Patient characteristics
Baseline characteristics are summarized in Table 1. Seventy-seven (27.8%) patients were older than 70. Mean Charlson’s comorbidity index was 4.6±1.3, and it was more than or equal to 6 in 63 (22.7%) patients. AJCC stage was most commonly stage IIB in 100 (36.1%) patients, followed by IB in 81 (29.2%), IA in 37 (13.4%), III in 53 (19.1%), and IIA in 6 (2.2%) patients. One hundred and eight (39.0%) patients had a safety margin of less than or equal to 0.1 cm. Preoperative CA19-9 was more than or equal to 100 U/mL in 153 (55.4%) patients. The mean follow-up duration was 32.2 ± 28.6 months.
Prognostic factors for OS
In total cohort, median OS was 35.1 (95% CI, 30.6-44.4) months. In univariable Cox proportional hazard regression analysis, variables that showed P<0.1 included safety margin ≤0.1 cm, poorly differentiated or undifferentiated histology, high AJCC stage, preoperative CA19-9≥100 U/mL, and lymphovascular or perineural invasion. In multivariable-adjusted Cox proportional hazard regression analysis, lymphovascular invasion and preoperative CA19-9 level were independent prognostic factors (P<0.001 and P=0.007, respectively). The number of patients and OS classified by each variable are summarized in Table 2. In the unmatched cohort, the proportion of patients with age≥70 and safety margin≤0.1 cm was higher in the SCT group than in the SCT-CRT. After propensity score-matching, there were no significant differences in variables associated with OS between the two groups (Table 3).
Therapeutic outcomes between SCT and SCT-CRT groups in the unmatched cohort
Adjuvant SCT was performed in 78 patients, including 44 patients receiving gemcitabine, 22 patients receiving FFA, 11 patients receiving gemcitabine plus nab-paclitaxel, and 1 patient receiving S-1. In the SCT group, the median treatment duration was 139.9 ± 49.1 days and 57 (73.1%) patients completed planned adjuvant protocols. Overall, 199 patients received adjuvant SCT-CRT; the most frequent chemotherapeutic agent for CRT was 5-fluorouracil (119/199, 59.8%), followed by gemcitabine (80/199, 40.2%). In the SCT-CRT group, 51 patients underwent induction chemotherapy with gemcitabine plus cisplatin and 10 patients with gemcitabine. After CRT, patients received gemcitabine most frequently (116/199, 58.3%), followed by FFA (70/199, 35.2%) for maintenance adjuvant chemotherapy. The median treatment duration was 196.9 ± 46.7 days in the SCT-CRT group, and 153 (76.9%) patients completed planned adjuvant protocols. The median treatment duration was significantly longer in the SCT-CRT group than in the SCT group (P<0.001), while there was no significant difference in completion rate of planned regimens between the two groups (P=0.534).
Median OS in the SCT group and the SCT-CRT group was 31.1 (95% CI, 26.9-47.4) months and 35.9 (95% CI, 30.7-47.8) months, respectively (P=0.681). During follow-up, recurrence occurred in 170 (61.4%) patients, and median RFS was 16.8 (95% CI 15.0-21.9) months. There was no significant difference in RFS between the SCT and SCT-CRT groups (15.4 [95% CI, 11.6-24.8] months and 17.7 [95% CI, 15.0-23.6] months, respectively; P=0.453). Figure 2A and 2B illustrate the differences in OS and RFS between the SCT and SCT-CRT groups in the unmatched cohort.
Therapeutic outcomes between SCT and SCT-CRT groups in the propensity score-matched cohort
The propensity score-matched cohort was comprised of 142 patients; 71 patients each were classified as SCT group and SCT-CRT group. The median OS was 35.1 (95% CI, 26.9-82.1) months in the SCT group and 34.8 (95% CI, 26.2-69.2) months in the SCT-CRT group (P=0.993). The median RFS of the patients who underwent SCT was 15.4 (95% CI, 12.1-31.1) months, which was not significant different from that of patients who received SCT-CRT (17.0 [95% CI, 13.2-33.9] months; P=0.789). Figure 3A and 3B show the differences in OS and RFS between the two groups in the propensity score-matched cohort
Differences in the recurrence pattern between SCT and SCT-CRT groups are summarized in Table 4. Recurrence was confirmed in 40 (56.3%) patients in the SCT group and 43 (60.6%) in the SCT-CRT group (P=0.734). There were no significant differences in the incidence of loco-regional and distant recurrence between the two groups (P=0.833 and P=0.491, respectively). The liver was the most common site of distant recurrence in both groups. There was no significant difference in the number of patients who could undergo further lines of treatment after relapse between SCT and SCT-CRT groups (42.1% and 47.9%, respectively; P=0.613).
Details of adverse events greater than or equal to moderate grade during adjuvant treatment are summarized in Table 5. No somatic adverse events were significantly different between the two groups. The incidences of neutropenia, anemia, and hypertransaminesemia were higher in the SCT-CRT group than in the SCT group. In total, adverse events greater than or equal to moderate grade occurred more frequently in the SCT-CRT group than in the SCT group (P=0.042.