Tumor Mutational Burden Predicts Progression-Free Survival and Local-Regional Control in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Chemoradiation and Durvalumab.
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| Title: | Tumor Mutational Burden Predicts Progression-Free Survival and Local-Regional Control in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Chemoradiation and Durvalumab. |
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| Authors: | Shaverdian, N.1 (AUTHOR), Shepherd, A.F.1 (AUTHOR), Offin, M.2 (AUTHOR), Gelblum, D.1 (AUTHOR), Wu, A.J.1 (AUTHOR), Simone II, C.B.3 (AUTHOR), Schoenfeld, A.J.2 (AUTHOR), Jones, D.4 (AUTHOR), Rimner, A.1 (AUTHOR), Chaft, J.4 (AUTHOR), Riaz, N.1 (AUTHOR), Gomez, D.R.1 (AUTHOR) |
| Source: | International Journal of Radiation Oncology, Biology, Physics. 2022 Supplement, Vol. 114 Issue 3, pe390-e391. 2p. |
| Subjects: | DNA repair, Non-small-cell lung carcinoma, Progression-free survival, Cancer patients, Chemoradiotherapy, Fanconi's anemia |
| Abstract: | The impact of tumor genomics on disease outcomes in locally advanced non-small cell lung cancers (NSCLC) treated with concurrent chemoradiation (cCRT) and durvalumab remains unclear. We assessed if tumor mutational burden (TMB) and mutations in genes associated with radiation sensitivity can predict for disease control. Consecutive patients treated with cCRT and durvalumab who underwent tumor genomic profiling were included. Genomic characteristics including TMB and 26 genes from three radio-sensitizing DNA damage and repair (DDR) pathways (DNA checkpoints, Fanconi Anemia and homologous recombination) and genes associated with radiation resistance (KEAP1, NFE2L2, STK11, PIK3CA) were examined. Cox modeling was used to assess associations between clinical features, TMB, and pathogenic mutations in DDR or radiation resistance genes with disease outcomes. Kaplan-Meier analysis was used to estimate overall survival (OS), progression-free survival (PFS) and local-regional failure (LRF) and compare PFS and LRF between patients with high-TMB (≥ 10 mt/Mb) and low-TMB. A p-value <0.05 was considered significant. Eighty-one patients with median follow-up of 26 months were assessed. Median age was 67 years, 71% (n=57) had stage IIIB/IIIC disease and PD-L1 expression was available for 67 (83%) patients, of whom 42 (63%) had PD-L1 ≥1%. Median TMB was 8.8 mt/Mb. In total, 17% (n=14) and 35% (n=28) of patients had pathogenic mutations in DDR and radiation resistance genes, respectively (Table 1). Among all patients, the 24-month OS, PFS and LRF estimates were 72% (95% CI: 62-82), 45% (34-56%) and 31% (1-43%), respectively. On Cox analysis, only TMB associated with PFS [HR: 0.95 (0.92-0.98), p=0.009] and LRF [HR: 0.89 (0.83-0.97, p=0.009]. Neither PDL1 expression, DDR or radiation resistance mutations, histology, stage nor ECOG associated with PFS or LRF. Compared to patients with low-TMB, patients with high-TMB had improved PFS and less LRF: 24-month PFS: 66% vs 27% (p=0.003) and 24-month LRF: 9% vs 52% (p=0.001). In patients with locally advanced NSCLC treated with cCRT and durvalumab, high-TMB predicts for improved progression-free survival and local-regional control. Potential underlying mechanisms include increased genomic instability and tumor immunogenicity enhancing sensitivity to this multimodal treatment. [ABSTRACT FROM AUTHOR] |
| Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
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| Header | DbId: egs DbLabel: Engineering Source An: 159166366 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Tumor Mutational Burden Predicts Progression-Free Survival and Local-Regional Control in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Chemoradiation and Durvalumab. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Shaverdian%2C+N%2E%22">Shaverdian, N.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shepherd%2C+A%2EF%2E%22">Shepherd, A.F.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Offin%2C+M%2E%22">Offin, M.</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gelblum%2C+D%2E%22">Gelblum, D.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wu%2C+A%2EJ%2E%22">Wu, A.J.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Simone+II%2C+C%2EB%2E%22">Simone II, C.B.</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Schoenfeld%2C+A%2EJ%2E%22">Schoenfeld, A.J.</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jones%2C+D%2E%22">Jones, D.</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rimner%2C+A%2E%22">Rimner, A.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chaft%2C+J%2E%22">Chaft, J.</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Riaz%2C+N%2E%22">Riaz, N.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gomez%2C+D%2ER%2E%22">Gomez, D.R.</searchLink><relatesTo>1</relatesTo> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Radiation+Oncology%2C+Biology%2C+Physics%22">International Journal of Radiation Oncology, Biology, Physics</searchLink>. 2022 Supplement, Vol. 114 Issue 3, pe390-e391. 2p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22DNA+repair%22">DNA repair</searchLink><br /><searchLink fieldCode="DE" term="%22Non-small-cell+lung+carcinoma%22">Non-small-cell lung carcinoma</searchLink><br /><searchLink fieldCode="DE" term="%22Progression-free+survival%22">Progression-free survival</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+patients%22">Cancer patients</searchLink><br /><searchLink fieldCode="DE" term="%22Chemoradiotherapy%22">Chemoradiotherapy</searchLink><br /><searchLink fieldCode="DE" term="%22Fanconi's+anemia%22">Fanconi's anemia</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The impact of tumor genomics on disease outcomes in locally advanced non-small cell lung cancers (NSCLC) treated with concurrent chemoradiation (cCRT) and durvalumab remains unclear. We assessed if tumor mutational burden (TMB) and mutations in genes associated with radiation sensitivity can predict for disease control. Consecutive patients treated with cCRT and durvalumab who underwent tumor genomic profiling were included. Genomic characteristics including TMB and 26 genes from three radio-sensitizing DNA damage and repair (DDR) pathways (DNA checkpoints, Fanconi Anemia and homologous recombination) and genes associated with radiation resistance (KEAP1, NFE2L2, STK11, PIK3CA) were examined. Cox modeling was used to assess associations between clinical features, TMB, and pathogenic mutations in DDR or radiation resistance genes with disease outcomes. Kaplan-Meier analysis was used to estimate overall survival (OS), progression-free survival (PFS) and local-regional failure (LRF) and compare PFS and LRF between patients with high-TMB (≥ 10 mt/Mb) and low-TMB. A p-value <0.05 was considered significant. Eighty-one patients with median follow-up of 26 months were assessed. Median age was 67 years, 71% (n=57) had stage IIIB/IIIC disease and PD-L1 expression was available for 67 (83%) patients, of whom 42 (63%) had PD-L1 ≥1%. Median TMB was 8.8 mt/Mb. In total, 17% (n=14) and 35% (n=28) of patients had pathogenic mutations in DDR and radiation resistance genes, respectively (Table 1). Among all patients, the 24-month OS, PFS and LRF estimates were 72% (95% CI: 62-82), 45% (34-56%) and 31% (1-43%), respectively. On Cox analysis, only TMB associated with PFS [HR: 0.95 (0.92-0.98), p=0.009] and LRF [HR: 0.89 (0.83-0.97, p=0.009]. Neither PDL1 expression, DDR or radiation resistance mutations, histology, stage nor ECOG associated with PFS or LRF. Compared to patients with low-TMB, patients with high-TMB had improved PFS and less LRF: 24-month PFS: 66% vs 27% (p=0.003) and 24-month LRF: 9% vs 52% (p=0.001). In patients with locally advanced NSCLC treated with cCRT and durvalumab, high-TMB predicts for improved progression-free survival and local-regional control. Potential underlying mechanisms include increased genomic instability and tumor immunogenicity enhancing sensitivity to this multimodal treatment. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.ijrobp.2022.07.1546 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 2 StartPage: e390 Subjects: – SubjectFull: DNA repair Type: general – SubjectFull: Non-small-cell lung carcinoma Type: general – SubjectFull: Progression-free survival Type: general – SubjectFull: Cancer patients Type: general – SubjectFull: Chemoradiotherapy Type: general – SubjectFull: Fanconi's anemia Type: general Titles: – TitleFull: Tumor Mutational Burden Predicts Progression-Free Survival and Local-Regional Control in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Chemoradiation and Durvalumab. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Shaverdian, N. – PersonEntity: Name: NameFull: Shepherd, A.F. – PersonEntity: Name: NameFull: Offin, M. – PersonEntity: Name: NameFull: Gelblum, D. – PersonEntity: Name: NameFull: Wu, A.J. – PersonEntity: Name: NameFull: Simone II, C.B. – PersonEntity: Name: NameFull: Schoenfeld, A.J. – PersonEntity: Name: NameFull: Jones, D. – PersonEntity: Name: NameFull: Rimner, A. – PersonEntity: Name: NameFull: Chaft, J. – PersonEntity: Name: NameFull: Riaz, N. – PersonEntity: Name: NameFull: Gomez, D.R. IsPartOfRelationships: – BibEntity: Dates: – D: 02 M: 11 Text: 2022 Supplement Type: published Y: 2022 Identifiers: – Type: issn-print Value: 03603016 Numbering: – Type: volume Value: 114 – Type: issue Value: 3 Titles: – TitleFull: International Journal of Radiation Oncology, Biology, Physics Type: main |
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