scholarly journals Evaluation of Survival, Recurrence Patterns and Adjuvant Therapy in Surgically Staged High-Grade Endometrial Cancer with Retroperitoneal Metastases

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2052
Author(s):  
Jennifer McEachron ◽  
Lila Marshall ◽  
Nancy Zhou ◽  
Van Tran ◽  
Margaux J. Kanis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Endometrial Cancer ◽  
Adjuvant Therapy ◽  
Clear Cell ◽  
High Grade ◽  
Stage Iiic ◽  
Treatment Delays ◽  
Recurrence Patterns ◽  
Grade 3

Background: We seek to evaluate the difference in recurrence patterns and survival among stage IIIC high-grade endometrial cancer treated with surgery followed by adjuvant chemotherapy alone, radiation therapy alone, or both (chemoradiation). Methods: A multicenter retrospective analysis of surgically staged IIIC HGEC receiving adjuvant therapy was conducted. HGEC was defined as grade 3 endometrioid adenocarcinoma, serous, clear cell and carcinosarcoma. Differences in the frequency of recurrence sites and treatment delays were identified using Pearson’s χ2 test. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier estimates. Results: A total of 155 patients were evaluable: 41.9% carcinosarcoma, 36.8% serous, 17.4% grade 3 and 3.9% clear cell. Of these, 67.1% received chemoradiation, 25.8% received chemotherapy and 7.1% received radiation therapy. There was no difference in the frequency of treatment delays between regimens (p = 0.571). There was a trend towards greater retroperitoneal recurrence with chemotherapy (25.9%) versus chemoradiation (8.4%) and radiation therapy (7.7%) (p = 0.252). Grade 3 tumors had improved progression-free and overall survival (26 and 42 months, respectively) versus serous (17 and 30 months, respectively), carcinosarcoma (14 and 24 months, respectively) and clear cell (24 and 30 months respectively) (p = 0.002, p < 0.001). Overall, chemoradiation was superior to chemotherapy and radiation therapy in PFS (p < 0.001) and OS (p < 0.001). Upon multivariate analysis, only histology and receipt of chemoradiation were independent predictors of survival. Conclusion: The majority of stage IIIC high-grade endometrial carcinomas recurred. Chemoradiation was associated with improved survival and less retroperitoneal recurrence. Grade 3 tumors demonstrated improved survival versus other histologies regardless of adjuvant treatment modality.

Disparities in adjuvant treatment of high-grade endometrial cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17572-e17572
Author(s):  
Logan Corey ◽  
Michele L. Cote ◽  
Julie J. Ruterbusch ◽  
Ira Seth Winer
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Adjuvant Therapy ◽  
Adjuvant Treatment ◽  
Surgical Outcomes ◽  
Figo Stage ◽  
Treatment Delay ◽  
Stage Ii ◽  
High Grade ◽  
Race Ethnicity

e17572 Background: To examine surgical outcomes, patterns of adjuvant therapy, and survival for non-Hispanic Black (NHB) women compared to non-Hispanic White (NHW) and Hispanic (HS) women who have undergone surgery for high grade endometrial cancer in the Medicare population. Methods: We utilized the SEER-Medicare linked database to identify women who underwent surgery as a primary treatment for uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma, or serous carcinoma between the years 2000 and 2015. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for receiving a treatment delay or not receiving adjuvant treatment (compared to those who received adjuvant treatment within 12 weeks) adjusted for clinical and demographic characteristics. Overall survival (OS) stratified by race/ethnicity, route of surgery, operative complications, and type and timing of adjuvant therapy were analyzed using the Kaplan-Meier method. Cox Proportional hazards regression was used to estimate hazard of death by race/ethnicity adjusted for known predictors, as well as surgical outcomes and adjuvant therapy patterns. Results: 12, 201 women met study inclusion criteria. NHB patients had a significantly worse five-year overall survival (OS) than HS and NHW patients (30.9 months vs 51.0 months vs 53.6 months, respectively). Approximately 8.6% of patients who received adjuvant treatment experienced a treatment delay (632/7, 282). Delay in treatment of greater than or equal to 12 weeks was significantly different by race/ethnicity (p=0.034), with 12% of HS, 9% of NHB, and 8% of NHW women experiencing a delay. After adjustment for number of complications, age, histology (endometrioid v. non-endometroid), FIGO stage, marital status, comorbidity count, surgical approach, lymph node dissection, and urban-rural code, HS had a 71% increased risk of treatment delay (OR 1.71, CI 1.23-2.38) for all stages of disease. In the same model, NHB race was independently predictive of decreased use of adjuvant treatment for FIGO stage II and higher (OR 1.32, CI 1.04-1.68). NHB race, number of perioperative complications, and non-endometrioid histology were predictive of worse OS in univariate models. Treatment delay was not independently predictive of worse 1- or 5-year survival at any stage. Conclusions: NHB race is predictive of worse 5-year survival across all stages and is also associated with omission of adjuvant treatment in ≥FIGO Stage II high grade endometrial cancers. HS ethnicity was associated with treatment delay across all stages. In unadjusted analyses, patients who experience treatment omission or delay experienced poorer OS, but these factors were not independently associated in multivariate analyses.

Adjuvant Chemotherapy With External BeamRadiation Therapy for High-Grade, Node-Positive Endometrial Cancer

2014 ◽  
Vol 24 (8) ◽  
pp. 1441-1448 ◽  
Author(s):  
Larissa J. Lee ◽  
Paula Bu ◽  
Colleen Feltmate ◽  
Akila N. Viswanathan
Keyword(s):  
Endometrial Cancer ◽  
Clinical Outcomes ◽  
Clear Cell ◽  
External Beam Radiation ◽  
High Grade ◽  
Beam Radiation ◽  
Histologic Subtype ◽  
Node Positive ◽  
Grade 3 ◽  
Histologic Subtypes

ObjectiveThe objective of this study was to evaluate clinical outcomes including disease-free survival (DFS) and overall survival (OS) for women with node-positive, high-grade adenocarcinoma of the uterus.MethodsDatabase review identified 73 patients with International Federation of Gynecology and Obstetrics stage IIIC 1/2 grade 3 endometrial cancer diagnosed from 1995 to 2009. Study inclusion required total abdominal hysterectomy/bilateral salpingo-oophorectomy and negative chest imaging. Histologic subtypes were endometrioid (22, 30%), papillary serous (20, 27%), clear cell (9, 12%), mixed (21, 29%), and undifferentiated (1, 1%). Adjuvant treatment was chemotherapy with external beam radiation therapy (EBRT) in 55 patients (75%), EBRT alone in 14 (19%), chemotherapy in 2 (3%), and no adjuvant therapy in 2 (3%).ResultsWith a median follow-up of 50 months, DFS/OS rates at 5 years were 44%/53%, respectively. Intraperitoneal relapse was more common in patients with positive cytology (30% vs 6%,P= 0.02) and nonendometrioid histology (16% vs 4%,P= 0.3). By histologic subtype, 5-year DFS/OS rates were 59%/82% for grade 3 endometrioid, 25%/30% for serous, 22%/17% for clear cell, and 50%/51% for mixed histology (P= 0.1/P< 0.001). The 5-year DFS/OS rates were 56%/68% for those who received both chemotherapy and EBRT. Among patients treated with adjuvant EBRT, pelvic control was 93%.ConclusionsFor node-positive, high-grade endometrial cancer, patients with endometrioid and mixed histologic subtypes had better clinical outcomes than did those with serous and clear cell cancers. Distinct patterns of relapse were observed with a greater risk of intraperitoneal failure for nonendometrioid histologic subtypes. Future studies are needed to define the optimal chemotherapy regimen and radiation fields.

scholarly journals Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment

2013 ◽  
Vol 23 (9) ◽  
pp. 1620-1628 ◽  
Author(s):  
Joyce N. Barlin ◽  
Robert A. Soslow ◽  
Megan Lutz ◽  
Qin C. Zhou ◽  
Caryn M. St. Clair ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Myometrial Invasion ◽  
Staging System ◽  
Stage I ◽  
Low Grade ◽  
List Type ◽  
High Grade ◽  
High Grade Carcinoma ◽  
Concordance Probability ◽  
Grade 3

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

scholarly journals A Comparison of Death Domain-Associated Protein 6 in Different Endometrial Carcinomas Histotypes

2019 ◽  
Vol 14 ◽  
pp. 117727191986489
Author(s):  
Cao Jin ◽  
Sean Hacking ◽  
Miglena K Komforti ◽  
Mansoor Nasim
Keyword(s):  
Clear Cell ◽  
Point Mutations ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Death Domain ◽  
Gynecology And Obstetrics ◽  
Grade 3 ◽  
Histologic Types ◽  
Endometrial Carcinomas

Background: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. Design: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. Results: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) ( P = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. Conclusions: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX’s role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.

Impact of vaginal brachytherapy on survival in stage I endometrioid endometrial carcinoma

2020 ◽  
Vol 30 (6) ◽  
pp. 789-796 ◽  
Author(s):  
Mariam AlHilli ◽  
Sudha Amarnath ◽  
Paul Elson ◽  
Lisa Rybicki ◽  
Sean Dowdy
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Endometrial Cancer ◽  
External Beam Radiation Therapy ◽  
Stage I ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation ◽  
Stage Ib ◽  
Stage Ia

ObjectiveTo evaluate trends in use of radiation therapy and its impact on overall survival in low- and high-grade stage I endometrioid endometrial carcinoma.MethodsPatients with stage I endometrial cancer who underwent hysterectomy from 2004 to 2013 were identified through the National Cancer Database and classified as: stage IA G1/2, stage IA G3, stage IB G1/2, and stage IB G3. Trends in use of vaginal brachytherapy and external beam radiation therapy were assessed. Overall survival was measured from surgery and estimated using the Kaplan-Meier method. The effect of radiation therapy on overall survival was assessed within each stage/grade group using Cox proportional hazards analysis in propensity-matched treatment groups.ResultsA total of 132 393 patients met inclusion criteria, and 81% of patients had stage IA and 19% had stage IB endometrial cancer. Adjuvant therapy was administered in 18% of patients: 52% received vaginal brachytherapy, 30% external beam radiation therapy, and 18% chemotherapy ±radiation therapy. External beam radiation therapy use decreased from 9% in 2004 to 4% in 2012, while vaginal brachytherapy use increased from 8% to 14%. Stage IA G1/2 patients did not benefit from either external beam radiation therapy or vaginal brachytherapy, while administration of vaginal brachytherapy improved overall survival in stage IB G1/2 compared with no treatment (p<0.0001). In stage IB G1/2 and stage IA G3, vaginal brachytherapy was superior to external beam radiation therapy (p=0.0004 and p=0.004, respectively). Stage IB G3 patients had improved overall survival with either vaginal brachytherapy or external beam radiation therapy versus no treatment but no difference in overall survival was seen between vaginal brachytherapy and external beam radiation therapy (p=0.94).ConclusionsThe delivery of adjuvant radiation therapy in patients with stage IA G1/2 endometrial carcinoma is not associated with improvement in overall survival. Patients with stage IB G1/2 and G3 as well as stage IA G3 are shown to benefit from improved overall survival when adjuvant radiation therapy is administered. These findings demonstrate potential opportunities to reduce both overtreatment and undertreatment in stage I endometrial cancer patients.

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clear Cell ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
Type Ii ◽  
Ovarian Serous Carcinoma ◽  
Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

Efficacy and safety of administration of gemcitabine and docetaxel with radiation therapy in patients with high-grade soft tissue sarcoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e21503-e21503
Author(s):  
G. G. Raval ◽  
R. Govindarajan
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Necrosis ◽  
Outpatient Basis ◽  
High Grade ◽  
Time Of Surgery ◽  
Neo Adjuvant Chemotherapy

e21503 Background: Neo-adjuvant therapy of soft tissue sarcoma is not standardized. Anthracyclines (A) improve disease free and overall survival in high grade extremity soft tissue sarcomas measuring more than 5 cm. A and ifosfamide (I) therapy require inpatient administration and is associated with significant toxicities when administered in combination with RT. G in combination with D has been shown to prolong progression free and overall survival in patients with advanced or metastatic STS after progression on A and I, and in patients unable to receive the combination. The safety of administration of G with radiation is not known. We evaluated the safety of neo-adjuvant G and D in combination with RT in patients with STS. Methods: Retrospective analysis of subjects with high grade STS treated with RT and neo-adjuvant chemotherapy with G and D was conducted. G 600mg/m2 was administered on days 1 and 8 along with D 75 mg/m2 on day 8 for a total of 3 cycles. 2200 cGY RT was administered in 11 daily fractions between cycles 1 and 2 and between cycles 2 and 3. 72 hour gap was given between RT and chemotherapy. Chemotherapy was administered on outpatient basis. Efficacy was evaluated by the extent of tumor necrosis at the time of surgery. Safety was evaluated by the presence of complications following chemotherapy. Results: GD + R was administered to 12 patients in the neo-adjuvant setting. 11 of them were evaluable for response. 10 of the 11 patients had evidence of tumor necrosis at the time of surgery. 1 patient had poor response. 3 of 11 patients had neutropenia complicating neo-adjuvant chemotherapy. 4 patients required hospital admission post chemotherapy. 3 for neutopenic fever, and 1 for fever, chills and pneumonia without neutropenia. Conclusions: Gemcitabine and taxotere combination with radiation therapy can be administered safely on outpatient basis with minimal toxicity. Further safety and efficacy evaluation of this therapy will need to be confirmed in a prospective phase II study. No significant financial relationships to disclose.

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