Brachytherapy quality assurance in the PORTEC-4a trial for molecular-integrated risk profile guided adjuvant treatment of endometrial cancer

BackgroundVaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients’ risk of recurrence based on molecular tumor characteristics.Primary objectivesTo compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapyStudy hypothesisAdjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs.Trial designA multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm).Major inclusion/exclusion criteriaWomen aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1).EndpointsThe primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs.Sample size500 eligible and evaluable patients.Estimated dates for completing accrual and presenting resultsEstimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023.Trial registrationThe trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

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Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: Evaluation of the pilot phase of the PORTEC-4a trial

Gynecologic Oncology ◽

10.1016/j.ygyno.2018.07.020 ◽

2018 ◽

Vol 151 (1) ◽

pp. 69-75 ◽

Cited By ~ 57

Author(s):

B.G. Wortman ◽

T. Bosse ◽

R.A. Nout ◽

L.C.H.W. Lutgens ◽

E.M. van der Steen-Banasik ◽

...

Keyword(s):

Endometrial Cancer ◽

Adjuvant Radiotherapy ◽

Risk Profile ◽

Pilot Phase ◽

Integrated Risk

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Whole Abdominal Radiotherapy in the Adjuvant Treatment of Patients With Stage III and IV Endometrial Cancer: A Gynecologic Oncology Group Study

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(08)70597-6 ◽

2006 ◽

Vol 2006 ◽

pp. 449-452

Author(s):

S.D. Yamada

Keyword(s):

Endometrial Cancer ◽

Adjuvant Treatment ◽

Gynecologic Oncology ◽

Stage Iii ◽

Gynecologic Oncology Group ◽

Oncology Group ◽

Oncology Group Study ◽

Abdominal Radiotherapy

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PROGNOSTIC BENEFIT OF POLE EXONUCLEASE DOMAIN MUTATIONS IN ENDOMETRIAL CANCER CANNOT BE EXPLAINED BY INCREASED SENSITIVITY TO ADJUVANT TREATMENT STRATEGIES

10.26226/morressier.599bdc7ad462b80296ca11ce ◽

2017 ◽

Author(s):

Inge Van Gool

Keyword(s):

Endometrial Cancer ◽

Adjuvant Treatment ◽

Treatment Strategies ◽

Exonuclease Domain ◽

Increased Sensitivity

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Defining optimal adjuvant treatment for high-risk early-stage endometrial cancer

Gynecologic Oncology ◽

10.1016/s0090-8258(21)00877-5 ◽

2021 ◽

Vol 162 ◽

pp. S123-S124

Author(s):

Olivia Khouri ◽

Anne Van Arsdale ◽

Nicole Vilardo ◽

Divya Gowthaman ◽

Gregory Gressel ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Adjuvant Treatment ◽

Early Stage ◽

Early Stage Endometrial Cancer

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Quality assurance of the 22961 EORTC trial. A phase III study of the optimal combination of hormonal adjuvant treatment by LHRH analogue and radiation therapy for the management of locally advanced prostate cancer: the dummy run

Radiotherapy and Oncology ◽

10.1016/j.radonc.2004.08.005 ◽

2004 ◽

Vol 73 (1) ◽

pp. 11-20 ◽

Cited By ~ 19

Author(s):

Vassilis E. Kouloulias ◽

Jean-Yves Giraud ◽

Bernard J. Davis ◽

Andrée Dusserre ◽

Alfredo Zurlo ◽

...

Keyword(s):

Prostate Cancer ◽

Quality Assurance ◽

Radiation Therapy ◽

Adjuvant Treatment ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Optimal Combination ◽

Phase Iii ◽

Locally Advanced Prostate Cancer ◽

Phase Iii Study

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Lymphadenectomy in Early-Stage Intermediate-/High-Risk Endometrioid Endometrial Cancer: Clinical Characteristics and Outcomes in an Australian Cohort

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001039 ◽

2017 ◽

Vol 27 (7) ◽

pp. 1379-1386 ◽

Cited By ~ 1

Author(s):

Rhonda Farrell ◽

Suzanne C. Dixon ◽

Jonathan Carter ◽

Penny M. Webb

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

High Risk ◽

Adjuvant Treatment ◽

Cox Regression ◽

Early Stage ◽

Cox Regression Analysis ◽

Cancer Study ◽

Stage Ib ◽

Australian Cohort

ObjectiveThe role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity.Materials and MethodsFrom a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ2 tests.ResultsMedian follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a “high-risk” group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P < 0.0001).ConclusionsIn this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.

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