Neoadjuvant chemotherapy with bevacizumab for locally advanced vulvar cancer.

OBJECTIVES: External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects. Radical vulvectomy post-radiation for persistent disease is often compromised with poor wound healing. We describe clinical outcomes for patients who received neoadjuvant chemotherapy plus bevacizumab followed by radical vulvectomy for locally advanced vulvar cancer. METHODS: We performed retrospective analyses of all patients at our institution who underwent radical vulvectomy from January 2015 to November 2023. Of 113 patients, 13 patients underwent neoadjuvant chemotherapy. Demographics and clinicopathologic data were extracted, and descriptive statistical analyses were performed. Cases with neoadjuvant chemotherapy plus bevacizumab were further evaluated for response, adverse effects, and survival. RESULTS: Neoadjuvant chemotherapy was administered to 13 patients with stage II-IV disease that involved the urethra, vagina, or anus. Lesion sizes ranged from 4 to 20 cm (median 7 cm). Patients received 2-6 cycles of carboplatin or cisplatin, paclitaxel, and bevacizumab. Nine (69.2%) patients had partial pathologic responses, and four patients had complete responses. All patients had negative surgical margins. Ten (76.9%) patients had radiographic evidence of inguinal lymph node metastasis prior to neoadjuvant chemotherapy, and four had residual nodal disease. Only one patient developed a superficial groin seroma. Three patients developed recurrence, two locally and one distant, and there was one death. The median follow-up was 23 months (range 6-84 months). CONCLUSIONS: Neoadjuvant chemotherapy using combination platinum/paclitaxel/bevacizumab was efficacious for locally advanced vulvar cancer, resulting in complete resections, negative margins, and excellent wound healing. A multi-institutional phase II trial is warranted to validate these findings.

Rapid recurrence of stage IIB non-gestational ovarian choriocarcinoma with minor yolk sac tumor: A rare case report and literature review.

Non-gestational ovarian choriocarcinoma (NGOC) is a rare phenomenon seldom reported in the literature. Patients often present with abdominopelvic pain, and sometimes a palpable adnexal mass. Surgical excision is paramount in treating this malignancy; however, fertility-preserving care is a debated topic among gynecologic oncologists. Most patients reported in the literature are nulliparous women of child-bearing age. It is important to consider fertility preservation whilst balancing oncologic outcomes. We present a case of an 18-year-old nulliparous female with stage IIB NGOC that had disease progression in the lungs and pelvis shortly after undergoing fertility-preserving surgery. She required emergent completion surgery and received etoposide (E), methotrexate (M), actinomycin-D (A), cyclophosphamide (C) and vincristine (O) (EMA-CO) with complete response. She remains disease-free after 21-months.

Prognostic features of the tumor microenvironment in high-grade serous ovarian cancer and dietary immunomodulation.

High-grade serous ovarian cancer (HGSOC) is a particularly lethal malignancy that is prognostically influenced by the immune profile of the tumor microenvironment (TME). TME immune profiles have been sub-categorized according to features associated with both survival outcomes as well as response to systemic therapies. Five suggested immune phenotypes have been described and correlated with overall survival outcomes. Phenotypes associated with shorter overall survival rates appear to have prominent immunosuppressive features within their TME. The opportunity to triage patients according to their prognostic TME profile might allow selection of individual patients with poor prognostic features who could most benefit from innovative immunomodulatory treatment strategies. Two potential strategies to indirectly manipulate the TME (and oncologic outcomes) are alteration of the gut microbiome composition and alteration of TME metabolism through dietary interventions. Experimental dietary modifications in humans designed for influencing cancer outcomes are only beginning to be studied in a prospective fashion. Herein we summarize prognostic TME features in HGSOC and potential opportunities for immunomodulation via dietary and gut microbial interventions.

Malignant peritoneal cytologic contamination with robotic hysterectomy for endometrial cancer.

BACKGROUND: Malignant peritoneal cytology in endometrial cancer (EC) is not considered an independent adverse prognostic factor for uterine-confined disease and is not a determinant factor in the International Federation of Gynecology and Obstetrics (FIGO) staging system. NCCN Guidelines still recommend obtaining cytologies. The aim of this study was to determine the prevalence of peritoneal cytologic contamination following robotic hysterectomy for EC. METHODS: Peritoneal cytology from the pelvis and diaphragm were obtained at the initiation of surgery, and from the pelvis only at the completion of robotic hysterectomy with sentinel lymph node mapping (SLNM). Cytology specimens were evaluated for the presence of malignant cells. Pre- and post-hysterectomy cytology results were compared, and pelvic contamination was defined as conversion from negative to positive cytology following surgery. RESULTS: 244 patients underwent robotic hysterectomy with SLNM for EC. Pelvic contamination was identified in 32 (13.1%) cases. In multivariate analysis, pelvic contamination was associated with >50% myometrial invasion, tumor size >2 cm, lymphovascular space invasion (LVSI), and lymph node metastasis. There was no association with FIGO stage or histology subtypes. CONCLUSIONS: Malignant peritoneal contamination occurred during robotic surgery for EC. Large lesions (>2 cm), deep invasion (>50%), LVSI, and lymph node metastasis were each independently associated with peritoneal contamination. Whether or not peritoneal contamination increases risk for disease recurrence should be studied in larger series, including an evaluation of patterns of recurrence and the potential impact of adjuvant therapies. Until the clinical impact of peritoneal contamination during hysterectomy for EC is better understood, methods to reduce peritoneal contamination are warranted.

Clinical Activity of Olvimulogene Nanivacirepvec-Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer: The Nonrandomized Phase 2 VIRO-15 Clinical Trial.

Importance: Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need. Objective: To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC. Design, Setting, and Participants: This open-label, nonrandomized multisite phase 2 VIRO-15 clinical trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022. Interventions: Olvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab. Main Outcomes and Measures: Primary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS). Results: Twenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths. Conclusions and Relevance: In this phase 2 nonrandomized clinical trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02759588.

Fused Clitoral Hood Presenting as a Periclitoral Mass.

BACKGROUND: Periclitoral masses are seldom reported. One cause is a congenitally fused clitoral prepuce (or clitoral hood). CASE: A patient was referred to our gynecologic oncology practice with a suspicious periclitoral mass for evaluation of possible malignancy. The clitoral hood was, in fact, fused such that the glans was completely covered. Surgical excision of the distal prepuce (or clitoral hood) expelled trapped sebaceous material and revealed a normal-appearing glans clitoris. Clitoral hood reconstruction restored the patient's external genitalia to normal anatomy. CONCLUSION: Fused clitoral prepuce causing trapped sebaceous material can mimic an expanding periclitoral mass and should be considered in the differential diagnosis.

Exploring Bias in Scientific Peer Review: An ASCO Initiative.

PURPOSE: To investigate implicit bias (IB) in the peer review process across ASCO and Conquer Cancer Foundation and to propose potential mitigation strategies. MATERIALS AND METHODS: We, ASCO Working Group on Implicit Bias, selected four data sources: (1) literature search [(a) defining IB in peer review, (b) evidence of IB in peer review, and (c) strategies to mitigate IB]; (2) created and analyzed an ASCO database for sex, race, and institutional affiliation regarding peer review success; (3) constructed and conducted qualitative interviews of key stakeholders within the ASCO board, publications, and grants committee, on experience with IB within ASCO; and (4) constructed, delivered, and analyzed results of member survey on perception of IB within ASCO. RESULTS: Historically uncommon, PubMed articles on IB in peer review subsequently increased exponentially in the past 2 decades. Qualitative interviews of ASCO key stakeholders reveal that system changes and IB training were priorities. The committee member survey reported that their peer review decisions could be affected by IB and that mitigating IB should be a priority. Most reported having never been trained on IB. Available data from ASCO database support stakeholder findings, suggesting that there exists a disproportionate representation of males and better-known institutions among both reviewer positions and awardees. Ethnicity/race data were insufficiently reported. Limited data on interventions/strategies to mitigate IB in the peer-reviewed literature suggest that there are feasible processes for grants, program committees, and journals. CONCLUSION: Limited data reveal that the peer review process at ASCO is not exempt from IB and suggest association with sex and institutional affiliation. Working Group on Implicit Bias recommends three actions to mitigate IB within peer review: (1) create awareness and a culture of inclusivity, (2) create systems to reduce IB, and (3) collect data for ongoing analysis.

Immunotherapy in the Treatment of Platinum-Resistant Ovarian Cancer: Current Perspectives.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The gold standard therapeutic approach is a combination of surgery plus chemotherapy. Unfortunately, 80% of patients with EOC suffer recurrence within 2-years and the overall response rate for platinum-resistant epithelial ovarian cancer to cytotoxic chemotherapy or poly-(adenosine diphosphate)-ribose polymerase (PARP) inhibitor is modest. New therapies are needed to improve overall survival. The role of immunotherapy has been established in endometrial and cervical cancers, however its effective use in EOC has been limited due to the intrinsic genomics and micro-immune environment associated with EOC. Studies evaluating immunotherapy, largely immune checkpoint inhibitors (ICI), have shown limited activity, yet some patients benefit greatly. Thus, significant efforts must be devoted to finding new strategies for the use of immunotherapy/immunomodulatory drugs (IMiDs). Immunotherapy has a well-tolerated safety profile; however, cost-effectiveness can be an obstacle. The aim of this article is to review the most recent research into the use of IMiDs in patients with platinum-resistant epithelial ovarian cancer.

Carcinomatosis in Early-Stage Cervical Cancer Treated with Robotic Radical Hysterectomy: Recurrence Patterns, Risk Factors, and Survival.

PURPOSE: Minimally invasive radical hysterectomy has been associated with increased recurrence of disease and worse survival compared with open radical hysterectomy for early-stage cervical cancer. We evaluated patterns of recurrence and histopathologic risk factors in patients who underwent robotic radical hysterectomy (RRH). METHODS: Patients who underwent RRH (4/2007-12/2018) were evaluated for specific locations of recurrent disease, disease-free survival, overall survival (OS), and histopathologic risk factors for recurrence. Inclusion criteria were follow-up ≥ 1 year, histology with adenocarcinoma, adenosquamous, or squamous carcinoma and clinical stage IA2 to IB ≤ 4-cm tumor size cervical cancers (FIGO-2018). RESULTS: A total of 140 patients underwent RRH and 112 met criteria. Median tumor size was 2.1 cm [interquartile range (IQR): 1.1-3.3]. Median follow-up was 61 months (IQR: 36-102). Fifty (45%) patients underwent adjuvant radiation ± cisplatin with either Sedlis' or Peters' risk factors. There were 11 (9.8%) recurrences with median disease-free survival of 12 (IQR 8.5) months. All patients with recurrence had measured tumor size ≥ 2 cm (median tumor size 3-cm (IQR: 2.6-4.0). Tumor size > 2 cm was associated with Sedlis' intermediate-risk factors (p < 0.05) and Peters' high-risk factors (p < 0.05). Forty patients underwent preoperative conization, and two (5%) with deep positive margins in lesions > 2 cm recurred. Five (4.5%) of patients had carcinomatosis representing 45% of all recurrences. Carcinomatosis was associated with reduced OS compared with other recurrence patterns (22 months vs. 7.8 years, p < 0.05). CONCLUSIONS: Carcinomatosis was observed in early-stage cervical cancers treated with RRH and was associated with reduced OS. All recurrences were associated with lesions ≥ 2 cm, and no recurrences were identified with negative conization margins.

Neoadjuvant chemotherapy followed by fertility sparing surgery in cervical cancers size 2-4 cm; emerging data and future perspectives.

BACKGROUND: Approach to the management of early stage cervical cancers with tumor size >2 cm in women who desire fertility preservation has been fraught with controversy. Fertility sparing surgery for FIGO 2018 stage IB cancers has been validated most for tumors ≤2 cm. In this review, our objective was to evaluate the oncologic and obstetric outcomes for women that underwent neoadjuvant chemotherapy (NACT) before fertility sparing surgery for tumors 2-4 cm. METHODS: We performed a systematic literature review and searched PubMed, Google Scholar, Cochrane Reviews and UpToDate (from January 2000 to February 2021) using the terms: cervical cancer, fertility preservation, trachelectomy, radical trachelectomy, neoadjuvant chemotherapy, cervical cancer treatment, stage IB1 or IB2 cervical cancer, and cervical cancer size 2-4 cm. We included manuscripts with information on patients with tumor sizes 2-4 cm, lymph node status, follow-up, obstetric and oncologic outcome. We excluded review articles or articles without all pertinent patient information. RESULTS: Eighteen articles were identified including 249 patients. For final analysis, 114 met inclusion criteria. All included patients had FIGO 2018 stage IB2 cervical cancer, underwent neoadjuvant chemotherapy and subsequent fertility sparing surgery. Vaginal radical trachelectomy, cold knife conization, abdominal radical trachelectomy, laparoscopic radical trachelectomy, simple vaginal trachelectomy, and cone laser were performed in 46 (40.4%), 26 (22.8%), 14 (12.3%), 13 (11.4%), 8 (7%), and 7 (6.1%) women, respectively. The most common regimen of chemotherapy was platinum-based therapy with cisplatin. The follow-up time reported in all studies ranged from 1 to 225 months. Of 64 attempted pregnancies, there were 49 (76.6%) viable deliveries which included 6 preterm births (9.4%). The recurrence rate was 6.1% and two patients (1.8%) died of disease. CONCLUSION: Fertility sparing surgery following NACT is an option for women with cervical cancers that are 2-4 cm that wish to preserve fertility without sacrificing oncologic or obstetric outcomes. Confirmation of these findings are anticipated from an ongoing international phase II clinical trial [1].

Isolated vulvar Langerhans cell histiocytosis.

•Primary vulvar Langerhans cell histiocytosis is rare with less than 40 reported cases.•Diagnosis of vulvar LCH requires prompt metastatic workup to rule out multisystem involvement.•Treatment protocols for isolated vulvar LCH vary widely and there is not an established standard of care.•Continue surveillance is warranted even after prolonged periods of remission.

Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer.

BACKGROUND: Nelfinavir (NFV), an HIV-1 protease inhibitor, has been shown to sensitize cancer cells to chemoradiation (CRT). The objectives of this phase 1 trial were to evaluate safety and identify the recommended phase 2 dose of NFV added to concurrent CRT for locally advanced cervical cancer. METHODS: Two dose levels of NFV were evaluated: 875 mg orally twice daily (dose level 1 [DL1]) and 1250 mg twice daily (DL2). NFV was initiated 7 days before CRT and continued through CRT completion. Toxicity, radiographic responses, and pathologic responses were evaluated. Serial tumor biopsies (baseline, after NFV monotherapy, on NFV + CRT, and posttreatment) were evaluated by immunohistochemistry, NanoString, and reverse-phase-protein-array analyses. RESULTS: NFV sensitized cervical cancer cells to radiation, increasing apoptosis and tumor suppression in vivo. Patients (n = 13) with International Federation of Gynecology and Obstetrics stage IIA through IVA squamous cell cervical carcinoma were enrolled, including 7 patients at DL1 and 6 patients at DL2. At DL1, expansion to 6 patients was required after a patient developed a dose-limiting toxicity, whereas no dose-limiting toxicities occurred at DL2. Therefore, DL2 was established as the recommended phase 2 dose. All patients at DL2 completed CRT, and 1 of 6 experienced grade 3 or 4 anemia, nausea, and diarrhea. One recurrence was noted at DL2, with disease outside the radiation field. Ten of 11 evaluable patients remained without evidence of disease at a median follow-up of 50 months. NFV significantly decreased phosphorylated Akt levels in tumors. Cell cycle and cancer pathways also were reduced by NFV and CRT. CONCLUSIONS: NFV with CRT is well tolerated. The response rate is promising compared with historic controls in this patient population and warrants further investigation.

The gut microbiome and cancer immunotherapeutics: A review of emerging data and implications for future gynecologic cancer research.

Investigation of the gynecologic tract microbial milieu has revealed potential new biomarkers. Simultaneously, immunotherapeutics are establishing their place in the treatment of gynecologic malignancies. The interplay between the microbiome, the tumor micro-environment and response to therapy is a burgeoning area of interest. There is evidence to support that microbes, through their genetic make-up, gene products, and metabolites affect human physiology, metabolism, immunity, disease susceptibility, response to pharmacotherapy, and the severity of disease-related side effects. Specifically, the richness and diversity of the gut microbiome appears to affect carcinogenesis, response to immunotherapy, and modulate severity of immune-mediated adverse effects. These effects have best been described in other tumor types and these have shown compelling results. This review summarizes the current understanding and scope of the interplay between the human microbiome, host factors, cancer, and response to treatments. These findings support further exploring whether these associations exist for gynecologic malignancies.

Robotic sentinel lymph node (SLN) mapping in endometrial cancer: SLN symmetry and implications of mapping failure.

PURPOSE: To establish the bilateral pelvic concordance rate of the sentinel lymph node (SLN) and determine the likelihood of lymph node metastasis in cases of mapping failure. METHODS: A database analysis was performed on 414 patients with clinical stage I endometrial cancer who underwent SLN mapping followed by robotic hysterectomy and completion pelvic (n=414, 100%) and aortic (n=186, 44.9%) lymphadenectomy from March 2011 to August 2016. Stage, histology, SLN sites, and surgico-pathologic findings were analyzed. The bilateral concordance rate of SLN location, successful unilateral and bilateral mapping rates, false negative rate, and non-SLN metastasis associated with mapping failure were calculated. RESULTS: Histologies included 354 (85.5%) endometrioid, 39 (9.4%) serous, 16 (3.9%) carcinosarcoma, 4 (1.0%) clear cell, and 1 (0.2%) undifferentiated. Final stages included 262 (63.3%) IA, 36 (8.7%) IB, 15 (3.6%) II, 6 (1.4%) IIIA, 68 (16.4%) IIIC1, and 27 (6.5%) IIIC2. Bilateral SLN mapping was successful in 355 (85.7%) patients, and 266 (74.9%) demonstrated mapping to the symmetrical lymphatic group contralaterally. The mapping failure rate was 13.5% (56/414) unilaterally and 0.7% (3/414) bilaterally. SLN locations were external iliac (69.1%), obturator (25.1%), internal iliac (2.2%), common iliac (1.9%), pre-sacral (0.9%), aortic (0.4%), parametrial (0.3%), and para-rectal (0.1%). Lymph node metastases were identified in 95 (22.9%) pelvic and 27 (6.5%) aortic nodes. 10 (16.9%) cases with mapping failure had lymph node metastasis on completion lymphadenectomy, similar to the proportion of SLNs with metastases (p=0.35). However, macro-metastases were more common in mapping failure completion lymphadenectomies than in the positive SLNs (80% vs 22.3%, p<0.001). CONCLUSION: The contralateral SLN location concordance rate was 75%. Most SLNs were along the medial external iliac or obturator locations. The rate of positive lymph nodes associated with SLN mapping failure was 16.9%, similar to the overall node-positive rate. The detection of pelvic node metastasis with SLN mapping failure was largely populated with macro-metastases and confirms the necessity of completion lymphadenectomy with mapping failure.

Sentinel lymph nodes (SLN) in endometrial cancer: The relationship between primary tumor histology, SLN metastasis size, and non-sentinel node metastasis.

OBJECTIVES: To examine sentinel lymph node pathology and describe relationships to uterine pathology, non-sentinel pelvic lymph nodes, and para-aortic lymph nodes. METHODS: Patients with apparent uterine-confined endometrial cancer underwent robotic hysterectomy, SLN mapping, completion pelvic lymphadenectomy (LND), and para-aortic (PaLND) directed by frozen section. Patients were risk stratified by histology: low-risk (LR) endometrioid <50% depth-of-invasion (DOI), intermediate-risk (IR) endometrioid ≥50% DOI, and high-risk (HR) type II histology for comparison to other pelvic/aortic metastases. RESULTS: 414 patients were stratified: 275 LR, 80 IR, and 59 HR cases. PaLND was performed in 84.2% of IR/HR patients and 25.1% LR patients. Pelvic node metastasis was detected in 11.6% LR, 50.0% IR, and 39.0% HR patients. PaLN metastasis was detected in 2.9% LR, 11.3% IR, and 16.9% HR patients. Proportionally, isolated tumor cells (ITC) SLNs were more common in LR or IR vs. HR group (51.6% and 44.7% vs. 15.0%, p < 0.05). The SLN false negative rates (FNR) were 0% LR, 2.5% IR, and 5.1% HR. Non-sentinel pelvic node metastases were present in 28(31.5%) of all SLN+ cases, but only 3(8.3%) of SLN with ITC. PaLN metastasis was found in 18.8% LR, 11.8% IR, and 33.3% HR cases with ITC SLNs. After controlling for DOI, LVSI, and grade, ITC-positive SLNs had a significant association with non-sentinel pelvic and aortic metastasis (p = 0.03 and p = 0.008, respectively). CONCLUSIONS: Patients with HR histology have more micro/macro-metastases in both SLNs and non-SLN metastases compared to LR/IR patients. SLN ITCs were associated with a clinically significant incidence of PaLN metastasis across all histology risk groups. There were no cases of isolated aortic node metastasis in this study. SLN mapping had an increased, although clinically acceptable FNR in the HR cohort compared to LR patients.

Fertility preserving options for gynecologic malignancies: A review of current understanding and future directions.

Gynecological malignancies affect significant proportion of women in whom fertility preservation is a priority. Advancing reproductive technology and modern surgical techniques are changing the way young women with cancer are counseled regarding their fertility plans at time of cancer diagnosis. This review article provides the reader with fertility preserving updates in gynecologic malignancies as well as those with genetic predisposition for gynecologic malignancies. The different types of gynecologic malignancies including cervical, endometrial, and ovarian cancers and their unique obstacles are addressed separately. New insights into conservative cervical cancer surgery and fertility preserving neoadjuvant chemotherapy followed by fertility preserving surgery for cervical cancer are discussed. Hormonal management of endometrial cancer are highlighted. Additionally, better understanding of ovarian failure with modern chemotherapy/radiation therapy is summarized. Finally, modern reproductive techniques such as ovarian cryopreservation are reviewed as well as those in early stages are development such as artificial ovarian tissue are previewed.