Cancer: A medical emergency.
Over the last decade clinical trials have established the effectiveness of adjuvant chemotherapy in eradicating micrometastases in many different cancers, including breast, colon, and lung. This success stands in sharp contrast to our failure to cure clinically evident metastatic cancer. These dramatic polarities illustrate the critical importance of treatment timing if residual cancer is to be eradicated. Adjuvant chemotherapy is started only after recovery from surgery, a period of time that can exceed 30 days. During this time any cancer that remains after surgery will continue to divide. Although adjuvant chemotherapy has proven effective despite this time delay, there are reasons, both conceptual and quantitative, to think that its effectiveness could be magnified by a more prompt administration. The extent of this magnification is mathematically modeled in this paper. Surgery and the process of wound healing after surgery create a very favorable environment for the growth of the metastatic clone. Surgery can increase the number of circulating tumor cells and induce an immunosuppressive effect that might facilitate metastatic spread. And the process of wound healing can stimulate growth factors that have been shown to accelerate tumor cell growth. This situation is a double-edged sword. Although the metastatic clone should proliferate rapidly during this time, it should also, at least theoretically, be more sensitive to the effects of chemotherapy as more cells are pushed into a cycling phase. We derive a mathematical model based upon empirical data predicting that the effectiveness of a given chemotherapeutic regimen is inversely proportional to the tumor burden that has to be eradicated, which, in turn, is a function of when chemotherapy is started after surgery. Although the critical importance of timing in the treatment of cancer is intuitive, this knowledge has not yet been fully translated into the clinical practice of medical oncology. If the model presented is accurate, many people are dying unnecessarily of their cancer today because we are waiting too long after surgery to use highly effective chemotherapies, following well-trod clinical paths and established paradigms for how cancer should be treated.
Harless
William
W
Department of Hematology and Oncology, West Virginia University, P.O. Box 9162, Mary Babb Randolph Cancer Center, Morgantown, WV 26506-9162, USA.
Qiu
Yang
Y
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division; D019049:Developed Countries / Q000706:statistics & numerical data; D004630:Emergencies; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000401:mortality / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery / Q000628:therapy*; D014945:Wound Healing
D000970:Antineoplastic Agents