Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study
Abstract Background Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as “oligo-metastatic dis...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11479-w |
| _version_ | 1797559067124695040 |
|---|---|
| author | Alessandro Ottaiano Antonella De Luca Mariachiara Santorsola Giosuè Scognamiglio Annabella Di Mauro Paolo Chiodini Matilde Lambiase Alessandra Sacco Antonella Petrillo Vincenza Granata Roberta Fusco Edoardo Mercadante Nicola Martucci Giuseppe De Luca Antonello La Rocca Egidio Celentano Anna Crispo Piergiacomo Di Gennaro Fabiana Tatangelo Gerardo Ferrara Francesco Izzo Andrea Belli Renato Patrone Paolo Delrio Daniela Rega Silvia De Franciscis Paolo Muto Vincenzo Ravo Rossella Di Franco Valentina Borzillo Sara Santagata Giuseppina Rea Daniela Castaldo Ugo Pace Gianfranco De Feo Stefania Scala Guglielmo Nasti Nicola Normanno |
| author_facet | Alessandro Ottaiano Antonella De Luca Mariachiara Santorsola Giosuè Scognamiglio Annabella Di Mauro Paolo Chiodini Matilde Lambiase Alessandra Sacco Antonella Petrillo Vincenza Granata Roberta Fusco Edoardo Mercadante Nicola Martucci Giuseppe De Luca Antonello La Rocca Egidio Celentano Anna Crispo Piergiacomo Di Gennaro Fabiana Tatangelo Gerardo Ferrara Francesco Izzo Andrea Belli Renato Patrone Paolo Delrio Daniela Rega Silvia De Franciscis Paolo Muto Vincenzo Ravo Rossella Di Franco Valentina Borzillo Sara Santagata Giuseppina Rea Daniela Castaldo Ugo Pace Gianfranco De Feo Stefania Scala Guglielmo Nasti Nicola Normanno |
| author_sort | Alessandro Ottaiano |
| collection | DOAJ |
| description | Abstract Background Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as “oligo-metastatic disease” (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. Methods The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. Discussion Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. Trial registration ClinicalTrials.gov ID NCT05806151. |
| first_indexed | 2024-03-10T17:40:27Z |
| format | Article |
| id | doaj.art-0f8b4dec1455442a95550e330fb15be2 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-10T17:40:27Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-0f8b4dec1455442a95550e330fb15be22023-11-20T09:43:06ZengBMCBMC Cancer1471-24072023-10-012311910.1186/s12885-023-11479-wOligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION studyAlessandro Ottaiano0Antonella De Luca1Mariachiara Santorsola2Giosuè Scognamiglio3Annabella Di Mauro4Paolo Chiodini5Matilde Lambiase6Alessandra Sacco7Antonella Petrillo8Vincenza Granata9Roberta Fusco10Edoardo Mercadante11Nicola Martucci12Giuseppe De Luca13Antonello La Rocca14Egidio Celentano15Anna Crispo16Piergiacomo Di Gennaro17Fabiana Tatangelo18Gerardo Ferrara19Francesco Izzo20Andrea Belli21Renato Patrone22Paolo Delrio23Daniela Rega24Silvia De Franciscis25Paolo Muto26Vincenzo Ravo27Rossella Di Franco28Valentina Borzillo29Sara Santagata30Giuseppina Rea31Daniela Castaldo32Ugo Pace33Gianfranco De Feo34Stefania Scala35Guglielmo Nasti36Nicola Normanno37Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Section of Statistics, Department of Mental Health and Public Medicine, Università degli Studi della Campania Luigi VanvitelliIstituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Istituto Nazionale Tumori, IRCCS “G. Pascale”Abstract Background Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as “oligo-metastatic disease” (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. Methods The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. Discussion Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. Trial registration ClinicalTrials.gov ID NCT05806151.https://doi.org/10.1186/s12885-023-11479-wOligometastatic diseasesColorectal cancerBiomarkersGeneticsPrognosis |
| spellingShingle | Alessandro Ottaiano Antonella De Luca Mariachiara Santorsola Giosuè Scognamiglio Annabella Di Mauro Paolo Chiodini Matilde Lambiase Alessandra Sacco Antonella Petrillo Vincenza Granata Roberta Fusco Edoardo Mercadante Nicola Martucci Giuseppe De Luca Antonello La Rocca Egidio Celentano Anna Crispo Piergiacomo Di Gennaro Fabiana Tatangelo Gerardo Ferrara Francesco Izzo Andrea Belli Renato Patrone Paolo Delrio Daniela Rega Silvia De Franciscis Paolo Muto Vincenzo Ravo Rossella Di Franco Valentina Borzillo Sara Santagata Giuseppina Rea Daniela Castaldo Ugo Pace Gianfranco De Feo Stefania Scala Guglielmo Nasti Nicola Normanno Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study BMC Cancer Oligometastatic diseases Colorectal cancer Biomarkers Genetics Prognosis |
| title | Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study |
| title_full | Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study |
| title_fullStr | Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study |
| title_full_unstemmed | Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study |
| title_short | Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study |
| title_sort | oligo metastatic neoplasms from the gastro intestinal tract identification of clinical and molecular drivers the prediction study |
| topic | Oligometastatic diseases Colorectal cancer Biomarkers Genetics Prognosis |
| url | https://doi.org/10.1186/s12885-023-11479-w |
| work_keys_str_mv | AT alessandroottaiano oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT antonelladeluca oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT mariachiarasantorsola oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT giosuescognamiglio oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT annabelladimauro oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT paolochiodini oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT matildelambiase oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT alessandrasacco oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT antonellapetrillo oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT vincenzagranata oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT robertafusco oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT edoardomercadante oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT nicolamartucci oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT giuseppedeluca oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT antonellolarocca oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT egidiocelentano oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT annacrispo oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT piergiacomodigennaro oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT fabianatatangelo oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT gerardoferrara oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT francescoizzo oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT andreabelli oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT renatopatrone oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT paolodelrio oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT danielarega oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT silviadefranciscis oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT paolomuto oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT vincenzoravo oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT rosselladifranco oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT valentinaborzillo oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT sarasantagata oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT giuseppinarea oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT danielacastaldo oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT ugopace oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT gianfrancodefeo oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT stefaniascala oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT guglielmonasti oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy AT nicolanormanno oligometastaticneoplasmsfromthegastrointestinaltractidentificationofclinicalandmoleculardriversthepredictionstudy |