Esophageal carcinoma is a highly aggressive neoplasm and is the eighth most common cancer worldwide [
Highly malignant tumors usually grow rapidly and metabolize actively and even lead to progressive body consumption and weight loss at diagnosis. This poor physical condition will hinder the treatment process, thereby affecting the survival. Excessive pretreatment weight loss has been shown to have an adverse effect on the survival outcome in many cancers, such as pancreatic cancer [
Until now, however, the impact of initial BMI on the survival of esophageal carcinoma patients remains contradictory [
The medical records of 189 consecutive nonmetastatic esophageal carcinoma patients treated in the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2012 and December 2013, were reviewed. The diagnosis of esophageal carcinoma was made based on postoperative pathological examination. The inclusion criteria were as follows: (1) being newly diagnosed with squamous cell carcinoma; (2) being with nonmetastatic disease; (3) undergoing radical surgery followed by adjuvant chemotherapy. The exclusion criteria were as follows: (1) being without weight measurements at 6 months before diagnosis, at baseline, after surgery, and/or at the end of chemotherapy; (2) age > 70 years; (3) being without postoperative chemotherapy treatment; (4) being with any other cancers; (5) nonsquamous cell carcinoma. A total of 121 patients were included based on the criteria. This study was approved by the institutional review board (IRB) of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, and written informed consent was waived by the IRB due to the retrospective nature of this study. All the data were analyzed anonymously.
Patient weight was recorded at the initial visit and weekly during hospitalization. Pretreatment weight loss was defined as unintentional weight loss during the 6 months before diagnosis. Preoperation weight was measured at the initial visit, and the final weight was recorded within 3 days before the final administration of chemotherapy. Weight loss during the whole treatment was defined as the difference between the preoperation weight and the final weight. Body mass index (BMI) was defined as the weight (kg) before the first chemotherapy divided by the square of height (meters) and was categorized according to the WHO recommendations for Asian populations [
All patients underwent transthoracic esophagectomy accompanied by mobilization of the stomach. The gastric tube was pulled up through the postmediastinal or retrosternal route, and a cervical or intrathoracic esophagogastric anastomosis was created. Total mediastinal and upper abdominal lymphadenectomy was routinely performed. Pathologic stage was determined according to the American Joint Committee on Cancer (AJCC) Staging System, 7th edition [
Adjuvant chemotherapy was carried out at 2–6 weeks after operation, consisting of docetaxel and oxaliplatin for 3–6 cycles, 4 weeks/cycle. 20 patients received only 1-2 cycles.
After treatment completion, patients were followed up monthly in the first 3 months, then every 3 months during the first 3 years, and then every 6 months during the next 2 years. The duration of follow-up was calculated from the completion of treatment to the final visit or death. The final follow-up was on August 1, 2016.
Data was analyzed using IBM SPSS Version 20 (SPSS Statistics V20, IBM Corporation, Somers, New York). The Chi-square test and Fisher’s exact test (for expected value < 5) were used to compare ordinal and categorical variables. Due to the limited sample size, the pT stage was divided into T1-2 and T3-4; the pN stage was divided into N0, N1, and N2-3; the location of the primary lesion was divided into superior, middle, and inferior thoracic ones, and the cervical primary subgroup was combined with the superior thoracic subgroup. The overall survival rate (OS) was estimated using the Kaplan-Meier method and the differences in survival curves were compared by the log-rank test. Univariate and multivariate Cox proportional hazards models were used to evaluate the survival results of the weight loss or BMI-based subgroups with covariates including age, sex, pT stage, pN stage, the location of the tumor, and pathological classification. An independent variable with significance in both univariate and multivariate analyses would be recognized as an associated factor of survival outcome. Two-tailed
A total of 121 patients with nonmetastatic esophageal carcinoma were included. The demographic and clinical characteristics were summarized in Table
Characteristics of the 121 patients with esophageal carcinoma enrolled in this study.
Characteristics | Pre-LWL | Pre-HWL |
|
LWL | HWL |
|
UW | NW | OW |
|
---|---|---|---|---|---|---|---|---|---|---|
Total | 54 | 67 | 30 | 91 | 14 | 86 | 21 | |||
Gender | 0.732 | 0.432 | 0.407 | |||||||
Male | 43 | 55 | 26 | 72 | 13 | 68 | 17 | |||
Female | 11 | 12 | 4 | 19 | 1 | 18 | 4 | |||
Age (years) | 0.043 | 0.082 | 0.353 | |||||||
<55 | 19 | 37 | 18 | 38 | 9 | 38 | 9 | |||
≥55 | 35 | 30 | 12 | 53 | 5 | 48 | 12 | |||
T stage |
0.020 | <0.001 | <0.001 | |||||||
T1-2 | 23 | 15 | 1 | 37 | 0 | 25 | 13 | |||
T3-4 | 31 | 52 | 29 | 54 | 14 | 61 | 8 | |||
N Stage |
0.231 | 0.369 | 0.201 | |||||||
N0 | 23 | 26 | 13 | 36 | 3 | 36 | 10 | |||
N1 | 19 | 17 | 6 | 30 | 3 | 28 | 5 | |||
N2-3 | 12 | 24 | 11 | 25 | 8 | 22 | 6 | |||
Location | 0.170 | 0.956 | 0.080 | |||||||
Cervical and superior | 11 | 14 | 6 | 19 | 3 | 13 | 9 | |||
Middle thoracic | 37 | 37 | 18 | 56 | 7 | 57 | 10 | |||
Inferior thoracic | 6 | 16 | 6 | 16 | 4 | 16 | 2 | |||
Pathology | 0.577 | 0.839 | 0.010 | |||||||
High differentiation | 17 | 17 | 8 | 26 | 3 | 21 | 10 | |||
Middle differentiation | 20 | 31 | 14 | 37 | 7 | 42 | 2 | |||
Low differentiation | 17 | 19 | 8 | 28 | 4 | 23 | 9 |
Pre-LWL, low pretreatment weight loss; pre-HWL, high pretreatment weight loss; LWL, low weight loss during treatment; HWL, high weight loss during treatment; UW, underweight; NW, normal weight; OW, overweight;
The initial BMI of all the patients ranged from 14.84 kg/m2 to 29.43 kg/m2 (median: 21.51 kg/m2). The patients were divided into underweight (UW, BMI < 18.5 kg/m2,
There was no difference in gender, pN stage, and location of the primary lesion among the subgroups stratified by pretreatment weight loss, weight loss during the whole treatment, and BMI (
The 3-year overall survival rate for all patients was 39.7%. The 3-year overall survival rate was compared among the subgroups. Kaplan-Meier survival curve analysis revealed that pre-LWL group had a significantly better 3-year overall survival rate as compared with the pre-HWL group (51.9% versus 29.9%, log-rank test,
Comparison of the 3-year overall survival in Kaplan-Meier analysis (
Overall survival (%) |
|
|
---|---|---|
Weight loss |
|
|
LWL | 36.7 | |
HWL | 40.7 | |
Pretreatment weight loss |
|
|
Pre-LWL | 51.9 | |
Pre-HWL | 29.9 | |
BMI |
|
|
UW | 21.4 | |
NW | 43.0 | |
OW | 38.1 | |
Location | 0.025 | |
Cervical and superior thoracic | 16.0 | |
Middle thoracic | 45.9 | |
Inferior thoracic | 45.5 | |
N stage | <0.001 | |
N0 | 63.3 | |
N1 | 25.0 | |
N2-3 | 22.2 | |
Age | 0.021 | |
<55 | 28.6 | |
≥55 | 49.2 | |
T stage | 0.018 | |
<55 | 55.3 | |
≥55 | 32.5 | |
Sex | 0.678 | |
Male | 38.8 | |
Female | 43.5 | |
Pathology | 0.050 | |
High differentiation | 38.2 | |
Middle differentiation | 51.0 | |
Low differentiation | 25.0 |
Pre-LWL, low pretreatment weight loss; pre-HWL, high pretreatment weight loss; LWL, low weight loss during treatment; HWL, high weight loss during treatment; UW, underweight; NW, normal weight; OW, overweight.
Kaplan-Meier survival curve analysis for the 3-year overall survival for the 121 patients with esophageal carcinoma undergoing surgery and adjuvant chemotherapy stratified by the (a) pretreatment weight loss (log-rank test,
The 3-year overall survival rate was also significantly different in the subgroups analyses stratified by the primary tumor location, pT stage, pN stage, age, and pathological classification (all
To identify the independent prognostic factors of the 3-year overall survival, all the significant factors mentioned above were further investigated by univariate and multivariate Cox proportional hazards analysis. In univariate model, age, T stage, N stage, location, pretreatment weight loss, and BMI groups were the significant factors associated with 3-year overall survival (all
Summary of Cox-regression analyses of the prognostic factors for 3-year overall survival (
Variables | Univariate | Multivariate | ||
---|---|---|---|---|
HR (95% CI) |
|
HR (95% CI) |
| |
Gender | 0.561 | 0.537 | ||
Male | Ref | Ref | ||
Female | 0.84 (0.46–1.53) | 0.82 (0.43–1.55) | ||
Age | 0.006 | 0.015 | ||
<55 | Ref | Ref | ||
≥55 | 0.52 (0.33–0.83) | 0.51 (0.29–0.87) | ||
T stage | 0.020 | 0.162 | ||
T1-2 | Ref | Ref | ||
T3-4 | 1.91 (1.11–3.29) | 1.56 (0.84–2.91) | ||
N stage | 0.006 | 0.027 | ||
N0 | Ref | - | Ref | - |
N1 | 2.43 (1.33–4.41) | 0.004 | 2.14 (1.14–3.99) | 0.017 |
N2-3 | 2.37 (1.31–4.29) | 0.004 | 2.31 (1.18–4.51) | 0.014 |
Location | 0.017 | 0.080 | ||
Cervical and superior thoracic | Ref | - | Ref | - |
Middle thoracic | 0.46 (0.27–0.79) | 0.004 | 0.50 (0.27–0.92) | 0.025 |
Inferior thoracic | 0.54 (0.26–1.10) | 0.091 | 0.58 (0.27–1.27) | 0.175 |
Pathology | 0.285 | 0.103 | ||
High differentiation | Ref | - | Ref | - |
Middle differentiation | 0.81 (0.45–1.46) | 0.485 | 1.18 (0.61–2.29) | 0.624 |
Low differentiation | 1.26 (0.71–2.23) | 0.425 | 1.89 (1.00–3.60) | 0.051 |
Pretreatment weight loss | <0.001 | 0.027 | ||
Pre-LWL | Ref | Ref | ||
Pre-HWL | 2.37 (1.46–3.86) | 1.89 (1.07–3.32) | ||
Weight loss | 0.305 | 0.497 | ||
LWL | Ref | Ref | ||
HWL | 0.76 (0.45–1.28) | 1.30 (0.61–2.75) | ||
BMI | 0.011 | 0.545 | ||
UW | Ref | - | Ref | - |
NW | 0.38 (0.19–0.73) | 0.004 | 0.61 (0.25–1.48) | 0.275 |
OW | 0.36 (0.16–0.80) | 0.013 | 0.61 (0.22–1.73) | 0.352 |
Pre-LWL, low pretreatment weight loss; pre-HWL, high pretreatment weight loss; LWL, low weight loss during treatment; HWL, high weight loss during treatment; UW, underweight; NW, normal weight; OW, overweight; BMI, body mass index; HR, hazard ratio; CI, confidence interval.
In this study, we investigated the effects of weight loss and BMI on the survival outcomes of patients with esophageal carcinoma receiving surgery and adjuvant chemotherapy. The results showed that the 3-year overall survival rate for all esophageal cancer patients was 39.7%. Kaplan-Meier analysis revealed that the 3-year overall survival rate was significantly higher in the pre-LWL group than in the pre-HWL group (
Our results showed that the pretreatment weight loss significantly affected the overall survival, which is consistent with Van Der Schaaf et al.’s study that revealed that an excessive preoperative weight loss (>10%) worsens the 5-year survival after esophageal cancer surgery [
In this study, 75.2% (91/121) patients had weight loss ≥ 5% during the whole treatment, which was much higher than in Jiang et al.’s report. Their study showed that 40.3% of esophageal cancer patients had a weight loss ≥ 5% during radiotherapy [
In this study, we found that BMI had no impact on the 3-year overall survival, which is in line with Miao et al.’s study that showed high BMI is not associated with increased overall morbidity following esophagectomy [
Our analysis showed that tumor N stage was an independent factor associated with 3-year overall survival. A lower N stage predicted a better overall survival, which is in agreement with the fact that lymph node metastasis predicts a poorer survival. On the other hand, our results also showed that patients with an age of ≥55 had a better 3-year overall survival rate. One of the possible explanations for this phenomenon is that young patients were at increased risk of developing more aggressive tumors as the trend found in breast cancer [
There are still several limitations in our study. First, it is a retrospective study and the sample size was relatively small. In addition, there was no obese patient in our study. A well-designed prospective study with large sample size should be conducted to further validate the findings of this study. All these limitations should be addressed in the following study.
In summary, our study showed that, for patients with esophageal carcinoma who received radical surgery and adjuvant chemotherapy, a higher age, earlier pN stage, and lower pretreatment weight loss were the prognostic factors for better survival outcome. However, BMI and weight loss during treatment had no impact on survival outcome. Our findings are helpful for better understanding of the prognostic value of weight loss and BMI in the esophageal carcinoma patients with radical surgery and adjuvant chemotherapy.
The authors declare that there are no conflicts of interest.
Xiao-Li Yu and Jin Yang contributed equally to this study.
This work was supported by Key Laboratory of Malignant Tumor Molecular Mechanism and Translation Medicine of Guangzhou Bureau of Science and Information Technology, Grant [