Journal List > J Gynecol Oncol > v.30(3) > 1148320

Onal, Sari, Yildirim, Yavas, Gultekin, Guler, Akyurek, and Yildiz: A multi-institutional analysis of sequential versus ‘sandwich' adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma

Abstract

Objective

To analyze the outcomes of sequential or sandwich chemotherapy (ChT) and radiotherapy (RT) in patients with node-positive endometrial cancer (EC).

Methods

Data from 4 centers were collected retrospectively for 179 patients with stage IIIC EC treated with postoperative RT and ChT (paclitaxel and carboplatin). Patients were either treated with 6 cycles of ChT followed by RT (sequential arm; 96 patients) or with 3 cycles of ChT, RT, and an additional 3 cycles of ChT (sandwich arm; 83 patients). Prognostic factors affecting overall survival (OS) and progression-free survival (PFS) were analyzed.

Results

The 5-year OS and PFS rates were 64% and 59%, respectively, with a median follow-up of 41 months (range, 5–167 months). The 5-year OS rates were significantly higher in the sandwich than sequential arms (74% vs. 56%; p=0.03) and the difference for 5-year PFS rates was nearly significant (65% vs. 54%; p=0.05). In univariate analysis, treatment strategy, age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology, rate of myometrial invasion, and grade were prognostic factors for OS and PFS. In multivariate analysis, non-endometrioid histology, advanced FIGO stage, and adjuvant sequential ChT and RT were negative predictors for OS, whereas only non-endometrioid histology was a prognostic factor for PFS.

Conclusion

Postoperative adjuvant ChT and RT for stage IIIC EC patients, either given sequentially or sandwiched, offers excellent clinical efficacy and acceptably low toxicity. Our data support the superiority of the sandwich regimen compared to the sequential strategy in stage IIIC EC patients for OS.

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Fig. 1.
(A) The OS and (B) PFS of patients treated with postoperative sandwich ChT (solid line) and adjuvant sequential ChT and RT (dashed line) in the entire cohort. ChT, chemotherapy; OS, overall survival; PFS, progression-free survival; RT, radiotherapy.
jgo-30-e28f1.tif
Fig. 2.
(A) The OS and (B) PFS of patients treated with postoperative sandwich ChT (solid line) and adjuvant sequential ChT and RT (dashed line) for patients with non-endometrioid histology. ChT, chemotherapy; OS, overall survival; PFS, progression-free survival; RT, radiotherapy.
jgo-30-e28f2.tif
Fig. 3.
(A) The OS and (B) PFS of patients treated with postoperative sandwich ChT (solid line) and adjuvant sequential ChT and RT (dashed line) for patients with endometrioid histology. ChT, chemotherapy; OS, overall survival; PFS, progression-free survival; RT, radiotherapy.
jgo-30-e28f3.tif
Table 1.
Patient and tumor characteristics according to ChT regimen
Patient characteristics All patients Sequential ChT Sandwich ChT p-value
Patient age       0.02
 <60 yr 89 (50) 55 (31) 34 (23)  
 ≥60 yr 90 (50) 41 (19) 49 (27)  
Stage       0.27
 IIIC1 120 (67) 62 (35) 58 (32)  
 IIIC2 59 (33) 34 (19) 25 (14)  
Pathology       0.12
 Endometrioid 129 (72) 65 (36) 64 (36)  
 Non-endometrioid 50 (28) 31 (17) 19 (11)  
LVSI       0.67
 Present 117 (65) 61 (34) 56 (31)  
 Absent 44 (25) 26 (15) 18 (10)  
 Unknown 18 (10) 9 (5) 9 (5)  
Myometrial invasion       0.07
 <50% 44 (24) 20 (11) 24 (13)  
 ≥50% 123 (69) 66 (37) 57 (32)  
 Unknown 12 (7) 10 (6) 2 (1)  
Grade       0.79
 I 33 (18) 16 (9) 17 (9)  
 II 59 (33) 32 (18) 27 (15)  
 III 87 (49) 48 (27) 39 (22)  
Vaginal BRT       0.07
 Absent 91 (51) 55 (31) 36 (20)  
 Present 88 (49) 41 (23) 47 (26)  

Values are presented as number (%).

BRT, brachytherapy; ChT, chemotherapy; LVSI, lymphovascular space invasion.

Table 2.
Univariate analysis of prognostic factors for OS and PFS
Patient characteristics 5-year OS (%) p-value 5-year PFS (%) p-value
Patient age   0.04   0.04
 <60 yr 72   68  
 ≥60 yr 56   50  
Stage   0.001   0.004
 IIIC1 74   68  
 IIIC2 45   45  
Pathology   <0.001   <0.001
 Endometrioid 72   67  
 Non-endometrioid 43   40  
LVSI   0.1   0.18
 Absent 72   67  
 Present 58   55  
Myometrial invasion   0.03   0.03
 <50% 82   78  
 ≥50% 62   56  
Grade   <0.001   0.003
 I–II 74   67  
 III 53   51  
Vaginal BRT   0.2   0.84
 Absent 67   60  
 Present 60   59  
ChT   0.03   0.05
 Sequential 56   54  
 Sandwich 74   65  

BRT, brachytherapy; ChT, chemotherapy; LVSI, lymphovascular space invasion; OS, overall survival; PFS, progression-free survival.

Table 3.
Multivariate analysis of prognostic factors for OS and PFS
Variables Risk factors HR (95% CI) p-value
OS      
 Age (yr) >60 vs. ≤60 1.69 (0.93–3.06) 0.08
 Pathology Non-endometrioid vs. endometrioid 2.16 (1.08–4.32) 0.03
 Stage IIIC2 vs. IIIC1 2.01 (1.15–3.53) 0.02
 Grade III vs. I and II 1.39 (0.67–2.86) 0.36
 Myometrial invasion ≥50% vs <50% 2.19 (0.93–5.18) 0.07
 ChT Sequential vs. sandwich 1.89 (1.04–3.45) 0.04
PFS      
 Age (yr) >60 vs. ≤60 1.67 (0.97–2.89) 0.07
 Pathology Non-endometrioid vs. endometrioid 2.44 (1.28–4.65) 0.007
 Stage IIIC2 vs. IIIC1 1.53 (0.90–2.58) 0.09
 Grade III vs. I and II 1.02 (0.53–1.97) 0.64
 Myometrial invasion ≥50% vs. <50% 2.00 (0.94–4.26) 0.07
 ChT Sequential vs. sandwich 1.57 (0.92–2.69) 0.09

ChT, chemotherapy; CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.

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