0360.3016/90 $3.00 + .X3 Copyright 0 1990 Pergamon Press plc
l Editorial
ARE CANCER
RESEARCHERS
SPEAKING
THE SAME
LANGUAGE?
THOMAS F. PAJAK, PH.D. AND CLARE E. GUSE, M.S. Parsonand his colleagues (1) should be commended for exposing the problem concerning the lack of uniform definition for the term “local control rate” in the radiotherapy literature which is just a symptom of a far more widespread problem throughout the oncology literature. Except for absolute survival where the patient is either alive or dead. investigators have reported on various endpoints, such as NED survival and loco-regional control, but their definitions and methods of estimation often differ widely. For statisticians like ourselves, we would ideally prefer to use only absolute survival because it is the most objective measure of treatment effect. It calls for no interpretation. whereas every other measure calls for varying degrees of subjective interpretation. Although absolute survival avoids the problems of subjective interpretation, it has its own possible problems. Survival is not a good measure in situations where there are highly effective salvage therapies which may produce dramatically prolonged disease control. For example, patients with early Hodgkin’s disease who have failed local field irradiation can be salvaged with combination chemotherapy so successfully now that cures can be obtained in an appreciable number of patients. The other situations where absolute survival may not be a good endpoint occur when a study population with the potential of long survivals die from causes unrelated to cancer therapy. This situation often occurs in trials for men with Stage B and stage C prostate cancer or for individuals with head and neck cancer. Since absolute survival is not a cure-all endpoint, other endpoints
must be used and then the problem of nonuniformity in definitions and estimation techniques must be addressed. Globally, journals such as this one should set guidelines about the definition and estimation of “key” endpoints such as local control. Specifically, papers should be accepted for publication only if local control is defined by the fourth method (time adjusted) described by Parsons et al. in this issue. Until the journals set such guidelines, they should require from the investigators sufficient details about how the endpoints were defined and estimated so that other investigators can apply them to other data sets. The journals should specifically demand a complete accounting of patients who are considered in the analysis as non-failures but have died! The overriding concern here is that the investigators may be tempted to creatively define their endpoints in a way which makes their results look good and perhaps even derive results in p-values less than .05. Parsons er a/. showed two such ways with method B (non-failure rate) and with method C (initial control rate). The short term effect of these methods is the promise of a new improved treatment to offer the cancer patients but in the long term they are actually cheated!
REFERENCE I. Parsons, J. T.; McCarty. P. J.; Rao, P. V.; Mendenhall, W. M.; Million, R. R. On the definition of local control. Int. J. Radiat. Oncol. Biol. Phys. 18:705-706. 1990.
Reprint requests to: Thomas F. Pajak, Ph.D., RTOG. 1101 Market St., 14th Floor, Philadelphia. PA 19107.
Accepted for publication
707
27 September 1989.
l Editorial
ARE CANCER
RESEARCHERS
SPEAKING
THE SAME
LANGUAGE?
THOMAS F. PAJAK, PH.D. AND CLARE E. GUSE, M.S. Parsonand his colleagues (1) should be commended for exposing the problem concerning the lack of uniform definition for the term “local control rate” in the radiotherapy literature which is just a symptom of a far more widespread problem throughout the oncology literature. Except for absolute survival where the patient is either alive or dead. investigators have reported on various endpoints, such as NED survival and loco-regional control, but their definitions and methods of estimation often differ widely. For statisticians like ourselves, we would ideally prefer to use only absolute survival because it is the most objective measure of treatment effect. It calls for no interpretation. whereas every other measure calls for varying degrees of subjective interpretation. Although absolute survival avoids the problems of subjective interpretation, it has its own possible problems. Survival is not a good measure in situations where there are highly effective salvage therapies which may produce dramatically prolonged disease control. For example, patients with early Hodgkin’s disease who have failed local field irradiation can be salvaged with combination chemotherapy so successfully now that cures can be obtained in an appreciable number of patients. The other situations where absolute survival may not be a good endpoint occur when a study population with the potential of long survivals die from causes unrelated to cancer therapy. This situation often occurs in trials for men with Stage B and stage C prostate cancer or for individuals with head and neck cancer. Since absolute survival is not a cure-all endpoint, other endpoints
must be used and then the problem of nonuniformity in definitions and estimation techniques must be addressed. Globally, journals such as this one should set guidelines about the definition and estimation of “key” endpoints such as local control. Specifically, papers should be accepted for publication only if local control is defined by the fourth method (time adjusted) described by Parsons et al. in this issue. Until the journals set such guidelines, they should require from the investigators sufficient details about how the endpoints were defined and estimated so that other investigators can apply them to other data sets. The journals should specifically demand a complete accounting of patients who are considered in the analysis as non-failures but have died! The overriding concern here is that the investigators may be tempted to creatively define their endpoints in a way which makes their results look good and perhaps even derive results in p-values less than .05. Parsons er a/. showed two such ways with method B (non-failure rate) and with method C (initial control rate). The short term effect of these methods is the promise of a new improved treatment to offer the cancer patients but in the long term they are actually cheated!
REFERENCE I. Parsons, J. T.; McCarty. P. J.; Rao, P. V.; Mendenhall, W. M.; Million, R. R. On the definition of local control. Int. J. Radiat. Oncol. Biol. Phys. 18:705-706. 1990.
Reprint requests to: Thomas F. Pajak, Ph.D., RTOG. 1101 Market St., 14th Floor, Philadelphia. PA 19107.
Accepted for publication
707
27 September 1989.
