Survival after relapse in patients with endometrial cancer: results from a randomized trial☆ (original) (raw)
Related papers
Treatment of vaginal recurrence in endometrial cancer: A review
Acta Obstetricia et Gynecologica Scandinavica, 1996
Background. We have reviewed the literature concerning vaginal recurrence in endometrial cancer with emphasis on prognostics and therapeutic results. Compared to the overall outcome of recurrences (1 1-17 per cent survive more than 3-19 years) the survival rate of strictly vaginal recurrence appears significantly higher (up to 60-70 per cent survive more than 5 years). However, the prognosis deteriorates significantly in cases where recurrences prove to be more widespread. Other factors towards predicting a poor outcome are high age, high stage, high grade, detection of papillary carcinoma, rapid recurrence. location to the lower part of vagina, large tumorsize, and previous radiation. Methods. Different methods of initial treatment and cross-relations between most prognostic factors renders any ranking of prognostic factors almost impossible. Results. Standard treatment of vaginal recurrence including combined external and intra vaginal radiation used for decades have been unable to improve survival rate. Conclusion. We suggest a more individualized treatment based on exact delineation of the disease.
Treatment Failure in Endometrial Carcinoma
International Journal of Gynecological Cancer, 2014
Objective: Our aim was to investigate the outcomes and prognostic factors after treatment failure of endometrial cancer. Methods: A total of 923 endometrial cancer patients were treated between 2000 and 2010, of which 109 experienced treatment failure. Treatment failure was defined as relapse after complete removal of all cancerous lesions or persistent/progressive disease despite treatment. Variables including clinicopathological features at initial treatment, type of primary treatment, failure pattern, salvage treatment, and outcomes were analyzed. Kaplan-Meier survival curves were compared with log-rank test. Cox proportional hazards regression model was used to identify significant prognostic factors. Results: Eighteen cases with persistent/progressive disease died shortly from primary diagnosis (1Y23 months). The remaining 91 patients had recurrences in vagina only (8.8%), pelvis (3.3%), distant (63.7%), and combined pelvic-distant sites (24.2%). Median time to recurrence was 13.3 months (3.2Y97.2 months). The median follow-up after recurrence of survivors was 60.5 months (10.6Y121.7 months). The median survival after recurrence (SAR) was 20.3 months (1.9Y121.7 months) with 5-year SAR rate of 32.4%. By multivariate analysis, initial stage II to IV (hazards ratio [HR], 3.41; 1.53Y7.60; P = 0.003), type II histology (HR, 2.50; 1.28Y4.90; P = 0.008), positive peritoneal cytology (HR, 2.23; 1.07Y4.68; P = 0.033), and recurrence at multiple sites (HR, 2.51; 1.30Y4.84; P = 0.006) were significantly associated with poor SAR. The 5-year SAR rates in patients with solitary vaginal, nodal/ liver, or pulmonary/bony recurrence were 83.3%, 50.5%, and 24.2%, respectively. Ten cases with resectable or irradiatable recurrence at multiple sites or multiple relapses attained SAR greater than 5 years after multimodality salvage therapy. Conclusions: Initial stage II to IV, type 2 histology, positive cytology, and recurrence at multiple sites were significant poor prognostic factors. Curative intent salvage therapy remains a viable option for cases with resectable or irradiatable multiple recurrences and solitary distant metastasis.
Lancet Oncology, 2019
Background The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis. Methods In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48•6 Gy in 1•8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m² given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m² given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138.
Journal of gynecologic oncology, 2017
To determine factors influencing overall survival following recurrence (OSFR) in women with low-risk endometrial cancer (EC) treated with surgery alone. A multicenter, retrospective department database review was performed to identify patients with recurrent "low-risk EC" (patients having less than 50% myometrial invasion [MMI] with grade 1 or 2 endometrioid EC) at 10 gynecologic oncology centers in Turkey. Demographic, clinicopathological, and survival data were collected. We identified 67 patients who developed recurrence of their EC after initially being diagnosed and treated for low-risk EC. For the entire study cohort, the median time to recurrence (TTR) was 23 months (95% confidence interval [CI]=11.5-34.5; standard error [SE]=5.8) and the median OSFR was 59 months (95% CI=12.7-105.2; SE=23.5). We observed 32 (47.8%) isolated vaginal recurrences, 6 (9%) nodal failures, 19 (28.4%) peritoneal failures, and 10 (14.9%) hematogenous disseminations. Overall, 45 relapses (6...
Follow-up after primary therapy for endometrial cancer: A systematic review
Gynecologic Oncology, 2006
What is the most appropriate strategy for the follow-up of patients with endometrial cancer who are clinically disease free after receiving potentially curative primary treatment? Specifically, do differences in follow-up intervals, diagnostic interventions, clinical setting, or specialty influence patient outcomes related to local or distant recurrence, survival, or quality of life?
Journal of Personalized Medicine
Radiation therapy (RT) is the standard of care in patients with locoregional or isolated vaginal recurrence who never underwent irradiation. It is often associated with brachytherapy (BT), whereas chemotherapy (CT) is a rare treatment option. We systematically searched the PubMed and Scopus databases in February 2023. We included patients with relapsed endometrial cancer, describing the treatment of locoregional recurrence, and reporting at least one outcome of interest—disease-free survival (DFS), overall survival (OS), recurrence rate (RR), site of recurrence, and major complications. A total of 15 studies fulfilled the inclusion criteria. Overall, 11 evaluated RT only, 3 evaluated CT, and 1 analyzed oncological outcomes after administration with a combination of CT and RT. In total, 4.5-year OS ranged from 16% to 96%, and DFS ranged from 36.3% to 100% at 4.5 years. RR ranged from 3.7% to 98.2% during a median follow-up of 51.5 months. Overall, RT showed a 4.5-year DFS from 40% to...
International Journal of Radiation Oncology Biology Physics, 2001
Objective: To evaluate the risk of pelvic recurrence (PVR) in high-risk pathologic Stage I-IV endometrial carcinoma patients after adjuvant chemotherapy alone. Methods: Between 1992 and 1998, 43 high-risk endometrial cancer patients received adjuvant chemotherapy. All patients underwent primary surgery consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patients received preoperative radiation therapy (RT). Regional lymph nodes and peritoneal cytology were sampled in 62.8% and 83.7% of cases, respectively. Most patients had Stage III-IV disease (83.7%) or unfavorable histology tumors (74.4%). None had evidence of extra-abdominal disease. All patients received 4 -6 cycles of chemotherapy as the sole adjuvant therapy, consisting primarily of cisplatin and doxorubicin. Recurrent disease sites were divided into pelvic (vaginal, nonvaginal) and extrapelvic (para-aortic, upper abdomen, liver, and extra-abdominal). Median follow-up was 27 months (range, 2-96 months). Results: Twenty-nine women (67.4%) relapsed. Seventeen (39.5%) recurred in the pelvis and 23 (55.5%) in extrapelvic sites. The 3-year actuarial PVR rate was 46.5%. The most significant factors correlated with PVR were cervical involvement (CI) (p ؍ 0.01) and adnexal (p ؍ 0.05) involvement. Of the 17 women who developed a PVR, 8 relapsed in the vagina, 3 in the nonvaginal pelvis, and 6 in both. The 3-year vaginal and nonvaginal PVR rates were 37.8% and 26%, respectively. The most significant factor correlated with vaginal PVR was CI (p ؍ 0.0007). Deep myometrial invasion (p ؍ 0.02) and lymph nodal involvement (p ؍ 0.03) were both correlated with nonvaginal PVR. Nine of the 29 relapsed patients (31%) developed PVR as their only (6) or first site (3) of recurrence. Factors associated with a higher rate of PVR (as the first or only site) were CI and Stage I-II disease. Conclusions: PVR is common in high-risk pathologic Stage I-IV endometrial cancer patients after adjuvant chemotherapy alone. These results support the continued use of locoregional RT in patients undergoing adjuvant chemotherapy. Further studies are needed to test the addition of chemotherapy to locoregional RT.
Vaginal vault recurrences of endometrial cancer in non-irradiated patients — Radiotherapy or surgery
Gynecologic Oncology Reports, 2015
Background: The treatment of locally recurrent endometrial cancer is based on limited evidence. The standard treatment is radiotherapy (RT) which is effective for local control and the effect has been documented in prospective studies. Investigations of surgical treatment (ST) of recurrences are few and limited to previously irradiated patients or patients with advanced disease. Investigation of surgical treatment for isolated vaginal vault recurrence is practically nonexistent. The aim of this study is to evaluate the efficacy of RT and ST in a nonirradiated group with recurrent endometrial cancer limited to the vaginal vault. Methods: Patients treated for recurrent endometrial cancer at Odense University Hospital, Denmark between 2003 and 2012 were identified, n = 118. Thirty-three patients had an isolated vaginal vault recurrence and were treated with either RT, ST or both. Re-recurrence rates and survival rates were calculated at 2 year follow-up using Fishers exact test. Results: Twenty-six patients were treated with RT, 5 with ST, 2 with both. The mean (SD) follow-up-time was 4.4 years (2.99) (RT) and 3.9 years (0.90) (ST). Two year re-recurrence rates were 40% (RT) (95 CI 9.2-48%) and 0% (ST) (95 CI 0-60%). Two-year survival rates were 83% (RT) (95 CI 71-100%) and 100% (ST) (95 CI 40-100%) ST had one re-recurrence at 2.3 years. Conclusion: This study indicates that ST is an appropriate treatment for locally recurrent endometrial cancer. Our study involves a limited number of patients and is made retrospectively, therefore prospective and ideally randomized trials evaluating both survival and complications are warranted.
Surgical treatment of recurrent endometrial carcinoma
Cancer, 2003
BACKGROUND. Surgery does not have a definite role in the treatment of patients with recurrent endometrial carcinoma, except for those with central pelvic recurrences. The authors describe their experience with surgery in patients with abdominal endometrial recurrences. METHODS. Between 1988 and 2000, 75 patients with abdominal and pelvic endometrial recurrences underwent secondary rescue surgery. Patients were classified according to the presence or absence of residual tumor after surgery. Therapy after rescue surgery was undertaken at the discretion of the medical oncologist. The progression-free interval and overall survival were defined as the time from secondary rescue surgery to the specific event and were evaluated by the Kaplan-Meier method and the log-rank test. A Cox proportional hazards regression model was used to compare survival with covariates. RESULTS. Fifty-six patients (74.7%) underwent optimal debulking. Major surgical complications were observed in 23 patients (30.7%). Only 1 postoperative death was observed, although the mortality rate for surgical complications after the postoperative period was 8%. Patients who underwent optimal debulking had a significantly better cumulative survival rate compared with patients who had residual disease (36% vs. 0% at 60 months; P Ͻ 0.05). Residual disease, chemotherapy after rescue surgery, and central pelvis-vagina as the only site of recurrence were associated significantly with survival. CONCLUSIONS. The authors found that this approach was very challenging in terms of the procedures involved, the incidence of major surgical complications, and the high mortality rate. It was useful in increasing overall survival, provided that patients were free of macroscopic disease. Careful selection of patients is needed to minimize mortality. Cancer 2004;100:89-96.
Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift
Annals of Surgical Oncology, 2015
Background. Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. Methods. Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. Results. Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At F. Bellati and A. Papadia have equally contributed to this work.
International Journal of Radiation Oncology Biology Physics, 1988
A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960-1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The lo-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25'%. Many of the deaths were due to intercurrent disease. Thus, the lo-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with tlhe following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30'L for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases. Adequate initial therapy is crucial in determining the probability of pelvic tumor control and survival in patients with invasive carcinoma of the cervix. Salvage procedures for pelvic recurrences, even in the absence of distant metastases, yields a low long-term survival.
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patientand treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) compared with those with resection alone (50%; p ؍ 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p ؍ 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients. © 2007 Elsevier Inc. Endometrial cancer, Stage III, Radiotherapy, Prognostic factors, Patterns of failure.
The role of surgery in recurrent endometrial cancer
Expert Review of Anticancer Therapy, 2016
Endometrial cancer is a common gynecologic malignancy in the United States and the recurrence rate depends on stage disease at diagnosis. The spread of the disease at recurrence can occur in several areas and follow different patterns. The role of surgery at the time of recurrence is not clearly defined. The aim of this review is to fully describe the current evidence available on this topic. In particular, we will describe that surgical treatment might be recommended for 1) vaginal or pelvic recurrences; 2) retroperitoneal or localized intra-abdominal recurrence, where a maximal cytoreductive effort is more likely to be successful; or 3) isolated distant recurrences when microscopically tumor-free margins can be achieved. Cases should be evaluated individually, considering factors such as comorbidities, risks of intervention, and impact of treatment on quality of life.
Recurrent Endometrial Cancer: Which Is the Best Treatment? Systematic Review of the Literature
Cancers
Background: Endometrial cancer is the most common gynaecological tumour in developed countries. The overall rate of relapse has remained unchanged in recent decades. Recurrences occur in approximately 20% of endometrioid and 50% of non-endometrioid cases. The aim of this systematic review is to compare different therapeutic strategies in the treatment of endometrial cancer recurrence to evaluate their prognostic and curative effects based on site and type of recurrence. Methods: This systematic review of literature was conducted in accordance with the PRISMA guidelines. The study protocol was registered on PROSPERO (CRD42020154042). PubMed, Embase, Chocrane and Cinahl databases were searched from January 1995 to September 2021. Five retrospective studies were selected. Results: A total of 3571 studies were included in the initial search. Applying the screening criteria, 299 articles were considered eligible for full-text reading, of which, after applying the exclusion criteria, 4 st...
Long-Term Survivors Using Intraoperative Radiotherapy for Recurrent Gynecologic Malignancies
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To analyze the outcomes of therapy and identify prognostic factors for patients treated with surgery followed by intraoperative radiotherapy (IORT) for gynecologic malignancies at a single institution. Methods and Materials: We performed a retrospective review of 36 consecutive patients treated with IORT to 44 sites with mean follow-up of 50 months. The primary site was the cervix in 47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%. Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38 IORT sessions, 84% included maximal cytoreductive surgery, including 18% exenterations. The mean age was 52 years (range, 30-74), mean tumor size was 5 cm (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured were locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Results: The Kaplan-Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and 47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC, DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic factors found on multivariate analysis (p #0.05) were the disease-free interval for LRC, tumor size for DMFS, and cervical primary, previous surgery, and locoregional relapse for DSS. Our cohort had 10 Grade 3-4 complications associated with treatment (surgery and IORT) and a Kaplan-Meier 5-year Grade 3-4 complication-free survival rate of 72%. Conclusions: Survival for pelvic recurrence of gynecologic cancer is poor (range, 0-25%). IORT after surgery seems to confer long-term local control in carefully selected patients. Ó 2007 Elsevier Inc.
The Effect of Postsurgical Therapy on Stage III Endometrial Carcinoma
Gynecologic Oncology, 1996
Postsurgical therapy for advanced endometrial carcinoma The records of 86 pathologic stage III endometrial carcinoma has evolved over the past several decades. In the 1960s and patients treated at Massachusetts General Hospital between 1974 1970s, preoperative radiation therapy with 40-50 Gy was and 1992 were retrospectively reviewed to identify predictors of believed to reduce tumor cell implantation . This approach poor outcome and to determine the effect of postsurgical therapy overtreated some patients with minimal disease and interon recurrence and survival. Patients underwent TAH/BSO with fered with interpretation of the extent of myometrial invasion selective lymphadenectomy and peritoneal washings. Cases prior . In the 1970s and 1980s, low-dose (10-20 Gy) preopto 1988 were retrospectively restaged using the FIGO surgical erative radiotherapy with individualized postoperative therstaging criteria. Postoperatively, patients received individualized apy was also reconsidered because surgical-pathologic studregimens of EBRT (external beam radiotherapy), brachytherapy, ies demonstrated a more complete understanding of disease and cytotoxic or hormonal chemotherapy. The 5-year survival and progression. These investigations identified high-risk prog-5-year disease-free survival (DFS) for all patients were 54 and 44%, respectively. Forty-two percent of stage IIIA/B patients recurred in nostic factors that could more reliably predict disease proa median time of 14 months. Fifty-four percent of stage IIIC gression and direct postsurgical therapy [6-9]. In 1988, the patients recurred in a median time of 16 months. Of patients who clinical staging system was abandoned in favor of the FIGO recurred, 90% stage IIIA/B and 71% stage IIIC patients recurred surgical staging system [10]. at extrapelvic sites. Age greater than 70, high-grade lesions, and
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Adjuvant radiotherapy for stage I endometrial cancer
Cochrane database of systematic reviews (Online), 2012
The role of adjuvant radiotherapy in stage I endometrial cancer has changed in recent years. This updated Cochrane systematic review aimed to reexamine the efficacy and toxicity of adjuvant radiotherapy vs no treatment in stage I endometrial cancer.
A tool to balance benefit and harm when deciding about adjuvant therapy
British journal of cancer, 2009
Adjuvant therapy aims to prevent outgrowth of residual disease but can induce serious side effects. Weighing conflicting treatment effects and communicating this information with patients is not elementary. This study presents a scheme balancing benefit and harm of adjuvant therapy vs no adjuvant therapy. It is illustrated by the available evidence on adjuvant pelvic external beam radiotherapy (RT) for intermediate-risk stage I endometrial carcinoma patients. The scheme comprises five outcome possibilities of adjuvant therapy: patients who benefit from adjuvant therapy (some at the cost of complications) vs those who neither benefit nor contract complications, those who do not benefit but contract severe complications, or those who die. Using absolute risk differences, a fictive cohort of 1000 patients receiving adjuvant RT is categorised. Three large randomised clinical trials were included. Recurrences will be prevented by adjuvant RT in 60 patients, a majority of 908 patients wil...
Cancers
Imaging of clinically relevant preclinical animal models is critical to the development of personalized therapeutic strategies for endometrial carcinoma. Although orthotopic patient-derived xenografts (PDXs) reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by the lack of appropriate imaging modalities. Here, we describe molecular imaging of a near-infrared fluorescently labeled monoclonal antibody targeting epithelial cell adhesion molecule (EpCAM) as an in vivo imaging modality for visualization of orthotopic endometrial carcinoma PDX. Application of this near-infrared probe (EpCAM-AF680) enabled both spatio-temporal visualization of development and longitudinal therapy monitoring of orthotopic PDX. Notably, EpCAM-AF680 facilitated imaging of multiple PDX models representing different subtypes of the disease. Thus, the combined implementation of EpCAM-AF680 and orthotopic PDX models crea...
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2018
To date, biomarkers are not routinely used in endometrial cancer diagnosis, prognosis, and follow-up. The purpose of this study was to evaluate whether serum HE4 was related to clinicopathological risk factors and outcome. Second, the role of serum HE4 and CA125 was assessed as indicator for recurrent disease during follow-up. A total of 174 patients with endometrial cancer between 1999 and 2009 were selected for this retrospective study. Serum HE4 and CA125 were analyzed at primary diagnosis, during follow-up, and at the time of recurrence. Correlations with clinicopathological factors were studied by univariate and multivariate survival analyses. Lead time was calculated in order to determine which serum marker was elevated prior to clinical detection of recurrent disease. Serum levels of HE4 and CA125 were significantly associated with high tumor grade, myometrial invasion, lymph node involvement, and advanced stage (p < 0.01). HE4 was an independent prognostic factor for redu...
The role of surgery in recurrent endometrial cancer
Expert Review of Anticancer Therapy, 2016
Endometrial cancer is a common gynecologic malignancy in the United States and the recurrence rate depends on stage disease at diagnosis. The spread of the disease at recurrence can occur in several areas and follow different patterns. The role of surgery at the time of recurrence is not clearly defined. The aim of this review is to fully describe the current evidence available on this topic. In particular, we will describe that surgical treatment might be recommended for 1) vaginal or pelvic recurrences; 2) retroperitoneal or localized intra-abdominal recurrence, where a maximal cytoreductive effort is more likely to be successful; or 3) isolated distant recurrences when microscopically tumor-free margins can be achieved. Cases should be evaluated individually, considering factors such as comorbidities, risks of intervention, and impact of treatment on quality of life.
Journal of Clinical Medicine
Circulating tumor markers are not routinely used in patients with endometrial cancer (EC). This pilot study evaluated the role of monitoring new biomarkers DJ1 and L1CAM, in correlation with CA125 and HE4, for the effects of anticancer treatment and preoperative management in EC patients. Serial serum levels of DJ1, L1CAM, CA125 and HE4 were collected in 65 enrolled patients. Serum DJ1, L1CAM, CA125 and HE4 levels were significantly higher at the time of diagnosis compared to those measured during follow-up (FU). In patients with recurrent disease, serum DJ1, CA125 and HE4 levels were significantly higher at the time of recurrence compared to levels in disease-free patients. Serum L1CAM levels were also higher in patients with recurrence but without reaching statistical significance. While DJ1 levels were not affected by any of the observed patient-related characteristics, L1CAM levels were significantly higher in patients with age ≥60 years who were overweight. At the time of EC di...
Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance
BMC cancer, 2015
BackgroundThe purpose of this study was to evaluate serum HE4 as a biomarker to detect recurrent disease during follow-up of patients with endometrial adenocarcinoma (EAC).MethodsWe performed a retrospective analysis of 98 EAC patients treated at Innsbruck Medical University, between 1999 and 2009. Twenty-six patients developed recurrent disease. Median follow-up was 5 years. Serum HE4 and CA125 levels were analyzed using the ARCHITECT assay (Abbott, Wiesbaden, Germany) pre-operatively (baseline), post-operative (interval) and after histological confirmation of recurrent disease or when patients returned for clinical review with no evidence of recurrent disease (recurrence/final)). Receiver operator curves (ROC), Spearman rank correlation coefficient, chi-squared and Mann¿Whitney tests were used for statistical analysis.ResultsHE4 levels decreased after initial treatment (p¿=¿0.001) and increased again at recurrence (p¿=¿0.002). HE4 was elevated (>70pmol/L) in 21 of 26 (81%) and ...
Implementation of radiation therapist cylinder insertion for vaginal vault brachytherapy
Journal of Medical Radiation Sciences, 2019
Vaginal vault brachytherapy is a common treatment for endometrial cancer. Historically, applicator insertion has been the domain of a radiation oncologist (RO). This commentary outlines a project to improve efficiency and workforce utilisation by introducing a competency framework and training module allowing entitled radiation therapists to perform single-channel cylinder applicator insertions and treatment delivery under RO supervision for fraction one and without supervision for subsequent fractions. The rationale, relevant regulations, implementation process and barriers are explored.
British Gynaecological Cancer Society (BGCS) uterine cancer guidelines: Recommendations for practice
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2022
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
PLoS ONE, 2014
Background: Yes-associated protein (YAP) is a transcriptional co-activator and regulates cell proliferation and apoptosis. We investigated the clinical and biological significance of YAP in endometrial cancer (EMCA). Methods: YAP expression in 150 primary tumor tissues from patients with EMCA was evaluated by immunohistochemistry and its association with clinicopathological data was assessed. The biological functions of YAP were determined in EMCA cell lines through knockdown/overexpression of YAP. The role of YAP in modulating radiation sensitivity was also investigated in EMCA cells. Results: Increased nuclear YAP expression was significantly associated with higher grade, stage, lympho-vascular space invasion, postoperative recurrence/metastasis and overall survival in estrogen mediated EMCA, called type 1 cancer (p = 0.019, = 0.028, = 0.0008, = 0.046 and = 0.015, respectively). In multivariate analysis, nuclear YAP expression was confirmed as an independent prognostic factor for overall survival in type 1 EMCA. YAP knockdown by siRNA resulted in a significant decrease in cell proliferation (p,0.05), anchorage-dependent growth (p = 0.015) and migration/invasion (p, 0.05), and a significant increase in the number of cells in G0/G1 phase (p = 0.002). Conversely, YAP overexpression promoted cell proliferation. Clonogenic assay demonstrated enhanced radiosensitivity by approximately 36% in YAP inhibited cells. Conclusions: Since YAP functions as a transcriptional co-activator, its differential localization in the nucleus of cancer cells and subsequent impact on cell proliferation could have important consequences with respect to its role as an oncogene in EMCA. Nuclear YAP expression could be useful as a prognostic indicator or therapeutic target and predict radiation sensitivity in patients with EMCA.
Cancers
Endometrial cancer is the most common gynecological tract malignancy in developed countries, and its incidence has been increasing globally with rising obesity rates and longer life expectancy. In endometrial cancer, extrauterine disease, in particular lymph node metastasis, is an important prognostic factor. Nevertheless, pelvic lymphadenectomy is not considered to have a therapeutic benefit, as it did not improve survival in randomized studies. However, lymphadenectomy may have a therapeutic benefit if adjuvant therapy can be omitted without decreasing oncological outcomes, as the long-term quality of life is maintained by avoiding morbidities associated with adjuvant therapy. In intermediate- and high-risk endometrioid endometrial carcinomas, adjuvant therapy may be safely omitted without decreasing long-term survival by open surgery including systematic pelvic and para-aortic lymphadenectomy when patients are node-negative. Systematic lymphadenectomy may remove undetectable low-...
Journal of Personalized Medicine
Radiation therapy (RT) is the standard of care in patients with locoregional or isolated vaginal recurrence who never underwent irradiation. It is often associated with brachytherapy (BT), whereas chemotherapy (CT) is a rare treatment option. We systematically searched the PubMed and Scopus databases in February 2023. We included patients with relapsed endometrial cancer, describing the treatment of locoregional recurrence, and reporting at least one outcome of interest—disease-free survival (DFS), overall survival (OS), recurrence rate (RR), site of recurrence, and major complications. A total of 15 studies fulfilled the inclusion criteria. Overall, 11 evaluated RT only, 3 evaluated CT, and 1 analyzed oncological outcomes after administration with a combination of CT and RT. In total, 4.5-year OS ranged from 16% to 96%, and DFS ranged from 36.3% to 100% at 4.5 years. RR ranged from 3.7% to 98.2% during a median follow-up of 51.5 months. Overall, RT showed a 4.5-year DFS from 40% to...
Geburtshilfe und Frauenheilkunde
Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat low-risk women with endometrial cancer prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer ...
Recurrent Endometrial Cancer: Which Is the Best Treatment? Systematic Review of the Literature
Cancers
Background: Endometrial cancer is the most common gynaecological tumour in developed countries. The overall rate of relapse has remained unchanged in recent decades. Recurrences occur in approximately 20% of endometrioid and 50% of non-endometrioid cases. The aim of this systematic review is to compare different therapeutic strategies in the treatment of endometrial cancer recurrence to evaluate their prognostic and curative effects based on site and type of recurrence. Methods: This systematic review of literature was conducted in accordance with the PRISMA guidelines. The study protocol was registered on PROSPERO (CRD42020154042). PubMed, Embase, Chocrane and Cinahl databases were searched from January 1995 to September 2021. Five retrospective studies were selected. Results: A total of 3571 studies were included in the initial search. Applying the screening criteria, 299 articles were considered eligible for full-text reading, of which, after applying the exclusion criteria, 4 st...