Pretherapeutic Assessment of Pancreatic Cancer: Comparison of FDG PET/CT Plus Delayed PET/MR and Contrast-Enhanced CT/MR

PurposeThis study aims to determine the diagnostic performance of whole-body FDG PET/CT plus delayed abdomen PET/MR imaging in the pretherapeutic assessment of pancreatic cancer in comparison with that of contrast-enhanced (CE)-CT/MR imaging.Materials and MethodsForty patients with pancreatic cancer underwent nonenhanced whole-body FDG PET/CT, delayed abdomen PET/MR imaging, and CE-CT/MR imaging. Two nuclear medicine physicians independently reviewed these images and discussed to reach a consensus, determining tumor resectability according to a 5-point scale, N stage (N0 or N positive), and M stage (M0 or M1). With use of clinical-surgical-pathologic findings as the reference standard, diagnostic performances of the two imaging sets were compared by using the McNemar test.ResultsThe diagnostic performance of FDG PET/CT plus delayed PET/MR imaging was not significantly different from that of CE-CT/MR imaging in the assessment of tumor resectability [area under the receiver operating characteristic curve: 0.927 vs. 0.925 (p = 0.975)], N stage (accuracy: 80% (16 of 20 patients) vs. 55% (11 of 20 patients), p = 0.125), and M stage (accuracy: 100% (40 of 40 patients) vs. 93% (37 of 40 patients), p = 0.250). Moreover, 14 of 40 patients had liver metastases. The number of liver metastases detected by CE-CT/MR imaging, PET/CT, and PET/MR imaging were 33, 18, and 61, respectively. Compared with CE-CT/MR imaging, PET/MR imaging resulted in additional findings of more liver metastases in 9/14 patients, of which 3 patients were upstaged. Compared with PET/CT, PET/MR imaging resulted in additional findings of more liver metastases in 12/14 patients, of which 6 patients were upstaged.ConclusionsAlthough FDG PET/CT plus delayed PET/MR imaging showed a diagnostic performance similar to that of CE-CT/MR imaging in the pretherapeutic assessment of the resectability and staging of pancreatic tumors, it still has potential as the more efficient and reasonable work-up approach for the additional value of metastatic information provided by delayed PET/MR imaging.

A Web-Based Prediction Model for Cancer-Specific Survival of Elderly Patients With Hypopharyngeal Squamous Cell Carcinomas: A Population-Based Study

Background: Hypopharyngeal squamous cell carcinomas (HPSCC) is one of the causes of death in elderly patients, an accurate prediction of survival can effectively improve the prognosis of patients. However, there is no accurate assessment of the survival prognosis of elderly patients with HPSCC. The purpose of this study is to establish a nomogram to predict the cancer-specific survival (CSS) of elderly patients with HPSCC.Methods: The clinicopathological data of all patients from 2004 to 2018 were downloaded from the SEER database. These patients were randomly divided into a training set (70%) and a validation set (30%). The univariate and multivariate Cox regression analysis confirmed independent risk factors for the prognosis of elderly patients with HPSCC. A new nomogram was constructed to predict 1-, 3-, and 5-year CSS in elderly patients with HPSCC. Then used the consistency index (C-index), the calibration curve, and the area under the receiver operating curve (AUC) to evaluate the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to assess the clinical value of the model.Results: A total of 3,172 patients were included in the study, and they were randomly divided into a training set (N = 2,219) and a validation set (N = 953). Univariate and multivariate analysis suggested that age, T stage, N stage, M stage, tumor size, surgery, radiotherapy, chemotherapy, and marriage were independent risk factors for patient prognosis. These nine variables are included in the nomogram to predict the CSS of patients. The C-index for the training set and validation was 0.713 (95% CI, 0.697–0.729) and 0.703 (95% CI, 0.678–0.729), respectively. The AUC results of the training and validation set indicate that this nomogram has good accuracy. The calibration curve indicates that the observed and predicted values are highly consistent. DCA indicated that the nomogram has a better clinical application value than the traditional TNM staging system.Conclusion: This study identified risk factors for survival in elderly patients with HPSCC. We found that age, T stage, N stage, M stage, tumor size, surgery, radiotherapy, chemotherapy, and marriage are independent prognostic factors. A new nomogram for predicting the CSS of elderly HPSCC patients was established. This model has good clinical application value and can help patients and doctors make clinical decisions.

A Non-Endemic Analysis of the Patterns and Prognosis of De Novo Metastatic Nasopharyngeal Carcinomas in Old Patients Aged ≥65 years

This study aimed to investigate the prognostic factors related to overall survival (OS) and cancer-specific survival (CSS) in patients with de novo metastatic nasopharyngeal carcinoma (NPC) aged ≥65 years in non-endemic areas. The Surveillance, Epidemiology, and End Results (SEER) database was queried for elderly patients with M1 stage NPC at initial diagnosis between 2004 and 2016. This study examined 100 patients and evaluated the relationship of gender, age, race, pathological grade, T stage, N stage, number of primary tumors, site of metastasis, number of metastatic organs, and other related factors with OS and CSS. The median survival and follow-up time were 10 and 48 months, respectively. The survival curves of race, N stage, bone metastasis, radiation, and chemotherapy significantly affected OS on the log-rank test. Race, bone metastasis, and chemotherapy were independent prognostic factors of OS. Bone metastasis was associated with poor survival. The survival curves of CSS were significantly differed between races, the number of primary tumors, and bone metastasis. In Cox regression multivariate analysis, only the number of primary tumors had an independent effect on prognosis. This study revealed that chemotherapy prolonged survival in elderly patients with metastatic NPC, whereas bone metastasis shortened survival.

Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.

Impact of Surgical Margins on Overall Survival after Gastrectomy for Gastric Cancer: A Validation of Japanese Gastric Cancer Association Guidelines on a Western Series

Purpose No consensus exists on the resection extent needed to ensure oncological safety in gastrectomy for gastric adenocarcinoma (GAC). This study aims to assess the impact of margin adequacy according to Japanese Gastric Cancer Association (JGCA) guidelines on overall survival (OS). Patients and Methods Patients who underwent surgery for stage I–III GAC at our institution between 2010 and 2017 were included. Margin adequacy according to JGCA, National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) guidelines was assessed, and their predictive value on OS was evaluated with Harrell’s C-index. Patients were analyzed according to their margins’ adherence to JGCA guidelines, and a propensity score matching (PSM) was run. Indication to either total gastrectomy (TG) or distal gastrectomy (DG) according to each guideline was also assessed. Results A total of 279 patients were included, of whom 220 (79%) underwent DG. Adequate margins according to JGCA were obtained in 209 patients (75%). On multivariate analysis, JGCA margin adequacy was independently associated with OS, together with American Society of Anesthesiologist class, neoadjuvant chemotherapy, lymphadenectomy extent, R0 resection, and postoperative N stage. After PSM, patients with JGCA adequate margins showed better OS, recurrence-free survival (RFS), and local RFS than patients with JGCA inadequate margins. For 220 DG, JGCA guidelines would have recommended TG in 25 patients (11%), NCCN in 30 (14%), and ESMO in 90 (41%) (p < 0.001). Conclusion Adequacy of surgical resection margins to JGCA guidelines leads to improved survival outcomes and allows for a more organ-preserving approach than Western guidelines.

Score for the Risk and Overall Survival of Lung Metastasis in Patients First Diagnosed With Soft Tissue Sarcoma: A Novel Nomogram-Based Risk Assessment System

Background: Metastatic soft tissue sarcoma (STS) patients have a poor prognosis with a 3-year survival rate of 25%. About 30% of them present lung metastases (LM). This study aimed to construct 2 nomograms to predict the risk of LM and overall survival of STS patients with LM. Materials and Methods: The data of patients were derived from the Surveillance, Epidemiology, and End Results database during the period of 2010 to 2015. Logistic and Cox analysis was performed to determine the independent risk factors and prognostic factors of STS patients with LM, respectively. Afterward, 2 nomograms were, respectively, established based on these factors. The performance of the developed nomogram was evaluated with receiver operating characteristic curves, area under the curve (AUC) calibration curves, and decision curve analysis (DCA). Results: A total of 7643 patients with STS were included in this study. The independent predictors of LM in first-diagnosed STS patients were N stage, grade, histologic type, and tumor size. The independent prognostic factors for STS patients with LM were age, N stage, surgery, and chemotherapy. The AUCs of the diagnostic nomogram were 0.806 in the training set and 0.799 in the testing set. For the prognostic nomogram, the time-dependent AUC values of the training and testing set suggested a favorable performance and discrimination of the nomogram. The 1-, 2-, and 3-year AUC values were 0.698, 0.718, and 0.715 in the training set, and 0.669, 0.612, and 0717 in the testing set, respectively. Furthermore, for the 2 nomograms, calibration curves indicated satisfactory agreement between prediction and actual survival, and DCA indicated its clinical usefulness. Conclusion: In this study, grade, histology, N stage, and tumor size were identified as independent risk factors of LM in STS patients, age, chemotherapy surgery, and N stage were identified as independent prognostic factors of STS patients with LM, these developed nomograms may be an effective tool for accurately predicting the risk and prognosis of newly diagnosed patients with LM.

Role of neoadjuvant therapy(chemotherapy and/or radiotherapy) in lymph node and primary rectal tumor regression and prognosis (Preprint)

UNSTRUCTURED Background: Rectal tumors are important malignancies and prediction of prognosis after neoadjuvant therapy is important to improve the prognosis process. The purpose of this study was to determine therole ofneoadjuvant therapy in lymph node regression and primary rectal tumor as well as its association with prognosis. Methods and materials: In this descriptive study, 40 consecutive patients with rectal tumor who were referred toTaleghani Hospital for surgery from 2011 to 2018 were enrolled. Moreover, theneoadjuvant therapy role in lymph node regression and primary rectal tumor was determined as well as its association with prognosis. Results: The results of this study demonstrate that there was no tumor regression in 20% of patients and it wasalso less than 25%, 25-50%, 50-75%, and complete in 22.5%, 35%, 20%, and 2.5% of the patients,respectively. The lymph node regression was complete in 5% of the patients and it wasalso less than 25% in 20% and more than 25% in 50% of them. In addition, it was with no regression in 25% of the patients. The lymph node regression was related to N stage (P=0.018), primary tumor regression grade (P=0.001), yPT (P=0.008), and yPN (P=0.020); however, it was not related to prognosis (P > 0.05). Conclusions: Totally, according to the obtained results, it can be concluded thatneoadjuvant therapy plays a good role in lymph node regression and primary rectal tumor, but it has no association with prognosis. Keywords:Neoadjuvant therapy, Lymph node regression, Primary rectal tumor, Prognosis

Exploration of a Modified Stage for pN0 Colon Cancer Patients

Purpose: Exploring a modified stage (mStage) for pN0 colon cancer patients.Methods: 39637 pN0 colon cancer patients were collected from the SEER database (2010-2015) (development cohort) and 455 pN0 colon cancer patients from the Second Affiliated Hospital of Harbin Medical University (2011-2015) (validation cohort). The optimal lymph nodes examined (LNE) stratification for cancer-specific survival (CSS) was obtained by X-tile software. LNE is combined with conventional T stage to form the mStage.Results: The novel N stage was built based on the LNE (N0a: LNE ≥ 26, N0b: LNE = 10-25 and N0c: LNE < 10). The mStage include mStageA (T1N0a, T1N0b, T1N0c and T2N0a), mStageB (T2N0b, T2N0c and T3N0a), mStageC (T3N0b), mStageD (T3N0c, T4aN0a and T4bN0a), mStageE (T4aN0b and T4bN0b) and mStageF (T4aN0c and T4bN0c). Cox regression model showed that mStage was an independent prognostic factor. AUC showed that the predictive accuracy of mStage was better than the conventional T stage for 5-year CSS in the development (0.700 vs 0.678, P < 0.001) and validation cohort (0.649 vs 0.603, P = 0.018). The C-index also showed that mStage had a superior model-fitting.Conclusions: For pN0 colon cancer patients, mStage might be superior to conventional T stage in predicting the prognosis.

Modulating Properties of Piroxicam, Meloxicam and Oxicam Analogues against Macrophage-Associated Chemokines in Colorectal Cancer

The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes NAG1, NFKBIA, MYD88, and RELA, as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated CCL4 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and NFKBIA, and downregulated MYD88. They inhibited CCL3 and CCL4, and their effect on CCL2 and CXCL2 depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only CCL19 and CXCL2 were not upregulated in tumors, nor was CXCL2 in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, CCL4 and CXCL2 were upregulated, while CCL2, CCL8, and CCL19 were downregulated in tumors. Tumor CCL2 and CCL7 increased along with advancing T and CCL3, and CCL4 along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating NAG1 and interfering with NF-κB signaling.

Prospective comparison of CT and 18F-FDG PET/MRI in N and M staging of primary breast cancer patients: Initial results

Objectives To compare the diagnostic accuracy of contrast-enhanced thoraco-abdominal computed tomography and whole-body 18F-FDG PET/MRI in N and M staging in newly diagnosed, histopathological proven breast cancer. Material and methods A total of 80 consecutive women with newly diagnosed and histopathologically confirmed breast cancer were enrolled in this prospective study. Following inclusion criteria had to be fulfilled: (1) newly diagnosed, treatment-naive T2-tumor or higher T-stage or (2) newly diagnosed, treatment-naive triple-negative tumor of every size or (3) newly diagnosed, treatment-naive tumor with molecular high risk (T1c, Ki67 >14%, HER2neu over-expression, G3). All patients underwent a thoraco-abdominal ceCT and a whole-body 18F-FDG PET/MRI. All datasets were evaluated by two experienced radiologists in hybrid imaging regarding suspect lesion count, localization, categorization and diagnostic confidence. Images were interpreted in random order with a reading gap of at least 4 weeks to avoid recognition bias. Histopathological results as well as follow-up imaging served as reference standard. Differences in staging accuracy were assessed using Mc Nemars chi2 test. Results CT rated the N stage correctly in 64 of 80 (80%, 95% CI:70.0–87.3) patients with a sensitivity of 61.5% (CI:45.9–75.1), a specificity of 97.6% (CI:87.4–99.6), a PPV of 96% (CI:80.5–99.3), and a NPV of 72.7% (CI:59.8–82.7). Compared to this, 18F-FDG PET/MRI determined the N stage correctly in 71 of 80 (88.75%, CI:80.0–94.0) patients with a sensitivity of 82.1% (CI:67.3–91.0), a specificity of 95.1% (CI:83.9–98.7), a PPV of 94.1% (CI:80.9–98.4) and a NPV of 84.8% (CI:71.8–92.4). Differences in sensitivities were statistically significant (difference 20.6%, CI:-0.02–40.9; p = 0.008). Distant metastases were present in 7/80 patients (8.75%). 18 F-FDG PET/MRI detected all of the histopathological proven metastases without any false-positive findings, while 3 patients with bone metastases were missed in CT (sensitivity 57.1%, specificity 95.9%). Additionally, CT presented false-positive findings in 3 patients. Conclusion 18F-FDG PET/MRI has a high diagnostic potential and outperforms CT in assessing the N and M stage in patients with primary breast cancer.