Restricted Mean Survival Time—Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors?
Background: Lung cancer (LC) is the first and most lethal cancer in the world; identifying new methods to treat it, such as immune checkpoint inhibitors (ICIs), is needed. ICIs treatment is very effective, but it comes bundled with a series of immune-related adverse events (irAEs). Restricted mean s...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/13/11/1892 |
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| author | Cristina-Florina Pîrlog Raluca Costache Andreea Ioana Paroșanu Cristina Orlov Slavu Mihaela Olaru Ana Maria Popa Cristian Iaciu Irina Niță Pompilia Moțatu Horia Teodor Cotan Alexandru Vlad Oprița Daniel Costache Loredana Sabina Cornelia Manolescu Cornelia Nițipir |
| author_facet | Cristina-Florina Pîrlog Raluca Costache Andreea Ioana Paroșanu Cristina Orlov Slavu Mihaela Olaru Ana Maria Popa Cristian Iaciu Irina Niță Pompilia Moțatu Horia Teodor Cotan Alexandru Vlad Oprița Daniel Costache Loredana Sabina Cornelia Manolescu Cornelia Nițipir |
| author_sort | Cristina-Florina Pîrlog |
| collection | DOAJ |
| description | Background: Lung cancer (LC) is the first and most lethal cancer in the world; identifying new methods to treat it, such as immune checkpoint inhibitors (ICIs), is needed. ICIs treatment is very effective, but it comes bundled with a series of immune-related adverse events (irAEs). Restricted mean survival time (RMST) is an alternative tool for assessing the patients’ survival when the proportional hazard assumption (PH) fails. Methods: We included in this analytical cross-sectional observational survey patients with metastatic non-small-cell lung cancer (NSCLC), treated for at least 6 months with ICIs in the first- and second-line settings. Using RMST, we estimated the overall survival (OS) of patients by dividing them into two groups. A multivariate Cox regression analysis was performed to determine the impact of the prognostic factors on OS. Results: Seventy-nine patients were included (68.4% men, mean age 63.8), and 34/79 (43%) presented irAEs. The OS RMST of the entire group was 30.91 months, with a survival median of 22 months. Thirty-two out of seventy-nine (40.5%) died before we ended our study. The OS RMST and death percentage favored the patients who presented irAEs (long-rank test, <i>p</i> = 0.036). The OS RMST of patients with irAEs was 35.7 months, with a number of deaths of 12/34 (35.29%), while the OS RMST of the patients without irAEs was 17 months, with a number of deaths of 20/45 (44.44%). The OS RMST by the line of treatment favored the first line of treatment. In this group, the presence of irAEs significantly impacted the survival of these patients (<i>p</i> = 0.0083). Moreover, patients that experienced low-grade irAEs had a better OS RMST. This result has to be cautiously regarded because of the small number of patients stratified according to the grades of irAEs. The prognostic factors for the survival were: the presence of irAEs, Eastern Cooperative Oncology Group (ECOG) performance status and the number of organs affected by metastasis. The risk of dying was 2.13 times higher for patients without irAEs than for the patients who presented irAEs, (CI) 95% of 1.03 to 4.39. Moreover, by increasing the ECOG performance status by one point, the risk of death increased by 2.28 times, with a CI 95% of 1.46 to 3.58, while the involvement of more metastatic organs was associated with a 1.60 times increase in the death risk, with a CI 95% of 1.09 to 2.36. Age and the type of tumor were not predictive for this analysis. Conclusions: The RMST is a new tool that helps researchers to better address the survival in studies with ICIs treatment where the PH fails, and the long-rank test is less efficient due to the existence of the long-term responses and delayed treatment effects. Patients with irAEs have a better prognosis than those without irAEs in the first-line settings. The ECOG performance status and the number of organs affected by metastasis must be considered when selecting patients for ICIs treatment. |
| first_indexed | 2024-03-11T03:09:36Z |
| format | Article |
| id | doaj.art-71eedd2c07834566a6a2ac720251c1ae |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-11T03:09:36Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-71eedd2c07834566a6a2ac720251c1ae2023-11-18T07:42:31ZengMDPI AGDiagnostics2075-44182023-05-011311189210.3390/diagnostics13111892Restricted Mean Survival Time—Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors?Cristina-Florina Pîrlog0Raluca Costache1Andreea Ioana Paroșanu2Cristina Orlov Slavu3Mihaela Olaru4Ana Maria Popa5Cristian Iaciu6Irina Niță7Pompilia Moțatu8Horia Teodor Cotan9Alexandru Vlad Oprița10Daniel Costache11Loredana Sabina Cornelia Manolescu12Cornelia Nițipir13Department of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Internal Medicine and Gastroenterology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Medical Oncology, Monza Oncology Hospital, 013821 Bucharest, RomaniaDepartment of Medical Oncology, Municipal Hospital Ploiesti, 100409 Ploiesti, RomaniaDepartment of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaThird Department, Discipline Dermatology II, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Microbiology, Parasitology and Virology, Faculty of Midwifery and Nursing, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Oncology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaBackground: Lung cancer (LC) is the first and most lethal cancer in the world; identifying new methods to treat it, such as immune checkpoint inhibitors (ICIs), is needed. ICIs treatment is very effective, but it comes bundled with a series of immune-related adverse events (irAEs). Restricted mean survival time (RMST) is an alternative tool for assessing the patients’ survival when the proportional hazard assumption (PH) fails. Methods: We included in this analytical cross-sectional observational survey patients with metastatic non-small-cell lung cancer (NSCLC), treated for at least 6 months with ICIs in the first- and second-line settings. Using RMST, we estimated the overall survival (OS) of patients by dividing them into two groups. A multivariate Cox regression analysis was performed to determine the impact of the prognostic factors on OS. Results: Seventy-nine patients were included (68.4% men, mean age 63.8), and 34/79 (43%) presented irAEs. The OS RMST of the entire group was 30.91 months, with a survival median of 22 months. Thirty-two out of seventy-nine (40.5%) died before we ended our study. The OS RMST and death percentage favored the patients who presented irAEs (long-rank test, <i>p</i> = 0.036). The OS RMST of patients with irAEs was 35.7 months, with a number of deaths of 12/34 (35.29%), while the OS RMST of the patients without irAEs was 17 months, with a number of deaths of 20/45 (44.44%). The OS RMST by the line of treatment favored the first line of treatment. In this group, the presence of irAEs significantly impacted the survival of these patients (<i>p</i> = 0.0083). Moreover, patients that experienced low-grade irAEs had a better OS RMST. This result has to be cautiously regarded because of the small number of patients stratified according to the grades of irAEs. The prognostic factors for the survival were: the presence of irAEs, Eastern Cooperative Oncology Group (ECOG) performance status and the number of organs affected by metastasis. The risk of dying was 2.13 times higher for patients without irAEs than for the patients who presented irAEs, (CI) 95% of 1.03 to 4.39. Moreover, by increasing the ECOG performance status by one point, the risk of death increased by 2.28 times, with a CI 95% of 1.46 to 3.58, while the involvement of more metastatic organs was associated with a 1.60 times increase in the death risk, with a CI 95% of 1.09 to 2.36. Age and the type of tumor were not predictive for this analysis. Conclusions: The RMST is a new tool that helps researchers to better address the survival in studies with ICIs treatment where the PH fails, and the long-rank test is less efficient due to the existence of the long-term responses and delayed treatment effects. Patients with irAEs have a better prognosis than those without irAEs in the first-line settings. The ECOG performance status and the number of organs affected by metastasis must be considered when selecting patients for ICIs treatment.https://www.mdpi.com/2075-4418/13/11/1892lung cancerimmune checkpoint inhibitorsimmune-related adverse eventsrestricted mean survival time |
| spellingShingle | Cristina-Florina Pîrlog Raluca Costache Andreea Ioana Paroșanu Cristina Orlov Slavu Mihaela Olaru Ana Maria Popa Cristian Iaciu Irina Niță Pompilia Moțatu Horia Teodor Cotan Alexandru Vlad Oprița Daniel Costache Loredana Sabina Cornelia Manolescu Cornelia Nițipir Restricted Mean Survival Time—Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors? Diagnostics lung cancer immune checkpoint inhibitors immune-related adverse events restricted mean survival time |
| title | Restricted Mean Survival Time—Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors? |
| title_full | Restricted Mean Survival Time—Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors? |
| title_fullStr | Restricted Mean Survival Time—Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors? |
| title_full_unstemmed | Restricted Mean Survival Time—Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors? |
| title_short | Restricted Mean Survival Time—Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors? |
| title_sort | restricted mean survival time can it be a new tool in assessing the survival of non small cell lung cancer patients treated with immune checkpoint inhibitors |
| topic | lung cancer immune checkpoint inhibitors immune-related adverse events restricted mean survival time |
| url | https://www.mdpi.com/2075-4418/13/11/1892 |
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