Prospective Evaluation of Radiotherapy-Induced Immunologic and Genetic Effects in Colorectal Cancer Oligo-Metastatic Patients with Lung-Limited Disease: The PRELUDE-1 Study

Autor: Vincenza Granata, Valerio Gigantino, Annabella Di Mauro, Fabiana Tatangelo, Angela Lombardi, Maurizio Di Bonito, Guglielmo Nasti, Maria Napolitano, Gerardo Botti, Rossella Di Franco, Michele Caraglia, Francesco Perri, Egidio Celentano, Giuseppe Totaro, Alessandro Ottaiano, Luisa Circelli, Sergio Buonopane, Marcello Serra, Angela Petito, Raffaella Ruggiero, Mariachiara Santorsola, Giuseppina Rea, Giovanni Savarese, Sara Santagata, Giosuè Scognamiglio, Anna Crispo, Stefania Scala, Esmeralda Scipilliti, Gianluca Ametrano, V. Borzillo, Roberta Penta, Maurizio Capuozzo, Daniela Fontanella, Anna Maria Grimaldi, Paolo Muto, Vincenzo Ravo, Gianfranco De Feo, Carlo Caputo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cancers, Vol 13, Iss 4236, p 4236 (2021)
Cancers
ISSN: 2072-6694
Popis: Simple Summary The management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). It is a safe and effective option, particularly in oligo-metastatic (om) CRC patients. 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. The aim of the PRELUDE-1 study is to assess the genetic and immunologic evolutions on tumor cancer/host cells induced by SRT in lung-limited omCRC through liquid biopsies and Next Generation Sequencing of tumor exome, HLA repertoire assessment, peripheral immune cells, and cytokine dynamics characterizations. An important secondary objective is the first prospective evaluation of the abscopal effect. The PRELUDE-1 results will help to identify subsets of patients more prone to show the abscopal effect. The PRELUDE-1 trial was registered into the clinicaltrials.gov registry on 22 April 2021, with identifier NCT04854213. 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.
Databáze: OpenAIRE
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