Interventional Oncology (IO) is a subspecialty field of Interventional Radiology (IR) that deals with the treatment of cancer and cancer-related problems using targeted minimally invasive procedures performed under image guidance. IO has successfully established itself as an essential pillar within the armamentarium of multidisciplinary oncologic care, alongside Medical, Surgical, and Radiation Oncology. IO uses X-ray including Cone Beam CT (CBCT), ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) to help the guidance of miniaturized instruments (e.g. biopsy needles, ablation system, intravascular catheters) to allow targeted minimally invasive treatment of solid tumors located in various organs, including liver, kidneys, lungs, and bones.
The 3 sites of Paris Cancer Institute: CARPEM have a strong activity in IO with dedicated IR division supported by a team of nurses, radiographic technicians and administrative staff providing comprehensive oncological interventional clinical service. A total of 6 interventional radiology suit are implanted (2 angio-suite and 1 Interventional CT scanner at HEGP, 1 angio-suit and 1 shared CT scanner with diagnostic department at Cochin, and one share CT scanner with diagnostic department at Necker).
All oncology specialties are involved and work closely with interventional radiologists. More than 10 full time senior interventional radiologist (IRs) are dedicated to patients care. IO activities are organized in outpatient or with a dictated hospitalization facility of 10 beds at HEGP. This original structure was built at the site of HEGP in 2017, and is co-administered by oncologists and IRs. This program took in charges 6000 patients during the last year. The leading activities are chemoembolization, intra-arterial chemotherapy port placement, trans-arterial radioembolization, solid organ tumor ablation, cimentoplasty, biopsies and other supportive care intervention (venous port placement, gastrostomy, pain management, biliary and urinary drainage, lymphatic and venous obstruction..). Moreover each group develops specifics skills. HEGP-IO group is recognized for its expertise in intra-arterial therapies of primary and secondary liver tumors. Necker-IO Group had a long experience in percutaneous ablation of renal cells cancer. Cochin-IO group is specialized in percutaneous is ablations liver, bone and chest tumors.
Homogenous and standardized protocols of patient care are deployed in all groups, and are fully integrated in oncologic patient pathway. All these activities are structured around 16 (7 HEGP + 7 CCH + 2 NCK) weekly cancer multidisciplinary team meetings including members of other program of the of Paris Cancer Institute: CARPEM. These meetings follow the INCA national guidelines, and ESMO guidelines.
IO clinical research is structured across a dedicated research organization and think-tank called GRETAC (groupe de recherche en traitement intra-arteriel du cancer).
The clinical research team is composed by research engineer (n=1) and clinical research technician (n=2). This organization is working closely with URC (Unité de Recherche Clinique). To date 5 ongoing clinical trials (2 phases VI 1 phase III, 2 phase II) in collaboration with oncologists and surgeons are actively recruiting patients (see annex 2.). More over a strong interaction with the CIC-CEPEC (Centre d’investigation Clinique – Centre d’essais précoces en cancérologie) allows the development of early stage clinical research such as first in man. In addition; because IO uses various medical devices, such as drug eluted beads, ablation probes, a robust collaboration with the pharmacy department has been established for a while that allows device dedicated clinical research in accordance with the new medical device regulation.
The GRETAC involve IOs, oncologists, radiotherapists and surgeons (all member of Paris Cancer Institute CARPEM). The goal of this group is to investigate any oncological unmet need, and to propose intra-arterial delivery of therapeutic compound as treatment. To date the group has already supports 3 original projects. The first one was a phase 2 clinical study of breast liver metastases chemoembolization (reference below). The second one investigates the feasibility of prostate cancer chemoembolization with docetaxel eluted beads in pet dogs model, before envisioning a phase clinical study. The publication of the animal model is ongoing. At last the 3rd is a gene directed enzyme prodrug therapy that is still on a preclinical stage.
The team is also investigating through different images modalities, in a pre- or an intra-procedural manner, predicting factors of treatment response within the goal to personalized patient care.
Translational research involves 17 senior researchers and mainly 4 Inserm research Team located to the PARCC and the Cordeliers research centers. These research teams are led by Bertrand Tavitian, Pierre Laurent-Puig, Stéphanie Allasonniere and Jérôme Bertherat. The main translational researches fields are about image guided therapies, artificial intelligence and Ultrasound technologies. Among the main the recent results we can mention:
The proof of concept of a “gene directed enzyme prodrug therapy” (GDEPT) vectorized by transduced mesenchymal stems cells (MSC) through intra-arterial delivery. This project is developing within the collaboration of to CARPEM affiliated research unit (INSERM 970 and INSERM 1138). This approach allows the complete eradication of VX2 liver tumor in rabbit and prevents the appearance of metastatic spread. This approach is based on an optimized suicide gene (CYP2B6* (patented PCT/EP2012/O58219).), 13-fold more efficient than CYP2B6wt to metabolize CPA This therapy works as a Trojan horse. MSC-CYP2B6* intra-arterially delivered into the tumor microenvironment are activating par intravenous injection of CPA. The tumor eradication mechanism is composed by a by-stander effect (cytotoxic metabolites diffuse free), induction of immune cell death, depression of Treg cells, and CD8+ T lymphocytes immune response against tumor cells. This last step protects against tumor recurrence and is blocking metastatic spread. The next step are the optimization of the Trojan therapy though dose step study to determine the maximum tolerated dose on the VX2 liver tumor model.
The feasibility of docetaxel-eluded beads chemoembolization in a canine native prostate cancer model using a comparative medicine concept. In this study were show the feasibility of Docetaxcel chemoembolization with complete eradication of the tumor with favorable pharmacokinetic profile and a low rate of adverse event. The next step is to initiate a phase I clinical study.
Use of machine learning to build a predictive model for patient outcome after Chemoembolization. This is using the imaging data provided by a series of patients treated with DEBIRI (Irinotecan drug eluted beads for colorectal liver metastases), we are learning the distribution of shape trajectories to compute ‘good outcome’ and ‘bad outcome’ spatiotemporal evolutions. This model will then be externally validated on a prospective cohort of patients with liver dominant colorectal cancer treated with DEBIRI. The objective is to narrow down two scenarios that will either encourage clinicians to pursue or to interrupt the chemoembolization treatment plan. This project is supported by a HEGP / Ecole Polytechnique collaboration.
The IO Program integrates 7 residents every 6 months and 5 fellows. In the 3 IR department are organize every week lessons around IR including clinical, and technical specificities.
Since 2017 a dedicated training pathway has been set for residents and fellows. The pathway is organized around simulation training sessions at Ilumens facility (http://fondation.parisdescartes.fr/ilumens). The pedagogic program content is based on the learning of Interventional radiology procedure. This is including knowledge acquisition of pathology, procedures indication, and procedure work-up and follow-up though interactive lessons, cased based discussion, and the use of virtual augmented reality phantoms, standardized patient (actors) around realistic scenarios. Technical skills are taught with dedicated simulators. These simulators are mimicking different aspect of IR such as endovascular network navigation for procedures such as chemoembolization, Ultrasound/ CT scanner guidance for percutaneous procedures eg. biopsies, thermal ablation, cimentoplasties… Serval metric have been deployed to serve student self-assessments. A Mentoring follow-up is organized to guide student in their knowledge acquisition.
In 2021, to fit perfectly the new national teaching program of interventional radiology (option radiologie interventionnelle avancée), trainee’s selection interview will be organized. Then IR trainees will be referred to a personalized training program.
This teaching Program is sponsored by an ARS-Ile de France (Agence Régional de Santé) Grant of 80K€.
Based on our skillness we would like to
Develop new intra-arterial therapies or tumor ablation strategies in combination with immunotherapies to enhance abscopal effect.
Extend the field of intra-arterial chemotherapies/ embolization delivery such as lung cancer, cervix cancer…
Develop homogeneous patient care and patient pathway over our 3 hospitals. This is including:
– Patient referral form oncologic specialties, – Facilitate patient access to biopsies – Morbidity and mortality indicators eg. rehospitalization rate at 30 days, pain management…
The selected following publications highlight the strength of clinical research developed in interventional oncology program:
Pellerin O, Pereira H, Van Ngoc Ty C, Moussa N, Del Giudice C, Pernot S, Déan C, Chatellier G, Sapoval M. Is dual-phase C-arm CBCT sufficiently accurate for the diagnosis of colorectal cancer liver metastasis during liver intra-arterial treatment? Eur Radiol. 2019 Oct;29(10):5253-5263.
Martelli N, Eskenazy D, Déan C, Pineau J, Prognon P, Chatellier G, Sapoval M, Pellerin O. New European Regulation for Medical Devices: What Is Changing? Cardiovasc Intervent Radiol. 2019 Sep;42(9):1272-1278.
Motte AF, Diallo S, van den Brink H, Châteauvieux C, Serrano C, Naud C,Steelandt J, Alsac JM, Aubry P, Cour F, Pellerin O, Pineau J, Prognon P, Borget I, Bonan B, Martelli N. Existing reporting guidelines for clinical trials are not completely relevant for implantable medical devices: a systematic review. J Clin Epidemiol. 2017 Nov;91:111-120.
Pellerin O, Pereira H, Moussa N, Del Giudice C, Pernot S, Dean C, Chatellier G, Sapoval M. Can cone-beam CT tumor blood volume predicts the response to chemoembolization of colorectal liver metastases? Results of an observational study. Eur Radiol. 2019 Sep;29(9):5022-5031.
Dohan A, Bouquot M, Rousset P, Eveno C. ASO Author Reflections: Proposal of a New Preoperative Score to Predict Resectability in Pseudomyxoma Peritonei. Ann Surg Oncol. 2019 Dec;26(Suppl 3):541-542.
Dohan A, Gallix B, Guiu B, Le Malicot K, Reinhold C, Soyer P, Bennouna J, Ghiringhelli F, Barbier E, Boige V, Taieb J, Bouché O, François E, Phelip JM, Borel C, Faroux R, Seitz JF, Jacquot S, Ben Abdelghani M, Khemissa-Akouz F, Genet D, Jouve JL, Rinaldi Y, Desseigne F, Texereau P, Suc E, Lepage C, Aparicio T, Hoeffel C; PRODIGE 9 Investigators and PRODIGE 20 Investigators. Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab. Gut. 2019 May 17.
Pernot S, Velut G, Kourie RH, Amouyal G, Sapoval M, Pointet AL, Landi B, Zaimi Y, Lepère C, Pellerin O, Taieb J. 5-FU or mitomycin C hepatic arterial infusion after failure of arterial oxaliplatin in patients with colorectal cancer unresectable liver metastases. Clin Res Hepatol Gastroenterol. 2018 Jun;42(3):255-260
Amouyal G, Pernot S, Déan C, Cholley B, Scotté F, Sapoval M, Pellerin O. Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance. Diagn Interv Imaging. 2017 Nov;98(11):793-799.
Lin YT, Médioni J, Amouyal G, Déan C, Sapoval M, Pellerin O. Doxorubicin-Loaded 70-150 μm Microspheres for Liver-Dominant Metastatic Breast Cancer: Results and Outcomes of a Pilot Study. Cardiovasc Intervent Radiol. 2017 Jan;40(1):81-89.
Annex 1: Main indicators of clinical activities
Intra-arterial treatments (TACE, IHAC, TARE…)
Supportive care interventions
Annex 2: Ongoing Clinical Trials
Cardiovascular and Interventional Radiological Society of Europe/ CIREL
P. Peirrera – O. Pellerin
Cardiovascular and Interventional Radiological Society of Europe / CIRT-Fr
I. Bilbao -O. Pellerin
Fédération Francophone de Cancérologie Digestive OSCAR
J. Taieb – O. Pellerin
Gustave Roussy, Cancer Campus, Grand Paris PACHA
D. Goéré – J. Taieb – O. Pellerin
UNICANCER / SULTAN
V. Boige – J. Taieb – O. Pellerin
University Hospital, Montpellier/ GEMOXIA
B. Guiu – O. Pellerin
NeuWave J&J / NOLA
Assistance Publique – Hôpitaux de Paris / WAZA-ARY
Gustave Roussy, Cancer Campus, Grand Paris / ISILI (In Situ Immunotherapy of LIver Metastases)