Disease-free Survival In Group Research Articles

Using Genomics Feature Selection Method in Radiomics Pipeline Improves Prognostication Performance in Locally Advanced Esophageal Squamous Cell Carcinoma-A Pilot Study.

Simple SummaryPrognosis for patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor mainly due to late diagnosis and limited curative treatment options. Neoadjuvant chemoradiotherapy (nCRT) plus surgery is considered the standard of care for patients with locally advanced ESCC. Currently, predicting prognosis remains a challenging task. Quantitative imaging radiomics analysis has shown promising results, but these methods are traditionally data-intensive, requiring a large sample size, and are not necessarily based on the underlying biology. Feature selection based on genomics is proposed in this work, leveraging differentially expressed genes to reduce the number of radiomic features allowing for the creation of a CT-based radiomic model using the genomics-based feature selection method. The established radiomic signature was prognostic for patients’ long-term survival. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.Purpose: To evaluate the prognostic value of baseline and restaging CT-based radiomics with features associated with gene expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiation (nCRT) plus surgery. Methods: We enrolled 106 ESCC patients receiving nCRT from two institutions. Gene expression profiles of 28 patients in the training set were used to detect differentially expressed (DE) genes between patients with and without relapse. Radiomic features that were correlated to DE genes were selected, followed by additional machine learning selection. A radiomic nomogram for disease-free survival (DFS) prediction incorporating the radiomic signature and prognostic clinical characteristics was established for DFS estimation and validated. Results: The radiomic signature with DE genes feature selection achieved better performance for DFS prediction than without. The nomogram incorporating the radiomic signature and lymph nodal status significantly stratified patients into high and low-risk groups for DFS (p < 0.001). The areas under the curve (AUCs) for predicting 5-year DFS were 0.912 in the training set, 0.852 in the internal test set, 0.769 in the external test set. Conclusions: Genomics association was useful for radiomic feature selection. The established radiomic signature was prognostic for DFS. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.

Simultaneous surgery for synchronous liver metastases of colorectal cancer: analysis of survival and negative prognosis factors

Aim. To improve the surgical treatment results among patients with synchronous liver metastasis of colorectal cancer. Materials and methods. From 2012 to 2019, the analysis of the results of treatment of 60 patients with colorectal cancer and synchronous metastatic liver disease was carried out. The study sample was divided into 2 groups of patients. The group 1 consisted of 30 patients who got simultaneous resection of liver metastases and primary colorectal cancer. The group 2 consisted of other 30 patients who got stage resections: surgery for the primary tumor at the first stage, and liver surgery for metastases at the second.Results. The median operative time was 340 ± 21.1 minutes in the group 1. In the group 2 it was 255 ± 21.1 minutes and only the liver resection stage was assessed. The median blood loss in patients of the group 1 was 520,0 [200,0;800,1] ml, in the group 2 it was 500,0 [175,0;1300,0] ml. In general, we identified 5 cases of complications. In the postoperative period, 4 patients died. The average follow-up period is 23 months. One-year survival in group 1 was 92.6%, in group 2 – 100%, three-year – 85.2% and 89.6%. One-year disease-free survival in group 1 is 70%, in group 2 – 83.3%, three-year disease-free survival – 43.3% and 36.7%.Overall and disease-free survival rates didn’t differ significantly between the two treatment strategies. We detected significant effect on the disease-free and overall survival of regional lymph nodes metastasis (both p &lt; 0.05).Conclusion. The long-term and immediate results of simultaneous surgery of synchronous liver metastasis of colorectal cancer are comparable to the results of the staged method of treatment. It indicates the safety and effectiveness of simultaneous procedure.

A propensity score-matched comparison of recurrence outcomes after immediate implant vs autologous flap reconstruction in patients receiving neoadjuvant chemotherapy for breast cancer.

We compared oncologic outcomes between breast cancer patients who underwent immediate implant-based breast reconstruction (IBBR) and those who underwent autologous flap reconstruction (AFR) after neoadjuvant chemotherapy (NACT). The study group comprised 536 patients with primary breast cancer who underwent NACT followed by immediate IBBR or AFR. After propensity score matching, 138 patients in the IBBR group and 276 patients in the AFR group were selected for comparisons of locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS). No significant differences were observed between the matched groups in locoregional recurrence rates (IBBR vs. AFR: 12.3% vs. 12%; P = 0.915) and distant metastasis (13% vs. 17%; P = 0.293). There was also no significant difference between the groups in LRRFS (P = 0.956), DFS (P = 0.606), DMFS (P = 0.283), or BCSS (P = 0.121). The 5- and 10-year LRRFS rates were 87.6% and 85.9% in the IBBR group, and 87.7% and 86.1% in the AFR group; the 5- and 10-year DFS rates were 79% and 77.5% in the IBBR group, and 77% and 75% in the AFR group; the 5- and 10-year DMFS rates were 85.9% and 85.9% in the IBBR group, and 83.2% and 81.8% in the AFR group; and the 5- and 10-year BCSS rates were 97.8% and 91.3% in the IBBR group, and 91.8% and 86% in the AFR group, respectively. In this propensity score-matched analysis of oncologic outcomes in breast cancer patients who underwent immediate reconstruction after NACT, no significant differences were observed between the IBBR and AFR groups.

Characteristics and prognosis of jejunoileal gastrointestinal stromal tumours (GISTs) in the era of imatinib: a comparative study with gastric GISTs

Gastrointestinal stromal tumours (GISTs) located in the jejunum or ileum (JI-GIST) are considered worse prognosis compared to those of gastric (G-GIST) location. It has been suggested that this dogma should be revised. The aim of this study was to describe the characteristics of jejunoileal GISTs and its prognosis and to compare them with G-GISTs in the era of imatinib. We retrospectively reviewed the clinical histories of all the patients diagnosed with GISTs between January 2000 and November 2016: Clinical and pathological data, as recurrence, metastatic state, disease-free survival (DFS) as well as overall survival (OS) rates of patients were reviewed. JI-GIST patients comprise 29 cases (37.7%). Compared to G-GIST, JI-GIST patients had undergone emergency surgery more frequently (37.9% vs. 10.4%, p = 0.007). According to the NIH-Fletcher classification, the low or very-low risk group represents 17.2% of JI-GISTs as opposed to 37.6% of G-GISTs (p < 0.005). When the AFIP-Miettinen system was used the low or very-low group represented 17.2% of JI-GISTs vs. 58.4% in the G-GISTs group (p < 0.001). Both local recurrence (24.1% vs. 12.5%, p < 0.05) and metastatic rate (34.5% vs. 22.9%, p < 0.05) were higher in the JI-GIST group than in G-GIST. 5- and 10-year DFS and 10-year OS rate were lower for JI-GIST (54.5% and 39.6% vs. 77.2% and 60.8%, and 57.9% vs. 65%, respectively, p < 0.05). The observed differences between both groups in DFS and OS rates at long term could be attributed to the effect of imatinib.

Neoadjuvant chemoradiotherapy followed by surgery for operable carcinoma esophagus: Ground reality in a tertiary care center of rural India - A retrospective audit

Background: Carcinoma of the esophagus and gastroesophageal junction is an aggressive disease with limited survival. Standard management consists of multimodality therapy, incorporating chemotherapy, radiation, and surgery.Objectives: We aimed to understand the obstacles in treating patients with resectable esophageal cancer with neoadjuvant chemoradiotherapy followed by surgery. We also assessed the disease outcomes in the patients who completed surgery.Materials and Methods: We included patients with resectable esophageal carcinoma who received neoadjuvant chemoradiation between March 2017 and August 2019 at the Homi Bhabha Cancer Hospital in Sangrur, Punjab, a tertiary care center in rural India. As surgery for esophageal cancer was not performed at our center, patients had to be referred to a higher center for this. Patients were divided into two groups, based on the therapy they received following neoadjuvant chemoradiation: those who completed surgery (Group A) and those who did not (Group B). The pathologic response rates were noted. The disease-free survival (DFS) and overall survival (OS) were compared between the two groups.Results: A total of 55 patients (32 in Group A and 23 in Group B) were included the study. In Group A, complete pathologic responses were noted in 19 (59.4%), partial responses in 11 (34.4%) and poor responses in 2 (6.2%) patients. The major reasons for not undergoing surgery were patient refusal as they were feeling better after chemoradiation (8, 34.8%) and the presence of advanced inoperable (5, 21.7%) or metastatic disease (3, 13%) on imaging after chemoradiation. The median DFS in Group A and Group B was 8 months (range, 0–38 months) and 14 months (range, 0–29 months), respectively, and the 2-year DFS was 57.8% and 73.3%, respectively (P = 0.28). Median OS in Group A and Group B was 17 months (range, 3–43 months) and 17 months (range, 2–31 months), respectively, and the 2-year OS was 52.6% and 53.5%, respectively (P = 0.70).Conclusions: Implementing neoadjuvant chemoradiation followed by surgery for resectable esophageal cancer in a center where esophageal cancer surgery cannot be performed is challenging. Among patients who undergo surgery following neoadjuvant chemoradiation, complete pathologic responses occur in 59.4% patients, and clinical outcomes appear to be similar to those reported in the literature.

Impact of pringle maneuver on the early recurrence of colorectal cancer liver metastasis after liver resection: a systematic review and meta-analysis

Purpose: Pringle maneuver (PM) includes continuous PM, intermittent PM (IPM), prolonged PM and other different types of blocking blood flow. The impact of PM on tumor recurrence of hepatectomy in patients with colorectal cancer liver metastases (CRLM) remains controversial. The present study aimed to assess whether different types of PM have an adverse effect on the recurrence of CRLM. Methods: PubMed, Embase, Web of Science, and the Cochrane Library databases were searched. We registered the protocol at the International Prospective Register of Systematic Reviews (PROSPERO registration number: CRD42020179534). The IPM is defined as the portal triad clamping for several min, followed by several min of reperfusion, repeated as needed. Prolonged PM was defined as ≥20 min continuous or ≥3 cycles for maximally 15-min intermittent ischemia. Results: Nine studies encompassing 3562 patients were included in this meta-analysis. The pooled HR did not show any significant difference between IPM and non-IPM groups for disease-free survival (DFS) (HR = 0.91, 95% CI 0.80–1.04, P = 0.18). The results showed significant differences between prolonged PM and non-PM groups for DFS (HR = 1.75, 95% CI 1.28–2.40, P = 0.0005) and 1-year DFS rate (odds ratio = 2.77, 95% CI 1.15–6.72, P = 0.02). Conclusion: These findings suggested that IPM has no effect on DFS, but prolonged PM has an adverse impact on the early recurrence of patients with CRLM; however, further prospective and multicenter studies are needed.

Staged management of cardiac disease and concomitant early lung cancer: a 20-year single-center experience.

The association of unstable heart disease and resectable lung cancer is rare. The impacts of staged management, cardiac surgery with cardiopulmonary bypass (CPB) versus angioplasty, on long-term survival and cancer recurrence remain debated. We report our experience using staged management. From 1997 to 2016, 107 patients were treated at the Quebec Heart and Lung Institute: 72 underwent cardiac surgery with CPB (group 1), 35 were treated with angioplasty (group 2), followed by oncological pulmonary resection. Two postoperative deaths (3%) and 1 ischaemic heart complication (1%) were reported in group 1. One death (3%) was reported in group 2. Two-year overall survival was 82% (59/72) in group 1 and 80% (28/35) in group 2; 5-year overall survival was 62% (33/53) in group 1 and 63% (19/30) in group 2. Two-year disease-free survival in group 1 was 79% (57/72) and 77% (27/35) in group 2; 5-year disease-free survival was 58% (31/53) in group 1 and 60% (18/30) in group 2. The independent risk factors for death after thoracic surgery were transfusions (P = 0.004) and grade ≥3 complications (P = 0.034). Independent risk factors for recurrence included the cancer stage (P < 0.001) and, paradoxically, a shorter delay between cardiac and lung procedures (P = 0.031). When a staged management remains feasible after cardiac procedure, oncological outcomes of patients with cardiopathy and lung cancer are satisfactory. CPB does not seem to be deleterious. The delay between procedures should intuitively be as small as possible but not at the expense of good recovery after the cardiac procedure.

Omission of MRI For Treatment Planning Does Not Affect Long-Term Outcomes after Prostate SBRT.

Stereotactic Body Radiation Therapy (SBRT) is increasingly being used to treat men with localized prostate cancer. Diagnostic MRI imaging as well as MRI-guided treatment for these patients have become widely utilized. A minority of patients are not candidates for MRI imaging due to pre-existing conditions or patient intolerance. To our knowledge, this is the largest series to investigate long-term outcomes in men for whom MRI imaging is not employed as a component of their prostate SBRT treatment. A total of 2775 patients with localized prostate cancer were treated with inhomogeneous-dosed SBRT at an academic institution between April 11, 2006 and November 23, 2019. By NCCN categorization, patients were treated for low (29.6%), favorable intermediate (26.0%), unfavorable intermediate (34.9%), and high risk (9.6%) disease. The majority (84.0%) of patients were treated with a median dose of 3500cGy (3500-3625) over 5 fractions. Androgen deprivation Therapy (ADT) was prescribed in 17.1% of cases. Disease Free Survival (DFS) was scored using the “nadir + 2” definition and long-term urinary and rectal toxicity was characterized as occurring ≥6 months post radiation. Correlation analyses were performed using the Pearson Chi-Square test. Estimates for DFS and toxicity were determined using the Kaplan-Meier method. 132 (4.8%) patients in this series received treatment without a planning MRI, with the most common reason being a history of implanted defibrillator (46.2%). Those treated without an MRI were slightly older (69.8 vs. 67.2 years, p<.001), and were more likely to have Gleason 8-10 histology (14.4% vs. 7.5%, p = .01) and high-risk disease (15.9% vs. 8.7%, p = .02). There was no difference in pre-treatment PSA. Those treated with MR imaging were more likely to be prescribed 3625cGy (12.1% vs. 4.6%, p = .004). The CTV was larger in men for whom an MRI was not utilized (84.3cc’s vs. 77.8cc’s, p = .029) as was maximum penile bulb dose (3061cGy vs. 2181cGy, p = .002). There was no difference in the use of ADT or in rectal or bladder dosimetry between these groups. Patients treated without MR imaging had no difference in 6-year freedom from grade 2+ rectal (96.6% vs. 97.1%, p = 0.42) and genitourinary toxicity (97.7% vs. 97.2%, p = 0.76). Similarly, there was no difference between these groups in 6-year DFS for low (97.7% vs. 97.2%, p = 0.60), favorable intermediate (100% vs. 83.1%, p = 0.61), unfavorable intermediate (84.3% vs. 84.5%, p = 0.19), or high-risk disease (64% vs. 67.5%, p = .06). This is the largest study to explore long-term outcomes in men treated with SBRT without MR imaging for localized prostate cancer. These patients are at risk for treatment with larger CTV size and penile bulb dose. Despite this, along with slight differences in baseline clinicopathologic features, the omission of MR imaging is safe and does not appear to affect long-term DFS or toxicity profiles.

&lt;p&gt;MRI-Based Radiomic Signature as a Prognostic Biomarker for HER2-Positive Invasive Breast Cancer Treated with NAC&lt;/p&gt;

PurposeTo identify MRI-based radiomics signature (Rad-score) as a biomarker of risk stratification for disease-free survival (DFS) in patients with HER2-positive invasive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC) and establish a radiomics-clinicoradiologic-based nomogram that combines Rad-score, MRI findings, and clinicopathological variables for DFS estimation.Patients and MethodsA total of 127 patients were divided into a training set and testing set according to the ratio of 7:3. Radiomic features were extracted from multiphase CE-MRI (CEm). Rad-score was calculated using the LASSO (least absolute shrinkage and selection operator) regression analysis. The cutoff point of Rad-score to divide the patients into high- and low-risk groups was determined by receiver operating characteristic curve analysis. A Kaplan–Meier survival curves and the Log rank test were used to investigate the association of the Rad-score with DFS. Univariate and multivariate Cox proportional hazards model were used to determine the association of Rad-score, MRI features, and clinicopathological variables with DFS. A radiomics-clinicoradiologic-based nomogram combining the Rad-score, MRI features, and clinicopathological findings was plotted to validate the radiomic signatures for DFS estimation.ResultsThe Rad-score stratified patients into high- and low-risk groups for DFS in the training set (P<0.0001) and was validated in the testing set (P=0.002). The radiomics-clinicoradiologic-based nomogram estimated DFS (training set: C-index=0.974, 95% confidence interval (CI)=0.954–0.994; testing set: C-index=0.917, 95% CI=0.842–0.991) better than the clinicoradiologic-based nomogram (training set: C-index=0.855, 95% CI=0.739–0.971; testing set: C-index=0.831, 95% CI=0.643–0.999).ConclusionThe Rad-score is an independent biomarker for the estimation of DFS in invasive HER2-positive breast cancer with NAC and the radiomics-clinicoradiologic-based nomogram improved individualized DFS estimation.

Prognostic biomarkers related to breast cancer recurrence identified based on Logit model analysis

BackgroundThis study intended to determine important genes related to the prognosis and recurrence of breast cancer.MethodsGene expression data of breast cancer patients were downloaded from TCGA database. Breast cancer samples with recurrence and death were defined as poor disease-free survival (DFS) group, while samples without recurrence and survival beyond 5 years were defined as better DFS group. Another gene expression profile dataset (GSE45725) of breast cancer was downloaded as the validation data. Differentially expressed genes (DEGs) were screened between better and poor DFS groups, which were then performed function enrichment analysis. The DEGs that were enriched in the GO function and KEGG signaling pathway were selected for cox regression analysis and Logit regression (LR) model analysis. Finally, correlation analysis between LR model classification and survival prognosis was analyzed.ResultsBased on the breast cancer gene expression profile data in TCGA, 540 DEGs were screened between better DFS and poor DFS groups, including 177 downregulated and 363 upregulated DEGs. A total of 283 DEGs were involved in all GO functions and KEGG signaling pathways. Through LR model screening, 10 important feature DEGs were identified and validated, among which, ABCA3, CCL22, FOXJ1, IL1RN, KCNIP3, MAP2K6, and MRPL13, were significantly expressed in both groups in the two data sets. ABCA3, CCL22, FOXJ1, IL1RN, and MAP2K6 were good prognostic factors, while KCNIP3 and MRPL13 were poor prognostic factors.ConclusionABCA3, CCL22, FOXJ1, IL1RN, and MAP2K6 may serve as good prognostic factors, while KCNIP3 and MRPL13 may be poor prognostic factors for the prognosis of breast cancer.

Serum lactate dehydrogenase is a possible predictor of platinum resistance in ovarian cancer.

ObjectiveThe need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinum-based chemotherapy in ovarian cancer.MethodsWe enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively.ResultsNLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P<0.001, <0.001, 0.029, and <0.001, respectively). The Kaplan-Meier curves revealed that high LDH level (≥250 U/L) was associated with reduced PFI (P=0.037 and 0.012) and DFS (P=0.007 and 0.002) in groups A and B, respectively. High NLR (≥4) was associated with reduced DFS in both groups (P=0.036 and 0.005, respectively). LDH showed higher area under the curve (AUC) values in predicting platinum resistance with a PFI of less than 6 months and 12 months (AUC=0.606 and 0.646, respectively) than NLR. In the multivariate analysis, LDH remained significant (P=0.019) after adjusting for the 9 blood parameters.ConclusionSerum LDH level may possibly predict platinum resistance and prognosis in ovarian cancer and may be useful when developing precision medicine for individual patients.

Abstract 3197: Serum CEA change predicts tumor regression and prognosis in locally advanced rectal cancer

Abstract Objective: To investigate the value of carcinoembryonic antigen (CEA) change in predicting pathological tumor regression and outcome for locally advanced rectal cancer (LARC) patients received neoadjuvant therapy. Material and methods: LARC patients who received neoadjuvant therapy and radical tumor resection were retrospectively collected. The predictive value of baseline CEA, post-treatment CEA and post/pre-treatment CEA ratio for tumor regression grade (TRG), overall survival and diseases free survival were estimated by logistic regression or cox proportional hazard regression. Results: 700 LARC patients were enrolled in the study with 475 (67.9%) cases of male patients and median age of 56 (20-87). Of the all patients enrolled, multivariate analysis showed post-treatment CEA (OR=1.142, 95% CI: 1.073-1.215, P&amp;lt;0.001) was an independent predictor for TRG. 284 patients with elevated baseline CEA were analyzed. Among them, 168 patients (59.2%) have normalized CEA. Multivariate analysis showed post-treatment CEA (OR=1.068, 95% CI: 1.007-1.133, P=0.027), CEA ratio (OR=3.463, 95% CI: 1.269-9.446, P=0.015) were independent predictors for TRG(Table 1). Of the all patients enrolled, multivariate analysis showed low preoperative albumin level (HR=0.919, 95% CI: 0.886-0.952, P&amp;lt;0.001), tumor deposit (HR=3.226, 95% CI: 1.470-7.077, P=0.003), nerve infiltration (HR=3.602, 95% CI: 1.736-7.476, P=0.001), high post-treatment CEA (HR=1.029, 95% CI: 1.010-1.049, P=0.003) were independent unfavored predictors for overall survival of LARC patients. 700 patients were divided into 3 groups: A group with normal baseline CEA (n=416,59.4%); B group with normalized CEA (n=168,24.0%); C group with elevated baseline and post-treatment CEA (n=116,16.6%). The overall survival and disease free survival of group B were comparable to that of group A (P=0.588,0.053) and significantly better than that of group C (B vs. C: P=0.010, 0.003; A vs. C: P=0.007, &amp;lt;0.001). Conclusion: 1. Post-treatment CEA is an independent predictor for TRG of LARC patients and higher post-treatment CEA precdicted poor overall survival. 2. Post/pre-treatment CEA ratio is an independent predictor for TRG of LARC patients with elevated baseline CEA. Citation Format: Zerong Cai, Lingyu Huang, Ping Lan, Xiaojian Wu. Serum CEA change predicts tumor regression and prognosis in locally advanced rectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3197.

A quantitative imaging biomarker for predicting disease-free-survival-associated histologic subgroups in lung adenocarcinoma.

Classification of histologic subgroups has significant prognostic value for lung adenocarcinoma patients who undergo surgical resection. However, clinical histopathology assessment is generally performed on only a small portion of the overall tumor from biopsy or surgery. Our objective is to identify a noninvasive quantitative imaging biomarker (QIB) for the classification of histologic subgroups in lung adenocarcinoma patients. We retrospectively collected and reviewed 1313 CT scans of patients with resected lung adenocarcinomas from two geographically distant institutions who were seen between January 2014 and October 2017. Three study cohorts, the training, internal validation, and external validation cohorts, were created, within which lung adenocarcinomas were divided into two disease-free-survival (DFS)-associated histologic subgroups, the mid/poor and good DFS groups. A comprehensive machine learning- and deep learning-based analytical system was adopted to identify reproducible QIBs and help to understand QIBs' significance. Intensity-Skewness, a QIB quantifying tumor density distribution, was identified as the optimal biomarker for predicting histologic subgroups. Intensity-Skewness achieved high AUCs (95% CI) of 0.849(0.813,0.881), 0.820(0.781,0.856) and 0.863(0.827,0.895) on the training, internal validation, and external validation cohorts, respectively. A criterion of Intensity-Skewness ≤ 1.5, which indicated high tumor density, showed high specificity of 96% (sensitivity 46%) and 99% (sensitivity 53%) on predicting the mid/poor DFS group in the training and external validation cohorts, respectively. A QIB derived from routinely acquired CT was able to predict lung adenocarcinoma histologic subgroups, providing a noninvasive method that could potentially benefit personalized treatment decision-making for lung cancer patients. • A noninvasive imaging biomarker, Intensity-Skewness, which described the distortion of pixel-intensity distribution within lesions on CT images, was identified as a biomarker to predict disease-free-survival-associated histologic subgroups in lung adenocarcinoma. • An Intensity-Skewness of ≤ 1.5 has high specificity in predicting the mid/poor disease-free survival histologic patient group in both the training cohort and the external validation cohort. • The Intensity-Skewness is a feature that can be automatically computed with high reproducibility and robustness.

Impact of BMI for clinical outcomes in Japanese breast cancer patients.

The relationship between the body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients has not yet been clarified. We investigated the impact of obesity for clinical outcomes in Japanese breast cancer patients. Women with primary breast cancer operated between 2002 and 2014 were identified. All patients are categorized into four groups according to BMI. The range of BMI is <18.5kg/m2, from 18.5 to 24.9kg/m2, 25 to 29.9kg/m2, >30kg/m2 in underweight, normal, overweight and obesity groups, respectively. The correlation between BMI and overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were statistically analyzed. From the database of our institution, we identified 3223 patients. The median follow-up period was 57months (1-149). We categorized 2257 (70.0%), 318 (9.9%), 545 (16.9%) and 103 (3.2%) patients into normal, underweight, overweight obesity groups respectively. There were189 patients (5.9%) deaths due to breast cancer recurrence (137 patients) and other disease (52 patients). Obesity groups was significantly high compared with normal groups for OS (adjusted HR, 2.43; 95% CI, 1.38-4.28; P<0.001), BCSS (adjusted HR, 2.73; 95% CI, 1.15-6.44; P=0.02) and DFS (adjusted HR, 1.83; 95% CI, 1.11-3.02; P=0.017) by multivariate analysis. Especially, OS (adjusted HR, 4.87; 95% CI, 2.15-11.04; P<0.001), BCSS (adjusted HR, 4.51; 95% CI, 1.52-13.34; P<0.001) and DFS (adjusted HR, 4.87; 95% CI, 1.02-4.89; P=0.04) were statistically insignificant in postmenopausal ER-positive breast cancer patients. Obesity might be risk factor for OS, BCSS and DFS, especially postmenopausal ER-positive women.

Integrative Bioinformatics Analysis of iNOS/NOS2 in gastric and colorectal cancer

Abstract Objective The aim of the present work was to investigate the expression of nitric oxide synthase 2 (iNOS/ NOS2) in colorectal and gastric cancers and evaluate its association with patient’s prognosis by integrated bioinformatics analysis. Methods The data for present study was obtained from the TCGA, GTEx, and STRING database. iNOS/NOS2 mRNA expression in normal tissue and colorectal, and gastric cancer tissuea were investigated through the GTEx and TCGA database. iNOS/NOS2 gene mutations and frequency were analyzed in the TCGA database using the cBioPortal online data analysis tool. The protein-protein interaction (PPI) network of iNOS/NOS2 was constructed by STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of iNOS/NOS2 and relevant proteins involved in the PPI network were enriched and demonstrated by the bubble plot. Comparison of the overall survival(OS) and disease free survival(DFS) between samples expressing high and low levels of iNOS/NOS2 was analysis based on the TCGA databases through the GEPIA online data analysis tool. Results For colon adenocarcinoma (COAD) and rectal adenocarcinoma(READ) iNOS/NOS2 mRNA expression levels in tumor tissue were significant higher than those of corresponding normal colorectal tissue (p&lt;0.05). iNOS/NOS2 mutations were identified in both colorectal cancer and gastric cancer. Missense substitutions and synonymous substitution were the top two mutation types for colorectal and gastric cancer. The top positive and negative co-expressed genes correlated with iNOS/ NOS2 were TRIM40 (rpearson=0.56, p&lt;0.05) and GDPD5 (rpearson=-0.41, p&lt;0.05) in colorectal cancer respectively andCASP5 (rpearson=0.63,p&lt;0.05) and PIAS3 (rpearson=-0.43,p&lt;0.05) in gastric cancer. Twenty one proteins were included in the PPI network with 51 nodes and 345 edges which indicated the PPI enrichment wassignificant (p=1.0e-16). The KEGG of the included genes were mainly enriched in metabolic pathway and Jak-STAT signaling pathway. There was a significant difference indisease free survival (DFS) between samples expressing high and low iNOS/NOS2 (HR=0.37, p=0.044) in rectal cancer. The difference was not statistical between iNOS/NOS2 high and low expressing groups for overall survival(OS) or DFS in the colon cancer or gastric cancer(p&gt;0.05). Conclusions iNOS/NOS2 mRNA isup-regulated in tumor tissue compared to corresponding normal tissue in colorectal and gastric cancer which implement it in the development of colorectal and gastric cancers.

Thoracoscopic Surgery Shows Non-Inferiority to Open Surgery for Clinical N0-N2 and Pathologic N2 Non-Small Cell Lung Cancer

Objectives Controversy has remained over the primary surgical management for stage IIIA-N2 non–small cell lung cancer. Minimal or non-bulky N2 disease defined as single-station nodal involvement may still be a candidate of radical surgery. The aim of this study was thus to assess the outcome of thoracoscopic surgery in clinical N0-N2 and pathologic N2 disease. Methods Seventy-nine cases of pathologic N2 diseases without induction therapy (clinical N0, 27; N1, 13; N2, 39) were operated on between September 2003 and December 2010 in our institute. Forty-seven patients underwent thoracoscopic surgery (group T) and 32 patients underwent standard thoracotomy (group S). Perioperative and oncologic outcomes were compared between the 2 groups. Results There were no significant differences between the 2 groups regarding dissected number of lymph nodes, operative time, morbidity, and mortality. However, blood loss in group T was less than in group S (Mean: T, 229 versus S, 534 mL, respectively; P = 0.0004). Although disease-free survival in group T did not differ from that in group S, overall survival in group T was better than in group S after propensity score matching to adjust confounding factors including tumor size and T factor (P = 0.03). Multivariate analysis showed that multinodal stations was significantly worse prognostic factor [hazard ratio (HR) = 4.79; 95% confidence interval (CI) = (1.6–14.3); P = 0.005) in disease-free and overall survivals [HR = 8.21; 95% CI = (1.9–35.4); P = 0.005]. Thoracoscopic surgery was favorable prognostic factor in overall survivals [HR = 0.13; 95% CI = (0.03–0.6); P = 0.009]. Conclusions Our study demonstrated that thoracoscopic surgery for non-bulky N2 disease was feasible and not inferior to standard thoracotomy in terms of oncologic outcome.

Clinical Outcomes of Volumetric Modulated Arc Therapy Following Intracavitary/Interstitial Brachytherapy in Cervical Cancer: A Single Institution Retrospective Experience.

Purpose: To evaluate treatment outcomes and toxicity in patients with cervical cancer (CC) treated with volumetric modulated arc therapy (VMAT), followed by three-dimensional high-dose-rate intracavity combined with interstitial brachytherapy (IC/IS BT) compared with intensity-modulated radiation therapy (IMRT) treatment.Materials and Methods: A total of 398 patients with stage IA–IVB CC treated with definitive radiotherapy with or without chemotherapy were retrospectively analyzed (331 VMAT and 67 IMRT). A total prescription dose of 45–50 Gy was delivered to pelvic field with VMAT/IMRT in 25/28 fractions, with five fractions per week. Every patient further received IC/IS BT for four to six 6.0-Gy fractions. Local control (LC), disease-free survival (DFS), overall survival (OS), and distant metastasis-free survival (DMFS) rates were calculated. Acute hematotoxicity and late toxicity were recorded.Results: The median follow-up period was 25.47 (range, 0.93–58.93) months for the VMAT and 35.07 (4.8–90.37) months for IMRT. The 3-year OS, DFS, LC, and DMFS rate were 80.5, 65.4, 88.7, and 78.1% in VMAT group, and 76.2, 76.4, 83.1, and 86.1% in the IMRT group, respectively. No significant differences were found between VMAT and IMRT groups for OS, DFS, LC, and DMFS rate. However, patients in the VMAT group had lower incidence of chronic enterocolitis complication (26.6 vs. 38.8%, p = 0.004). In addition, a total of 3 (0.9%) patients developed grade 3 chronic cystitis, and 7 (2.1%) patients developed grade 3 or greater chronic enterocolitis in VMAT group.Conclusion: VMAT combined with IC/IS BT can result in satisfactory curative outcomes and low incidences of late radiation enterocolitis and cystitis in CC treatment.

Does weekly versus daily low-dose of concurrent cisplatin have any effect on compliance and clinical outcomes in cases of locally advanced head and neck cancers?

e17569 Background: Concurrent Cisplatin with radiotherapy improves outcomes in locally advanced squamous cell carcinomas of the head neck.Cisplatin at 35mg/m2(weekly) raise compliance &amp; hospitalization. There are only few reports on efficacy and toxicity of low dose Cisplatin (6mg/m2). Hence the purpose of this study was to evaluate the compliance and clinical outcomes between two concurrent cisplatin chemotherapy regimens &amp; to see long term effects. Methods: Total 50 patients were included in study from Nov 2015 to Mar 2017 with 25 in each group. Radiotherapy given 70Gy/35# in 7weeks &amp; Cisplatin at 35mg/m2 weekly (Group I) and 6mg/m2 daily (Group II). Assessment of toxicity was done by RTOG scoring criteria. WHO Response criterion was used to assess clinical response. Median follow up was 6 months. Results: Group I(80%) and Group II(84%)patients completed Radiotherapy. In Group I 48% patients received less than 6 cycles and Group II 40% received ≤25 cycles chemotherapy. Median OTT in Group I &amp; II in was 51 &amp; 52days. Neutropenia &amp; Mucositis statistically insignificant between both groups.There was no statistical difference in complete response between the two groups. In Group I 40% patients developed Progressive disease on follow up as compared to 12% in Group II(p-0.02). After 1.5 years of follow up, Group I vs Group II 4 patients had complete response, 6 had recurrence &amp; 11 vs 4 patients expired (p-0.03). At a median follow up of 6 months overall survival in Group I and II was 56% and 44%(p-0.39). While as median disease free survival in Group I &amp; II was 6.6 &amp; 11.9 months(p-0.14). Conclusions: Low dose daily Cisplatin offers ease of administration in the outpatient clinic, better tolerability and better quality of life.Group II patients were more compliant in terms of patients receiving chemotherapy or completing radiotherapy. At median follow up of 6 months there was no statistical difference in terms of overall and disease-free survival. The statistical difference was seen in terms of patients expired in Group I (44%) as compared to Group II (16%). Therefore, we need a larger number of patients for the use of low dose Cisplatin to be evaluated in future clinical trials.

Oncologic safety of nipple-sparing mastectomy in patients with short tumor-nipple distance.

There is a tendency to avoid nipple-sparing mastectomy (NSM) when a tumor-nipple distance (TND) is <2cm due to the risk of occult nipple involvement. The purpose of the study was to determine whether the patients who undergo NSM with immediate reconstruction are oncologically safe when TND is <2cm. Patients who underwent NSM followed by immediate reconstruction for breast cancer were retrospectively analyzed. Patients who are negative for nipple-base in either frozen-section or paraffin histopathology were included. MRI was used to obtain TNDs to compare local-recurrence-free and disease-free survival in group I (TND <2cm) and group II (TND ≥2cm). Disease-free survival rates were determined to assess the outcome. Of the 214 cases with malignancy on MRI, 21 cases diagnosed with pure ductal carcinoma in situ were excluded. Among the 193 NSM cases diagnosed with invasive cancer, TND was <2.0cm in 59 (30.56%) cases and ≥2.0cm in 134 (69.43%) cases. No significant differences were found between groups in regards to ER, PR, HER2-neu status, and nodal involvement (P=0.34, P=0.41, P=0.54, and P=0.12 respectively). In a median follow-up time of 62months (range; 13-114), patients in group I had four local recurrences, whereas group II was found to have five local and three distant metastases. No significant differences were observed between groups concerning disease-free survival (10-year DFS 93.2% vs 96.3%; P=0.368 respectively). Patients who have invasive cancer diagnosis with a TND <2cm are eligible to undergo therapeutic NSM with immediate reconstruction.

Laparoscopic versus conventional open surgery in T4 rectal cancer: A case-control study.

Background:Laparoscopic surgery (LAS) for T4 rectal cancer (RC) is still controversial. This study aims to compare LAS with conventional open surgery in patients with T4 RC.Patients and Methods:Patients undergoing laparoscopic or open curative resection for T4 RC from January 2010 to September 2014 in our hospital were enrolled. Patients’ clinicopathological characteristics and survival outcomes were collected and compared. All statistical analysis was performed using SPSS 22.0.Results:A total of 125 patients (39 open, 86 LAS) were included in this study finally. The baseline information between the two groups were comparable except that LAS group had a more anterior resection (P = 0.012) and less combined resection (P = 0.003). The results demonstrated that patients in LAS group had less blood loss (P < 0.001), smaller incision length (P < 0.001), faster time to first soft diet (P = 0.010) and less incidence of post-operative complications, although it was not significantly different (P = 0.063). In addition, the operative time was also comparable (P = 0.140) and the conversion rate was low (2/86). The 3-year overall survival (OS) was 71.8%, 79.1% in open, LAS group respectively and the 3-year disease-free survival (DFS) was 66.7%, 68.6% in open, laparoscopic group, respectively. The Kaplan curves demonstrated that there was no significant difference between the two groups in OS (P = 0.981) or DFS (P = 0.900).Conclusions:LAS is safe and feasible in selected patients with T4 RC. It can achieve a better perioperative outcomes, and the long-time survival is not inferior to open surgery. Prospective studies should be conducted in the future to reduce the selection bias.