Search

ObjectiveSmall cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive tumor, with long term survival at ~30% in early stage disease. SCCOHT is caused by germline and somatic SMARCA4 mutations, but the effect of the mutation type on patients remains unknown. Furthermore, the rarity of SCCOHT has resulted in varied treatment, with no standardized protocols. We analyzed 293 cases to determine the effect of treatment modalities and SMARCA4 mutations on patient diagnosis and outcome.MethodsIn 293 SCCOHT patients we collected information on age and stage at diagnosis, treatment modality (surgery, chemotherapy, radiotherapy, and/or high-dose chemotherapy with autologous stem cell rescue (HDC-aSCR)), SMARCA4 mutation origin (germline/somatic), and overall survival. Cox analysis and log-rank tests were performed on 257 cases with available survival data.ResultsThe strongest prognostic factors were stage at diagnosis (p=2.72e-15) and treatment modality (p=3.87e-13). For FIGO stages II-IV, 5-year survival was 71% for patients who received HDC-aSCR, compared to 25% in patients who received conventional chemotherapy alone following surgery (p=0.002). Patients aged ≥40 had a worse outcome than younger patients (p=0.04). Twenty-six of 60 tested patients carried a germline SMARCA4 mutation, including all patients diagnosed

Background Improvement in clinical outcomes of patients with platinum-resistant disease is an unmet medical need and trials in this population are urgently needed. Checkpoint-inhibitors have already shown activity in multiple other tumor entities and ovarian cancer, especially in the combination with anti-angiogenic treatment. Primary objective To test if the activity of nonplatinum-based chemotherapy and bevacizumab could be improved by the addition of atezolizumab. study hypothesis The addition of atezolizumab to standard non-platinum combination of chemotherapy and bevacizumab improves median overall survival from 15 to 20 months. Trial design Patients are randomized to chemotherapy (paclitaxel weekly or pegylated liposomal doxorubicin) + bevacizumab + placebo vs chemotherapy + bevacizumab + atezolizumab. Stratification factors are: number of prior lines, planned type of chemotherapy, prior use of bevacizumab, and tumor programmed death-ligand 1 (PDL1) status. Major inclusion/exclusion criteria Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with up to three prior therapies and a treatmentfree interval after platinum of less than 6 months. Patients with three prior lines of chemotherapy are eligible irrespective of the platinum free-interval. A de novo tumor tissue sample biopsy for determination of PD-L1 status prior to randomization for stratification is mandatory. Major exclusion criteria consider bevacizumab-specific and immunotherapy-specific criteria. Primary endpoint Overall survival and progression-free survival are co-primary endpoints. sample size It is planned to randomize 664 patients. Trial registration NCT03353831. [ABSTRACT FROM AUTHOR]

Objective: High grade endometrial stromal sarcoma and undifferentiated uterine sarcomas are associated with a very poor prognosis. Although large surgical resection is the standard of care, the optimal adjuvant strategy remains unclear. Methods: A retrospective analysis of patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas (stages I–III) treated in 10 French Sarcoma Group centers was conducted. Results: 39 patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas treated from 2008 to 2016 were included. 24/39 patients (61.5%) were stage I at diagnosis. 38/39 patients underwent surgical resection, with total hysterectomy and bilateral oophorectomy completed in 26/38 (68%). Surgeries were mostly resection complete (R0, 23/38, 60%) and microscopically incomplete resection (R1, 6/38, 16%). 22 patients (58%) underwent postoperative radiotherapy (including brachytherapy in 11 cases), and 11 (29%) underwent adjuvant chemotherapy. After a median follow-up of 33 months (range 2.6–112), 17/39 patients were alive and 21/39 (54%) had relapsed (9 local relapses and 16 metastases). The 3 year and 5 year overall survival rates were 49.8% and 31.1%, respectively, and 3 year and 5 year disease free survival rates were 42.7% and 16.0%, respectively. Median overall survival and disease free survival were 32.7 (95% CI 16.3–49.1) and 23 (4.4–41.6) months, respectively. Medians were, respectively, 46.7 months and 39.0 months among those who underwent adjuvant radiotherapy and 41.0 months and 10.3 months for those who underwent adjuvant chemotherapy. In multivariate analysis, adjuvant radiotherapy was an independent prognostic factor for overall survival (P=0.012) and disease free survival (P=0.036). Chemotherapy, International Federation of Gynecology and Obstetrics I–II stages, and Eastern Cooperative Oncology Group-performance status 0 correlated with improved overall survival (P=0.034, P=0.002, P=0.006), and absence of vascular invasion (P=0.014) was associated with better disease free survival. Conclusions: The standard treatment of primary localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas is total hysterectomy and bilateral oophorectomy. The current study shows that adjuvant radiotherapy and adjuvant chemotherapy appear to improve overall survival. A prospective large study is warranted to validate this therapeutic management. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to report our institutional experience of a multimodal approach for treatment of locally advanced high-grade neuroendocrine cervical cancer. Methods and Materials: Patients with primary locally advanced neuroendocrine cervical cancer diagnosed between 2001 and 2014 were included. The scheduled treatment sequence was as follows: pelvic +/− para-aortic radiotherapy (according to tumor stage), associated with chemotherapy based on platine-derivate and etoposide regimen, followed with a brachytherapy boost, then completion surgery if there was no progression +/− consolidation etoposide chemotherapy (for a total of 5–6 cycles). Disease-free survival (DFS) and overall survival (OS) were reported and prognostic factors were searched. Results: A total of 24 patients fulfilled inclusion criteria. Median age was 48 (range 22–77 years). Fourteen patients (58%) had pelvic lymph node metastases. After chemoradiation/brachytherapy, a radical hysterectomy could be performed in 18 of 24 patients (75%). Histologically complete resection was achieved in 14 (78%) of 18 patients. Complete pathological response was reported in 7 (39%) of 18. With median follow-up of 29.7 months, 10 (42%) of 24 patients experienced tumor relapse, all associated with distant failure, including one local failure. The DFS and OS rates estimated at 3 years were 55% and 63%, respectively. Lymph node metastases and tumor stage were prognostic for DFS (P = 0.016 and P = 0.022, respectively). Complete resection was associated with a lower incidence of relapses, as compared with microscopically incomplete resection (P = 0.04). A total of 12 (86%) of 14 patients with histologically complete resection were in complete remission at last follow-up. Apart from manageable acute hematological toxicities, most treatment complications were mild to moderate. Conclusions: This series based on a multimodal management compares favorably with previously published data. Most patients could be eligible to surgery, and complete remission was achieved in 85% of those amenable to complete resection. [ABSTRACT FROM AUTHOR]

Background: The present study retrospectively determined the outcomes and prognoses in stage Imucinous ovarian carcinoma according to histological type (ie, expansile or infiltrative). Methods: A centralized pathologic review of tumors in patients treated from 1976 to 2016 for ovarian mucinous carcinoma was performed by 2 expert pathologists according to the 2014 World Health Organization classification. Only patients with stage I disease were analyzed. Tumors were typed as expansile or infiltrative and oncological issues analyzed. Results: A total of 114 cases were reviewed. Fifty were excluded (stage 9 I in 30 cases and no accessibility to a pathological review for 20 cases). Thus, 64 patients fulfilled the inclusion criteria: 29 had expansile-type and 35 infiltrative-type disease. The characteristics of both groups of patients were comparable, except the use of nodal staging surgery, which was more frequent in patients with infiltrative type. The International Federation of Gynecology and Obstetrics stages in expansile and infiltrative types were as follows: IA in 13 (45%) and 20 (57%), and IC in 16 (55%) and 15 (43%), respectively. Recurrence occurred in 3 patients with expansile type and 6 patientswith infiltrative type. Two cases of expansile recurrence had pelvic recurrence and were salvaged after secondary surgery and chemotherapy, whereas 5 cases of infiltrative recurrence had extrapelvic spread and died from disease or were alive with progressive disease. Conclusions: Recurrence occurred in both types of stage I mucinous ovarian cancer. However, lethal recurrences were observed mainly in infiltrative type. [ABSTRACT FROM AUTHOR]

Objective: Advanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer. Methods: This was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor–positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety. Results: Seventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0–31.4) versus 40 weeks (90% confidence interval, 16.3–64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2. Conclusions: Although irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the safety and efficacy of extending bevacizumab therapy beyond 15 months in nonprogressive ovarian cancer. Patients and Methods: In this multinational prospective single-arm study (ClinicalTrials.gov NCT01239732), eligible patients had International Federation of Gynecology and Obstetrics stage IIB to IV or grade 3 stage I to IIA ovarian cancer without clinical signs or symptoms of gastrointestinal obstruction or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the preceding 6 months. Prior neoadjuvant chemotherapy was permitted. After debulking surgery, patients received bevacizumab 15 (or 7.5) mg/kg every 3 weeks (q3w) with 4 to 8 cycles of paclitaxel (investigator's choice of 175 mg/m2 q3w or 80 mg/m2 weekly) plus carboplatin AUC 5 to 6 q3w. Single-agent bevacizumab was continued until progression or for up to 24 months. The primary end point was safety. Results: Between December 2010 and May 2012, 1021 patients from 35 countries began study treatment. Bevacizumab was administered at 15 mg/kg in 89% of patients and for more than 15 months in 53%. Median follow-up duration was 32 months (range, 1–50 months). The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%). The most common grade 3 or higher-grade adverse events were neutropenia (27%) and hypertension (25%). Bevacizumab was discontinued because of proteinuria in 5% of patients and hypertension in 3%. Median progression-free survival (PFS) was 25.5 months (95% confidence interval, 23.7–27.6 months). Conclusion: Extended bevacizumab demonstrated increased incidences of proteinuria and hypertension compared with 12 or 15 months of bevacizumab in previous trials, but these rarely led to bevacizumab discontinuation. Median PFS is the longest reported for frontline bevacizumab-containing therapy. The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safety. [ABSTRACT FROM AUTHOR]

Objective: In platinum-resistant ovarian cancer, adding pertuzumab to gemcitabine improved progression-free survival in the subgroup with low tumor HER3 messenger RNA expression. The 2-part PENELOPE trial (NCT01684878) is prospectively investigating pertuzumab plus chemotherapy in this population. Patients and Methods: Part 1 evaluated pertuzumab plus either topotecan or paclitaxel. Patients with platinum-refractory or platinum-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer and low HER3 messenger RNA expression (concentration ratio ⩽2.81 by central quantitative reverse transcriptase-polymerase chain reaction testing on Cobas z480) received intravenous pertuzumab (840 mg loading dose then 420 mg every 3 weeks) with the investigator's choice of topotecan (1.25 mg/m2 days 1-5 every 3 weeks) or weekly paclitaxel (80 mg/m2) until disease progression or unacceptable toxicity. The primary objective was to assess safety and tolerability. Results: Fifty patients were treated in part 1 (22 topotecan; 28 paclitaxel). In both cohorts, disease progression was the most common primary reason for discontinuing pertuzumab, and the most common all-grade adverse events (AEs) were fatigue/asthenia, anemia, and diarrhea. The most common grade ≥3 AEs were anemia (36%), neutropenia (27%), and fatigue/asthenia (18%) for topotecan, and peripheral sensory neuropathy (14%) and anemia (11%) for paclitaxel. Two patients receiving paclitaxel-pertuzumab died from AEs (abdominal infection; unexplained death). Median progression-free survival was 4.1 months (95% confidence interval, 1.9-6.1) with topotecan-pertuzumab and 4.2 months (95% confidence interval, 3.5-6.0) with paclitaxel-pertuzumab. Conclusions: Based on part 1 tolerability, the Independent Data Monitoring Committee had no objection to PENELOPE proceeding to part 2, a double-blind randomized comparison of chemotherapy (topotecan, paclitaxel, or gemcitabine) plus pertuzumab or placebo. [ABSTRACT FROM AUTHOR]

Small cell carcinoma of the cervix (SCCC) is a rare histological entity of uterine cervical cancer. Compared with other common histological types, squamous cell carcinoma or adenocarcinoma, the outcome of SCCC is poor because of the high incidence of nodal or distant metastasis even with early stage. In this review, current consensus of epidemiology, pathology, and initial treatment for SCCC will be discussed. [ABSTRACT FROM AUTHOR]

High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive behavior and poor prognosis. Cyclin D1 has been reported as a diagnostic immunomarker for high-grade endometrial stromal sarcoma with an YWHAE-FAM22 rearrangement. YWHAE-FAM22 endometrial stromal sarcomas (ESS) represent a clinically aggressive subtype of ESS classified as high-grade endometrial sarcomas, and its distinction from the usual low-grade ESS with JAZF1 rearrangement and from HGUS with no identifiable molecular aberration may be important in guiding clinical management. Median age of the patients is between 55 and 60 years. The most common symptoms are vaginal bleeding, abdominal pain, and increasing abdominal girth.Disease is usually advanced with approximately 70% of the patients staged III to IV according to the International Federation of Gynecology and Obstetrics classification. Preferential metastatic locations include peritoneum, lungs, intra-abdominal lymph nodes, and bone. Median progression-free survival ranged from 7 to 10 months, and median overall survival ranged from 11 to 23 months. There is no clear prognostic factor identified for HGUS, not even stage. The standard management for HGUS consists of total hysterectomy and bilateral salpingo-oophorectomy. Systematic lymphadenectomy is not recommended. Adjuvant therapies, such as chemotherapy and radiotherapy, have to be discussed in multidisciplinary staff meetings. [ABSTRACT FROM AUTHOR]

The Gynecologic Cancer InterGroup aimed to provide an overview of uterine and ovarian leiomyosarcoma management.Published articles and author experience were used to draft management overview. The draft manuscript was circulated to international members of the Gynecologic Cancer InterGroup for review and comment, and appropriate revisions were made.The approach to management of uterine and ovarian leiomyosarcoma management is reviewed.Uterine and ovarian leiomyosarcomas are rare and aggressive cancers that require specialized expertise for optimal management. [ABSTRACT FROM AUTHOR]

Small cell carcinomas of the ovary are uncommon and account for less than 1% of ovarian cancers. They were first recognized in 1979, and a number of reports appeared during the next 2 decades. They are highly aggressive tumors and usually carry a poor prognosis, although this may reflect that most are diagnosed at advanced stage; however, those diagnosed as stage 1A have only 30% to 40% of long-term survivors. More reports followed extending our experience in the diagnosis and management of these rare cancers. The classification is described below and shown in Table 1, but a revision is expected to be published from the World Health Organization in 2014. [ABSTRACT FROM AUTHOR]

Lapatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), also inhibits breast cancer resistance protein (BCRP) involved in resistance to topotecan. The aim of this multicenter study was to assess the efficacy of the combination topotecan-lapatinib in epithelial ovarian cancer relapsing after a first line of chemotherapy.Patients having relapsed within 6 months (n = 20) or between 6 and 12 months (n = 19) received weekly topotecan (3.2 mg/m2 given intravenously on days 1, 8, and 15) and daily oral lapatinib (1250 mg). Translational studies were performed on tumor and serum.An objective (partial) response was observed for 5 patients (14%), all with late relapse. The rates of overall benefits, including responses and stabilizations, were 37% and 62% in patients having relapsed within or after 6 months, respectively. Corresponding median time to progression were 58 and 94 days. The most frequent toxicity was hematological, including grade 4 neutropenia (18%) and thrombocytopenia (3%). None of the tumors overexpressed HER2 or EGFR, and no mutation was found. Two Kras mutations were identified. Positive expressions of BCRP and cyclin A (median, 70% and 40%) were not correlated to the response to treatment.This study failed to demonstrate a clinical benefit of lapatinib-topotecan compared to previously described activity with topotecan alone in a context of low levels of EGFR and HER2 expressions, and no biomarkers could be identified. The absence of correlation between BCRP expression and clinical outcomes suggests that other mechanisms of resistance to topotecan could predominate. [ABSTRACT FROM AUTHOR]

Surgical management of primary or recurrent ovarian cancer with extensive upper abdominal disease may require splenectomy to achieve complete cytoreduction. The aims of this series were to correlate the macroscopic exploration with the microscopic analysis of the spleen and to evaluate the morbidity of patients submitted to this procedure for primary and recurrent disease.Data concerning patients who underwent splenectomy at the time of management of the primary (initial group) or recurrent disease were reviewed. The characteristics and survival of patients were analyzed. The correlation between macroscopic suspected lesion and histological results and morbidity according to the Dindo classification was studied.From 1995 to 2008, 58 patients (42 in the initial group and 16 in the recurrence group) underwent a splenectomy in our institution. Except for 3 cases requiring splenectomy for hemostatic reasons, the macroscopically suspected splenic lesion was confirmed by histology in 32 (80%) of 40 cases in the initial group and in 14 (93%) of 15 cases in the recurrence group. Eighteen patients (26.5%) had a morbidity grade strictly superior to 2, and in all the factors we tested, only pelvic posterior exenteration was a risk factor for high morbidity (P = 0.02).When splenic lesions are macroscopically suspected during cytoreductive surgery for an ovarian cancer, most of the time the disease is confirmed by histology. When required to accomplish complete cytoreduction, splenectomy seemed to be justified. [ABSTRACT FROM AUTHOR]

Standard treatment of stage IB2/II cervical carcinoma is chemoradiation therapy. Residual disease is evaluated clinically and by magnetic resonance imaging. The place of surgery after this treatment is debated, except when there is suspicion of residual disease. There is no standard management when surgical resection is incomplete. The aim of this study was to describe the outcome of these patients.A retrospective review was undertaken of patients fulfilling the following inclusion criteria: (1) stage IB2/II cervical cancer, (2) external radiotherapy (45 Gy) with concomitant chemotherapy followed by uterovaginal brachytherapy (15 Gy), (3) magnetic resonance imaging performed between 3 and 8 weeks after brachytherapy, and (4) completion surgery with incomplete resection of pelvic disease. Patients with distant metastasis or carcinosis were excluded.Ten patients treated between 2003 and 2006 fulfilled all inclusion criteria. The locations of the incomplete resection were (some patients had several locations) the parametrium (n = 4), lateral limit of the cervix (n = 4), anterior (n = 2), posterior (n = 3), and vagina (n = 2). Further surgery had been proposed for 3 patients but only performed once and this patient had rapid disease progression. One patient had received chemotherapy for metastatic para-aortic nodes. Seven patients died with a median period of 11 months after surgery (range, 3-21 months). One patient is alive with recurrent disease, and 2 are free of disease with 23 and 33 months of follow-up.The prognosis is poor when resection is incomplete after chemoradiation therapy in advanced-stage cervical cancer, and further surgery does not seem to improve this outcome. [ABSTRACT FROM AUTHOR]

This study describes 45 cases of adult granulosa-cell tumors seen in our institution between 1976 and 1993. The median age was 46.5 years (12-77) and 18 women were postmenopausal. Vaginal bleeding was present in one-third of cases; other complaints were abdominal pain (28%) and the presence of a pelvic mass (47%). The tumor size was variable (<3 cm to 30 cm, median 11.5 cm). FIGO stages were: stage I: 30 (73%) (19 Ia, seven Ic, four I unknown); stage II: seven (17%) (two IIa, five IIC); stage III: three (7%)(one IIIb, two IIIc). Two adenocarcinomas and 13 cases of hyperplasia were found in 25 endometrial samples available. The initial therapy for all the cases was surgery, consisting in 34 patients of hysterectomy, bilateral salpingo-oophorectomy, ± tumor resection. Sixteen patients received adjuvant therapy as well: chemotherapy (CT) alone for 12, radiotherapy (RT) alone for two, and CT + RT for two patients. Among the 39 patients who achieved a complete response after initial therapy, 15 patients have relapsed(pelvic recurrences) (38.5%) including six stage Ia (three received only conservative surgery). All the recurrent tumors were resected and 14/15 had CT(13/14 with cisplatin). The overall survival rate was 77.2% at 5 years, 66.5% at 10 years, and 41.2% at 20 years. A statistically significant difference was found between the survival of patients with stage Ia disease (75% at 10 and 15 years) and that of other patients (60% at 10 years, and <50% at 15 years). Serum estradiol and serum inhibin were measured in some patients and the results are described. [ABSTRACT FROM AUTHOR]