Concurrent Chemoradiotherapy Response Research Articles

The Neoadjuvant Administration of PD-1 Inhibitor plus Concurrent Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous-Cell Carcinoma

Objective. Programmed cell death-1 (PD-1) inhibitors have shown potency for neoadjuvant therapy in several cancers, while their administration combined with concurrent chemoradiotherapy (CCRT) as a neoadjuvant therapy for locally advanced esophageal squamous-cell carcinoma (ESCC) is seldom reported. The current study aimed to investigate the pathological response, survival, and safety of neoadjuvant PD-1 inhibitor plus CCRT in locally advanced ESCC patients. Methods. Twenty-five locally advanced ESCC patients who underwent PD-1 inhibitor plus CCRT neoadjuvant therapy were retrospectively reviewed. Data regarding radiological response, pathological response, disease-free survival (DFS), overall survival (OS), and adverse events were retrieved. Results. Two (8.0%), 14 (56.0%), 9 (36.0%), and 0 (0.0%) patients had a clinical response of complete response, partial response, stable disease, and progressive disease after neoadjuvant therapy by radiological evaluations, respectively. Notably, 25 (100.0%) patients had successful tumor resections, 24 (96.0%) patients realized R0 resection, and 13 (52.0%) patients achieved pathological complete response (pCR) by pathological evaluations. Regarding survival profiles, the 1-year and 2-year accumulating DFS rates were 90.0% and 74.6%, respectively; then, the 1-year and 2-year accumulating OS rates were 95.5% and 90.4%, respectively. The top prevalent adverse events were fatigue (48.0%), nausea and vomiting (40.0%), leukopenia (36.0%), neutropenia (36.0%), and peripheral neuropathy (36.0%). In addition, grades 3-4 adverse events included peripheral neuropathy (12.0%), nausea and vomiting (4.0%), leukopenia (4.0%), neutropenia (4.0%), anemia (4.0%), and pruritus (4.0%). Conclusion. Neoadjuvant PD-1 inhibitor plus CCRT shows a good efficacy and acceptable tolerance for locally advanced ESCC treatment, but further large-scale study validation is needed.

Comparing deep learning and handcrafted radiomics to predict chemoradiotherapy response for locally advanced cervical cancer using pretreatment MRI

Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer (LACC), but its responsiveness varies among patients. A reliable tool for predicting CRT responses is necessary for personalized cancer treatment. In this study, we constructed prediction models using handcrafted radiomics (HCR) and deep learning radiomics (DLR) based on pretreatment MRI data to predict CRT response in LACC. Furthermore, we investigated the potential improvement in prediction performance by incorporating clinical factors. A total of 252 LACC patients undergoing curative chemoradiotherapy are included. The patients are randomly divided into two independent groups for the training (167 patients) and test datasets (85 patients). Contrast-enhanced T1- and T2-weighted MR scans are obtained. For HCR analysis, 1890 imaging features are extracted and a support vector machine classifier with a five-fold cross-validation is trained on training dataset to predict CRT response and subsequently validated on test dataset. For DLR analysis, a 3-dimensional convolutional neural network was trained on training dataset and validated on test dataset. In conclusion, both HCR and DLR models could predict CRT responses in patients with LACC. The integration of clinical factors into radiomics prediction models tended to improve performance in HCR analysis. Our findings may contribute to the development of personalized treatment strategies for LACC patients.

Peripheral Blood CD8+ CD28+ T Cells as an Independent Predictor of Treatment Response and Survival After Concurrent Chemoradiotherapy in Pediatric High-Grade Glioma Patients.

The tumor immune microenvironment influences the efficiency of concurrent chemoradiotherapy (CCRT) in high-grade glioma (HGG). This study investigated peripheral blood T lymphocyte subsets as clinical indicators of therapeutic response and prognosis in pediatric high-grade glioma (pHGG). This retrospective study included 77 patients with postoperative pHGG who were treated concurrently with temozolomide and external beam radiotherapy between January 1, 2012, and December 31, 2018. The median follow-up was 26 (range: 5-106) months. Peripheral venous blood samples were collected before and after CCRT. The proportions of peripheral blood T lymphocytes and their association with treatment outcome and survival were determined. Sixty-four (83.1%) patients achieved complete remission, partial remission, and stable disease, and 13 (16.9%) patients had progressive disease. Higher CD3+ T cell, CD4+ T cell, and CD8+ CD28+ T cell ratios were predictive of better response, while a higher CD8+ CD28- T cell ratio was predictive of poorer response. Binary logistic regression analysis showed that the CD8+ CD28+ T cell ratio was a significant independent predictor of CCRT response (odds ratio [OR] = 53.521, 95% confidence interval [CI] = 4.294-667.119, P = .002). Univariate and multivariate analysis of prognostic factors associated with survival showed that the CD8+ CD28+ T lymphocyte ratio was a significant independent predictor of progression-free survival (hazard ratio [HR] = 1.80, 95% CI = 1.06-3.08, P = .03), but none of the subsets were significantly associated with overall survival. Peripheral blood T lymphocytes have potential as predictors of CCRT response and prognosis in pHGG.

Predictive Value of the Interaction between CEA and Hemoglobin in Neoadjuvant CCRT Outcomes in Rectal Cancer Patients.

The adoption of neoadjuvant concurrent chemoradiotherapy (CCRT) has reshaped the therapeutic landscape, but response prediction remains challenging. This study investigates the interaction between pre-CCRT carcinoembryonic antigen (CEA) and post-CCRT hemoglobin (Hb) levels in predicting the response of locally advanced rectal cancer (LARC) to CCRT. Retrospective data from 93 rectal cancer patients receiving neoadjuvant CCRT were analyzed. Univariate analyses assessed clinical factors associated with tumor regression grade (TRG) and T-stage outcomes. Machine learning identified predictive biomarkers. Interaction effects between CEA and Hb were explored through subgroup analyses. Post-CCRT Hb varied between pre-CCRT CEA groups. The interaction between pre-CCRT CEA and post-CCRT Hb influenced TRG. Males with normal pre-CCRT CEA and anemia showed better treatment responses. Females with elevated pre-CCRT CEA and post-CCRT anemia exhibited poorer responses. The interaction effect between them was significant, indicating that their relationship with TRG was not additive. Inflammatory biomarkers, WBC, neutrophil count, and post-CCRT platelet level correlated with CCRT response. Contrasting with previous findings, anemia was a predictor of better treatment response in males with normal pre-CCRT CEA. The interaction between pre-CCRT CEA and post-CCRT Hb levels predicts the response of LARC to CCRT. CEA, Hb, and sex should be considered when assessing treatment response. Inflammatory biomarkers contribute to response prediction. Understanding these complex relationships can enhance personalized treatment approaches in rectal cancer patients.

The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy

Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.

Radiomic features derived from pretherapeutic MRI predict chemoradiation response in locally advanced rectal cancer.

The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant concurrent chemoradiotherapy (CRT) followed by surgical excision. Current evidence suggests a favorable prognosis for those with pathological complete response (pCR), and surgery may be spared for them. We trained and validated regression models for CRT response prediction with selected radiomic features extracted from pretreatment magnetic resonance (MR) images to recruit potential candidates for this watch-and-wait strategy. We retrospectively enrolled patients with LARC who underwent pre-CRT MR imaging between 2010 and 2019. Pathological complete response in surgical specimens after CRT was defined as the ground truth. Quantitative features derived from both unfiltered and filtered images were extracted from manually segmented region of interests on T2-weighted images and selected using variance threshold, univariate statistical tests, and cross-validation least absolute shrinkage and selection operator (Lasso) regression. Finally, a regression model using selected features with high coefficients was optimized and evaluated. Model performance was measured by classification accuracies and area under the receiver operating characteristic (AUROC). We extracted 1223 radiomic features from each MRI study of 133 enrolled patients. After tumor excision, 34 (26 %) of 133 patients had pCR in resected specimens. When 25 image-derived features were selected from univariate analysis, classification AUROC was 0.86 and 0.79 with the addition of six clinical features on the hold-out internal validation dataset. When 11 image-derived features were used, the optimized linear regression model had an AUROC value of 0.79 and 0.65 with the addition of six clinical features on the hold-out dataset. Among the radiomic features, texture features including gray level variance, strength, and cluster prominence had the highest coefficient by Lasso regression. Radiomic features derived from pretreatment MR images demonstrated promising efficacy in predicting pCR after CRT. However, radiomic features combined with clinical features did not result in remarkable improvement in model performance.

Performance of Pretreatment MRI-Based Radiomics in Recombinant Human Endostatin Plus Concurrent Chemoradiotherapy Response Prediction in Nasopharyngeal Carcinoma: A Retrospective Study.

To investigate the capability of an Magnetic resonance imaging (MRI) radiomics model based on pretreatment texture features in predicting the short-term efficacy of recombinant human endostatin (RHES) plus concurrent chemoradiotherapy (CCRT) for nasopharyngeal carcinoma (NPC). We retrospectively enrolled 65 patients newly diagnosed as having NPC and treated with RHES + CCRT. A total of 144 texture features were extracted from the MRI before RHES + CCRT treatment of all the NPC patients. The maximum relevance minimum redundancy (mRMR) method was used to remove redundant, irrelevant texture features, and calculate the Rad score of the primary tumor. Multivariable logistic regression was used to select the most predictive features subset, and prediction models were constructed. The performance of the 3 models in predicting the early response of RHES + CCRT for NPC was explored. The diagnostic efficiency of combined model and radiomics model in distinguishing between the effective and the ineffective groups of patients was found to be moderate. The area under the ROC curve (AUC) of the combined model and radiomics model was 0.74 (95% confidence interval [CI]: 0.62-0.86) and 0.71 (95% CI: 0.58-0.84), respectively, with both being higher than the AUC of the clinics model (0.63, 95% CI: 0.49-0.78). Compared with the radiomics model, the combined model showed marginally improved diagnostic performance in predicting RHES + CCRT treatment response. The accuracy of combined model and radiomics model for RHES + CCRT response assessment in NPC were higher than those of the clinics model (0.723, 0.723 vs 0.677). The pretreatment MRI-based radiomics may be a noninvasive and effective method for the prediction of RHES + CCRT early response in patients with NPC.

Serine protease inhibitor Kazal type 1 (SPINK1) promotes proliferation, migration, invasion and radiation resistance in rectal cancer patients receiving concurrent chemoradiotherapy: a potential target for precision medicine

Serine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is known to be associated with inflammation and pathogenesis. The aim in this study was to demonstrate the clinicopathological role and progression of SPINK1 in rectal cancer (RC) patients undergoing concurrent chemoradiotherapy (CCRT). Immunohistochemical staining for SPINK1 protein expression in 111 RC cases revealed high SPINK1 expression was significantly associated with perineural invasion and poor CCRT response in pre-CCRT specimens. In addition, multivariable analyses showed that pre-CCRT SPINK1 expression was a significant prognostic marker of both overall and disease-free survival in RC patients receiving pre-operative CCRT; furthermore, in vitro studies demonstrated SPINK1 interacted with EGFR to promote the abilities of proliferation, migration and invasion attenuated by SPINK1 si-RNA via ERK, p38, and JNK pathways. SPINK1 was also found to regulate radio-resistance in CRC cell lines. In conclusion, SPINK1 expression is an independent prognostic marker in patients receiving pre-operative CCRT, and SPINK1 regulates proliferation, migration and invasion via EGFR-downstream ERK, p38 and JNK pathways. The phenotypes of radiosensitivity that could be reversed with attenuation of SPINK1 levels suggest that targeting SPINK1 might offer a strategy for optimal precision medicine.

Concurrent Chemoradiotherapy-Driven Cell Plasticity by miR-200 Family Implicates the Therapeutic Response of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy with an increasing incidence worldwide. Over the past decade, concurrent chemoradiotherapy (CCRT) with or without surgery is an emerging therapeutic approach for locally advanced ESCC. Unfortunately, many patients exhibit poor response or develop acquired resistance to CCRT. Once resistance occurs, the overall survival rate drops down rapidly and without proper further treatment options, poses a critical clinical challenge for ESCC therapy. Here, we utilized lab-created CCRT-resistant cells as a preclinical study model to investigate the association of chemoradioresistantresistance with miRNA-mediated cell plasticity alteration, and to determine whether reversing EMT status can re-sensitize refractory cancer cells to CCRT response. During the CCRT treatment course, refractory cancer cells adopted the conversion of epithelial to mesenchymal phenotype; additionally, miR-200 family members were found significantly down-regulated in CCRT resistance cells by miRNA microarray screening. Down-regulated miR-200 family in CCRT resistance cells suppressed E-cadherin expression through snail and slug, and accompany with an increase in N-cadherin. Rescuing expressions of miR-200 family members in CCRT resistance cells, particularly in miR-200b and miR-200c, could convert cells to epithelial phenotype by increasing E-cadherin expression and sensitize cells to CCRT treatment. Conversely, the suppression of miR-200b and miR-200c in ESCC cells attenuated E-cadherin, and that converted cells to mesenchymal type by elevating N-cadherin expression, and impaired cell sensitivity to CCRT treatment. Moreover, the results of ESCC specimens staining established the clinical relevance that higher N-cadherin expression levels associate with the poor CCRT response outcome in ESCC patients. Conclusively, miR-200b and miR-200c can modulate the conversion of epithelial–mesenchymal phenotype in ESCC, and thereby altering the response of cells to CCRT treatment. Targeting epithelial–mesenchymal conversion in acquired CCRT resistance may be a potential therapeutic option for ESCC patients.

Usefulness of Short-Term Imaging and Squamous Cell Carcinoma Antigen to Early Predict Response to Concurrent Chemoradiotherapy in Patients With Cervical Cancer.

ObjectiveThe objective is to investigate the factors that can predict early treatment response in patients receiving concurrent chemoradiotherapy (CCRT) for cervical cancer.MethodsWe assessed clinical factors and treatment response in patients who underwent CCRT for cervical cancer at four time points: initial, 2.5 weeks, 6 weeks after starting CCRT, and 3 months after completing CCRT. The final treatment response was determined by positron emission tomography-computed tomography (PET-CT) 3 months after completion of CCRT. Patients were divided into two groups according to the final treatment response: complete response (CR) group or non-CR group. And the early CCRT response prediction model was developed using stepwise multivariate logistic regression analysis.ResultsOf the 62 patients who underwent CCRT for cervical cancer, 57 patients who completed all 4 time points examinations were included in the analyses and classified as CR (n = 32) and non-CR (n = 25) group. Tumor volume and serum squamous cell carcinoma antigen (SCC Ag) of the initial, 2.5 weeks, and 6 weeks after CCRT were significantly associated with the final treatment response. For the early treatment response prediction model, we selected patient age, tumor volume, and SCC Ag measured at initial and 2.5 weeks of CCRT as variables, and the equation of the final model was yielded. Using a cutoff of 0.433, this model had a sensitivity of 72.0%, a specificity of 84.4%, and a probability of 0.8225 (P < .0001).ConclusionShort-term (at 2.5 weeks after starting CCRT) measurements of tumor volume and serum SCC Ag were significant predictors of response to CCRT in patients with cervical cancer.

Utility of RGNEF in the Prediction of Clinical Prognosis in Patients with Rectal Cancer Receiving Preoperative Concurrent Chemoradiotherapy.

Rectal cancer is a heterogeneous malignancy with different clinical responses to preoperative concurrent chemoradiotherapy (CCRT). To discover the significant genes associated with CCRT response, we performed data mining of a transcriptomic dataset (GSE35452), including 46 rectal cancer patients who received preoperative CCRT and underwent standardized curative resection. We identified ARHGEF28 as the most significantly upregulated gene correlated with resistance to CCRT among the genes related to Rho guanyl-nucleotide exchange factor activity (GO:0005085). We enrolled 172 patients with rectal cancer receiving CCRT with radical surgery. The expression of ARHGEF28 encoded protein, Rho guanine nucleotide exchange factor (RGNEF), was assessed using immunohistochemistry. The results showed that upregulated RGNEF immunoexpression was considerably correlated with poor response to CCRT (p = 0.018), pre-CCRT positive nodal status (p = 0.004), and vascular invasion (p < 0.001). Furthermore, high RGNEF expression was significantly associated with worse local recurrence-free survival (p < 0.0001), metastasis-free survival (MeFS) (p = 0.0029), and disease-specific survival (DSS) (p < 0.0001). The multivariate analysis demonstrated that RGNEF immunoexpression status was an independent predictor of DSS (p < 0.001) and MeFS (p < 0.001). Using Gene Ontology enrichment analysis, we discovered that ARHGEF28 overexpression might be linked to Wnt/β-catenin signaling in rectal cancer progression. In conclusion, high RGNEF expression was related to unfavorable pathological characteristics and independently predicted worse clinical prognosis in patients with rectal cancer undergoing CCRT, suggesting its role in risk stratification and clinical decision making.

Dynamic 18F-FDG Total Body PET Imaging as a Predictive Marker of Induction Chemo-Immunotherapy Followed by Concurrent Chemoradiotherapy Response in Locally Advanced Non-Small Cell Lung Cancer

Purpose/Objective(s)The purpose of this study was to evaluate the efficacy of dynamic 18F-FDG total body PET imaging as a predictive maker of induction chemo-immunotherapy followed by concurrent chemoradiotherapy (CCRT) response in locally advanced non-small cell lung cancer (LA-NSCLC) by a prospective study.Materials/MethodsStage IIIA-IIIC NSCLC patients were prospectively enrolled in a prospective total body PETCT study (NCT04654234, GASTO-1067) and a randomized phase II clinical trial (NCT04085250) between September 2020 and December 2020. Patients underwent a dynamic total-body 18F-FDG PET/CT scan before any treatment, after 2 cycles of induction chemo-immunotherapy (docetaxel + cisplatin + nivolumab), then after CCRT. The primary lung tumor, metastatic regional lymph node and inflammatory lymph node before and after treatment were manually delineated by a nuclear medicine physician and a radiation oncologist. Total Body PET was acquired between 0 – 60 mins after the injection of FDG from the subject's feet. Patients was separated into high dynamic FDG metabolic (H-DFM) group and low DFM(L-DFM) group by the scatter plot of SUV-mean and Ki-mean of baseline scan for primary lung tumor. We compared lesion heterogeneity and different image-derived PET metrics including the metabolic tumor volume (MTV), SUV total lesion glycolysis (SUV-TLG), Patlak-derived influx rate constant (Ki) TLG (Ki-TLG).ResultsFifteen patients completed three scans (before treatment, after induction chemo-immunotherapy, after CCRT). Eight patients were in H-DFM group and 7 in L-DFM group by baseline scan. Patients in H-DFM group had significant decreased levels of MTV (P < 0.001), SUV-TLG (P < 0.001) and Ki-TLG (P < 0.001) both in primary lung tumor and metastatic lymph node by the induction chemo-immunotherapy and CCRT. However, patients in L-DFM group only had a significant reduction of MTV in primary lung tumor (P < 0.05). There was no significant difference in the MTV of metastatic lymph node (P > 0.5), the SUV-TLG (P > 0.5) and Ki-TLG (P > 0.5) of primary lung tumor and metastatic lymph node during the treatment course in L-DFM group.ConclusionPatients in H-DFM group had the better treatment response of induction chemo-immunotherapy and CCRT with significant decreased levels of MTV, SUV-TLG and Ki-TLG. Dynamic 18F-FDG Total body PET Imaging could be regarded as a potential predictive marker of induction chemo-immunotherapy and CCRT response in the setting of LA-NSCLC. The purpose of this study was to evaluate the efficacy of dynamic 18F-FDG total body PET imaging as a predictive maker of induction chemo-immunotherapy followed by concurrent chemoradiotherapy (CCRT) response in locally advanced non-small cell lung cancer (LA-NSCLC) by a prospective study. Stage IIIA-IIIC NSCLC patients were prospectively enrolled in a prospective total body PETCT study (NCT04654234, GASTO-1067) and a randomized phase II clinical trial (NCT04085250) between September 2020 and December 2020. Patients underwent a dynamic total-body 18F-FDG PET/CT scan before any treatment, after 2 cycles of induction chemo-immunotherapy (docetaxel + cisplatin + nivolumab), then after CCRT. The primary lung tumor, metastatic regional lymph node and inflammatory lymph node before and after treatment were manually delineated by a nuclear medicine physician and a radiation oncologist. Total Body PET was acquired between 0 – 60 mins after the injection of FDG from the subject's feet. Patients was separated into high dynamic FDG metabolic (H-DFM) group and low DFM(L-DFM) group by the scatter plot of SUV-mean and Ki-mean of baseline scan for primary lung tumor. We compared lesion heterogeneity and different image-derived PET metrics including the metabolic tumor volume (MTV), SUV total lesion glycolysis (SUV-TLG), Patlak-derived influx rate constant (Ki) TLG (Ki-TLG). Fifteen patients completed three scans (before treatment, after induction chemo-immunotherapy, after CCRT). Eight patients were in H-DFM group and 7 in L-DFM group by baseline scan. Patients in H-DFM group had significant decreased levels of MTV (P < 0.001), SUV-TLG (P < 0.001) and Ki-TLG (P < 0.001) both in primary lung tumor and metastatic lymph node by the induction chemo-immunotherapy and CCRT. However, patients in L-DFM group only had a significant reduction of MTV in primary lung tumor (P < 0.05). There was no significant difference in the MTV of metastatic lymph node (P > 0.5), the SUV-TLG (P > 0.5) and Ki-TLG (P > 0.5) of primary lung tumor and metastatic lymph node during the treatment course in L-DFM group. Patients in H-DFM group had the better treatment response of induction chemo-immunotherapy and CCRT with significant decreased levels of MTV, SUV-TLG and Ki-TLG. Dynamic 18F-FDG Total body PET Imaging could be regarded as a potential predictive marker of induction chemo-immunotherapy and CCRT response in the setting of LA-NSCLC.

Radiomic Alterations In Tumor Microenvironment By Induction Chemotherapy Predict Treatment Outcome Of Subsequent Concurrent Chemoradiotherapy For Locally Advanced Hypopharyngeal Cancer

Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, biomarkers to predict CCRT response for selecting larynx-preserving candidates remain lacking. This study aimed to develop an imaging biomarker using changes in radiomic features in tumor microenvironment (TME) by IC to predict treatment outcome of subsequent CCRT in LAHC. From 2006 to 2018, computed tomography (CT) scan images obtained by the same protocol before and after IC in LAHC patients were used to contour the gross tumor volumes (GTVs). By using LIFEx software (V.5.10), 47 delta-radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of TME. The data was divided to training/testing groups in the ratio of 8:2. Least absolute shrinkage and selection operator regression (LASSO) in R language was used to select features for establishing the model generating radiomic score (R score). The cutoff of R score for progression was determined by Youden index method. Multivariate regression model was used to identify prognostic factors for progression free survival (PFS). Hematoxylin and eosin stain of biopsied specimens were reviewed to identify histological phenotype of cancer-associated fibroblast (CAF). Mature (thin, wavy, and small spindle-shaped fibroblasts) and immature (large, plump spindle-shaped with prominent nucleoli) groups were categorized by using cutoff 50%. Total 59 LAHC patients with qualified paired CT images were subjected to delta-radiomic analysis. The median follow-up time was 33.5 (IQR 17.9-74.0) months. A model including 5 radiomic features from delta-GTV to predict better PFS of patients receiving subsequent CCRT was established (likelihood ratio test p < 0.05; Table). R score was validated with all dataset (area under the curve = 0.74). Low R score (< -0.34), but not volume changes of GTVs, was associated with better PFS in both univariate (p < 0.05) and multivariate (p < 0.05) analysis. In TME assessment, the histological phenotype of mature CAF, but not tumor infiltrating lymphocyte, correlated with better PFS. Low R score correlated with mature CAF category (positive and negative predictive values: 100% and 75%, respectively), implying CAF as a putative biological rationale behind delta-radiomics. The established model for TME from radiomic features of delta-GTV after IC might be a potential imaging biomarker to predict clinical outcome of subsequent CCRT in LAHC. Phenotype of CAF in TME may correlate with radiomic alterations and clinical outcome.Abstract 3864; TableThe radiomic features obtained from regression modelCoefficientHazard ratiop valueCONVENTIONAL_HUmin0.00021.00020.83HISTO_Skewness0.24721.28040.02SHAPE_Sphericity13.86051045981.78570.04GLRLM_GLNU-0.00030.99970.25GLZLM_LZLGE-0.00650.99360.64 Open table in a new tab

Potentialities of multi-b-values diffusion-weighted imaging for predicting efficacy of concurrent chemoradiotherapy in cervical cancer patients

BackgroundTo testify whether multi-b-values diffusion-weighted imaging (DWI) can be used to ultra-early predict treatment response of concurrent chemoradiotherapy (CCRT) in cervical cancer patients and to assess the predictive ability of concerning parameters.MethodsFifty-three patients with biopsy proved cervical cancer were retrospectively recruited in this study. All patients underwent pelvic multi-b-values DWI before and at the 3rd day during treatment. The apparent diffusion coefficient (ADC), true diffusion coefficient (Dslow), perfusion-related pseudo-diffusion coefficient (Dfast), perfusion fraction (f), distributed diffusion coefficient (DDC) and intravoxel diffusion heterogeneity index(α) were generated by mono-exponential, bi-exponential and stretched exponential models. Treatment response was assessed based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) at 1 month after the completion of whole CCRT. Parameters were compared using independent t test or Mann-Whitney U test as appropriate. Receiver operating characteristic (ROC) curves was used for statistical evaluations.ResultsADC-T0 (p = 0.02), Dslow-T0 (p < 0.01), DDC-T0 (p = 0.03), ADC-T1 (p < 0.01), Dslow-T1 (p < 0.01), ΔADC (p = 0.04) and Δα (p < 0.01) were significant lower in non-CR group patients. ROC analyses showed that ADC-T1 and Δα exhibited high prediction value, with area under the curves of 0.880 and 0.869, respectively.ConclusionsMulti-b-values DWI can be used as a noninvasive technique to assess and predict treatment response in cervical cancer patients at the 3rd day of CCRT. ADC-T1 and Δα can be used to differentiate good responders from poor responders.

Radiation dose escalation can improve local disease control and survival among esophageal cancer patients with large primary tumor volume receiving definitive chemoradiotherapy.

BackgroundThis study aimed to investigate the correlation between primary tumor volume and cancer failure patterns in esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT) and examine whether increasing radiation dose can improve the outcome.MethodsWe retrospectively reviewed 124 patients with stage III ESCC treated by definitive CCRT. The primary tumor volume calculated from the radiotherapy planning computed tomography scans was correlated to treatment response, time to disease progression, and overall survival. We further analyzed whether a higher radiation dose correlated with better disease control and patient survival.ResultsPatients with poor CCRT response had a larger primary tumor volume than those with good response (97.9 vs 64.3 cm3, P = 0.032). The optimal cutoff value to predict CCRT response was 55.3 cm3. Large primary tumor volume (≥ 55.3 cm3) correlated with shorter time to tumor progression in the esophagus (13.6 vs 48.6 months, P = 0.033) compared with small tumor volume (< 55.3 cm3). For the large esophageal tumors (≥ 55.3 cm3), radiation dose > 60 gray significantly prolonged the time to tumor progression in esophagus (20.3 vs 10.1 months, P = 0.036) and overall survival (12.2 vs 8.0 months, P = 0.030), compared with dose ≤ 60 gray. In contrast, higher radiation dose did not benefit local disease control or overall survival in the small esophageal tumors (< 55.3 cm3).ConclusionLarge primary tumor volume correlates with poor local control and overall survival in ESCC treated with definitive CCRT. Radiation dose > 60 gray can improve the outcomes in patients with large primary tumor. Further prospective dose escalation trials are warranted.

Effect of BRCA1 on the Concurrent Chemoradiotherapy Resistance of Cervical Squamous Cell Carcinoma Based on Transcriptome Sequencing Analysis.

Background Cervical squamous cell carcinoma (CSCC) is the main pathological type of cervical cancer, accounting for 80%–85% of cervical cancer. Owing to concurrent chemoradiotherapy (CCRT) resistance in a subset of CSCC patients, the treatment response is often unsatisfactory. Identifying predictors and therapeutic targets related to cisplatin-based CCRT resistance in CSCC is critical. Methods We reanalyzed GSE56363, an mRNA dataset from the GEO database with 21 patients with locally advanced CSCC, to identify differentially expressed genes (DEGs) related to CCRT resistance. The hub genes were screened from the protein-protein interaction network of DEGs using cytoHubba plug-in of Cytoscape software. Transcriptome sequencing technology was used to compare differential expression between SiHa cells overexpressing BRCA1 compared with control SiHa cells. Functional annotation for DEGs and gene set enrichment analysis (GSEA) was performed to identify DEG-enriched relative signaling pathways to examine the molecular mechanisms of BRCA1 in CCRT resistance of CSCC. qPCR was used to verify the expression of key genes in SiHa/DDP cells. Results A total of 609 DEGs including 223 upregulated DEGs and 386 downregulated DEGs were identified between the complete response to CCRT (CR) and noncomplete response to CCRT (NCR) CSCC patients based on the GSE56363 dataset. Ten hub genes with the highest degrees were identified via the plug-in CytoHubba in Cytoscape: BRCA1, CDCA8, ASPM, CDC45, RAD51, HMMR, CENPF, EXO1, DTL, and ZWINT genes, and BRCA1 ranked first. Through transcriptome sequencing analysis based on GSE141558, 1344 DEGs were identified in BRCA1-overexpressing SiHa cells, including 824 upregulated DEGs and 520 downregulated DEGs. GSEA results showed that CCRT-resistance related signaling pathways, such as the JAK/STAT signaling pathway and the WNT signaling pathway, were differentially enriched in BRCA1-expressing SiHa cells. STAT1, STAT2, and CCND1 were screened as the differentially expressed target genes of BRCA1 and may correlate with resistance of CSCC. qPCR results showed that only STAT1 was significantly increased in SiHa cells with GV230-BRCA1 plasmid transfection. Conclusion BRCA1 overexpression in SiHa cells may upregulate STAT1 to activate the JAK/STAT signaling pathway, suggesting a mechanism for enhanced CCRT resistance.

High EREG Expression Is Predictive of Better Outcomes in Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy

Background/Aim: A great proportion of patients with rectal cancer initially present with locally advanced disease and can potentially benefit from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before surgery. However, risk and clinical outcome stratification remain a great challenge. We aimed to find the potential biomarker to predict the effect of neoadjuvant CCRT on rectal cancer. Methods: We identified epiregulin (EREG) as the most significant predictive marker for neoadjuvant CCRT response from the published rectal cancer transcriptome data set GSE35452. We collected 172 biopsy specimens from rectal cancer patients who received neoadjuvant CCRT followed by radical proctectomy, performed EREG immunohistochemistry, and analyzed the H-scores. We further examined the correlations between the expression level of EREG and clinicopathological features, tumor regression grade, and survival, including disease-specific survival (DSS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MeFS). Results: High EREG expression was significantly related to early pretreatment (pre-Tx) and posttreatment (post-Tx) tumor status (T1, T2, p = 0.047 and p < 0.001), pre-Tx and post-Tx negative nodal status (N0, p < 0.001 and p = 0.004), less vascular and perineurial invasion (p = 0.015 and p = 0.023), and higher tumor regression grade (p < 0.001). In the survival analysis, high EREG expression was significantly associated with better DSS (p < 0.0001), LRFS (p = 0.0004), and MeFS (p < 0.0001). In the multivariate analysis, high EREG expression remained prognostically significant for better DSS (p = 0.003; hazard ratio: 5.599). Conclusion: These data suggest that EREG is a potential predictive marker and therapeutic target in rectal cancer patients receiving neoadjuvant CCRT.

Development and validation of a radiomics signature on differentially expressed features of 18F-FDG PET to predict treatment response of concurrent chemoradiotherapy in thoracic esophagus squamous cell carcinoma

Background and purposeTo investigate potential image markers for early prediction of treatment response on thoracic esophagus squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CCRT). Materials and methods159 thoracic ESCC patients enrolled from two institutions were divided into training and validation sets. A total of 944 radiomics features were extracted from pretreatment 18F-FDG PET images. We first performed the inter-observer reproducibility test in 10 pairs of patients (responders vs. nonresponders), and the limma package was used to identify differentially expressed features (DEFs). Then the least absolute shrinkage and selection operator (LASSO) logistic regression model with 10-fold cross-validation was used to construct a treatment response related radiomics signature. Finally, the performance was assessed in both sets with receiver operating characteristic (ROC) curves and Kaplan-Meier analysis. ResultsAfter the inter-observer test, 691 features were considered reproducible and been retained (ICC > 0.9). 61 DEFs were selected from limma and entered into the LASSO logistic regression model. The radiomics signature was significantly associated with treatment response in the training (p < 0.001) and validation set (p = 0.026), which achieved area under curve (AUC) values of 0.844 and 0.835, respectively. Delong test results of two ROCs showed no significant difference (p = 0.918). The cut-off value of the radiomics signature could successfully divide patients into high-risk and low-risk groups in both sets. ConclusionThis study indicated that the proposed radiomics signature could be a useful image marker to predict the therapeutic response of thoracic ESCC patients treated with CCRT.

Clinical Factors to Predict the Response to Concurrent Chemoradiotherapy and Survival in Esophageal Cancer Patients.

Background/AimsSeveral clinical factors have been used to predict the response for concurrent chemoradiotherapy (CCRT); however, these factors are insufficient for prognostic predictions. We investigated clinical factors to assess whether they could be used to predict the response to CCRT and the survival of patients with esophageal cancer.MethodsPatients with esophageal cancer underwent CCRT from January 2005 to December 2015. Response to CCRT was classified as progressive disease (PD), stationary disease (SD), partial remission (PR), or complete remission (CR). Factors to predict the response to CCRT and patient survival were subsequently investigated.ResultsA total of 535 esophageal cancer patients underwent CCRT. Four hundred ninety-three patients were followed up, and patient outcomes were investigated. In the adjusted analysis, patients with advanced stage disease (relative risk [RR], 0.28 in stage III and 0.12 in stage IV compared to stage I), poor performance status, circumferential involvement (RR, 0.61), and male sex (RR, 0.31) were less likely to achieve CR. Advanced stage disease (hazard ratio [HR], 1.71 in stage III/IV), poor CCRT response (HR, 2.82 in PR, 4.47 in SD, 4.77 in PD compared to CR), and poor performance status (HR, 1.38 in ECOG 2–4) were found to increase mortality.ConclusionsAdvanced stage disease, poor performance status, male sex, and circumferential involvement were independent predictive factors for a poor response to CCRT. Advanced stage, poor performance status, and poor CCRT response were independent factors for decreased survival.

Preoperative endoscopic tattooing technique improved lymph node retrieval in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy

AimsTo describe the clinical utility of lymph node retrieval and prognostic value of tattooing in rectal cancer (RC) patients undergoing neoadjuvant concurrent chemoradiotherapy (CCRT).MethodsA total 97 RC patients underwent preoperative...