Dataset Information

Clinical value of PET/CT in identifying patients with oligometastatic/oligoprogressive disease among first-line tyrosine kinase inhibitor-treated advanced EGFR-mutant non-small cell lung cancer: Implications from survival comparisons.

ABSTRACT:

Objective

Local therapy (LT) could potentially prolong the survival of patient with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) receiving tyrosine kinase inhibitors (TKIs) and harboring oligometastatic/oligoprogressive disease (OMD/OPD). However, the optimal imaging method for identifying patients with OMD/OPD remains controversial. The objective of this study was to investigate the clinical value of incorporating PET/CT in detecting patients with OMD/OPD.

Methods

Consecutive cases with metastatic EGFR-mutant NSCLC undergoing first-line EGFR-TKI treatment were retrospectively screened and those receiving baseline PET/CT and brain magnetic resonance imaging (MRI) or complete conventional imaging (CIM), including brain MRI, chest computed tomography (CT), abdomen ultrasound or CT and bone scintigraphy were included. OMD/OPD was defined as metastases/progressions documented at a maximum of five lesions and three organs, otherwise was defined as multiple metastatic/progressive disease (MMD/MPD). Progression-free survival (PFS) and overall survival (OS) were analyzed.

Results

Of the 392 patients evaluated, baseline OMD was detected in 22.7% (53/233) of patients by PET/CT and in 18.2% (29/159) of patients by CIM (p = 0.171). Among the patients evaluated with baseline PET/CT, patients with OMD had longer PFS (p = 0.016) and tendency of improved OS (p = 0.058) than those with MMD. However, this result was not observed with patients evaluated using baseline CIM. With a median follow-up of 24.2 (range, 1.1-124.6) months, 297 patients had their first disease progression (FPD), of whom 164 (55.2%) had adequate imaging scans to analyze the tumor distributions at FPD comprehensively. OPD was detected in 63.0% (34/54) and 35.0% (39/110) of patients among the PET/CT and CIM assessed group (p = 0.003), respectively. Among the PET/CT assessed group, patients with OPD had significantly longer post-progressive overall survival (OS2) than those with MPD (p = 0.011). However, no significant difference of OS2 in the CIM assessed group was found.

Conclusion

Patients with OMD/OPD, evaluated by PET/CT but not CIM, generally had more favorable survival outcomes than those with MMD/MPD among patients with metastatic NSCLC undergoing first-line EGFR-TKI treatment.

Advances in knowledge

PET/CT seems to affect the survival of patients under first-line EGFR-TKI treated metastatic NSCLC with OMD/OPD.

SUBMITTER: Xu D

PROVIDER: S-EPMC10162049 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Clinical value of PET/CT in identifying patients with oligometastatic/oligoprogressive disease among first-line tyrosine kinase inhibitor-treated advanced EGFR-mutant non-small cell lung cancer: Implications from survival comparisons.

Xu Dayu D Yu Fan F Guo Tiantian T Zhou Yue Y Zhang Jinmeng J Li Yida Y Jiang Shanshan S Mao Jiuang J Yang Xi X Chu Li L Chu Xiao X Wang Shengping S Ni Jianjiao J Zhu Zhengfei Z

The British journal of radiology 20220609 1136

<h4>Objective</h4>Local therapy (LT) could potentially prolong the survival of patient with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) receiving tyrosine kinase inhibitors (TKIs) and harboring oligometastatic/oligoprogressive disease (OMD/OPD). However, the optimal imaging method for identifying patients with OMD/OPD remains controversial. The objective of this study was to investigate the clinical value of incorporating PET/CT in detecting patient ...[more]

PMID: 35611637

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Project description:Tyrosine kinase inhibitors (TKIs) against the human epidermal growth factor receptor (EGFR) are now standard treatment in the clinic for patients with advanced EGFR mutant non-small-cell lung cancer (NSCLC). First-generation EGFR TKIs, binding competitively and reversibly to the ATP-binding site of the EGFR tyrosine kinase domain, have resulted in a significant improvement in outcome for NSCLC patients with activating EGFR mutations (L858R and Del19). However, after a median duration of response of ~12 months, all patients develop tumor resistance, and in over half of these patients this is due to the emergence of the EGFR T790M resistance mutation. The second-generation EGFR/HER TKIs were developed to treat resistant disease, targeting not only T790M but EGFR-activating mutations and wild-type EGFR. Although they exhibited promising anti-T790M activity in the laboratory, their clinical activity among T790M+ NSCLC was poor mainly because of dose-limiting toxicity due to simultaneous inhibition of wild-type EGFR. The third-generation EGFR TKIs selectively and irreversibly target EGFR T790M and activating EGFR mutations, showing promising efficacy in NSCLC resistant to the first- and second-generation EGFR TKIs. They also appear to have lower incidences of toxicity due to the limited inhibitory effect on wild-type EGFR. Currently, the first-generation gefitinib and erlotinib and second-generation afatinib have been approved for first-line treatment of metastatic NSCLC with activating EGFR mutations. Among the third-generation EGFR TKIs, osimertinib is today the only drug approved by the Food and Drug Administration and the European Medicines Agency to treat metastatic EGFR T790M NSCLC patients who have progressed on or after EGFR TKI therapy. In this review, we summarize the available post-progression therapies including third-generation EGFR inhibitors and combination treatment strategies for treating patients with NSCLC harboring EGFR mutations and address the known mechanisms of resistance.

Project description:BackgroundAndrogen deprivation therapy (ADT) remains the standard therapy for patients with oligometastatic prostate cancer (OMPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT)-based stereotactic body radiotherapy (SBRT) is emerging as an alternative option to postpone starting ADT and its associated side effects including the development of drug resistance. The aim of this study was to determine progression free-survival (PFS) and treatment failure free-survival (TFFS) after PSMA-PET/CT-based SBRT in OMPC patients. The efficacy and safety of single fraction radiosurgery (SFRS) and ADT delay were investigated.MethodsPatients with ≤5 metastases from OMPC, with/without ADT treated with PSMA-PET/CT-based SBRT were retrospectively analyzed. PFS and TFFS were primary endpoints. Secondary endpoints were local control (LC), overall survival (OS) and ADT-free survival (ADTFS).ResultsFifty patients with a total of 75 metastases detected by PSMA-PET/CT were analyzed. At the time of SBRT, 70% of patients were castration-sensitive. Overall, 80% of metastases were treated with SFRS (median dose 20 Gy, range: 16-25). After median follow-up of 34 months (range: 5-70) median PFS and TFFS were 12 months (range: 2-63) and 14 months (range: 2-70), respectively. Thirty-two (64%) patients had repeat oligometastatic disease. Twenty-four (48%) patients with progression underwent second SBRT course. Two-year LC after SFRS was 96%. Grade 1 and 2 toxicity occurred in 3 (6%) and 1 (2%) patients, respectively. ADTFS and OS rates at 2-years were 60.5% and 100%, respectively. In multivariate analysis, TFFS significantly improved in patients with time to first metastasis (TTM) >36 months (p = 0.01) and PSA before SBRT ≤1 ng/ml (p = 0.03).ConclusionFor patients with OMPC, SBRT might be used as an alternative to ADT. This way, the start/escalation of palliative ADT and its side effects can be deferred. Metastases treated with PSMA-PET/CT-based SFRS reached excellent LC with minimal toxicity. Low PSA levels and longer TTM predict elongated TFFS.

Dataset Information

Clinical value of PET/CT in identifying patients with oligometastatic/oligoprogressive disease among first-line tyrosine kinase inhibitor-treated advanced EGFR-mutant non-small cell lung cancer: Implications from survival comparisons.

Objective

Methods

Results

Conclusion

Advances in knowledge

Publications

Clinical value of PET/CT in identifying patients with oligometastatic/oligoprogressive disease among first-line tyrosine kinase inhibitor-treated advanced EGFR-mutant non-small cell lung cancer: Implications from survival comparisons.

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