Background : Perineural invasion (PNI) and lymphovascular invasion (LVI) are associated with poor prognosis in colorectal cancer, but their clinical significance is still controversial for patients with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) and surgical resection. The aim of this study was to confirm the correlation between PNI and/or LVI and clinical prognosis and to further confirm whether PNI and/or LVI can be used as potential prognostic indicators of adjuvant chemotherapy after nCRT and surgery in LARC. Methods : From February 2002 to December 2012, a total of 181 patients with LARC who had received nCRT and surgical resection were retrospectively reviewed. Overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression model. Results : The median follow-up time was 48 months (range, 3 to 162 months). All the PNI-positive and/or LVI-positive patients showed adverse DFS and OS ( P <0.001). In multivariate analysis, PNI and LVI were independent prognostic factors for DFS. PNI, rather than LVI, was also an independent prognostic factor for OS. In a subgroup analysis, PNI-positive, rather than LVI-positive, may benefit from adjuvant chemotherapy. Conclusion : For patients with LARC undergoing nCRT and surgery, PNI-positive and/or LVI positive were associated with poorer DFS and OS. And PNI-positive, rather than LVI-positive, may benefit from adjuvant chemotherapy.

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BackgroundIncreasing evidence suggests that cancer-associated inflammation is associated with poorer outcomes. The neutrophil-to-lymphocyte ratio (NLR), considered as a systemic inflammation marker, is thought to predict prognoses in colorectal cancer. In this study, we explored the association between the NLR and prognoses following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC).Material/MethodsFrom February 2002 to December 2012, a group of 202 patients diagnosed with LARC and receiving neoadjuvant CRT followed by radical surgery was included in our retrospective study. The associations between the pre-CRT NLR and clinicopathological characteristics, as well as the predictive value of pre-CRT NLR against survival outcomes, were analyzed.ResultsThe average NLR was 2.7±1.5 (median 2.4, range 0.6–12.8). There were 63 (31.2%) patients with NLR ≥3.0, and 139 (68.8%) patients with NLR <3.0. Correlation analyses showed that no clinicopathological characteristics except age were associated with NLR. We did not find an association between NLR and survival outcomes. In multivariate Cox model analyses, the R1/R2 resection, lymph node ratio ≥0.1, and perineural/lymphovascular invasion were independently associated with worse disease-free survival and overall survival.ConclusionsIn our cohort, the NLR did not correlate with survival outcomes in LARC patients undergoing neoadjuvant CRT. The prognostic value of NLR should be validated in large-scale prospective studies.

18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has the potential to improve the staging and radiation treatment (RT) planning of various tumor sites. However, from a clinical standpoint, questions remain with regard to what extent PET/CT changes the target volume and whether PET/CT reduces interobserver variability in target volume delineation. The present study analyzed the use of FDG-PET/CT images for staging and evaluated the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT in patients with non-small cell lung cancer (NSCLC) who were candidates for radiotherapy. Intraobserver variation in delineating tumor volumes was also observed. In total, 23 patients with stage I-III NSCLC were enrolled and treated with fractionated RT-based therapy with or without chemotherapy. FDG-PET/CT scans were acquired within two weeks prior to RT. PET and CT data sets were sent to the treatment planning system, Pinnacle, through compact discs. The CT and PET images were subsequently fused by means of a dedicated RT planning system. Gross tumor volume (GTV) was contoured by four radiation oncologists on CT (GTV-CT) and PET/CT images (GTV-PET/CT). The resulting volumes were analyzed and compared. For the first phase, two radiation oncologists outlined the contours together, achieving a final consensus. Based on PET/CT, changes in tumor-node-metastasis categories occurred in 8/23 cases (35%). Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in 12/20 patients (60%) in comparison with CT targeting. The most prominent changes in GTV were observed in cases with atelectasis. For the second phase, the variation in delineating tumor volumes was assessed by four observers. The mean ratio of largest to smallest CT-based GTV was 2.31 (range, 1.01–5.96). The addition of the PET results reduced the mean ratio to 1.46 (range, 1.02–2.27). PET/CT fusion images may have a potential impact on tumor staging and treatment planning. Implementing matched PET/CT results reduced observer variation in delineating tumor volumes significantly with respect to CT only.

Background While there have been encouraging preliminary clinical results for immune checkpoint inhibitors (ICIs) in BTCs, it remains a challenge to identify the subset of patients who may benefit. In this study, we evaluated the efficacy of ICI treatment in patients with advanced BTCs, and explored potential biomarkers that are predictive of response. Methods The study enrolled 26 patients with advanced microsatellite stable BTCs (15 with gallbladder cancers [GCs] and 11 with intrahepatic cholangiocarcinoma [ICCs]) who received ICI treatment. Targeted next‐generation sequencing (NGS) was performed on tumor tissue samples collected from 17 patients. Clinical and genomic characteristics were assessed for the correlation with clinical outcome. Results Analysis of the baseline clinical characteristics showed that performance score (PS) of 0 was associated with a better prognosis than PS of 1 (HR = 1.08 × 109; 95% CI, 0∼Inf; P = .002). No significant correlations were found between clinical outcome and inflammation‐related indicators. NGS profiling of the available tumor tissues, revealed largely non‐overlapping somatic alterations between GCs and ICCs. Mutations in LRP1B (HR = 0.26; 95% CI, 0.06‐1.21; P = .067), ERBB2 (HR = 0.15; 95% CI, 0.02‐1.19; P = .04), or PKHD1 (HR < 0.01; 95% CI, 0‐Inf; P = .04) showed strong association with increased progression‐free survival (PFS) benefit. Subsequent analysis showed that alterations in the RTK‐RAS pathway were associated with improved outcomes (HR = 0.12; 95% CI, 0.02‐0.63; P = .003). Tumor mutation burden (TMB) was higher in patients with GC than those with ICC, and was associated with LRP1B mutations (P = .032). We found that patients with 19q amplification (19q Amp) and 9p deletion (9p Del) had poor PFS outcome (19q Amp, HR = 15.4; 95% CI, 2.7‐88.5; P < .001; 9p Del; HR = 4.88 × 109; 95% CI, 0‐Inf; P < .001), while those with chromosomal instability derived PFS benefit (HR = 0.24; 95% CI, 0.05‐1.17; P = .057). Conclusion Our study identified several potential clinical and genomic features that may serve as biomarkers of clinical response to ICIs in advanced BTCs patients. A larger sample size is required for further verification.