Prognostic value of (18) F-fluoroazomycin arabinoside PET/CT in patients with advanced non-small-cell lung cancer.
ABSTRACT: This study evaluated the prognostic value of positron emission tomography/computed tomography (PET/CT) using (18) F-fluoroazomycin arabinoside (FAZA) in patients with advanced non-small-cell lung cancer (NSCLC) compared with (18) F-fluorodeoxyglucose (FDG). Thirty-eight patients with advanced NSCLC (stage III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before treatment. The PET parameters (tumor-to-muscle ratio [T/M] at 1 and 2 h for FAZA, maximum standardized uptake value for FDG) in the primary lesion and lymph node (LN) metastasis and clinical parameters were compared concerning their effects on progression-free survival (PFS) and overall survival (OS). In our univariate analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were independent predictors of PFS. Subgroup analysis of chemoradiotherapy-treated stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No parameter was a significant predictor of OS. In patients with advanced NSCLC, FAZA uptake in LNs, but not in primary lesions, was predictive of treatment outcome. These results suggest the importance of characterization of LN metastases in advanced NSCLC patients.
Project description:Purpose:This study investigated whether the metabolic avidity of primary tumors and/or metastatic lymph nodes (LNs) measured by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was related to survival after surgery in patients with advanced gastric cancer (AGC). Materials and Methods:One hundred sixty-eight patients with AGC who underwent preoperative 18F-FDG PET/CT and curative resection were included. The 18F-FDG avidity of the primary gastric tumor and LNs was determined quantitatively and qualitatively. The diagnostic performance of 18F-FDG PET/CT was calculated, and the prognostic significance of 18F-FDG avidity for recurrence-free survival (RFS) and overall survival (OS) was assessed. Results:In all, 51 (30.4%) patients experienced recurrence, and 32 (19.0%) died during follow-up (median follow-up duration, 35 months; range, 3-81 months); 119 (70.8%) and 33 (19.6%) patients showed 18F-FDG-avid primary tumors and LNs, respectively. 18F-FDG PET/CT showed high sensitivity (73.8%) for the detection of advanced pathologic T (pT ?3) stage and high specificity (92.2%) for the detection of advanced pN (?2) stage. 18F-FDG avidity of LNs was significantly associated with RFS (P=0.012), whereas that of primary tumors did not show significance (P=0.532). Univariate and multivariate analyses revealed that 18F-FDG avidity of LNs was an independent prognostic factor for RFS (hazard ratio=2.068; P=0.029). Conclusions:18F-FDG avidity of LNs is an independent prognostic factor for predicting RFS. Preoperative 18F-FDG PET/CT can be used to determine the risk and prognosis of patients with AGC after curative resection.
Project description:OBJECTIVES:(1.1) to evaluate the association between baseline 18F-FDG PET/CT semi-quantitative parameters of the primary lesion with progression free survival (PFS), overall survival (OS) and response to immunotherapy, in advanced non-small cell lung carcinoma (NSCLC) patients eligible for immunotherapy; (1.2) to evaluate the application of radiomics analysis of the primary lesion to identify features predictive of response to immunotherapy; (1.3) to evaluate if tumor burden assessed by 18F-FDG PET/CT (N and M factors) is associated with PFS and OS. MATERIALS AND METHODS:we retrospectively analyzed clinical records of advanced NCSLC patients (stage IIIb/c or stage IV) candidate to immunotherapy who performed 18F-FDG PET/CT before treatment to stage the disease. Fifty-seven (57) patients were included in the analysis (F:M 17:40; median age = 69 years old). Notably, 38/57 of patients had adenocarcinoma (AC), 10/57 squamous cell carcinoma (SCC) and 9/57 were not otherwise specified (NOS). Overall, 47.4% patients were stage IVA, 42.1% IVB and 8.8% IIIB. Immunotherapy was performed as front-line therapy in 42/57 patients and as second line therapy after chemotherapy platinum-based in 15/57. The median follow up after starting immunotherapy was 10 months (range: 1.5-68.6). Therapy response was assessed by RECIST 1.1 criteria (CT evaluation every 4 cycles of therapy) in 48/57 patients or when not feasible by clinical and laboratory data (fast disease progression or worsening of patient clinical condition in nine patients). Radiomics analysis was performed by applying regions of interest (ROIs) of the primary tumor delineated manually by two operators and semi-automatically applying a threshold at 40% of SUVmax. RESULTS:(1.1) metabolic tumor volume (MTV) (p = 0.028) and total lesion glycolysis (TLG) (p = 0.035) were significantly associated with progressive vs. non-progressive disease status. Patients with higher values of MTV and TLG had higher probability of disease progression, compared to those patients presenting with lower values. SUVmax did not show correlation with PD status, PFS and OS. MTV (p = 0.027) and TLG (p = 0.022) also resulted in being significantly different among PR, SD and PD groups, while SUVmax was confirmed to not be associated with response to therapy (p = 0.427). (1.2) We observed the association of several radiomics features with PD status. Namely, patients with high tumor volume, TLG and heterogeneity expressed by "skewness" and "kurtosis" had a higher probability of failing immunotherapy. (1.3) M status at 18F-FDG PET/CT was significantly associated with PFS (p = 0.002) and OS (p = 0.049). No significant associations were observed for N status. CONCLUSIONS:18F-FDG PET/CT performed before the start of immunotherapy might be an important prognostic tool able to predict the disease progression and response to immunotherapy in patients with advanced NSCLC, since MTV, TLG and radiomics features (volume and heterogeneity) are associated with disease progression.
Project description:Lymph node stage prior to treatment is strongly related to disease progression and poor prognosis in non-small cell lung cancer (NSCLC). However, few studies have investigated metabolic imaging features derived from pre-radiotherapy 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) of metastatic hilar/mediastinal lymph nodes (LNs). We hypothesized that these would provide complementary prognostic information to FDG-PET descriptors to only the primary tumor (tumor).Two independent cohorts of 262 and 50 node-positive NSCLC patients were used for model development and validation. Image features (i.e. Radiomics) including shape and size, first order statistics, texture, and intensity-volume histograms (IVH) (http://www.radiomics.io/) were evaluated by univariable Cox regression on the development cohort. Prognostic modeling was conducted with a 10-fold cross-validated least absolute shrinkage and selection operator (LASSO), automatically selecting amongst FDG-PET-Radiomics descriptors from (1) tumor, (2) LNs or (3) both structures. Performance was assessed with the concordance-index. Development data are publicly available at www.cancerdata.org and Dryad (doi:10.5061/dryad.752153b).Common SUV descriptors (maximum, peak, and mean) were significantly related to overall survival when extracted from LNs, as were LN volume and tumor load (summed tumor and LNs' volumes), though this was not true for either SUV metrics or tumor's volume. Feature selection exclusively from imaging information based on FDG-PET-Radiomics, exhibited performances of (1) 0.53 -external 0.54, when derived from the tumor, (2) 0.62 -external 0.56 from LNs, and (3) 0.62 -external 0.59 from both structures, including at least one feature from each sub-category, except IVH.Combining imaging information based on FDG-PET-Radiomics features from tumors and LNs is desirable to achieve a higher prognostic discriminative power for NSCLC.
Project description:BACKGROUND:Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. METHODS:In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3?cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21?days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a???20% decrease in the SUV of the primary lesion. RESULTS:Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62?years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95?months. The 5?year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18-21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18-21 FDG-PET scan. Responders had a 5?year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p?=?0.96 and 0.85). CONCLUSIONS:This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. TRIAL REGISTRATION:NCT00227539 registered September 28th, 2005.
Project description:We evaluated the reproducibility and predictive value of texture parameters and existing parameters of 18F-FDG PET/CT images in Stage I non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Twenty-six patients with Stage I NSCLC (T1-2N0M0) were retrospectively analyzed. All of the patients underwent an 18F-FDG PET/CT scan before treatment and were treated with SBRT. Each tumor was delineated using PET Edge (MIM Software Inc., Cleveland, OH), and texture parameters were calculated using open-source code CGITA. From 18F-FDG PET/CT images, three conventional parameters, including maximum standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and four texture parameters, including entropy and dissimilarity (derived from a co-occurrence matrix) and high-intensity large-area emphasis (HILAE) and zone percentage (derived from a size-zone matrix) were analyzed. Reproducibility was evaluated using two independent delineations conducted by two observers. The ability to predict local control (LC), progression-free survival (PFS) and overall survival (OS) was tested for each parameter. All of the seven parameters except zone percentage showed good reproducibility, with intraclass correlation coefficient values >0.8. In univariate analysis, only HILAE was a significant predictor for LC. Histology, dose fractionation, and maximum SUV were associated with PFS, and histology and dose fractionation were associated with OS. We showed that texture parameters derived from 18F-FDG PET/CT were reproducible and potentially beneficial for predicting LC in Stage I lung cancer patients treated with SBRT.
Project description:PURPOSE:Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. METHODS:The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan-Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. RESULTS:Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan-Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). CONCLUSION:In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020.
Project description:Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival.A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG.A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p?=?0.833; CTdiameter30 p?=?0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7?±?23 % vs. 19?±?14 %, p?=?0.016, respectively).The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment showed more tumor responders than CT-based response assessment (part of the [18F]FDG PET/CT); this was not correlated to survival. This might be due to timing of the [18F]FDG PET shortly after the bevacizumab infusion.
Project description:INTRODUCTION:The purpose of our present study was to assess the prognostic impact of FDG PET-CT after induction chemotherapy for patients with inoperable non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS:This retrospective study included 50 patients with inoperable stage II/III NSCLC from January 2012 to July 2015. They were treated for curative intent with induction chemotherapy, followed by concomitant chemoradiation therapy or sequential radiation therapy. FDG PET-CT scans were acquired at initial staging (PET1) and after the last cycle of induction therapy (PET2). Five parameters were evaluated on both scans: SUVmax, SUVpeak, SUVmean, TLG, MTV, and their respective deltas. The prognostic value of each parameter for overall survival (OS) and progression-free survival (PFS) was evaluated with Cox proportional-hazards regression models. RESULTS:Median follow-up was 19 months. PET1 parameters, clinical and histopathological data were not predictive of the outcome. TLG2 and ?TLG were prognostic factors for OS. TLG2 was the only prognostic factor for PFS. For OS, log-rank test showed that there was a better prognosis for patients with TLG2< 69g (HR = 7.1, 95%CI 2.8-18, p = 0.002) and for patients with ?TLG< -81% after induction therapy (HR = 3.8, 95%CI 1.5-9.6, p = 0.02). After 2 years, the survival rate was 89% for the patients with low TLG2 vs 52% for the others. We also evaluated a composite parameter considering both MTV2 and ?SUVmax. Patients with MTV2> 23cc and ?SUVmax> -55% had significantly shorter OS than the other patients (HR = 5.7, 95%CI 2.1-15.4, p< 0.01). CONCLUSION:Post-induction FDG PET might be an added value to assess the patients' prognosis in inoperable stage II/III NSCLC. TLG, ?TLG as well as the association of MTV and ?SUVmax seemed to be valuable parameters, more accurate than clinical, pathological or pretherapeutic imaging data.
Project description:PURPOSE: The aim of this study was to analyse the impact of FDG-PET staging on treatment results of neo-adjuvant radiochemotherapy in patients with advanced non-small cell lung cancer (NSCLC). We compared prospectively the outcome of two patient groups with stage III NSCLC undergoing the same neo-adjuvant radio-chemotherapy (NARCT). In one group, FDG-PET was part of the pretherapeutic staging, whereas in the other group, no PET scans were performed. METHODS: One hundred and eighty-eight patients with advanced stage III NSCLC were selected for a phase II trial of NARCT. The first 115 patients underwent conventional workup (CWU) and FDG-PET before inclusion (group I); the remaining 73 patients underwent CWU only (group II). All patients were followed up according to a standardised protocol for at least 11 months (up to 64 months). Overall survival and disease-free survival were used as parameters of therapeutic success and analysed statistically. RESULTS: After staging, 157/188 patients were included in the clinical trial. Thirty-one were excluded owing to the results of FDG-PET, in most cases because of the detection of previously unknown distant metastases. Overall survival and metastasis-free survival were significantly longer in patients of group I stratified by FDG-PET than in group II (p=0.006 and 0.02 respectively). Another significant factor for survival was complete tumour resection (p=0.02). Gender, histological tumour type, tumour grade and UICC stage had no significant influence. CONCLUSION: Pretherapeutic staging by FDG-PET significantly influences the results of NARCT and subsequent surgery by identifying patients not eligible for curative treatment.
Project description:Intratumoral heterogeneity has been suggested to be an important resistance mechanism leading to treatment failure. We hypothesized that radiologic images could be an alternative method for identification of tumor heterogeneity. We tested heterogeneity textural parameters on pretreatment FDG-PET/CT in order to assess the predictive value of target therapy. Recurred or metastatic non-small cell lung cancer (NSCLC) subjects with an activating EGFR mutation treated with either gefitinib or erlotinib were reviewed. An exploratory data set (n = 161) and a validation data set (n = 21) were evaluated, and eight parameters were selected for survival analysis. The optimal cutoff value was determined by the recursive partitioning method, and the predictive value was calculated using Harrell's C-index. Univariate analysis revealed that all eight parameters showed an increased hazard ratio (HR) for progression-free survival (PFS). The highest HR was 6.41 (P<0.01) with co-occurrence (Co) entropy. Increased risk remained present after adjusting for initial stage, performance status (PS), and metabolic volume (MV) (aHR: 4.86, P<0.01). Textural parameters were found to have an incremental predictive value of early EGFR tyrosine kinase inhibitor (TKI) failure compared to that of the base model of the stage and PS (C-index 0.596 vs. 0.662, P = 0.02, by Co entropy). Heterogeneity textural parameters acquired from pretreatment FDG-PET/CT are highly predictive factors for PFS of EGFR TKI in EGFR-mutated NSCLC patients. These parameters are easily applicable to the identification of a subpopulation at increased risk of early EGFR TKI failure. Correlation to genomic alteration should be determined in future studies.