Relapse Of Endometrial Cancer Research Articles

2446: Relapse in Endometrial Cancer: impact of salvage treatment and patients characteristics

2446: Relapse in Endometrial Cancer: impact of salvage treatment and patients characteristics

Major determinants of survival in recurrent endometrial cancer—the role of secondary cytoreductive surgery: a multicenter study

ObjectiveThe main objective of the study was to assess the influence of different clinical and therapeutic variables on the oncological outcomes of patients with endometrial cancer relapse. In particular, we...

Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival.

Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. “Immortality” of most cancer cells is dependent on telomerase, but the role of associated proteins in the endometrium is poorly understood. The Cancer Genome Atlas data highlighted telomere/telomerase associated genes (TTAGs) with prognostic relevance in the endometrium, and a recent in silico study identified a group of TTAGs and proteins as key regulators within a network of dysregulated genes in EC. We characterise relevant telomere/telomerase associated proteins (TTAPs) NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP in the endometrium using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). qPCR data demonstrated altered expression of multiple TTAPs; specifically, increased NOP10 (p = 0.03) and reduced NHP2 (p = 0.01), TERF2 (p = 0.01) and TERF2IP (p < 0.003) in EC relative to post-menopausal endometrium. Notably, we report reduced NHP2 in EC compared to post-menopausal endometrium in qPCR and IHC (p = 0.0001) data; with survival analysis indicating high immunoscore is favourable in EC (p = 0.0006). Our findings indicate a potential prognostic role for TTAPs in EC, particularly NHP2. Further evaluation of the prognostic and functional role of the examined TTAPs is warranted to develop novel treatment strategies.

Efficacy of Endometrial Cancer Follow-up Protocols: Time to Change?

The aim of the present study was to analyze relapse rates and patterns in patients with endometrial cancer with the aim of evaluating the effectiveness of current follow-up procedures in terms of patient survival, as well as the convenience of modifying the surveillance strategy. Retrospective descriptive study including all patients diagnosed with endometrial cancer relapse at the Department of Gynecology and Obstetrics of the Complejo Hospitalario Insular-Materno Infantil de Canarias, between 2005 and 2014. Recurrence was observed in 81 patients (10.04% of the sample); 66.7% of them suffered relapse within 2 years and 80.2% within 3 years after the termination of the primary treatment; 41.9% showed distant metastases while the rest corresponded to local-regional (40.7%) or ganglionar (17.4%) relapse; 42% of these were symptomatic; 14 patients showed more than 1 site of relapse. Relapse was detected mainly through symptoms and physical examination findings (54.3%), followed by elevated serum marker levels (29.6%), computed tomography (CT) images (9.9%) and abnormal vaginal cytology findings (6.2%). No differences in global survival were found between patients with symptomatic or asymptomatic relapse. Taking into account that the recurrence rate of endometrial cancer is low, that relapse occurs mainly within the first 3 years post-treatment and that symptom evaluation and physical examination are the most effective follow-up methods, we postulate that a modification of the current model of hospital follow-up should be considered.

The optimal cut-off value of immunohistochemical parameter P53 for predicting recurrence of endometrial cancer.

To explore the optimal cut-off value of immunohistochemical parameter P53 for predicting the recurrence of Stage I-III endometrial cancer. A total of 473 patients who were treated between October 2013 and May 2018 were retrospectively studied. Receiver operating characteristic (ROC) curves and the Youden index were used to calculate the optimal cut-off value of P53. Cox regression analysis was used to detect the association between the threshold of P53 and recurrence of endometrial cancer. Recurrence-free survival (RFS) and overall survival (OS) were exhibited by Kaplan-Meier curve. The study showed that 67% was the optimal cut-off value of P53 to predict the recurrence of endometrial cancer. P53 above 67% was an independent predictor for relapse of endometrial cancer (p<0.001). The 3-year RFS was 89.7% in the low-value group and 66.6% in the high-value group (p<0.001), while the 3-year OS was 93.9% and 76.4%, respectively (p<0.001). Furthermore, the 3-year RFS of patients who did not receive adjuvant chemotherapy or radiotherapy was 95.7% and 78.2% between the two groups (p<0.001). The optimal cut-off value of immunohistochemical parameter P53 for predicting recurrence was confirmed as 67% and a P53 index above 67% was an independent prognostic factor.

Outcomes and Toxicity following Salvage Radiotherapy for Vaginal Relapse of Endometrial Cancer

Outcomes and Toxicity following Salvage Radiotherapy for Vaginal Relapse of Endometrial Cancer

Outcomes and toxicity after salvage radiotherapy for vaginal relapse of endometrial cancer

ObjectivesStudies of salvage radiotherapy in locally recurrent endometrial cancer remain limited. The aim of this study was to evaluate the efficacy of salvage radiotherapy for vaginal relapse of endometrial cancer...

Prognostic Determinants of Salvage Image-Guided Brachytherapy for Vaginal Recurrence of Endometrial Cancer

In PORTEC-1, the 5-year survival after vaginal relapse from early stage endometrial cancer was 65% for patients in the observation arm. In this study, we evaluated clinical outcomes and toxicity in patients with vaginal relapse of endometrial cancer treated with salvage image-guided brachytherapy (BT). Retrospective review identified 62 patients with early stage endometrial cancer and biopsy-proven vaginal recurrence treated with external beam (EBRT) and image-guided BT with definitive intent between 10/04 and 05/17. All patients had prior hysterectomy without adjuvant radiotherapy (RT) and >3 months follow-up (FU). Rates of vaginal control (VC), recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate analysis was performed by Cox proportional hazards or log-rank test. Late toxicity was graded by CTCAE. Median FU was 31.8 months (r: 3.2 – 160.5). Baseline characteristics are summarized in table 1. The median time to recurrence after hysterectomy was 18.2 months (range [r]: 1.6 – 158). Median tumor size was 2.3 cm (r: 0.3-7.5). Median prescribed dose and HR-CTV D90 in EQD2 were 75.4 Gy and 75.3 Gy, respectively. Twenty patients had disease relapse at a median of 14.2 months after completion of BT (6 with vaginal failure only, 2 vaginal and distant, and 12 distant only). The 3-year rates of VC, RFS, and OS were 86%, 70% and 80%. respectively. Tumor grade at hysterectomy was a strong determinant of outcome, with 3-year RFS rates of 80% for grade 1 tumors, 78% for grade 2, and 13% for grade 3 (p<0.01). Age, stage at diagnosis, nodal involvement and BT modality were not associated with RFS (all p>0.2). Median HR-CTV D90 was 75.7 Gy for patients with vaginal failure and 75.2 Gy for those without (p=0.9). Age, BT modality, tumor grade, tumor size and cumulative prescribed dose were not prognostic for VC (all p>0.5). Late grade 3 toxicity included 2 patients with proctitis and 1 with urinary incontinence; all received interstitial BT. One cylinder patient had grade 3 vaginal stenosis. Salvage RT with image-guided BT results in excellent clinical outcomes for patients with grade 1 or 2 tumors and vaginal relapse. Those with grade 3 tumors or non-endometrioid histologies have high rates of distant recurrence and poor survival. Adjuvant treatment should be considered for all high risk patients given the low rates of salvage.Abstract 2796; Table 1Baseline characteristics for 62 patientsn (%)FIGO 2009 stage at diagnosis • IA• 56 (90%) • IB• 5 (8%) • II• 1 (2%)Histology • Endometrioid• 55 (89%) • Serous• 5 (8%) • Carcinosarcoma• 2 (3%)Grade • 1• 40 (65%) • 2• 13 (21%) • 3• 9 (14%)Median age at recurrence67 years (r: 41-86)Site(s) of recurrence • Vaginal only• 55 (89%) • Vaginal + nodal• 7 (11%)Image-guided BT modality • Intracavitary (cylinder)• 26 (42%) • Interstitial• 36 (58%)Median central EBRT dose• 45Gy (r: 44 – 54)Median BT dose• 25Gy (r: 16 – 35)Median D2cc OAR • Bladder• 65.8 Gy (r: 50.7 – 87.2) • Rectum• 64.7 Gy (r: 52.1 – 86.9) • Sigmoid• 53.7 Gy (r: 44.7 – 75.5)Chemotherapy use11 (18%) Open table in a new tab

CTCF genetic alterations in endometrial carcinoma are pro-tumorigenic

CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cancer.

L1 Cell Adhesion Molecule as a Predictor of Disease-Specific Survival and Patterns of Relapse in Endometrial Cancer.

The aim was to study the association of L1 cell adhesion molecule (L1CAM) expression with the outcome of patients with endometrial cancer, especially with regard to conventional risk variables, and to compare the patterns of relapse in L1CAM-positive and -negative cancers. This was a retrospective study of 805 women. The Kaplan-Meier method and univariate and multivariate Cox regression models were applied for survival analyses. Missing data were replaced using multiple imputation. The median follow-up time was 51 months (range, 1-98). One hundred twenty-one (15.0%) cases were L1CAM positive. L1CAM positivity was associated with high stage (I vs II-IV) (odds ratio [OR], 2.3), lymph node involvement (OR, 2.9), poor differentiation (OR, 6.1), non-endometrioid histology (OR, 9.9), lymphovascular space invasion (OR, 2.8), cervical stromal invasion (OR, 1.8), positive peritoneal cytology (OR, 4.1), and age older than 65 years (OR, 2.8). The frequencies of deep myometrial invasion (50% or deeper), tumor size 2 cm or greater, and body mass index 30 kg/m or greater were not significantly different between L1CAM-positive and -negative cases. L1CAM predicted poor disease-specific survival in endometrioid (P < 0.0001) but not in non-endometrioid carcinomas (P = 0.934). The negative impact of L1CAM on outcome was confirmed in a Cox multivariate disease-specific survival analysis. Univariate survival analyses in the different ESMO-ESGO-ESTRO endometrial cancer risk groups showed an association between L1CAM positivity and poor outcome in intermediate (hazard ratio, 12) and high-risk advanced metastatic (hazard ratio, 2.0) groups. Extra-abdominal relapses were more frequent in L1CAM-positive (13.2%) than L1CAM-negative (1.9%) stage I endometrioid carcinomas (P < 0.0001), whereas other site-specific relapses in local cancers were L1CAM independent. L1CAM is associated with the occurrence of poor prognostic variables and predicts advanced disease in endometrial cancer. L1CAM predicts extra-abdominal relapses and poor survival in endometrioid endometrial cancer, but seems not to be a prognostic factor in non-endometrioid carcinomas.

Early Relapse of Endometrial Cancer in a Patient Infected With HIV

Early Relapse of Endometrial Cancer in a Patient Infected With HIV

Classification of ovarian cancer by stromal gene expression related to relapse of endometrial cancer

Classification of ovarian cancer by stromal gene expression related to relapse of endometrial cancer

Factors Influencing Outcome After Relapse of Endometrial Cancer: Role of Brachytherapy in the Salvage Treatment

Factors Influencing Outcome After Relapse of Endometrial Cancer: Role of Brachytherapy in the Salvage Treatment

Intensity modulated radiation therapy for definitive treatment of paraortic relapse in patients with endometrial cancer

PurposeThe paraortic nodes are a common site of recurrence of endometrial cancer, especially among patients previously treated with pelvic radiation. Intensity modulated radiation therapy (IMRT) can be used to deliver a tumoricidal dose to paraortic disease while minimizing dose to normal adjacent structures. In this study, we reviewed the outcomes of patients treated with IMRT for unresected or incompletely resected paraortic recurrences of primary uterine cancer. Methods and MaterialsBetween 2000 and 2009, 27 patients with unresected (19 patients) or incompletely resected (8 patients) paraortic relapse of endometrial cancer were treated with curative intent using IMRT. The paraortic basin was generally treated to a dose of 45-50 Gy, and gross disease was treated to a mean total dose of 61.7 Gy (range, 54-66 Gy). Seventeen patients (63%) received neoadjuvant or adjuvant chemotherapy. Fifteen (56%) received cisplatin concurrently with IMRT. Rates of overall survival and progression-free survival following salvage IMRT were determined using the Kaplan-Meier method, and differences between subgroups were assessed using the log-rank statistic. ResultsOf the 27 patients, 19 (70%) had local control of paraortic disease after a median follow-up time of 25 months (range, 4-83 months). Two-year actuarial overall survival and progression-free survival rates were 63% and 53%, respectively. Five patients (19%) experienced severe late gastrointestinal toxic effects (grade 3-5). ConclusionsIMRT can serve as salvage therapy of paraortic recurrence of endometrial cancer. However, the risk of severe gastrointestinal toxic effects is high, and care should be taken during treatment planning to minimize the dose to the small bowel.

Controversies in the Adjuvant Therapy of Endometrial Cancer

Endometrial cancer is the most common malignancy of the female genital tract. Surgical treatment includes hysterectomy, bilateral salpingo-oophorectomy, and an appropriate staging procedure. Relapse of endometrial cancer may occur in patients with high risk factors, such as old age, grade 3 cancer, deep myometrial invasion, and papillary serous and clear cell types. In recent years, several randomized trials reported the results of adjuvant therapy for patients with high risk factors. Nonetheless, some controversies still exist. This paper presents and discusses the results of important randomized trials of adjuvant therapy for endometrial cancer with risk factors.

Surveillance Procedures for Patients Treated for Endometrial Cancer: A Review of the Literature

The aim of this review was to analyze the role of follow-up in patients treated for endometrial cancer and to provide some compelling issues that may contribute to improve daily practice while waiting for evidence-based guidelines. A literature search has been conducted in MEDLINE database using key words "endometrial neoplasms" and "follow up". Endometrial cancer represents the most common gynecologic malignancy after breast cancer. The overall recurrence rate is 13% and correlates with prognostic factors of the primary tumor. The anatomic sites of endometrial cancer relapse are mostly equivalently distributed between local (pelvic) and distant (abdominal and chest). Most endometrial cancer recurrences are symptomatic, even if vaginal vault relapses represent a particular setting of a more frequently asymptomatic disease. Most of endometrial cancer recurrences occur within 3 years since diagnosis of primary tumor. Long-term surveillance programs are mainly addressed to the early detection of recurrence, the rationale of follow-up being that an earlier diagnosis of relapse correlates with lower morbidity and mortality rates. Adjunctive objectives of routine follow-up are identification of treatment complications and detection of possible second tumors associated with endometrial cancer. No rationale (examination sensitivity/sensibility, cost-effectiveness, or patient's survival benefit) is available today for any particular follow-up protocol; follow-up procedures should probably be tailored according to different prognostic factors; only physical examination, including pelvic-rectal examination, showed some utility in detecting recurrence. In this uncertain setting, follow-up interval should be defined with the consideration of the patient's will.

Factors influencing survival in endometrial cancer relapsing patients: a Cooperation Task Force (CTF) study

The purpose of this study was to identify patterns of relapse and to determine the outcome of salvage treatment and the factors influencing survival of endometrial cancer relapsing patients. One thousand six hundred and six endometrial cancer (stages I to IV) patients treated at five Italian institutions were retrospectively reviewed. Of these, 209 (13%) subjects had recurred; the site of relapse was vagina in 35 cases (16.7%), pelvis in 67 (32.1%), and distant locations in 107 (51.2%). Most of the patients relapsed within 24 months: 45% (94) recurred within 1 year, 20.6% (43) between 1 and 2 years. Adjuvant radiotherapy (RT) seemed to reduce the percentage of pelvic recurrence in high risk early stages (IB-IIA) subjects and a higher proportion of patients failed at a distant site when postoperative external-beam pelvic RT was given. However survival curves were not statistically different in the two groups for stage IB endometrial cancer patients. Five and 10-year survival rates of patients with recurrent disease was 26% and 22%, respectively. Relapse of endometrial cancer is often early and at distant sites. Survival rate was related to site of relapse, disease-free interval, and postoperative treatment as independent prognostic variables. The site of relapse is the most important predictor of survival of patients with recurrent disease.

Factors influencing survival in endometrial cancer relapsing patients: a Cooperation Task Force (CTF) study

The purpose of this study was to identify patterns of relapse and to determine the outcome of salvage treatment and the factors influencing survival of endometrial cancer relapsing patients. One thousand six hundred and six endometrial cancer (stages I to IV) patients treated at five Italian institutions were retrospectively reviewed. Of these, 209 (13%) subjects had recurred; the site of relapse was vagina in 35 cases (16.7%), pelvis in 67 (32.1%), and distant locations in 107 (51.2%). Most of the patients relapsed within 24 months: 45% (94) recurred within 1 year, 20.6% (43) between 1 and 2 years. Adjuvant radiotherapy (RT) seemed to reduce the percentage of pelvic recurrence in high risk early stages (IB-IIA) subjects and a higher proportion of patients failed at a distant site when postoperative external-beam pelvic RT was given. However survival curves were not statistically different in the two groups for stage IB endometrial cancer patients. Five and 10-year survival rates of patients with recurrent disease was 26% and 22%, respectively. Relapse of endometrial cancer is often early and at distant sites. Survival rate was related to site of relapse, disease-free interval, and postoperative treatment as independent prognostic variables. The site of relapse is the most important predictor of survival of patients with recurrent disease.