IMPACT OF PRE-TREATMENT SYMPTOM BURDEN, RESPONSE TO TREATMENT, AND LABORATORY PARAMETERS ON SURVIVAL IN SMALL CELL LUNG CANCER

CHEST Journal ◽  
2005 ◽  
Vol 128 (4) ◽  
pp. 335S
Author(s):  
Anant Mohan ◽  
Abha Goyal ◽  
Preet P. Singh ◽  
Siddharth Singh ◽  
R.M. Pandey ◽  
...  
2022 ◽  
Vol 11 ◽  
Author(s):  
Elena Corral de la Fuente ◽  
Maria Eugenia Olmedo Garcia ◽  
Ana Gomez Rueda ◽  
Yolanda Lage ◽  
Pilar Garrido

Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is the most frequently altered oncogene in Non-Small Cell Lung Cancer (NSCLC). KRAS mutant tumors constitute a heterogeneous group of diseases, different from other oncogene-derived tumors in terms of biology and response to treatment, which hinders the development of effective drugs against KRAS. Therefore, for decades, despite enormous efforts invested in the development of drugs aimed at inhibiting KRAS or its signaling pathways, KRAS was considered to be undruggable. Recently, the discovery of a new pocket under the effector binding switch II region of KRAS G12C has allowed the development of direct KRAS inhibitors such as sotorasib, the first FDA-approved drug targeting KRAS G12C, or adagrasib, initiating a new exciting era. However, treatment with targeted KRAS G12C inhibitors also leads to resistance, and understanding the possible mechanisms of resistance and which drugs could be useful to overcome it is key. Among others, KRAS G12C (ON) tricomplex inhibitors and different combination therapy strategies are being analyzed in clinical trials. Another area of interest is the potential role of co-mutations in treatment selection, particularly immunotherapy. The best first-line strategy remains to be determined and, due to the heterogeneity of KRAS, is likely to be based on combination therapies.


Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 693 ◽  
Author(s):  
Subba R. Digumarthy ◽  
Dexter P. Mendoza ◽  
Jessica J. Lin ◽  
Marguerite Rooney ◽  
Andrew Do ◽  
...  

Rearranged during transfection proto-oncogene (RET) fusions represent a potentially targetable oncogenic driver in non-small cell lung cancer (NSCLC). Imaging features and metastatic patterns of advanced RET fusion-positive (RET+) NSCLC are not well established. Our goal was to compare the imaging features and patterns of metastases in RET+, ALK+ and ROS1+ NSCLC. Patients with RET+, ALK+, or ROS1+ NSCLC seen at our institution between January 2014 and December 2018 with available pre-treatment imaging were identified. The clinicopathologic features, imaging characteristics, and the distribution of metastases were reviewed and compared. We identified 215 patients with NSCLC harboring RET, ALK, or ROS1 gene fusion (RET = 32; ALK = 116; ROS1 = 67). Patients with RET+ NSCLC were older at presentation compared to ALK+ and ROS1+ patients (median age: RET = 64 years; ALK = 51 years, p < 0.001; ROS = 54 years, p = 0.042) and had a higher frequency of neuroendocrine histology (RET = 12%; ALK = 2%, p = 0.025; ROS1 = 0%, p = 0.010). Primary tumors in RET+ patients were more likely to be peripheral (RET = 69%; ALK = 47%, p = 0.029; ROS1 = 36%, p = 0.003), whereas lobar location, size, and density were comparable across the three groups. RET+ NSCLC was associated with a higher frequency of brain metastases at diagnosis compared to ROS1+ NSCLC (RET = 32%, ROS1 = 10%; p = 0.039. Metastatic patterns were otherwise similar across the three molecular subgroups, with high incidences of lymphangitic carcinomatosis, pleural metastases, and sclerotic bone metastases. RET+ NSCLC shares several distinct radiologic features and metastatic spread with ALK+ and ROS1+ NSCLC. These features may suggest the presence of RET fusions and help identify patients who may benefit from further molecular genotyping.


Lung Cancer ◽  
2019 ◽  
Vol 131 ◽  
pp. 6-13 ◽  
Author(s):  
Maurice Pérol ◽  
Katherine B. Winfree ◽  
Gebra Cuyun Carter ◽  
Zhanglin Lin Cui ◽  
Lee Bowman ◽  
...  

2019 ◽  
Vol 11 ◽  
pp. 175883591985319 ◽  
Author(s):  
Athanasios Kotsakis ◽  
Galatea Kallergi ◽  
Despoina Aggouraki ◽  
Zaharoula Lyristi ◽  
Filippos Koinis ◽  
...  

Background: Since tumor cells may escape from immune surveillance through the programmed cell death 1 (PD-1)/programmed death ligand (PD-L)1 axis, this study was designed in order to evaluate whether there is a correlation between the levels of PD-1+ and PD-L1+-expressing immune cells (ICs) and circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). Patients and methods: Peripheral blood was obtained from 37 chemotherapy-naïve patients with metastatic NSCLC before treatment. PD-1 and PD-L1 expression was evaluated (1) on ICs with anti-tumor function (CD4+ and CD8+ T-cells, B-cells, monocytes/dendritic cells) using flow cytometry, (2) on CTCs by immunofluorescence and (3) on cells from tumor tissues by immunohistochemistry. The levels of PD-1+ and PD-L1+-expressing ICs were correlated with progression-free survival (PFS). Results: The presence of PD-1+ CD8+ cells, with reduced interferon (IFN)-γ expression, but not other ICs, were positively correlated with PD-L1+ CTCs ( p < 0.04). Increased percentages of PD-1+ CD8+ T-cells, were associated with a worse response to treatment ( p = 0.032) and shorter PFS ( p = 0.023) which, in multivariate analysis, was revealed as an independent predictor for decreased PFS [hazard ratio (HR): 4.1, p = 0.0007]. Conclusion: The results of the current study, for first time, provide evidence for a possible interaction between ICs and CTCs in NSCLC patients via the PD-1/PD-L1 axis and strongly support that the levels of PD-1+ CD8+ in these patients may be of clinical relevance.


2018 ◽  
Vol 13 (10) ◽  
pp. S1001-S1002
Author(s):  
M. Whisenant ◽  
L. Williams ◽  
V. Vaghani ◽  
Q. Shi ◽  
A. Garcia Gonzalez ◽  
...  

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