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  • br invasion NOS not otherwise specified Gov other government agency

    2022-05-30


    invasion; NOS: not otherwise specified; Gov: other government agency; ref.: reference level.
    = 1.03, 95% CI, 0.94–1.13, P = 0.49; Table 3, Fig. 2F). Multivariable models of unadjusted analyses are presented in Tables S10–S11. When the number of days between RT and chemotherapy start dates for the patients who received RT after CT was plotted on a histogram there appeared to be a bimodal distribution (Fig. S2). One subset of pa-tients started RT between 50 and 100 d following the start of CT (peak ~65 d), while a second subset started RT between 110 and 200 d follow-ing the start of CT (peak ~145 d). To explore whether the start date of RT
    following CT was associated with survival benefit, a multivariable anal-ysis was performed of propensity-score matched cohorts of women whose RT start date was 126–200 d after her CT start date (and there-fore thought to have received 5 or 6 cycles of CT) and women whose RT start date was 61–125 d after her CT start date (and therefore thought to have received 3 or 4 cycles of CT). There was no association of this Tunicamycin variable with OS (TR = 0.87, 95% CI = 0.73–1.04, P = 0.13). When an expanded cohort including women with Grade 3 endometrioid histology was utilized, results were consistent those of the original cohort of Type 1 endometrioid histology alone. In this ex-panded cohort of women, treatment with RT after CT was associated with significantly longer OS compared to treatment with RT before CT (5 y OS: 72.6% vs 65.8%; time-ratio (TR) = 1.22, 95% CI = 1.05–1.42, P
    4. Discussion
    In this analysis of a large cohort of women from the NCDB with Stage III-IVA Type 1 EC following hysterectomy, treatment with RT after CT was associated with longer OS compared to treatment with RT before CT, or either treatment alone. Women who received RT before CT, how-ever, did not experience significantly longer OS than women who re-ceived CT or RT alone, nor did women who received CT alone experience significantly different survival than women who received RT alone. Treatment with multi-agent CT followed by RT may therefore 
    be the optimal adjuvant multimodality regimen for selected women with EC whose disease characteristics are prognostic for a high risk of LRR but a lower risk of distant recurrence. Historical randomized trials addressing women with locally ad-vanced EC have included heterogeneous cohorts and yielded results with limited applicability. An Italian trial of women with primarily Stage III non-serous or clear cell EC randomized after hysterectomy to RT to the pelvis ± para-aortic (PA) lymph node chain versus multi-agent CT found no difference in PFS or OS [16]. Similarly, a Japanese trial of women with a mix of stages and histological subtypes random-ized following hysterectomy and lymph node dissection (LND) to RT or to cisplatin/doxorubicin CT demonstrated no differences in PFS or OS between arms, although subset analyses suggested superior survival for those patients deemed “high risk” treated with CT [17]. Subset anal-yses of matched cohorts of patients treated with either RT or CT reflect these data (Fig. 2F). The role of adjuvant CT in this setting was cemented following GOG-122, in which women with Stage III-IVA EC randomized after hysterectomy and LND to cisplatin/doxorubicin experienced sig-nificantly longer PFS and OS compared to women who received whole abdominal RT with a pelvic boost. Recurrences in the pelvis, however, were more common in the CT arm, comprising 21% of all first failures [18]. It seemed logical to next explore treatment with a combination of CT and RT, addressing the potential for both local and systemic relapse.
    The GOG-258 and PORTEC-3 trials examined this question from complementary angles. PORTEC-3 enrolled 660 women with high-risk stage IB-III EC, weighted heavily towards stage III, randomized to re-ceive either RT alone or RT with concurrent cisplatin followed by 4 cycles of carboplatin and paclitaxel (CRT) [1]. The addition of CT to RT was associated with a trend towards improved 5 y PFS and OS in the entire cohort. In a subset analysis limited to women with stage III disease, the 5 y PFS benefit reached statistical significance at 69% versus 58% (P = 0.03). Asking a mirror image question, GOG-258 randomized 813 women with stage III-IVA EC to 6 cycles of chemotherapy alone (carboplatin and paclitaxel) versus CRT per PORTEC (RT followed by carboplatin/paclitaxel) [2]. While the 5 y rates of vaginal and pelvic or PA recurrences were higher in the CT arm (7% vs. 3% and 19% vs. 10%, re-spectively), the rate of distant recurrences was lower in the CT arm (21% vs. 27%). There was a small, but non-significant numerical advantage in PFS favoring the CRT arm (HR 0.9), but no difference in OS. Exploratory subset analyses did not identify subgroups that derived benefit from CRT. Consistent with these data, subset analyses presented in this man-uscript show no statistical difference in OS between women treated with RT before CT compared to either CT alone as was seen in GOG-258 (Fig. 2D), or RT alone, as was seen in PORTEC-3 (Fig. 2E).