ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up

Nicoletta Colombo, Carien Creutzberg, Frederic Amant, Tjalling Bosse, Antonio González-Martín, Jonathan Ledermann, Christian Marth, Remi Nout, Denis Querleu, Mansoor Raza Mirza, Cristiana Sessa, ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group, Nicoletta Colombo, Carien Creutzberg, Frederic Amant, Tjalling Bosse, Antonio González-Martín, Jonathan Ledermann, Christian Marth, Remi Nout, Denis Querleu, Mansoor Raza Mirza, Cristiana Sessa, ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group

Abstract

The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article.

References

    1. WHO. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. 2012; (3 April 2015, date last accessed).
    1. Lee NK, Cheung MK, Shin JY, et al. Prognostic factors for uterine cancer in reproductive-aged women. Obstet Gynecol. 2007; 109: 655– 662.
    1. National Cancer Institute. Endometrial cancer treatment Physician Data Query (PDQ). 2015; (1 April 2015, date last accessed).
    1. ACOG. ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol. 2005; 106: 413– 425.
    1. Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013; 497: 67– 73.
    1. Reid-Nicholson M, Iyengar P, Hummer AJ, et al. Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis. Mod Pathol. 2006; 19: 1091– 1100.
    1. Broaddus RR, Lynch HT, Chen LM, et al. Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer. 2006; 106: 87– 94.
    1. Colombo N, Preti E, Landoni F, et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 (suppl 6): vi33– vi38.
    1. Dykewicz CA. Summary of the Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis. 2001; 33: 139– 144.
    1. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Report. Food, Nutrition, Physical Activity, and the Prevention of Endometrial Cancer. 2013; (2 April 2015, date last accessed).
    1. Garg K, Soslow RA. Endometrial carcinoma in women aged 40 years and younger. Arch Pathol Lab Med. 2014; 138: 335– 342.
    1. Esposito K, Chiodini P, Capuano A, et al. Metabolic syndrome and endometrial cancer: a meta-analysis. Endocrine. 2014; 45: 28– 36.
    1. Zhang Y, Liu H, Yang S, et al. Overweight, obesity and endometrial cancer risk: results from a systematic review and meta-analysis. Int J Biol Markers. 2014; 29: e21– e29.
    1. Rosato V, Zucchetto A, Bosetti C, et al. Metabolic syndrome and endometrial cancer risk. Ann Oncol. 2011; 22: 884– 889.
    1. Luo J, Beresford S, Chen C, et al. Association between diabetes, diabetes treatment and risk of developing endometrial cancer. Br J Cancer. 2014; 111: 1432– 1439.
    1. Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2014; 20: 748– 758.
    1. Fader AN, Arriba LN, Frasure HE, von Gruenigen VE. Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship. Gynecol Oncol. 2009; 114: 121– 127.
    1. Ali AT. Reproductive factors and the risk of endometrial cancer. Int J Gynecol Cancer. 2014; 24: 384– 393.
    1. Peiretti M, Colombo N. Sex cord-stromal tumors of the ovary. In: Textbook of Gynaecological Oncology, Ankara and Istanbul: Günes Publishing, 2012: 453– 456.
    1. Brinton LA, Berman ML, Mortel R, et al. Reproductive, menstrual, and medical risk factors for endometrial cancer: results from a case-control study. Am J Obstet Gynecol. 1992; 167: 1317– 1325.
    1. Zucchetto A, Serraino D, Polesel J, et al. Hormone-related factors and gynecological conditions in relation to endometrial cancer risk. Eur J Cancer Prev. 2009; 18: 316– 321.
    1. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998; 90: 1371– 1388.
    1. Lancaster JM, Powell CB, Chen LM, Richardson DL. Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2015; 136: 3– 7.
    1. Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2009: a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin. 2009; 59: 27– 41.
    1. Jacobs I, Gentry-Maharaj A, Burnell M, et al. Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort. Lancet Oncol. 2011; 12: 38– 48.
    1. National Cancer Institute. Endometrial Cancer Screening Physician Data Query (PDQ). 2015; (2 April 2015, date last accessed).
    1. ACOG. Committee Opinion No. 601: Tamoxifen and uterine cancer. Obstet Gynecol. 2014; 123: 1394– 1397.
    1. Fu Y, Zhuang Z. Long-term effects of levonorgestrel-releasing intrauterine system on tamoxifen-treated breast cancer patients: a meta-analysis. Int J Clin Exp Pathol. 2014; 7: 6419– 6429.
    1. Manchanda R, Saridogan E, Abdelraheim A, et al. Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS). Arch Gynecol Obstet. 2012; 286: 1555– 1562.
    1. Vasen HF, Blanco I, Aktan-Collan K, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013; 62: 812– 823.
    1. Duska LR, Garrett A, Rueda BR, et al. Endometrial cancer in women 40 years old or younger. Gynecol Oncol. 2001; 83: 388– 393.
    1. Evans-Metcalf ER, Brooks SE, Reale FR, Baker SP. Profile of women 45 years of age and younger with endometrial cancer. Obstet Gynecol. 1998; 91: 349– 354.
    1. Rodolakis A, Biliatis I, Morice P, et al. European Society of Gynecological Oncology Task Force for Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients. Int J Gynecol Cancer. 2015; 25: 1258– 1265.
    1. Leitao MM, Jr, Kehoe S, Barakat RR, et al. Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol. 2009; 113: 105– 108.
    1. Ushijima K, Yahata H, Yoshikawa H, et al. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. 2007; 25: 2798– 2803.
    1. Kinkel K, Kaji Y, Yu KK, et al. Radiologic staging in patients with endometrial cancer: a meta-analysis. Radiology. 1999; 212: 711– 718.
    1. Minig L, Franchi D, Boveri S, et al. Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women. Ann Oncol. 2011; 22: 643– 649.
    1. Kim MK, Seong SJ, Song T, et al. Comparison of dilatation & curettage and endometrial aspiration biopsy accuracy in patients treated with high-dose oral progestin plus levonorgestrel intrauterine system for early-stage endometrial cancer. Gynecol Oncol. 2013; 130: 470– 473.
    1. Gallos ID, Yap J, Rajkhowa M, et al. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2012; 207:266 e1– e12.
    1. Park JY, Kim DY, Kim JH, et al. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013; 49: 868– 874.
    1. Tangjitgamol S, Manusirivithaya S, Hanprasertpong J. Fertility-sparing in endometrial cancer. Gynecol Obstet Invest. 2009; 67: 250– 268.
    1. Erkanli S, Ayhan A. Fertility-sparing therapy in young women with endometrial cancer: 2010 update. Int J Gynecol Cancer. 2010; 20: 1170– 1187.
    1. Yamazawa K, Hirai M, Fujito A, et al. Fertility-preserving treatment with progestin, and pathological criteria to predict responses, in young women with endometrial cancer. Hum Reprod. 2007; 22: 1953– 1958.
    1. Koskas M, Uzan J, Luton D, et al. Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma: systematic review and meta-analysis. Fertil Steril. 2014; 101: 785– 794.
    1. Mittal K, Soslow R, McCluggage WG. Application of immunohistochemistry to gynecologic pathology. Arch Pathol Lab Med. 2008; 132: 402– 423.
    1. Sun H, Enomoto T, Fujita M, et al. Mutational analysis of the PTEN gene in endometrial carcinoma and hyperplasia. Am J Clin Pathol. 2001; 115: 32– 38.
    1. Orbo A, Nilsen MN, Arnes MS, et al. Loss of expression of MLH1, MSH2, MSH6, and PTEN related to endometrial cancer in 68 patients with endometrial hyperplasia. Int J Gynecol Pathol. 2003; 22: 141– 148.
    1. Hecht JL, Pinkus JL, Pinkus GS. Enhanced detection of atypical hyperplasia in endometrial polyps by PTEN expression. Appl Immunohistochem Mol Morphol. 2004; 12: 36– 39.
    1. Monte NM, Webster KA, Neuberg D, et al. Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer. Cancer Res. 2010; 70: 6225– 6232.
    1. Allison KH, Upson K, Reed SD, et al. PAX2 loss by immunohistochemistry occurs early and often in endometrial hyperplasia. Int J Gynecol Pathol. 2012; 31: 151– 159.
    1. Quick CM, Laury AR, Monte NM, Mutter GL. Utility of PAX2 as a marker for diagnosis of endometrial intraepithelial neoplasia. Am J Clin Pathol. 2012; 138: 678– 684.
    1. Tashiro H, Isacson C, Levine R, et al. p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. Am J Pathol. 1997; 150: 177– 185.
    1. Zheng W, Khurana R, Farahmand S, et al. p53 immunostaining as a significant adjunct diagnostic method for uterine surface carcinoma: precursor of uterine papillary serous carcinoma. Am J Surg Pathol. 1998; 22: 1463– 1473.
    1. Jia L, Liu Y, Yi X, et al. Endometrial glandular dysplasia with frequent p53 gene mutation: a genetic evidence supporting its precancer nature for endometrial serous carcinoma. Clin Cancer Res. 2008; 14: 2263– 2269.
    1. Lax SF, Kendall B, Tashiro H, et al. The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer. 2000; 88: 814– 824.
    1. Castrillon DH, Lee KR, Nucci MR. Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study. Int J Gynecol Pathol. 2002; 21: 4– 10.
    1. Saad RS, Mashhour M, Noftech-Mozes S, et al. P16INK4a expression in undifferentiated carcinoma of the uterus does not exclude its endometrial origin. Int J Gynecol Pathol. 2012; 31: 57– 65.
    1. Netzer IM, Kerner H, Litwin L, et al. Diagnostic implications of p16 expression in serous papillary endometrial cancer. Int J Gynecol Cancer. 2011; 21: 1441– 1445.
    1. Bagby C, Ronnett BM, Yemelyanova A, et al. Clinically occult tubal and ovarian high-grade serous carcinomas presenting in uterine samples: diagnostic pitfalls and clues to improve recognition of tumor origin. Int J Gynecol Pathol. 2013; 32: 433– 443.
    1. Hashi A, Yuminamochi T, Murata S, et al. Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium, and peritoneum. Int J Gynecol Pathol. 2003; 22: 374– 377.
    1. Köbel M, Kalloger SE, Carrick J, et al. A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary. Am J Surg Pathol. 2009; 33: 14– 21.
    1. Al-Hussaini M, Stockman A, Foster H, McCluggage WG. WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma. Histopathology. 2004; 44: 109– 115.
    1. Egan JA, Ionescu MC, Eapen E, et al. Differential expression of WT1 and p53 in serous and endometrioid carcinomas of the endometrium. Int J Gynecol Pathol. 2004; 23: 119– 122.
    1. Eriksson LS, Lindqvist PG, Flöter Rådestad A, et al. Transvaginal ultrasound assessment of myometrial and cervical stromal invasion in women with endometrial cancer: interobserver reproducibility among ultrasound experts and gynecologists. Ultrasound Obstet Gynecol. 2015; 45: 476– 482.
    1. Epstein E, Blomqvist L. Imaging in endometrial cancer. Best Pract Res Clin Obstet Gynaecol. 2014; 28: 721– 739.
    1. Scholten AN, Smit VT, Beerman H, et al. Prognostic significance and interobserver variability of histologic grading systems for endometrial carcinoma. Cancer. 2004; 100: 764– 772.
    1. Helpman L, Kupets R, Covens A, et al. Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer. Br J Cancer. 2014; 110: 609– 615.
    1. Stephan JM, Hansen J, Samuelson M, et al. Intra-operative frozen section results reliably predict final pathology in endometrial cancer. Gynecol Oncol. 2014; 133: 499– 505.
    1. Antonsen SL, Høgdall E, Christensen IJ, et al. HE4 and CA125 levels in the preoperative assessment of endometrial cancer patients: a prospective multicenter study (ENDOMET). Acta Obstet Gynecol Scand. 2013; 92: 1313– 1322.
    1. Yildiz A, Yetimalar H, Kasap B, et al. Preoperative serum CA 125 level in the prediction of the stage of disease in endometrial carcinoma. Eur J Obstet Gynecol Reprod Biol. 2012; 164: 191– 195.
    1. Mutz-Dehbalaie I, Egle D, Fessler S, et al. HE4 is an independent prognostic marker in endometrial cancer patients. Gynecol Oncol. 2012; 126: 186– 191.
    1. Sun C, Chen G, Yang Z, et al. Safety of ovarian preservation in young patients with early-stage endometrial cancer: a retrospective study and meta-analysis. Fertil Steril. 2013; 100: 782– 787.
    1. Walker JL, Piedmonte MR, Spirtos NM, et al. Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2. J Clin Oncol. 2009; 27: 5331– 5336.
    1. Mourits MJ, Bijen CB, Arts HJ, et al. Safety of laparoscopy versus laparotomy in early-stage endometrial cancer: a randomised trial. Lancet Oncol. 2010; 11: 763– 771.
    1. Zullo F, Falbo A, Palomba S. Safety of laparoscopy vs laparotomy in the surgical staging of endometrial cancer: a systematic review and metaanalysis of randomized controlled trials. Am J Obstet Gynecol. 2012; 207: 94– 100.
    1. Pakish J, Soliman PT, Frumovitz M, et al. A comparison of extraperitoneal versus transperitoneal laparoscopic or robotic para-aortic lymphadenectomy for staging of endometrial carcinoma. Gynecol Oncol. 2014; 132: 366– 371.
    1. Tozzi R, Malur S, Koehler C, Schneider A. Analysis of morbidity in patients with endometrial cancer: is there a commitment to offer laparoscopy? Gynecol Oncol. 2005; 97: 4– 9.
    1. Siesto G, Uccella S, Ghezzi F, et al. Surgical and survival outcomes in older women with endometrial cancer treated by laparoscopy. Menopause. 2010; 17: 539– 544.
    1. Palomba S, Falbo A, Mocciaro R, et al. Laparoscopic treatment for endometrial cancer: a meta-analysis of randomized controlled trials (RCTs). Gynecol Oncol. 2009; 112: 415– 421.
    1. Palomba S, Falbo A, Russo T, Zullo F. Updating of a recent meta-analysis of randomized controlled trials to assess the safety and the efficacy of the laparoscopic surgery for treating early stage endometrial cancer. Gynecol Oncol. 2009; 114: 135– 136.
    1. Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012; 30: 695– 700.
    1. Fader AN, Seamon LG, Escobar PF, et al. Minimally invasive surgery versus laparotomy in women with high grade endometrial cancer: a multi-site study performed at high volume cancer centers. Gynecol Oncol. 2012; 126: 180– 185.
    1. Han KH, Park NH, Kim HS, et al. Peritoneal cytology: a risk factor of recurrence for non-endometrioid endometrial cancer. Gynecol Oncol. 2014; 134: 293– 296.
    1. Garg G, Gao F, Wright JD, et al. Positive peritoneal cytology is an independent risk-factor in early stage endometrial cancer. Gynecol Oncol. 2013; 128: 77– 82.
    1. Lutman CV, Havrilesky LJ, Cragun JM, et al. Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology. Gynecol Oncol. 2006; 102: 92– 97.
    1. Abu-Rustum NR, Iasonos A, Zhou Q, et al. Is there a therapeutic impact to regional lymphadenectomy in the surgical treatment of endometrial carcinoma? Am J Obstet Gynecol. 2008; 198: 457.e1– e5; discussion 457.e5–e6.
    1. Cragun JM, Havrilesky LJ, Calingaert B, et al. Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer. J Clin Oncol. 2005; 23: 3668– 3675.
    1. Kilgore LC, Partridge EE, Alvarez RD, et al. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol. 1995; 56: 29– 33.
    1. Creasman WT, Morrow CP, Bundy BN, et al. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987; 60 (suppl 8): 2035– 2041.
    1. Abu-Rustum NR, Gomez JD, Alektiar KM, et al. The incidence of isolated paraaortic nodal metastasis in surgically staged endometrial cancer patients with negative pelvic lymph nodes. Gynecol Oncol. 2009; 115: 236– 238.
    1. Dowdy SC, Aletti G, Cliby WA, et al. Extra-peritoneal laparoscopic para-aortic lymphadenectomy–a prospective cohort study of 293 patients with endometrial cancer. Gynecol Oncol. 2008; 111: 418– 424.
    1. Mariani A, Dowdy SC, Cliby WA, et al. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol. 2008; 109: 11– 18.
    1. Ballester M, Dubernard G, Lécuru F, et al. Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO). Lancet Oncol. 2011; 12: 469– 476.
    1. Abu-Rustum NR. Sentinel lymph node mapping for endometrial cancer: a modern approach to surgical staging. J Natl Compr Canc Netw. 2014; 12: 288– 297.
    1. Benedetti Panici P, Basile S, Maneschi F, et al. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst. 2008; 100: 1707– 1716.
    1. Kitchener H, Swart AM, Qian Q, et al. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet. 2009; 373: 125– 136.
    1. Naumann RW. The role of lymphadenectomy in endometrial cancer: was the ASTEC trial doomed by design and are we destined to repeat that mistake? Gynecol Oncol. 2012; 126: 5– 11.
    1. Smith DC, Macdonald OK, Lee CM, Gaffney DK. Survival impact of lymph node dissection in endometrial adenocarcinoma: a surveillance, epidemiology, and end results analysis. Int J Gynecol Cancer. 2008; 18: 255– 261.
    1. Trimble EL, Kosary C, Park RC. Lymph node sampling and survival in endometrial cancer. Gynecol Oncol. 1998; 71: 340– 343.
    1. Todo Y, Kato H, Kaneuchi M, et al. Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis. Lancet. 2010; 375: 1165– 1172.
    1. Chan JK, Cheung MK, Huh WK, et al. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer. 2006; 107: 1823– 1830.
    1. Kim HS, Suh DH, Kim MK, et al. Systematic lymphadenectomy for survival in patients with endometrial cancer: a meta-analysis. Jpn J Clin Oncol. 2012; 42: 405– 412.
    1. Vargas R, Rauh-Hain JA, Clemmer J, et al. Tumor size, depth of invasion, and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: a SEER analysis. Gynecol Oncol. 2014; 133: 216– 220.
    1. Takano M, Ochi H, Takei Y, et al. Surgery for endometrial cancers with suspected cervical involvement: is radical hysterectomy needed (a GOTIC study)? Br J Cancer. 2013; 109: 1760– 1765.
    1. Watanabe Y, Satou T, Nakai H, et al. Evaluation of parametrial spread in endometrial carcinoma. Obstet Gynecol. 2010; 116: 1027– 1034.
    1. Querleu D, Morrow CP. Classification of radical hysterectomy. Lancet Oncol. 2008; 9: 297– 303.
    1. Shih KK, Yun E, Gardner GJ, et al. Surgical cytoreduction in stage IV endometrioid endometrial carcinoma. Gynecol Oncol. 2011; 122: 608– 611.
    1. Vandenput I, Trovik J, Vergote I, et al. The role of adjuvant chemotherapy in surgical stages I-II serous and clear cell carcinomas and carcinosarcoma of the endometrium: a collaborative study. Int J Gynecol Cancer. 2011; 21: 332– 336.
    1. Gokce ZK, Turan T, Karalok A, et al. Clinical outcomes of uterine carcinosarcoma: results of 94 patients. Int J Gynecol Cancer. 2015; 25: 279– 287.
    1. Amant F, Moerman P, Neven P, et al. Endometrial cancer. Lancet. 2005; 366: 491– 505.
    1. Briët JM, Hollema H, Reesink N, et al. Lymphvascular space involvement: an independent prognostic factor in endometrial cancer. Gynecol Oncol. 2005; 96: 799– 804.
    1. Cohn DE, Horowitz NS, Mutch DG, et al. Should the presence of lymphvascular space involvement be used to assign patients to adjuvant therapy following hysterectomy for unstaged endometrial cancer? Gynecol Oncol. 2002; 87: 243– 246.
    1. Gadducci A, Cavazzana A, Cosio S, et al. Lymph-vascular space involvement and outer one-third myometrial invasion are strong predictors of distant haematogeneous failures in patients with stage I-II endometrioid-type endometrial cancer. Anticancer Res. 2009; 29: 1715– 1720.
    1. Gemer O, Arie AB, Levy T, et al. Lymphvascular space involvement compromises the survival of patients with stage I endometrial cancer: results of a multicenter study. Eur J Surg Oncol. 2007; 33: 644– 647.
    1. Guntupalli SR, Zighelboim I, Kizer NT, et al. Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer. Gynecol Oncol. 2012; 124: 31– 35.
    1. Blake P, Swart AM, Orton J, et al. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet. 2009; 373: 137– 146.
    1. Creutzberg CL, van Putten WL, Koper PC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. 2000; 355: 1404– 1411.
    1. Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004; 92: 744– 751.
    1. Kong A, Johnson N, Kitchener HC, Lawrie TA. Adjuvant radiotherapy for stage I endometrial cancer: an updated Cochrane systematic review and meta-analysis. J Natl Cancer Inst. 2012; 104: 1625– 1634.
    1. Soong R, Knowles S, Williams KE, et al. Overexpression of p53 protein is an independent prognostic indicator in human endometrial carcinoma. Br J Cancer. 1996; 74: 562– 567.
    1. Salvesen HB, Iversen OE, Akslen LA. Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study. J Clin Oncol. 1999; 17: 1382– 1390.
    1. AlHilli MM, Mariani A, Bakkum-Gamez JN, et al. Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer. Gynecol Oncol. 2014; 133: 485– 493.
    1. Zeimet AG, Reimer D, Huszar M, et al. L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation. J Natl Cancer Inst. 2013; 105: 1142– 1150.
    1. Bosse T, Nout RA, Stelloo E, et al. L1 cell adhesion molecule is a strong predictor for distant recurrence and overall survival in early stage endometrial cancer: pooled PORTEC trial results. Eur J Cancer. 2014; 50: 2602– 2610.
    1. Sorbe B, Nordström B, Mäenpää J, et al. Intravaginal brachytherapy in FIGO stage I low-risk endometrial cancer: a controlled randomized study. Int J Gynecol Cancer. 2009; 19: 873– 878.
    1. Nout RA, Smit VT, Putter H, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet. 2010; 375: 816– 823.
    1. Sorbe B, Horvath G, Andersson H, et al. External pelvic and vaginal irradiation versus vaginal irradiation alone as postoperative therapy in medium-risk endometrial carcinoma–a prospective randomized study. Int J Radiat Oncol Biol Phys. 2012; 82: 1249– 1255.
    1. Bosse T, Peters EE, Creutzberg CL, et al. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer - A pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer. 2015; 51: 1742– 1750.
    1. Bendifallah S, Canlorbe G, Raimond E, et al. A clue towards improving the European Society of Medical Oncology risk group classification in apparent early stage endometrial cancer? Impact of lymphovascular space invasion. Br J Cancer. 2014; 110: 2640– 2646.
    1. Creutzberg CL, van Putten WL, Koper PC, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003; 89: 201– 209.
    1. McMeekin DS, Filiaci VL, Aghajanian C, et al. A randomized phase III trial of pelvic radiation therapy (PXRT) versus vaginal cuff brachytherapy followed by paclitaxel/carboplatin chemotherapy (VCB/C) in patients with high risk (HR), early stage endometrial cancer (EC): A Gynecologic Oncology Group trial. Gynecol Oncol. 2014; 134:438 (abstract LBA 431).
    1. Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006; 95 (suppl 1): S105– S143.
    1. Greven KM, Randall M, Fanning J, et al. Patterns of failure in patients with stage I, grade 3 carcinoma of the endometrium. Int J Radiat Oncol Biol Phys. 1990; 19: 529– 534.
    1. Straughn JM, Huh WK, Orr JW, Jr, et al. Stage IC adenocarcinoma of the endometrium: survival comparisons of surgically staged patients with and without adjuvant radiation therapy. Gynecol Oncol. 2003; 89: 295– 300.
    1. Creutzberg CL, van Putten WL, Wárlám-Rodenhuis CC, et al. Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol. 2004; 22: 1234– 1241.
    1. Sagae S, Susumu N, Viswanathan AN, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for uterine serous carcinoma. Int J Gynecol Cancer. 2014; 24 (9 suppl 3): S83– S89.
    1. Morrow CP, Bundy BN, Homesley HD, et al. Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: a Gynecologic Oncology Group Study. Gynecol Oncol. 1990; 36: 166– 171.
    1. Susumu N, Sagae S, Udagawa Y, et al. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008; 108: 226– 233.
    1. Maggi R, Lissoni A, Spina F, et al. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial. Br J Cancer. 2006; 95: 266– 271.
    1. Hogberg T, Signorelli M, de Oliveira CF, et al. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer–results from two randomised studies. Eur J Cancer. 2010; 46: 2422– 2431.
    1. Greven K, Winter K, Underhill K, et al. Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer. Gynecol Oncol. 2006; 103: 155– 159.
    1. Cooke EW, Pappas L, Gaffney DK. Does the revised International Federation of Gynecology and Obstetrics staging system for endometrial cancer lead to increased discrimination in patient outcomes? Cancer. 2011; 117: 4231– 4237.
    1. Page BR, Pappas L, Cooke EW, Gaffney DK. Does the FIGO 2009 endometrial cancer staging system more accurately correlate with clinical outcome in different histologies? Revised staging, endometrial cancer, histology. Int J Gynecol Cancer. 2012; 22: 593– 598.
    1. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009; 105: 103– 104.
    1. Morrow CP, Bundy BN, Kurman RJ, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. 1991; 40: 55– 65.
    1. Wright JD, Fiorelli J, Kansler AL, et al. Optimizing the management of stage II endometrial cancer: the role of radical hysterectomy and radiation. Am J Obstet Gynecol. 2009; 200:419 e1– e7.
    1. Klopp A, Smith BD, Alektiar K, et al. The role of postoperative radiation therapy for endometrial cancer: Executive summary of an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2014; 4: 137– 144.
    1. Rossi PJ, Jani AB, Horowitz IR, Johnstone PA. Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis. Int J Radiat Oncol Biol Phys. 2008; 70: 134– 138.
    1. Randall ME, Wilder J, Greven K, Raben M. Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma. Int J Radiat Oncol Biol Phys. 1990; 19: 49– 54.
    1. Greven K, Winter K, Underhill K, et al. Preliminary analysis of RTOG 9708: Adjuvant postoperative radiotherapy combined with cisplatin/paclitaxel chemotherapy after surgery for patients with high-risk endometrial cancer. Int J Radiat Oncol Biol Phys. 2004; 59: 168– 173.
    1. Scotti V, Borghesi S, Meattini I, et al. Postoperative radiotherapy in stage I/II endometrial cancer: retrospective analysis of 883 patients treated at the University of Florence. Int J Gynecol Cancer. 2010; 20: 1540– 1548.
    1. Jobsen JJ, Lybeert ML, van der Steen-Banasik EM, et al. Multicenter cohort study on treatment results and risk factors in stage II endometrial carcinoma. Int J Gynecol Cancer. 2008; 18: 1071– 1078.
    1. Crosby MA, Tward JD, Szabo A, et al. Does brachytherapy improve survival in addition to external beam radiation therapy in patients with high risk stage I and II endometrial carcinoma? Am J Clin Oncol. 2010; 33: 364– 369.
    1. Secord AA, Geller MA, Broadwater G, et al. A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer. Gynecol Oncol. 2013; 128: 65– 70.
    1. Klopp AH, Jhingran A, Ramondetta L, et al. Node-positive adenocarcinoma of the endometrium: outcome and patterns of recurrence with and without external beam irradiation. Gynecol Oncol. 2009; 115: 6– 11.
    1. Randall ME, Filiaci VL, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2006; 24: 36– 44.
    1. Lee LJ, Viswanathan AN. Combined chemotherapy and radiation improves survival for node-positive endometrial cancer. Gynecol Oncol. 2012; 127: 32– 37.
    1. Mundt AJ, McBride R, Rotmensch J, et al. Significant pelvic recurrence in high-risk pathologic stage I–IV endometrial carcinoma patients after adjuvant chemotherapy alone: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys. 2001; 50: 1145– 1153.
    1. Viswanathan AN, Macklin EA, Berkowitz R, Matulonis U. The importance of chemotherapy and radiation in uterine papillary serous carcinoma. Gynecol Oncol. 2011; 123: 542– 547.
    1. Hasegawa K, Nagao S, Yasuda M, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for clear cell carcinoma of the uterine corpus and cervix. Int J Gynecol Cancer. 2014; 24 (9 suppl 3): S90– S95.
    1. Barney BM, Petersen IA, Mariani A, et al. The role of vaginal brachytherapy in the treatment of surgical stage I papillary serous or clear cell endometrial cancer. Int J Radiat Oncol Biol Phys. 2013; 85: 109– 115.
    1. Berton-Rigaud D, Devouassoux-Shisheboran M, Ledermann JA, et al. Gynecologic Cancer InterGroup (GCIG) Consensus Review for Uterine and Ovarian Carcinosarcoma. Int J Gynecol Cancer. 2014; 24 (9 suppl 3): S55– S60.
    1. Amant F. The rationale for comprehensive surgical staging in endometrial carcinosarcoma. Gynecol Oncol. 2005; 99: 521– 522; author reply 522–523.
    1. Reed NS, Mangioni C, Malmstrom H, et al. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur J Cancer. 2008; 44: 808– 818.
    1. Wright JD, Seshan VE, Shah M, et al. The role of radiation in improving survival for early-stage carcinosarcoma and leiomyosarcoma. Am J Obstet Gynecol. 2008; 199: 536.e1– e8.
    1. Clayton Smith D, Kenneth Macdonald O, Gaffney DK. The impact of adjuvant radiation therapy on survival in women with uterine carcinosarcoma. Radiother Oncol. 2008; 88: 227– 232.
    1. Nemani D, Mitra N, Guo M, Lin L. Assessing the effects of lymphadenectomy and radiation therapy in patients with uterine carcinosarcoma: a SEER analysis. Gynecol Oncol. 2008; 111: 82– 88.
    1. Wolfson AH, Brady MF, Rocereto T, et al. A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007; 107: 177– 185.
    1. Barlin JN, Puri I, Bristow RE. Cytoreductive surgery for advanced or recurrent endometrial cancer: a meta-analysis. Gynecol Oncol. 2010; 118: 14– 18.
    1. Creasman WT, Kohler MF, Odicino F, et al. Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium. Gynecol Oncol. 2004; 95: 593– 596.
    1. Jhingran A, Burke TW, Eifel PJ. Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy. Int J Radiat Oncol Biol Phys. 2003; 56: 1366– 1372.
    1. Vargo JA, Kim H, Houser CJ, et al. Definitive salvage for vaginal recurrence of endometrial cancer: the impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification. Radiother Oncol. 2014; 113: 126– 131.
    1. Podzielinski I, Randall ME, Breheny PJ, et al. Primary radiation therapy for medically inoperable patients with clinical stage I and II endometrial carcinoma. Gynecol Oncol. 2012; 124: 36– 41.
    1. Fishman DA, Roberts KB, Chambers JT, et al. Radiation therapy as exclusive treatment for medically inoperable patients with stage I and II endometrioid carcinoma with endometrium. Gynecol Oncol. 1996; 61: 189– 196.
    1. Gill BS, Kim H, Houser C, et al. Image-based three-dimensional conformal brachytherapy for medically inoperable endometrial carcinoma. Brachytherapy. 2014; 13: 542– 547.
    1. Thigpen JT, Brady MF, Alvarez RD, et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999; 17: 1736– 1744.
    1. Decruze SB, Green JA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer. 2007; 17: 964– 978.
    1. Tangen IL, Werner HM, Berg A, et al. Loss of progesterone receptor links to high proliferation and increases from primary to metastatic endometrial cancer lesions. Eur J Cancer. 2014; 50: 3003– 3010.
    1. Lentz SS, Brady MF, Major FJ, et al. High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 1996; 14: 357– 361.
    1. Thigpen T, Brady MF, Homesley HD, et al. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2001; 19: 364– 367.
    1. Ma BB, Oza A, Eisenhauer E, et al. The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers–a study of the National Cancer Institute of Canada Clinical Trials Group. Int J Gynecol Cancer. 2004; 14: 650– 658.
    1. Rose PG, Brunetto VL, VanLe L, et al. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000; 78: 212– 216.
    1. Whitney CW, Brunetto VL, Zaino RJ, et al. Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004; 92: 4– 9.
    1. Fiorica JV, Brunetto VL, Hanjani P, et al. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004; 92: 10– 14.
    1. van Wijk FH, Aapro MS, Bolis G, et al. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol. 2003; 14: 441– 448.
    1. Thigpen JT, Brady MF, Homesley HD, et al. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol. 2004; 22: 3902– 3908.
    1. Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2004; 22: 2159– 2166.
    1. Miller D, Filiaci V, Fleming G, et al. Late-Breaking Abstract 1: Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2012; 125: 771.
    1. Makker V, Hensley ML, Zhou Q, et al. Treatment of advanced or recurrent endometrial carcinoma with doxorubicin in patients progressing after paclitaxel/carboplatin: Memorial Sloan-Kettering Cancer Center experience from 1995 to 2009. Int J Gynecol Cancer. 2013; 23: 929– 934.
    1. Grisham RN, Adaniel C, Hyman DM, et al. Gemcitabine for advanced endometrial cancer: a retrospective study of the Memorial Sloan-Kettering Cancer Center experience. Int J Gynecol Cancer. 2012; 22: 807– 811.
    1. Nagao S, Nishio S, Michimae H, et al. Applicability of the concept of “platinum sensitivity” to recurrent endometrial cancer: the SGSG-012/GOTIC-004/Intergroup study. Gynecol Oncol. 2013; 131: 567– 573.
    1. Moore KN, Tian C, McMeekin DS, et al. Does the progression-free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?: a Gynecologic Oncology Group ancillary data analysis. Cancer. 2010; 116: 5407– 5414.
    1. Matias-Guiu X, Prat J. Molecular pathology of endometrial carcinoma. Histopathology. 2013; 62: 111– 123.
    1. Salvesen HB, Carter SL, Mannelqvist M, et al. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc Natl Acad Sci U S A. 2009; 106: 4834– 4839.
    1. Myers AP. New strategies in endometrial cancer: targeting the PI3K/mTOR pathway–the devil is in the details. Clin Cancer Res. 2013; 19: 5264– 5274.
    1. Yeramian A, Moreno-Bueno G, Dolcet X, et al. Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene. 2013; 32: 403– 413.
    1. Dutt A, Salvesen HB, Chen TH, et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci U S A. 2008; 105: 8713– 8717.
    1. Kamat AA, Merritt WM, Coffey D, et al. Clinical and biological significance of vascular endothelial growth factor in endometrial cancer. Clin Cancer Res. 2007; 13: 7487– 7495.
    1. Salvesen HB, Haldorsen IS, Trovik J. Markers for individualised therapy in endometrial carcinoma. Lancet Oncol. 2012; 13: e353– e361.
    1. Dedes KJ, Wetterskog D, Ashworth A, et al. Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol. 2011; 8: 261– 271.
    1. Aghajanian C, Sill MW, Darcy KM, et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011; 29: 2259– 2265.
    1. Colombo N, McMeekin DS, Schwartz PE, et al. Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial. Br J Cancer. 2013; 108: 1021– 1026.
    1. Tsoref D, Welch S, Lau S, et al. Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer. Gynecol Oncol. 2014; 135: 184– 189.
    1. Aghajanian C, Filiaci VL, Dizon DS, et al. A randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus and ixabepilone/carboplatin/bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG86P. J Clin Oncol. 2015; 33 (suppl):abstract 5500.
    1. Lorusso D, Ferrandina G, Colombo N, et al. Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III–IV) or recurrent endometrial cancer: The MITO END-2 trial. J Clin Oncol. 2015; 33 (suppl):abstract 5502.
    1. Werner HM, Salvesen HB. Current status of molecular biomarkers in endometrial cancer. Curr Oncol Rep. 2014; 16: 403.
    1. Weigelt B, Banerjee S. Molecular targets and targeted therapeutics in endometrial cancer. Curr Opin Oncol. 2012; 24: 554– 563.
    1. Konecny GE, Finkler N, Garcia AA, et al. Phase 2 study of second-line dovitinib (TKI258) in patients with fibroblast growth factor receptor 2 (FGFR2)-mutated or -nonmutated advanced and/or metastatic endometrial cancer. Ann Oncol. 2014; 25 (suppl 4): LBA27.
    1. Mackay HJ, Eisenhauer EA, Kamel-Reid S, et al. Molecular determinants of outcome with mammalian target of rapamycin inhibition in endometrial cancer. Cancer. 2014; 120: 603– 610.
    1. Korn EL, Freidlin B, Abrams JS, Halabi S. Design issues in randomized phase II/III trials. J Clin Oncol. 2012; 30: 667– 671.
    1. Redig AJ, Jänne PA. Basket trials and the evolution of clinical trial design in an era of genomic medicine. J Clin Oncol. 2015; 33: 975– 977.

Source: PubMed

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