PURPOSE:To evaluate the long-term overall survival (OS), cancer-specific survival (CSS), and local tumor progression-free survival (LTPFS) of patients who underwent percutaneous image-guided thermal ablation (TA) (cryoablation, microwave ablation, and radiofrequency ablation) of oligometastatic renal cell carcinoma (omRCC). MATERIALS AND METHODS:This study cohort included 50 patients (age, 64.6 years [SD ± 13.1]; 78% [39/50] men and 22% [11/50] women) who underwent image-guided TA for omRCC between 2008 and 2019. Accounting for patient demographics, tumor characteristics, and technical outcomes, the OS, CSS, and LTPFS were derived by Kaplan-Meier analysis. Subgroup analyses were performed to assess the impact of outcomes by target lesion size, histology, location, and thermal energy using the log-rank test. All adverse events were categorized with the Society of Interventional Radiology (SIR) classification scheme. RESULTS:The study cohort comprised 100 omRCC lesions treated in 91 procedures, with a follow-up of up to 10 years (mean follow-up, 8.0 years [SD ± 2.8]). Primary and secondary technical success rates were 99% and 100%, respectively. The 10-year OS and CSS rates were 68.5% and 75.5%, respectively, with no significant difference between clear cell (P = .87) or nonclear cell (P = .52) histology. The 10-year LTPFS rate was 87.6% with no significant differences based on tumor histology (P = .47), size (P = .88), disease location (P = .72), or TA energy (P = .26). The adverse event rate of 9.9% (9/91) included 2 mild (2.2%) and 7 moderate (7.7%), mostly self-limited, events. CONCLUSIONS:Image-guided TA of omRCC was safe and effective with excellent long-term OS, CSS, and LTPFS outcomes within 10 years.

Objective To evaluate chest high-resolution CT (HRCT) images in idiopathic inflammatory myositis (IIM) using both quantitative CT and visual assessment. Methods HRCT images from a single-centre longitudinal IIM cohort were reviewed both visually and by quantitative imaging analysis (QIA), which quantified the extent of ground glass (QGG), fibrosis (QLF) and total interstitial lung disease burden (QILD). Visual review identified ILD presence and pattern and excluded other comorbid disease processes. Linear regression assessed correlations between QIA measures and pulmonary function tests (PFTs). Trends of QIA and PFTs were analysed in patients with ≥2 measurements using mixed-effects models. Associations with all-cause mortality were evaluated using Cox regression. Results Among 277 patients (mean age 51 years; 74% female; 77% dermatomyositis; 22% had antisynthetase syndrome), 168 had HRCT evaluable by both methods. ILD was identified in 51% by visual review. QLF and QILD had strong correlations with forced vital capacity (β=−0.7 and −0.59) and diffusing capacity of the lung for carbon monoxide (β=−0.75 and −0.64) across all visits (p<0.0001 for all). Higher baseline QLF and QILD scores (HR 1.04, 95% CI 1.00 to 1.08) and HR 1.08, 95% CI 1.01 to 1.16) and worsening QLF and QILD trends in the first 12 months (HR 1.04, 95% CI 1.01 to 1.07 and HR 1.06, 95% CI 1.01 to 1.11) were associated with greater all-cause mortality (p<0.05 for all). Survival did not differ by the presence of visual ILD or by ILD pattern. Conclusions In this large, real-world IIM cohort, quantitative HRCT measures—particularly QLF and QILD—were strongly associated with lung function and predicted mortality. Higher baseline and early worsening of QLF and QILD were associated with increased mortality, whereas visual ILD presence and pattern did not predict survival.

This review summarizes the current NCCN recommendations for the surgical management of pleural mesothelioma, highlighting the clinical trials and retrospective analyses that have shaped current practice and informed guideline recommendations. Advances in systemic therapy, surgical technique, and radiation therapy have shifted management toward multidisciplinary care. Contemporary treatment paradigms emphasize the importance of histology, stage, performance status, and institutional expertise when considering surgical intervention. Surgery can still be considered part of the multimodality treatment strategy in carefully selected patients, despite recent evidence suggesting its possible lack of benefit. Further investigation is required to improve patient stratification, refine multimodal regimens, and develop novel therapeutic approaches. This review aims to provide a contemporary framework for understanding the current role of surgery within the broader management of pleural mesothelioma.

Background: Image-guided thermal ablation has been used for the treatment of primary lung carcinoma but its use in the treatment of multiple lung carcinoma and effects on survival have not been well established. Objective: This study compares the long-term survival metrics for stage 1 single primary lung cancer and multiple primary lung cancer (MPLC) in patients treated with image-guided thermal ablation (IGTA). Methods: A retrospective institutional review included 37 NSCLC patients (mean age 71.6 ± 8.8 years) with ≥5 years follow-up. In total, 119 IGTA procedures were performed. Among patients with a single tumor (n = 14, 37.8%), each underwent a single ablation session. In contrast, patients with MPLC (n = 23, 62.2%) underwent 88 ablation sessions to treat 105 tumors. Data included demographics, tumor features, procedural details, safety, adverse events, and outcomes. Primary endpoints were 5-year overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS). Results: All ablations were completed successfully. Severe AEs occurred in 5.8% (7/119) of the ablations and were limited to pneumothorax requiring chest tube placement with hospitalization. At the time of ablation, individual nodules were staged at T1A = 46 (38.7%), T1B = 54 (45.4%), T1C = 16 (13.5%) and T2A = 3 (2.5%). Local recurrence was observed in 4/119 (3.3%) ablated tumors, all at stage T1B, and all were retreated with ablation. The 5-year OS was better for patients with MPLC at 85.6% compared to patients with a single tumor at 35.7% (HR = 0.14, p = 0.003, 95% CI: 0.037, 0.51). The 5-year OS for tumors based on T classification for T1A, T1B, TIC and T2A was 71.4%, 66.8%,66.7% and 0%. The 5-year PFS was 77.4% for patients with MPLC compared to 35.7% for patients with single primary lung cancer (HR = 0.25, p = 0.014, 95% CI: 0.084, 0.76). The 5-year CSS was 95.2% for patients with MPLC compared to 83.1% for patients with single primary lung cancer (HR = 0.21, p = 0.16, 95% CI: 0.018, 2.33). Conclusions: IGTA is an effective and safe treatment for patients with stage 1 single primary lung cancer and MPLC with limited local recurrence. Tumor size up to 3 cm did not have significant impact on survival. Overall survival was improved in patients with MPLC compared to those with single NSCLC. Clinical Impact: IGTA can be safely performed in patients with single primary lung cancer and MPLC, with limited local recurrence rate. Highlights: Key Findings: IGTA effectively treats patients with stage 1 single primary lung cancer and MPLC, with 3.3% recurrence, which can be retreated with ablation. The five-year OS was higher in patients with MPLC (85.6%) versus those with single lung cancer (35.7%, p = 0.003). OS by T classification: 71.4% for T1A, 66.8% for T1B, 66.7% for TIC, and 0% for T2A. Importance: IGTA effectively treats patients with single primary lung cancer and MPLC with low recurrence. Tumor size < 3 cm showed no impact on overall survival.

BACKGROUND AND OBJECTIVE:Prediction of the progressive phenotype from baseline evaluation is challenging due to the variable clinical course of fibrosing interstitial lung disease (ILD). The aim of this study was to evaluate whether the Single Time Point Prediction (STP) score predicts disease progression better than other quantitative scores. METHODS:This is a retrospective two-centre study including patients with ILD other than idiopathic pulmonary fibrosis (IPF). Using an automated quantification system, quantitative lung fibrosis (QLF), quantitative ground-glass opacity (QGG), quantitative ILD (QILD; the sum of reticulation, honeycombing, and ground-glass opacity), quantitative normal lung (QNL), and STP scores were measured. Disease progression (DP) was defined as an absolute decline in forced vital capacity (FVC) ≥ 5% or DLCO ≥ 10% predicted, death or lung transplantation. RESULTS:Of 245 patients, 137 (55.9%) progressed during follow-up (median: 20.4 months). In the Kaplan-Meier analysis, patients with high QGG (≥ 10%), high QILD (≥ 30%), and high STP (≥ 30%) showed shorter DP free survival time than those without. After adjusting for age, sex, FVC, and types of non-IPF ILD, QGG scores ≥ 10%, QILD ≥ 30%, and STP ≥ 30% remained significant predictors of progression (hazard ratio [HR] = 1.71, p = 0.024; HR = 1.73, p = 0.006; and HR = 1.58, p = 0.020, respectively). Furthermore, higher QILD and QGG scores in STP-positive regions were independently associated with increased DP risk, whereas higher QNL in STP-negative regions was associated with lower DP risk. CONCLUSIONS:The STP score is a useful imaging biomarker for predicting DP and, when combined with conventional quantitative CT scores, may improve risk stratification in patients with non-IPF ILD.

RationaleDisease progression in idiopathic pulmonary fibrosis (IPF) is unpredictable at the time of diagnosis. Early change in Quantitative Lung Fibrosis (QLF) score has been shown to be predictive for progression but requires two sequential high-resolution CT (HRCT) scans. Predicting progression using a single diagnostic HRCT would have value in precision medicine. Our aim is to evaluate a previously developed machine-learning radiomic HRCT marker, single time point prediction (STP) score at baseline, as a predictor of progression-free survival (PFS) in an evaluation cohort of IPF patients.MethodsImaging Signature IPF (IS-IPF) study, a retrospective evaluation cohort, characterized CT-imaging markers in 250 IPF subjects collected from March 2004 and October 2019. Baseline mean (±SD) age was 64.6 (±8.3) years, the cohort was 75% male, and the percent predicted FVC and DLCO were 72.9% (±16.8) and 59.3% (±18.8), respectively. PFS was defined as a ≥10% relative decline in FVC or death. Log-rank tests and Cox regressions were used to evaluate the performance of STP and QLF scores.Results128 subjects (52%) demonstrated ≥10% decline in FVC over 36 months. Mean STP score was 30.6% (±12.3%). After adjusting for GAP stage, STP≥30% was significantly associated with predicting disease progression (HR=1.57; p=0.017), whereas QLF≥10% demonstrated a trend (HR=1.43; p=0.070). Both STP and QLF scores with 5% increments were associated with the high risk of overall survival (HR=1.12; p=0.024 and HR=1.16; p=0.007, respectively).ConclusionsRadiomic STP at initial HRCT is associated with predicting progression in IPF patients, and it numerically outperformed baseline QLF.

Pulmonary emboli (PE) are a common clinical problem seen when a peripheral deep vein thrombosis (DVT) migrates to the pulmonary arteries. However, emerging literature suggests that not all filling defects in the pulmonary arteries are the result of embolism, and that in situ pulmonary arterial thrombus (ISPAT) or low-flow stasis artifact (LFSA) within the pulmonary arteries can mimic acute PE. The proposed mechanism for ISPAT is chronic stasis due to abnormal perfusion in areas of parenchymal lung disease leading to in situ thrombosis. Similarly, LFSA occurs when stasis leads to persistent visualization of intravenous contrast which is then mistaken for thrombus. The clinical scenarios in which ISPAT and LFSA develop are not yet fully defined. We report here a series of patients with parenchymal lung disease leading to ventilation-perfusion mismatch who likely had ISPAT or LFSA and not acute PE. Our aim is to further define parenchymal lung disease as a subgroup of patients who are at high risk for ISPAT. Cases initially diagnosed as acute PE leading to activation of the UCLA pulmonary embolism response team (PERT) were reviewed. Inclusion criteria were all cases of PE that led to PERT activation. Inclusion criteria included absence of DVT, previously diagnosed pulmonary disease, and presence of thrombus only in areas of abnormal parenchyma. Cases were reviewed with radiology to identify cases in which ISPAT was the likely diagnosis, and five representative cases were selected to be discussed. These cases were then analyzed qualitatively for commonalities which are described below. The five representative cases described represent patients with known chronic lung disease who were diagnosed and initially managed as acute PE but, on review, met criteria for either ISPAT or stasis artifact. These cases, which were all rediagnosed as ISPAT or LFSA, were all seen in the absence of DVT, with thrombus specifically located in areas of significant parenchymal lung disease with suspected decrease in ventilation and perfusion in these areas. ISPAT or LFSA have been described in the literature, though its presence specifically in parenchymal lung disease has yet to be described. The authors recommend considering this diagnosis in patient's diagnosed with acute PE when the following are present: significant parenchymal lung disease, absence of DVT, absence of thrombus in the areas of the lung relatively spared of parenchymal lung disease, and suspected baseline decrease in both ventilation and perfusion to the affected areas of the lung. As this phenomenon may be physiologically beneficial, the authors suggest that not all cases of ISPAT or LFSA need anticoagulation, and that treatment should be considered on a case-by-case basis.

Purpose: To evaluate the effectiveness of track cautery for lung microwave ablation (MWA) to reduce postprocedural adverse events (AE). Materials and methods: Patients who underwent percutaneous lung MWA between 2012 and 2021 were divided into 2 cohorts: patients in whom track cautery was conducted during antenna removal and patients in whom the antenna was simply removed. Patient demographics, treatment history, tumor characteristics, and ablation details were collected. Postprocedural AEs including immediate, enlarging, and delayed pneumothorax (PTX), pleural effusion, and reinterventions were recorded. Univariate and multivariate logistic regression models were used to identify factors associated with AEs. Results: This study included 365 lung MWA sessions for 190 patients. Of the 165 patients in the cautery cohort, 78 (47%) had immediate PTX, 16 (10%) had enlarging PTX, 2 (1%) had delayed PTX, and 15 (9%) needed interventions. Of the 200 patients in the noncautery cohort, 85 (43%) had immediate PTX, 45 (23%) had enlarging PTX, 16 (8%) had delayed PTX, and 37 (19%) needed interventions. The cautery cohort had significantly reduced rates of enlarging PTX (odds ratio [OR], 0.67; 95% CI, 0.34-1.33; P = .002), delayed PTX (OR, 0.15; 95% CI, 0.03-0.89; P = .037), and pleural effusion (OR, 0.38; 95% CI, 0.15-0.99; P = .049). The presence of emphysema, large tumor size, and left lower lobe location were shown to be significant predictors of AEs and the need for interventions (P < .05). Conclusions: Track cauterization is associated with reduction of post-MWA enlarging PTX, delayed PTX, and pleural effusion. Presence of emphysema, lack of track cautery, large tumor size, and tumors in the left lower lobe were shown to be predictors of postprocedural AEs.

Rationale: Endobronchial value (EBV) is a minimally invasive alternative to lung volume reduction surgery for patients with emphysema. High-resolution CT (HRCT) scans are integral for patient selection, identifying heterogeneous emphysematous and fissure integrity. Recently, a quantitative fissure integrity score (FIS) was developed using deep learning (DL) 3D patch-based CNN approach. The aim of this study is (1) to identify additional CT-based features predictive of treatment success beyond FIS and (2) to compare the predictive performance of completeness FIS (i.e. binary variable) and raw FIS (continuous variable). Methods: The cohort consists of 106 subjects who underwent EBV treatments from 2004 to 2023 with available CT. Of these, 93 subjects had paired HRCT scans (baseline and follow-up) with an average interval of 8 months. Quantitative CT features included: emphysema score (relative area below -950HU), FIS (with continuous values of 0-100%), and pulmonary blood vessel volumes estimated from CT. The dataset was split into an independent training set (59 subjects) and a test set (34 subjects) to identify CT features that would predict successful EBV placement in terms of lobar volume reduction, which was defined as a volume decrease of more than 350cc between paired CT scans. A nested logistic model was used to include important feature sets sequentially and compared the performance between the nested models. Important features were identified in the training set and applied in the test set. Results: The targeted lobes for treatment (N=106) were distributed as 43.40%, 11.32%, 24.53%, and 20.75% in the right upper, right lower, left upper, and left lower lobes, respectively. In the training set, the FIS of targeted lobe and the blood volume in vessels with a cross-sectional area of less than 5mm2(BV5) of the ipsilateral lobe emerged as significant predictors of successful lobar volume reduction. Quantitative values were: (1) training set -mean FIS of 80.4%(±20.8) and BV5 of 71.4cc(±21.4); (2) test set -mean FIS of 81.5%(±19.1), and BV5 of 78.3cc(±18.8). In the test set, only FIS remained a significant predictor of treatment success (OR=33.8, 95%CI[2.55,446]), while BV5 did not reach significance (p=0.818). Model performances are comparable with an AUC of 0.825 for binary FIS and 0.815 for continuous FIS(p=0.814). Conclusions: The fissure completeness score at the target lobe is a strong predictor of lobar volume reduction success in EBV treatment. Although BV5 did not show significant in the test set, it warrants further investigation as a potential perfusion indicator in treatment response.

Purpose:We aim to develop and validate a prediction model using a previously developed fully automated quantitative fissure integrity score (FIS) extracted from pre-treatment CT images to identify suitable candidates for endobronchial valve (EBV) treatment. Approach:We retrospectively collected 96 anonymized pre- and post-treatment chest computed tomography (CT) exams from patients with moderate to severe emphysema and who underwent EBV treatment. We used a previously developed fully automated, deep learning-based approach to quantitatively assess the completeness of each fissure by obtaining the FIS for each fissure from each patient's pre-treatment CT exam. The response to EBV treatment was recorded as the amount of targeted lobe volume reduction (TLVR) compared with target lobe volume prior to treatment as assessed on the pre- and post-treatment CT scans. EBV placement was considered successful with a TLVR of ≥ 350    cc . The dataset was split into a training set ( N = 58 ) and a test set ( N = 38 ) to train and validate a logistic regression model using fivefold cross-validation; the extracted FIS of each patient's targeted treatment lobe was the primary CT predictor. Using the training set, a receiver operating characteristic (ROC) curve analysis and predictive values were quantified over a range of FIS thresholds to determine an optimal cutoff value that would distinguish complete and incomplete fissures, which was used to evaluate predictive values of the test set cases. Results:ROC analysis of the training set provided an AUC of 0.83, and the determined FIS threshold was 89.5%. Using this threshold on the test set achieved an accuracy of 81.6%, specificity (Sp) of 90.9%, sensitivity (Sn) of 77.8%, positive predictive value (PPV) of 62.5%, and negative predictive value of 95.5%. Conclusions:A model using the quantified FIS shows potential as a predictive biomarker for whether a targeted lobe will achieve successful volume reduction from EBV treatment.

Objective The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD).Method We analysed data from the Abatacept in Myositis Associated Interstitial Lung Disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD. 6MWD, forced vital capacity (FVC), diffusing capacity (DLCO), high-resolution CT and various physician-/patient-reported outcome measures were obtained during the trial. Spearman's correlations and repeated-measures analysis with linear mixed-effects models were used to estimate the associations between 6MWD and various physiologic, clinical and radiographic parameters both cross-sectionally and longitudinally.Results Twenty participants with a median age of 57 years, 55% male and 85% white were analysed. Baseline 6MWD did not associate with baseline pulmonary function tests. Repeated-measures analysis showed 6MWD over time associated with FVC over time, but not with DLCO. 6MWD over time also correlated with University of California San Diego Shortness of Breath questionnaire dyspnoea score, Borg scores, as well as global disease activity and muscle strength over time. Emotional role functioning, vitality, general health and physical functioning scores by Short Form 36 also correlated with 6MWD over time.Conclusions Exploratory work in a small cohort of MA-ILD demonstrated 6MWD over time associated with parallel changes in FVC and patient-reported outcomes of dyspnoea, but not with DLCO. Larger studies are needed to validate the reliability, responsiveness and utility of the 6MWT in MA-ILD.Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT03215927.

Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of 68Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis-associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUVmax and SUVmean showed a positive correlation with the immunohistochemical FAP expression score (SUVmax: r = 0.57, P = 0.001; SUVmean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.

Purpose: To evaluate the safety and effectiveness of track cauterization for lung cryoablation through comparison of postprocedural adverse event (AE) rates. Materials and Methods: Fifty-nine patients who underwent 164 percutaneous lung cryoablation procedures between 2013 and 2018 were included in this retrospective study. The study cohort was subdivided by whether track cauterization was conducted or not at the end of the procedure. The study cohort was also subdivided by the number of probes (1-2 probes vs 3-4 probes). Postablation AE rates were assessed by immediate and delayed (at 1 month or later) AEs, pneumothorax, hemothorax, pleural effusion, and whether intervention was required. Univariate and multivariate logistic regression analyses were used to compare differences in AE rates. Results: Patients who underwent procedures with track cautery were 2.6 times less likely to exhibit pleural effusion (P = .017). Patients who underwent procedures conducted with a higher number of probes were 3.8 times more likely to receive interventions (P < .001), 1.6 times more likely to experience pneumothorax (P = .037), and 2.1 times more likely to experience pleural effusion (P = .003). History of lung surgery, increased number of probes, size of the probe, and absence of track cautery were noted to be significant predictors of AEs and need for interventions (all P < .05). Conclusions: Track cauterization in lung cryoablation was proven to reduce pleural effusion, but no difference in pneumothorax or delayed AEs was noted. The use of fewer probes was associated with a lower rate of AEs.

Objectives: To differentiate invasive lepidic predominant adenocarcinoma (iLPA) from adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) of lung utilizing visual semantic and computer-aided detection (CAD)-based texture features on subjects initially diagnosed as AIS or MIA with CT-guided biopsy. Materials and Methods: From 2011 to 2017, all patients with CT-guided biopsy results of AIS or MIA who subsequently underwent resection were identified. CT scan before the biopsy was used to assess visual semantic and CAD texture features, totaling 23 semantic and 95 CAD-based quantitative texture variables. The least absolute shrinkage and selection operator (LASSO) method or forward selection was used to select the most predictive feature and combination of semantic and texture features for detection of invasive lung adenocarcinoma. Results: Among the 33 core needle-biopsied patients with AIS/MIA pathology, 24 (72.7%) had invasive LPA and 9 (27.3%) had AIS/MIA on resection. On CT, visual semantic features included 21 (63.6%) part-solid, 5 (15.2%) pure ground glass, and 7 (21.2%) solid nodules. LASSO selected seven variables for the model, but all were not statistically significant. “Volume” was found to be statistically significant when assessing the correlation between independent variables using the backward selection technique. The LASSO selected “tumor_Perc95”, “nodule surround”, “small cyst-like spaces”, and “volume” when assessing the correlation between independent variables. Conclusions: Lung biopsy results showing noninvasive LPA underestimate invasiveness. Although statistically non-significant, some semantic features showed potential for predicting invasiveness, with septal stretching absent in all noninvasive cases, and solid consistency present in a significant portion of invasive cases.

Purpose To investigate the effect of patient and tumor-specific characteristics on the size of immediate phase lung microwave ablation (MWA) zone and establish a prediction model. Methods and Materials This IRB-approved, HIPAA compliant cohort included 164 lesions from 99 patients who underwent CT-guided lung MWA and the two-dimensional elliptical ground-glass opacity ablation zone was measured. Duration, maximum temperature, tumor depth, presence of emphysema, history of ipsilateral lung ablation, surgery, and radiation were recorded. K-fold cross validation with k=5 and Least Absolute Shrinkage and Selection Operator were used to build prediction models for the major and minor axes, and area of the ablation zone. Results The median of immediate phase ablation duration was 2 minutes (IQR: 1.5 – 4.25) with 65W of power for all ablations. The mean major, minor axes, and area of ablation zone were 3.1±0.6cm, 2.0±0.5cm, and 5.1±2.1cm2. The major axis, minor axis, and area of immediate phase ablation zone dimensions were significantly associated with duration (p<0.001, p<0.001, p<0.001), maximum temperature (p<0.001, p<0.001, p<0.001), tumor depth (p=0.387, p<0.001, p<0.001), history of ipsilateral lung ablation (p=0.008, p=0.286, p=0.076), and lung radiation (p=0.001, p=0.042, p=0.015). The prediction model showed R2 values for major and minor axes and area of the ablation zone to be 0.50, 0.45, and 0.53, respectively. Conclusion Duration, maximum temperature, tumor depth, history of ipsilateral lung ablation, surgery, and radiation were significantly associated with the ablation zone dimensions and size and can be used to build the prediction model to approximate the immediate phase lung MWA zone.

Abstract Background: Effective immunotherapy options are lacking for patients with advanced non-small cell lung cancer (NSCLC) who progress on a programmed cell death-(ligand)1 [PD-(L)1] inhibitor and for those who are epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement positive after progression on tyrosine kinase inhibitor (TKI) therapy. One potential approach to improve immune checkpoint efficacy in these patient populations is to promote cytolytic T cell infiltration into tumors. This can be accomplished via in situ vaccination with chemokine gene-engineered functional antigen presenting cells (APCs) which can take advantage of the full repertoire of tumor antigens and convert the tumor into a lymph node-like environment to promote both local and systemic antitumor responses. The chemokine CCL21 promotes co-localization of naive T cells and antigen-experienced dendritic cells (DCs) to facilitate T cell activation. Our preclinical studies and phase I trial of intratumoral (IT) administration of DC genetically modified to overexpress CCL21 (CCL21-DC) revealed augmentation of tumor antigen presentation in situ, resulting in systemic antitumor immunity. However, increased PD-L1 expression was observed in some patient tumors, suggesting that tumor-mediated impairment of T cell function may be forestalling a more robust CCL21-DC mediated antitumor response. Similarly, improved PD-(L)1 inhibitor efficacy may be possible with enhanced T cell infiltration and augmented APC function following IT CCL21-DC. Therefore, we are conducting a phase I trial, combining IT CCL21-DC with pembrolizumab in patients with advanced NSCLC. Methods: Phase I, dose-escalating, multi-cohort trial followed by dose expansion. Maximum of 24 patients (9-12 escalation + 12 expansion) with stage IV NSCLC will be evaluated who have tumors accessible for IT injection and are either (1) EGFR/ALK wild-type after progression on a PD-(L)1 inhibitor or (2) EGFR/ALK mutant after progression on TKI therapy. Three IT injections of autologous CCL21-DC (days 0, 21, 42) will be concurrently administered with pembrolizumab, followed by pembrolizumab once every three weeks for up to 1 year. Primary objective of dose escalation is safety and determination of maximum tolerated dose (MTD) of IT CCL21-DC when combined with pembrolizumab. Primary objective of dose expansion is objective response rate at MTD. Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment, and this updated abstract will highlight the feasibility of repeated IT injections in treated patients. Citation Format: Bin Liu, Aaron Lisberg, Ramin Salehi-Rad, Michael Oh, Jay M. Lee, Linh M. Tran, Kostyantyn Krysan, Raymond J. Lim, Camelia Dumitras, Zhe Jing, Fereidoun Abtin, Robert D. Suh, Scott J. Genshaft, Scott S. Oh, Gregory A. Fishbein, Anita Kaul, Kanwarpal S. Kahlon, Shahryar A. Ashouri, Jonathan W. Goldman, David A. Elashoff, Edward Garon, Steven M. Dubinett. Phase I trial of intratumoral administration of autologous CCL21 gene-modified dendritic cells in combination with pembrolizumab for advanced NSCLC: Feasibility of repeated IT injections [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT153.