1. Adjuvant therapy for endometrial cancer in the era of molecular classification: radiotherapy, chemoradiation and novel targets for therapy.
期刊:International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
日期:2020-10-20
DOI :10.1136/ijgc-2020-001822
Endometrial cancer is primarily treated with surgery. Adjuvant treatment strategies for endometrial cancer, such as external beam pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and combined chemotherapy and radiotherapy, have been studied in several randomized trials. Adjuvant treatment is currently based on the presence of clinico-pathological risk factors. Low-risk disease is adequately managed with surgery alone. In high-intermediate risk endometrial cancer, adjuvant vaginal brachytherapy is recommended to maximize local control, with only mild side effects and without impact on quality of life. For high-risk endometrial cancer, recent large randomized trials support the use of pelvic radiotherapy, especially in stage I-II endometrial cancer with risk factors. For women with serous cancers and those with stage III disease, chemoradiation increased both recurrence-free and overall survival, while GOG-258 showed similar recurrence-free survival compared with six cycles of chemotherapy alone, but with better pelvic and para-aortic nodal control with combined chemotherapy and radiotherapy. Recent molecular studies, most notably the work from The Cancer Genome Atlas (TCGA) project, have shown that four endometrial cancer molecular classes can be distinguished; ultra-mutated, microsatellite instable hypermutated, copy-number-low, and copy-number-high. Subsequent studies, using surrogate markers to identify groups analogous to TCGA sub-classes, showed that all four endometrial cancer sub-types are found across all stages, histological types, and grades. Moreover, the molecular sub-groups have proved to have a stronger prognostic impact than histo-pathological tumor characteristics. This introduces an new era of molecular classification based diagnostics and treatment approaches. Integration of the molecular factors and new therapeutic targets will lead to molecular-integrated adjuvant treatment including targeted treatments, which are the rationale of new and ongoing trials. This review presents an overview of current adjuvant treatment strategies in endometrial cancer, highlights the development and evaluation of a molecular-integrated risk profile, and briefly discusses ongoing developments in targeted treatment.
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1区Q1影响因子: 41.9
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2. Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy.
期刊:Journal of clinical oncology : official journal of the American Society of Clinical Oncology
日期:2020-08-04
DOI :10.1200/JCO.20.00549
PURPOSE:The randomized Adjuvant Chemoradiotherapy Versus Radiotherapy Alone in Women With High-Risk Endometrial Cancer (PORTEC-3) trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus radiotherapy alone (RT) for women with high-risk endometrial cancer (EC). Because The Cancer Genome Atlas defined an EC molecular classification with strong prognostic value, we investigated prognosis and impact of chemotherapy for each molecular subgroup using tissue samples from PORTEC-3 trial participants. METHODS:Paraffin-embedded tissues of 423 consenting patients were collected. Immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for exonuclease domain were done to classify tumors as p53 abnormal (p53abn), ultramutated (mut), MMR-deficient (MMRd), or no specific molecular profile (NSMP). The primary end point was recurrence-free survival (RFS). Kaplan-Meier method, log-rank test, and Cox model were used for analysis. RESULTS:Molecular analysis was successful in 410 high-risk EC (97%), identifying the 4 subgroups: p53abn EC (n = 93; 23%), mut (n = 51; 12%), MMRd (n = 137; 33%), and NSMP (n = 129; 32%). Five-year RFS was 48% for patients with p53abn EC, 98% for mut EC, 72% for MMRd EC, and 74% for NSMP EC ( < .001). The 5-year RFS with CTRT versus RT for p53abn EC was 59% versus 36% ( = .019); 100% versus 97% for patients with mut EC ( = .637); 68% versus 76% ( = .428) for MMRd EC; and 80% versus 68% ( = .243) for NSMP EC. CONCLUSION:Molecular classification has strong prognostic value in high-risk EC, with significantly improved RFS with adjuvant CTRT for p53abn tumors, regardless of histologic type. Patients with mut EC had an excellent RFS in both trial arms. EC molecular classification should be incorporated in the risk stratification of these patients as well as in future trials to target specific subgroups of patients.
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3区Q2影响因子: 2.5
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3. [The PORTEC-3 trial for high-risk endometrial cancer: impact of molecular classification on prognosis and benefit from adjuvant therapy].
作者:Marnitz Simone , Schömig-Markiefka Birgid
期刊:Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]