Explore the vast range of titles available.

Clinical oncology heavily relies on the use of radiotherapy, which often leads to merely transient responses that are followed by local or distant relapse. The molecular mechanisms explaining radioresistance are largely elusive. Here, we identified a dual role of autophagy in the response of cancer cells to ionizing radiation. On one hand, we observed that the depletion of essential autophagy-relevant gene products, such as ATG5 and Beclin 1, increased the sensitivity of human or mouse cancer cell lines to irradiation, both in vitro (where autophagy inhibition increased radiation-induced cell death and decreased clonogenic survival) and in vivo , after transplantation of the cell lines into immunodeficient mice (where autophagy inhibition potentiated the tumour growth-inhibitory effect of radiotherapy). On the other hand, when tumour proficient or deficient for autophagy were implanted in immunocompetent mice, it turned out that defective autophagy reduced the efficacy of radiotherapy. Indeed, radiotherapy elicited an anti-cancer immune response that was dependent on autophagy-induced ATP release from stressed or dying tumour cells and was characterized by dense lymphocyte infiltration of the tumour bed. Intratumoural injection of an ecto-ATPase inhibitor restored the immune infiltration of autophagy-deficient tumours post radiotherapy and improved the growth-inhibitory effect of ionizing irradiation. Altogether, our results reveal that beyond its cytoprotective function, autophagy confers immunogenic properties to tumours, hence amplifying the efficacy of radiotherapy in an immunocompetent context. This has far-reaching implications for the development of pharmacological radiosensitizers.

Introduction/Background*The aim of this study was to assess prognostic factors and implications on further management in a large series of stage-II or III Serous Borderline Ovarian Tumors (SBOTs) with a long-term follow-up.MethodologyPatients with SBOTs and peritoneal implants treated in, or referred to, our institution were retrospectively reviewed. Prognostic factors on invasive recurrence, disease-free (DFS) and overall survival (OS) were analyzed.Result(s)*Between 1971 and 2017, 212 patients were identified and followed (33 having invasive implants). After a median follow-up of 115 months, 70 recurrences were observed, 28 of them under the form of invasive disease. DFS at 5 years and 10 years was 73% and 62% respectively. The use of a conservative treatment (HR=5.5[3.33-9.08], p<.0001), the presence of ≥ 3 peritoneal sites with implants (HR=1.65[1.01-2.72], p=.045) were unfavorable prognostic factors for DFS. The presence of ≥ 3 peritoneal sites with implants (HR=3.02[0.96-9.53], p=.049) and the presence of stromal microinvasion (HR=3.19[1.12-9.1], p=.022) were unfavorable prognostic factors for OS. Non-conservative surgery (HR=7[2.35-20.87], p=0.0002), invasive implants (HR=5.37[1.29-22.26], p=0.013), and ≥ 3 peritoneal sites with implants (HR=3.56 [1.11-11.39], p=0.024) were identified as predictors of recurrence in the form of an invasive disease. Invasive implants were not associated with DFS (HR=1.39[0.77-2.51], p=0.27), nor OS (HR=1.76[0.57-5.47], p=0.32).Conclusion*After a long-term follow-up, type of peritoneal implants is no longer a prognostic factor for OS. Implants ≥ 3 peritoneal sites seem to impact significantly OS and then require a specific follow-up in this subgroup of patients.

Introduction/Background*The aim of this study was to assess the outcomes of a large series of patients treated conservatively for a stage II or III serous borderline tumors of the ovary (SBOTs) with a long-term follow-up.MethodologyPatients with SBOTs and peritoneal implants, treated in or referred to our institution, were retrospectively reviewed. Outcomes of patients treated conservatively (preservation of the uterus and at least a part of one ovary) to promote subsequent fertility were specifically analyzed.Result(s)*Between 1971 and 2017, 212 patients were identified and followed-up. Among them, 65 underwent a conservative treatment. Eight patients had invasive implants. Among patients treated conservatively, 38 (58%) patients recurred. Twenty-eight recurrences were observed under the form of borderline tumor on spared ovary and/or noninvasive implants, but 8 patients had a recurrence under the form of invasive disease. Compared to radical surgery, the use of a conservative treatment (p<.0001) was a prognostic factors on disease free survival (DFS), but without impact on overall survival (OS). Nevertheless, 3 deaths occurred. Twenty-four pregnancies (13 spontaneous) were observed in 20 patients (29 patients wishing to be pregnant).Conclusion*In this series collecting the largest number of patients undergoing conservative surgery for stage II/III SBOTs, spontaneous pregnancies can be achieved after conservative treatment of advanced-stage disease, but the recurrence rate is high, and 3 deaths were observed. These patients spared their fertility but with a high rate of recurrence. Uncertainties about safety of conservative treatment should be exposed to them.

Introduction/Background*Most frequent borderline ovarian tumors are serous and mucinous subtypes. Less frequent borderline diseases are endometrioid, clear cell and Brenner tumors (BBOT). Very few are known about this later subtype and most of reports concerns very short series or case reports. The aim of this study was to determine the prognosis of a continuous series of BBOT and to analyze data published in the literature about this rare entity.MethodologyA retrospective review of patients with BBOT 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.Result(s)*Seventeen patients were identifiedMedian age was 62 (range 42-85) years. Six patients underwent a unilateral salpingo-oophorectomy and 11 a bilateral salpingo-oophorectomy +/- hysterectomy and/or staging surgery. Sixteen patients had unilateral tumor and all patients had a stage-I disease. Stromal microinvasion was observed in 3 cases. The median follow-up was 60 months (range 7-118 months). One patient had developed a recurrence in contralateral ovary after a unilateral salpingo-oophorectomy. One patient had previous history of urothelial tumor.Conclusion*Peritoneal staging surgery is not required, because all patients reported had stage-I disease. One recurrence occurred. When reviewing all the 82 cases reported in the literature (included ours), 9% had previous history or synchronous urothelial tumor suggesting then the need of at least careful checking of urological disease in patients with BBOT.

Immunotherapy is radically changing the clinical management of patients affected by an increasingly wide array of tumours. However, not all patients achieve long-term clinical benefits from immunotherapy as a standalone treatment, calling for the development of regimens that combine various interventions. Radiotherapy stands out as a particularly promising candidate in this setting, not only because of its established safety profile, but also because radiotherapy has the potential ability to mediate robust immunostimulatory effects that could synergise with immunotherapy in systemic tumour control. However, optimal radioimmunotherapy regimens might call for the redefinition of conventional radiotherapy doses and fractionation schedules. In this Series paper, we discuss current approaches to improve the efficacy and reduce the toxicity of radioimmunotherapy for the management of cancer.

Introduction/Background*The aim of this study was to investigate the relation between the PCI and overall survival (OS) and recurrence-free survival (RFS). The peritoneal cancer index (PCI) is one of the main prognostic factor for the evaluation of ovarian peritoneal carcinosis. Different thresholds have been reported in terms of prognosis and to help in the decision between chemotherapy or primary surgery, but no consensus was found.MethodologyPatients treated at Gustave Roussy between 2004 and 2017 for advanced epitoneal ovarian cancer in complete resection were included. The correlation between PCI and survival was studied using statistical modeling. Multivariate analysis was performed by a logistic regression model.Result(s)*Of the 351 patients included, 27% had initial surgery, 73% had interval surgery. The median follow-up was 52.7 months. The mean PCI was 10.8 (0-32). The linear model best represented the relationship between PCI and OS. Patients with neoadjuvant chemotherapy had a greater instantaneous risk of baseline death than those with initial surgery, as well as a more rapid increase in this risk as PCI increased. OS and PFS were better in the initial surgery group (103.4 months [79.1-NA] vs. 66.5 months [59.1-95.3] and 31.8 months [23.7-48.7] vs. 25.9 months [23.2-29] respectively). Risk factors for death were BMI, PCI and performance of neoadjuvant chemotherapy.Conclusion*PCI is a major prognostic element but its linear relationship with survival does not allow us to establish a cut-off. Moreover, the prognostic impact of PCI is even stronger in the case of primary chemotherapy.

Introduction/BackgroundThe aim of this study was to assess prognostic factors in patients with stage II or III serous borderline ovarian tumors (SBOT) after a long term follow up in a large series.MethodologyPatients with SBOT and peritoneal implants treated or referred to our institution were retrospectively reviewed. All specimens (ovary and peritoneal implants) were reviewed by our expert pathologist.ResultsBetween 1971 and 2017, 212 patients were identified. Thirty-three (16%) patients had invasive implants. Sixty-eight patients underwent a conservative (fertility sparing) surgery. After a median follow up of 115 (range 12–512) months, 70 recurrences (33%) were observed (range 4–271 months), 28 (40%) of them under the form of invasive disease. Disease-free survival (DFS) at 5 and 10 years were 73% and 62% respectively. Invasive implants (vs non-invasive) (HR=5.37[1.29–22.26], p=0.013), and 3 or more peritoneal sites with implants (vs <3) (HR=3.56[1.11–11.39], p=0.024) were identified as predictors of recurrence in the form of invasive disease.But invasive implants were not associated with DFS (HR=1.39[0.77–2.51], p=0.27) nor with Overall Survival (OS) (HR=1.76[0.57–5.47], p=0.32).The presence of implants in more than 3 peritoneal sites was the only factor associated with both OS and DFS (p=0.049 and p=0.045). Conservative surgery was associated with DFS (HR=5.5[3.33–9.08], p<0.0001) but not with OS (HR=0.94[0.26–3.41], p=0.93). Others factors studied: stage (II vs III), residual disease after surgery, presence of micropapillary patterns, nodal surgery and the use of adjuvant treatment had no impact on OS or PFS.ConclusionThis study demonstrates that after a long term follow up, the types of peritoneal implants is no longer a prognostic factor on OS.Presence of implants on at least three peritoneal sites seems to impact significantly the risk of recurrence under the form of invasive disease and OS requiring then a specific follow-up in these patients.DisclosureNothing to disclose.

Introduction/BackgroundThe aim of this study was to assess the outcomes of the largest series of conservative treatment for advanced stages serous borderline ovarian tumor.MethodologyBetween 1973 and 2017, 65 patients were treated conservatively for an advanced-stage serous borderline ovarian tumor. Patient outcomes were reviewed.Results28 patients had undergone a unilateral salpingo-oophorectomy, 12 a unilateral cystectomy and 25 unilateral salpingo-oophorectomy and controlateral cystectomy. Eight patients had invasive implants. The median duration of follow-up was 73 months (range, 12–369). The recurrence rate was high (58%). Eight recurrences were observed under the form of invasive disease: 2 (25%) and 6 (11%) in patients having initially respectively invasive implants and noninvasive implants. Three deaths had occurred, all of them in patients with noninvasive implants and micropapillary patterns (2 of them having a complete resection of peritoneal implants). Twenty-four pregnancies (13 spontaneous) were observed in 29 patients wishing to be pregnant. Seven patients had secondary infertility.ConclusionThis study demonstrates that the conservative treatment of advanced stage borderline ovarian tumors (with noninvasive implant) can be achieved to preserve the possibility of pregnancy but the recurrence rate is high. Nevertheless, three deaths were observed, all of them concerning patients with noninvasive implants and micropapillary patterns. Initial presence of invasive implant doesn’t seem to impact significantly the risk of recurrence under the form of invasive disease. This important data should be shared with such patient when a conservative approach is discussed. A careful follow-up should be done in this subgroup of patients.DisclosureNothing to disclose.

Introduction/BackgroundGranulosa cell tumors account for approximatively 3% of ovarian tumors. The juvenile histological type (JGCT) represents 5% of them, and remains relatively unknown. Our aim was to describe clinicopathologic characteristics and to evaluate prognostic factors.MethodologyWe retrospectively studied medical records of 40 patients referred to our center for JGCT between November 2010 and 2018.ResultsThirty-six patients had confirmed JGCT. The mean age was 19,9 years (range 2,5 months - 47,4 years). Abdominal pain (53%), vaginal bleeding (31%), palpable mass (28%), were the most common presenting symptoms. The distribution of FIGO stage was: 16 patients at stage Ia, 17 Ic, 1 IIa, 1 IIIb, 1 IIIc. Thirty-two patients (89%) had conservative surgery. Sixteen (44%) received adjuvant chemotherapy (Ic=13, IIa=1, IIIb=1, IIIc=1), mostly bleomycine/etoposide/cisplatine regimen. The mean follow up was 35 months (range 1 to 204 months). Nine patients recurred (Ia=1, Ic=6, IIa=1, IIIc=1) with a mean time of 12,1 months (range 1–47). Among them, 4 had a cystectomy at the initial surgery: 3 without adjuvant chemotherapy, 2 died of disease; 4 stage Ic did not received adjuvant chemotherapy neither. Three patients died after a mean of 21,2 months (range 9,5–32,4). At 36 months: progression free survival was 70,4% [54,9–90,2], overall survival was 85,6% [71,4–100]. The main prognosis factor of recurrence was advanced FIGO stage (p< 0,001). Age >15 years (p= 0,09)and cytonuclear atypia (p= 0,08)tended to be associated to relapse too. Intra operative tumor rupture (p= 0,03) was a significant risk factor of death.We observed 5 pregnancies with term deliveries.ConclusionThe main prognostic factors are: FIGO stage and intra operative tumor rupture. Fertility sparing surgery is safe for stage Ia, reasonable for stage Ic combined with adjuvant chemotherapy. Patients with cystectomy had poor outcome; unilateral salpingo-oophorectomy must be done sytematically.DisclosureNothing to disclose.

Introduction/BackgroundOvarian serous borderline tumors with invasive peritoneal implants (SBOT-IPI) are associated with serous low grade carcinomas (SLGC) in the 2016 WHO classification of ovarian neoplasms. Even if SBOT-IPI can relapse as SLGC in 30% of cases, long term survival is not well known. The aim of this study was to describe the frequency and the characteristics of the recurrences of OSBT-IPI.MethodologyRetrospective study of patients referred to our institution, from 1971 to 2018, for a SBOT-IPI with a minimal follow-up of 12 months.Results30 patients were identified; the median age at diagnosis was 36,5 [19–72] year. FIGO stage was up to IIIA for 26 patients and the average number of peritoneal areas involved was 4,5 [1–12]. The median follow-up was 106,6 [12–366] months. Twelve patients (40%) developed an invasive relapse (4 as SBOT-IPI and 7 as SLGC) with an average time of 53,6 [10,1–175,8] months. In this group, the mean age was 45,3 [23–72] year old at first diagnosis. The initial stage was up to IIIB in 75% of the cases and the average number of peritoneal areas involved was 5,2 [1–12]. Two patients died due to recurrence, one had a recurrence as SBOT-IPI 6 years after and one as SLGC 10 years after.ConclusionRelapsing as an invasive disease were more frequent than reported in other series and seems to be associated with the initial FIGO stage and with the number of peritoneal areas involved in the initial diagnosis. However, in this long term follow-up study, overall mortality of SBOT-IPI seems lower than mobility rate of SLGC. This study highlights that SBOT-IPI long term survival is poorly known. Finally, the prognosis of the SBOT-IPI should not be associated with the SLGC.DisclosureNothing to disclose.