Contributed equally
Neoadjuvant chemoradiotherapy (nCRT) has been shown to reduce tumor burden and achieve tumor regression in patients with esophageal cancer (ESC). However, the most beneficial time interval between the administration of nCRT and surgery remains unclear. Therefore, the aim of the present study was to explore the association of the duration of time between nCRT and surgery with the prognosis of patients with ESC. Patients with ESC who received nCRT following surgical resection (n=161) were reviewed and divided into the prolonged time interval group (time interval ≥66 days) and the short time interval group (time interval <66 days), according to the median value. Subsequent analysis revealed that the prolonged time interval group achieved a higher pathological complete response (pCR) rate compared with the short time interval group (49.4 vs. 26.3%; P=0.003). Furthermore, multivariate logistic regression analysis showed that it was possible to independently estimate a higher pCR rate based on a prolonged time interval (odds ratio, 2.131; P=0.042). However, no association between a prolonged time interval and disease-free survival (DFS) was detected using Kaplan-Meier curves (P=0.252) or multivariate Cox regression (P=0.607) analyses. Similarly, no association was identified between a prolonged time interval and overall survival (OS; P=0.946) based on Kaplan-Meier curve analysis, and subsequent multivariate Cox regression analyses showed that the time interval also failed to independently estimate OS (P=0.581). Moreover, female sex (P=0.001) and a radiation dose ≥40 Gy (P=0.039) served as independent factors associated with a higher pCR rate, and the pCR rate was an independent predictor of favorable DFS (P=0.002) and OS (P=0.015) rates. In conclusion, the present study revealed that a prolonged time interval from nCRT to surgery was associated with a higher pCR rate, but it failed to estimate the survival profile of patients with ESC.
Esophageal cancer (ESC) is ranked sixth in terms of cancer-associated mortality rates globally and was responsible for ~544,000 deaths in 2020 (
Neoadjuvant chemoradiotherapy (nCRT) is a common type of neoadjuvant therapy, which has been shown to achieve a high pathological complete response (pCR) rate, as well as longer disease-free survival (DFS) and higher overall survival (OS) rates, in patients who received surgery and nCRT compared with those who underwent surgery alone (
It is generally recommended that nCRT is completed within a 6–8-week period prior to surgery for patients with ESC; however, the optimal time interval between nCRT and surgery remains controversial, and the time interval that is most beneficial to the patient requires further investigation (
These inconsistent previous findings are the rationale for the exploration of the association of the time interval between nCRT and surgery with the treatment response and survival profile in patients with ESC in the present study. The aim of the study is to provide more evidence to support clinicians when making decisions regarding the optimal time interval between nCRT and surgery.
The present study retrospectively reviewed a total of 161 patients with resectable ESC who were treated with nCRT followed by surgical resection at West China Hospital, Sichuan University (Chengdu, China) between July 2017 and June 2020. The screening of patients was performed, and patients were included in the present study if they met the following criteria: i) The patient was diagnosed with ESC based on gastroscopy and pathological examinations; ii) the patient was >18 years old; iii) the patient received nCRT followed by surgical resection in line with National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Esophageal and Esophagogastric Junction Cancers (
The clinical characteristics of the patients were collected from the database of West China Hospital, Sichuan University. These characteristics included age, sex, tumor location, pathological type, tumor size, tumor-node-metastasis (TNM) stage according to the eighth edition of the American Joint Committee on Cancer (AJCC) TNM Staging System (
All patients underwent nCRT followed by surgical resection and none of the patients received conversion surgery. The nCRT regimens included synchronous chemoradiotherapy and sequential chemoradiotherapy. The appropriate treatment regimen was selected for each patient according to the patient's disease condition. The chemotherapy protocols were platinum-based doublet chemotherapy regimens, including albumin-bound paclitaxel + carboplatin (AC), albumin-bound paclitaxel + nedaplatin (AN), albumin-bound paclitaxel + cisplatin (AP), fluorouracil + cisplatin (FP), taxol + carboplatin (TC), taxol + nedaplatin (TN) and taxol + cisplatin (TP). The radiotherapy schedules differed slightly according to the specific conditions of the patients. In all cases, a planned total radiation dosage of 40.0-50.4 Gy was administered in 20–28 fractions of 1.8 or 2.0 Gy on 5 days of each week; no radiation was administered at weekends. The timing of surgery was dependent upon the performance status and nutrient status of the patient as well as the availability of operating rooms. The accessibility of surgery in patients after nCRT was determined in line with NCCN guidelines (
A contrast-enhanced CT scan was performed to assess the clinical response of the patients at the end of the neoadjuvant treatment, according to the RECIST guidelines (
SPSS 22.0 (IBM Corp.) was used to perform the statistical analysis, and GraphPad Prism 6.1 (GraphPad Software, Inc.) was used to plot figures. The median time interval between nCRT and surgery was 66 days (range, 0–196 days), and the patients were divided into two groups based on the median value: <66 days (n=76; designated the short time interval group) and ≥66 days (n=85; designated the prolonged time interval group). Differences between groups were compared using unpaired Student's t-test, Wilcoxon rank sum test, χ2 test or Fisher's exact test, as applicable. Factors associated with pCR and the objective response rate (ORR) were assessed using univariate and multivariate logistic regression analyses. DFS and OS were evaluated using Kaplan-Meier curves and compared using the log-rank test. The factors associated with DFS and OS were evaluated using univariate and multivariate Cox proportional hazards regression analyses.
P<0.05 was considered to indicate a statistically significant result.
The mean age of all recruited patients was 61.0±7.9 years (
McKeown surgery and Ivor Lewis surgery are two main surgical approaches for patients with resectable ESC (
In terms of the clinical response, 0 (0.0%), 111 (68.9%), 50 (31.1%) and 0 (0.0%) patients achieved CR, PR, SD and PD, respectively (
Regarding the pathological response, there were 62 (38.5%), 78 (48.4%), 9 (5.6%) and 12 (7.5%) patients with TRG1, TRG2, TRG3 and no assessment data, respectively. In detail, TRG1, TRG2 and TRG3 pathological responses were achieved by 42 (49.4%), 37 (43.5%) and 4 (4.7%) patients in the prolonged time interval group compared with 20 (26.3%), 41 (53.9%) and 5 (6.6%) patients in the short time interval group, respectively. In addition, 2 (2.4%) patients in the prolonged time interval group and 10 (13.2%) patients in the short time interval group had no assessment data. Moreover, 62 (38.5%) patients in the entire cohort achieved a pCR. Comparison of the two groups revealed that the pCR rate (49.4 vs. 26.3%; P=0.003) and the TRG grade (P=0.001) were higher in the prolonged time interval group compared with the short time interval group.
A prolonged time interval between nCRT and surgery was found to be associated with an improved pCR rate [odds ratio (OR): 2.735, 95% confidence interval (95%CI): 1.407-5.315, P=0.003] based on univariate Cox regression analyses, and independently associated with a higher pCR rate based on a multivariate Cox regression model (OR: 2.131, 95%CI: 1.028-4.418, P=0.042;
The median duration of follow-up was 15.8 months (range, 0.4-41.4 months). At the last date of follow-up, the DFS and OS rates had not attained the median value.
During the follow-up period, 27 (16.8%) total deaths were recorded among which 14 (16.5%) cases occurred in the prolonged time interval group and 13 (17.1%) cases occurred in the short time interval group; no difference in death rate was detected between these two groups (P=0.914;
Kaplan-Meier analyses revealed that DFS (P=0.252) and OS (P=0.946) did not differ between the prolonged and short time interval duration groups (
Univariate and multivariate Cox regression analyses revealed that the time interval between the completion of nCRT and surgery failed to enable DFS (
The effect of the time interval between nCRT and surgery on the pCR rate of patients with ESC is unclear. For example, a time interval of >13 weeks was found to be associated with an increased likelihood of a prolonged pCR rate in patients with ESC or gastroesophageal junction cancer (GEJC) in one study (
Aside from the pCR rate, the effect of the time interval between nCRT and surgery on the survival profile of patients with ESC is also of great interest. However, the findings from previous studies in this regard are also inconsistent. For example, one study reported that neither RFS nor OS differed among patients with esophageal squamous cell carcinoma cancer according to whether they experienced shorter or longer time intervals between nCRT and surgery (
The present study also identified that sex (female vs. male) and radiation dose (≥40 vs. <40 Gy) were independently associated with improved pCR rates in patients with ESC. These findings regarding sex and radiation dose may be explained as follows: i) Women are subjected to lower levels of androgenic hormones such as testosterone, dihydrotestosterone and androstenedione, compared with men, which may afford them some protection from carcinogenesis mediated via downstream androgen receptor signaling, thereby leading to improved pCR rates in female patients with ESC (
Although it is recommended that the surgery is performed 6–8 weeks after the completion of nCRT in patients with resectable ESC, the time interval between nCRT and surgery differs in the existing literature. Several studies observed a prolonged time interval of >8 weeks between nCRT and surgery for patients with resectable ESC, the reasons for which may be older age, more morbidities, advanced cancer stage or overloaded surgical schedules (
The present study applied contrast-enhanced CT rather than positron emission tomography (PET)/CT for the assessment of the treatment response in patients with resectable ESC. The reasons for this were as follows: i) Contrast-enhanced CT for the initial workup exhibited more sensitivity and a well-differentiated cT stage compared with PET/CT for patients with T1-T3 tumors (
The present study only enrolled patients with resectable ESC; therefore, preoperative chemoradiotherapy was applied in a neoadjuvant setting. Patients with unresectable ESC may be offered curative surgery following treatment with definitive chemotherapy or chemoradiotherapy preoperatively, which is known as conversion surgery. However, none of the patients included in the current study received conversion surgery. The reason for this was that conversion surgery is only available for a small proportion of patients, and most patients with unresectable ESC experienced rapid progression and distant metastasis. Therefore, the current study did not include any patients with conversion surgery, but this could be addressed in future studies.
The present study has certain limitations. First, the follow-up period was relatively short since most patients were not local residents and some of them transferred to local hospitals after discharge, which increased the difficulty of regular follow-up for these patients. Therefore, further studies with a longer follow-up period are required to address this issue. Moreover, further studies could explore the relationship between time interval and the change in the standardized uptake value obtained using PET/CT in resectable ESC patients. Also, a larger sample size is necessary to enable more subgroup analyses to be conducted, with the aim of identifying the optimal time interval for patients with ESC with different causes of death.
In conclusion, the present study shows that a prolonged time interval between nCRT and surgery is associated with a higher pCR rate, although it is not possible to estimate the DFS or OS in patients with ESC from the time interval. Based on these findings, the optimal time interval for balancing the benefit of pathological response with prognosis remains uncertain. This may serve as an interesting topic for clinicians and prompt them to perform more research into this topic.
Not applicable.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
YML designed and supervised the study. JQL and XXZ conceived the study. XJZ, YX and ZYD participated in the experiments and data collection. YH, YY and LQC performed the data analysis, and wrote the manuscript. JW and YL contributed to the analysis of the results and revised the manuscript. YML and JQL confirm the authenticity of all the raw data. All authors read and approved the final manuscript.
This study was approved by the Institutional Review Board of West China Hospital, Sichuan University (Chengdu, China).
Not applicable.
The authors declare that they have no competing interests.
Survival profiles in patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy and surgery. (A) Disease-free survival and (B) overall survival profiles.
Comparison of survival profiles between different groups of patients with esophageal cancer. Comparison of (A) DFS and (B) OS rates between patients whose time interval from nCRT to surgery was <66 days and those whose time interval from nCRT to surgery was ≥66 days. Comparison of the (C) DFS and (D) OS rates between patients who reached pCR and those who did not reach pCR. DFS, disease-free survival; OS, overall survival; nCRT, neoadjuvant chemoradiotherapy; pCR, pathological complete response.
Clinical characteristics.
Duration from nCRT to surgery | |||||
---|---|---|---|---|---|
Items | Patients (N=161) | <66 days (n=76) | ≥66 days (n=85) | t/χ2/Z-value | P-value |
Demographics | |||||
Age (years), mean ± SD | 61.0±7.9 | 61.5±8.4 | 60.6±7.4 | 0.707 | 0.481 |
Sex, n (%) | 4.379 | 0.036 | |||
Male | 131 (81.4) | 67 (88.2) | 64 (75.3) | ||
Female | 30 (18.6) | 9 (11.8) | 21 (24.7) | ||
Disease characteristics | |||||
Tumor location, n (%) | 1.048 | 0.592 | |||
Upper | 22 (13.7) | 12 (15.8) | 10 (11.8) | ||
Middle | 108 (67.1) | 48 (63.2) | 60 (70.6) | ||
Lower | 31 (19.3) | 16 (21.1) | 15 (17.6) | ||
Pathological type, n (%) | 0.267 | 0.763 |
|||
SCC | 152 (94.4) | 71 (93.4) | 81 (95.3) | ||
ADC | 9 (5.6) | 5 (6.6) | 4 (4.7) | ||
Tumor size (cm), median (IQR) | 5.0 (4.5-7.0) | 5.0 (4.5-7.0) | 5.0 (4.4-7.0) | −0.243 | 0.808 |
cT stage, n (%) | −0.800 | 0.424 | |||
cT2 | 16 (9.9) | 9 (11.8) | 7 (8.2) | ||
cT3 | 117 (72.7) | 55 (72.4) | 62 (72.9) | ||
cT4a | 28 (17.4) | 12 (15.8) | 16 (18.8) | ||
cN stage, n (%) | −0.082 | 0.935 | |||
cN0 | 16 (9.9) | 6 (7.9) | 10 (11.8) | ||
cN1 | 83 (51.6) | 41 (53.9) | 42 (49.4) | ||
cN2 | 51 (31.7) | 25 (32.9) | 26 (30.6) | ||
cN3 | 11 (6.8) | 4 (5.3) | 7 (8.2) | ||
cM stage, n (%) | 2.265 | 0.221 |
|||
cM0 | 159 (98.8) | 74 (97.4) | 85 (100.0) | ||
cM1 | 2 (1.2) | 2 (2.6) | 0 (0.0) | ||
cTNM stage, n (%) | −1.078 | 0.281 | |||
II | 22 (13.7) | 11 (14.5) | 11 (12.9) | ||
III | 100 (62.1) | 50 (65.8) | 50 (58.8) | ||
IV | 39 (24.2) | 15 (19.7) | 24 (28.2) | ||
Treatment information | |||||
nCRT sequence, n (%) | 1.318 | 0.251 | |||
Synchronous nCRT | 115 (71.4) | 51 (67.1) | 64 (75.3) | ||
Sequential nCRT | 46 (28.6) | 25 (32.9) | 21 (24.7) | ||
Chemotherapy cycle, n (%) | 0.064 | 0.801 | |||
<2 cycles | 18 (11.2) | 9 (11.8) | 9 (10.6) | ||
≥2 cycles | 143 (88.8) | 67 (88.2) | 76 (89.4) | ||
Chemotherapy regimens, n (%) | 16.809 | 0.330 | |||
TP | 96 (59.6) | 39 (51.3) | 57 (67.1) | ||
TN | 14 (8.7) | 6 (7.9) | 8 (9.4) | ||
TC | 13 (8.1) | 9 (11.8) | 4 (4.7) | ||
AN | 10 (6.2) | 5 (6.6) | 5 (5.9) | ||
AC | 7 (4.3) | 3 (3.9) | 4 (4.7) | ||
FP | 4 (2.5) | 4 (5.3) | 0 (0.0) | ||
AP | 3 (1.9) | 1 (1.3) | 2 (2.4) | ||
Others | 14 (8.7) | 9 (11.8) | 5 (5.9) | ||
Radiation dose (Gy), median (IQR) | 41.4 (40.0-45.0) | 41.4 (40.0-45.0) | 41.4 (40.0-45.5) | −0.650 | 0.516 |
Interruption of radiotherapy, n (%) | 0.087 | 0.768 | |||
No | 87 (54.0) | 42 (55.3) | 45 (52.9) | ||
Yes | 74 (46.0) | 34 (44.7) | 40 (47.1) |
P-values calculated by Fisher's exact test. nCRT, neoadjuvant chemoradiotherapy; SD, standard deviation; SCC, squamous cell carcinoma; ADC, adenocarcinoma; cT, clinical tumor; cN, clinical node; cM, clinical metastasis; cTNM, clinical tumor-node-metastasis; TP, taxol + cisplatin; TN, taxol + nedaplatin; TC, taxol + carboplatin; AN, albumin-bound paclitaxel + nedaplatin; AC, albumin-bound paclitaxel + carboplatin; FP, fluorouracil + cisplatin; AP, albumin-bound paclitaxel + cisplatin; IQR, interquartile range.
Treatment response.
Duration from nCRT to surgery | |||||
---|---|---|---|---|---|
Items | Patients (N=161) | <66 days (n=76) | ≥66 days (n=85) | Z/χ2-value | P-value |
Clinical response | |||||
Overall response, n (%) | 2.251 | 0.134 | |||
CR | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
PR | 111 (68.9) | 48 (63.2) | 63 (74.1) | ||
SD | 50 (31.1) | 28 (36.8) | 22 (25.9) | ||
PD | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
ORR, n (%) | 111 (68.9) | 48 (63.2) | 63 (74.1) | 2.251 | 0.134 |
DCR, n (%) | 161 (100.0) | 76 (100.0) | 85 (100.0) | - | - |
Pathological response | |||||
TRG, n (%) | −3.406 | 0.001 | |||
TRG1 | 62 (38.5) | 20 (26.3) | 42 (49.4) | ||
TRG2 | 78 (48.4) | 41 (53.9) | 37 (43.5) | ||
TRG3 | 9 (5.6) | 5 (6.6) | 4 (4.7) | ||
Not assessed | 12 (7.5) | 10 (13.2) | 2 (2.4) | ||
pCR, n (%) | 62 (38.5) | 20 (26.3) | 42 (49.4) | 9.039 | 0.003 |
nCRT, neoadjuvant chemoradiotherapy; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate; TRG, tumor regression grade; pCR, pathological complete response.
Logistic regression analysis for pCR.
Univariate logistic regression analysis | Multivariate logistic regression analysis | |||||
---|---|---|---|---|---|---|
Items | β-value | OR (95% CI) | P-value | β-value | OR (95% CI) | P-value |
Duration from nCRT to surgery (≥66 vs. <66 days) | 1.006 | 2.735 (1.407-5.315) | 0.003 | 0.757 | 2.131 (1.028-4.418) | 0.042 |
Age (≥60 vs. <60 years) | −0.474 | 0.622 (0.326-1.189) | 0.151 | −0.492 | 0.611 (0.291-1.283) | 0.193 |
Sex (female vs. male) | 1.444 | 4.238 (1.824-9.848) | 0.001 | 1.763 | 5.830 (2.038-16.678) | 0.001 |
Tumor location | ||||||
Upper | Reference | Reference | ||||
Middle | −0.067 | 0.935 (0.407-2.151) | 0.874 | 0.366 | 1.442 (0.507-4.104) | 0.493 |
Lower | 0.531 | 1.700 (0.676-4.276) | 0.260 | 0.319 | 1.376 (0.479-3.952) | 0.554 |
Pathological type (SCC vs. non-SCC) | 0.825 | 2.283 (0.459-11.360) | 0.313 | 0.911 | 2.487 (0.379-16.301) | 0.342 |
Tumor size (≥5 vs. <5 cm) | −0.087 | 0.917 (0.453-1.854) | 0.809 | 0.044 | 1.045 (0.467-2.337) | 0.915 |
cTNM stage (III–IV vs. II) | −0.332 | 0.717 (0.290-1.776) | 0.473 | −0.058 | 0.944 (0.301-2.961) | 0.921 |
nCRT sequence (sequential nCRT vs. synchronous nCRT) | −0.493 | 0.611 (0.295-1.266) | 0.185 | −0.243 | 0.784 (0.290-2.122) | 0.632 |
Chemotherapy cycle (≥2 vs. <2 cycles) | 0.871 | 2.388 (0.748-7.620) | 0.141 | 1.002 | 2.724 (0.587-12.638) | 0.201 |
Radiation dose (≥40 vs. <40 Gy) | 2.130 | 8.414 (1.066-66.417) | 0.043 | 2.326 | 10.235 (1.120-93.552) | 0.039 |
Interruption of radiotherapy (yes vs. no) | 0.053 | 1.055 (0.558-1.993) | 0.870 | 0.076 | 1.079 (0.511-2.278) | 0.843 |
pCR, pathological complete response; OR, odds ratio; CI, confidence interval; nCRT, neoadjuvant chemoradiotherapy; SCC, squamous cell carcinoma; cTNM, clinical tumor-node-metastasis.
Cox proportional hazards regression analysis for disease-free survival.
Univariate Cox regression analysis | Multivariate Cox regression analysis | |||||
---|---|---|---|---|---|---|
Items | β-value | HR (95% CI) | P-value | β-value | HR (95% CI) | P-value |
Duration from nCRT to surgery (≥66 vs. <66 days) | −0.334 | 0.716 (0.403-1.272) | 0.255 | −0.157 | 0.855 (0.471-1.552) | 0.607 |
Age (≥60 vs. <60 years) | −0.162 | 0.850 (0.483-1.498) | 0.574 | −0.307 | 0.735 (0.411-1.316) | 0.301 |
Sex (female vs. male) | −0.280 | 0.756 (0.339-1.683) | 0.493 | 0.007 | 1.007 (0.410-2.474) | 0.987 |
Tumor location | ||||||
Upper | Reference | Reference | ||||
Middle | −0.233 | 0.792 (0.366-1.716) | 0.555 | −0.346 | 0.707 (0.270-1.855) | 0.481 |
Lower | 0.304 | 1.355 (0.625-2.936) | 0.442 | 0.428 | 1.533 (0.656-3.587) | 0.324 |
Pathological type (SCC vs. non-SCC) | −0.214 | 0.807 (0.250-2.601) | 0.720 | −0.252 | 0.778 (0.179-3.370) | 0.737 |
Tumor size (≥5 vs. <5 cm) | 0.153 | 1.165 (0.607-2.236) | 0.647 | 0.186 | 1.205 (0.610-2.379) | 0.592 |
cTNM stage (III–IV vs. II) | 0.658 | 1.931 (0.694-5.375) | 0.208 | 0.533 | 1.704 (0.576-5.042) | 0.336 |
nCRT sequence (sequential nCRT vs. synchronous nCRT) | 0.106 | 1.112 (0.606-2.042) | 0.732 | 0.053 | 1.054 (0.494-2.248) | 0.891 |
Chemotherapy cycle (≥2 vs. <2 cycles) | −0.058 | 0.944 (0.401-2.218) | 0.894 | 0.162 | 1.176 (0.415-3.330) | 0.760 |
Radiation dose (≥40 vs. <40 Gy) | 0.153 | 1.165 (0.417-3.254) | 0.770 | 0.455 | 1.576 (0.543-4.578) | 0.403 |
Interruption of radiotherapy (yes vs. no) | −0.158 | 0.854 (0.486-1.501) | 0.584 | −0.112 | 0.894 (0.492-1.623) | 0.712 |
pCR (yes vs. no) | −1.163 | 0.313 (0.152-0.645) | 0.002 | −1.222 | 0.295 (0.135-0.641) | 0.002 |
HR, hazard ratio; CI, confidence interval; nCRT, neoadjuvant chemoradiotherapy; SCC, squamous cell carcinoma; cTNM, clinical tumor-node-metastasis; pCR, pathological complete response.
Cox proportional hazards regression analysis for overall survival.
Univariable Cox regression analysis | Multivariable Cox regression analysis | |||||
---|---|---|---|---|---|---|
Items | β-value | HR (95% CI) | P-value | β-value | HR (95% CI) | P-value |
Duration from nCRT to surgery (≥66 vs. <66 days) | 0.026 | 1.027 (0.481-2.192) | 0.946 | 0.226 | 1.254 (0.562-2.795) | 0.581 |
Age (≥60 vs. <60 years) | −0.071 | 0.931 (0.432-2.007) | 0.856 | −0.564 | 0.569 (0.217-1.489) | 0.251 |
Sex (female vs. male) | 0.079 | 1.082 (0.409-2.862) | 0.873 | 0.454 | 1.575 (0.497-4.993) | 0.440 |
Tumor location | ||||||
Upper | Reference | Reference | ||||
Middle | −0.118 | 0.889 (0.330-2.395) | 0.816 | −0.697 | 0.498 (0.110-2.265) | 0.367 |
Lower | 0.257 | 1.293 (0.436-3.832) | 0.643 | 0.368 | 1.445 (0.450-4.644) | 0.536 |
Pathological type (SCC vs. non-SCC) | −0.758 | 0.469 (0.141-1.557) | 0.216 | −1.384 | 0.251 (0.038-1.643) | 0.149 |
Tumor size (≥5 vs. <5 cm) | 0.451 | 1.569 (0.594-4.147) | 0.364 | 0.525 | 1.690 (0.626-4.561) | 0.300 |
cTNM stage (III–IV vs. II) | 0.231 | 1.260 (0.379-4.187) | 0.706 | −0.174 | 0.840 (0.227-3.116) | 0.795 |
nCRT sequence (sequential nCRT vs. synchronous nCRT) | 0.078 | 1.081 (0.473-2.470) | 0.853 | −0.087 | 0.916 (0.291-2.890) | 0.882 |
Chemotherapy cycle (≥2 vs. <2 cycles) | −0.536 | 0.585 (0.222-1.545) | 0.279 | −0.582 | 0.559 (0.145-2.153) | 0.398 |
Radiation dose (≥40 vs. <40 Gy) | 0.900 | 2.460 (0.333-18.145) | 0.377 | 1.156 | 3.179 (0.409-24.714) | 0.269 |
Interruption of radiotherapy (yes vs. no) | 0.023 | 1.023 (0.481-2.178) | 0.953 | 0.064 | 1.066 (0.468-2.426) | 0.879 |
pCR (yes vs. no) | −1.332 | 0.264 (0.091-0.763) | 0.014 | −1.478 | 0.228 (0.070-0.748) | 0.015 |
HR, hazard ratio; CI, confidence interval; nCRT, neoadjuvant chemoradiotherapy; SCC, squamous cell carcinoma; cTNM, clinical tumor-node-metastasis; pCR, pathological complete response.