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Dynamics of preventive vs post-diagnostic cancer control using low-impact measures.

Akhmetzhanov AR, Hochberg ME - Elife (2015)

Bottom Line: Cancer poses danger because of its unregulated growth, development of resistance, and metastatic spread to vital organs.We then compare and contrast preventive and post-diagnostic interventions assuming that only a single lesion progresses to invasive carcinoma during the life of an individual, and resection either leaves residual cells or metastases are undetected.Whereas prevention generally results in more positive therapeutic outcomes than post-diagnostic interventions, this advantage is substantially lowered should prevention initially fail to arrest tumour growth.

View Article: PubMed Central - PubMed

Affiliation: Institut des Sciences de l'Evolution de Montpellier, University of Montpellier, Montpellier, France.

ABSTRACT
Cancer poses danger because of its unregulated growth, development of resistance, and metastatic spread to vital organs. We currently lack quantitative theory for how preventive measures and post-diagnostic interventions are predicted to affect risks of a life threatening cancer. Here we evaluate how continuous measures, such as life style changes and traditional treatments, affect both neoplastic growth and the frequency of resistant clones. We then compare and contrast preventive and post-diagnostic interventions assuming that only a single lesion progresses to invasive carcinoma during the life of an individual, and resection either leaves residual cells or metastases are undetected. Whereas prevention generally results in more positive therapeutic outcomes than post-diagnostic interventions, this advantage is substantially lowered should prevention initially fail to arrest tumour growth. We discuss these results and other important mitigating factors that should be taken into consideration in a comparative understanding of preventive and post-diagnostic interventions.

No MeSH data available.


Related in: MedlinePlus

Treatments curb or eliminate tumours.Examples of single patient tumour growth for (A) no treatment. (B) σ = 0.6%. (C) σ = 1.0%. (D) σ = 2.0%. The shaded area shows the change in total tumour size and the hatched area, the resistant part of a tumour. The treatment intensity σ in this and all other figures are represented as cell arrest per day (σ/4). Parameter values as in Table 1.DOI:http://dx.doi.org/10.7554/eLife.06266.003
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fig1: Treatments curb or eliminate tumours.Examples of single patient tumour growth for (A) no treatment. (B) σ = 0.6%. (C) σ = 1.0%. (D) σ = 2.0%. The shaded area shows the change in total tumour size and the hatched area, the resistant part of a tumour. The treatment intensity σ in this and all other figures are represented as cell arrest per day (σ/4). Parameter values as in Table 1.DOI:http://dx.doi.org/10.7554/eLife.06266.003

Mentions: Figure 1 shows four examples of numerical experiments. An untreated tumour reaches the assumed detection threshold of 109 cells by about 18 years on average and because it is not subject to strong negative selection (we assume low c), any emerging resistant cell-lines are likely to remain at low frequency (0.03% at the detection time in the example of Figure 1A). In Figure 1B, low-treatment intensity delays tumour growth and thus time of detection by approximately 16 years, while an increase in dose tends to result in tumours dominated by resistant cells (Figure 1C). Despite being unaffected by treatment, resistant cell populations are sometimes observed to go extinct stemming from stochasticity (Figure 1D), and this tends to occur more at high-treatment levels, because there are fewer sensitive tumour cells to seed new (mutant) resistant cell populations.10.7554/eLife.06266.003Figure 1.Treatments curb or eliminate tumours.


Dynamics of preventive vs post-diagnostic cancer control using low-impact measures.

Akhmetzhanov AR, Hochberg ME - Elife (2015)

Treatments curb or eliminate tumours.Examples of single patient tumour growth for (A) no treatment. (B) σ = 0.6%. (C) σ = 1.0%. (D) σ = 2.0%. The shaded area shows the change in total tumour size and the hatched area, the resistant part of a tumour. The treatment intensity σ in this and all other figures are represented as cell arrest per day (σ/4). Parameter values as in Table 1.DOI:http://dx.doi.org/10.7554/eLife.06266.003
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524440&req=5

fig1: Treatments curb or eliminate tumours.Examples of single patient tumour growth for (A) no treatment. (B) σ = 0.6%. (C) σ = 1.0%. (D) σ = 2.0%. The shaded area shows the change in total tumour size and the hatched area, the resistant part of a tumour. The treatment intensity σ in this and all other figures are represented as cell arrest per day (σ/4). Parameter values as in Table 1.DOI:http://dx.doi.org/10.7554/eLife.06266.003
Mentions: Figure 1 shows four examples of numerical experiments. An untreated tumour reaches the assumed detection threshold of 109 cells by about 18 years on average and because it is not subject to strong negative selection (we assume low c), any emerging resistant cell-lines are likely to remain at low frequency (0.03% at the detection time in the example of Figure 1A). In Figure 1B, low-treatment intensity delays tumour growth and thus time of detection by approximately 16 years, while an increase in dose tends to result in tumours dominated by resistant cells (Figure 1C). Despite being unaffected by treatment, resistant cell populations are sometimes observed to go extinct stemming from stochasticity (Figure 1D), and this tends to occur more at high-treatment levels, because there are fewer sensitive tumour cells to seed new (mutant) resistant cell populations.10.7554/eLife.06266.003Figure 1.Treatments curb or eliminate tumours.

Bottom Line: Cancer poses danger because of its unregulated growth, development of resistance, and metastatic spread to vital organs.We then compare and contrast preventive and post-diagnostic interventions assuming that only a single lesion progresses to invasive carcinoma during the life of an individual, and resection either leaves residual cells or metastases are undetected.Whereas prevention generally results in more positive therapeutic outcomes than post-diagnostic interventions, this advantage is substantially lowered should prevention initially fail to arrest tumour growth.

View Article: PubMed Central - PubMed

Affiliation: Institut des Sciences de l'Evolution de Montpellier, University of Montpellier, Montpellier, France.

ABSTRACT
Cancer poses danger because of its unregulated growth, development of resistance, and metastatic spread to vital organs. We currently lack quantitative theory for how preventive measures and post-diagnostic interventions are predicted to affect risks of a life threatening cancer. Here we evaluate how continuous measures, such as life style changes and traditional treatments, affect both neoplastic growth and the frequency of resistant clones. We then compare and contrast preventive and post-diagnostic interventions assuming that only a single lesion progresses to invasive carcinoma during the life of an individual, and resection either leaves residual cells or metastases are undetected. Whereas prevention generally results in more positive therapeutic outcomes than post-diagnostic interventions, this advantage is substantially lowered should prevention initially fail to arrest tumour growth. We discuss these results and other important mitigating factors that should be taken into consideration in a comparative understanding of preventive and post-diagnostic interventions.

No MeSH data available.


Related in: MedlinePlus