
==== Front
Transl Oncol
Transl Oncol
Translational Oncology
1936-5233
Neoplasia Press

S1936-5233(24)00250-X
10.1016/j.tranon.2024.102123
102123
Original Research
Efficacy and safety of concurrent chemoradiotherapy with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma: A multi-center propensity-score matched study
Guo Yiyu a1
Wang Tian b1
Li Hui c1
Zhou Xuefeng d
Shi Haifeng e
Wu Daguang f
Shan Huiguo d
Zhou Guoren g
Zhang Zhi zz5223404@163.com
h⁎
Ye Jinjun jjye2004@163.com
a⁎
a Department of Radiation Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
b Department of Radiation Oncology, Xuzhou cancer hospital, Xuzhou, Jiangsu, China
c Department of Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Jiangsu, China
d Department of Oncology, Dongtai People's Hospital, Yancheng, China
e Department of Oncology, Sheyang County People's Hospital, Yancheng, China
f Department of Oncology, Funing County People's Hospital, Yancheng, China
g Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
h Department of Thoracic Surgery, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
⁎ Corresponding author. zz5223404@163.comjjye2004@163.com
1 These authors contributed equally to this work.

14 9 2024
12 2024
14 9 2024
50 1021234 6 2024
23 8 2024
11 9 2024
© 2024 The Authors. Published by Elsevier Inc.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Highlights

• Paclitaxel-based concurrent chemoradiotherapy is tolerable in elderly patients with esophageal squamous cell carcinoma.

• Paclitaxel-based concurrent chemoradiotherapy offers significant survival benefits over S-1 regimen concurrent chemoradiotherapy.

• Propensity score matching (PSM) was used to balance potential biases.

Background

Elderly patients with esophageal cancer can benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen remains undetermined. We aimed to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma (ESCC).

Methods

From January 2016 to November 2022, a total of 349 patients aged 70 and above with ESCC were included. The patient population was divided into two treatment groups: patients receiving paclitaxel-based CCRT were allocated to the TP group, and those receiving S-1 regimen CCRT were allocated to the S-1 group. Propensity score matching (PSM) was used to balance potential biases. Survival outcomes, overall response rate, and treatment-related toxicities were assessed.

Results

After PSM, there were 82 patients in each group. The median follow up of the surviving patients was 42.6 months (IQR 28.0–58.8 months). The 2-year overall survival (OS) rate (71.4% vs 65.4%; log-rank P = 0.010) and progression-free survival (PFS) rate (64.4% vs 58.0%; log-rank P = 0.048) were significantly higher in the TP group. Compared with the S-1 group, the TP group experienced a higher rate of grade 3 and above hematologic toxicities, such as leukopenia (47.6% vs 15.9%, P < 0.001) and neutropenia (35.4% vs 6.1%, P < 0.001). One patient in the TP group and two patients in the S-1 group had grade 5 toxic effects.

Conclusions

Our findings suggest that paclitaxel-based CCRT was well tolerated in elderly patients with ESCC and provided significant survival benefits over S-1 regimen.

Keywords

Esophageal cancer
Chemoradiotherapy
Elderly patients
Squamous cell cancer
==== Body
pmcIntroduction

In 2022, the World Health Organization (WHO) reported that esophageal cancer (EC) is the seventh leading cause of cancer-related mortality worldwide [1]. Furthermore, more than 40% of the patients are aged 70 years or older at the time of diagnosis [2]. In previous randomized clinical trials, most enrolled patients were under the age of 70, and there were very few studies on elderly patients with EC. With the extension of life expectancy and the aging of the population, it is very important to study and standardize the treatment strategies for elderly patients with EC.

Based on the results from the Radiation Therapy Oncology Group (RTOG) trial 85–01 [3], concurrent chemoradiotherapy (CCRT) using a regimen of fluorouracil and cisplatin has become the standard treatment option for inoperable locally advanced esophageal carcinoma. However, this regimen has substantial toxicity, with 64% of patients experiencing severe or life-threatening acute toxicities, and only 23% of enrolled patients were over the age of 70. Elderly patients with esophageal cancer often have coexisting medical conditions, poor organ function, and nutritional status, which may also affect their tolerance to treatment. Therefore, it is necessary to explore more efficient and less toxic chemotherapy regimens for elderly patients with esophageal cancer.

Paclitaxel is a microtubule stabilizer that can block the cell cycle at the G2 and M phases, and it is an effective anti-tumor drug that has been proven to be a radiosensitizer [4,5]. In China, approximately 90% of EC patients are diagnosed with squamous cell carcinoma (SCC) [6]. In the CROSS study [7], neoadjuvant chemoradiotherapy with carboplatin plus paclitaxel demonstrated significant survival benefits in patients with SCC compared with those with adenocarcinoma (median survival time: 81.6 vs 43.2 months). Some studies [8,9] have indicated that concurrent chemoradiotherapy regimens based on paclitaxel are more effective than those based on fluorouracil. The National Comprehensive Cancer Network (NCCN) [10] also listed the paclitaxel-based regimens as an alternative option.

S-1 is an oral chemotherapy agent of fluoropyrimidine, consisting of tegafur, gimeracil, and oteracil potassium. It has demonstrated good efficacy and safety in patients with digestive tract tumors [[11], [12], [13]]. A multicenter phase III clinical trial [11] showed that in elderly patients (age ≥ 70) with esophageal cancer, S-1 concurrent chemoradiotherapy is tolerable and can achieve a better survival rate compared with radiotherapy alone (hazard ratio [HR], 0.63; 95% confidence interval [CI] 0.47–0.85; P = 0.002). Therefore, in this study, we aim to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 regimens in treating elderly patients (age ≥ 70) with esophageal squamous cell carcinoma.

Methods

Patients

From January 2016 to November 2022, we retrospectively recruited esophageal cancer patients aged 70 years and above who underwent definitive radiotherapy at four sites in China. The study protocol was conducted in accordance with the Declaration of Helsinki and was approved by the clinical research ethics committee of Jiangsu Cancer Hospital (KY-2024–069). Written informed consent was waived. All patients underwent baseline tumor staging using the American Joint Committee on Cancer (AJCC) 8th edition TNM staging system [14], which included contrast-enhanced computed tomography (CT) scans of the chest and abdominal, esophagogram, cervical lymph node ultrasonography, and/or positron emission tomography fusion with CT (PET-CT) scans. The inclusion criteria were as follows: (1) aged 70 years and above; (2) received paclitaxel-based or S-1 chemotherapy regimens; (3) pathologically confirmed esophageal squamous cell carcinoma; (4) clinical stages of T2N1–3M0, T3N0–3M0, or T4N0–3M0 (stage Ⅱ-Ⅳa); (5) ECOG PS 0–2. Patients were excluded if they had received other treatments prior to chemoradiotherapy, had other malignant tumors, or did not have complete clinical data.

Treatment

Patients who received CCRT with the S-1 regimen were assigned to the S-1 group. Patients who received CCRT with a paclitaxel-based regimen were assigned to the TP group. The specific chemotherapy regimen can be found in Supplementary Table 1. Intensity-modulated radiotherapy (IMRT) was used in all the patients. A total dose of 50–61.2 Gy was designed to be delivered at 1.8–2.0 Gy with five daily fractions per week for 5–6.5 weeks.

Outcomes

The treatment-related adverse events (TRAEs) were assessed according to the NCI-CTCAE v5.0 [15], continuously throughout the study and until 90 days after treatment completion. The tumor responses (primary tumor and metastatic lymph node) were evaluated using the Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1 [16], with esophagogram and contrast-enhanced chest and abdominal CT scans 4 to 6 weeks after the completion of CCRT. The objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR).

Statistical

Survival curves were estimated using the Kaplan–Meier method. The log-rank test was used to compare survival curves and hazard ratios (HR) were estimated using Cox regression models. The t-test and Chi-square test were used to compare the differences between the two groups. Bilateral p-values < 0.05 were considered significant. Propensity score matching (PSM) was performed in R Version 4.2.0 and based on the “MatchIt” package, with a caliper 0.1, matching ratio = 1:1, and the “nearest” matching method to balance potential bias. A less than 10% standardized mean difference (SMD) was considered an adequate balance of matching [17].

SPSS version 26.0 and R software (version 4.2.0) were used for data analysis and visualization.

Results

Patients and treatment characteristics

From January 2016 to November 2022, a total of 349 eligible patients (152 in the TP group and 197 in the S-1 group) were included for further analysis (Fig. 1). A 1:1 propensity score matching was conducted based on age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (0/1/2), tumor location, T stage, N stage, clinical TNM stage, tumor length (<5 or ≥5 cm), and comorbidity, and then 82 pairs of patients were selected (Supplemental Table 2). Baseline characteristics before and after PSM for each group of 82 patients are shown in Table 1. There were no significant differences in clinical and demographic characteristics between the two groups after PSM. The propensity score distribution was similar in both groups following the matching process (Fig. 2A). Furthermore, the SMD of the matched covariates were all less than 0.1 (Fig. 2B).Fig. 1 Patient flowchart. SC, squamous cell carcinoma; ECOG PS, Eastern Cooperative Oncology Group Performance Status.

Fig 1

Table. 1 Patient characteristics.

Table 1	Before PSM, No. (%)	After PSM, No. (%)	
	TP (n = 152)	S-1 (n = 197)	P value	TP (n = 82)	S-1 (n = 82)	P value	
Age, y							
 Mean ± SD (min-max)	73.3 ± 2.0 (70–79)	76.8 ± 4.0 (70–91)	<0.001	74.0 ± 2.3 (70–79)	73.9 ± 2.9 (70–81)	0.810	
 Median (IQR)	73 (72–75)	77 (74–79)	<0.001	74 (72–76)	74 (72–76)		
 ≤74	114 (75.0)	53 (26.9)		51 (62.2)	44 (53.7)		
 >74	38 (25.0)	144 (73.1)		31 (37.8)	38 (46.3)		
Male	107 (70.4)	123 (62.4)	0.120	52 (63.4)	54 (65.9)	0.744	
ECOG PS			0.048			0.844	
 0	73 (48.0)	72 (36.5)		37 (45.1)	39 (47.6)		
 1	67 (44.1)	113 (57.4)		37 (45.1)	37 (45.1)		
 2	12 (7.9)	12 (6.1)		8 (9.8)	6 (7.3)		
Tumor location			0.117			0.952	
 Cervical	6 (3.9)	3 (1.5)		3 (3.7)	2 (2.4)		
 Upper thoracic	47 (30.9)	45 (22.8)		22 (26.8)	21 (25.6)		
 Middle thoracic	77 (50.7)	121 (61.4)		45 (54.9)	48 (58.5)		
 Lower thoracic	22 (14.5)	28 (14.2)		12 (14.6)	11 (13.4)		
T stage			0.437			0.954	
 T2	68 (44.7)	99 (50.3)		42 (51.2)	45 (54.9)		
 T3	64 (42.1)	82 (41.6)		33 (40.2)	31 (37.8)		
 T4a	13 (8.6)	11 (5.6)		3 (3.7)	3 (3.7)		
 T4b	7 (4.6)	5 (2.5)		4 (4.9)	3 (3.7)		
N stage			0.790			0.966	
 N0	15 (9.9)	23 (11.7)		9 (11.0)	8 (9.8)		
 N1	81 (53.3)	111 (56.3)		45 (54.9)	48 (58.5)		
 N2	50 (32.9)	57 (28.9)		25 (30.5)	23 (28.0)		
 N3	6 (3.9)	6 (3.0)		3 (3.7)	3 (3.7)		
Clinical TNM stage a			0.356			0.931	
 Ⅱ	50 (32.9)	78 (39.6)		30 (36.6)	32 (39.0)		
 Ⅲ	88 (57.9)	99 (50.3)		44 (53.7)	43 (52.4)		
 Ⅳa	14 (9.2)	20 (10.2)		8 (9.8)	7 (8.5)		
Tumor length, cm			0.272			0.531	
 <5cm	73 (48.0)	83 (42.1)		36 (43.9)	40 (48.8)		
 ≥5cm	79 (52.0)	114 (57.9)		46 (56.1)	42 (51.2)		
Comorbidity			0.233			>0.999	
 Yes	72 (47.4)	106 (53.8)		43 (52.4)	43 (52.4)		
 No	80 (52.6)	91 (46.2)		39 (47.6)	39 (47.6)		
Smoking History			0.360			0.429	
 Yes	90 (59.2)	107 (54.3)		45 (54.9)	50 (61.0)		
 No	62 (40.8)	90 (45.7)		37 (45.1)	32 (39.0)		
Drinking History			0.240			0.754	
 Yes	86 (56.6)	99 (50.3)		43 (52.4)	45 (54.9)		
 No	66 (43.4)	98 (74.2)		39 (47.6)	37 (45.1)		
a Clinical disease stage was assessed according to the criteria of the American Joint Committee on Cancer, 8th Edition; Abbreviation: SD, standard deviation; IQR, interquartile range; ECOG PS, Eastern Cooperative Oncology Group Performance Status.

Fig. 2 (A) Mirror histograms of propensity scores for patients. Matched patients are colored. (B) Standardized mean differences (SMD) of baseline variables before and after propensity score matching (PSM). ECOG, Eastern Cooperative Oncology Group.

Fig 2

The completion of treatment is shown in Supplementary Table 1. In the TP group, 64 patients (78.0%) completed all cycles of concurrent chemotherapy, and in the S-1 group, 68 patients (82.9%) completed all cycles of concurrent chemotherapy (P = 0.431). The mean dose of radiation was 57.4 ± 4.5 Gy (range 50–61.2 Gy) in the TP group, and 57.4 ± 6.0 Gy (range 19.8–61.2 Gy) in the S-1 group (P = 0.970). Both the TP group and the S-1 group had 76 patients (92.7%) who completed the planned dose of radiotherapy.

Survival

At the time of analysis (May 1, 2024), the median follow up of the surviving patients was 42.6 months (IQR 28.0–58.8 months). A total of 80 deaths (48.8%) were recorded, including 30 (36.6%) in the TP group and 50 (61.0%) in the S-1 group. The TP group had significantly better OS than the S-1 group (HR, 0.56; 95% CI, 0.35–0.88; log-rank P = 0.010) (Fig. 3A). The median OS was not reached in the TP group and 33.4 (95% CI 22.6–44.1) months in the S-1 group. The 1-, 2-, and 3-year OS rates were 89.0% (95% CI 82.5–96.1), 71.4% (95% CI 62.1–82.0), and 66.3% (95% CI 56.3–78.0), respectively, for the TP group, and 81.5% (96% CI 73.5–90.4), 65.4% (95% CI 55.9–76.7), and 47.6% (95% CI 37.6–60.3), respectively, for the S-1 group.Fig. 3 Kaplan-Meier curves of survival for patients in the matched groups. (A) Overall survival. (B) Progression-free survival. HR, hazard ratio; CI, confidence interval.

Fig 3

Seventy-seven patients (47.0%) were alive without disease progression at the time of analysis on May 1, 2024, including 47 (57.3%) in the TP group and 30 (36.6%) in the S-1 group. The TP group had significantly better PFS than the S-1 group (HR, 0.65; 95% CI 0.42–0.99; log-rank P = 0.048) (Fig. 3B). The median PFS was not reached in the TP group and 26.6 (95% CI 18.0–35.1) months in the S-1 group. The 1-, 2-, and 3-year PFS rates were 75.6% (95% CI 66.9%−85.5%), 64.4% (95% CI 54.8%−75.7%), and 57.8% (95% CI 47.6%−70.1%), respectively, for the TP group, and 71.6% (95% CI 62.4%−82.1%), 58.0% (95% CI 48.2%−69.8%), and 41.5% (95% CI 31.8%−54.2%), respectively, for the S-1 group. Patterns of initial treatment failure are shown in Supplemental Table 3.

The subgroup analyses revealed favorable OS outcomes in the TP arm for most subgroups based on the patient demographic and baseline clinical characteristics, such as age (e.g., >74: HR, 0.38; 95%

CI 0.17–0.87), ECOG PS (e.g., 0: HR, 0.19; 95% CI 0.04–0.82), clinical TNM stage (e.g., Ⅱ: HR, 0.26; 95% CI 0.10–0.70), T stage (e.g., T2: HR, 0.37; 95% CI 0.17–0.81), N stage (e.g., N0, 1: HR, 0.44; 95% CI 0.25–0.76), tumor length (e.g., <5cm: HR, 0.42; 95% CI 0.17–0.99), and comorbidity (e.g., Yes: HR, 0.33; 95% CI 0.16–0.66) (Fig. 4). Likewise, favorable PFS outcomes in the TP arm for most subgroups, such as sex (e.g., female: HR, 0.42; 95% CI, 0.19–0.93), age (e.g., >74: HR, 0.40; 95% CI, 0.19–0.83), ECOG PS (e.g., 0: HR, 0.24; 95% CI, 0.07–0.85), clinical TNM stage (e.g., Ⅱ: HR, 0.43; 95% CI, 0.19–0.99), N stage (e.g., N0, 1: HR, 0.54; 95% CI, 0.33–0.91), and comorbidity (e.g., Yes: HR, 0.44; 95% CI 0.24–0.82) (Fig. 4). The tumor responses to treatment are reported in Supplemental Table 4. The objective response rate was comparable between groups (84.1% vs 79.3%, P = 0.419).Fig. 4 Subgroup analyses of overall survival (OS) and progression-free survival (PFS). ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; CI, confidence interval.

Fig 4

Treatment-Related toxic effects

All grade 3 or higher adverse events and grade 1 to 2 adverse events with an incidence of more than

10% are listed in Table 2. The TP group showed higher incidence rates of grade 3 or higher neutropenia vs the S-1 group (35.4% vs 6.1%; P < 0.001) and leukopenia (47.6% vs 15.9%; P < 0.001). No significant differences were observed in the incidence of all-grade toxic effects between the TP and S-1 groups, except for fever (24.4% vs. 12.2%; P = 0.043). Grade 5 toxic effects occurred in 1 patient in the TP group and 2 in the S-1 group. Three patients died of radiation pneumonitis within three months after the completion of radiotherapy.Table 2 Incidence of adverse events.

Table 2	Grade, No. (%)		
TP (n = 82)	S-1 (n = 82)		
Adverse event a	1	2	3	4	5	1	2	3	4	5	P value b	
Neutropenia	13 (15.9)	22 (26.8)	19 (23.2)	10 (12.2)	0	16 (19.5)	12 (14.6)	3 (3.7)	2 (2.4)	0	<0.001	
Leukopenia	7 (8.5)	30 (36.6)	29 (35.4)	10 (12.2)	0	8 (9.8)	19 (23.2)	11 (13.4)	2 (2.4)	0	<0.001	
Anemia	33 (40.2)	15 (18.3)	5 (6.1)	0	0	33 (40.2)	7 (8.5)	1 (1.2)	1 (1.2)	0	0.443	
Thrombocytopenia	35 (42.7)	12 (14.6)	1 (1.2)	3 (3.7)	0	21 (25.6)	5 (6.1)	2 (2.4)	1 (1.2)	0	>0.999	
Nausea	26 (31.7)	4 (4.9)	0	0	0	21 (25.6)	3 (3.7)	0	0	0	0.319	
Constipation	17 (20.7)	3 (3.7)	0	0	0	20 (24.4)	4 (4.9)	0	0	0	0.481	
Increased ALT	11 (13.4)	0	1 (1.2)	0	0	5 (6.1)	0	0	0	0	0.073	
Increased AST	8 (9.8)	0	1 (1.2)	0	0	6 (7.3)	0	0	0	0	0.416	
Total bilirubin increased	17 (20.7)	0	0	0	0	23 (28.0)	0	0	0	0	0.275	
Hypokalemia	18 (22.0)	0	0	0	0	15 (18.3)	4 (4.9)	0	0	0	0.852	
Hyponatremia	16 (19.5)	0	0	0	0	9 (11.0)	0	0	0	0	0.128	
Hypoalbuminemia	28 (34.1)	3 (3.7)	0	0	0	19 (23.2)	4 (4.9)	0	0	0	0.184	
Fever	15 (18.3)	5 (6.1)	0	0	0	8 (9.8)	2 (2.4)	0	0	0	0.043	
Esophagitis	17 (20.7)	45 (54.9)	2 (2.4)	0	0	15 (18.3)	42 (51.2)	1 (1.2)	0	0	0.283	
Pneumonitis	6 (7.3)	8 (9.8)	1 (1.2)	0	1 (1.2)	12 (14.6)	9 (11.0)	0	0	2 (2.4)	0.199	
Abbreviation: ALT, alanine aminotransferase; AST, aspartate aminotransferase.

a All grade 3 or higher acute adverse events and grade 1 to 2 acute adverse events occurring in over 10% of patients that were reported during treatment.

b P values compared grade 3 or higher hematologic adverse events and all-grade nonhematologic adverse events between groups.

Discussion

Based on the RTOG 85–01 trial [18], CCRT using a fluorouracil and cisplatin regimen is the standard treatment option for unresectable locally advanced esophageal cancer, with only 23% of enrolled patients being over the age of 70. A retrospective study [19] showed that compared with non-elderly (age < 70) esophageal cancer patients, elderly patients (age > 71) experienced more grade 3 or higher hematologic adverse events (e.g., leukopenia, 70.0% vs 49.7%, P = 0.042; anemia, 51.5% vs 17.9%, P = 0.001), leading to more than 50% of elderly patients interrupting CCRT and significantly worse median survival time (14.7 months vs 35.1 months, P = 0.01). Considering the poor tolerance of elderly patients to intravenous chemotherapy, Wang et al. [13] conducted a randomized clinical trial in elderly ESCC patients (age ≥ 70), where CCRT with the S-1 regimen had higher survival benefits compared with radiotherapy alone, and was safe, with no more grade 3 or higher adverse events observed. Several other retrospective studies [20,21] showed that elderly esophageal cancer patients could benefit from CCRT with intravenous double-drug chemotherapy regimens. There have been no studies comparing the outcomes of CCRT with intravenous double-drug or oral S-1 chemotherapy regimens in elderly ESCC patients. To our knowledge, this study is the first to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 chemotherapy regimens in elderly ESCC patients.

Our results showed that compared with the S-1 group, the TP group had better 2-year OS (71.4% vs 65.4%; HR, 0.56; 95%CI 0.35–0.88; log-rank P = 0.010) and PFS (64.4% vs 58.0%; HR, 0.65; 95%CI 0.42–0.99; log-rank P = 0.048). Previous studies on esophageal cancer patients receiving definitive chemoradiotherapy are listed in Supplemental Table 5.

Several prospective studies [11,13,22] included elderly patients over 70 years of age, receiving CCRT with the S-1 regimen, with a median OS of 24.9–28.1 months and a 2-year OS rate of 53.2%−55.7%. In this study, the median OS in the S-1 group was 33.4 months, with a 2-year OS rate of 65.4%, slightly higher than previous studies, which may be related to the age of the patients included in this study being ≤ 81 years old. A retrospective study [23] included 46 elderly patients (age > 65), with those receiving CCRT based on the 5-Fu regimen assigned to the PF group, and those receiving paclitaxel-based assigned to the DP group. Compared with the PF group, the DP group had a higher 2-year OS rate (72% vs 52%), but the difference was not significant (P = 0.296), which may be related to the small sample size. Previous studies [[24], [25], [26]] showed that the 2-year OS rate for the general population (age 18–75) of patients receiving intravenous double-drug chemotherapy was 60.5%−86.2%. The 2-year OS rate in the TP group of this study was 71.4%, indicating that elderly patients can benefit from survival with paclitaxel-based intravenous double-drug chemotherapy.

Severe hematologic toxicity is the main reason for treatment discontinuation. In this study, compared with the S-1 group, the TP group experienced higher grade 3 or higher hematologic toxicity, such as leukopenia (47.6% vs 15.9%, P < 0.001) and neutropenia (35.4% vs 6.1%, P < 0.001). In previous studies of elderly patients receiving intravenous chemotherapy CCRT [19,20,23,27,28], the incidence of grade 3–4 leukopenia or neutropenia was 9.8%−76.0%. In the general population [[24], [25], [26]], the incidence of grade 3–4 leukopenia or neutropenia was 17.8%−64.4%. The incidence of grade 3–4 hematologic toxicity in this study was less than 50%, and no deaths related to bone marrow suppression were observed. With the advancement of supportive treatment for chemotherapy-induced bone marrow suppression, we believe this is acceptable. A retrospective study [29] analyzed locally advanced ESCC patients who received CCRT from 2014 to 2016. Compared with the S-1 regimen, the combination of docetaxel and cisplatin (DP) did not prolong PFS and OS, which may be related to the poor chemotherapy completion rate of the DP group (70.9% vs 86.1%, P = 0.027). In previous studies, the chemotherapy completion rate for elderly patients receiving intravenous regimens ranged from 33.3% to 84.4% [19,20,23,27,28], and for the general population [[24], [25], [26]] (age 18–75), the completion rate for intravenous chemotherapy was 55.1%−96.7%. In this study, the chemotherapy completion rate of the TP group was 78.0%, slightly lower than that of the S-1 group (82.9%), but the difference was not significant (P = 0.431). This indicates that most elderly patients can tolerate intravenous double-drug chemotherapy, but it should be noted that all patients who received intravenous chemotherapy in this study were aged 70–79 years and did not include patients over 80 years old.

The limitations of the current study lie in its retrospective design and the heterogeneity of concurrent chemotherapy regimens. Therefore, further multicenter prospective clinical trials are needed to confirm our results.

Conclusions

In this study, paclitaxel-based concurrent chemoradiotherapy was tolerable in elderly patients with esophageal cancer and provided significant survival benefits compared with S-1-based concurrent chemoradiotherapy. Considering the potential biases that may exist in this study, further prospective, randomized controlled clinical trials are necessary.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Funding

This study was financially supported by Bethune Charitable Foundation (BCF) [grant numbers: KY202301-49].

Ethics statement

The study protocol was conducted in accordance with the Declaration of Helsinki and was approved by the clinical research ethics committee of Jiangsu Cancer Hospital (KY-2024–069). Written informed consent was waive.

CRediT authorship contribution statement

Yiyu Guo: Writing – original draft, Visualization, Methodology, Formal analysis. Tian Wang: Writing – review & editing, Visualization, Methodology, Formal analysis. Hui Li: Writing – review & editing, Visualization, Methodology, Formal analysis. Xuefeng Zhou: Writing – review & editing, Validation, Investigation, Data curation. Haifeng Shi: Writing – review & editing, Investigation, Data curation. Daguang Wu: Writing – review & editing, Investigation, Data curation. Huiguo Shan: Writing – review & editing, Investigation, Data curation. Guoren Zhou: Writing – review & editing, Validation. Zhi Zhang: Writing – review & editing, Supervision, Resources, Conceptualization. Jinjun Ye: Writing – review & editing, Supervision, Resources, Funding acquisition, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix Supplementary materials

Image, application 1

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.tranon.2024.102123.
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Reference

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