As cancer therapy has progressed dramatically, its goal has shifted toward cure of the disease (curative therapy) rather than prolongation of time to death (life-prolonging therapy). Consequently, the proportion of cu...As cancer therapy has progressed dramatically, its goal has shifted toward cure of the disease (curative therapy) rather than prolongation of time to death (life-prolonging therapy). Consequently, the proportion of cured patients (c) has become an important measure of the long-term survival benefit derived from therapy. In 1949, Boag addressed this issue by developing the parametric log-normal cure model, which provides estimates of c and m where m is the mean of log times to death from cancer among uncured patients. Unfortunately, traditional methods based on the proportional hazards model like the Cox regression and log-rank tests cannot provide an estimate of either c or m. Rather, these methods estimate only the differences in hazard between two or more groups. In order to evaluate the long-term validity and usefulness of the parametric cure model compared with the proportional hazards model, we reappraised randomized controlled trials and simulation studies of breast cancer and other malignancies. The results reveal that: 1) the traditional methods fail to distinguish between curative and life-prolonging therapies;2) in certain clinical settings, these methods may favor life-prolonging treatment over curative treatment, giving clinicians a false estimate of the best regimen;3) although the Boag model is less sensitive to differences in failure time when follow-up is limited, it gains power as more failures occur. In conclusion, unless the disease is always fatal, the primary measure of survival benefit should be c rather than m or hazard ratio. Thus, the Boag lognormal cure model provides more accurate and more useful insight into the long-term benefit of cancer treatment than the traditional alternatives.展开更多
Background: To evaluate the effect of follow-up length on the outcome of breast cancer patients, we compared the 50- and 25-year follow-up results in terms of cure rate, overall mortality and mortalities from breast c...Background: To evaluate the effect of follow-up length on the outcome of breast cancer patients, we compared the 50- and 25-year follow-up results in terms of cure rate, overall mortality and mortalities from breast cancer, second cancer, and benign diseases. Methods: 763 patients treated for breast cancer between February 1953 and September 1976, were followed up until December 2014. They were divided into two cohorts;earlier cohort exclusively underwent radical mastectomy plus adjuvant radiotherapy, while later cohort had radical mastectomy alone. Assuming that in all patients follow-up was terminated at 50 or 25 years after diagnosis, likelihood ratio test and stratified Log-rank tests were performed to evaluate the differences in cure rate and overall survival between the two cohorts. Results: During the 50 years, radical mastectomy alone compared with radical mastectomy plus adjuvant radiotherapy is associated with a significantly higher cure rate, and higher survivals regardless of whether the death was from breast cancer, second cancer, benign causes or any causes. However, if follow-up information is limited to 25 years, the advantage of radical mastectomy alone is partly offset and the survival difference between the two cohorts becomes less significant. Conclusion: Radiotherapy to breast cancer may adversely affect not only mortality from breast cancer, but mortalities unrelated to breast cancer. Since such deaths occur later, they may fail to be detected unless follow-up is long enough. Thus, deleterious effects of radiotherapy may be underestimated. Exceedingly long follow-up is required to accurately estimate the cure rate and the long-term effect of radiotherapy.展开更多
文摘As cancer therapy has progressed dramatically, its goal has shifted toward cure of the disease (curative therapy) rather than prolongation of time to death (life-prolonging therapy). Consequently, the proportion of cured patients (c) has become an important measure of the long-term survival benefit derived from therapy. In 1949, Boag addressed this issue by developing the parametric log-normal cure model, which provides estimates of c and m where m is the mean of log times to death from cancer among uncured patients. Unfortunately, traditional methods based on the proportional hazards model like the Cox regression and log-rank tests cannot provide an estimate of either c or m. Rather, these methods estimate only the differences in hazard between two or more groups. In order to evaluate the long-term validity and usefulness of the parametric cure model compared with the proportional hazards model, we reappraised randomized controlled trials and simulation studies of breast cancer and other malignancies. The results reveal that: 1) the traditional methods fail to distinguish between curative and life-prolonging therapies;2) in certain clinical settings, these methods may favor life-prolonging treatment over curative treatment, giving clinicians a false estimate of the best regimen;3) although the Boag model is less sensitive to differences in failure time when follow-up is limited, it gains power as more failures occur. In conclusion, unless the disease is always fatal, the primary measure of survival benefit should be c rather than m or hazard ratio. Thus, the Boag lognormal cure model provides more accurate and more useful insight into the long-term benefit of cancer treatment than the traditional alternatives.
文摘Background: To evaluate the effect of follow-up length on the outcome of breast cancer patients, we compared the 50- and 25-year follow-up results in terms of cure rate, overall mortality and mortalities from breast cancer, second cancer, and benign diseases. Methods: 763 patients treated for breast cancer between February 1953 and September 1976, were followed up until December 2014. They were divided into two cohorts;earlier cohort exclusively underwent radical mastectomy plus adjuvant radiotherapy, while later cohort had radical mastectomy alone. Assuming that in all patients follow-up was terminated at 50 or 25 years after diagnosis, likelihood ratio test and stratified Log-rank tests were performed to evaluate the differences in cure rate and overall survival between the two cohorts. Results: During the 50 years, radical mastectomy alone compared with radical mastectomy plus adjuvant radiotherapy is associated with a significantly higher cure rate, and higher survivals regardless of whether the death was from breast cancer, second cancer, benign causes or any causes. However, if follow-up information is limited to 25 years, the advantage of radical mastectomy alone is partly offset and the survival difference between the two cohorts becomes less significant. Conclusion: Radiotherapy to breast cancer may adversely affect not only mortality from breast cancer, but mortalities unrelated to breast cancer. Since such deaths occur later, they may fail to be detected unless follow-up is long enough. Thus, deleterious effects of radiotherapy may be underestimated. Exceedingly long follow-up is required to accurately estimate the cure rate and the long-term effect of radiotherapy.
