Complete metabolic response in advanced non-small cell lung cancer patients with prolonged response to immune checkpoint inhibitor therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9050-9050
Author(s):  
Daniel Christian Christoph ◽  
Justin Ferdinandus ◽  
Martin Metzenmacher ◽  
Peter Kessler ◽  
Lale Umutlu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Fdg Pet ◽  
Metabolic Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Durable Response

9050 Background: Recently reported, extended follow-up data from KEYNOTE-024 or -010 indicates that non-small-cell lung cancer (NSCLC) patients can experience long-term benefit from immunotherapy irrespective of discontinuation (per protocol: 35 cycles ∼24 months) or type of response in computed tomography (CT). Similar results were observed in the pooled analysis of 5-year follow-up data from CheckMate-017 and -057. This raises the question, whether patients may safely discontinue immunotherapy after achieving durable response. However, recently published results from CheckMate-153 demonstrated inferior survival rates in patients ceasing immunotherapy after one year, therefore optimal treatment duration of immunotherapy in advanced NSCLC remains unknown. Protocols from published Phase-III trials implemented treatment for a period of approximately 24 months or until evidence of disease progression or unbearable toxicity. Therefore, the ideal duration of immunotherapy remains unclear, and finding markers of beneficial outcome is of great importance. Here, we determine the proportion of complete metabolic responses (CMR) in patients that have not progressed after 24 months of immunotherapy. Methods: This is a retrospective analysis of forty-five patients with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) imaging for assessment of residual metabolic activity after at least 24 months of immunotherapy. Lesion-uptake in FDG PET on or below background level (using mediastinum as reference) was considered as CMR. Time until best objective morphological response including disease stabilization was measured from start of immunotherapy until first stable CT-scan (i.e. no progression or further response compared to previous scan) using RECIST 1.1. Results: Out of 45 patients, 29 patients had a CMR (64%). CMR was observed more frequently in non-first line patients. Patients with CMR were younger (median 65.7 vs. 75.5, P = 0.03). Fourteen patients with CMR have discontinued therapy and have not progressed until time of analysis; however median follow-up was only 5.6 (range 0.8-17.0) months. Conclusions: After a minimum of 24 months of palliative immunotherapy for NSCLC, CMR occurred in almost two thirds of patients. Potentially, achievement of CMR might identify patients, for whom palliative immunotherapy may be safely discontinued.

FDG-PET imaging for the staging and follow-up of small cell lung cancer

2001 ◽  
Vol 28 (4) ◽  
pp. 483-488 ◽  
Author(s):  
Tilmann Schumacher ◽  
Ingo Brink ◽  
Michael Mix ◽  
Michael Reinhardt ◽  
Georg Herget ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Preselection of robust radiomic features does not improve outcome modelling in non-small cell lung cancer based on clinical routine FDG-PET imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carol Oliveira ◽  
Florian Amstutz ◽  
Diem Vuong ◽  
Marta Bogowicz ◽  
Martin Hüllner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Attenuation Correction ◽  
Cell Lung Cancer ◽  
Fdg Pet ◽  
Locally Advanced ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Single Centre

Abstract Background Radiomics is a promising tool for identifying imaging-based biomarkers. Radiomics-based models are often trained on single-institution datasets; however, multi-centre imaging datasets are preferred for external generalizability owing to the influence of inter-institutional scanning differences and acquisition settings. The study aim was to determine the value of preselection of robust radiomic features in routine clinical positron emission tomography (PET) images to predict clinical outcomes in locally advanced non-small cell lung cancer (NSCLC). Methods A total of 1404 primary tumour radiomic features were extracted from pre-treatment [18F]fluorodeoxyglucose (FDG)-PET scans of stage IIIA/N2 or IIIB NSCLC patients using a training cohort (n = 79; prospective Swiss multi-centre randomized phase III trial SAKK 16/00; 16 centres) and an internal validation cohort (n = 31; single centre). Robustness studies investigating delineation variation, attenuation correction and motion were performed (intraclass correlation coefficient threshold > 0.9). Two 12-/24-month event-free survival (EFS) and overall survival (OS) logistic regression models were trained using standardized imaging: (1) with robust features alone and (2) with all available features. Models were then validated using fivefold cross-validation, and validation on a separate single-centre dataset. Model performance was assessed using area under the receiver operating characteristic curve (AUC). Results Robustness studies identified 179 stable features (13%), with 25% stable features for 3D versus 4D acquisition, 31% for attenuation correction and 78% for delineation. Univariable analysis found no significant robust features predicting 12-/24-month EFS and 12-month OS (p value > 0.076). Prognostic models without robust preselection performed well for 12-month EFS in training (AUC = 0.73) and validation (AUC = 0.74). Patient stratification into two risk groups based on 12-month EFS was significant for training (p value = 0.02) and validation cohorts (p value = 0.03). Conclusions A PET-based radiomics model using a standardized, multi-centre dataset to predict EFS in locally advanced NSCLC was successfully established and validated with good performance. Prediction models with robust feature preselection were unsuccessful, indicating the need for a standardized imaging protocol.

scholarly journals Apatinib in patients with extensive-stage small-cell lung cancer after second-line or third-line chemotherapy: a phase II, single-arm, multicentre, prospective study

2019 ◽  
Vol 121 (8) ◽  
pp. 640-646 ◽  
Author(s):  
Yanjun Xu ◽  
Zhiyu Huang ◽  
Hongyang Lu ◽  
Xinming Yu ◽  
Yuping Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Term Survival ◽  
Extensive Stage

Abstract Background Small-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies. Methods Eligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate. Results Forty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand–foot syndrome, increased L-gamma-glutamyltransferase. Conclusions Apatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted. Trial registration NCT02945852.

scholarly journals Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer

2021 ◽  
Vol 39 (7) ◽  
pp. 723-733
Author(s):  
Hossein Borghaei ◽  
Scott Gettinger ◽  
Everett E. Vokes ◽  
Laura Q. M. Chow ◽  
Marco Angelo Burgio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Trials ◽  
Previously Treated

PURPOSE Immunotherapy has revolutionized the treatment of advanced non–small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m2 once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3–5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC.

Predictive Value of Interim 18F-FDG-PET in Patients with Non-Small Cell Lung Cancer Treated with Definitive Radiation Therapy

2020 ◽  
Author(s):  
Nalee Kim ◽  
Jin Sung Kim ◽  
Chang Geol Lee
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Value ◽  
Fdg Pet ◽  
Metabolic Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Pet Ct ◽  
Fdg Pet Ct

Abstract Background We evaluated that early metabolic response determined by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiotherapy (RT), predicts outcomes in non-small cell lung cancer. Methods Twenty-eight patients evaluated using pretreatment 18 F-FDG-PET/CT (PET pre ) and interim 18 F-FDG-PET/CT (PET interim ) after 11 fractions of RT were retrospectively reviewed. Maximum standardized uptake value (SUV max ) was calculated for primary lesion. Predictive value of gross tumor volume (△GTV) and SUV max (△SUV max ) changes was evaluated for locoregional control (LRC), distant failure (DF), and overall survival (OS). Metabolic responders were patients with △SUV max >40%. Results Metabolic responders showed better trends in 1-year LRC (90.9%) than non-responders (47.1%) (p=0.086). Patients with large GTV pre (≥120 cc) demonstrated poor LRC (hazard ratio 4.14, p = 0.022), while metabolic non-responders with small GTV pre (<120 cc) and metabolic responders with large GTV pre both had 1-year LRC rates of 75.0%. Reduction of 25% in GTV was not associated with LRC; however, metabolic responders without a GTV response showed better 1-year LRC (83.3%) than metabolic non-responders with a reduction in GTV (42.9%). Metabolic responders showed lower 1-year DF (16.7%) than non-responders (50.0%) (p=0.025). An ΔSUV max threshold of 40% yielded accuracy of 64% for predicting LRC, 75% for DF, and 54% for OS. However, ΔGTV > 25% demonstrated inferior diagnostic values than metabolic response. Conclusions Changes in tumor metabolism diagnosed using PET interim during RT better predicted treatment responses, recurrences, and prognosis than other factors historically used.

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