- Email: [email protected]
Regarding the Article “Thrombocytosis As a Predictor of Distant Recurrence in Patients with Rectal Cancer”
Archives of Medical Research 44 (2013) 77e78
LETTER TO THE EDITOR
Regarding the Article ‘‘Thrombocytosis As a Predictor of Distant Recurrence in Patients with Rectal Cancer’’ To the Editor:
Frequently I read with pleasure and interest Archives of Medical Research, especially in regard to the paper published recently about thrombosis entitled ‘‘Thrombocytosis As a Predictor of Distant Recurrence in Patients with Rectal Cancer’’ (1). In this regard, I would like to address, respectfully, the following observations to you and to the authors. Recent studies have shown an association between the increase of the platelet count and some clinical conditions including malignant tumors, predicting a reduction in the patient survival (2,3). The paper is congruent with medical literature but, in general, has serious methodological inconsistencies; nevertheless I will comment what I consider to be the most important ones. The Introduction does not describe the aim of the study. It undertakes themes that are not part of the study such as cytokines. In the Materials and Methods section there is no information on the total amount of files obtained from the Oncology Hospital and how the selection process resulted in 163 files used in the study. Also, the authors do not emphasize whether these 163 files were complete, for example, if they all had platelet counts of the patients. In the operational definition of thrombocytosis (O350,000), the authors omitted the measurement unit (mL). Also, note that the cut-off point according to previous publications is O400,000 mL. As for the results of this study, it is worth remembering that one of the most important assumptions to apply the proportional hazards regression or Cox model is that risks in both groups must be proportional, i.e., the survival curve of one group must always be above the survival curve of the other group. These must not cross. Some important aspects can be noticed in Figure 1: i) risks in the thrombocytosis group (platelets O350,000) are not proportional to the risk of the !350,000 group, ii) both survival curves intersect—in this case a log-rank test should have been applied in order to determine the statistical difference between them. Otherwise, both curves are equal, but if the risks are not proportional, the Wilcoxon test needed to be done, iii) only the thrombocytosis group shows a median survival time—the !350,000 group is not shown because according to the authors this group
had a 5-year survival rate of 81%, and iv) for the group with thrombocytosis (O350,000) the drop in the curve is sudden, as the failure had happened in all patients at the same time. Due to the fact that the risks for both groups are not proportional, it is incorrect to apply the Cox model because one of the compared estimators is the median survival time of both groups. In addition, the authors mention that the multivariate analysis includes all the variables that were significant in the univariate analysis. Table 5 shows the result of the multivariate analysis; nevertheless, the coefficients of the model or the hazards are not shown, just a percentage that matches the figures of the survival analysis section; p values are near to the null value ( p !0.001). In regard to Figure 1, there is a huge variation between both groups that can be verified with the rest of the numbers derived from the univariate analysis, which implies that there is a selection bias. Both groups are completely different, which is why those probability values were obtained.
0188-4409/$ - see front matter. Copyright Ó 2013 IMSS. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.arcmed.2012.11.005
Figure 1. Notes on the survival curves of both study groups.
78
Castillo-Perez / Archives of Medical Research 44 (2013) 77e78
It is well known that the comorbidities associated with other clinical conditions such as colorectal cancer play an important role in the evolution of the patient and it is interesting that there were no statistically significant differences. On the other hand, the authors should have discriminated or adjusted the model for both treatments (radiotherapy and chemotherapy) and the doses used because these modify the cell count. In some cases, the patients receive a combined treatment, which has been observed to be more efficient. Results seem tendentious because the only variables of interest for the authors resulted as being significant and were discussed in the paper. In the Discussion section, authors comment on a more immunological approach than the one stated in the title of the paper. They dedicate only one paragraph in the Results section and in the Discussion to the recurrence of rectal cancer when they should have centered the analysis and results on this topic. It would be highly useful to have information on the selection process of files in order to know if the characteristics of both groups are different. In this regard, we propose a more appropriate statistical analysis according to this specific medical condition, perhaps a semiparametric Bayesian analysis of survival data. For the observations made in regard to the Discussion, I consider it important to focus the discussion on the objective of the study and to incorporate the immunological information to the results of the study. Finally, the authors approach a topic important for clinical practice. Among the research efforts of the Instituto
Mexicano del Seguro Social, there are few studies and lines of research in regard to this topic with the principal purpose of prolonging the life of the patients. References 1. Cravioto-Villanueva A, Luna-Perez P, Gutierrez-de la Barrera M, et al. Thrombocytosis as a predictor of distant recurrence in patients with rectal cancer. Arch Med Res 2012;43:305e311. 2. Gucer F, Moser F, Tamussino K, et al. Thrombocytosis as a prognostic factor in endometrial carcinoma. Gynecol Oncol 1998;70: 210e214. 3. Suppiah R, Shaheen PE, Elson P, et al. Thrombocytosis as a prognostic factor for survival in patients with metastatic renal cell carcinoma. Cancer 2006;107:1793e1800.
JUAN CASTILLO-PEREZ JOSE Division de Evaluacion de la Investigacion Coordinacion de Investigacion en Salud, IMSS Mexico, D.F., Mexico Address reprint requests to: Jose Juan Castillo-Perez IMSS, Coordinacion de Investigacion en Salud Division de Evaluacion de la Investigacion Av. Cuauhtemoc 330. Col. Doctores C.P. 06725 Unidad de Congresos Bloque B, 4th floor Mexico, D.F., Mexico Phone: (þ52) (55) 5627-6900 Ext. 21223 E-mail: [email protected] Received for publication October 18, 2012; accepted October 29, 2012 (ARCMED-D-12-00596).
LETTER TO THE EDITOR
Regarding the Article ‘‘Thrombocytosis As a Predictor of Distant Recurrence in Patients with Rectal Cancer’’ To the Editor:
Frequently I read with pleasure and interest Archives of Medical Research, especially in regard to the paper published recently about thrombosis entitled ‘‘Thrombocytosis As a Predictor of Distant Recurrence in Patients with Rectal Cancer’’ (1). In this regard, I would like to address, respectfully, the following observations to you and to the authors. Recent studies have shown an association between the increase of the platelet count and some clinical conditions including malignant tumors, predicting a reduction in the patient survival (2,3). The paper is congruent with medical literature but, in general, has serious methodological inconsistencies; nevertheless I will comment what I consider to be the most important ones. The Introduction does not describe the aim of the study. It undertakes themes that are not part of the study such as cytokines. In the Materials and Methods section there is no information on the total amount of files obtained from the Oncology Hospital and how the selection process resulted in 163 files used in the study. Also, the authors do not emphasize whether these 163 files were complete, for example, if they all had platelet counts of the patients. In the operational definition of thrombocytosis (O350,000), the authors omitted the measurement unit (mL). Also, note that the cut-off point according to previous publications is O400,000 mL. As for the results of this study, it is worth remembering that one of the most important assumptions to apply the proportional hazards regression or Cox model is that risks in both groups must be proportional, i.e., the survival curve of one group must always be above the survival curve of the other group. These must not cross. Some important aspects can be noticed in Figure 1: i) risks in the thrombocytosis group (platelets O350,000) are not proportional to the risk of the !350,000 group, ii) both survival curves intersect—in this case a log-rank test should have been applied in order to determine the statistical difference between them. Otherwise, both curves are equal, but if the risks are not proportional, the Wilcoxon test needed to be done, iii) only the thrombocytosis group shows a median survival time—the !350,000 group is not shown because according to the authors this group
had a 5-year survival rate of 81%, and iv) for the group with thrombocytosis (O350,000) the drop in the curve is sudden, as the failure had happened in all patients at the same time. Due to the fact that the risks for both groups are not proportional, it is incorrect to apply the Cox model because one of the compared estimators is the median survival time of both groups. In addition, the authors mention that the multivariate analysis includes all the variables that were significant in the univariate analysis. Table 5 shows the result of the multivariate analysis; nevertheless, the coefficients of the model or the hazards are not shown, just a percentage that matches the figures of the survival analysis section; p values are near to the null value ( p !0.001). In regard to Figure 1, there is a huge variation between both groups that can be verified with the rest of the numbers derived from the univariate analysis, which implies that there is a selection bias. Both groups are completely different, which is why those probability values were obtained.
0188-4409/$ - see front matter. Copyright Ó 2013 IMSS. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.arcmed.2012.11.005
Figure 1. Notes on the survival curves of both study groups.
78
Castillo-Perez / Archives of Medical Research 44 (2013) 77e78
It is well known that the comorbidities associated with other clinical conditions such as colorectal cancer play an important role in the evolution of the patient and it is interesting that there were no statistically significant differences. On the other hand, the authors should have discriminated or adjusted the model for both treatments (radiotherapy and chemotherapy) and the doses used because these modify the cell count. In some cases, the patients receive a combined treatment, which has been observed to be more efficient. Results seem tendentious because the only variables of interest for the authors resulted as being significant and were discussed in the paper. In the Discussion section, authors comment on a more immunological approach than the one stated in the title of the paper. They dedicate only one paragraph in the Results section and in the Discussion to the recurrence of rectal cancer when they should have centered the analysis and results on this topic. It would be highly useful to have information on the selection process of files in order to know if the characteristics of both groups are different. In this regard, we propose a more appropriate statistical analysis according to this specific medical condition, perhaps a semiparametric Bayesian analysis of survival data. For the observations made in regard to the Discussion, I consider it important to focus the discussion on the objective of the study and to incorporate the immunological information to the results of the study. Finally, the authors approach a topic important for clinical practice. Among the research efforts of the Instituto
Mexicano del Seguro Social, there are few studies and lines of research in regard to this topic with the principal purpose of prolonging the life of the patients. References 1. Cravioto-Villanueva A, Luna-Perez P, Gutierrez-de la Barrera M, et al. Thrombocytosis as a predictor of distant recurrence in patients with rectal cancer. Arch Med Res 2012;43:305e311. 2. Gucer F, Moser F, Tamussino K, et al. Thrombocytosis as a prognostic factor in endometrial carcinoma. Gynecol Oncol 1998;70: 210e214. 3. Suppiah R, Shaheen PE, Elson P, et al. Thrombocytosis as a prognostic factor for survival in patients with metastatic renal cell carcinoma. Cancer 2006;107:1793e1800.
JUAN CASTILLO-PEREZ JOSE Division de Evaluacion de la Investigacion Coordinacion de Investigacion en Salud, IMSS Mexico, D.F., Mexico Address reprint requests to: Jose Juan Castillo-Perez IMSS, Coordinacion de Investigacion en Salud Division de Evaluacion de la Investigacion Av. Cuauhtemoc 330. Col. Doctores C.P. 06725 Unidad de Congresos Bloque B, 4th floor Mexico, D.F., Mexico Phone: (þ52) (55) 5627-6900 Ext. 21223 E-mail: [email protected] Received for publication October 18, 2012; accepted October 29, 2012 (ARCMED-D-12-00596).