Evaluation of the optimal sequence of adjuvant chemotherapy and radiation therapy in the treatment of advanced endometrial cancer

McEachron, Jennifer; Zhou, Nancy; Spencer, Christina; Shanahan, Lisa; Chatterton, Carolyn; Singhal, Pankaj; Lee, Yi-Chun

doi:10.3802/jgo.2020.31.e90

Cited by 7 publications

(5 citation statements)

References 24 publications

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“…We observed an increase in retroperitoneal recurrence in patients receiving adjuvant chemotherapy alone versus chemoradiation. These findings agree with existing retrospective as well as prospective data, suggesting the importance of radiation therapy in retroperitoneal disease control [13,[20][21][22]. Additionally, we observed a higher incidence of isolated positive para-aortic lymph nodes (18.1%) than previously reported in the literature.…”

Section: Discussionsupporting

confidence: 92%

Evaluation of Survival, Recurrence Patterns and Adjuvant Therapy in Surgically Staged High-Grade Endometrial Cancer with Retroperitoneal Metastases

McEachron

Marshall

Zhou

et al. 2021

Cancers

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Background: We seek to evaluate the difference in recurrence patterns and survival among stage IIIC high-grade endometrial cancer treated with surgery followed by adjuvant chemotherapy alone, radiation therapy alone, or both (chemoradiation). Methods: A multicenter retrospective analysis of surgically staged IIIC HGEC receiving adjuvant therapy was conducted. HGEC was defined as grade 3 endometrioid adenocarcinoma, serous, clear cell and carcinosarcoma. Differences in the frequency of recurrence sites and treatment delays were identified using Pearson’s χ2 test. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier estimates. Results: A total of 155 patients were evaluable: 41.9% carcinosarcoma, 36.8% serous, 17.4% grade 3 and 3.9% clear cell. Of these, 67.1% received chemoradiation, 25.8% received chemotherapy and 7.1% received radiation therapy. There was no difference in the frequency of treatment delays between regimens (p = 0.571). There was a trend towards greater retroperitoneal recurrence with chemotherapy (25.9%) versus chemoradiation (8.4%) and radiation therapy (7.7%) (p = 0.252). Grade 3 tumors had improved progression-free and overall survival (26 and 42 months, respectively) versus serous (17 and 30 months, respectively), carcinosarcoma (14 and 24 months, respectively) and clear cell (24 and 30 months respectively) (p = 0.002, p < 0.001). Overall, chemoradiation was superior to chemotherapy and radiation therapy in PFS (p < 0.001) and OS (p < 0.001). Upon multivariate analysis, only histology and receipt of chemoradiation were independent predictors of survival. Conclusion: The majority of stage IIIC high-grade endometrial carcinomas recurred. Chemoradiation was associated with improved survival and less retroperitoneal recurrence. Grade 3 tumors demonstrated improved survival versus other histologies regardless of adjuvant treatment modality.

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Section: Discussionsupporting

confidence: 92%

Evaluation of Survival, Recurrence Patterns and Adjuvant Therapy in Surgically Staged High-Grade Endometrial Cancer with Retroperitoneal Metastases

McEachron

Marshall

Zhou

et al. 2021

Cancers

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“…In a later cohort study assessing the same group of patients, the authors also identified a better 5-year OS (62% vs. 35%) and PFS (57% vs. 35%) using subgroup analyses among stage IIIC2 patients treated with a sandwich sequence when compared with sequential chemoradiotherapy (20). In addition, McEachron et al have demonstrated OS and PFS benefits in patients with stage III-IV EC treated with sandwich therapy when compared with those treated with alternate sequences (21). In this multicenter analysis assessing 152 patients with relatively poor histology, 44% had endometrioid, 47.5% presented serous EC, and 8.5% had clear cell EC.…”

Section: Discussionmentioning

confidence: 92%

“…The sandwich sequence, comprising 2 to 4 cycles of CT followed by irradiation and subsequent CT, has shown promising results in several phase II studies and retrospective cohorts (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). However, its efficacy has been inconsistent and was further limited by small study samples, as well as heterogeneous compositions of histology and staging across studies.…”

Section: Introductionmentioning

confidence: 99%

Outcomes of “sandwich” chemoradiotherapy compared with chemotherapy alone for the adjuvant treatment of FIGO stage III endometrial cancer

Wang

Sun

et al. 2022

Front. Oncol.

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ObjectiveTo analyze and compare outcomes of adjuvant chemoradiotherapy in patients with International Federation of Gynecology and Obstetrics (FIGO) stage III endometrial cancer (EC) patients using the “Sandwich” sequence and chemotherapy (CT) alone.MethodsFrom, 2005 to, 2019, we retrospectively reviewed 80 patients with FIGO stage III EC who received treatment at our institute. We analyzed 66 patients who had undergone complete surgical staging followed by adjuvant treatment with sandwich chemoradiotherapy (39 patients) and CT alone (27 patients). The 5-year overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) were calculated using the Kaplan–Meier method. Additional prognostic factors were analyzed using Cox proportional hazards regression.ResultsHerein, the analysis was conducted using 66 patients with a median follow-up period of 50 and 85 months in the sandwich and CT-alone arms. Comparing the sandwich sequence and CT-alone groups, the 5-year OS and PFS were 87% vs. 70% (p = 0.097) and 77% vs. 65% (p = 0.209), respectively. The sandwich therapy conferred an improved 5-year DSS (92% vs. 70%, p = 0.041) and a lower local recurrence rate (0% vs. 11%, p = 0.031). In multivariable analyses, grade 3 histology and deep myometrial invasion were independent risk factors for 5-year OS and DSS. The sandwich sequence was a positive predictor for 5-year DSS (hazard ratio [HR] = 0.23, p = 0.029). The sandwich arm demonstrated higher acute hematologic toxicity than the CT-alone arm. CT dose delay/reduction and treatment completion rates were similar in both groups.ConclusionFor patients with stage III EC, postoperative sandwich chemoradiotherapy appears to offer a superior 5-year DSS and local control with tolerable toxicity when compared with CT alone.

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“…In 2020, McEachron et al compared CT-RT-CT (36.8% of the population) vs. CT followed by RT (28.9%) or RT followed by CT (34.2%) in a sample of 152 patients. CT-RT-CT demonstrated superiority over CT-CR and RT-CT sequencing in terms of 3-year PFS (55% vs. 34% and 37%, respectively) and 3-year OS (71% vs. 50% and 52%, respectively) [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

The “Sandwich” Schedule: A Well-Tolerated Adjuvant Treatment Both in Intermediate–High- and High-Risk Endometrial Cancer

et al. 2022

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(1) Background: In intermediate–high- and high-risk endometrial cancer (EC), radiotherapy (RT) and chemotherapy (CT) play a basic role. However, there is controversy regarding the optimal timing of their combination. The “sandwich” schedule involves adjuvant CT followed by RT and subsequent CT. The aim of this study is to assess the tolerability and efficacy of the “sandwich” schedule. (2) Methods: A retrospective study was conducted in two gynecological oncology units in Torino, Italy, from 01/01/2003 until 31/12/2021. Intermediate–high- and high-risk patients with available clinical data were included. Compliance with treatment, CT and RT toxicities, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. (3) Results: A total of 118 patients were selected: 27,1% FIGO I-II stages and 72.9% III-IV. Most of the patients (75.4%) received a carboplatin–paclitaxel combination, and as much as 94.9% of CT cycles were completed. Chemotherapy-related G3-4 toxicities were detected in 5.3% of the patients, almost half of which were hematological. Grade 2 gastrointestinal and genitourinary toxicities were reported in 8.4% and 4.2% of cases, respectively. With a median follow-up of 46 months, DFS was 77.6%, CSS was 70% and 5-year OS was 54%. (4) Conclusions: The “sandwich” schedule for CT and RT combination is an effective adjuvant treatment with low toxicity both in intermediate–high- and high-risk EC.

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Evaluation of the optimal sequence of adjuvant chemotherapy and radiation therapy in the treatment of advanced endometrial cancer

Cited by 7 publications

References 24 publications

Evaluation of Survival, Recurrence Patterns and Adjuvant Therapy in Surgically Staged High-Grade Endometrial Cancer with Retroperitoneal Metastases

Evaluation of Survival, Recurrence Patterns and Adjuvant Therapy in Surgically Staged High-Grade Endometrial Cancer with Retroperitoneal Metastases

Outcomes of “sandwich” chemoradiotherapy compared with chemotherapy alone for the adjuvant treatment of FIGO stage III endometrial cancer

The “Sandwich” Schedule: A Well-Tolerated Adjuvant Treatment Both in Intermediate–High- and High-Risk Endometrial Cancer

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