Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial.

BACKGROUND: The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10-GEICO 68-C-JGOG1084-GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone. METHODS: In this investigator-initiated, randomised, open-label, phase 3 trial, patients from 92 sites in Europe, Japan, and the USA with metastatic (stage IVB), persistent, or recurrent cervical cancer that was measurable, previously untreated, and not amenable to curative surgery or radiation were randomly assigned 1:1 to receive standard therapy (cisplatin 50 mg/m2 or carboplatin area under the curve of 5, paclitaxel 175 mg/m2, and bevacizumab 15 mg/kg, all on day 1 of every 3-week cycle) with or without atezolizumab 1200 mg. Treatment was continued until disease progression, unacceptable toxicity, patient withdrawal, or death. Stratification factors were previous concomitant chemoradiation (yes vs no), histology (squamous cell carcinoma vs adenocarcinoma including adenosquamous carcinoma), and platinum backbone (cisplatin vs carboplatin). Dual primary endpoints were investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumours version 1.1 and overall survival analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03556839, and is ongoing. FINDINGS: Between Oct 8, 2018, and Aug 20, 2021, 410 of 519 patients assessed for eligibility were enrolled. Median progression-free survival was 13·7 months (95% CI 12·3-16·6) with atezolizumab and 10·4 months (9·7-11·7) with standard therapy (hazard ratio [HR]=0·62 [95% CI 0·49-0·78]; p<0·0001); at the interim overall survival analysis, median overall survival was 32·1 months (95% CI 25·3-36·8) versus 22·8 months (20·3-28·0), respectively (HR 0·68 [95% CI 0·52-0·88]; p=0·0046). Grade 3 or worse adverse events occurred in 79% of patients in the experimental group and in 75% of patients in the standard group. Grade 1-2 diarrhoea, arthralgia, pyrexia, and rash were increased with atezolizumab. INTERPRETATION: Adding atezolizumab to a standard bevacizumab plus platinum regimen for metastatic, persistent, or recurrent cervical cancer significantly improves progression-free and overall survival and should be considered as a new first-line therapy option. FUNDING: F Hoffmann-La Roche.

FcγR3A polymorphism influences natural killer cell activation and response to anti-PD-L1 (avelumab) in gestational trophoblastic neoplasia.

BACKGROUND: Low-risk gestational trophoblastic neoplasia (GTN) are currently receiving monochemotherapy as first-line therapy. In the case of a resistance, a second-line mono- or polychemotherapy is proposed. As an alternative to these toxic and historic chemotherapy agents, the efficacy of the anti-PD-L1 monoclonal antibody (avelumab) was assessed in the TROPHIMMUN phase II trial Cohort A. Avelumab yielded a 53% cure rate with an acceptable tolerance profile, including normal further pregnancy and delivery. Beyond the blockade of PD-1/PD-L1 interactions, avelumab effect could rely on the induction of antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by FcγR3A-expressing natural killer (NK) cells. OBJECTIVE: This translational study aimed at testing whether ADCC is involved in avelumab efficacy on GTN and if FcγR3A affinity polymorphism could help predicting the response to avelumab in GTN. STUDY DESIGN: The expression of PD-L1 by the tumor and the phenotype of NK cells infiltrating GTN were verified by performing transcriptomic and proteomic analyses. Then, JEG-3 choriocarcinoma cells were cocultured with human NK cells in presence and absence of avelumab. The impact of FcγR3A functional polymorphism was assessed on the activation status of NK cells and the viability of JEG-3 choriocarcinoma cells. Finally, the data from TROPHIMMUN trial were reanalyzed to determine the impact of the FcγR3A polymorphism of patients on their response to avelumab. RESULTS: We confirmed that FcγR3A+ NK cells infiltrated PD-L1-expressing GTN. In vitro, avelumab-coated JEG-3 choriocarcinoma cells induced NK cell activation, which promoted the destruction of JEG-3 cells. NK cell activation was abolished when the Fc portion of avelumab was removed, demonstrating the importance of Fcγ receptor in this process. Using this model of ADCC, we demonstrated that high-affinity FcγR3A polymorphism on NK cells was associated with better in vitro response to avelumab. In line with this result, patients from the TROPHIMMUN trial homozygous for the high affinity FcγR3A polymorphism had better clinical response to avelumab. CONCLUSIONS: Our work demonstrates that ADCC contributes to the therapeutic effect of avelumab in GTN and that the individual patient response is impacted by the FcγR3A polymorphism. The FcγR3A polymorphism could be used as a biomarker to identify patients diagnosed with monochemoresistant GTN who are most likely to respond to avelumab.

TEDOVA: vaccine OSE2101 +/- pembrolizumab as maintenance in platinum-sensitive recurrent ovarian cancer.

Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maintenance options involve bevacizumab and poly ADP-ribose polymerase inhibitors, but these lines of therapy can only be used once in the disease course. Patients in first or second platinum sensitive relapse after poly ADP-ribose polymerase inhibitors and bevacizumab represent an area of unmet medical need. This academic sponsored, international Phase II randomized trial is evaluating the combination of a therapeutic cancer vaccine (OSE2101) with anti-PD1 (pembrolizumab) as maintenance therapy, in patients with platinum-sensitive recurrence regardless of number of prior lines and no progression after platinum-based chemotherapy.Clinical Trial Registration: NCT04713514 (ClinicalTrials.gov).

Ongoing Phase II study randomizing vaccine OSE2101 +/- Pembrolizumab vs supportive care as maintenance in platinum-sensitive recurrent ovarian cancer.

Impact of metformin, statins, and beta blockers on survival in patients with primary ovarian cancer: combined analysis of four prospective trials of AGO-OVAR and ENGOT/GCIG collaborators.

OBJECTIVE: The aim of this study was to investigate the association of co-medication with metformin, a statin, or beta blocker with survival in patients with primary ovarian cancer. METHODS: Individual data from three phase III, randomized controlled trials (AGO-OVAR 11, AGO-OVAR 12, and AGO-OVAR 16) and one phase II trial (AGO-OVAR 15) were pooled and analyzed. Patients were classified as ever user if the specific co-medication was documented at least once during the trial, and were compared with never users as controls. Association of co-medications and outcomes were adjusted for potential confounders (age, International Federation of Gynecology and Obstetrics stage, histology, residual disease after surgery, Eastern Cooperative Oncology Group (ECOG) performance status, body mass index, Charlson Comorbidity Index, and assigned treatment within the trial) in multivariate Cox regression analyses. RESULTS: Overall, n=2857 patients were included. Ever users were: 100 patients received metformin (3.5%), 226 patients received statins (7.9%), and 475 (16.6%) patients received beta blockers (n=391 selective beta blockers; 84 non-selective beta blockers) as co-medication. There were no significant differences regarding the baseline characteristics except that ever users were significantly older, more obese, and had more comorbidities, according to the Charlson Comorbidity Index, compared with controls. Multivariate analyses for progression free survival and overall survival revealed neither a significant impact of metformin on survival (progression free survival hazard ratio (HR) 0.94, 95% confidence interval CI 0.69 to 1.29, p=0.7; overall survival HR 0.82, 95% CI 0.58 to 1.17, p=0.28) nor for statins (progression free survival HR 0.98, 95% CI 0.82 to 1.18, p=0.87; overall survival HR 0.91, 95% CI 0.74 to 1.12, p=0.37). In contrast, ever users of selective beta blockers had a significantly higher risk for recurrence and death (progression free survival HR 1.22, 95% CI 1.05 to 1.41, p=0.009; overall survival HR 1.25 95% CI 1.06 to 1.47, p=0.009). CONCLUSIONS: In this analysis, co-medication with metformin or statins had no significant impact on survival in patients with primary ovarian cancer. In contrast, co-medication with a beta blocker was associated with worse survival. However, whether this observation is related to the underlying condition rather than a direct negative impact on tumor biology remains unclear.

Updated progression-free survival and final overall survival with maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial.

OBJECTIVE: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status. METHODS: Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This post hoc analysis evaluated 5-year progression-free survival and mature overall survival in patients classified by clinical risk and HRD status. RESULTS: Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk. CONCLUSION: This post hoc analysis indicates that in patients with newly diagnosed advanced HRD-positive ovarian cancer, maintenance olaparib plus bevacizumab should not be limited to those considered at higher risk of disease progression. Five-year progression-free survival rates support long-term remission and suggest an increased potential for cure with particular benefit suggested in lower-risk HRD-positive patients.

Update on new treatments for rare ovarian tumours.

PURPOSE OF REVIEW: In spite of their rarity when considered individually, the sum of all rare ovarian tumours (ROT) represent almost half of all ovarian malignancies. As such, their appropriate inclusion within dedicated clinical trials is essential for enhanced management. RECENT FINDINGS: Supported by institutional expert national (e.g. TMRG) and international (e.g. ESGO) networks and owing to national (e.g. ARCAGY-GINECO) and international (e.g. ENGOT) collaborations dedicated to clinical research, the last few years have shown increased number of clinical trials dedicated to ROT. These either were based on specific molecular features of ROT (e.g. expression of oestrogen receptors for low-grade serous ovarian carcinomas and anastrazole evaluation in the PARAGON trial) or on the evaluation of innovative therapies (e.g. pembrolizumab within the ROT cohort from the AcSé Pembrolizumab multicentric basket trial). Furthermore, recent years have also shown the advent of randomized clinical trials. For instance, the ALIENOR trial positioned weekly paclitaxel as a new option for relapsed sex cord-stromal tumours, while the GOG281/LOGS trial raised trametinib as a new standard-of-care option for recurrent low-grade serous carcinomas. SUMMARY: The last few years have exhibited a paradigm shift towards the possibility to develop dedicated trials for ROT, owing to international collaborations supported by institutional networks. Current trials, molecular-driven and based on innovative designs, are highly promising, as they may bring ROT management towards more personalized medicine.

Atezolizumab Combined With Platinum and Maintenance Niraparib for Recurrent Ovarian Cancer With a Platinum-Free Interval >6 Months: ENGOT-OV41/GEICO 69-O/ANITA Phase III Trial.

PURPOSE: To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer. METHODS: The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1. RESULTS: Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA-mutated, 36% PD-L1-positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs. CONCLUSION: Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.

[Tertiary lymphoid structures in cancer: From biology to therapeutic guides]. / Structures lymphoïdes tertiaires : de la biogenèse à l'impact thérapeutique en cancérologie.

Tertiary lymphoid structures (TLS) are inducible ectopic lymphoid aggregates, which form in response to various inflammatory situations, including cancer. TLS are notably composed of B lymphocytes, T lymphocytes, mature dendritic cells and other key players such as high endothelial venules. Furthermore, TLS can present different levels of organization and maturation, from simple T/B lymphocyte aggregates to authentic mature B cell follicles with germinal centers adjacent to T cell rich areas. While over the past decade, TLS may have been associated with a favorable prognosis in various cancers, the year 2022 was marked by the first prospective trial (PEMBROSARC) that reported the interest of TLS as predictive biomarkers of pembrolizumab efficacy for the treatment of soft-tissue sarcomas. All along this review, we will first address the molecular and cellular bases of TLS as well as the different strategies for identifying them in clinical practice, then discuss the prognostic/predictive impact of their presence and finally, we will elaborate on the current limitations and perspectives in translational research.

Pelvic insufficiency fractures after intensity modulated radiation therapy combined with chemotherapy for cervix carcinoma: Incidence and impact of bone mineral density.

Background and Purpose: The aim of this study was to evaluate the incidence and predictive factors of Pelvic Insufficiency Fractures (PIFs) occurring after Intensity Modulated Radiation Therapy (IMRT) combined with chemotherapy for locally advanced cervical cancer (CC). Material and methods: Medical records of patients receiving radio-chemotherapy with IMRT between 2010 and 2020 for advanced CC were reviewed. PIFs were detected during follow-up on pelvic Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The cumulative incidence rate of PIFs and its confidence interval were calculated at 2 and 5 years of follow-up. Pre-therapeutic Bone Mineral Density (BMD) (g/cm3) was evaluated on CT simulation for sacrum and the fourth lumbar (L4) vertebrae. Sacrum dosimetric parameters (V30Gy, V40Gy, D50%, Dmean) were analyzed. Results: 136 patients were included. The median follow-up was 4.4 years. Median dose of D50% and V40Gy sacrum were 35.2 Gy (20.6-46.4) and 32.2% (7.2-73.4) respectively. The 2-year and 5-year cumulative incidence rates were 15.7% (95% CI: 9.88-22.71) and 22% (95% CI: 14.58-30.45) respectively. Median time interval between RT completion and PIFs' detection was 11.5 months (IQR: 7.4-22.3). Univariate analysis showed that older age (p < 0.01), postmenopausal status at baseline (p < 0.01), and lower sacral and spinal BMD at baseline (respectively p < 0.001 and p < 0.01) were significantly associated to all sites of PIFs, and lower sacral BMD with sacral fractures (p < 0.001). Conclusion: Post-IMRT PIFs were detected in 18.4% of patients with locally advanced CC. Individual predisposing factors as older age, postmenopausal status, decreased bone density on the CT simulation were mainly predictive.

[Uterine leiomyosarcoma - French guidelines from the GSF/NETSARC and TMRG groups]. / Léiomyosarcomes utérins ­ Référentiel de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG.

Uterine leiomyosarcomas represent the most common uterine sarcomas. The prognosis is poor with metastatic recurrence in more than half of the cases. The purpose of this review is to make French recommendations for the management of uterine leiomyosarcomas within the framework of the French Sarcoma Group - Bone Tumor Study Group (GSF-GETO)/NETSARC+ and Malignant Rare Gynecological Tumors (TMRG) networks in order to optimize their therapeutic management. The initial assessment includes a MRI with diffusion perfusion sequence. The diagnosis is histological with a review in an expert center (Reference Network in Sarcoma Pathology (RRePS)). Total hysterectomy with bilateral salpingectomy, en bloc without morcellation, is performed when complete resection is possible, whatever the stage. There is no indication of systematic lymph node dissection. Bilateral oophorectomy is indicated in peri-menopausal or menopausal women. Adjuvant external radiotherapy is not a standard. Adjuvant chemotherapy is not a standard. It can be an option and consists in doxorobucin based protocols. In the event of local recurrence, the therapeutic options are based on revision surgery and/or radiotherapy. Systemic treatment with chemotherapy is most often indicated. In case of metastatic disease, surgical treatment remains indicated when resecable. In cases of oligo-metastatic disease, focal treatment of metastases should be considered. In the case of stage IV, chemotherapy is indicated, and is based on first-line doxorubicin-based protocols. In the event of excessive deterioration in general condition, management by exclusive supportive care is recommended. External palliative radiotherapy can be proposed for symptomatic purposes.

[Endometrial stromal sarcoma: French Guidelines from the French Sarcoma Group and the Rare Malignant Gynecologic Tumors Group]. / Sarcomes du stroma endométrial de bas grade : référentiels de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG.

Low-grade endometrial stromal sarcoma (LG-ESS) accounts for approximately 15% of all uterine sarcomas. Median age of patients is around 50 years and half of the patients are premenopausal. In all, 60% of cases present with FIGO stage I disease. Preoperatively radiologic findings of ESS are not specific. Pathological diagnosis remains essential. This review aimed to present the French guidelines for low grade ESS treatment within the Groupe sarcome français - Groupe d'étude des tumeurs osseuse (GSF-GETO)/NETSARC+ and tumeur maligne rare gynécologique (TMRG) networks. Treatments should be validated in multidisciplinary team involved in sarcomas or rare gynecologic tumors. Hysterectomy is the cornerstone of treatment for localized ESS, and morcellation should be avoided. Systematic lymphadenectomy in ESS does not improve the outcome and is not recommended. Leaving the ovaries in situ in stage I tumors could be discussed for young women. Adjuvant hormonal treatment could be considered, for two years for stage I with morcellation or stage II and livelong for stages III or IV. Nevertheless, several questions remain, such as optimal doses, regimens (progestins or aromatase inhibitors) and duration of therapy. Tamoxifen is contraindicated. Secondary cytoreductive surgery if feasible for recurrent disease, appears to be an acceptable approach. Systemic treatment for recurrent or metastatic disease is mainly hormonal, with or without surgery.

[Treatments for rare ovarian tumors: What's new?] / Avancées thérapeutiques dans la prise en charge des tumeurs rares malignes ovariennes.

Even if each rare ovarian tumor (ROT) has a low incidence, the sum of all these entities represents almost the half of all ovarian neoplasms. Thus, development of dedicated clinical trial emerged as a prerequisite to improve their managements. Owing to the spreading of dedicated institutional networks and (supra)national collaborations, the number of clinical trials has increased the past few years, with different types of trials; while some focused on specific molecular features, others assessed innovative molecules. Furthermore, relevant randomized clinical trials were designed as a mean to position new treatment options. Currently, innovative molecular-driven trials, based on master protocol trials are emerging and may shed light towards the improvement of personalized medicine regarding ROT.

Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial.

PURPOSE: Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy. PATIENTS AND METHODS: ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1-positive populations (alpha .025 for each population). RESULTS: Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1-positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1-positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively). CONCLUSION: ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1-positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.

Incidence and prognostic factors of clinically meaningful toxicities of kinase inhibitors in older patients with cancer: The PreToxE study.

Most of the safety data of tyrosine and serine/threonine kinase inhibitors (TKIs) approved for cancer treatment are extrapolated from larger trials in which older patients generally accounted for a small fraction of the participants. The Predicting Severe Toxicity of Targeted Therapies in Elderly Patients With Cancer study (PreToxE)PreToxE study aims to describe the incidence and prognostic factors of clinically meaningful toxicities of TKI in patients with cancer aged over 70 years. The primary endpoint was incidence of severe toxicity, defined as treatment-related death, persistent or significant disability/incapacity, hospitalization or the discontinuation of TKI treatment for more than three weeks. Our results indicate that despite frequent upfront dose reduction, clinically meaningful toxicities occurred in approximately 40% of older patients treated with TKIs. The use of at least three concomitant medications is an independent predictor of clinically meaningful toxicities.

[Thyroid carcinoma on struma ovarii: Diagnosis and treatment]. / Cancer thyroïdien sur struma ovarii : généralités et principes de prise en charge.

Thyroid carcinoma on struma ovarii (TCSO) is a rare ovarian tumour, derivate from monodermic teratomas. It represents about 0.01% of overall ovarian tumours and 5 to 10% of struma ovarii. The diagnosis is histologic and retrospective after pelvic surgery; radiographic imaging being unspecific. Because of its rarity, the treatment of TCSO is not consensual and should be validated in multidisciplinary team involved in rare ovarian carcinoma. The first treatment is a surgical removal, with a laparoscopic approach. A fertility-conservative surgery is recommended for young women. If the tumour is unresectable and/or with metastatic spread, an adjuvant iodine 131 treatment might be proposed after thyroidectomy. Recurrence of TCSO should be taken care of as a thyroid carcinoma with tyrosine kinase inhibitor in case of progressive distant relapse, refractory to iodine 131 treatment. If the recurrence is localised, a complete surgery is the preferred option. There is no gold standard for the follow up.