Circulating Biomarkers in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus in the Pre-nephrectomy Setting.

Many drugs are available in renal cell carcinoma (RCC), yet clinicians are still looking for predictive biomarkers of disease recurrence or progression supporting more personalised treatments. An assessment of circulating biomarkers over time was carried out in this French, open-label, single-arm, multicentre trial conducted in 25 patients with either locally advanced (n = 14) or metastatic RCC (n = 11) who received everolimus (10 mg daily) for 6 weeks prior to nephrectomy (NEORAD, NCT01715935). Circulating biomarkers, including circulating tumour cells, haematopoietic and endothelial cells, plasma angiogenesis and inflammatory markers were quantified at baseline, upon everolimus and post-nephrectomy. We assessed tumour burden, objective response rate upon RECIST1.1, disease-free survival (DFS) and progression-free survival (PFS). The correlation between circulating biomarkers was evaluated with multiple factor analysis and biomarker association with DFS/PFS by Cox regression. No objective response rate was obtained before nephrectomy. Upon everolimus, neutrophils, platelets and sVEGFR2 significantly decreased. We did not find any association between circulating biomarkers and DFS/PFS, but patients with the highest tumour burden at baseline had significantly higher plasma levels of interleukin-6, an inflammatory circulating biomarker, and lower levels of sVEGFR2, related to angiogenesis. Further understanding of the link between these circulating biomarkers could help to optimise drug combinations in RCC.

[Epithelial ovarian cancers and minimally invasive cytoreductive surgery after neoadjuvant chemotherapy: A systematic review]. / Cancers épithéliaux de l'ovaire et chirurgie de cytoréduction par voie mini-invasive après chimiothérapie néoadjuvante : revue systématique de la littérature.

INTRODUCTION: Advanced epithelial ovarian cancer (EOC) is associated with high mortality and often managed first with neoadjuvant chemotherapy (NACT) followed by debulking surgery. Laparoscopic surgery with or without robotic assistance (Minimally Invasive Surgery (MIS)) may represent a beneficial option for these patients. The objective of this literature review is to clarify the place of MIS in the management of advanced EOC for selected patients. METHOD: Pubmed, Cochrane and Clinicaltrials.gov online databases were used for this review, to select English or French published articles. RESULTS: We selected 11 original articles published between 2015 and 2020, 6 of which compared MIS and laparotomy. Among these 11 studies, 8 were retrospective cohorts, 2 were phase II trials, and one was a case-control study. In total, there were 3721 patients, of which 854 (23%) were treated with MIS. The robotic assistance was used with 224 patients (26%) of those MIS patients. Looking specifically at MIS patients, the laparoconversion rate was 9.5%, the rate of complete resection (CC-0) was 83.4%. Finally, the MIS complication rate was 1% intraoperatively and 12% postoperatively. The rate of complete resection, postoperative complication, as well as overall survival (OS) were comparable between patients treated with MIS or laparotomy. One study found an improved disease-free survival (DFS) in MIS versus laparotomy (18 months versus 12 months; P=0.027). CONCLUSION: MIS seems feasible, effective, and reliable in comparison to laparotomy for the completion of cytoreductive surgery after NACT without compromising oncological safety. Prospective randomized controlled trials are needed to confirm the role of MIS in advanced EOC.

Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab.

BACKGROUND: An elevated pre-treatment neutrophil to lymphocytes ratio (NLR) is associated with poor prognosis in various malignancies. Optimal cut-off is highly variable across studies and could not be determined individually for a patient to inform his prognosis. We hypothesize that NLR variations could be more useful than baseline NLR to predict progression-free survival (PFS) and overall survival (OS) in patients (pts) receiving anti-PD1 treatment. PATIENTS AND METHODS: All pts with metastatic renal cell carcinoma (mRCC) and metastatic non-small cell lung cancer (mNSCLC) who received anti-PD1 nivolumab monotherapy in second-line setting or later were included in this French multicentric retrospective study. NLR values were prospectively collected prior to each nivolumab administration. Clinical characteristics were recorded. Associations between baseline NLR, NLR variations and survival outcomes were determined using Kaplan-Meier's method and multivariable Cox regression models. RESULTS: 161 pts (86 mRCC and 75 mNSCLC) were included with a median follow-up of 18 months. On the whole cohort, any NLR increase at week 6 was significantly associated with worse outcomes compared to NLR decrease, with a median PFS of 11 months vs 3.7 months (p < 0.0001), and a median OS of 28.5 months vs. 18 months (p = 0.013), respectively. In multivariate analysis, NLR increase was significantly associated with worse PFS (HR 2.2; p = 6.10-5) and OS (HR 2.1; p = 0.005). Consistent results were observed in each cohort when analyzed separately. CONCLUSION: Any NLR increase at week 6 was associated with worse PFS and OS outcomes. NLR variation is an inexpensive and dynamic marker easily obtained to monitor anti-PD1 efficacy.

Diffusion MRI: Technical principles and application to uterine cervical cancer.

Imaging is involved in the management of uterine cervical cancer with several objectives: 1/to assess local and lymph node extension of the initial disease; 2/evaluate treatment response to conservative therapy; 3/detect recurrences. Pelvic MRI is the first-line examination in all these indications. It is the key element for delineation after image fusion when the indication of chemoradiation therapy is made. It is also essential for guiding the placement of applicators and optimising the dosimetry of brachytherapy. The diffusion-weighted acquisition is a sequence sensitive to the motion of water molecules. It allows distinguishing water molecules with free diffusion from water molecules with diffusion restricted by obstacles such as cell membranes or the cytoskeleton. The diffusion is thus connected to the cellularity of the explored tissue, and the cancers, being hypercellular, will present a high signal. It thus provides additional information thanks to a high contrast between the tumour and the surrounding tissues, facilitating detection, evaluation of the volume and extent of the disease.

[Encapsulant peritonitis]. / Une péritonite encapsulante.

INTRODUCTION: Encapsulating peritonitis is a rare but severe chronic fibrotic condition related to the development of a white fibrous membrane surrounding the digestive tract. Idiopathic forms have been described, however the disease is most often secondary to peritoneal dialysis or more rarely to surgery. Treatment is difficult and not codified. CASE REPORT: We report here the observation of a 36-year-old patient whose diagnosis of encapsulating peritonitis was made after a long sub-occlusive history, eight years after a gastric ulcer perforation. DISCUSSION: We discuss the possible etiologies and we present a focus on this rare and little-known entity.

How to differentiate uterine leiomyosarcoma from leiomyoma with imaging.

Uterine leiomyomas, the most frequent benign myomatous tumors of the uterus, often cannot be distinguished from malignant uterine leiomyosarcomas using clinical criteria. Furthermore, imaging differentiation between both entities is frequently challenging due to their potential overlapping features. Because a suspected leiomyoma is often managed conservatively or with minimally invasive treatments, the misdiagnosis of leiomyosarcoma for a benign leiomyoma could potentially result in significant treatment delays, therefore increasing morbidity and mortality. In this review, we provide an overview of the differences between leiomyoma and leiomyosarcoma, mainly focusing on imaging characteristics, but also briefly touching upon their demographic, histopathological and clinical differences. The main indications and limitations of available cross-sectional imaging techniques are discussed, including ultrasound, computed tomography, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography. A particular emphasis is placed on the review of specific MRI features that may allow distinction between leiomyomas and leiomyosarcomas according to the most recent evidence in the literature. The potential contribution of texture analysis is also discussed. In order to help guide-imaging diagnosis, we provide an MRI-based diagnostic algorithm which takes into account morphological and functional features, both individually and in combination, in an attempt to optimize radiologic differentiation of leiomyomas from leiomyosarcomas.

Management of epithelial cancer of the ovary, fallopian tube, primary peritoneum. Long text of the joint French clinical practice guidelines issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, endorsed by INCa. (Part 2: systemic, intraperitoneal treatment, elderly patients, fertility preservation, follow-up).

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Long text of the Joint French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa. Part 1: Diagnostic exploration and staging, surgery, perioperative care, and pathology.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).

Five simultaneous artificial intelligence data challenges on ultrasound, CT, and MRI.

PURPOSE: The goal of this data challenge was to create a structured dynamic with the following objectives: (1) teach radiologists the new rules of General Data Protection Regulation (GDPR), while building a large multicentric prospective database of ultrasound, computed tomography (CT) and MRI patient images; (2) build a network including radiologists, researchers, start-ups, large companies, and students from engineering schools, and; (3) provide all French stakeholders working together during 5 data challenges with a secured framework, offering a realistic picture of the benefits and concerns in October 2018. MATERIALS AND METHODS: Relevant clinical questions were chosen by the Société Francaise de Radiologie. The challenge was designed to respect all French ethical and data protection constraints. Multidisciplinary teams with at least one radiologist, one engineering student, and a company and/or research lab were gathered using different networks, and clinical databases were created accordingly. RESULTS: Five challenges were launched: detection of meniscal tears on MRI, segmentation of renal cortex on CT, detection and characterization of liver lesions on ultrasound, detection of breast lesions on MRI, and characterization of thyroid cartilage lesions on CT. A total of 5,170 images within 4 months were provided for the challenge by 46 radiology services. Twenty-six multidisciplinary teams with 181 contestants worked for one month on the challenges. Three challenges, meniscal tears, renal cortex, and liver lesions, resulted in an accuracy>90%. The fourth challenge (breast) reached 82% and the lastone (thyroid) 70%. CONCLUSION: Theses five challenges were able to gather a large community of radiologists, engineers, researchers, and companies in a very short period of time. The accurate results of three of the five modalities suggest that artificial intelligence is a promising tool in these radiology modalities.

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Short text of the French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

[Part II drafted from the short text of the French guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Systemic and intraperitoneal treatment, elderly, fertility preservation, follow-up)]. / Partie 2 rédigée à partir de la synthèse de la recommandation nationale de bonnes pratiques cliniques intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Traitement systémique et intrapéritonéal, personnes âgées, préservation de la fertilité et suivi).

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

Combining Multiple Magnetic Resonance Imaging Sequences Provides Independent Reproducible Radiomics Features.

To evaluate the relative contribution of different Magnetic Resonance Imaging (MRI) sequences for the extraction of radiomics features in a cohort of patients with lacrimal gland tumors. This prospective study was approved by the Institutional Review Board and signed informed consent was obtained from all participants. From December 2015 to April 2017, 37 patients with lacrimal gland lesions underwent MRI before surgery, including axial T1-WI, axial Diffusion-WI, coronal DIXON-T2-WI and coronal post-contrast DIXON-T1-WI. Two readers manually delineated both lacrimal glands to assess inter-observer reproducibility, and one reader performed two successive delineations to assess intra-observer reproducibility. Radiomics features were extracted using an in-house software to calculate 85 features per region-of-interest (510 features/patient). Reproducible features were defined as features presenting both an intra-class correlation coefficient ≥0.8 and a concordance correlation coefficient ≥0.9 across combinations of the three delineations. Among these features, the ones yielding redundant information were identified as clusters using hierarchical clustering based on the Spearman correlation coefficient. All the MR sequences provided reproducible radiomics features (range 14(16%)-37(44%)) and non-redundant clusters (range 5-14). The highest numbers of features and clusters were provided by the water and in-phase DIXON T2-WI and water and in-phase post-contrast DIXON T1-WI (37, 26, 26 and 26 features and 14,12, 9 and 11 clusters, respectively). A total of 145 reproducible features grouped into 51 independent clusters was provided by pooling all the MR sequences. All MRI sequences provided reproducible radiomics features yielding independent information which could potentially serve as biomarkers.

[Part I drafted from the short text of the French Guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Diagnosis management, surgery, perioperative care, and pathological analysis)]. / Partie 1 rédigée sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Explorations diagnostiques et bilan d'extension, chirurgie, soins périopératoires et anatomopathologie).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

[Diagnostic value of imaging (ultrasonography, doppler, CT, MR, PET-CT) for the diagnosis of a suspicious ovarian mass and staging of ovarian, tubal or primary peritoneal cancer: Article drafted from the French Guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Valeur diagnostique de l'imagerie (échographie, doppler, scanner, IRM et TEP-TDM) pour le diagnostic d'une masse ovarienne suspecte et le bilan d'extension d'un cancer de l'ovaire, des trompes ou péritonéal primitif. Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

Transvaginal ultrasound is the first-line examination allowing characterizing 80 to 90% of adnexal masses (LP1). If performed by an expert, a subjective analysis is optimal. If performed by a non-expert, combining the use of Simple Rules with subjective analysis can achieve the diagnostic performance of an expert (LP1). Whichever the chosen model (subjective analysis by an expert or combination of the Simple Rules with a subjective analysis by a non-expert), a second-line examination will have to be proposed in the complex or indeterminate cases (about 20% of the masses) (grade A). The best-performing second-line test for characterization is pelvic MRI (LP1). If read by an expert, a pathological hypothesis can or should be suggested (grade D). In case of non-expert reading, the use of the ADNEXMR score allows a reliable assessment of the positive predictive value of malignancy to guide the patient towards the best management (gradeC). For preoperative assessment and evaluation of resectability of ovarian, fallopian tube or primary peritoneal cancer, it is recommended to perform a chest abdomen and pelvis CT with contrast agent injection (LP2, grade B). In the event of a contraindication to the injection of iodinated contrast agent (severe renal insufficiency, GFR <30mL/min), an abdomen and pelvis MRI completed with a non-injected chest CT may be proposed (LP3, grade C). By analogy, the same examinations are recommended to evaluate the disease after neo-adjuvant chemotherapy (LP3, Recommendation grade C). Further studies will be required to determine whether PET-CT provides better lymph node assessment before retroperitoneal and pelvic lymphadenectomy. PET-CT may be used to eliminate lymph node involvement in the absence of suspicious lymph nodes on morphological examination (LP3, grade C). The report should specify the localizations leading to a risk of incomplete cytoreductive surgery and lesions outside the field explored during surgery.

Morbidity of rectosigmoid resection in cytoreductive surgery for ovarian cancer. Risk factor analysis.

AIM: Rectosigmoid resection is often performed during cytoreductive surgery for ovarian cancer, to achieve the goal of no residual tumour. Here, we evaluated the morbidity associated with rectosigmoid resection and the underlying risk factors. METHODS: We retrospectively assessed consecutive patients managed with rectosigmoid resection during cytoreductive surgery for ovarian cancer at our centre in Paris, France, between 2005 and 2013. All previously identified risk factors were analysed. Major complications were defined as grade III-IV in the Clavien-Dindo classification. RESULTS: Of 228 patients, 116 had primary and 112 interval surgery; 43/228 [18.9%]; experienced major complications, and these were more common after primary surgery [24.1% vs. 13.4%, p = .04]. The 69 patients who had rectosigmoid resection [33 primary vs. 36 interval surgery, p = .32] had a higher morbidity rate compared to the other patients [30.4% vs. 14.6%, p = .006]. The anastomotic leakage rate was 2.89%. By multivariate logistic regression, independent risk factors for morbidity were postmenopausal status [adjusted odds ratio (aOR), 13.7; 95% confidence interval (95%CI), 1.2;161.9], surgery after neoadjuvant chemotherapy [aOR, 4.4; 95%CI, 1.1;18.8], and peritoneal stripping of the left; paracolic gutter [aOR, 11.3; 95%CI, 2.3;54.3]. CONCLUSION: The morbidity of rectosigmoid resection during cytoreductive surgery for ovarian cancer seems acceptable. Ileostomy does not seem associated with a lower risk of major complications or adjuvant bevacizumab with a higher complication rate.

Implementing diffusion-weighted MRI for body imaging in prospective multicentre trials: current considerations and future perspectives.

For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic information, assessing response and follow-up. Disease detection and staging involve qualitative, subjective assessment of images, whereas for prognosis, progression or response, quantitative evaluation of the apparent diffusion coefficient (ADC) is required. Validation and qualification of ADC in multicentre trials involves examination of i) technical performance to determine biomarker bias and reproducibility and ii) biological performance to interrogate a specific aspect of biology or to forecast outcome. Unfortunately, the variety of acquisition and analysis methodologies employed at different centres make ADC values non-comparable between them. This invalidates implementation in multicentre trials and limits utility of ADC as a biomarker. This article reviews the factors contributing to ADC variability in terms of data acquisition and analysis. Hardware and software considerations are discussed when implementing standardised protocols across multi-vendor platforms together with methods for quality assurance and quality control. Processes of data collection, archiving, curation, analysis, central reading and handling incidental findings are considered in the conduct of multicentre trials. Data protection and good clinical practice are essential prerequisites. Developing international consensus of procedures is critical to successful validation if ADC is to become a useful biomarker in oncology. KEY POINTS: • Standardised acquisition/analysis allows quantification of imaging biomarkers in multicentre trials. • Establishing "precision" of the measurement in the multicentre context is essential. • A repository with traceable data of known provenance promotes further research.

Image-guided transoral approach in severe craniovertebral junction malformations at the golden age of endoscopy: Regarding 2 cases.

INTRODUCTION: The image-guided transoral approach (IGTOA) provides a safe exposure to skull base midline lesions and the ventral aspect of the craniovertebral junction (CVJ). The IGTOA has several advantages: the head being placed in the extended position, it decreases the brainstem angulation during surgery; the approach being done through the avascular median pharyngeal raphe, not only lowers the bleeding risk but also provides a direct access to the bony pathology and granulation tissue accessible only via the ventral route. Wide field exposure and maneuverability are necessary to deal with the entire ventral brainstem compression in case of severe CVJ malformation to safely perform partial clivectomy and odontoidectomy. PRESENTATION OF TWO CASES: We illustrate the cases of two patients, 52-year-old and 42-year-old males, who presented with an impressive craniovertebral junction malformation, confirmed on CT and MRI images. They first underwent surgery by IGTOA, later completed by occipitocervical fixation. For the two patients, outcomes were assessed respectively at 4 and 5 years and showed satisfactory results both clinically and radiologically. CONCLUSION: In patients with marked ventral compression, the IGTOA provides direct and guided access to the anterior aspect of the CVJ and effective means for odontoidectomy and clivectomy. This approach is more easily maneuverable compared to the endonasal endoscopic approach. The IGTOA approach is quite a complex technique, requiring multidisciplinary skills, but it should primarily be used in difficult situations. We suggest that endonasal endoscopy is over-utilized. We consider that endoscopy should not be routinely performed and kept only for well-selected cases.