An overall strategy based on regression models to estimate relative survival and model the effects of prognostic factors in cancer survival studies.

Relative survival provides a measure of the proportion of patients dying from the disease under study without requiring the knowledge of the cause of death. We propose an overall strategy based on regression models to estimate the relative survival and model the effects of potential prognostic factors. The baseline hazard was modelled until 10 years follow-up using parametric continuous functions. Six models including cubic regression splines were considered and the Akaike Information Criterion was used to select the final model. This approach yielded smooth and reliable estimates of mortality hazard and allowed us to deal with sparse data taking into account all the available information. Splines were also used to model simultaneously non-linear effects of continuous covariates and time-dependent hazard ratios. This led to a graphical representation of the hazard ratio that can be useful for clinical interpretation. Estimates of these models were obtained by likelihood maximization. We showed that these estimates could be also obtained using standard algorithms for Poisson regression

On a general structure for hazard-based regression models: An application to population-based cancer research

The proportional hazards model represents the most commonly assumed hazard structure when analysing time to event data using regression models. We study a general hazard structure which contains, as particular cases, proportional hazards, accelerated hazards, and accelerated failure time structures, as well as combinations of these. We propose an approach to apply these different hazard structures, based on a flexible parametric distribution (exponentiated Weibull) for the baseline hazard. This distribution allows us to cover the basic hazard shapes of interest in practice: constant, bathtub, increasing, decreasing, and unimodal. In an extensive simulation study, we evaluate our approach in the context of excess hazard modelling, which is the main quantity of interest in descriptive cancer epidemiology. This study exhibits good inferential properties of the proposed model, as well as good performance when using the Akaike Information Criterion for selecting the hazard structure. An application on lung cancer data illustrates the usefulness of the proposed model

Performance of two formal tests based on martingales residuals to check the proportional hazard assumption and the functional form of the prognostic factors in flexible parametric excess hazard models.

: Net survival, the one that would be observed if the disease under study was the only cause of death, is an important, useful, and increasingly used indicator in public health, especially in population-based studies. Estimates of net survival and effects of prognostic factor can be obtained by excess hazard regression modeling. Whereas various diagnostic tools were developed for overall survival analysis, few methods are available to check the assumptions of excess hazard models. We propose here two formal tests to check the proportional hazard assumption and the validity of the functional form of the covariate effects in the context of flexible parametric excess hazard modeling. These tests were adapted from martingale residual-based tests for parametric modeling of overall survival to allow adding to the model a necessary element for net survival analysis: the population mortality hazard. We studied the size and the power of these tests through an extensive simulation study based on complex but realistic data. The new tests showed sizes close to the nominal values and satisfactory powers. The power of the proportionality test was similar or greater than that of other tests already available in the field of net survival. We illustrate the use of these tests with real data from French cancer registries.<br/

Estimation of screening test (Hemoccult®) sensitivity in colorectal cancer mass screening

3 controlled cohorts of mass-screening for colorectal cancer using a biennial faecal occult blood (HemoccultII®) test on well-defined European populations have demonstrated a 14% to 18% reduction in specific mortality. We aimed to estimate the sensitivity (S) of this HemoccultII®test and and also mean sojourn time (MST) from French colorectal mass-screening programme data. 6 biennial screening rounds were performed from 1988 to 1998 in 45 603 individuals aged 45–74 years in Saône-et-Loire (Burgundy, France). The prevalent/incidence ratio was calculated in order to obtain a direct estimate of the product S.MST. The analysis of the proportional incidence and its modelling was used to derive an indirect estimate of S and MST. The product S.MST was higher for males than females and higher for left colon than either the right colon or rectum. The analysis of the proportional incidence confirmed the result for subsites but no other significant differences were found. The sensitivity was estimated at 0.57 and the MST at 2.56 years. This study confirms that the sensitivity of the Hemoccult test is relatively low and that the relatively short sojourn time is in favour of annual screening. © 2001 Cancer Research Campaign http://www.bjcancer.co

Socioeconomic and geographic determinants of survival of patients with digestive cancer in France

Using a multilevel Cox model, the association between socioeconomic and geographical aggregate variables and survival was investigated in 81 268 patients with digestive tract cancer diagnosed in the years 1980–1997 and registered in 12 registries in the French Network of Cancer Registries. This association differed according to cancer site: it was clear for colon (relative risk (RR)=1.10 (1.04–1.16), 1.10 (1.04–1.16) and 1.14 (1.05–1.23), respectively, for distances to nearest reference cancer care centre between 10 and 30, 30 and 50 and more than 90 km, in comparison with distance of less than 10 km; P-trend=0.003) and rectal cancer (RR=1.09 (1.03–1.15), RR=1.08 (1.02–1.14) and RR=1.12 (1.05–1.19), respectively, for distances between 10 and 30 km, 30 and 50 km and 50 and 70 km, P-trend=0.024) (n=28 010 and n=18 080, respectively) but was not significant for gall bladder and biliary tract cancer (n=2893) or small intestine cancer (n=1038). Even though the influence of socioeconomic status on prognosis is modest compared to clinical prognostic factors such as histology or stage at diagnosis, socioeconomic deprivation and distance to nearest cancer centre need to be considered as potential survival predictors in digestive tract cancer

Age-period-cohort modelling of non-Hodgkin's lymphoma incidence in a French region: a period effect compatible with an environmental exposure

<p>Abstract</p> <p>Background</p> <p>The incidence of non-Hodgkin's lymphoma (NHL) has risen steadily during the last few decades in all geographic regions covered by cancer registration for reasons that remain unknown. The aims of this study were to assess the relative contributions of age, period and cohort effects to NHL incidence patterns and therefore to provide clues to explain the increasing incidence.</p> <p>Methods</p> <p>Population and NHL incidence data were provided for the Doubs region (France) during the 1980-2005 period. NHL counts and person-years were tabulated into one-year classes by age (from 20 to 89) and calendar time period. Age-period-cohort models with parametric smooth functions (natural splines) were fitted to the data by assuming a Poisson distribution for the observed number of NHL cases.</p> <p>Results</p> <p>The age-standardised incidence rate increased from 4.7 in 1980 to 11.9 per 100,000 person-years at risk in 1992 (corresponding to a 2.5-fold increase) and stabilised afterwards (11.1 per 100,000 in 2005). Age effects showed a steadily increasing slope up to the age of 80 and levelled off for older ages. Large period curvature effects, both adjusted for cohort effects and non-adjusted (p < 10^-4and p < 10^-5, respectively), showed departure from linear periodic trends; period effects jumped markedly in 1983 and stabilised in 1992 after a 2.4-fold increase (compared to the 1980 period). In both the age-period-cohort model and the age-cohort model, cohort curvature effects were not statistically significant (p = 0.46 and p = 0.08, respectively).</p> <p>Conclusions</p> <p>The increased NHL incidence in the Doubs region is mostly dependent on factors associated with age and calendar periods instead of cohorts. We found evidence for a levelling off in both incidence rates and period effects beginning in 1992. It is unlikely that the changes in classification (which occurred after 1995) and the improvements of diagnostic accuracy could largely account for the 1983-1992 period-effect increase, giving way to an increased exposure to widely distributed risk factors including persistent organic pollutants and pesticides. Continued NHL incidence and careful analysis of period effects are of utmost importance to elucidate the enigmatic epidemiology of NHL.</p

Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the <it>in vivo </it>imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield.</p> <p>Methods</p> <p>CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye. <it>In vivo </it>fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured.</p> <p>Results</p> <p>QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces.</p> <p>Conclusion</p> <p>Effective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was demonstrated. This work was done using very low doses of injected QDs and the detection was done using a minimally invasive method.</p

Cancer incidence and mortality trends in France over 1990-2018 for solid tumors: the sex gap is narrowing

OBJECTIVE: To analyze trends in cancer incidence and mortality (France, 1990-2018), with a focus on men-women disparities. METHODS: Incidence data stemmed from cancer registries (FRANCIM) and mortality data from national statistics (CépiDc). Incidence and mortality rates were modelled using bidimensional penalized splines of age and year (at diagnosis and at death, respectively). Trends in age-standardized rates were summarized by the average annual percent changes (AAPC) for all-cancers combined, 19 solid tumors, and 8 subsites. Sex gaps were indicated using male-to-female rate ratios (relative difference) and male-to-female rate differences (absolute difference) in 1990 and 2018, for incidence and mortality, respectively. RESULTS: For all-cancers, the sex gap narrowed over 1990-2018 in incidence (1.6 to 1.2) and mortality (2.3 to 1.7). The largest decreases of the male-to-female incidence rate ratio were for cancers of the lung (9.5 to 2.2), lip - oral cavity - pharynx (10.9 to 3.1), esophagus (12.6 to 4.5) and larynx (17.1 to 7.1). Mixed trends emerged in lung and oesophageal cancers, probably explained by differing risk factors for the two main histological subtypes. Sex incidence gaps narrowed due to increasing trends in men and women for skin melanoma (0.7 to 1, due to initially higher rates in women), cancers of the liver (7.4 to 4.4) and pancreas (2.0 to 1.4). Sex incidence gaps narrowed for colon-rectum (1.7 to 1.4), urinary bladder (6.9 to 6.1) and stomach (2.7 to 2.4) driven by decreasing trends among men. Other cancers showed similar increasing incidence trends in both sexes leading to stable sex gaps: thyroid gland (0.3 to 0.3), kidney (2.2 to 2.4) and central nervous system (1.4 to 1.5). CONCLUSION: In France in 2018, while men still had higher risks of developing or dying from most cancers, the sex gap was narrowing. Efforts should focus on avoiding risk factors (e.g., smoking) and developing etiological studies to understand currently unexplained increasing trends