1Department of Radiation Oncology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
2Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul, Korea
3Department of Medical Oncology, University of Ulsan College of Medicine, Seoul, Korea
4Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Seoul, Korea
5Department of Radiology, University of Ulsan College of Medicine, Seoul, Korea
6Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Copyright © 2022 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
This study was approved by the institutional review board of Asan Medical Center (Seoul, Korea; IRB number: 2020-1562) and written informed consent was waived because of the retrospective study.
Author Contributions
Conceived and designed the analysis: Yu J, Kim JH.
Collected the data: Yu J, Song KJ, Jang JY, Jo YY, Yoo YJ.
Contributed data or analysis tools: Kim JH, Kim SB, Park SR, Kim YH, Kim HR, Lee HJ, Song HJ.
Performed the analysis: Yu J.
Wrote the paper: Yu J, Kim JH.
Review the manuscript: Kim JH.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Oncologic outcomes | Method | HRa) | 95% CI | p-value |
---|---|---|---|---|
Overall survival | Univariate | 0.627 | 0.488–0.805 | < 0.001 |
Multivariable-adjustedb) | 0.651 | 0.487–0.870 | 0.004 | |
IPTW-adjusted | 0.693 | 0.514–0.933 | 0.016 | |
Local recurrence–free rate | Univariate | 0.362 | 0.252–0.519 | < 0.001 |
Multivariable-adjustedb) | 0.310 | 0.209–0.460 | < 0.001 | |
IPTW-adjusted | 0.352 | 0.235–0.528 | < 0.001 | |
Distant metastasis–free rate | Univariate | 0.585 | 0.388–0.883 | 0.011 |
Multivariable-adjustedb) | 0.474 | 0.303–0.740 | 0.001 | |
IPTW-adjusted | 0.529 | 0.332–0.843 | 0.007 |
Clinical response | Oncologic outcomes | HRa) | 95% CI | p-value | p-value for interaction |
---|---|---|---|---|---|
cCR | Overall survival | 1.027 | 0.561–1.880 | 0.93 | 0.13 |
Local recurrence–free rate | 0.247 | 0.097–0.624 | 0.003 | 0.44 | |
Distant metastasis–free rate | 0.905 | 0.324–2.524 | 0.85 | 0.24 | |
Non-cCR | Overall survival | 0.610 | 0.463–0.805 | < 0.001 | |
Local recurrence–free rate | 0.367 | 0.250–0.539 | < 0.001 | ||
Distant metastasis–free rate | 0.465 | 0.299–0.722 | 0.001 |
Patient characteristics
Trimodality (n=270) | CRT (n=142) | p-value | |
---|---|---|---|
Sex | |||
Male | 256 (94.8) | 135 (95.1) | 0.91 |
Female | 14 (5.2) | 7 (4.9) | |
Age (yr) | |||
≤ 60 | 127 (47.0) | 39 (27.5) | < 0.001 |
> 60 | 143 (53.0) | 103 (72.5) | |
Mean±SD | 61.36±7.09 | 66.14±8.8 | < 0.001 |
ECOG score | |||
0–1 | 267 (98.9) | 140 (98.6) > | 0.99 |
2 | 3 (1.1) | 2 (1.4) | |
Charlson-Deyo score | |||
0 | 199 (73.7) | 88 (62.0) | 0.029 |
1 | 56 (20.8) | 42 (29.6) | |
2 | 12 (4.4) | 6 (4.2) | |
3 | 3 (1.1) | 6 (4.2) | |
Alcohol | |||
No | 33 (12.2) | 18 (12.7) | 0.89 |
Yes | 237 (87.8) | 124 (87.3) | |
Smoking | |||
No | 53 (19.6) | 32 (22.5) | 0.49 |
Yes | 217 (80.4) | 110 (77.5) | |
T category | |||
≤ 2 | 112 (41.5) | 63 (44.7) | 0.53 |
> 2 | 158 (58.5) | 78 (55.3) | |
N category | |||
Negative | 74 (27.4) | 33 (23.2) | 0.36 |
Positive | 196 (72.6) | 109 (76.8) | |
Stage | |||
≤ II | 100 (37.0) | 56 (39.7) | 0.60 |
> II | 170 (63.0) | 85 (60.3) | |
Differentiation | |||
Well | 33 (12.2) | 15 (10.6) | 0.021 |
Moderate | 205 (75.9) | 94 (66.2) | |
Poor | 24 (8.9) | 22 (15.5) | |
Tumor location | |||
Upper | 35 (13.0) | 25 (17.6) | 0.21 |
Mid | 127 (47.0) | 55 (38.7) | |
Lower | 108 (40.0) | 62 (43.7) | |
Clinical response | |||
CR | 58 (21.5) | 34 (23.9) | 0.57 |
Non-CR | 212 (78.5) | 108 (76.1) |
Continuous variables were compared using the t test, and categorical variables were compared using the Fisher’s exact test or chi-squared test. CR, complete response; CRT, chemoradiotherapy; ECOG, Eastern Cooperative Oncology Group; SD, standard deviation.
Patterns of failure
TMT | CRT | Total | |
---|---|---|---|
cCR | 58 | 34 | 92 |
Local recurrence | 2 (3.4) | 10 (29.4) | 12 (13.0) |
Distant metastasis | 5 (8.6) | 3 (8.8) | 8 (8.7) |
Both | 4 (6.9) | 5 (14.7) | 9 (9.8) |
Non-cCR | 212 | 108 | 320 |
Local recurrence | 24 (11.3) | 30 (27.8) | 54 (16.9) |
Distant metastasis | 18 (8.5) | 14 (13.0) | 32 (10.0) |
Both | 26 (12.3) | 18 (16.7) | 44 (13.8) |
Values are presented as number (%). cCR, clinical complete res-ponse; CRT, chemoradiotherapy; TMT, trimodality treatment.
Hazard ratios for oncological outcomes in the entire cohort
Oncologic outcomes | Method | HR |
95% CI | p-value |
---|---|---|---|---|
Overall survival | Univariate | 0.627 | 0.488–0.805 | < 0.001 |
Multivariable-adjusted |
0.651 | 0.487–0.870 | 0.004 | |
IPTW-adjusted | 0.693 | 0.514–0.933 | 0.016 | |
Local recurrence–free rate | Univariate | 0.362 | 0.252–0.519 | < 0.001 |
Multivariable-adjusted |
0.310 | 0.209–0.460 | < 0.001 | |
IPTW-adjusted | 0.352 | 0.235–0.528 | < 0.001 | |
Distant metastasis–free rate | Univariate | 0.585 | 0.388–0.883 | 0.011 |
Multivariable-adjusted |
0.474 | 0.303–0.740 | 0.001 | |
IPTW-adjusted | 0.529 | 0.332–0.843 | 0.007 |
CI, confidence interval; HR, hazard ratio; IPTW, inverse probability of treatment weighting.
a)Chemoradiotherapy compared with trimodality treatment,
b)A multivariate analysis was performed using the variables used to calculate the propensity score.
IPTW-adjusted hazard ratios for oncological outcomes in the subgroups stratified by clinical complete response
Clinical response | Oncologic outcomes | HR |
95% CI | p-value | p-value for interaction |
---|---|---|---|---|---|
cCR | Overall survival | 1.027 | 0.561–1.880 | 0.93 | 0.13 |
Local recurrence–free rate | 0.247 | 0.097–0.624 | 0.003 | 0.44 | |
Distant metastasis–free rate | 0.905 | 0.324–2.524 | 0.85 | 0.24 | |
Non-cCR | Overall survival | 0.610 | 0.463–0.805 | < 0.001 | |
Local recurrence–free rate | 0.367 | 0.250–0.539 | < 0.001 | ||
Distant metastasis–free rate | 0.465 | 0.299–0.722 | 0.001 |
cCR, clinical complete response; CI, confidence interval; HR, hazard ratio; IPTW, inverse probability of treatment weighting.
a)Adjusted hazard ratio, chemoradiotherapy compared with trimodality treatment.
Treatment-related acute toxicity (grade ≥ 3)
Grade | TMT group (n=270) | No. | |
---|---|---|---|
From CRT | 3 | Dysphagia | 2 |
Odynophagia | 2 | ||
Hemorrhage | 1 | ||
From surgery | 3 | Vocal cord palsy | 19 |
Pneumonia | 9 | ||
Infection | 8 | ||
Anastomosis site leakage | 7 | ||
Chylothorax | 2 | ||
Fistula | 1 | ||
Diaphragmatic hernia | 1 | ||
Cardiac toxicity | 1 | ||
4 | Pneumonia | 9 | |
Chylothorax | 3 | ||
Anastomosis site leakage | 3 | ||
Cardiac toxicity | 2 | ||
Infection | 1 |
One case of grade 3 dysphagia was detected in the CRT group.
CRT, chemoradiotherapy; TMT, trimodality treatment.
Continuous variables were compared using the t test, and categorical variables were compared using the Fisher’s exact test or chi-squared test. CR, complete response; CRT, chemoradiotherapy; ECOG, Eastern Cooperative Oncology Group; SD, standard deviation.
Values are presented as number (%). cCR, clinical complete res-ponse; CRT, chemoradiotherapy; TMT, trimodality treatment.
CI, confidence interval; HR, hazard ratio; IPTW, inverse probability of treatment weighting. Chemoradiotherapy compared with trimodality treatment, A multivariate analysis was performed using the variables used to calculate the propensity score.
cCR, clinical complete response; CI, confidence interval; HR, hazard ratio; IPTW, inverse probability of treatment weighting. Adjusted hazard ratio, chemoradiotherapy compared with trimodality treatment.
One case of grade 3 dysphagia was detected in the CRT group. CRT, chemoradiotherapy; TMT, trimodality treatment.