Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer.

Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation. Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (κ). Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 0.70). Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over- or undertreatment, especially when treatment modalities with substantial toxicity are involved. This study is registered with ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov (NCT00411138).

Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma.

There is no standard for second-line chemotherapy in poorly differentiated grade 3 neuroendocrine carcinoma (G3-NEC) patients. We analyzed the antitumor efficacy of 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy in this population. A single-center retrospective analysis of consecutive G3-NEC patients treated with FOLFOX chemotherapy after failure of a cisplatinum-based regimen between December 2003 and June 2012 was performed. Progression-free survival (PFS), overall survival (OS), response rate, and safety were assessed according to RECIST 1.1 and NCI.CTC v4 criteria. Twenty consecutive patients were included (seven males and 13 females; median age 55; range 23-87 years) with a performance status of 0-1 in 75% of them. Primary location was gastroenteropancreatic in 12, thoracic in four, other in two, and unknown in two patients. There were 12 (65%) large-cell and 7 (30%) small-cell G3-NEC tumors, and 1 (5%) unknown. All patients had distant metastases. Twelve (60%) patients received FOLFOX as second-line treatment and 8 (40%) as third-line treatment or later and the median number of administered cycles was 6 (range 3-14). The median follow-up was 19 months. Median PFS was 4.5 months. Among the 17 evaluable patients, five partial responses (29%), six stable diseases (35%), and six progressive diseases (35%) were observed. Median OS was 9.9 months. Main Grade 3-4 toxicities were neutropenia (35%), thrombopenia (20%), nausea/vomiting (10%), anemia (10%), and elevated liver transaminases (10%). Our results indicate that the FOLFOX regimen could be considered as a second-line option in poorly differentiated G3-NEC patients after cisplatinum-based first-line treatment but warrant further confirmation in future larger prospective studies.

Actinomycin D, cisplatin, and etoposide regimen is associated with almost universal cure in patients with high-risk gestational trophoblastic neoplasia.

BACKGROUND: Patients with high-risk gestational trophoblastic neoplasia (GTN) need multi-agent chemotherapy to be cured. The most common regimen is etoposide (E), methotrexate (M) and actinomycin D (A), alternating weekly with cyclophosphamide (C) plus vincristine (O) (EMA/CO). Cisplatin (P) is a very active drug, but it is usually restricted to second-line therapies. Herein, we report the results of a cisplatin-based therapy: APE (actinomycin D, cisplatin, and etoposide). PATIENTS AND METHODS: The efficacy and safety of APE for high-risk GTN (defined by Institut Gustave-Roussy (IGR) criteria and/or an International Federation of Gynaecology and Obstetrics (FIGO) score >6) are reported. Patients with brain metastasis or placental-site trophoblastic tumour were excluded. RESULTS: Between 1985 and 2013, 95 patients were treated with APE for high-risk GTN: 59 patients as first-line, 36 as ⩾ 2nd-line therapy. There was 94.7% complete remission, though five patients relapsed. One patient died from GTN after multiple lines of chemotherapy. The five-year overall survival rate (median follow-up 5.7 years) was 97% (95% confidence interval (CI): 91-99%). No death from toxicity occurred. Long-term, six grade-1 neuro-toxicities, three grade-1 and two grade-2 oto-toxicities, and one grade-1 renal toxicity were recorded. One patient developed AML-M4 after APE and EMA/CO. Thirty-four of 35 women, who wished to become pregnant, succeeded and all had at least one live birth. CONCLUSION: With a 97% long-term overall survival rate, limited long-term toxicity, and an excellent reproductive outcome, APE could be regarded as an alternative option to EMA/CO as a standard therapy for high-risk GTN.

Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments.

BACKGROUND: The overall prognosis of stage I borderline ovarian tumors (BOT) is excellent but a small percentage of patients die to their disease. The prognostic factors for such a rare event are still not clearly defined. The aim of this study was to determine these factors for recurrence per se and recurrence in the form of invasive carcinoma in a large series of stage I tumors. METHODS: A retrospective review of patients with BOT. Three inclusion criteria were defined: (i) a centralized histological review; (ii) macroscopic stage I tumors; (iii) exclusion of metastatic disease to the ovaries. RESULTS: From 2000 to 2010, 254 patients fulfilled inclusion criteria [140 had mucinous BOT (MBOT) and 114 a serous BOT (SBOT)], and 191 had undergone conservative management. After a median follow-up of 45 months, 43 patients had developed recurrences (31 borderline and 12 invasive). The risks of recurrences were statistically increased after conservative treatment, particularly after a cystectomy, in patients with stage IB and among patients with incompletely staged tumors. In the subgroup of conservatively treated patients (representing 75% of our population), the risks of recurrences were statistically increased in patients affected by a SBOT, in patients who had undergone a cystectomy, in patients with stage IB disease and in patients with a micropapillary pattern (MPP). MBOT and the presence of a MPP were identified as prognostic factors for invasive disease. CONCLUSIONS: In the present series of BOT with the largest number of patients treated conservatively to date, the presence of a MPP and the mucinous subtype were associated with a higher rate of progression to carcinoma after conservative management. These important results suggest that MBOT belong to a 'high-risk' group likely to develop an invasive recurrence after fertility-sparing surgery in stage I BOT.

Prognostic factors for recurrence after conservative treatment in a series of 119 patients with stage I serous borderline tumors of the ovary.

BACKGROUND: The aim of this study was to evaluate prognostic factors for recurrence after conservative treatment of a large series of 'apparent' stage I serous borderline ovarian tumors (SBOTs). PATIENTS AND METHODS: A review of 119 patients treated conservatively between 2000 and 2009 with follow-up data. All pathological slides were reviewed by the same expert pathologist. Prognostic factors for recurrence were studied (age, histological subtypes and surgical procedure). RESULTS: Conservative surgical procedures were: unilateral cystectomy (n = 43, 36%); unilateral adnexectomy (UA; n = 50, 42%); bilateral cystectomies (n = 11, 9%) and UA + contralateral cystectomy (n = 15, 13%). Stromal microinvasion and/or a micropapillary pattern was present in 21 (18%) and 13 (11%) patients, respectively. With a median follow-up of 45 months, 38 (32%) patients relapsed (10 also had peritoneal disease in the form of noninvasive implants at the first recurrence). In 2 of these 38 patients, progression-to-invasive disease occurred at the second and third relapse (one patient died to the recurrence). Three prognostic factors for recurrence were identified in the univariate analysis: a young age (< or >30 years old), the type of conservative treatment (adnexectomy versus cystectomy) and tumor bilaterality. In the multivariate analysis, only age remained statistically significant. CONCLUSION: In this series (the largest reported, to date, on recurrences after the conservative management of stage I SBOT), the risk of relapse was not related to tumor histological subtypes (micropapillary and stromal microinvasion) nor to the use of complete staging surgery. Invasive recurrences were very rare in stage I SBOT, but did occur. A young age, tumor bilaterality and the use of a cystectomy were identified as risk factors for recurrence, suggesting that management of fertility preservation (particularly in very young patients) should be associated with a meticulously conducted follow-up.

Comprehensive study of ovarian metastases in young women with peritoneal pseudomyxoma: is a preservation of fertility possible?

OBJECTIVE: To determine whether ovaries can be preserved in selected young women with peritoneal pseudomyxoma (PMP). BACKGROUND DATA: The traditional rule is to systematically perform a bilateral oophorectomy. PATIENTS AND METHODS: A new policy was developed to preserve the ovaries when they are macroscopically normal in young women with PMP, strongly desiring a future pregnancy. RESULTS: Thirty-three women younger than 41 years were selected after undergoing complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for PMP. A normal ovary was preserved in 6 of them, but in 6 of the 14 women who strongly desired a future pregnancy. Subsequently, ovarian preservation was only performed in cases of grade-1 PMP. Ovarian invasion was correlated with the grade (p < 0.05) and with the extent of peritoneal disease (p < 0.01). After a median follow-up of 54 months, none of the 6 women with preserved ovaries has developed an ovarian or a peritoneal recurrence. One woman became pregnant and egg harvesting and cryopreservation were performed for 4 women with a partially normal ovary. CONCLUSION: This new policy allowed ovarian preservation in 43% of the young women desiring a future pregnancy and has already resulted in one birth. It exclusively concerned low-grade PMP. Recurrence in the preserved ovary was 0% with our selection criteria.

A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group.

BACKGROUND: There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. METHODS: Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. RESULTS: Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). CONCLUSION: API adjuvant CT statistically increases the 3 year-DFS of patients with US.

Management and prognosis of endometrioid borderline tumors of the ovary.

BACKGROUND: The Endometrioid Borderline ovarian tumor (EBOT) is the third most common histological subtype of borderline ovarian tumors. Very little is known about the prognosis and management of this entity. This paper consists of a review of the literature and an analysis of clinical series. STUDY DESIGN: A review of the literature on this topic was conducted identifying series reporting consecutive cases of EBOT using 2 search engines (MEDLINE and Pubmed). Personal data on this topic have been included and concern a series of patients treated between 1985 and 2009 for EBOT. These cases included in this series had complete data concerning patient management and follow-up > 12 months. RESULTS: 16 patients were studied: 7 had been treated conservatively and 9 radically. All 16/16 patients had stage I disease at the initial diagnosis but one patient had also developed synchronous endometrioid adenocarcinoma of the uterine corpus. After a median time of 24 months (range, 12-132) post treatment, one (1/16) patient had developed two recurrences. She remains disease-free 42 months after the end of treatment of the last recurrence. These data were compared to the results of 4 series previously reported in the literature. In fact, the present series reports on the first recurrence in EBOT (which was an invasive lesion). CONCLUSION: Endometrioid borderline ovarian tumors carry a good prognosis. Most EBOT tumors are stage I, therefore surgical staging is not necessary in most of the cases. However, uterine curettage is required in cases of uterine preservation.

Prognostic factors for and prognostic value of mesenteric lymph node involvement in advanced-stage ovarian cancer.

AIM OF THIS STUDY: To determine the prognosis of and prognostic factors for mesenteric node involvement in patients undergoing a bowel resection at the time of debulking surgery for primary treatment of advanced-stage ovarian cancer (ASOC). METHODS: A retrospective review of patients treated between 2005 and 2008 for ASOC and undergoing initial and interval debulking surgery with bowel resection (whatever the bowel segment). The characteristics and prognostic impact of mesenteric node involvement were studied. RESULTS: During the study period, 52 patients underwent debulking surgery for ASOC with bowel resection. Eighteen and 34 patients underwent initial or interval debulking surgery respectively. The most frequent site of the bowel resection was the rectosigmoid colon (38 patients; 73%) and 12 patients had resection of at least 2 intestinal segments. All patients had a complete macroscopic resection of peritoneal disease. Nineteen patients (37%) had mesenteric node involvement with a median of 4 involved nodes (range, 1-12). The degree of involvement of the intestinal wall and retroperitoneal node involvement (pelvic or para-aortic) had no impact on the risk of mesenteric node involvement. Overall survival and the location of recurrent disease were similar in patients with or without spread to mesenteric nodes. CONCLUSIONS: This study suggests that mesenteric node involvement is frequent in patients undergoing bowel resection in ASOC. Such spread does not appear to have an impact on patient survival. Modifying peroperative (particularly the extent of the mesocolon resection) or postoperative management is therefore unnecessary.

[The accuracy of FDG-PET/CT in early-stage cervical and vaginal cancers]. / Intérêt de la TEP-FDG dans les cancers du col de l'utérus et du vagin de stade précoce.

OBJECTIVE: [(18)F]fluoro-deoxy-glucose positron-emission tomography combined with integrated computed tomography (FDG-PET/CT) is commonly used for advanced stage cervical cancer but its efficiency is discussed in early stage. The aim of this study was to evaluate false negative rate of FDG-PET/CT in early-stage cervical and vaginal cancer. PATIENTS AND METHODS: Patients treated between 2005 and 2008 for stage IB1 cervical cancer and stage I vaginal cancer who underwent a FDG-PET/CT followed by a pelvic lymphadenectomy were studied. RESULTS: Eighteen patients were included with bilateral pelvic lymphadenectomy (16 cervical cancer, two vaginal cancer). The median age of patients was 41 years. Radical hysterectomy was performed for 16 patients, by a laparoscopic approach in 15 cases and by a laparotomic approach in one case. One patient had a simple hysterectomy and one had exclusive radiotherapy. No patient had pelvic or para-aortic fixation on FDG-PET/CT. Three patients have proven pelvic involvement and one had para-aortic metastases. The false-negative rate and negative predictive value of FDG-PET/CT were 17% and 83% respectively. DISCUSSION AND CONCLUSION: The accuracy of FDG-PET/CT imaging in predicting the pelvic nodal status is very low in patients with early-stage cervical and vaginal cancer and is not able to replace surgical exploration.

How to follow up advanced-stage borderline tumours? Mode of diagnosis of recurrence in a large series stage II-III serous borderline tumours of the ovary.

BACKGROUND: The aim of this study was to describe how recurrences were diagnosed in the largest series of patients treated for an advanced-stage serous borderline ovarian tumour. PATIENTS AND METHODS: From 1973 to 2006, 45 patients with a serous borderline tumour and peritoneal implants relapsed among 162 patients with a follow-up exceeding 1 year. Data concerning recurrences and the mode of diagnosis were reviewed. RESULTS: The median follow-up interval was 8.2 years (range 19-286 months). The mode of diagnosis of recurrences was imaging (n = 19), clinical symptoms (n = 8), cancer antigen (CA) 125 elevation (n = 7), secondary surgery (n = 5) and unknown (n = 6). The median time to recurrence was 31 months (range 4-242 month). The type of recurrence was invasive low-grade serous carcinoma in 14 patients. Five patients died of recurrent tumour. Among the 39 patients with a known mode of diagnosis of recurrence, the most frequent diagnostic method for invasive recurrences was blood CA 125 elevation (6 of 13) and the majority of noninvasive recurrences were diagnosed by imaging (16 of 23). CONCLUSIONS: This study demonstrates that ultrasound is the most relevant follow-up procedure in this context. Nevertheless, the blood CA 125 test is of particular interest for detecting invasive recurrent disease, which is the most crucial event.

[Melanoma in HIV patients: 14 cases]. / Mélanomes chez des patients séropositifs pour le VIH : 14 cas.

BACKGROUND: a clinical study of 14 patients presenting both malignant melanoma and HIV infection, and analysis of the literature to determine the frequency and specific features of this association. PATIENTS AND METHODS: ten men and four women of median age 43 years were included. In 50% of cases, the primary melanoma consisted of spreading superficial melanoma with a mean Breslow thickness of 2.83 mm. In two cases, regional lymph node metastasis was discovered but with no primary melanoma being identified. HIV infection was already documented on diagnosis of melanoma in 11 cases, and it was discovered in three cases at the time of surgery for melanoma (treatment of the primary melanoma in two cases, and in one case, regional lymph node dissection two years after the initial diagnosis). Eight patients died within a mean period of 39 months, with melanoma being the cause of death in six cases. Following relapse of melanoma, the course of the disease was severe, with mean stage IV survival of 3.6 months. No response to chemotherapy was observed where such treatment was feasible. DISCUSSION: the presence of HIV appears to be an aggravating factor for the outcome of metastatic melanoma. CONCLUSION: our study suggests the importance of clinical examination of pigmented lesions in HIV patients in order to ensure early identification of melanoma.

[Postoperative morbidity after completion surgery following homogeneous chemoradiation therapy in locally advanced cervical cancer]. / Morbidité de la chirurgie de clôture après radio-chimiothérapie chez des patientes atteintes d'un cancer du col de stade avancé.

OBJECTIVE: To evaluate the morbidity rate in patients following completion surgery (hysterectomy±lymphadenectomy) after chemoradiation therapy (CRT) for an advanced stage cervical cancer. PATIENTS AND METHODS: Patients fulfilling the following inclusion criteria were studied: (1) stage IB2-IVA cervical carcinoma; (2) tumor initially confined to the pelvic cavity; (3) pelvic external radiation therapy with delivery of 45Gy with concomitant chemotherapy (cisplatin 40mg/m(2)/week) followed by utero-vaginal brachytherapy; (4) completion surgery after the end of radiation therapy including at least a hysterectomy. RESULTS: One-hundred and fifty patients treated between 1998 and 2007 fulfilled inclusion criteria. Thirty-seven (25%) patients had 55 post-operative complications (17 had severe complications requiring surgical or radiological treatment). Two deaths related to postoperative morbidity had occurred. The risk of complications was increased with a radical hysterectomy (OR=2.4; P=0.04) and the presence of residual cervical disease (≤1cm: OR=4.3, >1cm: OR=2.5; P=0.01). CONCLUSION: In the present study, the morbidity of completion surgery (based on hysterectomy with or without lymphadenectomy) is very high in patients treated with initial CRT for locally advanced cervical cancer whereas the therapeutic value of such surgery remains unproven.

[Para-aortic lymphadenectomy in advanced-stage cervical cancer: standard procedure in 2010?]. / Lymphadénectomie lomboaortique dans les cancers du col de stade avancé : un standard en 2010 ?

With tumour size, node involvement is the most important prognosis factor in advanced stage cervical cancer. Para-aortic (PA) disease is observed in 15 to 30% of these patients. CT scan and magnetic resonance imaging (MRI) are not efficient enough to detect these lesions and PET CT have false negatives. Surgical staging is useful to detect carcinosis associated and to adapt therapy (radiotherapy fields are extended if PA nodes are involved). Laparoscopy was crucial to develop this staging because its morbidity associated to chemoradiotherapy is limited. If prognosis impact of PA lymphadenectomy is well established, therapeutic impact is still discussed. The systematic extension of this staging to pelvic nodes that are included in the basic radiotherapy fields is debated because it does not modify therapeutic management and is morbid. Radiotherapy progress, especially with boost and combination to MRI (MRIT), will impact on future therapeutic management.

[Tumour regression is not predictive for higher risk of sentinel node involvement in thin melanomas (Breslow thickness < or = 1 mm)]. / La régression tumorale n'est pas un facteur de risque d'atteinte du ganglion sentinelle dans les mélanomes fins (indice de Breslow < or = 1 mm).

BACKGROUND: Thin melanomas (Breslow thickness < or = 1 mm) are considered highly curable. The aim of this study was to evaluate the correlation between histological tumour regression and sentinel lymph node (SLN) involvement in thin melanomas. PATIENTS AND METHODS: This was a retrospective single-centre study of 34 patients with thin melanomas undergoing SLN biopsy between April 1998 and January 2005. RESULTS: The study included 14 women and 20 men of mean age 56.3 years. Melanomas were located on the neck (n=3), soles (n=4), trunk (n=13) and extremities (n=14). Pathological examination showed 25 SSM, four acral lentiginous melanomas, three in situ melanomas, one nodular melanoma and one unclassified melanoma with a mean Breslow thickness of 0.57 mm. Histological tumour regression was observed in 26 over 34 cases and ulceration was found in one case. Clark levels were as follows: I (n=3), II (n=20), III (n=9), IV (n=2). Growth phase was available in 15 cases (seven radial and eight vertical). Mitotic rates, available in 24 cases, were: 0 (n=9), 1 (n=11), 2 (n=2), 3 (n=1), 6 (n=1). One patient with histological tumour regression (2.9% of cases and 3.8% of cases with regressing tumours) had a metastatic SLN. One patient negative for SLN had a lung relapse and died of the disease. Mean follow-up was 26.2 months. CONCLUSION: The results of the present study and the analysis of the literature show that histological regression of the primary tumour does not seem predictive of higher risk of SLN involvement in thin melanomas. This suggests that screening for SLN is not indicated in thin melanomas, even those with histological regression.

Impact of adjuvant treatment modalities on the management of patients with stages I-II endometrial stromal sarcoma.

PURPOSE: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination. PATIENTS AND METHODS: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out. RESULTS: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005). CONCLUSIONS: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence.

Sunitinib efficacy in the treatment of metastatic skin adnexal carcinomas: report of two patients with hidradenocarcinoma and trichoblastic carcinoma.

BACKGROUND: Adnexal carcinomas are rare and diverse cutaneous tumours. They are locally aggressive and have the potential for distant metastasis. Metastatic adnexal carcinomas are very resistant to conventional chemotherapies. Sunitinib, an oral tyrosine kinase inhibitor, is reportedly effective for the treatment of various solid cancers. Its use in adnexal carcinomas has never been reported. OBSERVATIONS: The first patient had metastatic clear cell hidradenocarcinoma and was stabilized over 8 months with sunitinib, before she relapsed. The second patient had a metastatic malignant hair follicle tumour (trichoblastic carcinoma) and achieved a partial remission with sunitinib, and disease stabilized after 10 months. Dynamic contrast-enhanced ultrasound (DCE-US) performed to evaluate tumour vascularization during treatment depicted a dramatic and early decrease in the tumour blood volume. CONCLUSIONS: Sunitinib was effective in controlling the disease in our two patients. DCE-US using linear raw data may have an early predictive value for tumour response to sunitinib. Further studies involving larger cohorts of patients are warranted in order to confirm the efficacy of sunitinib in these rare tumours.

Outcomes after conservative treatment of advanced-stage serous borderline tumors of the ovary.

BACKGROUND: The aim of this study was to assess the outcomes of the largest series of patients treated conservatively for a stage II or III serous borderline ovarian tumor. MATERIALS AND METHODS: From 1969 to 2006, 41 patients were treated conservatively for an advanced-stage serous borderline ovarian tumor. Patient outcomes were reviewed. RESULTS: Twenty patients had undergone a unilateral salpingo-oophorectomy, 18 a unilateral cystectomy and two bilateral cystectomy (unknown for one patient). Three patients had invasive implants. The median duration of follow-up was 57 months (range 4-235). The recurrence rate was high (56%), but overall survival remained excellent (100% at 5 years, 92% at 10 years). One death had occurred due to an invasive ovarian recurrence. Eighteen pregnancies (nine spontaneous) were observed in 14 patients. CONCLUSIONS: This study demonstrates that spontaneous pregnancies can be achieved after conservative treatment of advanced-stage borderline ovarian tumors (with noninvasive implants) but the recurrence rate is high. Nevertheless, this high rate has no impact on survival. Conservative surgery can be proposed to patients with a borderline tumor of the ovary and noninvasive peritoneal implants. Should infertility persist following treatment of the borderline tumor, an in vitro fertilization procedure can be cautiously proposed.

[Rare ovarian tumours: therapeutic strategies in 2010, national website observatory for rare ovarian cancers and delineation of referent centers in France]. / Les tumeurs rares de l'ovaire: stratégies thérapeutiques en 2010, Observatoire francophone des tumeurs rares de l'ovaire et émergence des centres de références.

Majorities of the rare ovarian cancers were represented by germ cell tumours and sex cords ovarian tumours with borderline tumours, clear cell carcinoma and mucinous carcinoma and are extremely rare malignant diseases of the ovaries. Tumors of the stromal (Leydig cells) and/or sex cords (Sertoli cells) represent approximately 7% of ovarian cancers and develop from the conjunctive tissue (respectively, interstitial and nurse cells) of the ovaries. All together, they represented less than 5% of the adult malignant and non malignant ovarian tumours. Treatment of rare ovarian tumors is currently as follows. Surgery is the same as that for ovarian adenocarcinoma, with one major difference: conservation of reproductive function in women of reproductive age is usual case for this type of tumor. Chemotherapy for germ cell and sex cords tumors, based on data reported in the literature is the same as that prescribed for testicular germ-cell tumors. For rare epithelial carcinoma, carboplatin plus paclitaxel remains the standard attitude with a well-known less efficiency than for other epithelial subtypes. Surgery, chemotherapy and possible surgical intervention for residual lesions are highly complex. Too rare to be included in randomized studies, treatment of these tumors has benefited from the therapeutic advancements made against testicular germ-cell tumors or with publications using retrospective data. Effectively, some prognostic factors such stage, histology, number of managed patients seems to be prognostic for survival. Because of the rarity of these tumours a specialized website (www.ovaire-rare.org) was developed in France in 2002. Objectives were: to delineate prognostic factors of these very rare diseases, to favour patient inclusion in a clinical trial available online, to provide access to online medical expert forum (disease-related) for complex cases, and finally to demonstrate the impact of these tools on improving medical practice. The website provides very interesting data for a better knowledge of these rare tumors and will possibly help improve medical practice. Since 2008, referent centers were delineated to promote optimal management of these tumors, organization of clinical and molecular research at a national or international level and to elaborate guidelines. The other new scientific data concern surgical procedures for sex cords tumors, evidence for presence of FOXL2 mutation in adult granulosa cell tumors, the use of paclitaxel plus carboplatin for sex cords tumors.

[First line chemotherapy of advanced epithelial ovarian cancer]. / Chimiothérapie de première ligne des adénocarcinomes ovariens de stades avancés.

The treatment of the advanced ovarian adenocarcinoma, most frequently stage at diagnostic, relies on association of surgery and chemotherapy. The current standard is the association carboplatine-paclitaxel. In spite of this treatment, relapses are frequent, and the prognosis thus remains very reserved. Presently the current areas of research aim at both improving the efficiency of treatments and decreasing their toxicity. So the various trials dealt with the use of the other cytotoxics having proved efficiency against relapses either in double-agent therapy or in association in the current standard, or in the administration of the chemotherapy by intra peritoneal way. They also investigated the possibility of pursuing the therapeutic sequence by a treatment of maintenance or consolidation. As for numerous cancerous pathologies, the targeted therapies, notably the antiangiogenic one, represent an important hope in the treatment of the ovarian cancer.