DOI:10.2214/AJR.06.5076
AJR 2006; 187:W552
© American Roentgen Ray Society
Measuring Hepatic Metastases to Colon Cancer
Lawrence H. Schwartz,
David M. Panicek and
Madhu Mazumdar
Memorial Sloan-Kettering Cancer Center New York, NY 10021
Weill Medical College of Cornell University New York, NY
10021
WEBThis is a Web exclusive article.
We read with both interest and dismay the recent article by Zacharia et al.
[1] reporting on the minimum
number of hepatic metastases from colon cancer required to be measured to
appropriately gauge a patient's response to therapy. Although we share the
authors' keen interest in this topic and their motivation for potentially
decreasing the number of lesions that must be measured, we have substantial
concerns about the methodology used in their study and the conclusions that
were drawn.
In the Materials and Methods section, the authors state that 30 consecutive
patients with metastatic colon cancer were recruited for this study from a
larger cohort enrolled in a multi-institutional trial; only patients with a
minimum of five well-defined, nonconfluent, and nonnecrotic liver metastases
were eligible for inclusion in the study. The resulting study population was
thus highly selective, and the lesion assessment reflective neither of the
goal of the RECIST criteria nor of the vast majority of therapeutic
trials-which, namely, is to assess the response to therapy in an entire
patient, not just in one organ. In colon cancer, metastases often occur in
various nonhepatic sites, such as lung and lymph nodes; disease in all sites
must be measured to gauge the response to therapy. Thus, assessing therapeutic
response only on the basis of hepatic metastases would not be valid in many
patients with metastatic colon cancer.
Also, even if one elected to assess the minimum number of lesions to be
measured only in the liver, the lesion selection criteria chosen by the
authors are quite biased because lesions were selected only if well-defined,
nonconfluent, and nonnecrotic. In colon cancer (as well as many other primary
tumors), liver metastases frequently are ill-defined, confluent, and necrotic.
The selection of only homogeneous metastases thus favored "easier"
measurements, and it is not at all surprising that the number of such lesions
that needed to be measured was low. The authors' conclusion that only one
liver metastasis must be measured (and in only one dimension) cannot be
generalized to the common, real-world situation in which liver metastases from
colon cancer are typically ill-defined, confluent, or necrotic.
The authors understate the conclusions of our research on this topic
[2], in which we evaluated the
critical issue of variance, using both unidimensional (RECIST) and
bidimensional (World Health Organization [WHO]) criteria in response
assessment. Our conclusions about the number of tumor deposits (selected from
all sites of metastases) that needed to be measured were applicable to either
RECIST or WHO criteria, and were based upon the particular level of variance
that would be acceptable for the purposes of a specific study or clinical
trial. Moreover, the authors seem to have overlooked our theoretical
derivation [3], in which we
provided a formula for calculating the incremental increase in variability
that results when a subset of tumors, rather than all available tumors, is
selected for measurement. The number of lesions selected to be measured
depends in large part upon the percentage of variability in response
assessment that is acceptable (or unacceptable) for a given purpose: The less
variability that is acceptable, the larger the number of lesions that will
have to be measured.
Because the authors reached their conclusions on the basis of an
artificial, highly selective subset of patients with nonrepresentative hepatic
metastases, and because measurement of hepatic lesions alone does not
constitute overall response assessment for a patient, those conclusions cannot
be generalized to all patients with metastatic colon cancer. Thus, the
authors' final statement in the Discussion section that "This fact has
significant clinical implications and needs to be applied in routine oncologic
practice and pharmaceutical trials" far oversteps its actual scientific
underpinnings, and we caution anyone from implementing this
recommendation.
References
- Zacharia TT, Saini S, Halpern EF, Sumner JE. CT of colon cancer
metastases to the liver using modified RECIST criteria: determining the ideal
number of target lesions to measure. AJR2006; 186:1067
-1070[Abstract/Free Full Text]
- Schwartz LH, Mazumdar M, Brown W, Smith A, Panicek DM. Variability
in response assessment in solid tumors: effect of number of lesions chosen for
measurement. Clin Cancer Res 2003;9
: 4318-4323[Abstract/Free Full Text]
- Mazumdar M, Smith A, Debroy PP, Schwartz LH. A theoretical approach
to choosing the minimum number of multiple tumors required for assessing
treatment response. J Clin Epidemiol2005; 58:150
-153[CrossRef][Medline]

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