Intratumoral heterogeneity characterized by pretreatment PET in non-small cell lung cancer patients predicts progression-free survival on EGFR tyrosine kinase inhibitor

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.

Fully automated identification of brain abnormality from whole-body FDG-PET imaging using deep learning-based brain extraction and statistical parametric mapping

Background The whole brain is often covered in [18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) in oncology patients, but the covered brain abnormality is typically screened by visual interpretation without quantitative analysis in clinical practice. In this study, we aimed to develop a fully automated quantitative interpretation pipeline of brain volume from an oncology PET image. Method We retrospectively collected 500 oncologic [18F]FDG-PET scans for training and validation of the automated brain extractor. We trained the model for extracting brain volume with two manually drawn bounding boxes on maximal intensity projection images. ResNet-50, a 2-D convolutional neural network (CNN), was used for the model training. The brain volume was automatically extracted using the CNN model and spatially normalized. For validation of the trained model and an application of this automated analytic method, we enrolled 24 subjects with small cell lung cancer (SCLC) and performed voxel-wise two-sample T test for automatic detection of metastatic lesions. Result The deep learning-based brain extractor successfully identified the existence of whole-brain volume, with an accuracy of 98% for the validation set. The performance of extracting the brain measured by the intersection-over-union of 3-D bounding boxes was 72.9 ± 12.5% for the validation set. As an example of the application to automatically identify brain abnormality, this approach successfully identified the metastatic lesions in three of the four cases of SCLC patients with brain metastasis. Conclusion Based on the deep learning-based model, extraction of the brain volume from whole-body PET was successfully performed. We suggest this fully automated approach could be used for the quantitative analysis of brain metabolic patterns to identify abnormalities during clinical interpretation of oncologic PET studies.This research was supported by the National Research Foundation of Korea (NRF-2019R1F1A1061412 and NRF2019K1A3A1A14065446). This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: 202011A06) and Seoul R&BD Program (BT200151)

Tumor immune profiles noninvasively estimated by FDG PET with deep learning correlate with immunotherapy response in lung adenocarcinoma

Rationale: The clinical application of biomarkers reflecting tumor immune microenvironment is hurdled by the invasiveness of obtaining tissues despite its importance in immunotherapy. We developed a deep learning-based biomarker which noninvasively estimates a tumor immune profile with fluorodeoxyglucose positron emission tomography (FDG-PET) in lung adenocarcinoma (LUAD). Methods: A deep learning model to predict cytolytic activity score (CytAct) using semi-automatically segmented tumors on FDG-PET trained by a publicly available dataset paired with tissue RNA sequencing (n = 93). This model was validated in two independent cohorts of LUAD: SNUH (n = 43) and The Cancer Genome Atlas (TCGA) cohort (n = 16). The model was applied to the immune checkpoint blockade (ICB) cohort, which consists of patients with metastatic LUAD who underwent ICB treatment (n = 29). Results: The predicted CytAct showed a positive correlation with CytAct of RNA sequencing in validation cohorts (Spearman rho = 0.32, p = 0.04 in SNUH cohort; spearman rho = 0.47, p = 0.07 in TCGA cohort). In ICB cohort, the higher predicted CytAct of individual lesion was associated with more decrement in tumor size after ICB treatment (Spearman rho = -0.54, p < 0.001). Higher minimum predicted CytAct in each patient associated with significantly prolonged progression free survival and overall survival (Hazard ratio 0.25, p = 0.001 and 0.18, p = 0.004, respectively). In patients with multiple lesions, ICB responders had significantly lower variance of predicted CytActs (p = 0.005). Conclusion: The deep learning model that predicts CytAct using FDG-PET of LUAD was validated in independent cohorts. Our approach may be used to noninvasively assess an immune profile and predict outcomes of LUAD patients treated with ICB.

Radioembolization for Hepatocellular Carcinoma: The Effects of Arterioportal Shunts on Nontargeted Liver Hypertrophy

© 2022 SIRPurpose: To determine whether arterioportal shunting to the contralateral lobe attenuates liver function and hypertrophy of the nontargeted liver after radioembolization in patients with hepatocellular carcinoma (HCC). Materials and Methods: The current retrospective study included 46 patients who received radioembolization for HCC contained within the right lobe between 2012 and 2020. The patients were divided into the following groups on the basis of the presence and extent of arterioportal shunting: patients with retrograde arterioportal shunting to the left lobe (contralateral group) and patients with arterioportal shunt limited to the right lobe or no arterioportal shunt (control group). Safety profiles, including adverse events, tumor response, and overall survival, were compared. With the volume of the left lateral segment used as a surrogate marker for nontarget liver, the degree of hypertrophy was compared between the 2 groups at 3 and 6 months. Results: Liver function significantly deteriorated in the contralateral group in a month (P ≤ .05). Tumor response and overall survival did not significantly differ between the 2 groups. The degree of hypertrophy was significantly higher in the control group than in the contralateral group at 3 months (10.6% vs 3.5%; P = .008) and 6 months (20.7% vs 2.4%; P &lt; .001). Conclusions: In patients with arterioportal shunting to the contralateral lobe, hypertrophy of the nontarget liver may not occur and the liver function may be worsened.N

Improvement of myocardial stress perfusion after off-pump revascularization using bilateral internal thoracic in situ grafts versus Y-composite grafts

BACKGROUND: There is a concern that revascularization using bilateral internal thoracic arteries (ITA) as a composite graft may not supply sufficient blood flow to a wider area of myocardium when compared with grafting using bilateral in situ ITAs. METHODS: One-hundred three patients who underwent off-pump coronary artery bypass using bilateral ITAs for revascularization of the left coronary system were studied prospectively. Bilateral ITAs were used as in situ grafts in 49 patients (group 1) and as a Y-composite graft in 54 patients (group 2). Resting and stress myocardial single-photon emission computed tomography (SPECT) was performed preoperatively and 3 months postoperatively. Myocardial perfusion was automatically quantified and expressed as a percentage of the maximal uptake. The left coronary territory was divided into 16 segments. A total of 379 segments (154 segments in group 1; 225 segments in group 2) that indicated decreased stress perfusion preoperatively were included in this study. RESULTS: Resting myocardial perfusion revealed no significant differences with regard to both the preoperative (77.5 +/- 9.3% vs 78.8 +/- 8.8%) and postoperative SPECT (78.3 +/- 10.0% vs 77.2 +/- 10.5%) between groups 1 and 2 (p = not significant [NS]). However, stress myocardial perfusion was significantly lower in group 1 preoperatively (62.5 +/- 10.8% vs 65.4 +/- 10.1%, p < 0.01). Although it improved postoperatively, there were no differences regarding postoperative stress myocardial perfusion between the two groups (75.5 +/- 11.3% vs 75.0 +/- 11.7%; p = NS). The degree of improvement regarding stress myocardial perfusion (difference between the preoperative and postoperative values) was higher in group 1 than in group 2 (13.0 +/- 9.4% vs 9.6 +/- 10.0%, p < 0.005). CONCLUSIONS: Myocardial SPECT demonstrated that revascularization using bilateral in situ ITAs exhibited a greater level of improvement with regard to stress perfusion postoperatively compared with Y-composite grafts. However, because there was no considerable difference with regard to postoperative stress perfusion between the two groups, revascularization using a Y-composite graft might also be sufficient for revascularization of the left coronary territory

Cancer screening using (18)F-FDG PET/CT in Korean asymptomatic volunteers: a preliminary report

This study was performed to evaluate the clinical value of (18)F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) for cancer screening in Korean asymptomatic people. Between February 2004 and December 2006, 1,587 asymptomatic individuals underwent FDG PET/CT as part of a cancer screening program with some other diagnostic tests at the healthcare center of our hospital. After excluding patients with a history of malignant tumor, 1,336 subjects were enrolled. All PET/CT images were visually analyzed. In subjects showing positive findings for PET/CT or other screening tests, further diagnostic tests and pathological confirmation were performed. Of the 1,336 subjects, malignant tumors were found in 16 participants (1.2%, thyroid cancer: 9, lung cancer: 2, stomach cancer: 2, and others: 4). There were 47 cases (3.6%) of positive PET/CT findings-11 cases were true positive (thyroid cancer: 8, lung cancer: 1, renal cancer: 1, and invasive thymoma), and 36 false positive, and five cases were false negative. The overall detection rate of PET/CT was 0.8%, and the sensitivity, specificity, positive-predictive value, and negative-predictive value of PET/CT were 68.8, 97.2, 23.4, and 99.6%, respectively. Fluorodeoxyglucose positron-emission tomography has the potential to detect various kinds of malignant tumors in cancer screening test, and the overall detection rate of PET/CT was 0.8%. FDG PET/CT can be a useful cancer screening modality with the selection of high-risk group and appropriate combination with other screening modalities.Terauchi T, 2008, ANN NUCL MED, V22, P379, DOI 10.1007/s12149-008-0130-7KO D, 2008, NUCL MED MOL IMAGING, V42, P444Minamimoto R, 2007, ANN NUCL MED, V21, P481, DOI 10.1007/s12149-007-0061-8Cook GJR, 2007, Q J NUCL MED MOL IM, V51, P235Kojima S, 2007, EUR J CANCER, V43, P1842, DOI 10.1016/j.ejca.2007.05.010Ghotbi N, 2007, ASIAN PAC J CANCER P, V8, P93Ono K, 2007, ANN NUCL MED, V21, P65Brix G, 2005, J NUCL MED, V46, P608Weckesser M, 2005, EUR J NUCL MED MOL I, V32, P342, DOI 10.1007/s00259-005-1775-2Chen YK, 2004, ANTICANCER RES, V24, P4103Rohren EM, 2004, RADIOLOGY, V231, P305, DOI 10.1148/radiol.2312021185Bar-Shalom R, 2003, J NUCL MED, V44, P1200Stahl A, 2003, EUR J NUCL MED MOL I, V30, P288, DOI 10.1007/s00259-002-1029-5Shen YY, 2003, NEOPLASMA, V50, P217Barratt A, 2002, J EPIDEMIOL COMMUN H, V56, P899Yasuda S, 2000, BRIT J CANCER, V83, P1607, DOI 10.1054/bjoc.2000.1496Charron M, 2000, CLIN NUCL MED, V25, P905Higashi K, 1998, J NUCL MED, V39, P1016Deloar HM, 1998, EUR J NUCL MED, V25, P565*ICRP, 1991, ICRP PUBL, V60*WHO, WHO FACT SHEETS