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Cancers
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Radiotherapy in Endometrial Cancer
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Radiotherapy in Endometrial Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 22834

Special Issue Editor

Prof. Dr. Dirk Vordermark

E-Mail Website
Guest Editor
Department of Radiation Oncology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany
Interests: radiation oncology; radiotherapy; radiobiology; tumor microenvironment; tumor oxygenation;
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue focuses on recent developments in the application of all forms of radiotherapy in the treatment of endometrial cancer of all histologic types. The role of external-beam radiotherapy and brachytherapy as elements of multi-modality treatment concepts for endometrial cancer is under intensive discussion as a result of recently completed clinical trials.
This Special Issue will include reports of preclinical data on the tumor and radiation biology of endometrial cancer and the development of novel treatment strategies. Clinical contributions will address the emerging role of modern radiotherapy techniques, including intensity-modulated and stereotactic external-beam radiotherapy and individualized brachytherapy concepts, with a focus on technical aspects (including radiotherapy planning) and the integration of radiotherapy with systemic therapy (e.g., chemotherapy, immunotherapy). Reports from prospective trials are welcome, but retrospective analyses in sufficiently large patient groups and health service research data (cancer registry data, billing data) will also be included in this Special Issue.

Prof. Dr. Dirk Vordermark
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • uterine cancer
  • uterine carcinoma
  • uterine sarcoma
  • endometrial cancer
  • endometrial carcinoma
  • endometrial sarcoma
  • radiotherapy
  • radiobiology
  • radiotherapy planning
  • brachytherapy
  • radiosurgery
  • chemoradiation
  • chemoradiotherapy
  • immunotherapy

Published Papers (7 papers)

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Research

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13 pages, 2273 KiB  
Article
Real-World Evaluation of Modern Adjuvant Radiotherapy in Women with Stage IB Endometrial Cancer
by Jenny Ling-Yu Chen, Chao-Yuan Huang, Yu-Sen Huang, Che-Yu Hsu, Keng-Hsueh Lan, I-Lun Shih, Wen-Fang Cheng, Chi-An Chen, Bor-Ching Sheu and Sung-Hsin Kuo
Cancers 2021, 13(6), 1386; https://doi.org/10.3390/cancers13061386 - 18 Mar 2021
Cited by 1 | Viewed by 2070
Abstract
The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern [...] Read more.
The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI); low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS); patients with age >60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients. Full article
(This article belongs to the Special Issue Radiotherapy in Endometrial Cancer)
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13 pages, 1464 KiB  
Article
Effect of Radiotherapy in Addition to Surgery in Early Stage Endometrial Cancer: A Population-Based Study
by Daniel Medenwald, Susan Langer, Cornelia Gottschick and Dirk Vordermark
Cancers 2020, 12(12), 3814; https://doi.org/10.3390/cancers12123814 - 17 Dec 2020
Cited by 3 | Viewed by 1603
Abstract
Background: The role of radiotherapy in the management of early (FIGO I) endometrial cancer is controversial with limited availability of prospective data from randomized trials. Methods: German Epidemiologic Cancer Registries provided by the Robert Koch Institute. We considered FIGO I cases with recorded [...] Read more.
Background: The role of radiotherapy in the management of early (FIGO I) endometrial cancer is controversial with limited availability of prospective data from randomized trials. Methods: German Epidemiologic Cancer Registries provided by the Robert Koch Institute. We considered FIGO I cases with recorded operative treatment (n = 12,718, 2000–2017). We computed hazard ratios (HR) from relative survival models in relation to the mortality of the general population with 95% confidence intervals (CI). Multivariate models were adjusted for age, stage (IA vs. IB), grading, and chemotherapy. Radiotherapy included external radiotherapy and brachytherapy. Results: Cases with a favorable risk profile (FIGO IA, G1/G2) had a slightly lower survival rate, relative to the general population (FIGO IA: 0.9, G1: 0.91). The proportion of FIGO IA cases was lower in the radiotherapy group (52.6%) vs. cases without radiotherapy (78.6%). Additional treatment with radiotherapy was beneficial in FIGO IB (HR = 0.74) and all histopathological grades, but not FIGO IA cases (HR = 0.93) cases. Compared to IA tumors, IB cases had a HR of 1.51 (95% CI: 1.34–1.7). Conclusions: Radiotherapy in addition to surgery is beneficial for patients in a FIGO IB stage. Further studies need to address the impact of new techniques and risk assessment. Full article
(This article belongs to the Special Issue Radiotherapy in Endometrial Cancer)
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13 pages, 1445 KiB  
Article
Evaluation of Prognosticators and Treatment-Related Side Effects in Patients Irradiated Postoperatively for Endometrial Cancer
by Martin Leu, Jacqueline Possiel, Markus A. Schirmer, Andrea Hille, Stefan Rieken and Leif Hendrik Dröge
Cancers 2020, 12(12), 3613; https://doi.org/10.3390/cancers12123613 - 03 Dec 2020
Cited by 1 | Viewed by 1315
Abstract
Numerous clinical trials sought to improve outcomes in endometrial cancer patients with multimodal treatment strategies. We tested the hypothesis that specific histopathological and clinical parameters are prognosticators for outcomes at our Gynecological Cancer Center. A total of 203 patients (median age, 69.5 years) [...] Read more.
Numerous clinical trials sought to improve outcomes in endometrial cancer patients with multimodal treatment strategies. We tested the hypothesis that specific histopathological and clinical parameters are prognosticators for outcomes at our Gynecological Cancer Center. A total of 203 patients (median age, 69.5 years) was included. They were irradiated postoperatively (n = 184: Brachytherapy, n = 19: Teletherapy) between 05/2007 and 03/2020. The median follow-up was 37.2 months. As statistical methods, we used the univariable Cox proportional hazards regression, and log-rank statistics. First, we found a significant influence of grading and nodal stage on outcomes. These findings underline the recommendations of more intense treatment in these patient groups, as already reflected in current guidelines. Secondly, we found that patient age had a significant influence on survival be it due to comorbidities and/or due to too hesitant treatment regimen in the elderly. Thus, it should be aimed at particular strategies in treatment of these patients. Lastly, we found very low rates of treatment-related side effects in patients treated with brachytherapy and moderate rates of side effects in patients treated with teletherapy. Overall, our study serves as basis for further improvement of treatment strategies and for conceptualization of clinical trials. Full article
(This article belongs to the Special Issue Radiotherapy in Endometrial Cancer)
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13 pages, 452 KiB  
Article
Evaluation of Uterine Brachytherapy as Primary Treatment Option for Elderly Patients with Medically Inoperable Endometrial Cancer—A Single-Center Experience and Review of the Literature
by Nathalie Arians, Jan Tobias Oelmann-Avendano, Daniela Schmitt, Eva Meixner, Antje Wark, Juliane Hoerner-Rieber, Rami A. El Shafie, Kristin Lang, Markus Wallwiener and Jürgen Debus
Cancers 2020, 12(8), 2301; https://doi.org/10.3390/cancers12082301 - 15 Aug 2020
Cited by 4 | Viewed by 2280
Abstract
We aimed to gain more evidence regarding the feasibility, toxicity, and oncological outcome of primary brachytherapy in patients with medically inoperable endometrial cancer. Thirteen patients receiving primary brachytherapy ± external beam radiotherapy (EBRT) for endometrial cancer due to medical inoperability were identified. The [...] Read more.
We aimed to gain more evidence regarding the feasibility, toxicity, and oncological outcome of primary brachytherapy in patients with medically inoperable endometrial cancer. Thirteen patients receiving primary brachytherapy ± external beam radiotherapy (EBRT) for endometrial cancer due to medical inoperability were identified. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS). Univariate outcome analyses were performed using the log-rank test. Peri-interventional complications, acute and chronic toxicities were evaluated. Additionally, we performed a Pubmed search and review of the literature of the last 10 years. Mean age at time of diagnosis was 73.9 years (60.4–87.1 years). Eleven patients were staged FIGO IA/B and one patient each with FIGO IIIA and IIIC. Kaplan–Meier-estimated 2-/5-year LFFS were 76.2%/56.4%, respectively. High grading correlated with a worse LFFS (p = 0.069). Kaplan–Meier-estimated 2-/5-year PFS were 76.9%/53.8% and 2-/5-year-OS were 76.9%/69.2%, respectively. No acute toxicities > grade II and only two late toxicities grade II/III occurred. We observed three peri-interventional complications. The available evidence suggests high rates of local control after definitive brachytherapy for inoperable endometrial cancer with a favorable toxicity profile. Definitive brachytherapy +/− EBRT should be considered as the preferred approach for this patient group. Full article
(This article belongs to the Special Issue Radiotherapy in Endometrial Cancer)
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Review

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11 pages, 1714 KiB  
Review
The TCGA Molecular Classification of Endometrial Cancer and Its Possible Impact on Adjuvant Treatment Decisions
by Matthias Alexa, Annette Hasenburg and Marco Johannes Battista
Cancers 2021, 13(6), 1478; https://doi.org/10.3390/cancers13061478 - 23 Mar 2021
Cited by 65 | Viewed by 9527
Abstract
Adjuvant treatment decisions for endometrial cancer (EC) are based on stage, the histological grade of differentiation, histological subtype, and few histopathological markers. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identified four risk groups of EC patients using a combination of immunohistochemistry [...] Read more.
Adjuvant treatment decisions for endometrial cancer (EC) are based on stage, the histological grade of differentiation, histological subtype, and few histopathological markers. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identified four risk groups of EC patients using a combination of immunohistochemistry and mutation analysis: Polymerase Epsilon exonuclease domain mutated (POLE EDM), mismatch repair deficient (MMRd), p53 wild-type/copy-number-low (p53 wt), and p53-mutated/copy-number-high (p53 abn). Patients allocated to the POLE or abnormal p53 expression subtype are faced with a significantly altered outcome possibly requiring a modified adjuvant treatment decision. Within this review, we summarize the development of ProMisE, characterize the four molecular subtypes, and finally discuss its value in terms of a patient-tailored therapy in order to prevent significant under or overtreatment. Full article
(This article belongs to the Special Issue Radiotherapy in Endometrial Cancer)
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10 pages, 210 KiB  
Review
The Role of Postoperative Radiotherapy for Carcinosarcoma of the Uterus
by Dirk Vordermark, Daniel Medenwald, Victor Izaguirre, Frank Sieker and Simone Marnitz
Cancers 2020, 12(12), 3573; https://doi.org/10.3390/cancers12123573 - 30 Nov 2020
Cited by 6 | Viewed by 1858
Abstract
The role of postoperative radiotherapy delivered as external-beam radiotherapy (EBRT), vaginal brachytherapy (VBT) or a combination of both, in the management of carcinosarcoma of the uterus is not clearly defined, as only limited randomized trial data are available, indicating a reduction in locoregional [...] Read more.
The role of postoperative radiotherapy delivered as external-beam radiotherapy (EBRT), vaginal brachytherapy (VBT) or a combination of both, in the management of carcinosarcoma of the uterus is not clearly defined, as only limited randomized trial data are available, indicating a reduction in locoregional recurrences after EBRT. We performed a structured review of data published from 2010. Although no relevant new data from prospective trials or meta-analyses were identified, 14 analyses of cancer registry data from the United States or Europe, focusing predominantly on the endpoint for overall survival, were identified, four of them using propensity-score matching to compare subgroups treated with vs. without radiotherapy. Although stage-by-stage data are rare, the registry analyses support the idea of a beneficial effect, especially of VBT, on overall survival in International Federation of Gynecology and Obstetrics (FIGO) stage IA patients (to a lesser extent in stage IB). For stages II to III, the data sets indicate the largest effects on overall survival for the combination of EBRT and VBT. In all stages, survival effects of radiotherapy apparently persist when given in addition to chemotherapy. Whereas some studies see the strongest survival effects in patients with positive lymph nodes, propensity-score matched data indicate an overall survival effect of radiotherapy (EBRT + VBT or VBT alone) in FIGO stages I to III regardless of lymph node surgery. Full article
(This article belongs to the Special Issue Radiotherapy in Endometrial Cancer)
26 pages, 3402 KiB  
Review
Determinants of Sensitivity to Radiotherapy in Endometrial Cancer
by Maria Alba Sorolla, Eva Parisi and Anabel Sorolla
Cancers 2020, 12(7), 1906; https://doi.org/10.3390/cancers12071906 - 15 Jul 2020
Cited by 16 | Viewed by 3429
Abstract
Radiotherapy is one of the cornerstone treatments for endometrial cancer and has successfully diminished the risk of local recurrences after surgery. However, a considerable percentage of patients suffers tumor relapse due to radioresistance mechanisms. Knowledge about the molecular determinants that confer radioresistance or [...] Read more.
Radiotherapy is one of the cornerstone treatments for endometrial cancer and has successfully diminished the risk of local recurrences after surgery. However, a considerable percentage of patients suffers tumor relapse due to radioresistance mechanisms. Knowledge about the molecular determinants that confer radioresistance or radiosensitivity in endometrial cancer is still partial, as opposed to other cancers. In this review, we have highlighted different central cellular signaling pathways and processes that are known to modulate response to radiotherapy in endometrial cancer such as PI3K/AKT, MAPK and NF-κB pathways, growth factor receptor signaling, DNA damage repair mechanisms and the immune system. Moreover, we have listed different clinical trials employing targeted therapies against some of the aforementioned signaling pathways and members with radiotherapy. Finally, we have identified the latest advances in radiotherapy that have started being utilized in endometrial cancer, which include modern radiotherapy and radiogenomics. New molecular and genetic studies in association with the analysis of radiation responses in endometrial cancer will assist clinicians in taking suitable decisions for each individual patient and pave the path for personalized radiotherapy. Full article
(This article belongs to the Special Issue Radiotherapy in Endometrial Cancer)
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