Impact of young age on platinum response in women with epithelial ovarian cancer: Results of a large single-institution registry.

OBJECTIVE: In young women, EOC is a rare disease with an uncertain genetic and biological substrate. METHODS: We report a long follow-up of EOC patients treated at Gustave Roussy between 1990 and 2009. We matched young patients aged ≤30 years to randomly selected older patients aged ≥40 years according to known prognostic factors (i.e. FIGO stage, histology and surgical residual disease) and the date of diagnosis with a threshold at the year 2000 to balance the treatment procedures. RESULTS: EOC was diagnosed in 68 patients aged ≤30 years matched with 111 patients aged ≥40 years. Low-grade (LG) (i.e. serous and endometrioid) (52%, n = 35) and mucinous (i.e. 23%, n = 16 infiltrative and 12% n = 8 expansile) tumors are prevalent. High-grade (HG) tumors are rare (7%, n = 5). Early stage diseases (53%, n = 36 FIGO I/II) are predominant. Response to platinum based chemotherapy is observed to be inferior in young patients as compared to matched older patients (ORR, 29 vs 84% p = 0.0002). For HG tumors the PFS is of 0% at 5 and 10 years in younger as compared to 30% in older patients. No difference in PFS (median 4.9 vs 9.8 ms, p = 0.58) and OS (not reached vs 15.3 ms, p = 0.47) is found overall among younger and older patients respectively. The median follow-up was 72 months (range, 11-288 months). No genetic abnormalities were found. CONCLUSIONS: Young EOC patients are most often diagnosed at an early FIGO stage with LG serous or mucinous histology. Tumors are significantly more resistant to platinum-based chemotherapy in younger patients.

Post-Radiation Grade 3 Neuroendocrine Carcinoma: A New Entity?

BACKGROUND: Cancer survivors have a 14% increased risk of developing a malignancy compared with the general population. Second radiation-induced malignancies with different histologies have been described in different organs. Based on individual observations, we hypothesized that neuroendocrine carcinoma (NEC) could arise in irradiated organs. METHODS: In a retrospective analysis of Gustave Roussy database of NEC patients (small cell lung cancer excluded) diagnosed as a second cancer, we looked for the frequency of grade 3 NEC that arose in patients who had received previous radiation therapy for a first cancer. Radiation therapy for the first cancer, dose, location of radiation therapy, pathological characteristics, overall survival, and response to treatment of secondary NEC were analyzed. RESULTS: From January 1995 to December 2017, 847 cases of NEC were seen at Gustave Roussy. Among them, 95 (11.2%) patients had a history of previous malignancy of which 36 (4%) had been treated with radiation therapy. Out of these 36 patients, 12 (1.4% of all NEC patients) developed a NEC within the previous irradiated organ (median dose of 50 Gy, range 36-67.5). Most frequent first cancers were breast cancer (n = 4) and Hodgkin lymphoma (n = 3). NEC arose within a median time of 21.7 years (range 5.1-36.4) from radiation in the thorax (n = 5), digestive tract (n = 3), and other sites. Five large cell NEC, 3 small cell NEC, 1 mixed neuroendocrine neoplasm and 3 not otherwise specified NEC were diagnosed. Ten patients had stage IV disease at diagnosis; median overall survival was 37.8 months (95% CI [17.6 to NA]). Three patients (25%) achieved complete response with multimodal treatment. CONCLUSIONS: NEC can arise from previously irradiated organs and may have a better outcome in this setting. Other risk factors should be investigated to explain the high rate of previous cancer in this population of neuroendocrine neoplasm.

Uterine smooth muscle tumor analysis by comparative genomic hybridization: a useful diagnostic tool in challenging lesions.

The diagnosis and management of uterine smooth muscle tumors with uncertain malignant potential (STUMP) is often challenging, and genomic data on these lesions as well as on uterine smooth muscle lesions are limited. We tested the hypothesis that genomic profile determination by array-CGH could split STUMP into a benign group with scarce chromosomal alterations akin to leiomyoma and a malignant group with high chromosomal instability akin to leiomyosarcoma. Array-CGH genomic profile analysis was conducted for a series of 29 cases of uterine STUMP. A group of ten uterine leiomyomas and ten uterine leiomyosarcomas served as controls. The mean age was 50 years (range, 24-85) and the follow-up ranged from 12 to 156 months (average 70 months). Since STUMP is a heterogenous group of tumors with genomic profiles that can harbor few to many chromosomal alterations, we compared genomic indices in leiomyomas and leiomyosarcomas and set a genomic index=10 threshold. Tumors with a genomic index <10 were classified as nonrecurring STUMPs and those with a genomic index >10 represented STUMPs with recurrences and unfavorable outcomes. Hence, the genomic index threshold splits the STUMP category into two groups of tumors with different outcomes: a group comparable to leiomyomas and another similar to leiomyosarcomas, but more indolent. In our STUMP series, genomic analysis by array-CGH is an innovative diagnostic tool for problematic smooth muscle uterine lesions, complementary to the morphological evaluation approach. We provide an improved classification method for distinguishing truly malignant tumors from benign lesions within the category of STUMP, especially those with equivocal morphological features.

Surgical Outcomes After Debulking Surgery for Intraabdominal Ovarian Growing Teratoma Syndrome: Analysis of 38 Cases.

BACKGROUND: The goal, methods, and results of surgery for growing teratoma syndrome (GTS) in men after testicular cancer have been well described. The main surgical challenge relates to the need for vascular or thoracic procedures. But little is known about GTS in women, particularly regarding the optimal management of intraabdominal disease. This study aimed to evaluate the surgical management and outcomes (recurrences and fertility) for a large series of ovarian GTS. METHODS: This study retrospectively analyzed patients treated for an ovarian immature teratoma (IT) who subsequently experienced abdominal GTS requiring surgery. RESULTS: Between 1983 and 2014, 196 cases of IT were referred to the authors' institution or treated there, and 38 patients (19 %) subsequently experienced a GTS, including 10 cases of gliomatosis peritonei (containing exclusively pure mature glial tissue). The median age at diagnosis was 26 years (range 8-41 years), and the mean delay between IT and GTS diagnosis was 7 months (range 3-84 months). Surgical resection included peritonectomy (n = 22), diaphragmatic peritoneal resection (n = 14), bowel resection (n = 8), and splenectomy (n = 5). Conservative surgery was possible for 20 patients. Complete cytoreductive surgery was achieved for 25 patients. The mean follow-up period was 73 months (range 3-263 months). At least one recurrence developed for 10 patients (in the form of mature disease in all, and 8 of these patients had an initial complete resection. Five patients had a pregnancy. One patient died of complications from the disease (pulmonary embolism in a patient with bowel obstruction). CONCLUSIONS: The overall prognosis of abdominal GTS is good. The surgical procedures for GTS are similar to those used in debulking surgery for epithelial cancer. Whenever technically possible, a conservative surgery should be performed because spontaneous fertility is possible. Recurrent GTS is frequent even after complete surgery.

Outcome of patients with advanced-stage borderline ovarian tumors after a first peritoneal noninvasive recurrence: impact on further management.

OBJECTIVES: The aims of this study were to report the outcome of patients with advanced-stage serous borderline ovarian tumors (SBOT) after a first noninvasive recurrence and the impact of conservative treatment in that context and to define the best management for those patients. STUDY DESIGN: From 1973 to 2006, 168 patients were treated at or referred to our institution for an SBOT with peritoneal implants. Their slides were reviewed by the same expert pathologist. Selection criteria were as follows: advanced stage (International Federation of Gynecology and Obstetrics ≥ II), with at least 1 recurrence (only noninvasive ones) and more than 5 years of follow-up. RESULTS: Twenty patients met the inclusion criteria. The median duration of follow-up was 12 years (range, 6-23 years). Median age was 26 years (14-61 years). Initial surgical management was conservative for 14 patients and radical for 6. In the study population, 4 patients recurred, all with invasive disease. Time to invasive recurrence was at least 3 years for 3 of 4 patients. None of those 4 patients had a second-look surgery initially or after the first recurrence. Two patients had small-sized residual disease after initial management; only 1 of these 4 patients is currently alive and disease-free. There was no significant difference between conservative and radical treatment of the risk of second recurrence. CONCLUSIONS: This study emphasizes the need for a long follow-up after recurrence of advanced-stage SBOT and the risk of a new invasive recurrence after a first noninvasive peritoneal recurrence. Conservative treatment does not seem as a risk factor and is still justified after a first noninvasive recurrence for young patients who desire to preserve fertility.

Gliomatosis peritonei: a particular entity with specific outcomes within the growing teratoma syndrome.

OBJECTIVES: Ovarian immature teratoma may be associated with peritoneal spread that could, after adjuvant chemotherapy, develop into disease exclusively composed of mature implants (growing teratoma syndrome) and/or gliomatosis peritonei (GP), defined as the presence of pure mature glial tissue. However, very few specific series are devoted to the outcomes of pure GP. This was the aim of the present study. PATIENTS: From 1997 to 2013, data concerning patients treated for stage II/III immature teratoma were reviewed. All slides were reviewed by an expert pathologist. Patients with ovarian cancer associated with peritoneal spread in the form of pure GP (initially if patients were treated without adjuvant treatment or after adjuvant chemotherapy if done) were analyzed. RESULTS: Ten patients fulfilled the inclusion criteria. The median age of patients at diagnosis was 36 years (range, 14-41 years). Six patients had undergone a conservative treatment. Five patients had macroscopic residual disease at the end of surgery.The median duration of follow-up from the diagnosis of GP was 39 months (range, 6-114 months). Six patients had undergone secondary surgery. Among them, 5 had incompletely resected macroscopic GP. No patients had died of their disease. All patients were asymptomatic at the time of the last consultation (1 of them with abnormal radiologic imaging). CONCLUSIONS: Gliomatosis peritonei is a particular entity of the condition described as growing teratoma syndrome because residual peritoneal disease can be asymptomatic totally stable over a long period which raises the question of a more conservative surgical approach in patients with massive peritoneal spread.

Multimodal treatment with doxorubicin, cisplatin, and ifosfamide for the treatment of advanced or metastatic uterine leiomyosarcoma: a unicentric experience.

OBJECTIVE: Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy characterized by a poor prognosis due to a high rate of local and metastatic recurrences. Chemotherapy with doxorubicin or ifosfamide or both is associated with a 10% to 30% objective response rate. We report a monocentric experience with doxorubicin, cisplatin, and ifosfamide (API) combination in the setting of multimodal treatment of advanced or metastatic ULMS. PATIENTS AND METHODS: This monocentric retrospective study included patients with metastatic or locally advanced ULMS with a physiological age younger than 65 years treated in first line with a multimodal aggressive approach with API chemotherapy. Treatment consisted of doxorubicin 50 mg/m2 d1, ifosfamide 3 g/m2 per day d1d2 plus mesna, cisplatin 75 mg/m2 d3, plus G-CSF; every 3 weeks up to 6 cycles. Surgery, radiation therapy, or radiofrequency ablation therapy of metastatic sites was associated whenever possible. RESULTS: Thirty-eight patients received API for metastatic or locally advanced ULMS. Median age was 51 years (40-64 years); 4 (11%) patients were treated for a locally advanced disease and 34 (89%) for metastatic disease. Sixteen patients responded (4 complete responses+12 partial responses) among 33 evaluable patients (objective response rate, 48%); 8 and 9 patients had, respectively, stable and progressive disease. Twelve patients had surgeries with 9 surgical complete responses and 3 surgical partial responses. Median progression-free and overall survival in the whole population were 9.8 and 27 months, respectively. Main grade 3-4 toxicities in 38 patients were neutropenia (74%), thrombocytopenia (60%), anemia (55%), fatigue (18%), and vomiting (13%). Febrile neutropenia was observed in 37% of patients. CONCLUSIONS: Despite the toxicity observed, API is an effective treatment which compares favorably with other first-line therapies for patients with metastatic or advanced ULMS.

Adjuvant platinum-based chemotherapy for borderline serous ovarian tumors with invasive implants.

BACKGROUND: Most borderline ovarian tumors (BOTs) are cured with surgery. However BOTs with invasive implants have a poor prognosis with a mortality of 20-40%. The benefit of adjuvant chemotherapy (CT) in this setting remains poorly defined. METHODS: Retrospective study of serous BOT+invasive implants treated with adjuvant CT. RESULTS: 36 patients were referred with serous BOTs+invasive implants and treated with surgery and platinum-based CT between 06/1982 and 02/2011. 83% were stage III/IV. Tumors demonstrated microinvasion, micropapillary pattern or desmoplastic implants in 53%, 47% and 67% of cases, respectively. 8% had fertility-sparing surgery. Taking into account initial and completion surgeries, R0 was achieved in 84% (27/32) (NA, N=4). The majority (72%) received a combination of platinum+taxane. 11% of patients experienced a G3/G4 toxicity. 13 of 36 (36%) patients relapsed at a median of 27.3 months after diagnosis of invasive implants. Among 12 patients with histologically confirmed relapse, 8 patients progressed with invasive disease in the form of carcinoma or invasive implants. 5 year PFS/OS were 67%/96%. Neither microinvasion, micropapillary pattern, nor desmoplastic implants predicted relapse. In cases with evaluable disease, an objective response to chemotherapy was observed in 4 of 6 patients. CONCLUSION: This is the largest study of BOT with invasive implants treated with surgery and adjuvant platinum-based CT. Treatment was well tolerated and the invasive relapse rate was 22% (8/36). Although numbers are small, the objective responses suggest a possible role for adjuvant CT in BOTs with invasive implants.

Malignant germ cell-like tumors, expressing Ki-1 antigen (CD30), are revealed during in vivo differentiation of partially reprogrammed human-induced pluripotent stem cells.

Because many of the genes used to produce induced pluripotent stem cells (iPSCs) from somatic cells are either outright established oncogenes, such as c-myc and Klf4, or potentially related to tumorigenesis in various cancers, both the safety and the risks of tumorigenesis linked to iPSC generation require evaluation. In this work, we generated, by lentivirus-mediated gene transfer of Oct4, Sox2, Nanog, and Lin28, two types of iPSCs from human mesenchymal stem cells and human amniotic fluid-derived cells: fully reprogrammed iPSCs with silencing of the four transgenes and partially reprogrammed iPSCs that still express one or several transgenes. We assessed the behavior of these cells during both their differentiation and proliferation using in vivo teratoma assays in nonobese diabetic mice with severe combined immunodeficiency. In contrast to fully reprogrammed iPSCs, 43% of partially reprogrammed iPSC cases (6 of 14 teratomas) generated major dysplasia and malignant tumors, with yolk sac tumors and embryonal carcinomas positive for α-fetoprotein, cytokeratin AE1/AE3, and CD30. This correlated with the expression of one or several transgenes used for the reprogramming, down-regulation of CDK 1A mRNA (p21/CDKN1A), and up-regulation of antiapoptotic Bcl-2 mRNA. Therefore, the oncogenicity of therapeutically valuable patient-specific iPSC-derived cells should be scrupulously evaluated before they are used for any clinical applications.

A new policy regarding ovarian resection in young women treated for peritoneal carcinomatosis.

OBJECTIVE: To appreciate if the ovaries can be preserved in selected young women with peritoneal carcinomatosis (PC). BACKGROUND: The traditional rule is to resect the ovaries systematically when PC is found at surgery. METHODS: A new policy was developed to preserve the ovaries when they were macroscopically normal in young women with PC of different origin who expressed a strong desire for future pregnancy. RESULTS: A total of 106 women younger than age 41 years underwent complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy. At least one ovary was preserved in 29 % of them (and in 44 % of those who strongly wished future pregnancy). Among resected "normal" ovaries, 17 % were involved by tumor at the final pathologic examination. Among the resected "suspicious" ovaries, 38 % were involved. Among the 29 preserved ovaries (in 21 women), after a median follow-up of 32 months, 4 (14 %) developed ovarian recurrence, in 3 of them associated with other metastases. Two women became pregnant. In five women with partially normal ovary, egg harvesting and cryopreservation was performed. CONCLUSIONS: This new policy allowed ovarian preservation in 44 % of the young women wishing childbearing and allowed two births. Recurrence in the preserved ovary was 14 % with our criteria of selection. This policy is promising but can be further improved.

Placental site and epithelioid trophoblastic tumours: diagnostic pitfalls.

OBJECTIVE: To describe the clinical and histological pitfalls in the diagnosis of placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT), two rare types of gestational trophoblastic neoplasia (GTN). METHODS: This retrospective, observational, study was carried out in the French Trophoblastic Disease Reference Centre, Lyon, between 2000 and 2011. Due to the many similarities in the diagnosis, treatment and prognosis of PSTT and ETT, these two types of tumour were investigated together. Twenty-two patients with PSTT or ETT were analysed. RESULTS: The clinical presentation of these two types of tumour was irregular vaginal bleeding (55%) or amenorrhoea (27%), with a median plasma hCG level of 205IU/L. Seven of the 22 patients (32%) were initially misdiagnosed as an ectopic pregnancy. Median age at presentation was 35-years, with a median interval of 12months between the antecedent pregnancy and diagnosis of PSTT or ETT. The initial histological diagnosis was incorrect in 7/18 (39%) patients; there was a major disagreement with the referral pathologist in five of these seven patients (28%). CONCLUSIONS: PSTT and ETT are the most difficult types of GTN to diagnose clinically and histologically. An incorrect diagnosis can lead to significant therapeutic deviations from the recommended first-line treatment, namely hysterectomy. Clinical and histological expertise is essential to avoid the pitfalls in the diagnosis of PSTT and ETT.

Sentinel lymph node in endometrial cancer: a review.

Lymph node status is a major prognostic factor in endometrial cancer (EC). Sentinel lymph node (SLN) biopsy has been reported in EC for more than 15 years but has not yet been incorporated as a standard-of-care procedure in EC. Complex uterine drainage, the various modalities of tracer injection, and the lack of large prospective series may explain this situation. In this review, we report an SLN detection rate of 81.7 %, a 10.9 % rate of metastatic SLN involvement, and a false-negative rate of 12.3 % in the main clinical trials. Thirty-five percent of SLN metastases were low-volume disease (micrometastases or isolated tumor cells). These data raise the question of the clinical significance of low-volume disease in EC. SLN biopsy could allow upstaging in supposedly low- or intermediate-risk patients in whom adjuvant therapy could be omitted. Further studies are required to precise the interest on the survival of this procedure in this subset of patients.

Villoglandular papillary adenocarcinoma of the cervix: a series of 28 cases including two with lymph node metastasis.

OBJECTIVE: To investigate the clinicopathologic features, the management, and the outcome of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix. METHODS: A retrospective review of patients' clinical characteristics, pathology, and the disease management, together with outcome information. RESULTS: A total of 28 patients with VGPA were treated. The median age of the patients was 38 years with a range of 26 to 65 years. Sixteen of the 21 patients presented with abnormal bleeding, and 5 patients had an abnormal Papanicolaou (Pap) test result. Nineteen patients had International Federation of Gynecology and Obstetrics stage IB disease, and 5 patients had stage IIB disease. Two of 24 patients, where the lymph node status was known, had positive nodes. Twenty patients underwent different types of radical surgery with or without pelvic radiotherapy, and 8 patients received platinum-based chemotherapy and pelvic radiotherapy with no surgery. The follow-up ranged from 5 to 168 months with a median of 35 months. Twenty-one patients are alive with no evidence of recurrent disease, 5 patients have died because of the disease recurrence, and 2 patients were lost to follow-up. The overall and disease-free 5-year survival for these patients was 82% and 75%, respectively. CONCLUSION: This study confirms the excellent prognosis of VGPA overall compared to the common forms of cervical cancer, but the prognosis is related to stage and pathology. A large multicenter prospective study is warranted to determine the most appropriate treatment for the disease. Until then, a meta-analysis on the subject would be of benefit.

Analysis of a continuous series of 34 young patients with early-stage cervical cancer selected for a vaginal radical trachelectomy: should "staging" conization be systematically performed before this procedure?

OBJECTIVE: Vaginal radical trachelectomy (VRT) is the most widely evaluated form of conservative management of young patients with early-stage (IB1) cervical cancer. Patients with nodal involvement or a tumor size greater than 2 cm are not eligible for such treatment. The aim of this study is to report the impact of a "staging" conization before VRT. METHODS: This is a retrospective study of 34 patients potentially selected for VRT for a clinical and radiologic cervical tumor less than 2 cm. Among them, 28 underwent finally a VRT (20 of them having a previous conization before this procedure) and 6 patients with macroscopic cervical cancer, confirmed by punch biopsies, "eligible" for VRT (<2 cm) had undergone "staging" conization (without further VRT) to confirm the tumor size and lymphovascular space involvement (LVSI) status. RESULTS: Six patients having "staging" conization before VRT had finally been deemed contraindications to VRT due to the presence of a histologically confirmed tumor greater than 2 cm and/or associated with multiple foci of LVSI. Among 28 patients who underwent VRT, 1 received adjuvant chemoradiation (this patient recurred and died of disease). Two patients treated with RVT (without postoperative treatment) recurred. Ten pregnancies (9 spontaneous and 1 induced) were observed in 9 patients. Among 4 patients with macroscopic "visible" tumor who do not underwent a "staging" conization before VRT, 2 recurred. Among 11 patients who underwent VRT and having LVSI, 3 recurred. CONCLUSIONS: These results suggest that if a conization is not performed initially, it should then be included among the staging procedures to select patients for VRT.

Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence.

By comparison with ovarian carcinomas, borderline ovarian tumours are characterised clinically by superior overall survival, even in women with peritoneal spread. In this Review, we aimed to clarify the histological and clinical factors potentially defining a high-risk group in whom disease is likely to evolve to invasive disease. Invasive peritoneal implants (in serous borderline ovarian tumours) and residual disease after surgery were the two factors clearly identified. Other factors are controversial owing to increased risk of invasive recurrence: micropapillary patterns in serous borderline ovarian tumour, intraepithelial carcinoma in mucinous lesions, stromal microinvasion in serous lesions, and use of cystectomy in mucinous borderline ovarian tumours. The pathologist has a pivotal role in assessment of the borderline nature of ovarian tumours and in identification of high-risk criteria, most of which are histological. But, reproducibility of the histological interpretation of some of these potential criteria--eg, classification of peritoneal implants (particularly in desmoplastic subtype), stromal microinvasion, micropapillary patterns, and intraepithelial carcinoma in mucinous borderline ovarian tumours--remains unclear, and should be investigated.

Management and prognosis of borderline ovarian Brenner tumors.

OBJECTIVE: The borderline ovarian Brenner tumor (BOBT) of the ovary is a rare tumor, and fewer than 25 cases have been reported in the literature. The aim of this study was to determine the prognosis of a series of BOBT collected in 2 reference centers. METHODS: A retrospective review of patients with BOBT treated or referred to our institutions. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion. RESULTS: Ten patients were identified between 2000 and 2010. The median age of patients was 69 years (range, 52-84 years). Eight patients had pure BOBT and 2 had mixed histotype (mucinous and Brenner tumor). All patients had unilateral tumor and a stage I disease. No case of stromal microinvasion or intraepithelial carcinoma was observed. Among 5 patients with data on the follow-up, 1 lethal recurrence (50 months after initial surgery) was observed (the first reported in the literature). CONCLUSIONS: During the management of BOBT, peritoneal staging surgery is not required because all patients reported in the present series (and all but one in the literature) had stage I disease. One recurrence had occurred in this retrospective series. Nevertheless, among 35 cases (including those in the present study) reported in the literature with outcomes, this tumor carries a good prognosis. The power of this conclusion is, however, limited because of the relatively small number of patients studied (but this is a rare entity) and the short follow-up period.

Management and prognosis of clear cell borderline ovarian tumor.

BACKGROUND: The clear cell borderline ovarian tumor (CCBOT) of the ovary is a rare tumor accounting for less than 1% of BOT. Fewer than 25 cases have been reported in the literature (including details on clinical management and outcomes). The aim of this study was to determine the prognosis of a series of CCBOTs collected in 2 reference centers. PATIENTS AND METHODS: This was a retrospective review of patients with CCBOT treated or referred to our institutions. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion. RESULTS: Twelve patients were identified between 2000 and 2010. The median age of patients was 68 years (range, 36-83 years). Two had been treated conservatively and 9 radically (data unknown in 1). The tumor was unilateral in 11 cases. All patients had stage I disease. All cases were CCBOT with an adenofibromatous pattern. Stromal microinvasion or intraepithelial carcinoma was histologically associated in 2 and 3 cases, respectively. Four of the 12 patients had synchronous endometrial disorders (but no endometrioid carcinoma). No cases were histologically associated with endometriosis. Four patients were lost to follow-up. Among 8 other patients, after a median period of 28 months (range, 2-129 months), no recurrence had occurred (1 patient had died of another disease). CONCLUSION: Clear cell borderline ovarian tumor carries a good prognosis. All tumors are stage I; therefore, surgical staging is not necessary in most of the cases. Conservative treatment could be proposed to young patients, but uterine curettage would then be required in cases of uterine preservation.

Clear cell adenocarcinoma of the female genital tract: long-term outcome and fertility aspects after brachytherapy aimed at a conservative treatment.

OBJECTIVES: To assess the outcome and the fertility aspects in the particular population of cervical and/or vaginal clear cell adenocarcinoma (CCA) associated or not to previous in utero diethylstilbestrol exposure. METHODS: From January 1970 to December 2003, data from 61 consecutive patients with cervical and/or vaginal histologically proven CCA treated with brachytherapy (BT) aimed at a conservative treatment at the Institut Gustave Roussy as a part of treatment were retrospectively analyzed. RESULTS: The median follow-up was 9.4 years, ranging from 0.3 to 27.4 years. The 5-year specific overall survival rate was 79%. The median time of disease-free survival was 5.8 years. In the subgroup of 42 patients with a cervical CCA, 12 patients tried to be pregnant, 2 patients became pregnant and had miscarriages (P2M2 and P1M1). No pregnancy has been observed in 10 patients exclusively owing to anomalies of the reproductive tract: 6 patients had partial or total diaphragm, 2 patients had an anatomical alteration of the uterus, 1 patient had atrophic endometrium, and 1 patient had primary infertility. In the subgroup of 19 patients with a vaginal CCA, 7 patients tried to be pregnant. All of them had no morphological and/or functional anomalies of the genital tract. Three of 7 patients had delivered healthy babies (P1D1, P2D2, and P3M2D1), and another one had a miscarriage (P1M1). Moreover, all babies were delivered by cesarean section. The pregnancy rate was 10% (6 of 61 patients) with 3 healthy babies. CONCLUSION: Conservative approach in patients with female genital tract CCA including BT gives good results with good survival rates and an interesting global pregnancy rate.

Low-dose-rate definitive brachytherapy for high-grade vaginal intraepithelial neoplasia.

BACKGROUND: Treatment of high-grade vaginal intraepithelial neoplasia (VAIN) is controversial and could include surgical excision, topical medication, brachytherapy, or other treatments. We report the results of low-dose-rate (LDR) vaginal brachytherapy for grade 3 VAIN (VAIN-3) over a 25-year period at Gustave Roussy Institute. PATIENTS AND METHODS: We retrospectively reviewed the files of all patients treated at Gustave Roussy Institute for VAIN-3 since 1985. The treatment consisted of LDR brachytherapy using a personalized vaginal mold and delivered 60 Gy to 5 mm below the vaginal mucosa. All patients had at least an annual gynecological examination, including a vaginal smear. RESULTS: Twenty-eight patients were eligible. The median follow-up was 41 months. Seven patients had a follow-up <2 years, and the median follow-up for the remaining 21 patients was 79 months. The median age at brachytherapy was 63 years (range, 38-80 years). Twenty-six patients had a history of VAIN recurring after cervical intraepithelial neoplasia and 24 had a previous hysterectomy. The median brachytherapy duration was 4.5 days. Median doses to the International Commission of Radiation Units and Measurements rectum and bladder points were 68 Gy and 45 Gy, respectively. The median prescription volume (60 Gy) was 74 cm(3). Only one "in field" recurrence occurred, corresponding to a 5- and 10-year local control rate of 93% (95% confidence interval, 70%-99%). The treatment was well tolerated, with no grade 3 or 4 late toxicity and only one grade 2 digestive toxicity. No second cancers were reported. CONCLUSION: LDR brachytherapy is an effective and safe treatment for vaginal intraepithelial neoplasia.

Prognosis and prognostic factors of the micropapillary pattern in patients treated for stage II and III serous borderline tumors of the ovary.

BACKGROUND: To determine the prognosis of a micropapillary (MP) pattern in patients with stage II and stage III serous borderline tumor of the ovary (SBOT). METHODS: Review of patients with stage II and stage III SBOT treated or referred to our institution with characterization of an MP pattern and its clinical impact. RESULTS: In 1969-2006, 168 patients were reviewed. Fifty-six patients had SBOT-MP. The rate of conservative surgery was lower in the SBOT-MP group than in the typical SBOT group, but the rate of patients with more than three peritoneal sites with implants was higher in the SBOT-MP group. The rate of invasive implants was not statistically different between the two groups. Eighteen recurrences were observed (six of them in the form of invasive disease) in the SBOT-MP group. Only one death was observed. The overall survival times and recurrence-free intervals were similar in both groups. The only prognostic factor for recurrence in the SBOT-MP group was the use of conservative surgery. CONCLUSIONS: In the present series, an MP pattern doesn't appear to signify a poor prognosis. The only prognostic factor for recurrence in SBOT-MP was the use of conservative surgery. Further studies on the MP pattern are needed to evaluate prognosis and the results of conservative surgery.