Tumor Volume Decrease at 8 Weeks Is Associated with Longer Survival in EGFR-Mutant Advanced Non–Small-Cell Lung Cancer Patients Treated with EGFR TKI

Nishino, Mizuki; Dahlberg, Suzanne E.; Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Hatabu, Hiroto; Jänne, Pasi A.; Johnson, Bruce E.

doi:10.1097/jto.0b013e318294c909

Cited by 52 publications

(92 citation statements)

References 54 publications

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“…A small study of 13 patients with resectable locally advanced NSCLC found that both pre- and post-treatment gross tumor volume predicted PFS [27], using automatic deformable image registration software for volumetric measurements. Nishino et al evaluated a group of 56 NSCLC patients with EGFR mutations treated with first-line tyrosine kinase inhibitors [28] and similar to our results found that an early decrease in tumor volume was associated with overall survival.…”

Section: Discussionsupporting

confidence: 86%

Comparison of CT volumetric measurement with RECIST response in patients with lung cancer

Hayes

Pietanza

O’Driscoll

et al. 2016

European Journal of Radiology

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Purpose To examine the correlations between uni-dimensional RECIST and volumetric measurements in patients with lung adenocarcinoma and to assess their association with overall survival (OS) and progression-free survival (PFS). Materials and Methods In this study of patients receiving chemotherapy for lung cancer in the setting of a clinical trial, response was prospectively evaluated using RECIST 1.0. Retrospectively, volumetric measurements were recorded and response was assessed by two different volumetric methods at each followup CT scan using a semi-automated segmentation algorithm. We subsequently evaluated the correlation between the uni-dimensional RECIST measurements and the volumetric measurements and performed landmark analyses for OS and PFS at the completion of the first and second follow-ups. Kaplan-Meier curves together with log-rank tests were used to evaluate the association between the different response criteria and patient outcome. Results Forty-two patients had CT scans at baseline, after the first follow up scan and second followup scan, and then every 8 weeks. The uni-dimensional RECIST measurements and volumetric measurements were strongly correlated, with a Spearman correlation coefficient (ρ) of 0.853 at baseline, ρ = 0.861 at the first followup, ρ = 0.843 at the 2nd followup, and ρ = 0.887 overall between-subject. On first follow-up CT, partial responders and non responders as assessed by an “ellipsoid” volumetric criteria showed a significant difference in OS (p=0.008, 1-year OS of 70% for partial responders and 46% for non responders). There was no difference between the groups when assessed by RECIST criteria on first follow-up CT (p=0.841, 1-year OS rate of 64% for partial responders and 64% for non responders). Conclusion Volumetric response on first follow-up CT may better predict OS than RECIST response. Clinical Relevance Statement Assessment of tumor size and response is of utmost importance in clinical trials. Volumetric measurements may help to better predict OS than uni-dimensional RECIST criteria.

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Section: Discussionsupporting

confidence: 86%

Comparison of CT volumetric measurement with RECIST response in patients with lung cancer

Hayes

Pietanza

O’Driscoll

et al. 2016

European Journal of Radiology

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“…In addition, an 8-week time point has been previously studied to identify early markers for outcome in advanced NSCLC patients. (31–33)…”

Section: Resultsmentioning

confidence: 99%

“…As tumor volume has also been shown to be a reproducible marker to characterize tumor response and progression and predict survival for advanced NSCLC treated with molecular targeted therapy including EGFR inhibitors(33,35,36), the utility of tumor volume in the setting of immune-related response evaluations can be tested in future studies. The response assessment of irRECIST is based on the sum of the target lesion measurements in each patient, and does not reflect different behaviors of individual lesions in one patient.…”

Section: Discussionmentioning

confidence: 99%

Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome

Nishino

Dahlberg

Adeni

et al. 2017

Clinical Cancer Research

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Purpose We evaluated tumor burden dynamics in advanced non-small-cell lung cancer (NSCLC) patients treated with commercial PD-1 inhibitors to identify imaging markers associated with improved overall survival (OS). Experimental Design The study included 160 advanced NSCLC patients treated with commercial nivolumab or pembrolizumab monotherapy as a part of clinical care. Tumor burden dynamics were studied for the association with OS. Results Tumor burden change at best overall response (BOR) ranged from −100% to +278% (median: +3.5%). Response rate (RR) was 18% (29/160). Current and former smokers had a higher RR than never smokers (p=0.04). Durable disease control for at least 6 months was noted in 26 patients (16%), which included 10 patients with stable disease as BOR. Using a landmark analysis, patients with <20% tumor burden increase from baseline within 8 weeks of therapy had longer OS than patients with ≥20% increase (median OS:12.4 vs. 4.6 months, p<0.001). Patients with <20% tumor burden increase throughout therapy had significantly reduced hazards of death (HR=0.24, Cox p<0.0001) after adjusting for smoking (HR=0.86, p=0.61) and baseline tumor burden (HR=1.55, p=0.062), even though some patients met criteria for RECIST progression while on therapy. One patient (0.6%) had atypical response pattern consistent with pseudoprogression. Conclusions Objective response or durable disease control was noted in 24% of advanced NSCLC patients treated with commercial PD-1 inhibitors. A tumor burden increase of <20% from baseline during therapy was associated with longer OS, proposing a practical marker of treatment benefit. Pseudoprogression is rare in NSCLCs treated with PD-1 inhibitors.

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“…Our observations are consistent with these findings and those demonstrated in other malignancies treated with targeted therapy, including KRAS wild-type metastatic colorectal cancer and advanced non-small cell lung cancer, in which early tumor shrinkage has been shown to be a powerful predictor of outcome. [10, 11] Compared to previously published studies in mRCC, our study has many novel aspects. This is the first and largest comprehensive study demonstrating that the best tumor response on imaging is an independent prognostic factor for survival in mRCC, irrespective of line of treatment or agent applied.…”

Section: Discussionmentioning

confidence: 99%

Depth of Remission is a Prognostic Factor for Survival in Patients with Metastatic Renal Cell Carcinoma

Grünwald¹,

McKay²,

Krajewski³

et al. 2015

European Urology

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Background Response remains an important endpoint in clinical cancer trials. However, the prognostic utility of best tumor response in metastatic renal cell carcinoma (mRCC) remains vague. Objective To define the prognostic relevance of the depth of remission in mRCC Design, setting, and participants Pooled data of 2,749 patients from phase II and III clinical trials of the Pfizer data-base in mRCC was analyzed. Tumor-shrinkage was categorized by fractions of best percent change in the sum of the largest diameter of target lesions. Outcome was computed by Kaplan-Meier curves and correlation was assessed by Cox regression, including a 6-month landmark. Intervention Sunitinib, sorafenib, axitinib, temsirolimus, temsirolimus and/or IFN-α. Outcome Measurements and Statistical Analysis Categorized tumor-shrinkage, overall survival (OS), progression free survival (PFS). Results and limitations Major tumor shrinkage of 60% or more occurred in about 10% of patients and was associated with a median overall survival (OS) of 54.5 months. With depth of remission, OS expectations declined steadily (26.4, 16.6, 10.4, and 7.3 months). The association was maintained when stratified by type of therapy, line of therapy, and performance status. The 6-month landmark Cox proportional regression analyses confirmed the prognostic relevance of major tumor shrinkage (HR 0.29; CI 95% 0.22–0.39; p<0.001). The major limitation of our study is the variability of imaging intervals among studies. Conclusions This is the first and largest analysis of best tumor response in mRCC. We demonstrate that depth of remission is an independent prognostic factor in mRCC. Patient summary It remains unknown whether tumor shrinkage during therapy is needed to achieve clinical activity in mRCC. Our analysis shows that the magnitude of tumor shrinkage correlates with a better survival in patients. This observation may be used as a clinical research tool in future trials. Trial registration NCT00054886, NCT00077974, NCT00267748, NCT00338884, NCT00137423, NCT00083889, NCT00065468, NCT00678392

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Tumor Volume Decrease at 8 Weeks Is Associated with Longer Survival in EGFR-Mutant Advanced Non–Small-Cell Lung Cancer Patients Treated with EGFR TKI

Cited by 52 publications

References 54 publications

Comparison of CT volumetric measurement with RECIST response in patients with lung cancer

Comparison of CT volumetric measurement with RECIST response in patients with lung cancer

Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome

Depth of Remission is a Prognostic Factor for Survival in Patients with Metastatic Renal Cell Carcinoma

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