Another way to look at latent growth modeling is to examine metastatic (met) process. In mouse models, the effects of met in various organs can be examined by using various cell lines with different tropism towards organs leading to difference in burden. We recently published a paper (attached) examining different methods of induction route in a brain met model and also compared two different cell line with different brain tropism. We monitored the mouse weight over time since the induction of the met as a surrogate marker of morbidity. Interestingly the weight loss (paper attached: supplemental data S4) was closely following the met process likely reflecting the effect of cell infiltration and growth on vital organs. Using different cell lines with different tropism on vital organs (data S5) would lead to a change in morbidity and weight pattern following induction. This could be one way to examine trajectories of change.

I am, among other methods.

Attached is an entirely new approach to the problem you pose. Hope you find it useful.

John Gamel, MD

[email protected]

complete bio: jwgamel.com

Daer Collegaue,

Interesting question , and to my mind linked to the following: "during cancer , what is the cause of death, the terminal evolution of the process" ? and the different corresponding steps at the level of the entire body, compared to the mechanism described for cancer at the molecular level.

If the expansion of the tumor is not in a closed organ (ie brain), or if the local destruction doesn't touch a vital structure (ie main vessels), the local growth is not the cause of death, and the tumor can follow the "natural" process of metastasis, and the person dies from the "metastatic disease" (expansion altering other vital structure at distance; or simply consumming all the ressources of the organism when the mass of the tumor increase from 1g to 1kg).

It's the first point but at a stage of acute expansion of a cancer.

Previously to this step, you can have only a local growth, or the different steps of cell transformation in cancer cell (dysplasia to cancer), or simply infraclinical transformzation (in general when inferior to 1 cm of size), or finally the case of residual disease after treatment, , that can be put in parralel to your notion of latent growth model.

The problem can be conisdered as similar when "chronic" tumor is transforming in acute cancer (chronic myeloid leukemia to acute myeloid leukemia; latent myeloma to acute one). In these cases, comprehension of the mechanism are not completed, and interaction with the micro-environment of the tumor is essentail.

Added to that interacts the role of the immune system: when the size is infraclinic, it can eliminate cancer cells (also the case in residual disease); and its role is important in the passage from a chronic to an acute phase also.

If we retunr to your initial quersiton, that is relatively general compared to the multiple elements acting and interfering with evolution and prognosis, can we individualize markers of prognostic (if I well understand your problem), and could be determined a correlation between general parameters as weight, so a general response and adaptation of an individual to the growth of the tumor, to the evolution of the disease ? Perhaps and it has to be validated, to show that it could be superior to models measuring (x) factors implicated in the prognosis, with a multifactorial and parameter analysis.

Best regards

Didier

PS but perhaps hadn't I understood your preoccupation ?

http://www.sciencedirect.com/science/article/pii/S0090825810001800