Cancers (Aug 2021)
Prospective Evaluation of Radiotherapy-Induced Immunologic and Genetic Effects in Colorectal Cancer Oligo-Metastatic Patients with Lung-Limited Disease: The PRELUDE-1 Study
- Alessandro Ottaiano,
- Angela Petito,
- Mariachiara Santorsola,
- Valerio Gigantino,
- Maurizio Capuozzo,
- Daniela Fontanella,
- Rossella Di Franco,
- Valentina Borzillo,
- Sergio Buonopane,
- Vincenzo Ravo,
- Esmeralda Scipilliti,
- Giuseppe Totaro,
- Marcello Serra,
- Gianluca Ametrano,
- Roberta Penta,
- Fabiana Tatangelo,
- Giosuè Scognamiglio,
- Annabella Di Mauro,
- Maurizio Di Bonito,
- Maria Napolitano,
- Stefania Scala,
- Giuseppina Rea,
- Sara Santagata,
- Angela Lombardi,
- Anna Grimaldi,
- Carlo Caputo,
- Anna Crispo,
- Egidio Celentano,
- Gianfranco De Feo,
- Luisa Circelli,
- Giovanni Savarese,
- Raffaella Ruggiero,
- Francesco Perri,
- Vincenza Granata,
- Gerardo Botti,
- Michele Caraglia,
- Guglielmo Nasti,
- Paolo Muto
Affiliations
- Alessandro Ottaiano
- SSD—Innovative Therapies for Abdominal Metastases Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Angela Petito
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Mariachiara Santorsola
- SSD—Innovative Therapies for Abdominal Metastases Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Valerio Gigantino
- Innovalab Scarl, Molecular Biology, Centro Direzionale, Isola A2, 80143 Naples, Italy
- Maurizio Capuozzo
- Innovalab Scarl, Molecular Biology, Centro Direzionale, Isola A2, 80143 Naples, Italy
- Daniela Fontanella
- Innovalab Scarl, Molecular Biology, Centro Direzionale, Isola A2, 80143 Naples, Italy
- Rossella Di Franco
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Valentina Borzillo
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Sergio Buonopane
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Vincenzo Ravo
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Esmeralda Scipilliti
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Giuseppe Totaro
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Marcello Serra
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Gianluca Ametrano
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Roberta Penta
- Oncohaematology Department, A.O.R.N. Santobono-Pausilipon di Napoli, 80123 Naples, Italy
- Fabiana Tatangelo
- Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Giosuè Scognamiglio
- Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Annabella Di Mauro
- Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Maurizio Di Bonito
- Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Maria Napolitano
- Functional Genomics, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Stefania Scala
- Functional Genomics, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Giuseppina Rea
- Functional Genomics, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Sara Santagata
- Functional Genomics, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Angela Lombardi
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, via de Crecchio 7, 80138 Naples, Italy
- Anna Grimaldi
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, via de Crecchio 7, 80138 Naples, Italy
- Carlo Caputo
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, via de Crecchio 7, 80138 Naples, Italy
- Anna Crispo
- Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Egidio Celentano
- Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Gianfranco De Feo
- Scientific Directorate, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Luisa Circelli
- AMES, Centro Polidiagnostico Strumentale srl, 80013 Naples, Italy
- Giovanni Savarese
- AMES, Centro Polidiagnostico Strumentale srl, 80013 Naples, Italy
- Raffaella Ruggiero
- AMES, Centro Polidiagnostico Strumentale srl, 80013 Naples, Italy
- Francesco Perri
- Head&Neck Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Vincenza Granata
- Radiology Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Gerardo Botti
- Scientific Directorate, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Michele Caraglia
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, via de Crecchio 7, 80138 Naples, Italy
- Guglielmo Nasti
- SSD—Innovative Therapies for Abdominal Metastases Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- Paolo Muto
- Radiotherapy Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
- DOI
- https://doi.org/10.3390/cancers13164236
- Journal volume & issue
-
Vol. 13,
no. 16
p. 4236
Abstract
Background: in recent years, the management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). The administration of SRT has been demonstrated, particularly in oligo-metastatic (om) CRC, to be a safe and effective option. Interestingly, it has been demonstrated that SRT can induce regression of tumors in non-irradiated regions (“abscopal effect”) through stimulation of anti-tumor immune effects (“radiation-induced immunity”). We have recently shown that lung-limited omCRC is characterized by regression of tumor clones bearing specific key driver gene mutations. Aims: to assess the genetic evolution on tumor cancer cells induced by SRT in lung-limited omCRC. Secondary objectives included descriptions of the abscopal effect, responses’ duration, toxicity, and progression-free survival. A translational research will be performed to evaluate tumor genetic evolution (through liquid biopsies and Next Generation Sequencing), HLA class I repertoire, peripheral immune cells, and cytokine dynamics. Methods: PRELUDE-1 is a prospective translational study. SRT will be administered only to the largest nodule (with a maximum diameter ≤ 25 mm) in omCRC with two or three radiologically evident lesions. The sample size is based on the innovative hypothesis that radiation-induced immunity could induce regression of tumor clones bearing KRAS oncogene mutations. According to the binomial test, considering the frequency of KRAS mutations and assuming a probability of mutant KRAS→wild type KRAS of p0 = 0.0077, with α = 0.05 and 1-β = 0.60, the final sample size is 25 patients.
Keywords