PMID- 35724442
OWN - NLM
STAT- MEDLINE
DCOM- 20220816
LR  - 20221108
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 172
DP  - 2022 Sep
TI  - Feasibility, safety and efficacy of human intra-tumoral immuno-therapy. Gustave 
      Roussy's initial experience with its first 100 patients.
PG  - 1-12
LID - S0959-8049(22)00303-3 [pii]
LID - 10.1016/j.ejca.2022.05.024 [doi]
AB  - PURPOSE: Many intratumoural (IT) immunotherapies are currently developed in the 
      clinic with the aim of overcoming primary and secondary resistance and/or to 
      limit on-target/off-tumour toxicities of immune checkpoint targeted therapies. 
      This study aimed to describe the feasibility, safety and efficacy of IT 
      immunotherapy treatments. DESIGN: This retrospective single-centre study included 
      the first 100 consecutive patients enrolled in Gustave Roussy's Human 
      IntraTumoral-ImmunoTherapy (HIT-IT) program. Patient characteristics, target 
      description, image guidance, safety and response according to iRECIST (Response 
      Evaluation Criteria in Solid Tumours for immunotherapy trials) were recorded. 
      Predictive factors of complications and responses were analysed. Survival was 
      also reported. RESULTS: From 09/2015 to 05/2020, 100 patients had 115 tumours 
      injected during 423 treatment cycles. Most frequent primary tumour arose from the 
      skin (n = 49), digestive track (n = 4) or head and neck (n = 8). Injected 
      tumours' mean diameter was 37 +/- 23 mm, and a median number of 4 IT injections per 
      patient (interquartile range:3-5) were performed. Targeted tumours for IT 
      injections were superficial lymph nodes (36.5%), subcutaneous lesions (25.2%), 
      liver tumours (20.9%) and others (17.4% including tumour sites such as deep lymph 
      nodes or lung). Most patients (72%) received systemic immunotherapy in 
      combination with HIT-IT. Procedure- and drug-related adverse events (AEs) 
      occurred in 11.3% and 33.3% of the treatment cycles, respectively. Only 3 
      procedure-related AEs were grade-3 (0.7%); and no grade-4 or 5 occurred. Among 
      all cycles, 7 grade-3 and 1 grade-5 drug-related AEs were reported. Complete and 
      partial responses were achieved for 5% and 18% of patients, respectively, while 
      stable disease was the best response for 11%. Patients receiving HIT-IT as a 
      1st-line treatment (24%), or not previously pre-treated with immunotherapy (53%) 
      responded better, p = 0.001 and p = 0.004, respectively. From 1st cycle of IT, 
      12-month overall progression-free survival and overall survival were 21% (14-31%) 
      and 57% (47-68%), respectively. CONCLUSIONS: This retrospective study, conducted 
      on patients with cancer and treated within clinical trials at Gustave Roussy, 
      demonstrates the feasibility and safety of the IT immunotherapy strategy.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Tselikas, Lambros
AU  - Tselikas L
AD  - Centre D'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France; 
      Radiologie Interventionnelle, Gustave Roussy, Villejuif, France; Laboratoire de 
      Recherche Translationnelle en Immunotherapie (LRTI), INSERM U1015, Villejuif, 
      France; Faculte de Medecine, Universite Paris Saclay, Le Kremlin-Bicetre, France. 
      Electronic address: lambros.tselikas@gustaveroussy.fr.
FAU - Dardenne, Antoine
AU  - Dardenne A
AD  - Departement D'Innovation Therapeutique et D'Essais Precoces (DITEP), Gustave 
      Roussy, Villejuif, France.
FAU - de Baere, Thierry
AU  - de Baere T
AD  - Centre D'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France; 
      Radiologie Interventionnelle, Gustave Roussy, Villejuif, France; Faculte de 
      Medecine, Universite Paris Saclay, Le Kremlin-Bicetre, France.
FAU - Faron, Matthieu
AU  - Faron M
AD  - Oncostat U1018, INSERM, Paris-Saclay University, Labeled Ligue Contre le Cancer, 
      Villejuif, France.
FAU - Ammari, Samy
AU  - Ammari S
AD  - Departement de Radiologie, Gustave Roussy, Villejuif, France.
FAU - Farhane, Siham
AU  - Farhane S
AD  - Centre D'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France.
FAU - Suzzoni, Steve
AU  - Suzzoni S
AD  - Departement Pharmacie, Gustave Roussy, Villejuif, France.
FAU - Danlos, Francois-Xavier
AU  - Danlos FX
AD  - Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), INSERM U1015, 
      Villejuif, France; Departement D'Innovation Therapeutique et D'Essais Precoces 
      (DITEP), Gustave Roussy, Villejuif, France.
FAU - Raoult, Thibault
AU  - Raoult T
AD  - Service de Promotion des Essais Cliniques, Gustave Roussy, Villejuif, France.
FAU - Susini, Sandrine
AU  - Susini S
AD  - Centre D'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France; 
      Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), INSERM U1015, 
      Villejuif, France.
FAU - Al Shatti, Nael
AU  - Al Shatti N
AD  - Centre D'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France; 
      Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), INSERM U1015, 
      Villejuif, France.
FAU - Mouraud, Severine
AU  - Mouraud S
AD  - Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), INSERM U1015, 
      Villejuif, France.
FAU - Deschamps, Frederic
AU  - Deschamps F
AD  - Radiologie Interventionnelle, Gustave Roussy, Villejuif, France.
FAU - Kobe, Adrian
AU  - Kobe A
AD  - Radiologie Interventionnelle, Gustave Roussy, Villejuif, France.
FAU - Delpla, Alexandre
AU  - Delpla A
AD  - Radiologie Interventionnelle, Gustave Roussy, Villejuif, France.
FAU - Roux, Charles
AU  - Roux C
AD  - Radiologie Interventionnelle, Gustave Roussy, Villejuif, France.
FAU - Baldini, Capucine
AU  - Baldini C
AD  - Departement D'Innovation Therapeutique et D'Essais Precoces (DITEP), Gustave 
      Roussy, Villejuif, France.
FAU - Soria, Jean-Charles
AU  - Soria JC
AD  - Faculte de Medecine, Universite Paris Saclay, Le Kremlin-Bicetre, France.
FAU - Barlesi, Fabrice
AU  - Barlesi F
AD  - Departement de Medecine Oncologique, Gustave Roussy, Villejuif, France; Aix 
      Marseille University, CNRS, INSERM, CRCM, Marseille, France.
FAU - Massard, Christophe
AU  - Massard C
AD  - Faculte de Medecine, Universite Paris Saclay, Le Kremlin-Bicetre, France; 
      Departement D'Innovation Therapeutique et D'Essais Precoces (DITEP), Gustave 
      Roussy, Villejuif, France.
FAU - Robert, Caroline
AU  - Robert C
AD  - Faculte de Medecine, Universite Paris Saclay, Le Kremlin-Bicetre, France; 
      Departement de Medecine Oncologique, Gustave Roussy, Villejuif, France.
FAU - Champiat, Stephane
AU  - Champiat S
AD  - Centre D'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France; 
      Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), INSERM U1015, 
      Villejuif, France; Departement D'Innovation Therapeutique et D'Essais Precoces 
      (DITEP), Gustave Roussy, Villejuif, France.
FAU - Marabelle, Aurelien
AU  - Marabelle A
AD  - Centre D'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France; 
      Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), INSERM U1015, 
      Villejuif, France; Faculte de Medecine, Universite Paris Saclay, Le 
      Kremlin-Bicetre, France; Departement D'Innovation Therapeutique et D'Essais 
      Precoces (DITEP), Gustave Roussy, Villejuif, France.
LA  - eng
PT  - Journal Article
DEP - 20220618
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Immunologic Factors)
SB  - IM
MH  - Feasibility Studies
MH  - Humans
MH  - Immunologic Factors
MH  - *Immunotherapy/adverse effects/methods
MH  - *Liver Neoplasms
MH  - Response Evaluation Criteria in Solid Tumors
MH  - Retrospective Studies
OTO - NOTNLM
OT  - Combination
OT  - Immuno-oncology
OT  - In situ
OT  - Interventional radiology
OT  - Intratumoral
OT  - Local immunotherapy
COIS- Conflict of interest statement The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Lambros Tselikas received honoraria from the following companies: 
      Amgen, Boston Scientific, Medincell, GE Healthcare, Guerbet, SIRTEX, Quantum 
      Surgical, and received grants from BMS foundation and Terumo. Thierry de Baere, 
      has consulted or received advisory fees from: AstraZeneca, Boston Scientific, 
      Eisai, GE Healthcare, Guerbet, Johnson & Johnson, Medtronic, Nanobiotix, 
      Roche, Terumo, Quantum surgical, Frederic Deschamps, has received honoraria from: 
      Ablatech, Boston Scientific, General Electric, Medtronic and Terumo. Capucine 
      Baldini, reports research funding from BMS, honoraria from Sanofi, BMS, Astra 
      Zeneca, and Abbvie Jean-Charles Soria, received honoraria from Astex, 
      AstraZeneca, Bayer, Blend Therapeutics, Boehringer-Ingelheim, Clovis, Eli Lily, 
      Gammamabs, Merus, Mission Therapeutics, Pfizer, Pharmamar, Pierre Fabre, Roche, 
      Sanofi, Servier, Symhogen, Tarveda; is a Gritstone stockholder and was an 
      AstraZeneca full time employee from Sept 2017 to Dec 2019 and is an AMGEN full 
      time employee since July 2021. Fabrice Barlesi, reports personal fees from 
      AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli Lilly 
      Oncology, F. Hoffmann-La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer 
      and Takeda. Christophe Massard, has consulted or received advisory fees from: 
      Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, 
      Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi 
      and Orion. Caroline Robert, has consulted for BMS, Pierre Fabre, Novartis, Amgen, 
      Merck, MSD, Roche, Sanofi, Biothera, Ultimovacs. Stephane Champiat, has received 
      honoraria or consulted for the following companies: Amgen, AstraZeneca, BMS, 
      Janssen, MSD, Novartis and Roche. Aurelien Marabelle, has participated to 
      Scientific Advisory Boards or Consulted for the following companies: MSD, Astra 
      Zeneca/Medimmune, Bayer, Pillar Partners, Bioncotech, Rigontec, Curevac, Servier, 
      Amgen. Antoine Dardenne, , Matthieu Faron, , Samy Ammari, Siham Farhane, Steve 
      Suzzoni, Francois-Xavier Danlos, Thibault Raoult, Sandrine Susini, Nael 
      Al-Shatti, Severine Mouraud, Adrian Kobe, Alexandre Delpla, Charles Roux, have no 
      conflict of interest to declare *No specific funding was obtained for this study. 
      The Intratumoral programm of Gustave Roussy is partially funded by the Centre 
      d'Investigation Clinique BIOTHERIS (CIC1428 INSERM)
EDAT- 2022/06/21 06:00
MHDA- 2022/08/17 06:00
CRDT- 2022/06/20 18:03
PHST- 2022/01/07 00:00 [received]
PHST- 2022/05/10 00:00 [revised]
PHST- 2022/05/13 00:00 [accepted]
PHST- 2022/06/21 06:00 [pubmed]
PHST- 2022/08/17 06:00 [medline]
PHST- 2022/06/20 18:03 [entrez]
AID - S0959-8049(22)00303-3 [pii]
AID - 10.1016/j.ejca.2022.05.024 [doi]
PST - ppublish
SO  - Eur J Cancer. 2022 Sep;172:1-12. doi: 10.1016/j.ejca.2022.05.024. Epub 2022 Jun 
      18.