Journal List > J Gynecol Oncol > v.29(4) > 1148308

Wang, Christie, Folkert, Xie, and Albuquerque: Value of combined adjuvant chemotherapy and radiation on survival for stage III uterine cancer: is less radiation equal to more?

Abstract

Objective

Locally advanced endometrioid adenocarcinoma (LA-EAC) accounts for the majority of deaths for this cancer, yet there is no consensus on adjuvant treatment after surgery. Past studies suggest that combined modality treatment (CMT) may improve outcomes over treatment with chemotherapy (CT) or radiation therapy (RT, either external beam radiotherapy [EBRT] or vaginal brachytherapy [VBT]) alone. Using a large US-based population-based registry, we evaluated adjuvant CMT in LA-EAC and the relative benefit of regional EBRT compared to focused VBT.

Methods

We studied patients diagnosed with Stage III LA-EAC between 2004 and 2013 from the National Cancer Data Base (NCDB). We used Cox regression and a log-rank test to assess survival based on treatment with CT alone, EBRT alone, VBT alone, or CMT with EBRT and/or VBT. We used a χ2 test to compare covariates between patients receiving CMT with EBRT or VBT.

Results

Patients who received CMT had better survival than those who received CT or EBRT/VBT alone. Compared to CMT with VBT, patients who received CMT with EBRT were slightly older and had more advanced-stage or positive nodes, and fewer had lymph node surgery. We found no survival difference between CMT with EBRT and CMT with VBT even when categorizing patients as high or low risk according to age, grade, and stage (low-risk p=0.3460; high-risk p=0.2158).

Conclusion

CMT was associated with superior survival outcomes compared to monotherapy. We observed no survival difference between radiation modalities in CMT, which highlights the effectiveness of a more focused treatment like brachytherapy.

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Fig. 1.
CONSORT diagram of patients with stage III endometrioid adenocarcinoma from NCDB receiving adjuvant therapy. CT, chemotherapy; EBRT, external beam radiotherapy; EC, endometrial cancer; NCDB, National Cancer Data Base; RT, radiation therapy; VBT, vaginal brachytherapy.
jgo-29-e49f1.tif
Fig. 2.
Survival of patients with LA-EAC according to adjuvant treatment modality. CMT with either EBRT or VBT had better survival compared to monotherapy. CI, confidence interval; CMT, combined modality treatment; CT, chemotherapy; EBRT, external beam radiotherapy; HR, hazard ratio; LA-EAC, locally advanced endometrioid adenocarcinoma; OS, overall survival; VBT, vaginal brachytherapy.
jgo-29-e49f2.tif
Fig. 3.
Survival of patients receiving adjuvant hemoradiation. (A) Low-risk (age <60, grade 1–2, stage IIIA) patients according to type of adjuvant radiation modality. (B) High-risk (age >60, grade 3–4, stage IIIC) patients according to type of adjuvant radiation modality. CT, chemotherapy; EBRT, external beam radiotherapy; OS, overall survival; VBT, vaginal brachytherapy.
jgo-29-e49f3.tif
Table 1.
Demographics and clinical characteristics according to adjuvant CMT
Characteristics CT+EBRT (n=3,161) CT+VBT (n=707) p
Age (yr)     0.006
<60 1,560 (49.4) 389 (55.0)
≥60 1,601 (50.6) 318 (45.0)
Race     0.032
White 2,703 (86.6) 609 (87.8)
Black 260 (8.3) 65 (9.4)
Other 160 (5.1) 20 (2.9)
Median miles from hospital (IQR) 10.7 (4.7–25.2) 12.3 (5.6–26.1) 0.008
Charlson-Deyo score     0.547
0 2,460 (77.8) 539 (76.2)
1 579 (18.3) 142 (20.1)
2 122 (3.9) 26 (3.7)
Geographic location     <0.001
Central 1,182 (38.6) 284 (41.6)
Mountains 142 (4.6) 26 (3.8)
Northeast 166 (5.4) 105 (15.4)
Pacific 448 (14.6) 38 (5.6)
Southeast 1,125 (36.7) 230 (33.7)
LN surgery     0.017
No LN surgery 603 (19.2) 108 (15.3)
LN surgery 2,534 (80.8) 596 (84.7)
Pathological stage     <0.001
3A 1,215 (43.7) 354 (53.9)
3B 295 (10.6) 66 (10.0)
3C 1,193 (42.9) 212 (32.3)
3NOS 76 (2.7) 25 (3.8)
Grade     0.810
1 or 2 1,472 (46.6) 320 (45.3)
3 or 4 1,259 (39.8) 287 (40.6)
Unknown 430 (13.6) 100 (14.1)
FIGO grade (2010–2013)     0.711
Type I 428 (23.4) 105 (23.9)
Type II 303 (16.6) 79 (18.0)
Type II Unknown 303 (16.6)1,097 (60.0) 79 (18.0) 255 (58.1)
Pelvic node status (2010–2013)     <0.001
Negative 817 (44.7) 250 (56.9)
Positive 596 (32.6) 111 (25.3)
Unknown 415 (22.7) 78 (17.8)
Para-aortic node status (2010–2013)     <0.001
Negative 696 (38.1) 221 (50.3)
Positive 266 (14.6) 55 (12.5)
Unknown 866 (47.4) 163 (37.1)

Values are presented as number of patients (%) not otherwise specified. CMT, combined modality treatment; CT, chemotherapy; EBRT, external beam radiotherapy; FIGO, International Federation of Gynecology and Obstetrics; IQR, nterquartile range; LN, lymph node; VBT, vaginal brachytherapy.

Table 2.
Multivariate analysis of survival by CMT
Characteristics CT+EBRT CT+VBT
HR (95% CI) p HR (95% CI) p
Age (yr)
<60 Reference   Reference  
≥60 1.94 (1.64–2.30) <0.001 2.52 (1.67–3.80) <0.001
Race
White Reference   Reference  
Black 1.49 (1.17–1.91) 0.001 1.27 (0.75–2.15) 0.375
Other 1.13 (0.76–1.67) 0.557 2.91 (1.02–8.25) 0.045
Charlson-Deyo score
0 Reference   Reference  
1 1.39 (1.14–1.69) 0.001 1.00 (0.66–1.54) 0.983
2 1.41 (0.99–2.01) 0.058 4.96 (2.57–9.57) <0.001
LN surgery
No LN surgery Reference    
LN surgery 0.42 (0.33–0.53) <0.001  
Pathological stage
3A Reference   Reference  
3B 1.47 (1.10–1.96) 0.009 2.27 (1.24–4.16) 0.008
3C 2.16 (1.78–2.62) <0.001 2.81 (1.90–4.15) <0.001
3NOS 1.22 (0.73–2.04) 0.445 0.42 (0.10–1.77) 0.237
Grade
1 or 2 Reference   Reference  
3 or 4 1.88 (1.57–2.24) <0.001 1.44 (0.98–2.12) 0.065
Unknown 1.41 (1.05–1.89) 0.022 1.24 (0.69–2.23) 0.474

CI, confidence interval; CMT, combined modality treatment; CT, chemotherapy; EBRT, external beam radiotherapy; HR, hazard ratio; LN, lymph node; VBT, vaginal brachytherapy; NOS, non-organ specific.

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