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Objective: This multicenter study aimed to retrospectively evaluate the impact of high boost simultaneous integrated boost (SIB) to pathologic lymph nodes compared to Sequential boost (Seq) in patients with locally advanced cervical cancer (LACC). Materials and methods: 97 patients with pelvic and/or para-aortic (PAo) node-positive LACC treated by definitive chemoradiation were included. Two groups were analyzed: Sequential boost group and simultaneous integrated boost (SIB) group. Endpoints were Distant Recurrence Free Survival (DRFS), Recurrence Free Survival (RFS), Overall Survival (OS), locoregional pelvic and PAo control and toxicities. Results: 3-years DRFS in SIB and Seq groups was 65% and 31% respectively (log-rank p < 0.001). 3-years RFS was 58% and 26% respectively (log-rank p = 0.009). DRFS prognostic factors in multivariable analysis were SIB, PAo involvement and maximum pelvic node diameter ≥ 2cm. Adenocarcinoma histology and absence of brachytherapy tended to be prognostic factors. SIB provided the best pelvic control at first imaging with 97%. There was no significant difference in terms of toxicities between groups. Conclusions: Nodal SIB seems to be unavoidable in the treatment of node-positive LACC. It provides the best DRFS, RFS and pelvic control without additional toxicity, with a shortened treatment duration.
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BACKGROUND: Ovarian cancer is the first cause of death from gynecological malignancies mainly due to development of chemoresistance. Despite the emergence of PARP inhibitors, which have revolutionized the therapeutic management of some of these ovarian cancers, the 5-year overall survival rate remains around 45%. Therefore, it is crucial to develop new therapeutic strategies, to identify predictive biomarkers and to predict the response to treatments. In this context, functional assays based on patient-derived tumor models could constitute helpful and relevant tools for identifying efficient therapies or to guide clinical decision making. METHOD: The OVAREX study is a single-center non-interventional study which aims at investigating the feasibility of establishing in vivo and ex vivo models and testing ex vivo models to predict clinical response of ovarian cancer patients. Patient-Derived Xenografts (PDX) will be established from tumor fragments engrafted subcutaneously into immunocompromised mice. Explants will be generated by slicing tumor tissues and Ascites-Derived Spheroids (ADS) will be isolated following filtration of ascites. Patient-derived tumor organoids (PDTO) will be established after dissociation of tumor tissues or ADS, cell embedding into extracellular matrix and culture in specific medium. Molecular and histological characterizations will be performed to compare tumor of origin and paired models. Response of ex vivo tumor-derived models to conventional chemotherapy and PARP inhibitors will be assessed and compared to results of companion diagnostic test and/or to the patient's response to evaluate their predictive value. DISCUSSION: This clinical study aims at generating PDX and ex vivo models (PDTO, ADS, and explants) from tumors or ascites of ovarian cancer patients who will undergo surgical procedure or paracentesis. We aim at demonstrating the predictive value of ex vivo models for their potential use in routine clinical practice as part of precision medicine, as well as establishing a collection of relevant ovarian cancer models that will be useful for the evaluation of future innovative therapies. TRIAL REGISTRATION: The clinical trial has been validated by local research ethic committee on January 25th 2019 and registered at ClinicalTrials.gov with the identifier NCT03831230 on January 28th 2019, last amendment v4 accepted on July 18, 2023.
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Biomarcadores de Tumor , Neoplasias Ováricas , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Femenino , Humanos , Ratones , Biomarcadores de Tumor/metabolismo , Modelos Animales de Enfermedad , Organoides , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Terapias en Investigación/métodosRESUMEN
Epithelial ovarian cancers (EOCs) are a heterogeneous collection of malignancies, each with their own developmental origin, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis and a 5-year survival of 11% for advanced stages (III/IV). At the early stages, these malignant forms are clinically difficult to distinguish from borderline (15%) and benign (80%) forms with a better prognosis due to the large size and heterogeneity of mucinous tumors. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in tumor progression and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, the comparison of miRNA microarray expression profiles between malignant and borderline tumor FFPE samples identified 10 down-regulated and 5 up-regulated malignant miRNAs, which were validated by individual RT-qPCR. To overcome normalization issues and to improve the accuracy of the results, a ratio analysis combining paired up-regulated and down-regulated miRNAs was performed. Although 21/50 miRNA expression ratios were significantly different between malignant and borderline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 pairs of miRNA ratios (double ratio) showed high discriminatory potential, with 100% of accuracy in distinguishing malignant and borderline ovarian tumors, which suggests that miRNAs may hold significant clinical potential as a diagnostic tool. In summary, these ratio miRNA-based signatures may help to improve the precision of histological diagnosis, likely to provide a preoperative diagnosis in order to adapt surgical procedures.
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Adenocarcinoma Mucinoso , MicroARNs , Neoplasias Quísticas, Mucinosas y Serosas , Neoplasias Ováricas , Lesiones Precancerosas , Femenino , Humanos , MicroARNs/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Carcinoma Epitelial de Ovario , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
PURPOSE: Psammocarcinoma (PK) is a rare disease of unknown origin. We aimed to report the characteristics, management and survival of patients operated on for PK within the French Network for Rare Peritoneal Malignancies (RENAPE) expert centers. PATIENTS AND METHODS: All consecutive cases of PK operated within all 26 RENAPE centers between 1997 and 2018 were retrospectively analyzed. RESULTS: Twenty-five patients were identified. The median age was 53 years [range 17-78]. None of the patients had extra peritoneal metastases at diagnosis. A median of 6 cycles of carboplatin-based systemic chemotherapy was delivered in 52% preoperatively (nâ¯=â¯13) and 56% postoperatively (nâ¯=â¯14); associated with placlitaxel for 12 patients. All patients were operated on. The median PCI was 23 [0-33]. Eighty-four percent had a complete cytoreductive surgery through digestive (nâ¯=â¯7), spleen (nâ¯=â¯3), pancreas (nâ¯=â¯1) resections and/or multiple peritonectomies (nâ¯=â¯11). Five patients (20%) had intraperitoneal chemotherapy. Morbidity (Dindo-Clavien ≥3) was 12%. No postoperative death occurred. After a median follow-up of 42 months (range [2-194]), the median overall (OS) and progression-free (DFS) survival times were respectively 128 months and 31 months. Eighteen patients recurred (72%), mainly in the peritoneum (nâ¯=â¯16). Four of them (22%) were reoperated. The 5 and 10-year DFS rates were both 20.3%. The 5 and 10-year OS rates were 62% and 51.7%, respectively. A complete cytoreductive surgery was associated with a better OS and DFS in a univariate analysis. CONCLUSION: Complete cytoreductive surgery is the cornerstone of the PK's management as a primary treatment. Recurrence remains common and new adjuvant strategies seem needed.
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Antineoplásicos/administración & dosificación , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Terapia Neoadyuvante , Neoplasias Quísticas, Mucinosas y Serosas/terapia , Neoplasias Ováricas/terapia , Neoplasias Peritoneales/terapia , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante , Femenino , Francia , Humanos , Infusiones Parenterales , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Ováricas/patología , Neoplasias Peritoneales/patología , Supervivencia sin Progresión , Tasa de Supervivencia , Adulto JovenRESUMEN
A 35 year old woman with chronic pelvic endometriosis suffered from right scapular pain. MRI imaging showed a right diaphragmatic rupture with liver herniation. Surgical procedure was performed by thoracotomy. The liver was put back into the abdomen, endometriosis was resected from the diaphragm, interrupted non absorbable suture of the diaphragm was performed and an absorbable mesh was placed. Endometriosis was confirmed on histological analysis of the resected diaphragm. To study this pathology, we performed a systematic review of the literature and found 12 similar cases of diaphragmatic rupture due to endometriosis. Right diaphragm is often involved and rupture is always located on the tendinous portion. Symptoms are mainly cyclic right scapular pain and cathamenial pneumothorax. MRI should be performed in case of suggestive symptoms and a systematic exploration of the diaphragm should be performed at laparoscopy for an early treatment of the lesions to prevent progression to rupture.