“Lazarus effect” in patient affected by lung adenocarcinoma carrying EGFR, CTNNB1, MET exon 11 and PIK3CA mutations treated with gefitinib

Conci, Nicole; Dall’Olio, Filippo Gustavo; Comellini, Vittoria; Brocchi, Stefano; Golfieri, Rita; Ardizzoni, Andrea

doi:10.21037/pcm-20-32

Cited by 2 publications

(4 citation statements)

References 7 publications

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“…Our study has a novelty as compared to the mentioned above investigations, as it included a relatively large number of patients and involved a serial blood-takes performed within first hours after TKI administration. The justification of this effort was based on published observations describing a very rapid treatment response in a subset of patients [26,27,36] as well as on the data obtained in preclinical experiments [37][38][39]. Our results suggest that good responders to TKIs can be identified already at 48 h after the start of the EGFR-targeted therapy.…”

Section: Discussionmentioning

confidence: 76%

“…The therapeutic doses of the EGFR TKIs are significantly higher than the minimal drug concentrations, which exert some antitumor effect [33][34][35]. Consequently, it is explainable, that some patients experience evident symptomatic relief within the first hours after the beginning of the treatment [26,27,36]. Studies of EGFR inhibition in cell lines revealed, that the administration of anti-EGFR drugs results in immediate biological consequences.…”

Section: Discussionmentioning

confidence: 99%

“…EGFR inhibitors are also characterized by the "Lazarus effect", i.e. dramatic symptomatic relief occurring within first hours after the drug administration [26,27]. It is well established that the reduction of tumor size, which is observed during regular patient check-ups, is paralleled by the decline of the amount of EGFR-mutated ctDNA.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the concentration of EGFR-mutated plasma DNA in the first hours of targeted therapy allow the prediction of tumor response in patients with EGFR-driven lung cancer

et al. 2022

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Purpose This study aimed to analyze changes in the plasma concentration of EGFR-mutated circulating tumor DNA (ctDNA) occurring immediately after the start of therapy with EGFR tyrosine kinase inhibitors (TKIs). Methods Serial plasma samples were collected from 30 patients with EGFR-driven non-small cell lung cancer before intake of the first tablet and at 0.5, 1, 2, 3, 6, 12, 24, 36 and 48 h after the start of the therapy. The content of EGFR alleles (exon 19 deletions or L858R) in ctDNA was measured by ddPCR. Results ctDNA was detected at base-line in 25/30 (83%) subjects. Twelve (50%) out of 24 informative patients showed > 25% reduction of the ctDNA content at 48 h time point; all these patients demonstrated disease control after 4 and 8-12 weeks of therapy. The remaining 12 individuals showed either stable content of EGFR-mutated ctDNA (n = 5) or the elevation of ctDNA concentration (n = 7). 10 of 12 patients with elevated or stable ctDNA level achieved an objective response at 4 weeks, but only 5 of 10 evaluable patients still demonstrated disease control at 8-12 weeks (p = 0.032, when compared to the group with ctDNA decrease). The decline of the amount of circulating EGFR mutant copies at 48 h also correlated with longer progression-free survival (14.7 months vs. 8.5 months, p = 0.013). Conclusion Comparison of concentration of EGFR-mutated ctDNA at base-line and at 48 h after the start of therapy is predictive for the duration of TKI efficacy.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

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Changes in the concentration of EGFR-mutated plasma DNA in the first hours of targeted therapy allow the prediction of tumor response in patients with EGFR-driven lung cancer

et al. 2022

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“…In conclusion, the treatment of MS caused by NSCLC is based on molecular characterization. In fact, in oncogene-addicted disease, treatment with TKIs can determine a rapid and impressive response such as the so called “Lazarus effect” ( 33 ). Target therapy can lead to a reduction in tumor volume with consequent resolution of symptoms.…”

Section: Discussionmentioning

confidence: 99%

Principles of medical and oncological management of giant masses of the mediastinum: a narrative review

Conci¹,

Grilli²,

Dall’Olio³

2022

Mediastinum

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Background and Objective Giant mediastinal tumors are represented by well-defined histological variants originating from different structures and compartments while their clinical presentation may be similar and characterized by the same set of symptoms, the well-known mediastinal syndrome (MS). In 80% of cases the MS is caused by malignant neoplasms, such as lung tumors, in 10–18% of cases by hematological neoplasms and in 2–3% by benign causes. In this review we investigated the medical treatment of main giant mediastinal tumors, focusing our interest on the objective response rate (ORR), as it represents the most suitable parameter to predict the volumetric reduction of the neoplasm and, consequently, the regression of their most severe complication, the MS. We will also cover the supportive and symptomatic treatment of MS. Methods We performed a deep analysis of the recent international literature published on PUBMED, UpToDate and Medline. The literature search was undertaken from origin until November 30th, 2021, and we only considered publications in English. Key Content and Findings Considering the variety of pathologies that can occur in the mediastinum, a rapid histological characterization of the neoplasm is mandatory. In fact, the treatment of these neoplasms includes different approaches, sometimes used in combination, which include chemotherapy, radiotherapy, and surgery. The vena cava syndrome (VCS), due to its high mortality, is considered an oncological emergency and, therefore, requires effective treatments carried out urgently, evaluated in multidisciplinary meeting. Conclusions The treatment of MS includes both antiblastic treatments and therapies directed to the symptoms. Among the former, chemotherapy, target therapy, radiation and surgery may be used, according to the etiology of MS. Among the latters, supportive therapies, interventional radiology procedures such as stenting may help manage this syndrome, despite the prognosis is poor in most cases and linked to the histology of the tumor, which therefore represents the most important prognostic factor.

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“Lazarus effect” in patient affected by lung adenocarcinoma carrying EGFR, CTNNB1, MET exon 11 and PIK3CA mutations treated with gefitinib

Cited by 2 publications

References 7 publications

Changes in the concentration of EGFR-mutated plasma DNA in the first hours of targeted therapy allow the prediction of tumor response in patients with EGFR-driven lung cancer

Changes in the concentration of EGFR-mutated plasma DNA in the first hours of targeted therapy allow the prediction of tumor response in patients with EGFR-driven lung cancer

Principles of medical and oncological management of giant masses of the mediastinum: a narrative review

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