Concomitant genomic alterations in KRAS mutant advanced lung adenocarcinoma

Gibert, Joan; Clavé, Sergi; Hardy-Werbin, Max; Taus, Álvaro; Rocha, Pedro; Longarón, Raquel; Piquer, Gabriel; Chaib, Imane; Carcereny, Enric; Morán, Teresa; Salido, Marta; Dalmases, Alba; Bellosillo, Beatríz; Arriola, Edurne

doi:10.1016/j.lungcan.2019.12.003

Cited by 17 publications

(16 citation statements)

References 14 publications

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“…In our ICI cohort, STK11 mutations were identified in 9% of patients, in line with previous reports (range: 8% to 13%) (47,(50)(51)(52). Patients carrying a pathogenic variant of STK11 and receiving ICIs showed a trend for shorter OS.…”

Section: Discussionsupporting

confidence: 90%

“…In the setting of advanced disease, a large report on over 1,400 metastatic patients showed similar results and median OS of TP53 mutated was 8 months shorter than the wild-type counterpart (48). Other reports did not confirm significant prognostic value of TP53 mutations in advanced NSCLC (49)(50)(51). To date, to the best of our knowledge, ours is the first report describing such correlation using only plasma as source material for NGS.…”

Section: Discussionmentioning

confidence: 51%

“…Patients carrying a pathogenic variant of STK11 and receiving ICIs showed a trend for shorter OS. The prognostic role of STK11 has been already investigated in tissue samples, and previous retrospective studies found a negative impact on outcome (50,52). These studies included patients treated with firstline platinum-based chemotherapy, with no details about further lines of treatment.…”

Section: Discussionmentioning

confidence: 99%

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Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome

Pavan

Bragadin

Calvetti

et al. 2021

Transl Lung Cancer Res

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Background: Characterization of tumor-related genetic alterations is promising for the screening of new predictive markers in non-small cell lung cancer (NSCLC). Aim of the study was to evaluate prognostic and predictive role of most frequent tumor-associated genetic alterations detected in plasma before starting immune checkpoint inhibitors (ICIs).Methods: Between January 2017 and October 2019, advanced NSCLC patients were prospectively screened with plasma next-generation sequencing (NGS) while included in two trials: VISION (NCT02864992), using Guardant360 ® test, and MAGIC (Monitoring Advanced NSCLC through plasma Genotyping during Immunotherapy: Clinical feasibility and application), using Myriapod NGS-IL 56G Assay. A control group of patients not receiving ICIs was analyzed.Results: A total of 103 patients receiving ICIs were analyzed: median overall survival (OS) was 20.8 (95% CI: 16.7-24.9) months and median immune-related progression free disease (irPFS) 4.2 (95% CI: 2.3-6.1) months. TP53 mutations in plasma negatively affected OS both in patients treated with ICIs and in control group (P=0.001 and P=0.009), indicating a prognostic role. STK11 mutated patients (n=9) showed a trend for worse OS only if treated with ICIs. The presence of KRAS/STK11 co-mutation and KRAS/STK11/TP53 co-mutation affected OS only in patients treated with ICIs (HR =10.936, 95% CI: 2.337-51.164, P=0.002; HR =17.609, 95% CI: 3.777-82.089, P<0.001, respectively), indicating a predictive role.Conclusions: Plasma genotyping demonstrated prognostic value of TP53 mutations and predictive value of KRAS/STK11 and KRAS/STK11/TP53 co-mutations.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

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Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome

Pavan

Bragadin

Calvetti

et al. 2021

Transl Lung Cancer Res

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“…Molecular biology of lung cancer appears to be the hallmark and the most signifi cant marker of patient prognosis. For lung cancer treatment, blocking tumor growth by targeting the surrounding angiogenesis, protumorigenic growth factor activation, anti-apoptotic cascades and other cancer-promoting signal transduction events are extremely important and incredibly effective for prolonging patient survival [12][13][14][15][16]…”

Section: Discussionmentioning

confidence: 99%

Correlation of clinical, radiologic and pathologic manifestations with prognosis in lung cancer patients

Yanardağ¹,

Tetikkurt²,

Papila³

et al. 2020

Arch Pulmonol Respir Care

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Many different factors that are extremely variable for each individual affect the survival of lung cancer patients. Prognosis in lung cancer depends upon tumor type, patient immunity and treatment modalities. The objective of our study was to determine the infl uence of clinical manifestations including the patient symptoms, laboratory findings, imaging modalities and histopathologic tumor features on the prognosis in lung cancer. Another aim was to evaluate whether the collaboration of these data predicted a more accurate prognostic assessment. A total of 1800 lung cancer patients evaluated at our clinic between 1984 and 2005 years were included in the study. The patients had blood chemistry, chest x-ray, pulmonary function tests, chest computed tomography and histopathology. Prognosis of the patients was evaluated in regard to initial clinical symptoms, performance status, laboratory findings, pulmonary function test results, radiologic, CT and histopathologic manifestations. For patient performance BODE and Karnofsky index were used. Statistical analysis was performed by using Pearson correlation and chi-square tests. Patient performance status and symptoms had a weak correlation with prognosis. The routine laboratory and the pulmonary function test results were incoherent predictors of survival. Chest x-ray and computed tomography findings displayed a noteworthy correlation for the prognostic outcome. Histopathologic features including tumor type, differentiation profile and microscopic invasive features of the airways, nerves, blood or lymphatic vessels were the hallmark of prognostic evaluation along with immunohistochemistry findings. The above criteria other than the pathologic manifestations showed a poor or a moderate correlation by themselves for an accurate prognostic outcome. Collaboration of the clinical manifestations revealed a significantly high correlation for the prognostic evaluation of lung cancer. The most accurate prognostic determination was achieved in advanced stage cases. The results of our study indicate that the more specific the clinical criteria are considered in a lung cancer patient, the more accurate the prognostic assessment will be since cancer pathogenesis is associated with many different complex mechanisms.

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“…Thus, in the presence of these co-mutations, specific inhibitors targeting KRASG12C could be considered and given instead of immunotherapy with anti-PD1/PD-L1 medication. However, interestingly, some studies have shown that mutations in STK11 are less frequent in KRAS mutated tumors than in wild-type KRAS tumors [220]. It should be noted that, despite the association of these mutations, a rare number of tumors are still sensitive to ICIs [221,222].…”

Section: Kras G12c Mutationsmentioning

confidence: 99%

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

Hofman

2021

JMP

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The discovery and clinical validation of biomarkers predictive of the response of non-squamous non-small-cell lung carcinomas (NS-NSCLC) to therapeutic strategies continue to provide new data. The evaluation of novel treatments is based on molecular analyses aimed at determining their efficacy. These tests are increasing in number, but the tissue specimens are smaller and smaller and/or can have few tumor cells. Indeed, in addition to tissue samples, complementary cytological and/or blood samples can also give access to these biomarkers. To date, it is recommended and necessary to look for the status of five genomic molecular biomarkers (EGFR, ALK, ROS1, BRAFV600, NTRK) and of a protein biomarker (PD-L1). However, the short- and more or less long-term emergence of new targeted treatments of genomic alterations on RET and MET, but also on others’ genomic alteration, notably on KRAS, HER2, NRG1, SMARCA4, and NUT, have made cellular and blood samples essential for molecular testing. The aim of this review is to present the interest in using cytological and/or liquid biopsies as complementary biological material, or as an alternative to tissue specimens, for detection at diagnosis of new predictive biomarkers of NS-NSCLC.

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Concomitant genomic alterations in KRAS mutant advanced lung adenocarcinoma

Cited by 17 publications

References 14 publications

Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome

Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome

Correlation of clinical, radiologic and pathologic manifestations with prognosis in lung cancer patients

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

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