Intravoxel incoherent motion imaging kinetics during chemoradiotherapy for human papillomavirus‐associated squamous cell carcinoma of the oropharynx: preliminary results from a prospective pilot study

This study aims to identify the temporal kinetics of intravoxel incoherent motion (IVIM) MRI in patients with human papillomavirus‐associated (HPV+) oropharyngeal squamous cell carcinoma. Patients were enrolled under an Institutional Review Board (IRB)‐approved protocol as part of an ongoing prospective clinical trial. All patients underwent two MRI studies: a baseline scan before chemoradiotherapy and a mid‐treatment scan 3–4 weeks after treatment initiation. Parametric maps representing pure diffusion coefficient (D), pseudo‐diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) were generated. The Mann–Whitney U‐test was used to assess the temporal variation of IVIM metrics. Bayesian quadratic discriminant analysis (QDA) was used to evaluate the extent to which mid‐treatment changes in IVIM metrics could be combined to predict sites that would achieve complete response (CR) in multivariate analysis. Thirty‐one patients were included in the final analysis with 59 lesions. Pretreatment ADC and D values of the CR lesions (n = 19) were significantly lower than those of non‐CR lesions (n = 33). Mid‐treatment ADC, D and f values were significantly higher (p < 0.0001) than pretreatment values for all lesions. Each increase in normalized ΔADC of size 0.1 yielded a 1.45‐fold increase in the odds of CR (p < 0.0003), each increase in normalized ΔD of size 0.1 yielded a 1.53‐fold increase in the odds of CR (p < 0.0002), and each unit increase in Δf yielded a 2.29‐fold increase in the odds of CR (p < 0.02). Combined ΔD and ΔADC were integrated into a multivariate prediction model and attained an AUC of 0.87 (95% confidence interval: 0.79, 0.96), as well as a sensitivity of 0.63, specificity of 0.85 and accuracy of 0.78, under leave‐one‐out cross‐validation. In conclusion, IVIM is feasible and potentially useful in the prediction and assessment of the early response of HPV+ oropharyngeal squamous cell carcinoma to chemoradiotherapy. Copyright © 2015 John Wiley & Sons, Ltd.     

Defining and predicting early recurrence in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

BackgroundThe definition of “early recurrence (ER)” after rectal cancer surgery is currently unclear.ObjectiveTo determine an evidence-based cut-off to distinguish early and late recurrence (LR) for patients with rectal cancer and compare the clinicopathological factors between the two groups.MethodsPatients who underwent neoadjuvant chemoradiotherapy (nCRT) and radical resection for locally advanced rectal cancer were included. A minimum p-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into ER and LR groups based on overall survival. A logistic regression model was used to assess risk factors for ER.ResultsA total of 763 patients were included, of which 167 (21.9%) experienced recurrence. The optimal cut-off value of recurrence-free survival to differentiate between ER (n = 125, 74.9%) and LR (n = 42, 25.1%) was 24 months (P = 0.000001). The median postrecurrence survival of ER and LR was 12 months and 22 months, respectively (p = 0.028). The most common recurrent sites in patients with ER and LR were lung metastases, the incidence of liver metastases, however, differed considerably in ER and LR (27.2% vs 9.5%, P = 0.019). Risk factors including elevated preoperative carcinoembryonic antigen (CEA), higher ypTNM stage, positive circumferential resection margin (CRM), and perineural invasion were significantly associated with ER.ConclusionA recurrence-free interval of 24 months is the optimal cut-off value for defining ER versus LR. Elevated preoperative CEA, higher ypTNM staging, positive CRM, and perineural invasion were associated with ER of locally advanced rectal cancer.     

Endostar,an Antiangiogenesis Inhibitor,Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.     

Heparanase-1 is downregulated in chemoradiotherapy orbital rhabdomyosarcoma and relates with tumor growth as well as angiogenesis

AIM:To determine the role of heparanase-1(HPSE-1)in orbital rhabdomyosarcoma(RMS),and to investigate the feasibility of HPSE-1 targeted therapy for RMS.METHODS:Immunohistochemistry was performed to analyze HPSE-1 expression in 51 cases of orbital RMS patients(including 28 cases of embryonal RMS and 23 cases of alveolar RMS),among whom there were 27 treated and 24 untreated with preoperative chemoradiotherapy.In vitro,studies were conducted to examine the effect of HPSE-1 silencing on RMS cell proliferation and tube formation of human umbilical vein endothelial cells(HUVECs).RD cells(an RMS cell line)and HUVECs were infected with HPSE-1 sh RNA lentivirus at a multiplicity of infection(MOI)of 10 and 30 separately.Real-time PCR and Western blot were applied to detect the m RNA and protein expression levels of HPSE-1.Cell viability of treated or control RD cells was evaluated by cell counting kit-8(CCK-8)assay.Matrigel tube formation assay was used to evaluate the effect of HPSE-1 RNAi on the tube formation of HUVECs.RESULTS:Immunohistochemistry showed that the expression rate of HPSE-1 protein was 92.9%in orbital embr yonal RMS and 91.3%in orbital alveolar RMS.Tissue from alveolar orbital RMS did not show relatively stronger staining than that from the embryonal orbital RMS.However,despite the types of RMS,comparing the cases treated chemoradiotherapy with those untreated,we have observed that chemoradiotherapy resulted in weaker staining in patients’tissues.The expression levels of HPSE-1 declined significantly in both the m RNA and protein levels in HPSE-1 sh RNA transfected RD cells.The CCK-8 assay showed that lentivirus-mediated HPSE-1 silencing resulted in significantly reduced RD cells viability in vitro.Silencing HPSE-1 expression also inhibited VEGF-induced tube formation of HUVECs in Matrigel.CONCLUSION:HPSE-1 silencing may be a promising therapy for the inhibition of orbital RMS progression.     

Smartphone-based inertial sensors technology – Validation of a new application to measure spatiotemporal gait metrics

BackgroundSmartphones are increasingly recognized as the future technology for clinical gait assessment.ResearchQuestion: To determine the concurrent validity of gait parameters obtained using the smartphone technology and application in a group of patients with musculoskeletal pathologies.MethodsPatients with knee, lower back, hip, or ankle pain were included in the study (n = 72). Spatiotemporal outcomes were derived from the walkway and the smartphone simultaneously. Pearson’s correlations and limits of agreement (LoA) determined the association between the two methods.ResultsCadence and gait cycle time showed excellent correlation and agreement between the smartphone and the walkway (cadence: r = 0.997, LoA=1.4%, gait cycle time: r = 0.996, LoA = 1.6%). Gait speed, double-limb support and left and right step length demonstrated strong correlations and moderate agreement between methods (gait speed: r = 0.914, LoA=15.4%, left step length: r = 0.842, LoA = 17.0%, right step length: r = 0.800, LoA=16.4%). The left and right measures of single-limb support and stance percent showed a consistent 4% bias across instruments, yielding moderate correlation and very good agreement between the smartphone and the walkway (r = 0.532, LoA = 9% and r = 0.460, LoA=9.8% for left and right single-limb support; r = 0.463, LoA = 5.1% and r = 0.533, LoA = 4.4% for left and right stance).Significance: The examined application appears to be a valid tool for gait analysis, providing clinically significant metrics for the assessment of patients with musculoskeletal pathologies. However, additional studies should examine the technology amongst patients with severe gait abnormalities.     

Prognostic impact of sterilized lymph nodes in esophageal squamous cell carcinomas after neoadjuvant chemoradiotherapy

BackgroundThe prognostic importance of sterilized lymph nodes (SLN) remains unclear in patients with esophageal squamous cell carcinomas (ESCC) treated by neoadjuvant chemoradiotherapy (nCRT). This study aimed to determine whether SLN predicted disease-free survival (DFS) in ESCC.MethodsWe enrolled 246 eligible patients who were divided into SLN (+) and SLN (-) group according to the presence or absence of fibrosis, necrosis, calcifications and/or foreign body giant cell reactions in the negative lymph nodes specimens. The prognostic value of SLN was determined using univariate and multivariate analyses. The prognostic strength of counting SLN as positive lymph nodes was evaluated using the difference of Akaike information criterion (ΔAIC).ResultsA total of 61 SLN were identified in 38 (15.4%) patients. There was no significant difference in baseline characteristics between SLN (+) and SLN (-) group. The most frequently detected SLN in the thoracic cavity and abdominal cavity were those along bilateral recurrent laryngeal nerve (21/38,55.3%) and left gastric artery (13/24,60.9%), respectively. The univariate and multivariate analyses showed SLN was an independent prognostic factor for worse DFS in the whole cohort (HR = 2.05, 95%CI = 1.08–3.90, P = 0.029). The SLN (+) group additionally correlated with worse 5-year DFS than SLN (-) group in the ypT0, ypN0 and pCR subgroups. Counting SLN as positive lymph nodes showed better prognostic strength than ignoring them.ConclusionSLN was of prognostic significance for worse DFS in patients with ESCC, particularly in patients with good response to nCRT.     

Reproducibility and prognostic significance of area of residual tumor (ART) in post-neoadjuvant resections of pancreatic ductal adenocarcinoma

BackgroundThe pathologic assessments of tumor response after neoadjuvant chemoradiotherapy (NACRT) are critical to improving the prognostic stratification for patients with pancreatic ductal adenocarcinoma (PDAC). Here we clarified the utility of our new grading system based on the area of residual tumor (ART) as compared to existing systems, such as the College of American Pathologists (CAP) and MD Anderson (MDA) score. Methods: Eight reviewers individually evaluated the tumor regression grade of 30 patients with PDAC based on three types of grading systems. The interobserver concordance and clinicopathological characteristics were compared between the three systems. Results: The interobserver concordance (kappa value) of the ART, CAP, and MDA score were 0.61, 0.48, and 0.53, respectively. Discrepant cases, which were 27% of the cases, exhibited smaller tumor and tumor bed sizes than concordant cases. The reduction in tumor size evaluated by microscopy showed a correlation with the rate of change in carcinoembryonic antigen (CEA) level, CA19-9 level, and tumor size on computed tomography (CT). The ART score was correlated with the tumor size on CT before and after NACRT and disease-free survival. The CAP and MDA scores were not associated with prognosis. Conclusion: The ART grading system may be the most practical system to assess the tumor response in post-NACRT resections of PDAC.