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

Wortman, Bastiaan G; Bosse, Tjalling; Nout, R.A.; Lutgens, L.; Steen-Banasik, Elzbieta M. van der; Westerveld, Henrike; Berg, H. van den; Slot, Annerie; Winter, K. De; Verhoeven-Adema, Karen W; Smit, Vincent T.H.B.M.; Creutzberg, Carien L.

doi:10.1016/j.ygyno.2018.07.020

Cited by 148 publications

(95 citation statements)

References 28 publications

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“…Apart from cervical cancer, major indications for brachytherapy are endometrial, prostate, and breast cancer (Table ). For these tumor sites, the level of evidence for brachytherapy has come from randomized controlled studies focusing not only on local control but also including OS and QOL analysis (Table ) …”

Section: Brachytherapy In the Global Oncological Landscapementioning

confidence: 99%

“…Therefore, the modern management of endometrial cancers is tailored to each specific situation and is part of a multimodal approach aimed at decreasing morbidity without jeopardizing the probability of survival. The phase 3 Post‐Operative Radiation Therapy in Endometrial Carcinoma 4 (PORTEC‐4) study evaluates the possibility of guiding adjuvant treatments in high‐intermediate risk endometrial cancer based on a molecular‐integrated risk profile . Thus, regarding endometrial cancer treatment, a close collaboration is required with gynecological oncologists to move from a standard approach to risk‐adapted strategies.…”

Section: Brachytherapy In the Global Oncological Landscapementioning

confidence: 99%

“…Therefore, strategies tailored to the metastatic risk (eg, adjuvant chemotherapy) are attractive for combining dose escalation and systemic optimization, reinforced by the finding that ionizing radiation may contribute to inducing metastasis, cancer stem cell phenotype, and oncogenic metabolism in surviving cancer cells . The example of endometrial carcinoma illustrates the trend to guide brachytherapy indications from molecular‐integrated risk profiles . Immunological perspectives may be opportunities for pharmacological approaches .…”

Section: Tailoring Treatments: Biological and Radiological Insightsmentioning

confidence: 99%

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Brachytherapy: An overview for clinicians

Chargari

Deutsch

Blanchard

et al. 2019

CA A Cancer J Clinicians

207

125

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Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

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Section: Brachytherapy In the Global Oncological Landscapementioning

confidence: 99%

Section: Brachytherapy In the Global Oncological Landscapementioning

confidence: 99%

Section: Tailoring Treatments: Biological and Radiological Insightsmentioning

confidence: 99%

See 1 more Smart Citation

Brachytherapy: An overview for clinicians

Chargari

Deutsch

Blanchard

et al. 2019

CA A Cancer J Clinicians

207

125

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“…For women with tumors harboring a POLE mutation, 10-year CSS was 100%, in contrast to 96.2% for no specific molecular profile, 84.8% for MSI and 62.3% for p53-mutant tumors (p < 0.001) [32]. This knowledge is being tested in the on-going PORTEC IVA trial [45] where molecular testing is stratifying patients to observation, VCB, or WPRT.…”

Section: Adjuvant Management Of Early Stage Endometrial Cancermentioning

confidence: 99%

LVSI positive and NX in early endometrial cancer: Surgical restaging (and no further treatment if N0), or adjuvant ERT?

Harris

Maurer

Jarboe

et al. 2020

Gynecologic Oncology

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“…2D and Figure S2E) but had much worse prognosis than wide types ( Fig. 2F) (5,31). Multivariable Cox models further demonstrated that CTNNB1 mutation was an unfavorable prognostic factor independent of CIN signatures in OB and EBRT subgroups ( Table 2 and Table 3).…”

Section: Relationships Between Cin and Prognostic Factors Of Moleculamentioning

confidence: 82%

Integrating Pathology, Chromosomal Instability and Mutations for Risk Stratification in Early-stage Endometrioid Endometrial Carcinoma

Guo

et al. 2020

Preprint

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Background: Risk stratifications for endometrial carcinoma (EC) depend on histopathology and molecular pathology. Histopathological risk stratification lacks reproducibility, neglects heterogeneity and contributes little to surgical procedures. Existing molecular stratification is useless in patient with specific pathological or molecular characteristics, and cannot guide postoperative adjuvant radiotherapies. Chromosomal instability (CIN), the numerical and structural alterations of chromosome resulting from ongoing errors of chromosome segregation, is an intrinsic biological mechanism for the evolution of different prognostic factors of histopathology and molecular pathology, which may be applicable to the risk stratification of EC.Results: By analysis of CIN25 and CIN70, two reliable gene expression signatures for CIN, we found that EC with unfavorable prognostic factors of histopathology or molecular pathology had serious CIN. However, POLE-mutant, as a favorable prognostic factor, had elevated CIN signatures, and CTNNB1-mutant, as an unfavorable prognostic factor, had decreased CIN signatures. Only if these two mutations were excluded were CIN signatures strongly prognostic for outcomes in different adjuvant radiotherapy subgroups. Integrating pathology, CIN signatures and POLE / CTNNB1 mutation stratified stageⅠendometrioid EC into four groups with improved risk prognostication and treatment recommendations.Conclusions:We revealed the possibility of integrating histopathology and molecular pathology by CIN for risk stratification in early-stage EC. Our integrated risk model deserves for further improvement and validation.

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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

Cited by 148 publications

References 28 publications

Brachytherapy: An overview for clinicians

Brachytherapy: An overview for clinicians

LVSI positive and NX in early endometrial cancer: Surgical restaging (and no further treatment if N0), or adjuvant ERT?

Integrating Pathology, Chromosomal Instability and Mutations for Risk Stratification in Early-stage Endometrioid Endometrial Carcinoma

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