Up-Front Immune Checkpoint Inhibitors in Patients with Multiple Synchronous Primary Tumors, Including dMMR/MSI-H Gastrointestinal Malignancies: A Case Series and Review of the Literature.
5 affiliations
- 1Medical Oncology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
- 2Medical Oncology Unit, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy.
- 3Department of Oncology and Hematology, Modena University Hospital, University of Modena and Reggio Emilia, 41124 Modena, Italy.
- 4Pathology Unit, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy.
- 5Nuclear Medicine Unit, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy.
Abstract
The management of patients with multiple synchronous primary tumors remains challenging, particularly in individuals who are not candidates for surgery. While immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors, evidence supporting their use as a non-operative strategy in patients with multiple malignancies is limited, as this population is excluded from clinical trials. We report three cases of patients with synchronous primary tumors, including gastrointestinal malignancies with dMMR status, treated with up-front ICIs. Treatment strategies were individualized based on the patient's clinical condition, tumor burden, and molecular profile. All patients achieved meaningful and durable responses with long-term survival exceeding two to four years, supporting the feasibility of a non-operative strategy and organ preservation in carefully selected patients, including the frail subgroup population. Immunotherapy-based approaches were well tolerated, with a manageable safety profile. Notably, none of our patients underwent surgical resection. However, these observations are hypothesis-generating and cannot establish the efficacy or equivalence of immunotherapy to standard surgical management. Our findings extend current evidence to a largely underrepresented population and support a personalized, multidisciplinary, response-adapted approach. Prospective studies are warranted to better define patient selection, optimal treatment duration, and long-term outcomes of non-operative strategies in this setting.
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BibTeX
@article{damato2026upfront,
title = {{Up-Front Immune Checkpoint Inhibitors in Patients with Multiple Synchronous Primary Tumors, Including dMMR/MSI-H Gastrointestinal Malignancies: A Case Series and Review of the Literature.}},
author = {Angela Damato and Martina Rotolo and Nicoletta Sparacino and Eleonora Borghi and Giacomo Santandrea and Angelina Filice and Mario Larocca and Carmine Pinto},
journal = {Current oncology (Toronto, Ont.)},
year = {2026},
month = oct,
doi = {10.3390/curroncol33100594},
url = {https://europepmc.org/article/MED/42930161},
note = {CC BY},
}
RIS
TY - JOUR
TI - Up-Front Immune Checkpoint Inhibitors in Patients with Multiple Synchronous Primary Tumors, Including dMMR/MSI-H Gastrointestinal Malignancies: A Case Series and Review of the Literature.
AU - Angela Damato
AU - Martina Rotolo
AU - Nicoletta Sparacino
AU - Eleonora Borghi
AU - Giacomo Santandrea
AU - Angelina Filice
AU - Mario Larocca
AU - Carmine Pinto
PY - 2026
DA - 2026/10/01
JO - Current oncology (Toronto, Ont.)
DO - 10.3390/curroncol33100594
UR - https://europepmc.org/article/MED/42930161
AB - The management of patients with multiple synchronous primary tumors remains challenging, particularly in individuals who are not candidates for surgery. While immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors, evidence supporting their use as a non-operative strategy in patients with multiple malignancies is limited, as this population is excluded from clinical trials. We report three cases of patients with synchronous primary tumors, including gastrointestinal malignancies with dMMR status, treated with up-front ICIs. Treatment strategies were individualized based on the patient's clinical condition, tumor burden, and molecular profile. All patients achieved meaningful and durable responses with long-term survival exceeding two to four years, supporting the feasibility of a non-operative strategy and organ preservation in carefully selected patients, including the frail subgroup population. Immunotherapy-based approaches were well tolerated, with a manageable safety profile. Notably, none of our patients underwent surgical resection. However, these observations are hypothesis-generating and cannot establish the efficacy or equivalence of immunotherapy to standard surgical management. Our findings extend current evidence to a largely underrepresented population and support a personalized, multidisciplinary, response-adapted approach. Prospective studies are warranted to better define patient selection, optimal treatment duration, and long-term outcomes of non-operative strategies in this setting.
SN - 1198-0052
SN - 1718-7729
ER -