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.

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.

Antitumour activity of somatostatin analogues in sporadic, progressive, metastatic pulmonary carcinoids.

PURPOSE: Antiproliferative activity of somatostatin analogues (SSAs) has been demonstrated in digestive neuroendocrine tumours but few data have been published on pulmonary carcinoids (PC). The aim of this retrospective study was to report the antitumour activity of SSAs in patients with progressive, metastatic PC. METHODS: Patients with PC and treated with SSA monotherapy were reviewed. Disease was classified according to the tumour slope prior to SSA initiation as rapidly progressive (at least 20% increase in the sum of the longest diameter of target lesions or the appearance of one or more new lesions within 6 months) or slowly progressive (if progression occurred over 6 months). Survival outcomes were progression-free survival (PFS) and overall survival (OS). We additionally examined the overall response rate and safety. Prognostic factors associated with PFS and OS were sought. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox model. RESULTS: Among 67 patients reviewed, 61 were included in the study. Forty-one (67%) of them exhibited slowly progressive disease prior to SSAs, 41 (67%) had atypical carcinoids and 29 (48%) had functioning tumours. Forty-six (76%) patients had received SSAs as first-line therapy. The best overall response was stable disease in 47 (77%) patients. The median duration of SSAs was 13.7 months. With a median follow-up of 5.8 years, median PFS and OS were 17.4 (95% CI: 8.7-26.0) and 58.4 (95% CI: 44.2-102.7) months, respectively. Functioning tumours and slowly progressive disease were significantly associated with longer PFS: HR = 0.48 ([95% CI: 0.24-0.95], p = 0.03) and HR = 7.43 ([95% CI: 3.02-18.25], p < 0.0001), respectively. Only functioning tumours remained significantly associated with OS: HR = 0.33 ([95% CI: 0.14-0.79], p = 0.01). Treatment had been discontinued in two patients due to side-effects. CONCLUSIONS: Median PFS observed in our study is encouraging for PC patients. Patients with functioning tumours and slowly progressive disease treated with SSAs have better prognosis.

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.

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.

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.

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.

[Uterine leiomyosarcoma: epidemiology, pathology, biology, diagnosis, prognosis and treatment]. / Léiomyosarcomes utérins : épidémiologie, histologie, biologie, diagnostic, pronostic et traitement.

Uterine leiomyosarcoma is a rare disease with a poor prognosis. The rarity of this tumor needs a specialized management in tertiary reference centers in order to provide patients with optimal diagnostic, prognostic and therapeutic care. The pathological diagnosis relies on the presence of three characteristics in proliferating smooth muscle cells: necrosis, cytologic atypia and mitosis. Despite progress in the knowledge of the biology of these tumors, no oncogenic driver has been found. Prognosis depends mainly on the age of the patient, race, FIGO stage, mitotic index and hormonal receptor expression in the tumor. Surgery is one of the cornerstones of management and cytotoxic chemotherapy is the mainstay of treatment in metastatic disease with a potential role in the adjuvant setting. In locally advanced or metastatic disease, prognosis is poor with a median overall survival of about 12 to 14 months despite a 30% response rate to polychemotherapy regimens. Anti-angiogenics and hormonal therapy have a role to play in the setting of metastatic disease. It is mandatory to include such patients in clinical trials aiming to improve the therapeutic management of these patients. Multimodal therapy can improve the prognosis of selected patients too.

Results of oxaliplatin-based hyperthermic intraperitoneal chemotherapy in recurrent ovarian granulosa cell tumors.

OBJECTIVES: To assess the efficacy and morbidity of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) for relapsed ovarian granulosa cell tumors (OGCT). STUDY DESIGN: Between 2007 and 2009, patients with relapsed OGCT who had been treated with HIPEC after CRS in our institution were retrospectively analyzed. RESULTS: We identified 7 patients who had undergone CRS plus HIPEC. Macroscopically complete cytoreduction had been performed in all patients. The location of the recurrence was exclusively the pelvis in 2 cases and both the pelvis and abdomen in 5 cases. We had administered an intraperitoneal perfusion of oxaliplatin (460 mg/m(2)) or oxaliplatin (360 mg/m(2)) plus irinotecan (360 mg/m(2)) heated up to 41-43°C for 30 min. No post-operative mortality nor any grade IV morbidity (according to the Clavien and Dindo classification) had occurred. One lymphocyst (grade III) had appeared which had twice required percutaneous drainage. Six patients had experienced extra-abdominal complications (all grade II). Median follow-up after CRS plus HIPEC was 32 months (range, 25-56). Among the 7 patients, 2 are disease free, 3 had relapsed with peritoneal carcinomatosis and 2 had relapsed with liver metastases. CONCLUSIONS: HIPEC (using oxaliplatin or oxaliplatin plus irinotecan) should not be recommended to treat relapsed OGCT.

Are G3 ENETS neuroendocrine neoplasms heterogeneous?

The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.

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.

Prognostic factors and outcome of undifferentiated endometrial sarcoma treated by multimodal therapy.

OBJECTIVE: To describe the natural history, prognostic factors, and optimal treatment modalities of undifferentiated endometrial sarcoma (UES). METHODS: A retrospective review was conducted of 30 patients with UES treated at Institut Gustave-Roussy, France, between January 1978 and December 2008. Clinical and pathologic variables, treatment modalities, and outcomes were assessed. RESULTS: Disease was advanced in most cases: FIGO stage III-IV in 70% of patients. Overall, 29 patients (96.7%) underwent hysterectomy as part of the initial surgical treatment; however, only 18 (60.0%) attained complete macroscopic resection. The incidence of pelvic and/or para-aortic lymph-node involvement at primary surgery or first recurrence was 44.4%. Median postoperative follow-up was 5 years; progression-free survival (PFS) and overall survival (OS) were 9.7 and 23 months, respectively. No differences in OS and PFS were observed by staging subgroup (FIGO vs the American Joint Committee on Cancer). Only postoperative pelvic radiotherapy with or without brachytherapy correlated with improved PFS (19.1 vs 6.5 months; P=0.04) and OS (54.5 vs 16.7 months; P=0.01) in a univariate analysis. CONCLUSION: Neither staging system was optimal for risk stratification. Multimodal therapy was recommended after surgery.

Frequency and characterization of gastro-entero-pancreatic neuroendocrine tumor patients with high-grade of uptake at somatostatin receptor scintigraphy.

Recent studies suggest that the somatostatin receptor scintigraphy (SRS) grade of uptake is a predictor of response to peptide receptor radionuclide therapy (PRRT). To identify and characterize patients with well-differentiated (WD) neuroendocrine neoplasm (NEN) displaying a high-grade uptake at SRS. Patients with WD-NEN, whose SRS films were available for review, were retrospectively included. SRS was reviewed by three independent readers and classified into four subgroups based on a modified Krenning's scale (mKS): no uptake (group-0), homogeneous grade 1-2 uptake (group-1), homogeneous grade 3-4 (group-2), and heterogeneous grade 1-4 (group-3). A simplified scale (sS) of SRS was also used to look for characteristics of patients with high-grade uptake. One hundred and six WD-NEN patients were enrolled. Group-0, group-1, group-2, and group-3 were found in 17, 8, 33, and 42% of cases respectively. High-grade uptake at sS (75% of cases) was correlated with older age, functioning NEN, high chromogranin-A level, and grade 1 (G1) NEN based on mitotic count. Based on the mKS or sS scales, no difference on survival was found. Thirty-three to seventy-five percent of metastatic NEN patients can be considered candidates for PRRT based on homogeneous or heterogeneous high-grade uptake. Functioning G1 NEN patients could be the best candidates for PRRT. Randomized trials are expected to confirm this result.

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.