Key Clinical Implications Based on
How an Advanced Cancer Evolves
H. Jack West, MD
Cancer Evolves and Adapts
• A cancer is especially prone to developing new, potentially
adaptive mutations as it grows and...
The Efficacy of Anti-Cancer Treatment
Diminishes Over Time
• Over the course of treatment, the efficacy of treatment is
gr...
Implications for Advanced
Cancer Treatment
• When a cancer cannot be entirely removed
or radiated, treatment is typically ...
Cancer Can Become More
Aggressive Over Time
• We use the observed pace of the
cancer to predict the future behavior
of tha...
The Challenge of Treating an Incurable
Cancer as it Becomes More Resistant
Tumor
burden
Time
First line
treatment
Maintena...
For questions, comments, and
further information, check out
CancerGRACE.org
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Key Clinical Implications of how a Cancer Evolves

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Cancer adapts and evolves over time and under the selective pressure of systemic treatment, becoming increasingly resistant over time. This brief slidedoc fo summarizes key points in how cancer adaptation leads to resistance and changes our treatment recommendations.

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Key Clinical Implications of how a Cancer Evolves

  1. 1. Key Clinical Implications Based on How an Advanced Cancer Evolves H. Jack West, MD
  2. 2. Cancer Evolves and Adapts • A cancer is especially prone to developing new, potentially adaptive mutations as it grows and divides faster and less well controlled than normal cells. • Cancer typically follows a pattern of being most responsive to treatment early, then becomes more resistant over time, as mutated, resistant cancer cells grow under “selective pressure” of the anticancer therapy. • Cancer is caused by a collection of mutations in a cell that lead to loss of control of the cell growth process, typically a combination of faster growth & cell division along with loss of inhibitory controls.
  3. 3. The Efficacy of Anti-Cancer Treatment Diminishes Over Time • Over the course of treatment, the efficacy of treatment is greatest early on, as the treatment kills a greater proportion of the cancer cells. For many cancers, even a very effective systemic therapy kills a proportion but not all of a cancer. • As treatment continues, a greater proportion of the cancer cells that remain are resistant to that therapy. As the sensitive cells die, the remaining ones grow, leaving more of the cancer newly resistant to the same treatment that was effective previously. Sensitive cancer cell Resistant cancer cell Time/Ongoing treatment Untreated Cancer Partial Response Progression with Resistance
  4. 4. Implications for Advanced Cancer Treatment • When a cancer cannot be entirely removed or radiated, treatment is typically with the most effective systemic (whole body) therapy, producing the greatest tumor shrinkage early on. • In advanced lung cancer, for example, initial chemotherapy treatment is typically 4-6 cycles, when it reaches a point of diminishing returns. • Beyond that point, we often offer a break from treatment or transition to a less intensive maintenance therapy that is not likely to further shrink the cancer but can control it and slow the time before it progresses. • Over time, the cancer develops acquired resistance to ongoing treatment and requires a change to a different approach to which the cancer cells may be more sensitive.
  5. 5. Cancer Can Become More Aggressive Over Time • We use the observed pace of the cancer to predict the future behavior of that cancer. • Some cancers are very aggressive and grow quickly. Some are much more indolent and grow slowly. • A cancer can gradually or suddenly develop a new mutation and change its behavior. Under the microscope, a biopsy may show a change from well to poorly differentiated as it changes from clinically indolent to more aggressive. Well differentiated adenocarcinoma Poorly differentiated adenocarcinoma
  6. 6. The Challenge of Treating an Incurable Cancer as it Becomes More Resistant Tumor burden Time First line treatment Maintenance Second line Third line • As treatment continues and a patient experiences cumulative side effects and more weakness from growing cancer, risks of further treatment grow. • As treatment continues and the cancer becomes more resistant, treatment works less effectively and for a shorter period with ongoing lines of treatment. Side effects • At a point that varies from patient to patient, further treatment is more likely to cause harm than benefit. It is appropriate to favor a transition to symptomatic care exclusively at that time.
  7. 7. For questions, comments, and further information, check out CancerGRACE.org
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