Evaluation Of Chemotherapy Response Research Articles

Prognostic Value of Residual Circulating Tumor DNA in Metastatic Pancreatic Ductal Adenocarcinoma.

Circulating tumor DNA (ctDNA) is a potential biomarker in pancreatic ductal adenocarcinoma (PDAC). However, studies on residual ctDNA in patients post-chemotherapy are limited. We assessed the prognostic value of residual ctDNA in metastatic PDAC relative to that of carbohydrate antigen 19-9 (CA19-9). ctDNA analysis using a targeted next-generation sequencing panel was performed at baseline and during chemotherapy response evaluation in 53 patients. Progression-free survival (PFS) and overall survival (OS) were first evaluated based on ctDNA positivity at baseline. For further comparison, patients testing ctDNA-positive at baseline were subdivided based on residual ctDNA into ctDNA responders (no residual ctDNA post-chemotherapy) and ctDNA non-responders (residual ctDNA post-chemotherapy). Additional survival analysis was performed based on CA19-9 levels. The baseline ctDNA detection rate was 56.6%. Although clinical outcomes tended to be poorer in patients with baseline ctDNA positivity than in those without, the differences were not significant. Residual ctDNA post-chemotherapy was associated with reduced PFS and OS. The prognosis of ctDNA responders was better than that of non-responders but did not significantly differ from that of ctDNA-negative individuals (no ctDNA both at baseline and during post-chemotherapy). Compared with ctDNA responses to chemotherapy, a ≥ 50% decrease in the CA19-9 level had less effect on both PFS and OS based on hazard ratios and significance levels. ctDNA could be monitored in half of the patients whose baseline CA19-9 levels were within the reference range. Residual ctDNA analysis post-chemotherapy is a promising approach for predicting the clinical outcomes of patients with metastatic PDAC.

Spectral CT-based nomogram for evaluation of neoadjuvant chemotherapy response in esophageal squamous cell carcinoma.

To establish a spectral CT-based nomogram for predicting the response to neoadjuvant chemotherapy (NAC) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). This retrospective study included 172 patients with ESCC who underwent spectral CT scans before NAC followed by resection. Based on postoperative tumor regression grades (TRG), 34% (58) of patients were responsive (TRG1) and 66% (114) were non-responsive (TRG2-3). The data was divided into a primary set of 120 and a validation set of 52, maintaining a 7:3 random ratio. Measurements included iodine concentration (IC), normalized iodine concentration (nIC), CT40kev, CT70kev, spectral attenuation curve slope (λHU), and effective atomic number (Zeff) during non-contrast and venous phases (VP). Clinicopathologic characteristics were collected. Univariable and multivariable logistic regressions identified independent predictors of NAC response. The model was visualized using nomograms, and its efficacy was assessed via receiver operating characteristic (ROC) curves. Multivariable logistic regression analysis identified the neutrophil-to-lymphocyte ratio (NLR), clinical stage, ZeffVP, and nICVP as independent predictors of NAC response. The nomogram incorporating all four independent predictors, outperformed spectral CT and the clinical model with the highest AUCs of 0.825 (95% CI: 0.746-0.895) for the primary set and 0.794 (95% CI: 0.635-0.918) for the validation set (DeLong test: all p < 0.05). The spectral CT and clinical models were useful in predicting NAC response in ESCC patients. Combining spectral CT imaging parameters and clinicopathologic characteristics in a nomogram improved predictive accuracy. Question Developing a non-invasive, practical tool to predict ESCC's response to chemotherapy is crucial and has not yet been done. Findings This nomogram, incorporating clinicopathologic characteristics and spectral CT-derived parameters, predicted NAC response in ESCC patients. Clinical relevance This spectral CT-based nomogram is a non-invasive and easily obtainable tool for accurately predicting ESCC response to NAC, aiding clinicians in personalized treatment planning.

Comparison of efficacy and safety of nab-paclitaxel and oxaliplatin + S-1 and standard S-1 and oxaliplatin chemotherapy regimens for treatment of gastric cancer.

Gastric cancer (GC) is a relatively frequent clinical phenomenon, referring to malignant tumors emerging in the gastric mucosal epithelial cells. It has a high morbidity and mortality rate, posing a significant threat to the health of patients. Hence, how to diagnose and treat GC has become a heated topic in this research field. To discuss the effectiveness and safety of nab-paclitaxel in combination with oxaliplatin and S-1 (P-SOX) for the treatment of GC, and to analyze the factors that may influence its outcomes. A total of 219 eligible patients with advanced GC, who were treated at Qinghai University Affiliated Hospital Gastrointestinal Oncology between January 2018 and March 2020, were included in the study. Among them, 149 patients received SOX regimen and 70 patients received S-1 regimen. All patients underwent both preoperative and postoperative chemotherapy consisting of 2-4 cycles each, totaling 6-8 cycles, along with parallel D2 radical surgical treatment. The patients were followed up for a period of three years or until reaching the event endpoint. The short-term and long-term efficacy of the P-SOX group was significantly higher than that of the SOX group, and the safety was manageable. Cox multivariate analysis revealed that progression-free survival was associated with perioperative chemotherapy efficacy, tumor diameter ≤ 2cm, high differentiation, and early cTNM (T stands for invasion depth; N stands for node metastasis; M stands for distant invasion) stage. In comparison to the SOX regimen, the P-SOX regimen demonstrates improved short-term and long-term efficacy with tolerable adverse reactions. It is anticipated that the P-SOX regimen will emerge as a first-line chemotherapy option for GC. Patients with GC who receive effective perioperative chemotherapy (Response Evaluation Criteria in Solid Tumors 1.1, Tumor Regression Grade), have a tumor diameter ≤ 2cm, exhibit high degree of differentiation, and are at an early cTNM stage show better prognosis.

PSMA PET/CT for treatment response evaluation at predefined time points is superior to PSA response for predicting survival in metastatic castration-resistant prostate cancer patients

BackgroundIn metastatic castration-resistant prostate cancer (mCRPC), using serum prostate-specific antigen (PSA) levels to evaluate treatment response is not always accurate. This study aimed to assess the efficacy of PSMA PET/CT at specific time points for evaluating treatment response and predicting survival in mCRPC patients, compared to PSA. MethodsSixty mCRPC patients underwent [18F]PSMA-1007 PET/CT at baseline and for treatment response evaluation of either androgen receptor-targeted agents (after 3 months) or chemotherapy (after completion), and were retrospectively analysed. Visual assessment categorised overall response and response of the worst responding lesion as partial response, stable disease, or progressive disease, using the EAU/EANM criteria. Additionally, percentage changes in SUVmax, total tumour volume and total lesion uptake (tumour volume * SUVmean) were calculated. PSA response was defined according to the PCWG3 criteria. Cox regression analysis identified predictors of overall survival. ResultsPSMA PET/CT and PSA response were discordant in 47 % of patients, and PSMA PET/CT response was worse in 89 % of these cases. Overall response on PSMA PET/CT independently predicted overall survival (progression versus non-progression: HR = 4.05, p < 0.001), outperforming PSA response (progression versus non-progression: HR = 2.53, p = 0.010) and other PSMA PET/CT parameters. Among patients with a PSA decline of > 50 %, 31 % showed progressive disease on PSMA PET/CT, correlating with higher mortality risk (progression versus non-progression: HR = 4.38, p = 0.008). No flare in PSMA uptake was observed in this cohort. ConclusionsPSMA PET/CT for assessing treatment response at predefined time points was superior to PSA-based response for predicting overall survival in mCRPC patients treated with androgen receptor-targeted agents and chemotherapy. PSMA PET/CT showed the ability to detect disease progression earlier than PSA levels, which can affect treatment decisions and has the potential to improve patient outcomes. We recommend further research to validate these findings in larger patient cohorts, to extend the number of treatments, and to evaluate cost-effectiveness and impact on patient outcomes.

Dynamic Contrast Enhanced MRI Mapping of Vascular Permeability for Evaluation of Breast Cancer Neoadjuvant Chemotherapy Response Using Image-to-Image Conditional Generative Adversarial Networks.

Dynamic contrast enhanced (DCE) MRI is a non-invasive imaging technique that has become a quantitative standard for assessing tumor microvascular permeability. Through the application of a pharmacokinetic (PK) model to a series of T1-weighed MR images acquired after an injection of a contrast agent, several vascular permeability parameters can be quantitatively estimated. These parameters, including Ktrans, a measure of capillary permeability, have been widely implemented for assessing tumor vascular function as well as tumor therapeutic response. However, conventional PK modeling for translation of DCE MRI to PK vascular permeability parameter maps is complex and time-consuming for dynamic scans with thousands of pixels per image. In recent years, image-to-image conditional generative adversarial network (cGAN) is emerging as a robust approach in computer vision for complex cross-domain translation tasks. Through a sophisticated adversarial training process between two neural networks, image-to-image cGANs learn to effectively translate images from one domain to another, producing images that are indistinguishable from those in the target domain. In the present study, we have developed a novel image-to-image cGAN approach for mapping DCE MRI data to PK vascular permeability parameter maps. The DCE-to-PK cGAN not only generates high-quality parameter maps that closely resemble the ground truth, but also significantly reduces computation time over 1000-fold. The utility of the cGAN approach to map vascular permeability is validated using open-source breast cancer patient DCE MRI data provided by The Cancer Imaging Archive (TCIA). This data collection includes images and pathological analyses of breast cancer patients acquired before and after the first cycle of neoadjuvant chemotherapy (NACT). Importantly, in good agreement with previous studies leveraging this dataset, the percentage change of vascular permeability Ktrans derived from the DCE-to-PK cGAN enables early prediction of responders to NACT.

Intra‐tumoral tumor infiltrating Lymphocyte‐T CD8+ and chemotherapy response in colorectal cancer: A prospective observational study

Background: The immunotherapy approach to colorectal cancer is becoming one of the key approaches to colorectal cancer treatment. One of the components of immune responses is tumor‐infiltrating lymphocyte CD8+ cells (TILs CD8+). While chemotherapy is one of the main treatments for colorectal cancer, we need to consider immunotherapy for advanced colorectal cancer. Thus, this study is aimed at finding the association between TIL CD8+ expression and chemotherapy response. Methods: This is a prospective cohort study with colorectal cancer patients in the Digestive Surgery division of a tertiary general hospital in West Java, Indonesia. An immunohistochemistry examination was used to evaluate the expression of TIL CD8+. The response evaluation criteria in solid tumors (RECIST) were used for the evaluation of chemotherapy response. Results: There were 53 research subjects included. There were 20 (37.7%) subjects with high expression of TILs CD8+; there were 30 (56.6%) subjects in stage III, followed by stage IV (17.32%) and stage II (6.11%). There were 18 subjects (34%) who showed progressive disease, 17 subjects (32.1%) showed partial response, and 16 subjects (30.2%) with high expression of TILs CD8+ showed partial chemotherapy response. The TILs CD8+ expression showed no significant relationship with age, sex, subtype, grade, or tumor location, but showed a significant relationship with stage and chemotherapy response (P &lt; 0.05). Conclusion: High TILs CD8+ expression show a relationship with better chemotherapy response and a better prognosis based on disease stage in colorectal cancer patients.

Evaluation of Epirubicin, Cyclophosphamide and Paclitaxel-based Chemotherapy Response for Treatment of Breast Cancer Patients as Neo-Adjuvant: A Case-Series in a Tertiary Care Hospital in Bangladesh

Background: Breast cancer is the most common cancer among women across the world. Various treatment modalities in terms of radiotherapy, chemotherapy or surgery along with several neoadjuvant or adjuvant therapies are already established for the better survival of the patients. New modalities are still under research every other day for improvement of quality of life of cancer victims. Objective: This case series was conducted to assess the efficacy and safety profile of primary breast cancer patients by adding Paclitaxel to the established regimen of Epirubicin and Cyclophosphamide. Methods: This was performed during January 2019 to January 2021 with 9 cases of clinically diagnosed breast cancer patients at Combined Military Hospital, Dhaka. Patients included in our study received Epirubicin in the dose of 75-100 mg/m2 dl, Cyclophosphamide 600 mg/m2 dl, every 3 weeks for a total of 4 cycles followed by Paclitaxel at a dose of 175 mg/m2, every 3 weeks for a sum of 4 cycles. After every cycle of neoadjuvant chemotherapy and at the end of it, response was assessed by ultrasound. Results: The findings revealed 6 out of 9 patients showed pathological complete response at the end of this neoadjuvant regimen. The remaining 3 cases showed partial response. Toxicity was minimal and well-managed. 5 patients developed leukopenia in terms of haematological events, whereas for other effects, nausea and fatigue was commonly encountered. Conclusion: Overall, this treatment modality turned out to be feasible and a good option for neoadjuvant therapy in terms of efficacy and safety profile for the breast cancer patients.

Intravoxel incoherent motion and dynamic contrast-enhanced magnetic resonance imaging for neoadjuvant chemotherapy response evaluation in patients with osteosarcoma

ObjectivesThis study aims to explore the role of quantitative intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in characterizing changes in osteosarcoma (OS) patients receiving neoadjuvant chemotherapy (NACT). Material and methodsTwenty-seven patients with histologically proven OS were examined prospectively and divided into good-response group (n = 14) and poor-response group (n = 13). IVIM and DCE-MRI sequences were performed at baseline (pre-NACT) and after three cycles of NACT (post-NACT). Apparent diffusion coefficient (ADC) and IVIM bi-exponential model parameters, including diffusion coefficient (D-Bi), perfusion coefficient (D*-Bi), and perfusion fraction (f-Bi), were evaluated. DCE-MRI parameters, including quantitative parameters (volume transfer constant [Ktrans], elimination rate constant [Kep], and extravascular extracellular space volume ratio [Ve]) and semi-quantitative parameters (initial area under the gadolinium curve [IAUGC] and contrast enhancement rate [CER]), were also measured. ResultsD-Bi, D*-Bi, and f-Bi post-NACT and ΔD-Bi were statistically different between the good- and poor-response groups (Z1 = − 3.348, Z2 = − 2.572, Z3 = − 2.378, t = 2.235, P < 0.05). ADC, f-Bi, Ktrans, IAUGC, Kep, and CER post-NACT were statistically different from those at pre-NACT (P < 0.05). The receiver operating characteristic curve showed that f-Bi post-NACT had the best performance among all parameters, with area under the curve of 0.769, sensitivity of 1, and specificity of 0.538. The correlation analysis showed that the efficacy of NACT was negatively correlated with D-Bi, D*-Bi post-NACT, and ΔD-Bi (r1 = − 0.530, r2 = − 0.411, r3 = − 0.434, P1 = 0.008, P2 = 0.046, P3 = 0.034) and significantly positively correlated with f-Bi post-NACT (r = 0.482, P = 0.017). ConclusionsThe IVIM quantitative parameters D-Bi, D*-Bi, and f-Bi post-NACT and ΔD-Bi could be used as noninvasive imaging biomarkers for early response assessment of NACT in OS.

Tumour infiltrating lymphocyts (TILs) as an excellent predictive factor for neoadjuvant chemotherapy response on locally advanced rectal cancer patient

Background: In Indonesia, 16,000 new cases of rectal cancer were found in 2020, with a mortality rate up to 50%. Most of the cases were locally advanced rectal cancer which requires neoadjuvant therapy. A predictive marker that can indicate how neoadjuvant therapy is responding is thus required, and TILs is a biomarker that has been extensively studied as a reliable predictive and prognostic marker in colorectal cancer. This study aims to determine if the response to neoadjuvant chemotherapy in locally advanced rectal cancer (LARC) patients correlated with the density of TILs. Methods: This study was a retrospective cohort study with samples taken from rectal cancer patients who visited Dr. Soetomo General Hospital between 2017 and 2021. TILs density measurements were taken from stromal tumors on pre-NAC biopsy examination with H&amp;E staining. Evaluation of chemotherapy response based on abdominal CT scan. The density of TILs using 45% cut-off. Results: A total 38 samples were studied, 21 were male and 17 were female. Twenty-nine samples (86.2%) with weak TILs density showed negative chemotherapy response or progressive tumors. There is a significant correlation between the density of TILs and the chemotherapy response of the sample studied (p=0.002). Conclusion: TILs are an excellent predictive marker for neoadjuvant chemotherapy response in LARC patients and can be examined using H&amp;E staining method which is cheap and fast but still has predictive value.

201 (PB-114) Poster - Evaluation of neoadjuvant chemotherapy response in breast cancer: radiological and pathological concordance

Background: MRI is the most used test for the evaluation of neoadjuvant chemotherapy (NAC) response in breast cancer. However, sometimes the pathological analysis of surgical piece revels discordance with pre-surgical radiological result. The purpose of the study was to evaluate radiological-pathological concordance of NAC response and to define which factors are associated with this coincident result.

Prediction of response to lomustine-based chemotherapy in glioma patients at recurrence using MRI and FET PET.

We evaluated O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET and MRI for early response assessment in recurrent glioma patients treated with lomustine-based chemotherapy. Thirty-six adult patients with WHO CNS grade 3 or 4 gliomas (glioblastoma, 69%) at recurrence (median number of recurrences, 1; range, 1-3) were retrospectively identified. Besides MRI, serial FET PET scans were performed at baseline and early after chemotherapy initiation (not later than two cycles). Tumor-to-brain ratios (TBR), metabolic tumor volumes (MTV), the occurrence of new distant hotspots with a mean TBR >1.6 at follow-up, and the dynamic parameter time-to-peak were derived from all FET PET scans. PET parameter thresholds were defined using ROC analyses to predict PFS of ≥6months and OS of ≥12months. MRI response assessment was based on RANO criteria. The predictive values of FET PET parameters and RANO criteria were subsequently evaluated using univariate and multivariate survival estimates. After treatment initiation, the median follow-up time was 11months (range, 3-71months). Relative changes of TBR, MTV, and RANO criteria predicted a significantly longer PFS (all P ≤ .002) and OS (all P ≤ .045). At follow-up, the occurrence of new distant hotspots (n ≥ 1)predicted a worse outcome, with significantly shorter PFS (P=.005) and OS (P < .001). Time-to-peak changes did not predict a significantly longer survival. Multivariate survival analyses revealed that new distant hotspots at follow-up FET PET were most potent in predicting non-response (P < .001; HR, 8.578). Data suggest that FET PET provides complementary information to RANO criteria for response evaluation of lomustine-based chemotherapy early after treatment initiation.

Chemotherapy response evaluation using diffusion weighted MRI in Ewing Sarcoma: A single center experience.

Non-invasive biomarkers for early chemotherapeutic response in Ewing sarcoma family of tumors (ESFT) are useful for optimizing existing treatment protocol. To assess the role of diffusion-weighted magnetic resonance imaging (MRI) in the early evaluation of chemotherapeutic response in ESFT. A total of 28 patients (mean age = 17.2 ± 5.6 years) with biopsy proven ESFT were analyzed prospectively. Patients underwent MRI acquisition on a 1.5-T scanner at three time points: before starting neoadjuvant chemotherapy (baseline), after first cycle chemotherapy (early time point), and after completion of chemotherapy (last time point). RECIST 1.1 criteria was used to evaluate the response to chemotherapy and patients were categorized as responders (complete and partial response) and non-responders (stable and progressive disease). Tumor diameter, absolute apparent diffusion coefficient (ADC), and normalized ADC (nADC) values in the tumor were measured. Baseline parameters and relative percentage change of parameters after first cycle chemotherapy were assessed for early detection of chemotherapy response. The responder:non-responder ratio was 21:7. At baseline, ADC ([0.864 ± 0.266 vs. 0.977 ± 0.246]) × 10-3mm2/s; P = 0.205) and nADC ([0.740 ± 0.254 vs. 0.925 ± 0.262] × 10-3mm2/s; P = 0.033) among responders was lower than the non-responders and predicted response to chemotherapy with AUCs of 0.6 and 0.735, respectively. At the early time point, tumor diameter (27% ± 14% vs. 4.6% ± 10%; P = 0.002) showed a higher reduction and ADC (75% ± 44% vs. 52% ± 72%; P = 0.039) and nADC (81% ± 44% vs. 48% ± 67%; P = 0.008) showed a higher increase in mean values among responders than the non-responders and identified chemotherapy response with AUC of 0.890, 0.723, and 0.756, respectively. Baseline nADC and its change after the first cycle of chemotherapy can be used as non-invasive surrogate markers of early chemotherapeutic response in patients with ESFT.

Abbreviated and Standard Breast MRI in Neoadjuvant Chemotherapy Response Evaluation: A Comparative Study.

This study aims to investigate the efficacy of abbreviated breast magnetic resonance imaging (MRI) in neoadjuvant chemotherapy (NAC) response evaluation. MR images of 50 locally advanced breast cancer patients who underwent standard protocol (SP) breast MRI before and after NAC were re-evaluated retrospectively. Abbreviated protocol (AP) was obtained by extracting images from SP and then evaluating them in a separate session. Protocols were compared with the histological findings after surgery as the reference standard. A statistically significant difference was found between the two protocols in response evaluation by the McNemar test (p=0.018). However, the Kappa value was 0.62 (p<0.001), which indicates substantial agreement. No statistically significant differences were found between the two protocols (AP and SP) and pathological results in the McNemar test (p=0.12, p=0.60, respectively). Kappa values were 0.48 (p<0.001) and 0.60 (p<0.001), respectively, which indicates moderate agreement for both protocols with higher values by SP evaluation. The residual maximum median diameters were smaller than the pathology, with both protocols (p<0.001). Despite the statistical differences, there was a significant correlation in response evaluation between the two protocols. The pathological results were moderately correlated with both protocols, with SP slightly higher. However, the residual maximum median diameters were smaller than the pathology with both protocols. These results may limit the use of AP in evaluating the local extent of the tumor, especially in patients who will undergo breast-conserving surgery.

Mitochondrial-Related Transcriptome Feature Correlates with Prognosis, Vascular Invasion, Tumor Microenvironment, and Treatment Response in Hepatocellular Carcinoma.

Background Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer, which was highly correlated with metabolic dysfunction. Nevertheless, the association between nuclear mitochondrial-related transcriptome and HCC remained unclear. Materials and Methods A total of 147 nuclear mitochondrial-related genes (NMRGs) were downloaded from the MITOMAP: A Human Mitochondrial Genome Database. The training dataset was downloaded from The Cancer Genome Atlas (TCGA), while validation datasets were retrieved from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The univariate and multivariate, and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were applied to construct a NMRG signature, and the value of area under receiver operating characteristic curve (AUC) was utilized to assess the signature and nomogram. Then, data from the Genomics of Drug Sensitivity in Cancer (GDSC) were used for the evaluation of chemotherapy response in HCC. Results Functional enrichment of differentially expressed genes (DEGs) between HCC and paired normal tissue samples demonstrated that mitochondrial dysfunction was significantly associated with HCC development. Survival analysis showed a total of 35 NMRGs were significantly correlated with overall survival (OS) of HCC, and the LASSO Cox regression analysis further identified a 25-NMRG signature and corresponding prognosis score based on their transcriptional profiling. HCC patients were divided into high- and low-risk groups according to the median prognosis score, and high-risk patients had significantly worse OS (median OS: 27.50 vs. 83.18 months, P < 0.0001). The AUC values for OS at 1, 3, and 5 years were 0.79, 0.77, and 0.77, respectively. The prognostic capacity of NMRG signature was verified in the GSE14520 dataset and ICGC-HCC cohort. Besides, the NMRG signature outperformed each NMRG and clinical features in prognosis prediction and could also differentiate whether patients presented with vascular invasions (VIs) or not. Subsequently, a prognostic nomogram (C-index: 0.753, 95% CI: 0.703~0.804) by the integration of age, tumor metastasis, and NMRG prognosis score was constructed with the AUC values for OS at 1, 3, and 5 years were 0.82, 0.81, and 0.82, respectively. Notably, significant enrichment of regulatory and follicular helper T cells in high-risk group indicated the potential treatment of immune checkpoint inhibitors for these patients. Interestingly, the NMRG signature could also identify the potential responders of sorafenib or transcatheter arterial chemoembolization (TACE) treatment. Additionally, HCC patients in high-risk group appeared to be more sensitive to cisplatin, vorinostat, and methotrexate, reversely, patients in low-risk group had significantly higher sensitivity to paclitaxel and bleomycin instead. Conclusions In summary, the development of NMRG signature provided a more comprehensive understanding of mitochondrial dysfunction in HCC, helped predict prognosis and tumor microenvironment, and provided potential targeted therapies for HCC patients with different NMRG prognosis scores.

Development and Validation of TACE Refractoriness-Related Diagnostic and Prognostic Scores and Characterization of Tumor Microenvironment Infiltration in Hepatocellular Carcinoma.

BackgroundTranscatheter arterial chemoembolization LIHC, Liver hepatocellular carcinoma; (TACE) is a valid therapeutic method for hepatocellular carcinoma (HCC). However, many patients respond poorly to TACE, thus leading to an adverse outcome. Therefore, finding new biomarkers for forecasting TACE refractoriness occurrence and prognosis becomes one of the current research priorities in the field of HCC treatment.Materials and MethodsBased on microarray datasets and a high-throughput sequencing dataset, the TACE refractoriness–related genes (TRGs) were identified by differential expression analysis. LASSO and Cox regression were applied to construct TACE refractoriness diagnostic score (TRD score) and prognostic score (TRP score) and validated their accuracy in external datasets. Functional correlation of TRP score was analyzed by gene set variation analysis and Gene Ontology. CIBERSORT and IMMUNCELL AI algorithms were performed to understand the correlation between the two scores and immune activity. We further carried out the efficacy analysis of immunotherapy and targeted drugs in the different TRP score groups. Furthermore, a nomogram was built by integrating various independent prognostic factors and validated its effectiveness in different datasets.ResultsWe identified 487 TRGs combined with GSE104580 and TCGA datasets. Then four novel TRGs (TTK, EPO, SLC7A11, and PON1) were screened out to construct TRD score and TRP score models, and both two scores had good predictive ability in external datasets. Tumors with high TRP score show an immunosuppressive phenotype with more infiltrations of regulatory T cells and macrophages. Immunotherapy and chemotherapy response evaluation revealed patients with a high TRP score demonstrated well reactions to immune checkpoint inhibitors (ICIs) and sorafenib. TRP score, TNM stage, and cancer type were brought into the combined nomogram with optimum prediction.ConclusionsOur research provided dependable and simplified methods for patients with HCC to assess tumors’ susceptibility to TACE refractoriness and prognosis and guide patients’ clinical therapy choices.

Four-quadrant fast compressive tracking of breast ultrasound videos for computer-aided response evaluation of neoadjuvant chemotherapy in mice

Background and objectiveNeoadjuvant chemotherapy (NAC) is a valuable treatment approach for locally advanced breast cancer. Contrast-enhanced ultrasound (CEUS) potentially enables the assessment of therapeutic response to NAC. In order to evaluate the response accurately, quantitatively and objectively, a method that can effectively compensate motions of breast cancer in CEUS videos is urgently needed. MethodsWe proposed the four-quadrant fast compressive tracking (FQFCT) approach to automatically perform CEUS video tracking and compensation for mice undergoing NAC. The FQFCT divided a tracking window into four smaller windows at four quadrants of a breast lesion and formulated the tracking at each quadrant as a binary classification task. After the FQFCT of breast cancer videos, the quantitative features of CEUS including the mean transit time (MTT) were computed. All mice showed a pathological response to NAC. The features between pre- (day 1) and post-treatment (day 3 and day 5) in these responders were statistically compared. ResultsWhen we tracked the CEUS videos of mice with the FQFCT, the average tracking error of FQFCT was 0.65 mm, reduced by 46.72% compared with the classic fast compressive tracking method (1.22 mm). After compensation with the FQFCT, the MTT on day 5 of the NAC was significantly different from the MTT before NAC (day 1) (p = 0.013). ConclusionsThe FQFCT improves the accuracy of CEUS video tracking and contributes to the computer-aided response evaluation of NAC for breast cancer in mice.

T1 mapping as a surrogate marker of chemotherapy response evaluation in patients with osteosarcoma

ObjectivesTo characterize baseline T1 values of tumors, measure changes after the course of chemotherapy, and evaluate its potential as a marker of response assessment in patients with osteosarcoma. Materials and MethodsA total of 35 patients (male:female = 27:8; age = 17.9 ± 6 years; metastatic:localized = 11:24) with biopsy-proven osteosarcoma were analyzed prospectively. All patients underwent magnetic resonance imaging before neoadjuvant chemotherapy (NACT) (baseline) and after NACT completion (follow-up), followed by surgery and histopathological evaluation. Histopathological necrosis served as the gold standard for assessing chemotherapy response (responder: ≥50% necrosis and non-responder: <50% necrosis). Three-dimensional spoiled gradient recalled echo images were acquired with varying flip angles (50, 100, 200, and 300) using a 1.5 Tesla scanner. T1 values were estimated in healthy muscle tissue and tumors at baseline and follow-up, and the relative percentage changes after NACT (ΔT1) were evaluated, and histogram analysis was performed to characterize the T1 value of the tumor and predict the NACT response using the Pearson correlation coefficient (r) and receiver operating characteristic curve analysis. ResultsAt baseline, a significantly higher T1-mean (830.96 ± 193.88 msec versus 683.29 ± 210.00 msec; p = 0.003) and lower T1-skewness (0.86 ± 1.66 versus 1.60 ± 1.55; p = 0.02) were observed in osteosarcoma than healthy tissue. Responder:non-responder ratio was 13:22. At baseline, a significantly higher T1-mean (936.14 ± 193.17 msec versus 768.82 ± 169.25 msec; p = 0.018) and lower T1-skewness (-0.17 ± 0.85 versus 1.47 ± 1.73; p = 0.003) were observed among responders, than non-responders. After NACT, ΔT1 in tumor was significantly higher among responders than non-responders (-27.22 ± 12.17% versus −15.70 ± 18.99%; p = 0.034). ΔT1-mean and ΔT1-skewness after NACT were moderately correlated (r = − 0.4, p = 0.030; r = 0.4, p = 0.011) with histopathological necrosis. For predicting NACT response, T1-mean and T1-skewness jointly produced an area under the curve (AUC) = 0.80 at baseline, and ΔT1-mean and ΔT1-skewness jointly produced AUC = 0.76 after NACT. ConclusionThe mean and skewness of T1 values in osteosarcoma are potential non-invasive imaging markers for chemotherapy response assessment.

Evaluation of metronomic chemotherapy response using diffusion and dynamic contrast-enhanced MRI.

To investigate the feasibility of using diffusion MRI (dMRI) and dynamic contrast-enhanced (DCE) MRI to evaluate the treatment response of metronomic chemotherapy (MCT) in the 4T1 mammary tumor model of locally advanced breast cancer. Twelve Balb/c mice with metastatic breast cancer were divided into treated and untreated (control) groups. The treated group (n = 6) received five treatments of anti-metabolite agent 5-Fluorouracil (5FU) in the span of two weeks. dMRI and DCE-MRI were acquired for both treated and control groups before and after MCT. Immunohistochemically staining and measurements were performed after the post-MRI measurements for comparison. The control mice had significantly (p<0.005) larger tumors than the MCT treated mice. The DCE-MRI analysis showed a decrease in contrast enhancement for the control group, whereas the MCT mice had a more stable enhancement between the pre-chemo and post-chemo time points. This confirms the antiangiogenic effects of 5FU treatment. Comparing amplitude of enhancement revealed a significantly (p<0.05) higher enhancement in the MCT tumors than in the controls. Moreover, the MCT uptake rate was significantly (p<0.001) slower than the controls. dMRI analysis showed the MCT ADC values were significantly larger than the control group at the post-scan time point. dMRI and DCE-MRI can be used as potential biomarkers for assessing the treatment response of MCT. The MRI and pathology observations suggested that in addition to the cytotoxic effect of cell kills, the MCT with a cytotoxic drug, 5FU, induced changes in the tumor vasculature similar to the anti-angiogenic effect.

Early Interim Chemotherapy Response Evaluation by F-18 FDG PET/CT in Diffuse Large B Cell Lymphoma.

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after one cycle of standard chemotherapy in patients with diffuse large B cell lymphoma (DLBCL) was assessed. Prospectively enrolled 51 patients had four PET/CT studies using the same protocol and system: at baseline and after one, three, and six cycles of chemotherapy (PET0, PET1, PET3, PET6). The PET1 and PET6 Deauville five-point score (D5PS) agreed in 60.8%, while PET3 and PET6 D5PS agreed in 90.2%. The absolute and percent changes of peak standard uptake value corrected for lean body mass (SULpeak) compared to baseline were significantly different between PET1 and PET3 (p = 0.001, p < 0.001) and PET1 and PET6 (p = 0.002, p = 0.001), but not between PET3 and PET6 (p = 0.276, p = 0.181). The absolute SULpeak from PET1 predicted treatment failure with accuracy of 78.4% (area under the curve 0.73, p = 0.023). D5PS, SULpeak, and metabolic tumor volume (MTV) were not statistically different between responders versus non-responders, or the one year disease-free versus relapse groups. D5PS and PERCIST responses showed 100% agreement at end-of-therapy. In conclusion, the responses after three and six cycles of therapy showed high degree of agreement. D5PS or MTV after one cycle of chemotherapy could not predict response or one-year disease-free status, but the SULpeak from PET1 was associated with response to first line therapy in DLBCL. Deauville and PERCIST criteria show high concordance.

Texture analysis for chemotherapy response evaluation in osteosarcoma using MR imaging.

The efficacy of MRI-based statistical texture analysis (TA) in predicting chemotherapy response among patients with osteosarcoma was assessed. Forty patients (male: female = 31:9; age = 17.2 ± 5.7 years) with biopsy-proven osteosarcoma were analyzed in this prospective study. Patients were scheduled for three cycles of neoadjuvant chemotherapy (NACT) and diffusion-weighted MRI acquisition at three time points: at baseline (t0), after the first NACT (t1) and after the third NACT (t2) using a 1.5 T scanner. Eight patients (nonsurvivors) died during NACT while 34 patients (survivors) completed the NACT regimen followed by surgery. Histopathological evaluation was performed in the resected tumor to assess NACT response (responder [≤50% viable tumor] and nonresponder [>50% viable tumor]) and revealed nonresponder: responder = 20:12. Apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) parameters, diffusion coefficient (D), perfusion coefficient (D*) and perfusion fraction (f) were evaluated. A total of 25 textural features were evaluated on ADC, D, D* and f parametric maps and structural T1-weighted (T1W) and T2-weighted (T2W) images in the entire tumor volume using 3D TA methods gray-level cooccurrence matrix (GLCM), neighborhood gray-tone-difference matrix (NGTDM) and run-length matrix (RLM). Receiver-operating-characteristic curve analysis was performed on the selected textural feature set to assess the role of TA features (a) as marker(s) of tumor aggressiveness leading to mortality at baseline and (b) in predicting the NACT response among survivors in the course of treatment. Findings showed that the NGTDM features coarseness, busyness and strength quantifying tumor heterogeneity in D, D* and f maps and T1W and T2W images were useful markers of tumor aggressiveness in identifying the nonsurvivor group (area-under-the-curve [AUC] = 0.82-0.88) at baseline. The GLCM features contrast and correlation, NGTDM features contrast and complexity and RLM feature short-run-low-gray-level-emphasis quantifying homogeneity/terogeneity in tumor were effective markers for predicting chemotherapeutic response using D (AUC = 0.80), D* (AUC = 0.80) and T2W (AUC = 0.70) at t0, and D* (AUC = 0.80) and f (AUC = 0.70) at t1. 3D statistical TA features might be useful as imaging-based markers for characterizing tumor aggressiveness and predicting chemotherapeutic response in patients with osteosarcoma.