Treatment Of Endometrial Adenocarcinoma Research Articles

The past, present, and future of immunotherapy for endometrial adenocarcinoma.

Incidences of endometrial adenocarcinoma are increasing in the USA with poor prognosis for patients with advanced disease. The current treatment standard is surgery including total hysterectomy and bilateral oophorectomy with surgical staging and adjunct treatment, such as chemotherapy or radiation. However, these methods do not present as an effective treatment option for poorly differentiated advanced cancers. Advancements in immunotherapy now offer a new approach for various types of cancer and specifically show promise in the treatment of endometrial adenocarcinoma. This review summarizes immunotherapeutic treatment options relevant to endometrial adenocarcinoma, such as immune checkpoint blockades, bispecific T-cell engager antibodies, vaccinations, and adoptive cell transfer. This study could be helpful for clinicians to identify treatment options more suitable for women with late-stage endometrial adenocarcinoma.

Outcomes of in vitro fertilization cycles following fertility-sparing treatment in stage IA endometrial cancer

This study aimed to present cases involving in vitro fertilization (IVF) cycles in patients with stage IA endometrial adenocarcinoma (EC) who underwent fertility-sparing conservative treatment. Twenty-two patients who underwent IVF cycles in a single fertility center between May 2005 and February 2017 after progestin treatment for stage IA EC were chosen for this study. Outcomes of IVF cycles were analyzed retrospectively. Women of a median age of 34years (range 26-41years) underwent a total of 49 embryo transfers within an average of 2months after their last progestin treatment. The clinical pregnancy rate per transfer was 26.5%, implantation rate was 16.7%, and live birth rate was 14.3%. The cumulative clinical pregnancy rate was 50% (11/22), resulting in 6 live births (27.3%) within 3 cycles of embryo transfer. The median endometrial thickness on the day of human chorionic gonadotropin injection in 34 fresh cycles was 9.0mm (range 4-10mm) in live births, 7.5mm (range 6-9mm) in miscarriages, and 6.0mm (range 4-15mm) in no pregnancy cases. During a median post-cancer treatment follow-up period of 41months (range9-150months), 6 (27.3%) women underwent definitive hysterectomy for EC relapse. This study showed an acceptable cumulative pregnancy rate after the IVF procedure in patients with early-stage EC who were treated conservatively. Considering the high relapse rate, it is of great importance that these patients are closely monitored after the IVF cycles.

Clinicopathologic characteristics and treatment features of women with the incidental diagnosis of endometrial adenocarcinoma during infertility follow-up in Ankara, Turkey

ObjectiveThe aim of this study was to investigate the clinical and laboratory features of patients with the incidental diagnosis of endometrial adenocarcinoma (EC) during infertility work-up, with special attention given to treatment approaches, recurrence rate, and fertility outcome. Material and MethodsThe medical records of 577 patients who were diagnosed with EC and treated between 2007 and 2013 were included in the study. Out of 577 EC patients, 5.1% (n = 30) were ≤ 40 years of age. However, 10 patients had a history of infertility and had been diagnosed during evaluation for infertility. Patients' clinical and laboratory data were reviewed retrospectively. ResultsThe mean age at diagnosis was 34.3 ± 4.5 years and the mean duration of infertility was 5.1 ± 4.7 years. Immediate staging surgery was performed on three patients. The others were treated with oral megestrol acetate and/or a levonorgestrel-containing intrauterine device (IUD) for 6 months. The mean duration of postoperative or postdiagnostic follow-up was 44.7 ± 25.9 months. The disease persistence and recurrence rates were 11.1% and 22.2%, respectively. Two patients achieved pregnancy naturally or by assisted reproductive technology (ART) trial. ConclusionThe investigation of patients during infertility work-up provides an opportunity to evaluate the endometrium and its malignancies in young women, when the disease is in its early stage and symptom free. The standard surgical treatment for early-stage EC is total hysterectomy with bilateral salpingo-oophorectomy. However, conservative management of early stage EC with progestational drugs, especially in young patients who wish to preserve their fertility, is acceptable with the possibility of future pregnancies.

Levonorgestrel-releasing intrauterine system Mirena® (Bayer) for the prevention and treatment of endometrial adenocarcinoma and the incidence of other malignancies in women

The use of hormone-releasing intrauterine devices has been on the increase for the last three decades. To date, evidence of their long-term efficiency is available. The aim of the present paper was to briefly review beneficial prophylactic effects of the levonorgestrel-releasing intrauterine system on the incidence of a variety of malignancies in women. Such an influence is of a particular importance in the light of the currently observed increased prevalence of endometrial and cervical adenocarcinomas. Low-dose releasing intrauterine systems are also available, but the hard evidence-based medical data have been derived primarily for Mirena® (Bayer) device, which topically releases from 20 to 14 pg of levonorgestrel daily. Consequently the risk of developing endometrial carcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk To a lesser extent, the intrauterine system decreases the risk for cervical adenocarcinoma and squamous cell carcinoma, as well as ovarian, pancreas, and lung carcinomas. In one population-based study Mirena® increased the risk for breast carcinoma by approximately 20%, whereas a number of other studies failed to demonstrate such a hazard. In the recent decades of the increased predominance of insulin resistance and obesity and an occurrence of hormone-dependent carcinomas at earlier age, a broad application of levonorgestrel-releasing intrauterine systems may become a particularly important component of primary prevention of malignancies in women. Both obese and overweight patients seem perfect candidates for such a hormonal intervention.

Recidiva vaginal e inguinal en una paciente con adenocarcinoma de endometrio temprano tratado por vía laparoscópica

Surgery is the optimal treatment for early-stage endometrial adenocarcinoma, with lesions confined to the uterus (stages I/II). Although laparotomy is still frequently employed, the use of laparoscopy to treat these tumors is increasing. The results obtained by laparoscopic surgery in the treatment of endometrial adenocarcinoma are excellent, similar to those of laparotomy, with multiple benefits and similar costs. Therefore, laparoscopy is becoming the preferred option for many gynecological oncologists. We report a case of endometrial carcinoma, pT: Ib/G1 treated by laparoscopy consisting of laparoscopic assisted vaginal hysterectomy + double annexectomy + cytology + pelvic lymphadenectomy, which progressed to vaginal introitus metastasis at 7 months of treatment and inguinal metastasis at 14 months.

Apoptotic effects of Tian-Long compound on endometrial adenocarcinoma cells in vitro

The Tian-Long (TL) compound is a water-soluble extract of six Chinese medicinal herbs. To explore its antitumor properties and the mechanism for activity in gynecological malignancies, the present studies were carried out using Ishikawa cells derived from uterine endometrial adenocarcinoma. Morphologically, cell death and decrease in the number of viable cells were observed in the presence of the TL compound. The proliferation of Ishikawa cells was significantly suppressed in a time- and dose-dependent manner, as indicated by both the WST-1 and the BrdU incorporation assay. Results from both the WST-1 and the BrdU incorporation assay demonstrated that the compound could inhibit the cell proliferation despite the presence of 17beta-estradiol in the medium. It is generally noted that the disturbance in mitochondrial function and DNA synthesis during cell proliferation can result in apoptosis. Being consistent with this notion, redistribution of the plasma membrane phosphatidylserine was identified with fluoromicroscopy and flow cytometry. Analysis of the fluorescent patterns of JC-1 staining revealed depolarization of the mitochondrial membrane in the exposed cells. Moreover, the amount of Bcl-2 enhanced in the presence of 17beta-estradiol was repressed by the compound. The present results indicate that the ingredients of TL compound are very promising for use in the treatment of endometrial adenocarcinoma. Further studies are necessary to elucidate the therapeutic mechanisms in its antitumor activity.

A sequential doublet chemotherapy regimen in patients (pts) with advanced endometrial adenocarcinoma (EC) and gynecological mixed müllerian tumors (MMT). Maintaining activity with tolerability?

5079 Background: Carboplatin (C), doxorubicin (D) and paclitaxel (P) have significant activity in advanced EC and MMT. Concurrent 3 drug regimens are associated with high activity but also significant toxicity. Sequential doublet regimens combining all three drugs may retain high levels of efficacy with acceptable levels of toxicity. Methods: Pts with Stage III-IV advanced EC or MMT received first line treatment, from 2001–2004, with 4 cycles of CD (C=AUC5, D=50mg/m2, d1q21) followed by 4 cycles of CP (C=AUC5, P=175mg/m2, d1q21). The primary endpoint was the % of pts completing all planned treatment. Results: 25 pts have completed treatment (19 EC, 6 MMT, median age 59) of whom 72% competed all 8 cycles of treatment (primary endpoint reached). 86% of all planned cycles of chemotherapy were delivered (172 out of a max possible of 200). Toxicity: 20% of cycles were delayed (85% by 1w, 12% by 2w and 3% by 3w), all for hematological toxicity (90% neutropenia, 10% thrombocytopenia). Non hematological toxicity ≥Gd3 was myalgia (1 pt), parasthesia (2pt) fainting and nausea (1pt). 8 consultations (in 7 pts) resulted in dose reduction (cause; 5 neutropenia, 2 parasthesia, 1 myalgia). Response: Of 18 radiologically evaluable patients; 3 had a complete response (17%), 10 partial response (55%), 1 differential response (5%), 3 progressive disease (17%) and 1 taken off trial due to toxicity (5%). Median duration of response was 5.8 months (1.5–29.4 months). 5 deaths have occurred all due to PD (2 on treatment, 1 after 3m and 2 after 6m follow-up). Conclusions: The sequential doublet as described is a feasible and highly active regimen (72% overall response rate) in the first line treatment of EC and MMT. This schedule should be considered for more formal evaluation using larger studies in both diseases. No significant financial relationships to disclose.

Brachytherapy of endometrial cancers

Endometrial adenocarcinomas rank third as tumoral sites en France. The tumors are confined to the uterus in 80% of the cases. Brachytherapy has a large place in the therapeutic strategy. The gold standard treatment remains extrafascial hysterectomy with bilateral annexiectomy and bilateral internal iliac lymph node dissection. However, after surgery alone, the rate of locoregional relapses reaches 4-20%, which is reduced to 0-5% after postoperative brachytherapy of the vaginal cuff. This postoperative brachytherapy is delivered as outpatients treatment, by 3 or 4 fractions, at high dose rate. The uterovaginal preoperative brachytherapy remains well adapted to the tumors which involve the uterine cervix. Patients presenting a localized tumor but not operable for general reasons (< 10%) can be treated with success by exclusive irradiation, which associates a pelvic irradiation followed by an uterovaginal brachytherapy. A high local control of about 80-90% is obtained, a little lower than surgery, with a higher risk of late complications. Last but not least, local relapses in the vaginal cuff, or in the perimeatic area, can be treated by interstitial salvage brachytherapy, associated if possible with external beam irradiation. The local control is reached in half of the patients, but metastatic dissemination is frequent. We conclude that brachytherapy has a major role in the treatment of endometrial adenocarcinomas, in combination with surgery, or with external beam irradiation for not operable patients or in case of local relapses. It should use new technologies now available including computerized afterloaders and 3D dose calculation.

Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo.

Missile therapy, which destroys cancer cells specifically, has been regarded as an effective treatment modality for carcinoma. The monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, was combined with adriamycin (ADM) by a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane. Its selective cytotoxicity against SNG-II was examined in a colony formation in vitro, and on athymic mice in vivo. The results of our study suggest that the <inhibitory concentration> or IC50, of the MSN-1-ADM immunoconjugate against SNG-II to be 57 times that of ADM alone in vitro. The reductions in resected weights of target tumor cells, at the local site of the MSN-1-ADM immunoconjugate treatment, were 25% with caudal vein administration, and 38% with local administration, as compared with the untreated group, in vivo. There was no weight loss in treated mice. Our results suggest that this MSN-1-ADM immunoconjugate has potential clinical application in the treatment of endometrial adenocarcinomas.

Effect of gelonin immunoconjugate with monoclonal antibody MSN-1 to endometrial adenocarcinoma on antigen-producing tumor cells in vivo.

Missile therapy, which destroys cancer cells specifically, has been advocated as an effective modality for the treatment of carcinoma. We have developed an immunoconjugate consisting of the monoclonal antibody MSN‐1 (IgM), which reacts strongly with endometrial adenocarcinomas, combined with a plant hemitoxin named gelonin via a disulfide bond using N‐succinimidyl‐3‐(2‐pyridyldithio)propionate and 2‐iminothiolane, and examined its selective cytotoxicity in athymic mice. The reductions in resected weights of target tumor cells, at the local site of MSN‐1‐gelonin immunoconjugate treatment, were 96% with local administration and 75% with caudal vein administration, as compared with the untreated group. There was no weight loss in treated mice. Our results suggest that this MSN‐1‐gelonin immunoconjugate has potential clinical applications in the treatment of endometrial adenocarcinomas.

Effects of gelonin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma on antigen-producing tumor cells in vitro

Missile therapy, which destroys cancer cells specifically, has been considered to be an effective modality for treatment of carcinoma. We have developed a monoclonal antibody MSN-1 (immunoglobulin class: IgM), of which the immunogen is the endometrial adenocarcinoma cell line SNG-II, which strongly reacts with endometrial adenocarcinomas. We describe an immunoconjugate consisting of the MSN-1 and a plant hemitoxin named gelonin which has revealed to assume selective cytotoxicity against the SNG-II in a colony formation assay in vitro. The results of our study suggest that the 'inhibitory concentration' or IC50, of the MSN-1-gelonin immunoconjugate against the SNG-II was 188 fold that of gelonin alone. These results indicated that the MSN-1-gelonin immunoconjugate exhibited highly selective cytotoxicity to endometrial adenocarcinoma, which expressed an epitope against the MSN-1, and it is suggested that the MSN-1-gelonin immunoconjugate has possibility of clinical application to treatment of endometrial adenocarcinomas.

Is there any value in the long term follow up of women treated for endometrial cancer?

To evaluate the clinical benefit of routine follow up of women after treatment for endometrial adenocarcinoma. Retrospective case analysis. All cases diagnosed and treated for endometrial adenocarcinoma in Tayside, Scotland during 1982 to 1984 inclusive. Case-note and cancer registration document review. Of 102 patients, 97 had complete follow up for 10 years or until death. Recurrent disease was diagnosed in 17 women, only six of whom were asymptomatic at the time of diagnosis. There was no difference in survival between cases with symptomatic and asymptomatic recurrences. No recurrences were diagnosed more than six years after initial diagnosis. The diagnosis of asymptomatic recurrent endometrial carcinoma was not associated with improved long term survival. This small study showed no evidence of improved survival from the current practice of routine clinical review following treatment for endometrial adenocarcinoma. The effect of follow up on patient anxiety remains to be assessed.

Hormonoprophylaxis and hormonotherapy in the treatment of endometrial adenocarcinoma by means of medroxyprogesterone acetate

Oral administration of 1 g of medroxyprogesterone per week inhibits the hypothalamohypophyseal axis but especially exerts a direct and local action on hormone-dependent endometrial adenocarcinoma. The possibility of substituting for a radioprotective purpose a medroxyprogesterone-releasing intrauterine Silastic device for the conventional radium packing as a preoperative procedure is evaluated. Adjuvant medroxyprogesterone therapy in Stage I endometrial adenocarcinoma reduces recurrence rates and yields higher 5-year survival rates. Prognostic factors are established for medroxyprogesterone therapy achieving significant remission in 53% of advanced and recurrent endometrial adenocarcinoma.

Purification of human uterine progesterone receptor

IT is now generally accepted that before the physiological response to the androgens1, oestrogens2, glucocorticoids3 and progesterone4–7 can be manifested, these hormones must complex with specific receptors in their target tissue. Since progesterone is important both in the mechanisms associated with transport of the ovum through the oviduct8,9 and in preparing the endometrium for implantation of the blastocyst10, a greater understanding of the action of the hormone–receptor complex at the molecular level will lead to a more detailed knowledge of the mechanisms involved in reproductive biology. This understanding may be utilised to develop new contraceptive methods and to investigate the genesis and treatment of endometrial adenocarcinoma.

ENDOMETRIAL CANCER. SURVEY OF 610 CASES AT WOMAN'S HOSPITAL (1919-1960).

CancerVolume 16, Issue 8 p. 1057-1064 ArticleFree Access Endometrial cancer. Survey of 610 cases treated at Woman's hospital (1919–1960) Carl T. Javert M.D., Carl T. Javert M.D. Departments of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, and the Woman's Hospital division of St. Luke's Hospital, 141 W. 109th St., New York 25, N.Y.Search for more papers by this authorElise L. Renning M.D., Elise L. Renning M.D. Departments of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, and the Woman's Hospital division of St. Luke's Hospital, 141 W. 109th St., New York 25, N.Y.Search for more papers by this author Carl T. Javert M.D., Carl T. Javert M.D. Departments of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, and the Woman's Hospital division of St. Luke's Hospital, 141 W. 109th St., New York 25, N.Y.Search for more papers by this authorElise L. Renning M.D., Elise L. Renning M.D. Departments of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, and the Woman's Hospital division of St. Luke's Hospital, 141 W. 109th St., New York 25, N.Y.Search for more papers by this author First published: August 1963 https://doi.org/10.1002/1097-0142(196308)16:8<1057::AID-CNCR2820160813>3.0.CO;2-MCitations: 24AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Ewing, J.: Neoplastic Diseases, 3d ed. Philadelphia, Pa. W. B. Saunders Company. 1928; p. 594. 2 Healy, W. P.: Carcinoma of body of uterus. In A. H. Curtis; Ed.: Obstetrics and Gynecology, vol. 2. Philadelphia, Pa. W. B. Saunders Company. 1933; pp. 922– 937. 3 Heymax, J.: Some problems of current interest relating to classification and treatment of uterine carcinoma. Am. J. Obst. & Gynec. 69: 502– 509, 1955. 4 Javert, C. T.: Prognosis of endometrial cancer. Obst. & Gynec. 12: 556– 571, 1958. 5 Javert, C. T.; and Douglas, R. G.: Treatment of endometrial adenocarcinoma; study of 381 cases at New York Hospital; preliminary report. Am. J. Roentgenol. 75: 508– 514, 1956. 6 Javert, C. T.; and Hofammann, K.: Observations on surgical pathology, selective lymphadenectomy, and classification of endometrial adenocarcinoma. Cancer 5: 485– 498, 1952. 7 McLennan, C. A.: Argument against preopcrative radium for endometrial cancer. Tr. Pacific Coast Obst. & Gynec. Soc. 25: 122– 131, 1957. 8 Metropolitan Life Insurance Company: Personal communication. 9 Nathanson, B. N.; and Ammann, M.: Carcinoma of corpus at Woman's Hospital; follow-up study. Bull. Woman's Hosp. 1: 32– 39, 1958. 10 Pack, W. G.; and Barnes, L.: Endometrial adenocarcinoma 11 years after pelvic radiation for cervical epidermoid carcinoma. Am. J. Obst. & Gynec. 75: 175– 179, 1958. 11 Rutledge, F. N.; Tan, S. K.; and Fletcher, G. H.: Vaginal metastases from adenocarcinoma of corpus uteri. Am. J. Obst. & Gynec. 75: 167– 174, 1958. 12 Sackett, N. B.: Cancer of uterus. Virginia M. Monthly 64: 129– 134, 1937. 13 Sackett, N. B.: Surgical treatment of cancer of corpus uteri. In G. T. Pack; and E. M. Livingston; Eds.: Treatment of Cancer and Allied Diseases, vol. 2, New York, N.Y. Paul B. Hoeber, Inc. 1940; pp. 1648– 1666. 14 Thiede, H.; and Lund, C. L.: Prognostic factors in endometrial adenocarcinoma. Obst. & Gynec. 20: 149– 155, 1962. 15 Ward, G. G.: Radium therapy of carcinoma uteri; 10 years of clinical experience and results at Woman's Hospital. Am. J. Obst. & Gynec. 17: 1– 13, 1929. 16 Ward, G. G.: Present status of treatment of carcinoma of uterus; Citizen's Aid Society memorial cancer lecture. Minnesota Med. 14: 943– 952, 1931. 17 Ward, G. G.: Present status of radium therapy in cancer of uterus. [Edit]. Surg. Gynec. & Obst. 57: 546– 547, 1933. 18 Ward, G. G.: Evaluation of radiotherapy for carcinoma of uterus after 15 years' experience at Woman's Hospital. South. M. J. 29: 282– 289, 1936. 19 Ward, G. G.; and Sackett, N. B.: Results of radiation therapy for carcinoma of uterus at Woman's Hospital, New York, 1919–1932. J. A. M. A. 110: 323– 327, 1938. Citing Literature Volume16, Issue8August 1963Pages 1057-1064 ReferencesRelatedInformation