Biopsy-proven Non-small Cell Lung Cancer Research Articles

Contrast Agent Dynamics Determine Radiomics Profiles in Oncologic Imaging.

The reproducibility of radiomics features extracted from CT and MRI examinations depends on several physiological and technical factors. The aim was to evaluate the impact of contrast agent timing on the stability of radiomics features using dynamic contrast-enhanced perfusion CT (dceCT) or MRI (dceMRI) in prostate and lung cancers. Radiomics features were extracted from dceCT or dceMRI images in patients with biopsy-proven peripheral prostate cancer (pzPC) or biopsy-proven non-small cell lung cancer (NSCLC), respectively. Features that showed significant differences between contrast phases were identified using linear mixed models. An L2-penalized logistic regression classifier was used to predict class labels for pzPC and unaffected prostate regions-of-interest (ROIs). Nine pzPC and 28 NSCLC patients, who were imaged with dceCT and/or dceMRI, were included in this study. After normalizing for individual enhancement patterns by defining seven individual phases based on a reference vessel, 19, 467 and 128 out of 1204 CT features showed significant temporal dynamics in healthy prostate parenchyma, prostate tumors and lung tumors, respectively. CT radiomics-based classification accuracy of healthy and tumor ROIs was highly dependent on contrast agent phase. For dceMRI, 899 and 1027 out of 1118 features were significantly dependent on time after contrast agent injection for prostate and lung tumors. CT and MRI radiomics features in both prostate and lung tumors are significantly affected by interindividual differences in contrast agent dynamics.

The effect of harmonization on the variability of PET radiomic features extracted using various segmentation methods

PurposeThis study aimed to examine the robustness of positron emission tomography (PET) radiomic features extracted via different segmentation methods before and after ComBat harmonization in patients with non-small cell lung cancer (NSCLC).MethodsWe included 120 patients (positive recurrence = 46 and negative recurrence = 74) referred for PET scanning as a routine part of their care. All patients had a biopsy-proven NSCLC. Nine segmentation methods were applied to each image, including manual delineation, K-means (KM), watershed, fuzzy-C-mean, region-growing, local active contour (LAC), and iterative thresholding (IT) with 40, 45, and 50% thresholds. Diverse image discretizations, both without a filter and with different wavelet decompositions, were applied to PET images. Overall, 6741 radiomic features were extracted from each image (749 radiomic features from each segmented area). Non-parametric empirical Bayes (NPEB) ComBat harmonization was used to harmonize the features. Linear Support Vector Classifier (LinearSVC) with L1 regularization For feature selection and Support Vector Machine classifier (SVM) with fivefold nested cross-validation was performed using StratifiedKFold with ‘n_splits’ set to 5 to predict recurrence in NSCLC patients and assess the impact of ComBat harmonization on the outcome.ResultsFrom 749 extracted radiomic features, 206 (27%) and 389 (51%) features showed excellent reliability (ICC ≥ 0.90) against segmentation method variation before and after NPEB ComBat harmonization, respectively. Among all, 39 features demonstrated poor reliability, which declined to 10 after ComBat harmonization. The 64 fixed bin widths (without any filter) and wavelets (LLL)-based radiomic features set achieved the best performance in terms of robustness against diverse segmentation techniques before and after ComBat harmonization. The first-order and GLRLM and also first-order and NGTDM feature families showed the largest number of robust features before and after ComBat harmonization, respectively. In terms of predicting recurrence in NSCLC, our findings indicate that using ComBat harmonization can significantly enhance machine learning outcomes, particularly improving the accuracy of watershed segmentation, which initially had fewer reliable features than manual contouring. Following the application of ComBat harmonization, the majority of cases saw substantial increase in sensitivity and specificity.ConclusionRadiomic features are vulnerable to different segmentation methods. ComBat harmonization might be considered a solution to overcome the poor reliability of radiomic features.

Longitudinal Radiomics-Based Prediction of Local Recurrence after Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

Computed tomography (CT)-based radiomic analysis is an emerging tool that can help predict recurrence after radiation in non-small cell lung cancer (NSCLC). Most studies have focused on using radiomic features obtained from pre-treatment CT scans but not on post-treatment CTs. Our goal was to determine if radiomic features derived from post-treatment CTs perform better than those from pre-treatment CTs in predicting local recurrence after stereotactic body radiation therapy (SBRT) in patients with early-stage NSCLC. Patients with T1/T2 N0 early-stage NSCLC were retrospectively reviewed. Criteria for selection included patients with biopsy-proven NSCLC, non-ground glass solid lesions, 4-5 fraction SBRT treatments, and non-contrast thin-slice CTs available at pre-treatment baseline and at 3 and 6 months post-SBRT. Clinical and tumor characteristics were compared using Chi-square and Student's t-tests. CT image pre-processing was performed and 107 radiomic features were extracted using 3D Slicer and open-source software. Univariate analysis for local recurrence was determined by Cox regression with death as a competing risk. The Benjamini-Hochberg Procedure was applied to control the false discovery rate. Pearson correlation analysis was used to exclude redundant features (r > 0.8), and multivariate analysis was conducted with Random Forest on the top-performing features found on univariate logistic regression. Models were trained on a class-balanced loss to account for class imbalance. Twenty iterations of stratified 3 k-fold cross-validation were used to select the best model by the area under the receiver operating characteristic curve (AUC). We identified and analyzed 86 patient tumors, including 76 non-local recurrences and 10 local recurrences (49 males, 37 females; age, median 72, range 52-91 years). No differences in age, histology, standardized uptake values on positron emission tomography scans, gross tumor volume, and radiation dose were found between patients with and without local recurrence (all p >0.05). The median time to local recurrence was 18.9 months (range 5.5-45.6 months). At the baseline, 3-month, and 6-month timepoints, 2, 10, and 10 radiomic features predicted local recurrence on Cox regression univariate analysis, respectively (all q <0.01). On multivariate analysis of top-performing radiomic features, the 3-month timepoint performed the best with a mean (±standard deviation) AUC score of 0.82 (±0.13) compared to a mean AUC of 0.73 (±0.086) at baseline and a mean AUC of 0.74 (±0.10) at 6 months. Post-treatment radiomic features at 3 months outperformed pre-treatment radiomic features in predicting local recurrence after SBRT for NSCLC. These results suggest radiomic data from follow-up CTs may be helpful when developing radiomic models to predict local recurrence in patients with NSCLC.

Volumetric parameters of the primary tumor and whole-body tumor burden derived from baseline 18F-FDG PET/CT can predict overall survival in non-small cell lung cancer patients: initial results from a single institution

BackgroundMetabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters derived from 18F-FDG PET/CT, suggested to have a prognostic value in cancer patients. Our study aimed to test whether these volumetric parameters of the primary tumor and whole-body tumor burden (WBTB) can predict overall survival (OS) in non-small cell lung cancer (NSCLC) patients.Materials and methodsThirty biopsy-proven NSCLC patients who had not begun anti-tumor therapy were included in this prospective study. A baseline 18F-FDG PET/CT study was acquired. Scans were interpreted visually and semi-quantitatively by drawing a 3D volume of interest (VOI) over the primary tumor and all positive lesions to calculate metabolic, volumetric parameters, and WBTB. The PET parameters were used to stratify patients into high- and low-risk categories. The overall survival was estimated from the date of scanning until the date of death or last follow-up.ResultsAt a median follow-up of 22.73 months, the mean OS was shorter among patients with higher tu MTV and tu TLG and high WBTB. High WB TLG was independently associated with the risk of death (p < 0.025). Other parameters, e.g., SUVmax, SUVpeak, and SUVmean, were not predictive of outcomes in these patients. Conclusion: In patients with NSCLC, tu MTV, tu TLG, and WBTB determined on initial staging 18F-FDG PET/CT seems to be a strong, independent imaging biomarker to predict OS, superior to the clinical assessment of the primary tumor. The WB TLG was found to be the best predictor of OS.

Multidisciplinary Postoperative Validation of 18F-FDG PET/CT Scan in Nodal Staging of Resected Non-Small Cell Lung Cancer.

The aim of this study was to examine the validity of PET/CT scans in the preoperative identification of lymph node metastases (LNM) and compare them with postoperative outcomes. In this retrospective study, we included 87 patients with a solitary lung nodule or biopsy-proven non-small cell lung cancer treated in our institution from 2009 to 2015. Patients were divided into two groups and four subgroups, depending on pre- and postoperative findings. According to our analysis, PET/CT scan has a sensitivity of 50%, a specificity of 88.89%, a positive predictive value of 63.16%, and a negative predictive value of 82.35%. Among the patients, 13.8% were downstaged in PET-CT, while 8% were upstaged. In 78.2% of cases, the PET/CT evaluation was consistent with the histology. Metastases without extracapsular invasion were seldom recognized on PET/CT. This analysis showed the significance of extracapsular tumor invasion, which causes an inflammatory reaction, on LNM, which is probably responsible for preoperative false-positive findings. In conclusion, PET/CT scans are very effective in identifying patients without tumors. Furthermore, it is highly probable that patients with negative findings are free of disease.

LUSTRE: A Phase III Randomized Trial of Stereotactic Body Radiotherapy (SBRT) vs. Conventionally Hypofractionated Radiotherapy (CRT) for Medically Inoperable Stage I Non-Small Cell Lung Cancer (NSCLC)

LUSTRE: A Phase III Randomized Trial of Stereotactic Body Radiotherapy (SBRT) vs. Conventionally Hypofractionated Radiotherapy (CRT) for Medically Inoperable Stage I Non-Small Cell Lung Cancer (NSCLC)

Circulating Tumor-Macrophage Fusion Cells and Circulating Tumor Cells Complement Non-Small-Cell Lung Cancer Screening in Patients With Suspicious Lung-RADS 4 Nodules.

Low-dose computed tomography (LDCT) screening of high-risk patients decreases lung cancer-related mortality. However, high false-positive rates associated with LDCT result in unnecessary interventions. To distinguish non-small-cell lung cancer (NSCLC) from benign nodules, in the present study, we integrated cellular liquid biomarkers in patients with suspicious lung nodules (lung cancer screening reporting and data system [Lung-RADS] 4). Prospectively, 7.5 mL of blood was collected from 221 individuals (training set: 90 nonscreened NSCLC patients, 74 high-risk screening patients with no/benign nodules [Lung-RADS 1-3], and 20 never smokers; validation set: 37 patients with suspicious nodules [Lung-RADS 4]). Circulating tumor cells (CTCs), CTC clusters, and tumor-macrophage fusion (TMF) cells were identified by blinded analyses. Screening patients underwent a median of two LDCTs (range, 1-4) with a median surveillance time of 30 (range, 11-50) months. In the validation set of 37 Lung-RADS 4 patients, all circulating cellular biomarker counts (P < .005; Wilcoxon test) and positivity rates were significantly higher in 23 biopsy-proven NSCLC patients (CTCs: 23 of 23 [100%], CTC clusters: 6 of 23 [26.1%], and TMF cells: 15 of 23 [65.2%]) than in 14 patients with biopsy-proven benign nodules (6 of 14 [42.9%], 0 of 14 [0%], and 2 of 14 [14.3%]). On the basis of cutoff values from the training set, logistic regression with receiver operating characteristic and area under the curve analyses demonstrated that CTCs (sensitivity: 0.870, specificity: 1.0, and area under the curve: 0.989) and TMF cells (0.652; 0.880; 0.790) complement LDCT in diagnosing NSCLC in Lung-RADS 4 patients. Cellular liquid biomarkers have a potential to complement LDCT interpretation of suspicious Lung-RADS 4 nodules to distinguish NSCLC from benign lung nodules. A future prospective, large-scale, multicenter clinical trial should validate the role of cellular liquid biomarkers in improving diagnostic accuracy in high-risk patients with Lung-RADS 4 nodules.

The “digital biopsy” in non-small cell lung cancer (NSCLC): a pilot study to predict the PD-L1 status from radiomics features of [18F]FDG PET/CT

The present pilot study investigates the putative role of radiomics from [18F]FDGPET/CT scans to predict PD-L1 expression status in non-small cell lung cancer (NSCLC) patients. In a retrospective cohort of 265 patients with biopsy-proven NSCLC, 86 with available PD-L1 immunohistochemical (IHC) assessment and [18F]FDGPET/CT scans have been selected to find putative metabolic markers that predict PD-L1 status (< 1%, 1-49%, and ≥ 50% as per tumor proportion score, clone 22C3). Metabolic parameters have been extracted from three different PET/CT scanners (Discovery 600, Discovery IQ, and Discovery MI) and radiomics features were computed with IBSI compliant algorithms on the original image and on images filtered with LLL and HHH coif1 wavelet, obtaining 527 features per tumor. Univariate and multivariate analysis have been performed to compare PD-L1 expression status and selected radiomic features. Of the 86 analyzed cases, 46 (53%) were negative for PD-L1 IHC, 13 (15%) showed low PD-L1 expression (1-49%), and 27 (31%) were strong expressors (≥ 50%). Maximum standardized uptake value (SUVmax) demonstrated a significant ability to discriminate strong expressor cases at univariate analysis (p = 0.032), but failed to discriminate PD-L1 positive patients (PD-L1 ≥ 1%). Three radiomics features appeared the ablest to discriminate strong expressors: (1) a feature representing the average high frequency lesion content in a spherical VOI (p = 0.009); (2) a feature assessing the correlation between adjacent voxels on the high frequency lesion content (p = 0.004); (3) a feature that emphasizes the presence of small zones with similar grey levels inside the lesion (p = 0.003). The tri-variate linear discriminant model combining the three features achieved a sensitivity of 81% and a specificity of 82% in the test. The ability of radiomics to predict PD-L1 positive patients was instead scarce. Our data indicate a possible role of the [18F]FDG PET radiomics in predicting strong PD-L1 expression; these preliminary data need to be confirmed on larger or single-scanner series.

Evaluation of response to stereotactic body radiation therapy for nonsmall cell lung cancer: PET response criteria in solid tumors versus response evaluation criteria in solid tumors.

Recommendations for surveillance after stereotactic body radiation therapy (SBRT) for early-stage nonsmall cell lung cancer (NSCLC) are not well defined. Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a new standardized method to assess radiotherapeutic response both quantitatively and metabolically. The aim of this study was to evaluate therapeutic response following SBRT in early-stage NSCLC patients by comparing PERCIST with the currently widely used RECIST. Forty-nine patients with early-stage NSCLC who had been prescribed SBRT were studied. Responses of lesion were evaluated using CT and 18F-FDG PET according to the RECIST and PERCIST methods. PET-CT scans were obtained before SBRT and 3-6 months after SBRT. Associations between overall survival (OS) and clinicopathologic results (histology, tumor location, tumor size, lymphatic invasion, clinical stage, and radiotherapeutic responses in RECIST and PERCIST) were statistically analyzed. The median patient follow-up was 30 months. Thirteen patients had stage IA, 9 stage IB, 10 stage IIA, and 17 stage IIB biopsy-proven NSCLC. Three-year OS was 79.6%. CT scans indicated three regional recurrences. PET-CT/chest indicated three regional recurrences and distant metastasis. Significant differences were observed in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P = 0.0041). Univariate analysis showed that clinical stage, RECIST, and PERCIST were significant factors associated with OS, whereas by multivariate analysis PERCIST was the only predictor of OS. SMD, PMD/PMR, and CMR in PERCIST criteria were indicative of a 9.900-fold increase in the risk of OS in early NSCLC patients [risk ratio, 9.900 (95% CI, 1.040-21.591); P = 0.001]. RECIST based on the anatomic size reduction rate did not demonstrate the correlation between radiotherapeutic response and prognosis in patients with early-stage NSCLC receiving SBRT. However, PERCIST was shown as the strongest independent predictor of outcomes. PERCIST might be considered more suitable for the evaluation of NSCLC tumor response to SBRT than RECIST.

Dosimetric parameters related to occurrence of distant metastases and regional nodal relapse after SBRT for early-stage non-small cell lung cancer

PurposePrevious studies have suggested that the dose immediately outside the PTV may impact the incidence of distant metastases after stereotactic body radiation therapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC). In particular, Diamant et al. [1,2] reported a correlation between the mean EQD2 of a 30 mm shell around the PTV and both local control and the rate of distant metastases. In this study, we assess this parameter and others in a series of patients with radiographically presumed or biopsy-proven early-stage NSCLC treated at our institution with stereotactic body radiotherapy (SBRT) between 2017 and 2019. Materials/MethodsWe reviewed the dosimetry, local control, regional nodal relapse, and rate of distant metastases for 304 patients with 325 lesions treated with SBRT at our institution. Dosimetric parameters investigated include the prescribed dose, minimum and mean doses to the PTV, conformity index, and the mean EQD2 to a 30 mm shell around the PTV. Time to each event was defined from date of last fraction of SBRT to date of event, with event-free patients censored at last radiographic follow-up. Univariate (UVA) Cox regression analysis was performed on the collected parameters to assess for correlation with regional nodal relapse and rate of distant metastases. ResultsThere was no significant correlation between the mean EQD2 dose to a 30 mm shell around the PTV and the rate of distant metastases. On UVA Cox proportional hazards analysis, positive predictors of reduced incidence of distant metastases were PTV <22 cc (vs. ≥22 cc, p = 0.01) and GTV <10 cc (vs. ≥10 cc, p < 0.01), with GTV <10 cc also being a positive predictor of reduced incidence of regional nodal relapse (p < 0.01). In the subset of patients treated with 4–5 fractions, mean EQD2 dose to the 30 mm shell around the PTV ≥21 Gy was associated with increased incidence of distant metastases (HR 2.42, 95% CI 1.06–5.53, p = 0.04), differing from prior data from Diamant et al. ConclusionsWe did not observe a correlation between the rate of distant metastases and dose outside the PTV, as reported by other groups; rather, we noted an opposite trend in patients treated with 4–5 fractions. Our data show additional correlations between distant metastases and tumor size.

Early-Stage Non-Small Cell Lung Cancer Stereotactic Body Radiation Therapy Outcomes in a Single Institution.

IntroductionThe gold standard treatment of stage I non-small cell lung cancer (NSCLC) is surgical resection. For medically inoperable patients, stereotactic body radiation therapy (SBRT) can provide comparable local control (LC) and overall survival (OS). The objectives of this study are to determine the three-year LC and OS for SBRT compared to early-stage NSCLC patients treated with alternative radiation modalities at our institution.Materials and methodsThis retrospective study included a total of 139 consecutive patients who were diagnosed with stage I (T1-2 N0 M0) NSCLC and treated with radiation therapy at our institution between 2015 and 2020. Patient demographics and clinical data were obtained from chart reviews. Treatment subgroups were: SBRT (48Gy/4 or 60Gy/8), hypofractionation (60Gy/15), conventional fractionation (60Gy/30 or 50Gy/20), and palliative radiation (20Gy/5, 30Gy/10, or 40Gy/15). Kaplan-Meier curves were plotted for LC and OS. We also performed Cox’s proportional hazard regression analysis.ResultsThe median patient age was 74 (range 52-91). The numbers of patients in each treatment subgroup were: SBRT (44), hypofractionation (78), conventional fractionation (8), and palliative (9). Differences in age, gender, and histopathological cell type between subgroups were not statistically significant. Metastatic progression was the most common outcome amongst treatment failures, followed by local recurrence and regional spread. Median post-treatment follow-up in months for each subgroup was: SBRT (20.2), hypofractionated (20.7), conventional fractionation (13.9), and palliative (14.4). Post-treatment three-year LC was found to be significantly better with SBRT (94%) versus hypofractionation (71%), conventional fractionation (80%), and palliative (71%). OS at three years were SBRT (67%), hypofractionation (59%), conventional fractionation (66%), and palliative (44%). As a whole, 72% (100/139) of patients had biopsy-proven NSCLC. Analysis showed biopsy status had no statistical significance with regards to LC or OS. Every 20 years of age had a 3.2x risk of death (95% CI: 1.425-7.268). Concerning the treatment modalities, there were significant differences for the hazard of death compared to SBRT: hypofractionation had 2.58x increased risk while palliative had 5.83x increased risk.The proportion of patients who experienced post-treatment radiation pneumonitis or dermatitis were: SBRT (7%, 2%), hypofractionation (8%, 3%), conventional fractionation (13%, 25%), and palliative (0%, 0%), respectively. No patients who experienced grade III or higher toxicities were observed as defined by Common Terminology Criteria for Adverse Events (CTCAE). ConclusionOur experience confirms SBRT can provide durable three-year local control with a comparable rate of post-treatment complications versus other radiation modalities for early-stage NSCLC. SBRT appears to be non-inferior to hypofractionation with regards to three-year LC.

No Difference in Outcomes for Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Pathologic Diagnosis

According to society guidelines, stereotactic body radiotherapy (SBRT) can be delivered in patients who have a lung lesion that is clinically and radiographically consistent with non-small cell lung cancer (NSCLC) and refuse biopsy, have undergone a nondiagnostic biopsy, or are at prohibitive risk of biopsy. The purpose of this study is to report outcomes of patients with stage I-II NSCLC, with or without pathologic diagnosis, treated with SBRT at our institution.We performed a single-institution retrospective review of patients with early-stage node-negative NSCLC who received curative-intent SBRT between 2005 and 2018. We included patients with biopsy-proven NSCLC or presumed NSCLC based on radiographic findings. We calculated outcomes using the Kaplan-Meier method and used a log-rank test to assess prognostic impact.The study population consisted of 175 patients and 186 individual lung nodules with a median follow-up time of 2.6 (range, 0.1 - 12) years for all patients, and 3.5 (range, 0.2 - 8.4) years for living patients. The median age was 70.2 (range, 43 - 90) years and the median maximum tumor diameter was 1.9 (range, 0.7 - 5.6) cm. Twenty-three (13.1%) patients had a history of previously treated NSCLC, and more than a third (n = 66, 37.7%) of patients were oxygen-dependent at the time of SBRT. One hundred and seven (61.1%) patients were treated empirically with SBRT without a pathologic diagnosis. Most tumors were peripheral with only 9.7% (n = 18) centrally located, and most were located in the upper lobes (n = 123, 70.3%). The median prescription dose was 50 (range, 48 - 62.5) Gy in 5 (range, 4-10) fractions. Among the entire cohort, the 3-year rates (95% confidence interval) of local control, regional control, cause-specific survival, and overall survival were 81.0% (73.8% - 86.5%), 89.5% (82.7% - 93.8%), 72.4% (64.5% - 79.1%), and 48.3% (40.7% - 55.9%), respectively. There was no difference in local-regional control (P = 0.76), cause-specific survival (P = 0.75), or overall survival (P = 0.33) between patients with a pathologic diagnosis and those without. We observed late grade 3 toxicities in 2.3% of patients and no higher-grade toxicities.Patients without a pathologic diagnosis of NSCLC had no difference in disease outcomes compared with patients that had biopsy-proven disease, suggesting that empirically treating patients with a radiographic diagnosis of NSCLC is a reasonable alternative when a biopsy cannot safely be attained.

Reirradiation With Stereotactic Radiosurgery After Local or Marginal Recurrence of Brain Metastases From Previous Radiosurgery

Brain metastases represent a major indication for stereotactic radiosurgery (SRS), but further study is needed regarding repeat SRS (SRS2) after local or marginal recurrence after prior SRS (SRS1). We report local tumor control (LC) after SRS2 and identify predictors of radiation necrosis (RN) and symptomatic RN (SRN). Patients had biopsy-proven non-small cell lung cancer and at least 1 brain metastasis previously treated with SRS. SRS2 was performed from 2015 to 2020 and required overlap of the prescription isodose lines with those from SRS1. Patients treated with preoperative SRS were excluded. Primary endpoints were LC by Response Assessment in Neuro-oncology criteria, RN, and SRN. From 8 institutions, 102 patients with 123 treated lesions were included. SRS2 was performed at a median 12 months after SRS1. SRS2 delivered a median 18 Gy (interquartile range [IQR], 16-18) margin dose to the 50% (IQR, 50%-70%) isodose line, maximum dose of 30.5 Gy (IQR, 25.0-36.0), and V12Gy of 3.38 cm3 (IQR, 0.83-7.64). One-year and 2-year LC were 79% and 72%, respectively. Local tumor control was improved with tumor volume ≤1 cm3 (P < .005). There were 25 (20%) cases of RN and 9 (7%) cases of SRN. For SRS1 and SRS2, SRN rates were higher with maximum doses ≥40 Gy or SRS2 V12Gy >9 cm3 (P < .025 for each). SRS1 and SRS2 maximum dose ≥40 Gy was also predictive of increased RN (P < .05 for each). Prior immunotherapy was not predictive of RN or SRN. Repeat SRS afforded a high rate of local tumor control and a low rate of SRN. At SRS2, V12Gy ≤9 cm3 and maximum dose <40 Gy may reduce the risks of RN and SRN. These results are most applicable to lesions with approximately 1 cm3 volume and 1-year interval between SRS courses.

Using predictive models to determine the presence of non-small cell lung cancer metastasis to N2 and N3 regions.

e20560 Background: Accurate assessment of non-small cell lung cancer (NSCLC) mediastinal involvement is key to developing treatment plans and determining prognosis. To date, there is no reliable imaging-based means to determine the presence or absence of mediastinal involvement. Current computed tomogram (CT) and fluorodeoxyglucose-positron emission tomography/ computed tomogram (PET-CT) technologies provide numerous derived automated variables have not been sufficiently evaluated to determine the presence of metastasis to the mediastinum. We have developed predictive models to determine the presence or lack of metastatic NSCLC in N2 and N3 regions. Methods: Consecutive patients from 2012-2017 with biopsy-proven NSCLC who had CT and PET-CT, as well as biopsy of the mediastinum had their images reread by a team of blinded specialty radiologists and nuclear medicine specialists. Patients with no mediastinal malignancy on biopsy were followed for 6 months from the initial evaluation to confirm lack of mediastinal malignancy.278 regions (N2 and N3) from 139 patients were included. Logistic regression models were used to build a baseline model, as well as models with additional nodal station maximum standard uptake valuve (SUVm) measurements (SUVm, SUVm-SUVmeanbloodpool and SUV lymph node/tumor (LN/T)) for N2 and N3 regions, respectively. When nodal station SUVm was not measured, SUVmeanbloodpool was used. The SUVm within each region was used. Stepwise selection was used to select variables in the baseline model. Cross-validated ROC curve and area under the curve (AUC) were reported. All analyses were done in SAS 9.4 (SAS Institute, Inc., Cary, NC). Results: 40/139 N2 regions had malignancy, 4/139 N3 regions had malignancy. Baseline models for N2 regions selected lung laterality (OR right vs left: 4.84 (1.79, 13.05)) and nodal station short-axis diameter &gt; 1 cm (OR yes vs no: 5.49 (1.71, 17.54)) while no variables were selected for the baseline model for N3 regions due to lack of statistical power. We used the same variables for the N3 baseline model. Conclusions: We have identified models that use a more advanced analysis of predicting the presence or absence of metastatic NSCLC in both N2 and N3 regions with respect to the primary lesion. All models perform better with SUVm related measurements. From this information, we are developing a clinical application to provide practitioners a better means of assessing the presence of mediastinal involvement of NSCLC. [Table: see text]

Fully Integrated Quantitative Multiparametric Analysis of Non-Small Cell Lung Cancer at 3-T PET/MRI: Toward One-Stop-Shop Tumor Biological Characterization at the Supervoxel Level.

The aim of this study was to study the feasibility of a fully integrated multiparametric imaging framework to characterize non-small cell lung cancer (NSCLC) at 3-T PET/MRI. An 18F-FDG PET/MRI multiparametric imaging framework was developed and prospectively applied to 11 biopsy-proven NSCLC patients. For each tumor, 12 parametric maps were generated, including PET full kinetic modeling, apparent diffusion coefficient, T1/T2 relaxation times, and DCE full kinetic modeling. Gaussian mixture model-based clustering was applied at the whole data set level to define supervoxels of similar multidimensional PET/MRI behaviors. Taking the multidimensional voxel behaviors as input and the supervoxel class as output, machine learning procedure was finally trained and validated voxelwise to reveal the dominant PET/MRI characteristics of these supervoxels at the whole data set and individual tumor levels. The Gaussian mixture model-based clustering clustering applied at the whole data set level (17,316 voxels) found 3 main multidimensional behaviors underpinned by the 12 PET/MRI quantitative parameters. Four dominant PET/MRI parameters of clinical relevance (PET: k2, k3 and DCE: ve, vp) predicted the overall supervoxel behavior with 97% of accuracy (SD, 0.7; 10-fold cross-validation). At the individual tumor level, these dimensionality-reduced supervoxel maps showed mean discrepancy of 16.7% compared with the original ones. One-stop-shop PET/MRI multiparametric quantitative analysis of NSCLC is clinically feasible. Both PET and MRI parameters are useful to characterize the behavior of tumors at the supervoxel level. In the era of precision medicine, the full capabilities of PET/MRI would give further insight of the characterization of NSCLC behavior, opening new avenues toward image-based personalized medicine in this field.

Clinical Outcomes After Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancer: A Single Institutional Study.

IntroductionThe standard of care for early-stage non-small cell lung cancer (NSCLC) is surgery. However, for medical inoperable patients stereotactic body radiation therapy (SBRT) is an alternative method. The aim of the study is to assess the overall survival (OS), progression-free survival (PFS) and local control (LC) of patients diagnosed with NSCLC in Manitoba, Canada, between 2013 and 2017 and managed with SBRT.Materials and methodsThis retrospective study included a total of 158 patients (60.13% of the population were females) that were diagnosed with stage I-II NSCLC and were treated with lung SBRT between 2013 and 2017 in Manitoba. Demographics and clinical data were retrospectively extracted from the electronic patient record. Kaplan-Meier and Cumulative incidence curves were used to describe the OS, PFS, and LC outcomes.ResultsFrom the 158 patients, 32 patients were treated with 60 Gy in eight fractions, while 121 patients were treated with 48 Gy in four fractions. Only 85 patients had biopsy-proven NSCLC. The median OS was 2.87 years (95% confidence interval [CI] 2.16-3.43). OS rates at one and two years were 85% and 66%, respectively. The median PFS was 2.03 years (95% CI 1.65-2.77). Furthermore, one-year and two-year PFS rates were 77% and 51%, respectively. Only 10 patients progressed locally at one year and 17 at two years, making the LC rate 93% at the one-year and 87% at the two-year mark.ConclusionThese findings add to a growing evidence base supporting SBRT in the treatment of clinically suspected and biopsy-proven early-stage NSCLC patients.

Expanding Role of Stereotactic Body Radiation Therapy (SBRT) for Lung Nodules in a Prospective Screening Cohort following Multidisciplinary Evaluation

The number of pulmonary nodules identified incidentally or through lung cancer screening programs has dramatically increased. The role of radiation therapy (RT) in this patient population is not defined. Our institution established a multidisciplinary Pulmonary Nodule and Lung Cancer Screening Clinic (PNLCSC) to optimize the management of these patients. In this study, we describe the role of radiation oncologists in the multidisciplinary evaluation and management of incidental and screening-identified pulmonary nodules. This study included patients referred to the PNLCSC between 10/2012 and 9/2019. Indications for referral included a Lung-RADS 4 finding on screening CT or an incidental pulmonary nodule measuring ≥6 mm. At each clinic session, a multidisciplinary team including diagnostic/interventional radiologists, pulmonologists, medical oncologists, thoracic surgeons, and radiation oncologists made recommendations regarding the work-up, management, and follow-up of each patient. Demographic and clinical characteristics as well as data on follow-up and treatments were prospectively recorded. Collection and analysis of the data was approved by institutional IRB. Of 1,150 patients evaluated by the PNLCSC, 234 (20.3%) were screening patients, and 916 (79.7%) had incidental nodules. Among screening patients, 41 (17.5%) underwent therapeutic intervention, 31 (13.2%) with surgical resection and 10 (4.3%) with RT. RT represented 24.4% of all treatments received by screening patients. Among patients with incidental pulmonary nodules, 227 underwent therapeutic intervention, with 167 (18.2%) and 60 (6.6%) receiving surgery and RT, respectively. The overall rate of patients undergoing RT was stable over time, ranging from 6.0% in 2014-2016 to 6.7% in 2017-2019. However, the rate of screening patients receiving RT increased from 1.7% in 2014-2016 to 4.3% in 2017-2019. Among the 70 RT patients, 58 (82.9%) were treated for clinically diagnosed lung cancer, while 12 (17.1%) had biopsy-proven non-small cell lung cancer. Nearly all (95.7%) patients treated with RT, and 100% of those with screening detected nodules, had stage I disease and received SBRT to a median dose of 50 Gy (range 48–50 Gy) in 5 fractions (range 4–5 fractions). Compared to patients who underwent surgical intervention, those receiving RT were older (median age 67.6 vs. 73.8 years, p < 0.001) and more likely to be current/former smokers (76.8% vs. 95.7%, p = 0.001). In this large prospective cohort, 24.4% of all screening patients with lung nodules requiring intervention were treated with SBRT. The high percentage of patients receiving RT without biopsy may reflect careful multidisciplinary evaluation. Altogether, this unique data highlights the important role radiation oncologists can play in the diagnosis and treatment of patients with screening-detected and incidental lung nodules.

18F-FDG PET and DCE kinetic modeling and their correlations in primary NSCLC: first voxel-wise correlative analysis of human simultaneous [18F]FDG PET-MRI data

ObjectivesTo decipher the correlations between PET and DCE kinetic parameters in non-small-cell lung cancer (NSCLC), by using voxel-wise analysis of dynamic simultaneous [18F]FDG PET-MRI.Material and methodsFourteen treatment-naïve patients with biopsy-proven NSCLC prospectively underwent a 1-h dynamic [18F]FDG thoracic PET-MRI scan including DCE. The PET and DCE data were normalized to their corresponding T1-weighted MR morphological space, and tumors were masked semi-automatically. Voxel-wise parametric maps of PET and DCE kinetic parameters were computed by fitting the dynamic PET and DCE tumor data to the Sokoloff and Extended Tofts models respectively, by using in-house developed procedures. Curve-fitting errors were assessed by computing the relative root mean square error (rRMSE) of the estimated PET and DCE signals at the voxel level. For each tumor, Spearman correlation coefficients (rs) between all the pairs of PET and DCE kinetic parameters were estimated on a voxel-wise basis, along with their respective bootstrapped 95% confidence intervals (n = 1000 iterations).ResultsCurve-fitting metrics provided fit errors under 20% for almost 90% of the PET voxels (median rRMSE = 10.3, interquartile ranges IQR = 8.1; 14.3), whereas 73.3% of the DCE voxels showed fit errors under 45% (median rRMSE = 31.8%, IQR = 22.4; 46.6). The PET-PET, DCE-DCE, and PET-DCE voxel-wise correlations varied according to individual tumor behaviors. Beyond this wide variability, the PET-PET and DCE-DCE correlations were mainly high (absolute rs values > 0.7), whereas the PET-DCE correlations were mainly low to moderate (absolute rs values < 0.7). Half the tumors showed a hypometabolism with low perfused/vascularized profile, a hallmark of hypoxia, and tumor aggressiveness.ConclusionA dynamic “one-stop shop” procedure applied to NSCLC is technically feasible in clinical practice. PET and DCE kinetic parameters assessed simultaneously are not highly correlated in NSCLC, and these correlations showed a wide variability among tumors and patients. These results tend to suggest that PET and DCE kinetic parameters might provide complementary information. In the future, this might make PET-MRI a unique tool to characterize the individual tumor biological behavior in NSCLC.

Does institutional patient accrual volume impact overall survival in patients with inoperable non-small-cell lung cancer receiving radical (chemo)radiation? A secondary analysis of TROG 99.05.

Increased hospital patient volume, reflecting greater experience, has been shown to be associated with improved survival for some cancers. However, there is no evidence to support the volume-outcome hypothesis for inoperable non-small-cell lung cancer (NSCLC) patients within the Australasian setting. We examined the relationship between overall survival (OS) and institutional patient accrual volume (IPAV) in a large prospective Australasian NSCLC database (TROG 99.05). TROG 99.05 was an observational study which accrued patients from 1999 to 2007 to examine the relationship between primary lung cancer volume and survival. To be eligible for inclusion, patients had to have inoperable, biopsy-proven NSCLC planned for radiotherapy to a minimum dose of 50Gy in 20 fractions, with or without chemotherapy. Participating institutions were de-identified and grouped according to whether accrual was low, medium or high. OS was compared between groups and adjusted for prognostic factors using Cox regression. About 509 patients were accrued from 16 centres. Median potential follow-up time was 60months. Median survival for all groups was 20months (95% CI 18.3-21.8months). There were no statistically significant differences in OS with increasing patient accrual across the three groups after adjustment for prognostic factors (P=0.84, 2 df). The hazard ratios (HR) for group accrual volumes, relative to that for high-accrual volume, were as follows: low, 1.18; medium, 1.14. Test for trend: HR=0.91 per group (95% CI 0.76-1.09, P=0.31). In the setting of a clinical trial with rigorous quality assurance, we found no evidence for an association between institutional accrual and survival.

The diagnostic role of microRNA 21 in patients with nonsmall cell lung cancer: An exploratory study.

Background:Although histopathological examination of the biopsy specimen is the gold standard for the diagnosis of non small cell lung cancer (NSCLC), a blood-based noninvasive test (liquid biopsy) may prove to be helpful in patients with repeatedly negative biopsy or for response assessment following neoadjuvant therapy. The present study was conducted to explore the diagnostic value of circulating serum microRNA (miRNA) 21 in patients with NSCLC.Methods:This case–control analytical study was carried out in a tertiary care teaching hospital in Northern India. The study consisted of 30 cases of biopsy-proven NSCLC and 30 controls. Serum miRNA-21 expression levels were estimated by extracting total RNA from the serum sample, reverse transcribing it to cDNA and quantified in relation to U6 reference miRNA.Results:A total of 30 patients with NSCLC and 30 controls were included in the study. The subjects were comparable in two groups with reference to age, gender, and smoking. Pathological types were adenocarcinoma in 19 (63.3%) and squamous cell carcinoma in 11 (36.6%) patients. Majority of the patients had advanced disease-AJCC stage III in 15 patients and AJCC Stage IV in 13 patients; two patients had stage II disease. There was a significant upregulation of serum miRNA 21 gene expression in the patients with lung cancer compared to controls (median fold change, 3.39 vs. −2.81, P = 0.00). A fourfold change in serum miRNA 21 is significantly associated with the diagnosis of NSCLC with a high specificity of 97% and area under curve of 0.84 (95% confidence interval of 0.74–0.94).Conclusion:Estimation of serum miRNA 21 expression has potential to be used as liquid biopsy for the diagnosis of NSCLC. Further studies with large sample sizes are warranted to confirm the diagnostic accuracy of serum miRNA 21 expression.