Research team Luigi De Petris

Clinical factors of importance for immunotherapy in non-small cell (NSCLC), and biomarker studies in relation to treatment pathways in small-cell lung cancer (SCLC)

NSCLC Immunotherapy cohorts.
NSCLC Immunotherapy cohorts.

Research

Lung cancer is a common disease characterized by high mortality rates. From a clinico-pathological point of view, lung cancer can be divided into small-cell lung cancer (SCLC, 15%) and non-small cell lung cancer (NSCLC, 85%). The former is an aggressive tumor form where no major advances in treatment have been obtained during the last decades. On the contrary, immunotherapy (IT) based on check-point inhibitors represents a real breakthrough in NSCLC.

Although targeting the programmed cell death protein 1 (PD1) pathway with monoclonal antibodies has reached clinically meaningful effects in NSCLC, still little is known about which patients benefit most from this approach.

Aims: To improve patient selection for IT in NSCLC based on clinical and molecular biomarkers (BM). To integrate individual treatment pathways with clinical and BM data to increase personalized medicine possibilities even in SCLC.

Design and methods: The NSCLC IT program is based on the analysis of retrospective patient material (n=200) with additional focus on cases with brain metastasis (n=50), a setting where IT is particularly challenging. Our findings will be further validated on a cohort of similar patients on a national basis through the Swedish National Cancer Registry. In addition, liquid biopsies from patients receiving IT in clinical practice (n=200) will also be collected and analyzed for circulating BM (such as proteins on exosomes). Within the SCLC program, we analyze tumor tissues (n=100) in search of subgroup of patients that by a given immune profile (expression of PD-L1, PD1 and STING) might most likely benefit from IT. In addition, we will extract exosomes from liquid biopsies from 50 SCLC and matched cases with NSCLC and benign lung diseases, respectively, in search for SCLC-specific signatures.

Finally, in collaboration with researchers at KTH, we are applying Artificial intelligence models to a cohort of 544 SCLC treated ad our institution, in order to map individual treatment pathways and examine the impact of decision support tools, in precision medicine and precision dosing, on treatment outcomes for this disease. All studies will have direct impact on healthcare, supporting patient selection and exploring novel treatment strategies.

Team members

Luigi De Petris, MD/PhD
Salomon Tendler, MD PhD
Asaf Dan, MD

Selected Publications

Clinicopathological significance of the expression of PD-L1 in non-small cell lung cancer.
Montero MA, Aricak O, Kis L, Yoshikawa A, De Petris L, Grundberg O, Pham HHN, Roden AC, Fukuoka J, Attanoos R, Guijarro R, Alarcón F, Lindström K, Ortiz-Villalón C
Ann Diagn Pathol 2021 Apr;51():151701

Effect of corticosteroids on the outcome of patients with advanced non-small cell lung cancer treated with immune-checkpoint inhibitors.
Skribek M, Rounis K, Afshar S, Grundberg O, Friesland S, Tsakonas G, Ekman S, De Petris L
Eur J Cancer 2021 Mar;145():245-254

The prognostic implications of Notch1, Hes1, Ascl1, and DLL3 protein expression in SCLC patients receiving platinum-based chemotherapy.
Tendler S, Kanter L, Lewensohn R, Ortiz-Villalón C, Viktorsson K, De Petris L
PLoS One 2020 ;15(10):e0240973

Caring for patients with cancer in the COVID-19 era.
van de Haar J, Hoes LR, Coles CE, Seamon K, Fröhling S, Jäger D, Valenza F, de Braud F, De Petris L, Bergh J, Ernberg I, Besse B, Barlesi F, Garralda E, Piris-Giménez A, Baumann M, Apolone G, Soria JC, Tabernero J, Caldas C, Voest EE
Nat Med 2020 05;26(5):665-671

Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal.
Tamborero D, Dienstmann R, Rachid MH, Boekel J, Baird R, Braña I, De Petris L, Yachnin J, Massard C, Opdam FL, Schlenk R, Vernieri C, Garralda E, Masucci M, Villalobos X, Chavarria E, , Calvo F, Fröhling S, Eggermont A, Apolone G, Voest EE, Caldas C, Tabernero J, Ernberg I, Rodon J, Lehtiö J
Nat Med 2020 07;26(7):992-994

Treatment patterns and survival outcomes for small-cell lung cancer patients - a Swedish single center cohort study.
Tendler S, Zhan Y, Pettersson A, Lewensohn R, Viktorsson K, Fang F, De Petris L
Acta Oncol 2020 Apr;59(4):388-394

Educational level, management and outcomes in small-cell lung cancer (SCLC): A population-based cohort study.
Tendler S, Holmqvist M, Wagenius G, Lewensohn R, Lambe M, De Petris L
Lung Cancer 2020 01;139():111-117

Differential prognostic impact of platelet-derived growth factor receptor expression in NSCLC.
Kilvaer TK, Rakaee M, Hellevik T, Vik J, Petris L, Donnem T, Strell C, Ostman A, Busund LR, Martinez-Zubiaurre I
Sci Rep 2019 07;9(1):10163

Validation of the 8th TNM classification for small-cell lung cancer in a retrospective material from Sweden.
Tendler S, Grozman V, Lewensohn R, Tsakonas G, Viktorsson K, De Petris L
Lung Cancer 2018 06;120():75-81

Prognostic factors affecting survival after whole brain radiotherapy in patients with brain metastasized lung cancer.
Tsakonas G, Hellman F, Gubanski M, Friesland S, Tendler S, Lewensohn R, Ekman S, de Petris L
Acta Oncol 2018 Feb;57(2):231-238

Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer.
Gadgeel SM, Shaw AT, Govindan R, Gandhi L, Socinski MA, Camidge DR, De Petris L, Kim DW, Chiappori A, Moro-Sibilot DL, Duruisseaux M, Crino L, De Pas T, Dansin E, Tessmer A, Yang JC, Han JY, Bordogna W, Golding S, Zeaiter A, Ou SI
J Clin Oncol 2016 12;34(34):4079-4085

Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.
Ou SH, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, Lena H, Moro-Sibilot D, Bearz A, Ramirez SV, Mekhail T, Spira A, Bordogna W, Balas B, Morcos PN, Monnet A, Zeaiter A, Kim DW
J Clin Oncol 2016 Mar;34(7):661-8