| کلیدواژههای انگلیسی مقاله |
Cure model, Rectal neoplasms, Recurrence, Lymph node ratio, Survival, What&,rsquo s Known Understanding the prognostic factors affecting recurrence-free survival of patients with rectal cancer is the mainstay of care. Prognostic factors such as age, sex, genetic factors, pathologic variables, surgical techniques, and neoadjuvant therapy have been shown to affect the recurrence-free survival of patients with rectal cancer. What&,rsquo s New The factors affecting short-term recurrence-free survival of patients with rectal cancer might be different from those affecting long-term recurrence-free survival. A lower body mass index was related to a poorer prognosis in patients with rectal cancer. Early diagnosis leads to a lower tumor-node-metastasis stage and could increase the probability of long-term recurrence-free survival. IntroductionColorectal cancer (CRC) is the third most common malignancy in the world and the leading cause of cancer-related deaths in women after breast cancer. 1,- 4, Rectal cancer (RC) constitutes one-third of all CRC cases. 1,, 3,, 4, Age, family history of RC, and Western lifestyle have been reported as the major risk factors of RC. 5, The epidemiology and treatment methods of RC have been continuously changing over time. 1,, 2, To date, neoadjuvant chemoradiotherapy following total mesorectal excision (TME) is considered the standard treatment for locally advanced RC. 6,, 7, Locally advanced RC is associated with a high risk of local recurrence (LR) and metastasis. 7,- 9, Dissemination of the disease and recurrence have been reported as the leading causes of death in patients with RC. 10, Several studies have been conducted to specify the factors affecting recurrence in patients with RC. 11,, 12, Most of these studies have mainly used the Cox-adjusted regression model for data analysis. In some of these studies, a large plateau on the estimated Kaplan-Meier curve indicated that a high percentage of patients did not experience the desired outcome at the end of the follow-up. Therefore, the multivariate cure model analysis might be more appropriate than the traditional Cox regression models provided that the follow-up period is long enough. Note that the hypothesis of a sufficient follow-up period is evaluated using the non-parametric &,alpha _n-test. The two basic categories of cure models are non-mixture and mixture models. 13,, 14, The benefit of mixture models over the Cox-adjusted regression model is the ability to separately seek for the effects of various factors on both short- and long-term survivals.To the best of our knowledge, no studies have been conducted on short- and long-term recurrence-free survival (RFS) of patients with RC using multivariate cure models. Hence, the present study aimed to examine the impact of a wide range of clinical and pathological variables on RC recurrence in short-term (uncured cases) and long-term (cured cases) survivors. Patients and MethodsThe current historic cohort survey aimed to assess the data of 376 patients with RC, collected during 2007-2017 at the Colorectal Research Center affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. This research center also gathered data from two other main referral centers for surgical/palliative treatment of CRC in Shiraz, Southern Iran (Colorectal Surgery Department of Shahid Faghihi Hospital and Radiotherapy Department of Nemazee Hospital).Tumor-node-metastasis (TNM) staging is the most accepted classification system to define rectal tumor invasion and its prognostic implication. 9, LR was defined as histologically, radiologically, and clinically ascertained tumor regrowth in the pelvis. 9, All patients were diagnosed as new cases of RC and those with malignant lesions in the anal canal were enrolled in the study. The exclusion criteria were suffering from simultaneous malignancies of the colon and rectum or metastatic recurrence, those presented with recurrent cancer at the time of diagnosis, and loss to follow-up. Besides, cases with a considerable amount of missing data were excluded from the analysis. In cases where patients did not have any recurrences during the follow-up period, the interval between TME and the end of follow-up was considered the censored time. Concerning the method of treatment, some patients received neoadjuvant chemoradiotherapy, some had adjuvant radiotherapy after surgery, and others did not receive radiotherapy at all. Regarding follow-up, visits were scheduled according to the protocols of both the colorectal surgery and radiotherapy departments, which required patients to be followed up every three months during the first year, every six months during the second year, and then annually. The last update of the follow-up protocol was performed in December 2017. The study was approved by the Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran (code, IR.SUMS.REC.1395.S1103).The probability of RFS in patients with RC was estimated using the Kaplan-Meier curve. The log-rank test was used to compare different groups of categorical variables of survival. Additionally, the mixture cure model was applied to calculate the percentage of patients with RC without recurrence (cured cases) and the probability of RFS among those with recurrence (uncured cases). The cure model is a mixed model the Cox proportional and the logit models were used to model short- and long-term survival, respectively. The estimated cure rate could be immediately determined by long-term survival. The empirical cure rate (the ratio of individuals without recurrence at the end of the follow-up period) was calculated. The selection of variables for modeling was based on the clinical significance and statistical tests. If the P value of the desired factor was &,lt 0.2 in the univariate cure model, that factor was a candidate for the multivariate cure model. All statistical analyses were performed using the smcure package in R 3.5.1 (2018-07-02) software. P&,lt 0.05 was considered statistically significant. ResultsOut of 376 eligible patients with RC who were followed up during 2007-2017 (approximately 112 months), 157 (41.8%) patients were female (figure 1,). A total of 283 (75.3%) patients with RC did not have a recurrence, while the remaining patients (24.7%) had. As a result, the empirical cure rate over a 9-year follow-up period was 75.3%. The mean age and body mass index (BMI) of the patients were 57.0&,plusmn 13.8 years (range, 23-94) and 23.6&,plusmn 3.6 kg/m2 (range, 15.6-35.8), respectively. The mean survival time was 49 months (range, 3-112). Demographic characteristics, radiological and pathological findings of the patients with RC and their effects on RFS are presented in tables 1, and 2,. As shown, abdominal pain (P=0.011), TNM stage (P&,lt 0.001), and CT-scan detected pelvic lymph nodes involvement (P=0.017) had a significant impact on the overall RFS of the patients with RC.Figure 1. Flow diagram indicates the selection process of the patients. No recurrence n (%)Recurrence n (%)P value*,SexMale166 (44.2)53 (14.1)0.630Female117 (31.0)40 (10.7)Age (years)&,lt 50 75 (20.0)29 (7.7)0.470&,ge 50 208 (55.3)64 (17.0)BMI (Kg/m2)&,lt 25204 (54.3)74 (19.7)0.155&,ge 25 79 (21.0)19 (5.0)FHX of CRCNo238 (63.3)83 (22.0)0.195Yes45 (12.0)10 (2.7)FHX of OMNo218 (58.0)74 (19.7)0.737Yes65 (17.3)19 (5.0)*Log-rank statistic P&,lt 0.05 was considered significant BMI, Body mass index, FHX of CRCs, Family history of colorectal cancer, FHX of OM, Family history of other malignancies |
| نویسندگان مقاله |
Seyed Vahid Hosseini |
Colorectal Research Center, Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
Abbas Rezaianzadeh |
Colorectal Research Center, Department of Epidemiology, Shiraz University of Medical Sciences, Shiraz, Ira
Salar Rahimikazerooni |
Colorectal Research center, Shiraz University of Medical Sciences, Shiraz, Iran
Leila Ghahramani |
Colorectal Research Center, Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
Alimohammad Bananzadeh |
Colorectal Research Center, Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
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