Genomic and Glycolytic Entropy Are Reliable Radiogenomic Heterogeneity Biomarkers for Non-Small Cell Lung Cancer.

Radiogenomic heterogeneity features in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) have become popular in non-small cell lung cancer (NSCLC) research. However, the reliabilities of genomic heterogeneity features and of PET-based glycolytic features in different image matrix sizes have yet to be thoroughly tested. We conducted a prospective study with 46 NSCLC patients to assess the intra-class correlation coefficient (ICC) of different genomic heterogeneity features. We also tested the ICC of PET-based heterogeneity features from different image matrix sizes. The association of radiogenomic features with clinical data was also examined. The entropy-based genomic heterogeneity feature (ICC = 0.736) is more reliable than the median-based feature (ICC = -0.416). The PET-based glycolytic entropy was insensitive to image matrix size change (ICC = 0.958) and remained reliable in tumors with a metabolic volume of <10 mL (ICC = 0.894). The glycolytic entropy is also significantly associated with advanced cancer stages (p = 0.011). We conclude that the entropy-based radiogenomic features are reliable and may serve as ideal biomarkers for research and further clinical use for NSCLC.

Predicting the risk of interval distant metastases in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy.

BACKGROUND: This study was conducted to identify risk factors for distant interval metastases (IM) in patients with esophageal squamous cell carcinoma (ESCC) who underwent chemoradiotherapy (CRT). METHODS: We retrospectively reviewed the clinical records of 358 patients with ESCC treated with CRT between 2006 and 2017. Distant IM were defined as systemic metastases developing during or shortly after CRT and identified during the restaging work-up period. A risk prediction nomogram for distant IM was developed based on independent pretreatment risk factors identified using multivariable logistic regression analysis. RESULTS: Distant IM occurred in 26 (7.3%) patients and had a significant adverse impact on survival (median survival: 8.7 months). The most common site of distant IM was the lung (n = 9), followed by non-regional lymph nodes (n = 8) and the bone (n = 8). Multivariable logistic regression analysis revealed that high baseline tumor SUVmax values were independently associated with an increased risk of distant IM (odds ratio [OR] = 1.059, p = 0.019), whereas older age was an independent protective factor (OR = 0.946, p = 0.032). A nomogram based on age, tumor SUVmax, tumor length, and the chemotherapy regimen showed a good predictive performance (c-statistic = 0.761), which was internally validated using 200 bias-corrected bootstrap replicates (c-statistic = 0.71). CONCLUSION: Distant IM were identified in 7.3% of patients with ESCC undergoing CRT. The nomogram described in our study may prove useful to predict the risk of distant IM in this patient group.

Prospective comparison of early interim 18F-FDG-PET with 18F-FLT-PET for predicting treatment response and survival in metastatic breast cancer.

BACKGROUND: To compare the value of interim 18F-FLT-PET and 18F-FDG-PET for predicting treatment outcomes in patients with metastatic breast cancer after salvage therapy. METHODS: Patients with metastatic breast cancer received PET/CT using 18F-FLT and 18F-FDG at baseline, after the 1st and 2nd cycle of systemic chemotherapy. The clinical response was classified according to Response Evaluation Criteria in Solid Tumors 1.1 based on contrast-enhanced CT after 3 months of systemic chemotherapy. The metabolic response on PET was assessed according to European Organization for Research and Treatment of Cancer criteria or PET Response Criteria in Solid Tumors (PERCIST) and was correlated to the clinical response, overall survival (OS), and progression-free survival (PFS). RESULTS: Twenty-five patients entered final analysis. On 18F-FDG-PET, clinical responders after 2 chemotherapy cycles (post-2c) had a significantly greater reduction of maximal standardized uptake value (SUV) and the peak SUV corrected for lean body mass (SULpeak) of the tumor than non-responders (P = 0.030 and 0.003). Metabolic response determined by PERCIST on post-2c 18F-FDG-PET showed a high area under the receiver operating characteristics curve of 0.801 in predicting clinical response (P = 0.011). Patients who were metabolic responders by PERCIST on post-2c 18F-FDG-PET had a significantly longer PFS (53.8% vs. 16.7%, P = 0.014) and OS (100% vs. 47.6%, P = 0.046) than non-responders. Survival differences between responders and non-responders in the interim 18F-FLT-PET were not significant. CONCLUSIONS: 18F-FLT-PET failed to show an advantage over 18F-FDG-PET in predicting the treatment response and survival in patients with metastatic breast cancer. Assessment of treatment outcome by interim 18F-FDG-PET may aid treatment. TRIAL REGISTRATION: The study was retrospectively registered on 02/06/2020 on Clinicaltrials.gov (identifier NCT04411966 ).

Comparison of 18F-FDG PET/MRI, MRI, and 18F-FDG PET/CT for the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma.

PURPOSE: In this prospective study, we sought to compare the clinical utility of fluorodeoxyglucose PET/MRI, MRI, and PET/CT in the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC). METHODS: We examined 198 consecutive patients with biopsy-proven OHSCC who agreed to receive chemoradiation. All patients underwent pretreatment PET/MRI and PET/CT on the same day. Patients were followed-up for a minimum of 12 months or until death. The McNemar's test and receiver-operating characteristic (ROC) curves were used to compare sensitivity/specificity and the diagnostic capabilities of PET/MRI, MRI, and PET/CT, respectively. RESULTS: We identified 55 patients (27.7%) who had synchronous cancers and/or distant metastases (number of involved sites: 83). The results of site-based analysis revealed that the sensitivity of PET/MRI was 15.7% higher than that of MRI (73.5% versus 57.8%, p < 0.001) and 3.6% higher compared with PET/CT (73.5% versus 69.9%, p = 0.083), whereas the sensitivity of PET/CT was 12.1% higher than that of MRI (69.9% versus 57.8%, p = 0.012). On a patient-basis, ROC curve analysis demonstrated that PET/MRI yielded a greater area under curve than MRI (0.930 versus 0.905, p = 0.023). There were no significant differences in terms of diagnostic capability between MRI and PET/CT (0.905 versus 0.917, p = 0.469) and between PET/MRI and PET/CT (0.930 versus 0.917, p = 0.062). CONCLUSIONS: In our cohort, PET/MRI showed a significantly higher diagnostic capability than MRI and no significant difference compared with PET/CT for the detection of synchronous cancers or distant metastases in patients with OHSCC.

Value of early evaluation of treatment response using 18F-FDG PET/CT parameters and the Epstein-Barr virus DNA load for prediction of outcome in patients with primary nasopharyngeal carcinoma.

PURPOSE: To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) using 18F-FDG PET-derived parameters and the Epstein-Barr virus (EBV) DNA titre in outcome prediction in patients with primary nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with primary NPC were prospectively enrolled. All patients underwent 18F-FDG PET/CT before and during CCRT. The plasma EBV DNA titre was measured along with the PET/CT-derived parameters. Changes in EBV DNA titre and PET/CT-derived parameters during CCRT were analysed in relation to response to treatment, recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of >0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p < 0.001 versus p = 0.175). CONCLUSION: Early evaluation of response to CCRT using 18F-FDG PET-derived parameters and the EBV DNA titre can predict outcome in patients with primary NPC. A combination of interim PET parameters and the EBV DNA titre enables better stratification of patients into subgroups with different survival rates.

Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS. CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.

Clinical utility of simultaneous whole-body 18F-FDG PET/MRI as a single-step imaging modality in the staging of primary nasopharyngeal carcinoma.

PURPOSE: Both head and neck magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) play a crucial role in the staging of primary nasopharyngeal carcinoma (NPC). In this study, we sought to prospectively investigate the clinical utility of simultaneous whole-body 18F-FDG PET/MRI for primary staging of NPC patients. METHODS: We examined 113 patients with histologically confirmed NPC who underwent pretreatment, simultaneous whole-body PET/MRI and PET/CT for primary tumor staging. The images obtained with the different imaging modalities were interpreted independently and compared with each other. RESULTS: PET/MRI increased the accuracy of head and neck MRI for assessment of primary tumor extent in four patients via addition of FDG uptake information to increase the conspicuity of morphologically subtle lesions. PET/MR images were more discernible than PET/CT images for mapping tumor extension, especially intracranial invasion. Regarding the N staging assessment, the sensitivity of PET/MRI (99.5%) was higher than that of head and neck MRI (94.2%) and PET/CT (90.9%). PET/MRI was particularly useful for distinguishing retropharyngeal nodal metastasis from adjacent nasopharyngeal tumors. For distant metastasis evaluation, PET/MRI exhibited a similar sensitivity (90% vs. 86.7% vs. 83.3%), but higher positive predictive value (93.1% vs. 78.8% vs. 83.3%) than whole-body MRI and PET/CT, respectively. CONCLUSIONS: For tumor staging of NPC, simultaneous whole-body PET/MRI was more accurate than head and neck MRI and PET/CT, and may serve as a single-step staging modality.

Dynamic contrast-enhanced MRI, diffusion-weighted MRI and 18F-FDG PET/CT for the prediction of survival in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation.

OBJECTIVES: We prospectively investigated the roles of pretreatment dynamic contrast-enhanced MR imaging (DCE-MRI), diffusion-weighted MR imaging (DWI) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT for predicting survival of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with chemoradiation. METHODS: Patients with histologically proven OHSCC and neck nodal metastases scheduled for chemoradiation were eligible. Clinical variables as well as DCE-MRI-, DWI- and 18F-FDG PET/CT-derived parameters of the primary tumours and metastatic neck nodes were analysed in relation to 3-year progression-free survival (PFS) and overall survival (OS) rates. RESULTS: Eighty-six patients were available for analysis. Multivariate analysis identified the efflux rate constant (K ep)-tumour < 3.79 min-1 (P = 0.001), relative volume of extracellular extravascular space (V e)-node < 0.23 (P = 0.004) and SUVmax-tumour > 19.44 (P = 0.025) as independent risk factors for both PFS and OS. A scoring system based upon the sum of each of the three imaging parameters allowed stratification of our patients into three groups (patients with 0/1 factor, patients with 2 factors and patients with 3 factors, respectively) with distinct PFS (3-year rates = 72 %, 38 % and 0 %, P < 0.0001) and OS (3-year rates = 81 %, 46 % and 20 %, P < 0.0001). CONCLUSIONS: K ep-tumour, V e-node and SUVmax-tumour were independent prognosticators for OHSCC treated with chemoradiation. Their combination helped survival stratification. KEY POINTS: • K ep -tumour, V e -node and SUV max -tumour are independent predictors of survival rates. • The combination of these three prognosticators may help stratification of survival. • MRI and FDG-PET/CT play complementary roles in prognostication of head and neck cancer.

Predictors of pathological complete response to neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUNDS: In this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC). METHODS: Pre-nCRT parameters in ESCC patients treated between 1999 and 2006 were analyzed to identify predictors of pCR. All patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam radiation followed by scheduled esophagectomy. Variables were analyzed using univariate and multivariate analyses with pCR as the dependent variable. Estimated pCR rate was calculated with a regression model. RESULTS: Fifty-nine (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient factors (age, smoking status, drinking history and hypertension), one pre-nCRT parameter (tumor length) as significant predictors of pCR (all P <0.05). On multivariate analysis, tumor length ≤3 cm (favorable, odds ratio (OR): 4.85, P = 0.001), patient age >55 years (favorable, OR: 1.95, P = 0.035), and being a non-smoker (favorable, OR: 3.6, P = 0.003) were independent predictors of pCR. The estimated pCR rates based on a logistic regression including those three predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12% for patients with 3, 2, 1 and 0 predictors, respectively. CONCLUSION: Age, smoking habit and tumor length were important pCR predictors. These factors may be used to predict outcomes for ESCC patients receiving nCRT, to develop risk-adapted treatment strategies, and to select patients who could participate in trials on new therapies.

Interval between neoadjuvant chemoradiotherapy and surgery for esophageal squamous cell carcinoma: does delayed surgery impact outcome?

BACKGROUND: Although esophagectomy traditionally is recommended to perform within 8 weeks after neoadjuvant chemoradiotherapy (nCRT), data from neoadjuvantly treated rectal cancer patients demonstrate that delayed surgery ([8 weeks) can maximize the effect of CRT. Despite these promising data, investigators are concerned that delayed surgery may lead to tumor repopulation. We report the impact of delayed surgery in patients with esophageal cancer who were treated with nCRT. METHODS: We retrospectively studied 276 esophageal cancer patients treated with nCRT and surgery between 2002 and 2008. We compared perioperative complication, rate of pathological complete response (pCR), distribution of tumor regression grade (TRG), and overall survival (OS) in patients who underwent surgery within 8 weeks (group A) and after 8 weeks (group B) after nCRT. RESULTS: There were 138 patients in each group with similar pre/post-nCRT characteristics. Delayed surgery did not result in lower surgical risk or higher pCR rate. Survival outcome also did not improve following a longer surgery interval (5-year OS: group A vs. group B, 29 vs. 23 %; P = 0.3). On the contrary, a subgroup analysis showed that delayed surgery might be hazardous, especially in patients who demonstrate a good response after nCRT. The amount of residual cancer, as measured by TRG, increased significantly after a longer surgical interval (P = 0.024). Survival also decreased after a longer surgical interval (5-year OS B8 vs. [8 weeks, 50 vs. 35 %; P = 0.038). CONCLUSIONS: After nCRT, esophagectomy should be performed within 8 weeks, especially in patients with good response.

Baseline and interim [18F]FDG-PET/MRI to assess treatment response and survival in patients with M0 esophageal squamous cell carcinoma treated by curative-intent therapy.

BACKGROUND: To investigate the value of [18F]FDG-PET/MRI in predicting treatment response and survival in patients with primary M0 esophageal squamous cell carcinoma. METHODS: Patients with esophageal squamous cell carcinoma received [18F]FDG-PET/MRI at baseline and during neoadjuvant or definitive chemoradiotherapy. The treatment response was classified according to the Response Evaluation Criteria for Solid Tumors 1.1. We used Kaplan-Meier and Cox regression analyses to assess the association between PET/MRI parameters and overall survival (OS) or progression-free survival (PFS). RESULTS: We included 40 M0 patients in the final analysis. The volume transfer constant (Ktrans) from baseline PET/MRI (area under the curve (AUC) = 0.688, P = 0.034) and total lesion glycolysis (TLG) from baseline PET/MRI (AUC = 0.723, P = 0.006) or interim PET/MRI (AUC = 0.853, P < 0.001) showed acceptable AUC for predicting treatment response. The TLG from interim PET/MRI (interim TLG, P < 0.001) and extracellular volume fraction (Ve) on interim PET/MRI (interim Ve, P = 0.001) were identified as independent prognostic factors for OS. Baseline Ve (P = 0.044) and interim TLG (P = 0.004) were significant predictors of PFS. The c-indices of the prognostic models combining interim TLG with Ve for predicting OS, and baseline Ve and interim TLG for predicting PFS were 0.784 and 0.699, respectively. These values were significantly higher than the corresponding c-indices of the TNM staging system (P = 0.002 and P = 0.047, respectively). CONCLUSIONS: Combining the baseline and interim [18F]FDG-PET/MRI qualitative imaging parameters aids in predicting the prognosis of patients with M0 esophageal squamous cell carcinoma. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (identifier: NCT05855291 and NCT05855278).

18F-Fluorodeoxyglucose PET/CT for Early Prediction of Outcomes in Patients with Advanced Lung Adenocarcinomas and EGFR Mutations Treated with First-Line EGFR-TKIs.

This study aims to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in early prediction of response and survival following epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy in patients with advanced lung adenocarcinomas and EGFR mutations. Thirty patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKIs were prospectively evaluated between November 2012 and May 2015. EGFR mutations were quantified by delta cycle threshold (dCt). 18F-FDG PET/CT was performed before and 2 weeks after treatment initiation. PET response was assessed based on PET Response Criteria in Solid Tumors (PERCIST). Baseline and percentage changes in the summed standardized uptake value, metabolic tumor volume (bsumMTV and ΔsumMTV, respectively), and total lesion glycolysis of ≤5 target lesions/patient were calculated. The association between parameters (clinical and PET) and non-progression disease after 3 months of treatment in CT based on the Response Evaluation Criteria in Solid Tumors Version 1.1 (nPD3mo), progression-free survival (PFS), and overall survival (OS) were tested. The median follow-up time was 19.6 months. The median PFS and OS were 12.0 and 25.3 months, respectively. The PERCIST criteria was an independent predictor of nPD3mo (p = 0.009), dCt (p = 0.014) and bsumMTV (p = 0.014) were independent predictors of PFS, and dCt (p = 0.014) and ΔsumMTV (p = 0.005) were independent predictors of OS. 18F-FDG PET/CT achieved early prediction of outcomes in patients with advanced lung adenocarcinomas and EGFR mutations receiving EGFR-TKIs.

Tumor glycolytic heterogeneity improves detection of regional nodal metastasis in patients with lung adenocarcinoma.

OBJECTIVE: The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma. METHODS: We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS). RESULTS: The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001). CONCLUSIONS: Our preliminary results show that the primary tumor entropy may improve 18F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma.

Prospective Investigation of 18FDG-PET/MRI with Intravoxel Incoherent Motion Diffusion-Weighted Imaging to Assess Survival in Patients with Oropharyngeal or Hypopharyngeal Carcinoma.

To prospectively investigate the prognostic value of 18F-FDG PET/MRI in patients with oropharyngeal or hypopharyngeal squamous cell carcinomas (OHSCC) treated by chemoradiotherapy. The study cohort consisted of patients with OHSCC who had undergone integrated PET/MRI prior to chemoradiotherapy or radiotherapy. Imaging parameters derived from intravoxel incoherent motion (IVIM), dynamic contrast-enhanced MRI (DCE-MRI), and 18F-FDG PET were analyzed in relation to overall survival (OS) and recurrence-free survival (RFS). In multivariable analysis, T classification (p < 0.001), metabolic tumor volume (p = 0.013), and pseudo-diffusion coefficient (p = 0.008) were identified as independent risk factors for OS. The volume transfer rate constant (p = 0.015), initial area under the curve (p = 0.043), T classification (p = 0.018), and N classification (p = 0.018) were significant predictors for RFS. The Harrell's c-indices of OS and RFS obtained from prognostic models incorporating clinical and PET/MRI predictors were significantly higher than those derived from the traditional TNM staging system (p = 0.001). The combination of clinical risk factors with functional parameters derived from IVIM and DCE-MRI plus metabolic PET parameters derived from 18F-FDG PET in integrated PET/MRI outperformed the information provided by traditional TNM staging in predicting the survival of patients with OHSCC.

MRI Radiomics for Predicting Survival in Patients with Locally Advanced Hypopharyngeal Cancer Treated with Concurrent Chemoradiotherapy.

A reliable prognostic stratification of patients with locally advanced hypopharyngeal cancer who had been treated with concurrent chemoradiotherapy (CCRT) is crucial for informing tailored management strategies. The purpose of this retrospective study was to develop robust and objective magnetic resonance imaging (MRI) radiomics-based models for predicting overall survival (OS) and progression-free survival (PFS) in this patient population. The study participants included 198 patients (median age: 52.25 years (interquartile range = 46.88-59.53 years); 95.96% men) who were randomly divided into a training cohort (n = 132) and a testing cohort (n = 66). Radiomic parameters were extracted from post-contrast T1-weighted MR images. Radiomic features for model construction were selected from the training cohort using least absolute shrinkage and selection operator-Cox regression models. Prognostic performances were assessed by calculating the integrated area under the receiver operating characteristic curve (iAUC). The ability of radiomic models to predict OS (iAUC = 0.580, 95% confidence interval (CI): 0.558-0.591) and PFS (iAUC = 0.625, 95% CI = 0.600-0.633) was validated in the testing cohort. The combination of radiomic signatures with traditional clinical parameters outperformed clinical variables alone in the prediction of survival outcomes (observed iAUC increments = 0.279 [95% CI = 0.225-0.334] and 0.293 [95% CI = 0.232-0.351] for OS and PFS, respectively). In summary, MRI radiomics has value for predicting survival outcomes in patients with hypopharyngeal cancer treated with CCRT, especially when combined with clinical prognostic variables.

Association of early changes of circulating cancer stem-like cells with survival among patients with metastatic breast cancer.

Background: This study aimed to investigate the role of circulating tumor cells (CTCs) and circulating cancer stem-like cells (cCSCs) before and after one cycle of chemotherapy and assessed the effects of early changes in CTCs and cCSCs on the outcomes of patients with metastatic breast cancer. Methods: Patients with stage IV invasive ductal carcinoma of the breast who received first-line chemotherapy between April 2014 and January 2016 were enrolled. CTCs and cCSCs were measured before the first cycle of chemotherapy (baseline) and on day 21, before the second cycle of chemotherapy commenced; a negative selection strategy and flow cytometry protocol were employed. Results: CTC and cCSC counts declined in 68.8 and 45.5% of patients, respectively. Declines in CTCs and cCSCs following the first chemotherapy cycle were associated with superior chemotherapy responses, longer progression-free survival (PFS), and longer overall survival (OS). An early decline in cCSCs remained an independent prognostic indicator for OS and PFS in multivariate analysis. Conclusions: A cCSC decline after one cycle of chemotherapy for metastatic breast cancer is predictive of a superior chemotherapy response and longer PFS and OS, implying that cCSC dynamic monitoring may be helpful in early prediction of treatment response and prognosis.

PET/CT and 3-T whole-body MRI in the detection of malignancy in treated oropharyngeal and hypopharyngeal carcinoma.

PURPOSE: We performed a prospective comparison of the diagnostic capability of integrated fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (PET/CT), 3-T whole-body magnetic resonance imaging (WB-MRI) and their combination in detecting malignancy in treated oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC). METHODS: Seventy-nine OHSCC patients at a high risk of residual disease or suspected to have recurrence after the completion of chemoradiation were included in the study. All patients underwent PET/CT and WB-MRI within 10 days of each other. Histology and follow-up data were used as the reference standard. The McNemar test was used to compare sensitivity and specificity, while the area under the receiver-operating characteristic curve (AUC) was used for comparison of diagnostic capabilities. RESULTS: Twenty-nine patients (36.7%) had residual/recurrent tumours or second primary tumours. Overall, there was a trend towards increased sensitivity and diagnostic capability for PET/CT compared with WB-MRI (72.4 vs 55.2%, p = 0.13; 0.826 vs 0.753, p = 0.24, respectively). The diagnostic capability of combined interpretation of PET/CT and WB-MRI was similar to PET/CT alone (0.827 vs 0.826, p = 0.97) but was significantly higher than WB-MRI alone (0.827 vs 0.753, p = 0.04). CONCLUSION: PET/CT showed a trend towards higher diagnostic capability than 3-T WB-MRI in detecting residual/recurrent tumours or second primary tumours in OHSCC. The combined use of PET/CT and WB-MRI provided more added value to WB-MRI alone than to PET/CT alone. Additional PET/CT can be useful in patients with questionable MRI findings of malignancy.

¹8F-FDG PET/CT and 3.0-T whole-body MRI for the detection of distant metastases and second primary tumours in patients with untreated oropharyngeal/hypopharyngeal carcinoma: a comparative study.

PURPOSE: The aim of this prospective study was to compare the diagnostic value of (18)F-FDG PET/CT and 3.0-T whole-body MRI (WB-MRI) for the assessment of distant metastases and second primary cancer (SPC) in patients with untreated oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC). METHODS: A total of 103 patients were enrolled. All participants underwent 3.0-T WB-MRI and (18)F-FDG PET/CT. The diagnostic capabilities of the two imaging modalities were compared using the area under the receiver-operating-characteristic curve. Histology and follow-up data were used as the reference standard. RESULTS: Of the 103 patients, 18 (17.5%) were found to have either distant metastases or SPC. A total of 21 sites were involved. On a lesion-based analysis, (18)F-FDG PET/CT showed a trend toward a higher sensitivity than WB-MRI (81.0% vs. 61.9%, P = 0.125). The area under the curve (AUC) for PET/CT was also higher than for WB-MRI, although not significantly so (0.932 vs. 0.866, P = 0.189). On a patient-based analysis, the sensitivity of WB-MRI was lower than that of PET/CT (66.7% vs. 83.3%, P = 0.625). In terms of diagnostic capability, the AUC was higher for PET/CT than WB-MRI (0.886 vs. 0.813, P = 0.355). The maximal SUV of the regional lymph nodes (SUVn) above the median value (8.7 g/ml) was significantly associated with the occurrence of distant metastasis (P = 0.026). CONCLUSION: (18)F-FDG PET/CT showed a consistent trend toward higher sensitivity and diagnostic capability than 3.0-Tesla WB-MRI for the detection of distant metastases and SPCs in patients with untreated OHSCC. Our data also suggest that SUVn assessed by PET/CT can provide additional information for the prediction of distant metastases.

Multiparametric positron emission tomography/magnetic resonance imaging in nasopharyngeal carcinoma: Correlations between magnetic resonance imaging functional parameters and 18F-fluorodeoxyglucose positron emission tomography imaging biomarkers and their predictive value for treatment failure.

OBJECTIVES: The clinical significance of positron emission tomography/magnetic resonance imaging (PET/MRI) functional parameters in nasopharyngealcarcinoma (NPC) remains unclear. The purpose of this prospective study was two-fold: (1) to investigate the associations between simultaneously acquired PET/MRI perfusion, diffusion, and glucose metabolism parameters in patients with NPC and (2) to analyze their predictive value with respect to treatment failure. MATERIALS AND METHODS: We enrolled 85 patients with primary NPC who simultaneously underwent18F-fluorodeoxyglucose PET/CT and PET/MRI before definitive treatment. The following variables were determined: (1) functional parameters from the MRI component, including perfusion values (Ktrans ,kep ,ve , and initial area under the enhancement curve) and apparent diffusion coefficient (ADC) values, and (2) PET parameters, including metabolic tumor volume (MTV). The reciprocal interrelationships between these parameters and their correlations with treatment failure were examined. RESULTS: We observed significant negative associations between Ktrans and ADC (r = -0.215, P = 0.049) as well as between ve and ADC (r = -0.22, P = 0.04). Correlations between PET and MRI functional parameters were not statistically significant. Treatment failures were observed in 21.2% of patients without distant metastases. Multivariate analysis identified ve as a significant independent predictor for treatment failure (P = 0.022), whereas MTV showed a borderline significance (P = 0.095). Patients in whom both ve and MTV values were increased had a significantly higher rate of treatment failure (62.5%) than those with either one (21.9%) or no (7.7%) increased parameter (P = 0.004). CONCLUSION: Correlation analyses revealed complex interrelationships among PET and MRI indices measured in patients with NPC. These parameters may have a complementary role in predicting treatment failure in this clinical setting.

Combing MRI Perfusion and 18F-FDG PET/CT Metabolic Biomarkers Helps Predict Survival in Advanced Nasopharyngeal Carcinoma: A Prospective Multimodal Imaging Study.

We prospectively investigated the prognostic value of imaging parameters for nasopharyngeal carcinoma (NPC) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography (18F-FDG PET)/computed tomography (CT). Patients with stage III-IVb NPC underwent F-FDG PET/CT, DCE-MRI, and DWI before treatment. Kaplan-Meier and Cox-regression analyses were used to assess associations of PET and MRI imaging biomarkers with overall survival (OS) and recurrence-free survival (RFS). We used independent prognosticators to establish prognostic models; model performance was examined using Harrell's concordance index (c-index). Sixty-one patients were available for analysis, as 13 patients died and 20 experienced recurrence. Total lesion glycolysis (TLG) (p = 0.002) from PET/CT and the initial area under the curve (iAUC) (p = 0.036) from DCE-MRI were identified as independent prognosticators of OS; Epstein-Barr virus (EBV) DNA (p = 0.027), the extracellular volume fraction (Ve) (p = 0.027) from DCE-MRI, and TLG/iAUC (p = 0.025) were significant predictors of RFS. The c-indices of the prognostic models incorporating TLG + iAUC in predicting OS and incorporating EBV DNA + Ve + TLG/iAUC in predicting RFS were 0.79 and 0.76, respectively. These were significantly higher than the corresponding c-indices of the TNM staging system (p = 0.047 and 0.025, respectively); they were also higher than those of models with only MRI or PET biomarkers. In conclusion, the combination of pretreatment DCE-MRI and 18F-FDG PET/CT imaging biomarkers helps survival prediction in advanced NPC. Integrating MRI perfusion with PET metabolism and plasma EBV information may aid clinicians in planning the optimal personalized management strategy.