Gynecologic oncology research and practice最新文献

The Fifth Annual Advanced Course in Cytoreductive Surgery for Ovarian Cancer and Peritoneal Surface Malignancies was held at and sponsored by the Division of Gynecologic Oncology at the the University of California, Irvine on Friday and Saturday, October 9-10, 2015. The workshop was comprised of didactic modules, historical treatise, an impassioned tribute, a cadaver laboratory, and heated intraperitoneal chemotherapy demonstration. This was a not-for-profit workshop, and registration fees were used to support course faculty travel to U.C. Irvine and to pay for the cadavers. The original 56 available spots were filled within three weeks of the initial announcement, prompting procurement of two additional cadavers to satisfy registration overflow and accommodate the six U.C. Irvine fellows-in-training. While international participation in the Workshops continues to rise, we have also noted more U.S.-trained Gynecologic Oncologists among the registrants.

Background: Cervical cancer is the fourth most common cancer among women worldwide, many of who are still within their reproductive lifespan. Advances in screening and treatment have increased the 5-year survival for early stage disease to over 90 % in developed countries. The focus is now shifting to reducing morbidity and improving fertility outcomes for cervical cancer patients. Radical trachelectomy with lymph node assessment became the standard of care for selected women with lesions <2 cm who desire fertility preservation. However, several questions still remain regarding the degree of surgical radicality required for tumors <2 cm, and fertility-sparing options for women with early-stage disesase ≥2 cm, and those with more advanced disease. Here, we compile a narrative review of the evidence for oncologic and pregnancy outcomes following radical trachelectomy, non-radical fertility-sparing surgery, and the use of neoadjuvant chemotherapy prior to surgery for larger lesions. We also review the literature for assisted reproductive technologies in women with more advanced disease.

Findings: Available literature suggests that the crude recurrence and mortality rates after radical trachelectomy are <5 and <2 %, respectively (approx. 11 and 4 % for tumors ≥ 2 cm). Among 1238 patients who underwent fertility-sparing surgery for early cervical cancer there were 469 pregnancies with a 67 % live birth rate. Among 134 cases with lesions ≥ 2 cm, there were ten conceptions with a live birth rate of 70 %. Outcomes after non-radical surgery (simple trachelectomy or cervical conization) are similar, although only applicable among a highly selected patient population. For patients ineligible for fertility-preserving surgery or who require adjuvant radiation therapy, current options include ovarian transposition and cryopreservation of oocytes or embryos but other techniques are under investigation.

Conclusion: Today, many cervical cancer survivors have successful pregnancies. For those with early-stage disease, minimally invasive and fertility sparing techniques have resulted in improved obstetrical outcomes without compromising oncologic safety. Results from three ongoing trials on non-radical surgery for low-risk tumors <2 cm will further inform the need for radical surgery in such patients. For those in whom natural childbearing is unachievable, advances in assisted reproductive technologies provide reproductive options. Despite our advances, the effects of cervical cancer survivorship on quality of life are not fully elucidated.

Background: Although cancer in general affects an aged population, a significant number of women develop cancer at childbearing age. Long-term survival rates after gynecological cancer, especially in young patients are increasing and all quality-of-life aspects, including preservation of fertility have become of major relevance.

Outcomes: Surgical techniques aimed at sparing reproductive organs and preserving fertility have been developed for women presenting with gynecological cancer found at early stages. Indications for fertility-sparing surgery are in general restricted to women presenting with a well-differentiated low-grade tumor in its early stages or with low malignant potential. Up to now, use of fertility-sparing techniques in well-selected patients has not been shown to affect overall survival negatively and fertility outcomes reported have been favorable. Still larger amounts of data and longer follow-up periods are needed. Several current fertility-sparing cancer treatments may result in sub-fertility and in those cases assisted reproductive techniques are indicated. Overall quality of life has been satisfactory in cancer patients after fertility-sparing surgery.

Conclusions: Fertility-sparing surgery is a viable tool to enable gynecological cancer patients of young age to fulfill their family building without impairment of oncological outcome. Cancer patients of reproductive age should undergo fertility counseling to analyze this sensitive subject. Further studies are needed to investigate the role of fertility-sparing treatment and combined adjuvant therapy in higher-grade cancers.

Background: The management of patients with recurrent gynecological malignancy is complex, and often contentious. While historically, patients with metastases in the lungs, liver or brain have been treated with palliative intent, surgery is proving to have an increasing role in the management of such patients.

Methods: In this review article, the surgical management of lung, liver and brain metastases from gynecological cancers is examined. A search of the English language literature over the last 25 years was conducted using the Medline and PubMed databases.

Results: The results for management of metastases from the endometrium, ovary and cervix to the lung, brain and liver show that surprisingly good long-term survival results can be achieved for resection of metastases from all three organs. Patient selection is critical, and surgery is often used in conjunction with other treatment modalities.

Conclusions: From this review, it is apparent that surgery should play an increasing role in the management of patients with parenchymal metastases from gynecological cancers. The surgery should ideally be performed in high volume, tertiary centers where there is a committed multi-disciplinary team with the necessary infrastructure to achieve the best possible outcomes in terms of both survival and morbidity.

Background: Our objective was to determine if previously reported overall survival (OS) and progression-free survival (PFS) rates are maintained long term following multimodal therapy for advanced and recurrent endometrial cancer and to assess the lymphedema rates associated with this therapy.

Methods: Women with advanced-stage or recurrent endometrial cancer were recruited between 9/2004 and 6/2009 to our previously published Phase II trial. Patients received intravenous docetaxel (75 mg/m2) and carboplatin (AUC = 6) every 3 weeks for 3 cycles before and after radiation therapy. Patient outcomes were updated in July 2014. Data abstracted included presence of lymphedema, disease progression, and death. OS and PFS estimates at 5 years were calculated using Kaplan-Meier methods.

Results: Of the 41 patients enrolled, 10 (24 %) had stage IIIA and 21 (51 %) had stage IIIC disease; 32 (78 %) had endometrioid histology; and 35 (85 %) completed the protocol. With a median follow-up of 5 years, 15 of 41 patients have died. The Kaplan-Meier estimate and 95 % CI for OS at 5 years was 70 % (53-82 %). Excluding the two patients with recurrent disease at enrollment, 15 of 39 patients progressed or died during follow-up. The Kaplan-Meier estimate and 95 % CI for PFS at 5 years was 66 % (48-78 %). Fifteen patients (37 %) had medical record documentation of lymphedema following treatment.

Conclusions: After additional follow-up, OS and PFS estimates remain high and in-field recurrences low following "sandwich" therapy. The "sandwich" method remains efficacious for women with stage III-IV or recurrent endometrial cancer.

Background: Selumetinib is a potent, selective, orally available, and non-ATP competitive small molecule inhibitor of mitogen-activated protein kinase kinase 1/2 (MEK1/2) that has demonstrated single agent activity in a number of solid tumor including recurrent low-grade serous ovarian carcinoma (LGSOC). However, the long-term prognosis of patients who receive selumetinib, as well as the late toxicity of the agent, have not yet been described.

Case presentation: In this case report, we present a patient with recurrent LGSOC with KRAS mutation whose tumor has not progressed and who has maintained a good general condition without severe toxicities following treatment with selumetinib for more than 7 years. Next generation sequencing of her tumor revealed a G12V mutation in KRAS. MAPK signaling inhibition plays a role in the biology of LGSOC.

Conclusions: Although biomarkers have yet to definitively define patients with LGSOC who are likely to respond to therapy, exploration of specific alterations should be pursued in an excersie to develop a reliable companion diagnostic test.