scholarly journals Clinical patterns and genomic profiling of recurrent ‘ultra-low risk’ endometrial cancer

2020 ◽  
Vol 30 (6) ◽  
pp. 717-723 ◽  
Author(s):  
Marina Stasenko ◽  
Noah Feit ◽  
Simon S K Lee ◽  
Cassandra Shepherd ◽  
Robert A Soslow ◽  
...  

ObjectiveDespite good prognosis for patients with low-risk endometrial cancer, a small subset of women with low-grade/low-stage endometrial cancer experience disease recurrence and death. The aim of this study was to characterize clinical features and mutational profiles of recurrent, low-grade, non-myoinvasive, ‘ultra-low risk’ endometrioid endometrial adenocarcinomas.MethodsWe retrospectively identified patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA endometrioid endometrial cancers who underwent primary surgery at our institution, between January 2009 and February 2017, with follow-up of ≥12 months. ‘Ultra-low risk’ was defined as FIGO tumor grade 1, non-myoinvasive, and lacking lymphovascular space invasion. Tumor-normal profiling using massively parallel sequencing targeting 468 genes was performed. Microsatellite instability was assessed using MSIsensor. DNA mismatch repair (MMR) protein proficiency was determined by immunohistochemistry.ResultsA total of 486 patients with ultra-low risk endometrioid endometrial cancers were identified: 14 (2.9%) of 486 patients developed a recurrence. Median follow-up for non-recurrent endometrioid endometrial cancers: 34 (range 12–116) months; for recurrent endometrioid endometrial cancers: 50.5 (range 20–116) months. Patients with recurrent disease were older, had lower body mass index, and were most commonly non-White (p=0.025, p<0.001, and p<0.001, respectively). Other clinical characteristics did not differ. MMR immunohistochemistry was obtained for 211 (43%) tumors: 158 (75%) MMR-proficient and 53 (25%) MMR-deficient. Primary tumors of 9 recurrent and 27 non-recurrent endometrioid endometrial cancers underwent mutational profiling. Most were microsatellite stable (6/9, 67% recurrent; 25/27, 93% non-recurrent). Recurrent PTEN and PIK3CA mutations were present in both groups. Exon 3 CTNNB1 hotspot mutations were found in 4/9 (44%) recurrent and 8/27 (30%) non-recurrent (p=0.44).ConclusionsPatients diagnosed with ultra-low risk endometrioid endometrial cancers have an overall excellent prognosis. However, in our study, 2.9% of patients with no identifiable clinical or pathologic risk factors developed recurrence. Further work is warranted to elucidate the mechanism for recurrence in this population.

2020 ◽  
Vol 30 (8) ◽  
pp. 1177-1182
Author(s):  
Sarah Coleridge ◽  
Jo Morrison

ObjectiveRecurrence of low-risk endometrioid endometrial cancer is rare, and traditional hospital follow-up has a cost to both the patient and the healthcare system, without evidence of benefit. We examined the uptake of patient-initiated follow-up, pattern of recurrences, and survival for women following surgical treatment of low-risk endometrial cancer and compared estimated costs with hospital follow-up.MethodsThis study was a prospective audit of outcomes following implementation of a patient-initiated follow-up policy in a UK-based gynecological cancer center for women with low-risk endometrial cancer treated surgically (International Federation of Gynecology and Obstetrics (FIGO) stage 1A, G1-2) from January 2010 to December 2015. Women were identified following multidisciplinary team meetings and data were collected from the electronic cancer register, paper, and electronic clinical records. Health service costs were calculated based on standard tariffs for follow-up appointments; patient costs were estimated from mileage traveled from home postcode and parking charges. Progression-free survival and overall survival were assessed. Estimated financial costs to the health service and patients of hospital follow-up were compared with actual patient-initiated follow-up costs.ResultsA total of 129 women were offered patient-initiated follow-up (declined by four; accepted by another 11 after hospital follow-up for 6 months to 3.5 years) with median follow-up of 60.7 months (range 1.4–109.1 months). Ten women recurred: four vaginal vault recurrences (all salvaged), three pelvic recurrences (all salvaged), and three distant metastatic disease (all died). Five-year disease-specific survival was 97.3%. Ten women in the cohort died: three from endometrial cancer and seven from unrelated causes. The cost saving to the health service of patient-initiated follow-up compared with a traditional hospital follow-up regimen was £116 403 (median £988.60 per patient,range £0–£1071). Patients saved an estimated £7122 in transport and parking costs (median £57.22 per patient,range £4.98–£147.70).ConclusionPatient-initiated follow-up for low risk endometrial cancer has cost benefits to both health service and patients. Those with pelvic or vault recurrence had salvageable disease, despite patient-initiated follow-up.


2021 ◽  
pp. ijgc-2021-002903
Author(s):  
Asma Sarwar ◽  
Jennifer Van Griethuysen ◽  
Jasmine Waterhouse ◽  
Hakim-Moulay Dehbi ◽  
Gemma Eminowicz ◽  
...  

ObjectiveHospital based follow-up has been the standard of care for endometrial cancer. Patient initiated follow-up is a useful adjunct for lower risk cancers. The purpose of this study was to evaluate outcomes of endometrial cancer patients after stratification into risk groupings, with particular attention to salvageable relapses.MethodsAll patients treated surgically for International Federation of Gynecology and Obstetrics (FIGO) stage I–IVA endometrial cancer of all histological subtypes, from January 2009 until March 2019, were analyzed. Patient and tumor characteristics, treatment details, relapse, death, and last follow-up dates were collected. Site of relapse, presence of symptoms, and whether relapses were salvageable were also identified. The European Society of Medical Oncology–European Society of Gynecological Oncology 2020 risk stratification was assigned, and relapse free and overall survival were estimated.Results900 patients met the eligibility criteria. Median age was 66 years (range 28–96) and follow-up duration was 35 months (interquartile range 19–57). In total, 16% (n=144) of patients relapsed, 1.3% (n=12) from the low risk group, 3.9% (n=35) from the intermediate risk group, 2.2% (n=20) from the high–intermediate risk group, and 8.7% (n=77) from the high risk group. Salvageable relapses were less frequent at 2% (n=18), of which 33% (n=6) were from the low risk group, 22% (n=4) from the intermediate risk group, 11% (n=2) from the high–intermediate risk group, and 33% (n=6) from the high risk group. There were only three asymptomatic relapses in the low risk patients, accounting for 0.33% of the entire cohort.ConclusionsRelapses were infrequent and most presented with symptoms; prognosis after relapse remains favorable. Overall salvageable relapses were infrequent and cannot justify intensive hospital based follow-up. Use of patient initiated follow-up is therefore appropriate, as per the British Gynaecological Cancer Society's guidelines, for all risk groupings.


2020 ◽  
Author(s):  
Y Naaman ◽  
T Hodge ◽  
A Jones ◽  
F Chin ◽  
D Neesham ◽  
...  

2017 ◽  
Vol 59 (3) ◽  
pp. 363-370 ◽  
Author(s):  
Bin Yan ◽  
Tingting Zhao ◽  
Xiufen Liang ◽  
Chen Niu ◽  
Caixia Ding

Background Diffusion-weighted imaging (DWI) provides useful information for the identification of benign and malignant uterine lesions. However, the use of the apparent diffusion coefficient (ADC) for histopathological grading of endometrial cancer is controversial. Purpose To explore the use of ADC values in differentiating the preoperative tumor grading of endometrioid adenocarcinomas and investigate the relationship between the ADC values of endometrial cancer and the histological tumor subtype. Material and Methods We retrospectively evaluated 98 patients with endometrial cancers, including both endometrioid adenocarcinomas (n = 80) and non-endometrioid adenocarcinomas (n = 18). All patients underwent DWI procedures and ADC values were calculated. The Kruskal–Wallis test and the independent samples Mann–Whitney U test were used to compare differences in the ADC values between different tumor grades and different histological subtypes. Results The mean ADC values (ADCmean) for high-grade endometrioid adenocarcinomas were significantly lower than the values for low-grade tumors (0.800 versus 0.962 × 10–3 mm2/s) ( P = 0.002). However, no significant differences in ADCmean and minimum ADC values (ADCmin) were found between tumor grades (G1, G2, and G3) of endometrial cancer. Compared with endometrioid adenocarcinomas, the adenocarcinoma with squamous differentiation showed lower ADC values (mean/minimum = 0.863/0.636 versus 0.962/0.689 × 10–3 mm2/s), but the differences were not significant ( Pmean = 0.074, Pmin = 0.441). Moreover, ADCmean for carcinosarcomas was significantly higher than the value for G3 non-carcinosarcoma endometrial cancers (1.047 versus 0.823 × 10–3 mm2/s) ( P = 0.001). Conclusion The ADCmean was useful for identifying high-grade and low-grade endometrioid adenocarcinomas. Additionally, squamous differentiation may decrease ADCmean and ADCmin of endometrioid adenocarcinoma, and carcinosarcomas showed relatively high ADCmean.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23518-e23518
Author(s):  
Silvia Gasperoni ◽  
Francesca Castiglione ◽  
Margherita Vannucchi ◽  
Laura Papi ◽  
Elena Fumagalli ◽  
...  

e23518 Background: In patients with GIST, literature reports a risk of second primary tumors between 4.5% and 33% with different distribution in the worldwide. The network of 7 italian EURACAN centers has collected clinical and molecular features of GIST patients with second primary tumors. Methods: We reviewed the clinical characteristics of 201 patients with GIST and second primary tumors in order to evaluate association between risk of dead and each possible factor, using Kaplan meier curve, log-rank test and Cox model for Hazard Ratio and it’s interval Confidence 95% estimation. Furthermore, NGS analysis ( 56 gene onco panel) in 72 patients with GIST was performed. Results: On the basis of the significant correlation previously observed between the Miettinen risk criteria of GIST (low/very low) and the incidence of second primary tumors (gastrointestinal tumors),P < 0.001 (Abstr 11032 ASCO 2019), we observed in these patients a median age of diagnosis of GIST of 68, with prevalent gastric site localization ( KIT exon 11 mutation), NF1 and Lynch (kit/pdgfra WT) syndromes in the low risk subgroup. The more frequent site of second epithelial tumor in gastrointestinal tract was the colon followed by gastric, pancreatic and biliary tract. In patients with GIST with low-very low risk according Miettinen classification, after a median follow-up period of 25 years, we have observed that the gastroenteric site of second tumors occurrence is significantly related to the survival (p < .0003). In the NGS analysis of the GIST we observed the pathogenetic somatic mutations in the following genes: BRCA 2 (p.Thr2125fs), but germline test negative, TP53 (p.Arg192*,p.Gly244Ser,p.His168Leu), RET (p.Lys120Asn, p.His168Leu, p.Thr930Met ), NRAS (p.Gly134Asp), CTNNB1 (p.Ser45Phe), MSH6 (P.Ala164Val), SMARCB1 (p.Arg192), VHL (p.Gly93Val), PTEN(p.Val158Ile, p.Asn323fs), STK1I (p.Arg40Cys), SMO (p.Glu194Lys), EGFR (p.Gly721Asp), ATM (p.Asp2708Asn), ERBB4 (p.Asn181Ile). Conclusions: In our analysis patients with GIST (low-very low classes according to Miettinen) have significant risk to death because of second primary tumors in gastrointestinal tract. Specific attention to gastrointestinal screening during the follow-up of GIST (low and very low risk) is required.


2018 ◽  
Vol 104 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Hulya Ayik Aydin ◽  
Tayfun Toptas ◽  
Selen Bozkurt ◽  
Elif Pestereli ◽  
Tayup Simsek

Purpose: Despite the common occurrence of adenomyosis in endometrial cancer (EC), there is a paucity and conflict in the literature regarding its impact on outcomes of patients. We sought to compare outcomes of patients with endometrioid type EC with or without adenomyosis. Methods: A total of 314 patients were included in the analysis. Patients were divided into 2 groups according to the presence or absence of adenomyosis. Adenomyosis was identified in 79 patients (25.1%). A propensity score-matched comparison (1:1) was carried out to minimize selection biases. The propensity score was developed through multivariable logistic regression model including age, stage, and tumor grade as covariates. After performing propensity score matching, 70 patients from each group were successfully matched. Primary outcome of the study was disease-free survival (DFS), and the secondary outcomes were overall survival (OS) and disease-specific survival (DSS). Results: Median follow-up time was 61 months for the adenomyosis positive group and 76 months for the adenomyosis negative group. There were no statistically significant differences in 3- and 5-year DFS, OS, and DSS rates between the 2 groups. Five-year DFS was 92% vs 88% (hazard ratio [HR] 1.54 [0.56-4.27]; p = 0.404), 5-year OS was 94% vs 92% (HR 1.60 [0.49-5.26]; p = 0.441), and 5-year DSS was 94% vs 96% (HR 2.51 [0.46-13.71]; p = 0.290) for patients with and without adenomyosis, respectively. Conclusions: Coexistent adenomyosis in EC is not a prognostic factor and does not impact survival outcomes.


2021 ◽  
Author(s):  
Reed Ritterbusch ◽  
Lia M. Halasz ◽  
Jerome J. Graber

Abstract Purpose Criteria by the Radiologic Assessment in Neuro-Oncology (RANO) group outline the diagnosis of pseudoprogression (Ps) after photon therapy for gliomas based on timing and location. We noted that patients receiving proton therapy manifested radiographic changes that appear different than Ps after photon therapy, which could be interpreted as tumor progression. In this study, we retrospectively reviewed MR imaging after proton or photon radiation for gliomas. We propose criteria to characterize proton pseudoprogression (ProPs) as distinct from Ps seen after photons. Methods Post-treatment MR imaging, clinical and pathological data of low grade glioma patients were reviewed. Overall, 57 patients receiving protons were reviewed for the presence of ProPs, and 43 patients receiving photons were reviewed for any equivalent imaging changes. Data collected included the location and timing of the new enhancement, tumor grade, molecular subtype, chemotherapy received, and clinical symptoms. Results Fourteen patients (24.6%) had new enhancement following radiation therapy that was unique to treatment with protons. The mean time to development of the ProPs was 15.4 months (7–27 months). We established the following criteria to characterize ProPs: located at the distal end of the proton beam; resolves without tumor-directed therapy; and subjectively multifocal, patchy, and small (< 1 cm). In the group receiving photons, none had changes that met our criteria for ProPs. Conclusion Patients who receive protons have unique imaging changes after radiation therapy. ProPs could be mistaken for tumor progression, but typically resolves on follow up. Further studies are needed to understand the radiobiology and pathophysiology underlying these imaging changes.


2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
D Goodman ◽  
R Taggart ◽  
J Salmond ◽  
E H Day

Abstract Aim This study addresses surveillance cystoscopy in patients diagnosed with bladder and upper tract cancer. Managed Clinical Network (MCN) guidelines have clear recommendations for the timetable of follow-up cystoscopy, and we conducted this audit to study regional compliance. Method Using a multisite pathology database of bladder cancer cases from 2016, we collected and analysed data on 100 non-muscle invasive bladder cancers. We took the first 10 cases from each month to ensure cross-regional representation. Each case was stratified according to MCN guidelines. Electronic medical records were examined to assess upper tract follow up. We allowed for +/- 1 month each side of the target timeframe. Results We had 64 male and 36 female subjects. In our risk categories, we had 31 low risk, 37 intermediate risk and 32 high risk bladder cancers. 67 were new cases, 33 were recurrent tumours. 10 (43.4%) of low-risk and 19 (79.2%) of intermediate-risk patients underwent surveillance cystoscopy earlier than the recommended 12-month timeframe. 18 (78.3%) of low-risk patients continued to have further surveillance cystoscopies after a 12-month disease-free period. Conclusions 43.4% of low-risk bladder cancer patients are receiving surveillance cystoscopy earlier than recommended. 78.3% of these patients are then undergoing unnecessary procedures following a 12-month disease-free period against regional guidelines and recommendations. This places an increased burden on clinic/theatre time and contributes to patient anxiety surrounding cancer follow-up. Evidence-based medicine guidelines have shown that less is more when it comes to low-grade bladder cancer surveillance. We now need to assess why we are deviating from our own guidelines.


Author(s):  
Sanjay Badesara ◽  
Ashitha R. Gangadharan ◽  
Rambeer Singh ◽  
Adarsh Dharmarajan

Background: Incomplete surgical staging in carcinoma endometrium is not an uncommon entity in developing world. Proper surgical staging has got a role in prognostication and planning adjuvant treatment. So, an audit was done to assess the extent of upstaging in women with endometrial cancers who were referred to index centre from outside hospitals with incomplete surgical staging.Methods: It is a retrospective study. The demographic, clinical and treatment details of women with complete data having at-least one follow up after completion surgery were analyzed. Patients who had any other anticancer treatment elsewhere were excluded. The extent of upstaging was studied based on International federation of gynecology and obstetrics (FIGO) 2008 staging.Results: A total of 88 patients of endometrial cancer were evaluated retrospectively, of which 10 had completion surgery. 10% of the patients were upstaged according to the FIGO stage (one from IA to IB), while one patient upstaged from IIIA to IVB after slide review by index centre. According to FIGO Grade, 40% patient upgraded (one upgraded from I to II, three from II to III) while one downgraded from II to I. Recurrence rate was 40%.Conclusions: Upstaging is seen in 10% of patient after completion surgery, which requires the necessity of evaluation by gynecologic oncologist selectively. However, larger and multi-centric studies needed to draw definite conclusion. There is a significant discordance in grade and histology after the review at index centre.


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