore transfers some risk to individuals, even though pension providers have access to perfect insurance markets. Indeed, this offers a “hedging” strategy where the prospect of a shorter life (e.g. emerging diseases) entails higher consumption while the prospect of a longer life is combined with lower consumption levels. Chapter II illustrates the benefits of applying models borrowed from finance to the life- cycle literature. In addition, empirical and experimental research refines our understand- ing of human behavior, triggering further improvements in the modeling of decision- making processes. Recent experiments indicate that individuals are more averse to im- mediate risk than to delayed ones. Because it involves risk attitudes and temporal delays, this bias may affect the decision to purchase insurance for long-run risks such as long-term care insurance. Chapter III considers individuals whose propensity to take risks decreases when old. Unaware of their changing taste for risk, naives delay the purchase of long-term care insurance, although this is a dominated strategy. Sophisticates, on the other hand, do not delay their purchase and, provided the elasticity of intertemporal substitution is below unity, end up better insured than naives. Delay-dependent risk aversion may also affect the pricing of financial assets. In fact, recent empirical evidence suggests that risk premia are sometimes higher for short-term yields than for long-term ones. Existing asset pricing models cannot reproduce this feature. Chapter IV contains a consumption-based model with a dynamically inconsistent rep- resentative agent whose risk aversion decreases with the delay. When this agent is naive, this model’s achievements are similar to those of existing asset pricing models: Equity risk premia are high and interest rates are low. The innovation is that the term structure of equity premia is decreasing

Would you Prefer your Retirement Income to Depend on your Life Expectancy?

We study the demand for retirement income of agents who gradually learn about their life expectancy. For a given expected budget, temporally risk-averse agents prefer that pension levels respond to incoming information about life ex- pectancy rather than being fixed ex-ante. Indeed, this offers a hedging strategy that couples shorter lives with higher consumption levels, and longer lives with lower consumption levels. A calibrated life-cycle model provides an order of mag- nitude of the effects at play.ISSN:0022-0531ISSN:1095-723

L'hyperleucocytose et la neutrophilie, facteurs pronostiques avant chimioradiothérapie des carcinomes épidermoïdes du canal anal

Objectif : cette étude visait à étudier l'association pronostique de l'hyperleucocytose et la neutrophilie chez les patients traités par chimioradiothérapie concomitante pour un carcinome épidermoïde du canal anal. Matériels et Méthodes : les données cliniques des patients traités entre 2006 et 2016 à l'Institut Gustave Roussy ont été analysées pour former la cohorte d'entrainement. Les patients traités à l'hôpital Tenon (Paris) et à l'Institut Paoli Calmettes (Marseille) constituaient la cohorte de validation. L'hyperleucocytose étaitdéfinie comme un taux de leucocytes circulants au diagnostic = 10 G/L, et la neutrophilie un taux de neutrophiles circulants au diagnostic = 7 G/L. L'association pronostique entre l'hyperleucocytose et la neutrophilie a été étudiée rétrospectivement. Résultats : la cohorte d'entrainement incluait 103 patients. La majorité (78%) ont reçu une chimiothérapie concomitante. Une hyperleucocytose ou une neutrophilie étaient présentes au diagnostic chez 12% et 8% des patients, respectivement. Les survies globale et sans progression à 3 ans étaient respectivement de 88% et 67%. En analyse univariée, l'hyperleucocytose et la neutrophilie étaient fortement associées à une survie globale, une survie sans progression, sans rechute locale ou à distance diminuées (p<0,01). En analyse multivariée, l'hyperleucocytose et la neutrophilie restaient des facteurs pronostiques indépendamment associés à une survie globale et sans récidive altérée. Ces résultats ont été validés dans la cohorte de validation, qui incluait 133 patients. Conclusion : l'hyperleucocytose et la neutrophilie sont des facteurs pronostiques indépendants associés à une survie globale et sans progression inférieure dans ces deux cohortes indépendantes de patients traités par chimioradiothérapie d'un carcinome épidermoïde du canal anal. Ces biomarqueurs simples et peu onéreux pourraient aider à sélectionner les patients les plus à risque de rechute, afin de leur proposer des protocoles d'essais cliniques spécifiques

L'arthroplasie par prothèse totale de cheville : étude préliminaire à propos de 54 cas

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