Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer

被引：5

作者：

Alessi, Joao, V ^{[1
]}

Price, Adam ^{[2
]}

Richards, Allison L. ^{[2
]}

Ricciuti, Biagio ^{[1
]}

Wang, Xinan ^{[3
]}

Elkrief, Arielle ^{[4
,5
,6
]}

Pecci, Federica ^{[1
]}

Di Federico, Alessandro ^{[1
]}

Gandhi, Malini M. ^{[1
]}

Lebow, Emily S. ^{[7
,8
]}

Santos, Patricia Mae G. ^{[7
]}

Thor, Maria ^{[9
]}

Rimner, Andreas ^{[7
]}

Schoenfeld, Adam J. ^{[4
]}

Chaft, Jamie E. ^{[4
]}

Johnson, Bruce E. ^{[1
]}

Gomez, Daniel R. ^{[7
]}

Awad, Mark M. ^{[1
]}

Shaverdian, Narek ^{[7
]}

机构：

[1] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA USA

[2] Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, New York, NY USA

[3] Harvard Univ, Environm Hlth, Boston, MA USA

[4] Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, New York, NY USA

[5] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA

[6] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY USA

[7] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA

[8] Univ Penn, Dept Radiat Oncol, Philadelphia, PA USA

[9] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY USA

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2023年 / 11卷 / 11期

关键词：

immune checkpoint inhibitors; tumor biomarkers; non-small cell lung cancer; tumor microenvironment;

D O I：

10.1136/jitc-2023-007618

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

There is a need to identify predictive biomarkers to guide treatment strategies in stage III non-small cell lung cancer (NSCLCs). In this multi-institutional cohort of 197 patients with stage III NSCLC treated with concurrent chemoradiation (cCRT) and durvalumab consolidation, we identify that low tumor aneuploidy is independently associated with prolonged progression-free survival (HR 0.63; p=0.03) and overall survival (HR 0.50; p=0.03). Tumors with high aneuploidy had a significantly greater incidence of distant metastasis and shorter median distant-metastasis free survival (p=0.04 and p=0.048, respectively), but aneuploidy level did not associate with local-regional outcomes. Multiplexed immunofluorescence analysis in a cohort of NSCLC found increased intratumoral CD8-positive, PD-1-positive cells, double-positive PD-1 CD8 cells, and FOXP3-positive T-cell in low aneuploid tumors. Additionally, in a cohort of 101 patients treated with cCRT alone, tumor aneuploidy did not associate with disease outcomes. These data support the need for upfront treatment intensification strategies in stage III NSCLC patients with high aneuploid tumors and suggest that tumor aneuploidy is a promising predictive biomarker.

引用

页数：5

共 12 条

[1] Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in NSCLC [J].

Alessi, Joao, V ;

Wang, Xinan ;

Elkrief, Arielle ;

Ricciuti, Biagio ;

Li, Yvonne Y. ;

Gupta, Hersh ;

Spurr, Liam F. ;

Rizvi, Hira ;

Luo, Jia ;

Pecci, Federica ;

Lamberti, Giuseppe ;

Recondo, Gonzalo ;

Venkatraman, Deepti ;

Di Federico, Alessandro ;

Gandhi, Malini M. ;

Vaz, Victor R. ;

Nishino, Mizuki ;

Sholl, Lynette M. ;

Cherniack, Andrew D. ;

Ladanyi, Marc ;

Price, Adam ;

Richards, Allison L. ;

Donoghue, Mark ;

Lindsay, James ;

Sharma, Bijaya ;

Turner, Madison M. ;

Pfaff, Kathleen L. ;

Felt, Kristen D. ;

Rodig, Scott J. ;

Lin, Xihong ;

Meyerson, Matthew L. ;

Johnson, Bruce E. ;

Christiani, David C. ;

Schoenfeld, Adam J. ;

Awad, Mark M. .

JOURNAL OF THORACIC ONCOLOGY, 2023, 18 (11) :1524-1537

[2] Impact of TMB/PD-L1 expression and pneumonitis on chemoradiation and durvalumab response in stage III NSCLC [J].

Alessi, Joao V. V. ;

Ricciuti, Biagio ;

Wang, Xinan ;

Pecci, Federica ;

Di Federico, Alessandro ;

Lamberti, Giuseppe ;

Elkrief, Arielle ;

Rodig, Scott J. J. ;

Lebow, Emily S. S. ;

Eicholz, Jordan E. E. ;

Thor, Maria ;

Rimner, Andreas ;

Schoenfeld, Adam J. J. ;

Chaft, Jamie E. E. ;

Johnson, Bruce E. E. ;

Gomez, Daniel R. R. ;

Awad, Mark M. M. ;

Shaverdian, Narek .

NATURE COMMUNICATIONS, 2023, 14 (01)

[3] Immunotherapy in unresectable stage III non-small-cell lung cancer: state of the art and novel therapeutic approaches [J].

Cortiula, F. ;

Reymen, B. ;

Peters, S. ;

Van Mol, P. ;

Wauters, E. ;

Vansteenkiste, J. ;

De Ruysscher, D. ;

Hendriks, L. E. L. .

ANNALS OF ONCOLOGY, 2022, 33 (09) :893-908

[4] Combined Evaluation of Tumor-Infiltrating CD8+and FoxP3+Lymphocytes Provides Accurate Prognosis in Stage IA Lung Adenocarcinoma [J].

Kinoshita, Fumihiko ;

Takada, Kazuki ;

Yamada, Yuichi ;

Oku, Yuka ;

Kosai, Keisuke ;

Ono, Yuki ;

Tanaka, Kensuke ;

Wakasu, Sho ;

Oba, Taro ;

Osoegawa, Atsushi ;

Tagawa, Tetsuzo ;

Shimokawa, Mototsugu ;

Oda, Yoshinao ;

Mori, Masaki .

ANNALS OF SURGICAL ONCOLOGY, 2020, 27 (06) :2102-2109

[5] The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies [J].

Kumagai, Shogo ;

Togashi, Yosuke ;

Kamada, Takahiro ;

Sugiyama, Eri ;

Nishinakamura, Hitomi ;

Takeuchi, Yoshiko ;

Vitaly, Kochin ;

Itahashi, Kota ;

Maeda, Yuka ;

Matsui, Shigeyuki ;

Shibahara, Takuma ;

Yamashita, Yasuho ;

Irie, Takuma ;

Tsuge, Ayaka ;

Fukuoka, Shota ;

Kawazoe, Akihito ;

Udagawa, Hibiki ;

Kirita, Keisuke ;

Aokage, Keiju ;

Ishii, Genichiro ;

Kuwata, Takeshi ;

Nakama, Kenta ;

Kawazu, Masahito ;

Ueno, Toshihide ;

Yamazaki, Naoya ;

Goto, Koichi ;

Tsuboi, Masahiro ;

Mano, Hiroyuki ;

Doi, Toshihiko ;

Shitara, Kohei ;

Nishikawa, Hiroyoshi .

NATURE IMMUNOLOGY, 2020, 21 (11) :1346-+

[6] Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab [J].

Lebow, Emily S. ;

Shepherd, Annemarie ;

Eichholz, Jordan E. ;

Offin, Michael ;

Gelblum, Daphna Y. ;

Wu, Abraham J. ;

Simone, Charles B. ;

Schoenfeld, Adam J. ;

Jones, David R. ;

Rimner, Andreas ;

Chaft, Jamie E. ;

Riaz, Nadeem ;

Gomez, Daniel R. ;

Shaverdian, Narek .

JAMA NETWORK OPEN, 2023, 6 (01) :E2249591

[7] Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer [J].

Spigel, David R. ;

Faivre-Finn, Corinne ;

Gray, Jhanelle E. ;

Vicente, David ;

Planchard, David ;

Paz-Ares, Luis ;

Vansteenkiste, Johan F. ;

Garassino, Marina C. ;

Hui, Rina ;

Quantin, Xavier ;

Rimner, Andreas ;

Wu, Yi-Long ;

Ozguroglu, Mustafa ;

Lee, Ki H. ;

Kato, Terufumi ;

de Wit, Maike ;

Kurata, Takayasu ;

Reck, Martin ;

Cho, Byoung C. ;

Senan, Suresh ;

Naidoo, Jarushka ;

Mann, Helen ;

Newton, Michael ;

Thiyagarajah, Piruntha ;

Antonia, Scott J. .

JOURNAL OF CLINICAL ONCOLOGY, 2022, 40 (12) :1301-+

[8] Tumor aneuploidy predicts survival following immunotherapy across multiple cancers [J].

Spurr, Liam F. ;

Weichselbaum, Ralph R. ;

Pitroda, Sean P. .

NATURE GENETICS, 2022, 54 (12) :1782-1785

[9] Highly aneuploid non-small cell lung cancer shows enhanced responsiveness to concurrent radiation and immune checkpoint blockade [J].

Spurr, Liam F. ;

Martinez, Carlos A. ;

Kang, Wenjun ;

Chen, Mengjie ;

Zha, Yuanyuan ;

Hseu, Robyn ;

Gutiontov, Stanley, I ;

Turchan, William T. ;

Lynch, Connor M. ;

Pointer, Kelli B. ;

Chang, Paul ;

Murgu, Septimiu ;

Husain, Aliya N. ;

Cody, Brittany ;

Vokes, Everett E. ;

Bestvina, Christine M. ;

Patel, Jyoti D. ;

Diehn, Maximilian ;

Gajewski, Thomas F. ;

Weichselbaum, Ralph R. ;

Chmura, Steven J. ;

Pitroda, Sean P. .

NATURE CANCER, 2022, 3 (12) :1498-+

[10] Quantification of aneuploidy in targeted sequencing data using ASCETS [J].

Spurr, Liam F. ;

Touat, Mehdi ;

Taylor, Alison M. ;

Dubuc, Adrian M. ;

Shih, Juliann ;

Meredith, David M. ;

Pisano, William, V ;

Meyerson, Matthew L. ;

Ligon, Keith L. ;

Cherniack, Andrew D. ;

Li, Yvonne Y. ;

Beroukhim, Rameen .

BIOINFORMATICS, 2021, 37 (16) :2461-2463

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