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@article{Cortellini:2022:10.1186/s13045-022-01226-2,
author = {Cortellini, A and Giusti, R and Filetti, M and Citarella, F and Adamo, V and Santini, D and Buti, S and Cantini, L and Di, Maio M and Aerts, C and Bria, E and Bertolini, F and Ferrara, MG and Ghidini, M and Grossi, F and Guida, A and Berardi, R and Morabito, A and Genova, C and Mazzoni, F and Antonuzzo, L and Gelibter, A and Marchetti, P and Chiari, R and Macerelli, M and Rastelli, F and Della, Gravara L and Gori, S and Tuzi, A and De, Tursi M and Di, Marino P and Mansueto, G and Pecci, F and Zoratto, F and Ricciardi, S and Migliorino, MR and Passiglia, F and Metro, G and Spinelli, GP and Banna, GL and Friedlaender, A and Addeo, A and Ficorella, C and Porzio, G and Tiseo, M and Russano, M and Russo, A and Pinato, D},
doi = {10.1186/s13045-022-01226-2},
journal = {Journal of Hematology and Oncology},
title = {High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status},
url = {http://dx.doi.org/10.1186/s13045-022-01226-2},
volume = {15},
year = {2022}
}

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TY  - JOUR
AB  - Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case–control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46–0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48–0.89]; p = 0.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p = 0.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of ≥ 1 somatic DDR gene mutation was 20% and 24.5% (p = 0.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p = 0.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted.
AU  - Cortellini,A
AU  - Giusti,R
AU  - Filetti,M
AU  - Citarella,F
AU  - Adamo,V
AU  - Santini,D
AU  - Buti,S
AU  - Cantini,L
AU  - Di,Maio M
AU  - Aerts,C
AU  - Bria,E
AU  - Bertolini,F
AU  - Ferrara,MG
AU  - Ghidini,M
AU  - Grossi,F
AU  - Guida,A
AU  - Berardi,R
AU  - Morabito,A
AU  - Genova,C
AU  - Mazzoni,F
AU  - Antonuzzo,L
AU  - Gelibter,A
AU  - Marchetti,P
AU  - Chiari,R
AU  - Macerelli,M
AU  - Rastelli,F
AU  - Della,Gravara L
AU  - Gori,S
AU  - Tuzi,A
AU  - De,Tursi M
AU  - Di,Marino P
AU  - Mansueto,G
AU  - Pecci,F
AU  - Zoratto,F
AU  - Ricciardi,S
AU  - Migliorino,MR
AU  - Passiglia,F
AU  - Metro,G
AU  - Spinelli,GP
AU  - Banna,GL
AU  - Friedlaender,A
AU  - Addeo,A
AU  - Ficorella,C
AU  - Porzio,G
AU  - Tiseo,M
AU  - Russano,M
AU  - Russo,A
AU  - Pinato,D
DO  - 10.1186/s13045-022-01226-2
PY  - 2022///
SN  - 1756-8722
TI  - High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status
T2  - Journal of Hematology and Oncology
UR  - http://dx.doi.org/10.1186/s13045-022-01226-2
UR  - http://hdl.handle.net/10044/1/94069
VL  - 15
ER  -

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