Predictors Of Better Overall Survival Research Articles

Detection of occult neoplastic infiltration in the corpus callosum and prediction of overall survival in patients with glioblastoma using diffusion tensor imaging

ObjectiveCorpus callosum (CC) involvement is a poor prognostic factor in patients with glioblastoma (GBM). The purpose of this study was to determine whether diffusion tensor imaging (DTI) can quantify occult tumor infiltration in the CC and predict the overall survival in GBM patients. MethodsForty-eight patients with pathologically proven GBM and 17 normal subjects were included in this retrospective study. Patients were divided into four groups based on CC invasion and overall survival: long survivors without CC invasion; short survivors without CC invasion; long survivors with CC invasion; short survivors with CC invasion. All patients underwent DTI at 3T MRI scanner. Fractional anisotropy (FA) and mean diffusivity (MD) values were measured from genu, mid-body, and splenium of the CC. The mean values of these parameters were compared between different groups and Kaplan Meier curves were used for prediction of overall survival. ResultsPatients with short survival and CC invasion had the lowest FA values (0.64 ± 0.05) from the CC compared with other groups (p < 0.05). Receiver operator characteristic curve (ROC) analysis indicated that a FA cutoff value of 0.70 was the best predictor for overall survival with an area under the curve (AUC) of 0.77, sensitivity 1, specificity 0.59. Kaplan-Meier survival curves demonstrated that the mean survival time was significantly longer for patients with high FA (>0.70) compared with those with low FA (<0.70) (p < 0.001). ConclusionsFA values from the CC can quantify occult tumor infiltration and serve as a sensitive prognostic marker for prediction of overall survival in GBM patients.

Combined morphologic and metabolic pipeline for Positron emission tomography/computed tomography based radiotherapy response evaluation in locally advanced pancreatic adenocarcinoma.

Adaptive radiation planning for pancreatic adenocarcinoma (PA) relies on accurate treatment response assessment, while traditional response evaluation criteria inefficiently characterize tumors with complex morphological features or intrinsically low metabolism. To better assess treatment response of PA, we quantify and compare regional morphological and metabolic features of the 3D pre- and post-radiation therapy (RT) tumor models. Thirty-one PA patients with pre and post-RT Positron emission tomography/computed tomography (PET/CT) scans were evaluated. 3D meshes of pre- and post-RT tumors were generated and registered to establish vertex-wise correspondence. To assess tumor response, Mahalanobis distances (M dist∣Fusion) between pre- and post-RT tumor surfaces with anatomic and metabolic fused vectors were calculated for each patient. M dist∣Fusion was evaluated by overall survival (OS) prediction and survival risk classification. As a comparison, the same analyses were conducted on traditional imaging/physiological predictors, and distances measurements based on metabolic and morphological features only. Among all the imaging/physiological parameters, M dist∣Fusion was shown to be the best predictor of OS (HR = 0.52, p = 0.008), while other parameters failed to reach significance. Moreover, M dist∣Fusion outperformed traditional morphologic and metabolic measurements in patient risk stratification, either alone (HR = 11.51, p < 0.001) or combined with age (HR = 9.04, p < 0.001). We introduced a PET/CT-based novel morphologic and metabolic pipeline for response evaluation in locally advanced PA. The fused M dist∣Fusion outperformed traditional morphologic, metabolic, and physiological measurements in OS prediction and risk stratification. The novel fusion model may serve as a new imaging-marker to more accurately characterize the heterogeneous tumor RT response.

The Use of HPV16-E5, EGFR, and pEGFR as Prognostic Biomarkers for Oropharyngeal Cancer Patients.

Background: Anti-epidermal-growth-factor-receptor (EGFR) therapies in combination with radiotherapy are being studied on de-escalation clinical trials for HPV-related oropharyngeal cancer (OPC) patients. The HPV16-E5 oncoprotein increases recycling of activated EGFR to the cell surface, enhancing factor signal transduction. Our aim was to evaluate viral HPV16-E5 oncogene expression as well as EGFR and phosphorylated-EGFR (pEGFR), protein levels as biomarkers for clinical outcome in a retrospective cohort of OPC patients.Methods: Formalin-fixed-paraffin-embedded OPCs were collected from 1990 to 2013. OPC samples containing HPV-DNA were subject to viral E6*I mRNA detection and p16INK4a immunohistochemistry (IHC). HPV16-positive cases were evaluated for HPV16-E5 (RT-PCR) and EGFR/pEGFR (IHC). A stratified and matched random sample of HPV-negative samples was used as control and evaluated for EGFR/pEGFR. Overall survival (OS) and disease free survival (DFS) estimates were assessed for locally advanced OPC patients (stage III, IVa,b 7th edition).Results: Among 788 OPC patient samples, 53 were double positive for HPV16-DNA/p16INK4a. HPV16-E5 expression was found in 41 of 53 samples (77.4%). EGFR expression was observed in 37.7 vs 70.8% of HPV16-positive vs HPV-negative samples, respectively; (adjusted OR = 0.15) 5% CI = 0.04–0.56]). Expression of pEGFR followed an inverse pattern with 39.6 and 24.9% detection in HPV16-positive and HPV-negative samples; (adjusted OR = 1.58 [95% CI = 0.48–5.17]). Within HPV16-positive cases, no association between HPV16-E5/EGFR nor pEGFR was observed. With a median follow-up of 39.36 months (min = 0.03 – max = 272.07), the combination of HPV status and EGFR or pEGFR expression were predictors of better OS (p < 0.001, for both) and DFS (p < 0.001 for EGFR and p = 0.003 for pEGFR).Conclusions: HPV16-E5 is highly expressed on HPV16-positive OPCs. Interestingly, HPV16-positive cases expressed significantly more pEGFR while HPV-negative cases expressed more EGFR. The combinations of HPV status and EGFR or pEGFR may be useful biomarkers for evaluating prognosis outcome in OPC patients.

Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre

BackgroundBone metastases (BMs) are associated with significant morbidity and shorter survival in renal cell carcinoma (RCC). Our purpose was to identify prognostic factors for overall survival (OS) in RCC patients with BMs. MethodsData from patients with BMs from RCC treated at Gustave Roussy between April 1992 and March 2016 were retrospectively collected. Age, sex, Eastern Cooperative Oncology Group-Performance Status, Memorial Sloan-Kettering Cancer Center (MSKCC) risk groups, histology, number and site of bone lesions, concomitant metastases (presence and sites), therapy for BMs (radical resection or palliative surgery, radiotherapy and other local and systemic treatments) and time from diagnosis to BMs were analysed. Synchronous solitary bone metastasis (SSBM) was defined as a single BM without concomitant visceral lesions at the initial diagnosis of RCC. OS was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan–Maier method and modelled with Cox regression analysis. ResultsFrom 1750 patients with diagnosis of RCC followed at Gustave Roussy Cancer Campus, 300 patients with BMs were identified. Median time from diagnosis to BMs was 32.4 months (range 0–324 months). In 64 patients (21%), bone was the only metastatic site, and 22 patients (7%) had an SSBM and 236 patients (79%) had concomitant metastases in other sites. Median OS was 23.2 months (95% confidence interval 19.9–26.2). SSBM patients had better OS than those with concomitant metastases (40 vs 20 months; P < 0.001). At multivariate analysis, concomitant metastases remained predictor of poor prognosis, while MSKCC risk group, radical resection and SSBM were predictors of better OS. ConclusionsThis study suggests that MSKCC score, numbers of BMs and radical resection are important prognostic factors for RCC patients with BMs. Additionally, in the presence of solitary BM without concomitant metastases at the initial diagnosis of RCC, bone surgery should be considered to achieve local tumour control and likely increase OS.

Prognostic value of neutrophil to lymphocyte ratio in lung metastasectomy for colorectal cancer.

Neutrophil to lymphocyte ratio (NLR) has been shown to be a promising biomarker in several cancers. Prognostic biomarkers are still needed to define good candidates for lung metastasectomy for colorectal cancer. We aimed to evaluate the role of NLR. Data from 574 patients who underwent lung metastasectomy for colorectal cancer in 3 departments of thoracic surgery from 2004 to 2014 were retrospectively reviewed. Overall survival (OS) and the time to pulmonary recurrence (TTPR) were the main end points. Correlations between NLR and OS (R2 = 0.53), and NLR and TTPR (R2 = 0.389) were significant (P < 0.0001 for both), with corresponding Pearson R of -0.728 (P < 0.0001) and -0.624 (P < 0.0001), respectively. A receiver operating characteristic curve analysis highlighted an NLR cut-off value of 4.05 as the best predictor of OS and TTPR. NLR ≤4.05 was observed in 238 patients (41.4%). In the univariable analysis, the median OS was 117 months for patients with NLR ≤4.05 and decreased to 40 months for patients with NLR >4.05 (P < 0.0001). The median TTPR reached 52 months in case of NLR ≤4.05 and decreased to 12 months in patients with NLR >4.05. In the multivariable analysis, NLR ≤4.05 remained an independent favourable prognostic factor on both OS [hazard ratio [HR] 0.29, 95% confidence interval (CI) 0.167-0.503; P < 0.0001] and TTPR (HR 0.346, 95% CI 0.221-0.54; P < 0.0001). Significant correlations between NLR >4.05 and KRAS (Cramer's V = 0.241, P < 0.0001) and BRAF (Cramer's V = 0.153, P = 0.003) mutations were observed. NLR is a simple and powerful predictor of outcomes in patients undergoing pulmonary metastasectomy for colorectal cancer.

Predictors of Response in Patients Receiving CD34-Selected Stem Cell Infusions without Conditioning to Correct Graft Failure Following Allogeneic Stem Cell Transplantation

▪Introduction: Graft failure (GF) is an infrequent but serious complication of following matched related or unrelated donor peripheral blood stem cell transplantation. Although infusion of CD34+-selected stem cells without additional conditioning is currently one strategy to treat this complication, few studies have reported predictors of response.Methods: We report the outcome of consecutive patients identified at two UK transplant centres between 1999 and 2017 who had primary or secondary GF after an allogeneic peripheral blood stem cell transplant and who underwent a CD34+ selected stem cell infusion without further conditioning. GF was confirmed by chimerism, bone marrow examination and exclusion of relapsed disease. Primary GF was defined by failure to ever achieve count recovery in one or more lineages (neutrophils >0.5x109/L, untransfused platelets >20 x109/L and untransfused Hb >8 g/L) post transplantation. Secondary GF was defined by loss of counts after the initial achievement of engraftment. A complete response (CR) was defined as haematological improvement (HI) in all cell lines (Hb>8g/L, platelets > 30x109/L and neutrophils > 1.5x109/L). A partial response (PR) was defined as HI within the first 30 days but not in all cell lineages. Responses were categorized as early (<30 days after infusion) versus late (>30 days); in the latter case, the role of the CD34+ infusion in count recovery was not known.Results: We identified 62 patients with GF, male:female 35:27, with a median age of 43 years (range, 10-66). Fifty-six patients (90%) had had reduced intensity conditioning. Median follow up was 6.4 years. Diagnoses included acute leukemia (n=18), non-Hodgkin's lymphoma (n=18), Hodgkin's Lymphoma (n=7), MDS (n= 6), multiple myeloma (n=3), myelofibrosis (n=2), CLL (n=2), severe aplastic anaemia (n=2), primary immunodeficiency (n=2), CML (n=1) and sickle cell disease (n=1). The original graft source was peripheral blood stem cells from a matched related donor (n=29), matched unrelated donor (n=18) and mismatched unrelated donor (n=15). Twenty-one (34%) patients had primary GF and 41 (66%) had secondary GF. Forty-three patients (69%) had GF in all 3 lineages and 19 patients (31%) had GF in 1 or 2 lineages. The median CD34+ cell dose/kg recipient weight was 3.2 x 106/kg (range, 0.47-14.2 x 106/kg) at a median of 181 days (range, 21-2718 days) following transplant. No response to CD34+ infusion was seen in 15 (24%) patients. Of the remaining 47 patients who responded (76%), 19 patients achieved a CR <30 days, 19 patients had a CR >30 days, 5 had a PR <30 days and 4 had a PR >30 days. Of those who responded, the median number of days required for neutrophil recovery was 29 days (6-1182), platelets recovery was 18 days (5-600) and haemoglobin recovery was 25 days (6-511). In a multivariate analysis, parameters significantly associated with response were CMV serostatus negative for both patient and donor (OR: 20.12, CI 95%= 1.6 - 248) and matched patient/donor sex (OR: 73, CI 95%= 3.3- 1605). Other factors including CD34+ dose, unrelated/related donor, underlying disease, disease risk score, timing of infusion, recipient/donor age, primary or secondary GF and presence or absence of GVHD did not predict for response. Overall survival (OS) for all patients at 1 and 5 years was 70% (95% CI 58-82) and 54% (95% CI 41-68) respectively. OS at 1 and 5 years was 86.4% (95% CI 75-98) and 73.6% (95% CI 54-92) in patients showing a CR versus 66.7% (95% CI 35-98) and 27.8% (95% CI 3-60) in patients with PR (Figure 1). Patients showing no response had poor outcomes with OS of 33.3% (95% CI 9-58) and 22.2% (CI 95% 5-47) at 1 and 5 years. In responding patients, those who initially had GF in 1-2 lineages had 5-year OS of 93.8% (95% CI 82-99) versus GF in 3 lineages who had a 5-year OS of 53% (95% CI 34-88) (Figure 2).Conclusions: This analysis represents the largest report of outcomes in patients who have received a CD34+ selected stem cell infusion without conditioning for GF. Negative donor/recipient CMV serostatus and sex matching predicted response. In responding patients, GF initially affecting <3 lineages was a predictor of better OS at 5 years. New strategies including cytokine or agonist support, or second transplant need to be investigated in partially or non-responding patients. [Display omitted] DisclosuresHough:University College London Hospital's NHS Foundation Trust: Employment.

Efficacy and toxicity of Decitabine in patients with acute myeloid leukemia (AML): A multicenter real-world experience

BackgroundThe hypomethylating agent Decitabine (DAC) is a valuable treatment option in acute myeloid leukemia (AML), particularly in elderly patients (pts) not suitable for intensive chemotherapy (CHT). However, limited data are available about efficacy and safety of DAC in clinical practice. Patients and methodsWe retrospectively reviewed data of 104 AML pts treated with DAC in eight Italian Hematological Centers from 2015 to 2017. The objective of this study was to evaluate the efficacy and safety of DAC in older AML pts outside of clinical trial. Seventy-five (75%) pts received DAC as first line treatment (Cohort 1) and 29 pts as salvage therapy (Cohort 2). All pts received a DAC schedule of 20 mg/sqm IV for 5-days, every 28 days. The median age was 72.5 years (74 in cohort 1 and 66 in cohort 2) and 16% of pts had an ECOG performance status >2 at the start of DAC treatment (with non-significant difference in the two cohorts). The cumulative illness rating scale (CIRS) was > 6 in 27% of pts. Forty-five pts (43%) had secondary AML. Bone marrow blast count was > 30% in 64% of patients (67/104). In the relapsed cohort 17/29 (59%) patients were treated with DAC after conventional CHT, 5/29 (17%) after allo-SCT and 7/29 (24%) after azacitidine therapy. ResultsA total of 469 DAC cycles were given to the 104 pts with a median of 3 cycles (range 1–21) and 45/104 (43%) pts received > 4 cycles. The Overall Response Rate (ORR = Complete Remission-CR plus Partial Remission-PR) was 33%, significantly higher in Cohort 1 (42%) compared to Cohort 2 (14%) (p = 0.009). The median duration of response was 6 months (range 1–20). In Cohort 1 the best response (CR or PR) was obtained between 3th and 6th cycle. In multivariate Cox regression analysis, achievement of CR or PR (HR = 0.78; p = 0.0004), CIRS < 6 (HR = 0.9; p = 0.04) and complex karyotype (HR = 0.8; p = 0.03) were significant predictors of better overall survival (OS). Median OS from the start of DAC therapy was 11 months for the whole population with a significant OS advantage in Cohort 1 (median OS 12.7 mths vs 6.3 mths; p = 0.003); median OS was significantly longer in responders compared to non-responders (22.6 mths vs 5.7 mths; p < 0.0001). At the last follow-up, 56 patients (54%) are still alive and 48 (46%) are dead (71% due to disease progression). The most common toxicities were myelosuppression and documented infectious complications that occurred mainly during the first 4 cycles. ConclusionThese data confirm the efficacy (ORR 33%) and the acceptable safety profile of DAC in the real life management of AML in elderly pts unsuitable for intensive CHT, with a significant better performance in first line therapy (ORR 42%, median OS 12.7 mths). The efficacy of DAC, both in first line and as salvage therapy, may probably be improved with combined treatment strategies and/or with different DAC schedules that could increase its anti-leukemic effect.

Clinical Validation of Automatable Gaussian Normalized CBV in Brain Tumor Analysis: Superior Reproducibility and Slightly Better Association with Survival than Current Standard Manual Normal Appearing White Matter Normalization

PURPOSE: To validate Gaussian normalized cerebral blood volume (GN-nCBV) by association with overall survival (OS) in newly diagnosed glioblastoma patients and compare this association with current standard white matter normalized cerebral blood volume (WN-nCBV). METHODS: We retrieved spin-echo echo-planar dynamic susceptibility contrast MRI acquired after maximal resection and prior to radiation therapy between 2006 and 2011 in 51 adult patients (28 male, 23 female; age 23-87 years) with newly diagnosed glioblastoma. Software code was developed in house to perform Gaussian normalization of CBV to the standard deviation of the whole brain CBV. Three expert readers manually selected regions of interest in tumor and normal-appearing white matter on CBV maps. Receiver operating characteristics (ROC) curves associating nCBV with 15-month OS were calculated for both GN-nCBV and WN-nCBV. Reproducibility and interoperator variability were compared using within-subject coefficient of variation (wCV) and intraclass correlation coefficients (ICCs). RESULTS: GN-nCBV ICC (≥0.82) and wCV (≤21%) were superior to WN-nCBV ICC (0.54-0.55) and wCV (≥46%). The area under the ROC curve analysis demonstrated both GN-nCBV and WN-nCBV to be good predictors of OS, but GN-nCBV was consistently superior, although the difference was not statistically significant. CONCLUSION: GN-nCBV has a slightly better association with clinical gold standard OS than conventional WM-nCBV in our glioblastoma patient cohort. This equivalent or superior validity, combined with the advantages of higher reproducibility, lower interoperator variability, and easier automation, makes GN-nCBV superior to WM-nCBV for clinical and research use in glioma patients. We recommend widespread adoption and incorporation of GN-nCBV into commercial dynamic susceptibility contrast processing software.

Comparison of extracorporeal membrane oxygenation outcome for influenza-associated acute respiratory failure in Japan between 2009 and 2016.

BackgroundSince the 2009 pandemic influenza, we have nationally established a committee of the extracorporeal membrane oxygenation (ECMO) project. This project involves adequate respiratory management for severe respiratory failure using ECMO. This study aimed to investigate the correlations between changes in respiratory management using ECMO in Japan and outcomes of patients with influenza-associated acute respiratory failure between 2009 and 2016.MethodsWe investigated the incidence, severity, characteristics, and prognosis of influenza-associated acute respiratory failure in 2016 by web-based surveillance. The correlations between clinical characteristics, ventilator settings, ECMO settings, and prognosis were evaluated.ResultsA total of 14 patients were managed with ECMO in 2016. There were no significant differences in age, sex, and the acute physiology and chronic health evaluation II score between 2009 and 2016. The maximum sequential organ failure assessment score and highest positive end-expiratory pressure were lower in 2016 than in 2009 (p = 0.03 and p = 0.015, respectively). Baseline and lowest partial pressure of arterial oxygen (PaO2)/fraction of inspiratory oxygen (FIO2) ratios were higher in 2016 than in 2009 (p = 0.009 and p = 0.002, respectively). The types of consoles, circuits, oxygenators, centrifugal pumps, and cannulas were significantly changed between 2016 and 2009 (p = 0.006, p = 0.003, p = 0.004, p < 0.001, respectively). Duration of the use of each circuit was significantly longer in 2016 than in 2009 (8.5 vs. 4.0 days; p = 0.0001). Multivariate analysis showed that the use of ECMO in 2016 was an independent predictor of better overall survival in patients with influenza-associated acute respiratory failure (hazard ratio, 7.25; 95% confidence interval, 1.35–33.3; p = 0.021).ConclusionsRespiratory management for influenza-associated acute respiratory failure using ECMO was significantly changed in 2016 compared with 2009 in Japan. The outcome of ECMO use had improved in 2016 compared with the outcome in 2009 in patients with influenza-associated acute respiratory failure.

Body mass index and weight change during initial period of chemotherapy affect survival outcome in advanced biliary tract cancer patients.

BackgroundThe impact of obesity on survival is known to vary in different cancers. Advanced biliary tract cancer was rarely analyzed about the relationship between obesity and prognosis. We performed this study to evaluate the BMI and body weight change as prognostic factors for advanced biliary tract cancer patients with palliative chemotherapy.MethodsBetween January 2005 and December 2016, two hundred and seventy-six patients who underwent chemotherapy for biliary tract cancer were retrospectively analyzed. The relationship between BMI (kg/m2) and clinical outcomes including overall and progression-free survival was assessed. Additionally the relationship between change in body composition and overall survival was evaluated.ResultsMedian overall survival was 9.7 months for underweight patients, 10.1 months for normal patients, 15.8 months for overweight group, 13.1 months for obese patients, respectively. (p = 0.047) Univariate analysis showed that BMI, stage III, age less than 64 year-old, gallbladder cancer, operation, radiotherapy and ECOG performance were significantly associated with better survival. Compared with normal patients, overweight patients (BMI 23–24.9kg/m2) had a reduced risk of mortality in multivariate analysis (HR 0.632; 95% CI 0.436–0.918, p = 0.016). In the additional analysis for the effect of changes in body weight and BMI to the overall survival, decrease in body weight and BMI (HR 1.410, 95% CI 1.168–1.986, p = 0.046) was associated with a shorter in overall survival.ConclusionOverweight status and the maintenance of body weight during the initial period of chemotherapy are important and independent predictors of better overall survival in advanced biliary tract cancer patients.

Pathological complete response to chemotherapy in pancreatic cancer: frequency, predictors and impact on overall survival

Background: While Pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) in pancreatic cancer has been associated with improved overall survival (OS), the rate of pCR and its predictors have not been elucidated yet. Our aim was to study factors predicting rate of pCR in a large data set and the impact on OS. Methods: Patients listed in the National Cancer Data Base from 1998 to 2011 were studied. We included patients with NCT followed by surgery. Demographics, cancer characteristics, and treatment modalities including NCT to surgery (NCT-S) interval were studied. Results: A total of 2093 patients were included. Mean age was 62, 51% were male, and 71% had neoadjuvant radiotherapy (NRT). NCT-S was divided into time quintiles in weeks: 8–11, 12–14, 15–19, 20–29 and >29 weeks; as well as a continuous variable). Median follow up was 74 months. Rate of pCR was 2.1% (44/2093). OS in pCR vs non-pCR: 61 vs. 31 months, HR 0.3, 95% CI 0.1–0.9, p 0.03). There was a significant increase in pCR with longer NCT-S interval (quintiles: (5/510 = 1.0%, 9/551 = 1.6%, 8/462 = 1.7%, 12/403 = 3.0% and 10/167 = 6.0%, p < 0.001). In logistic regression: NRT (OR 2.5, 95% CI: 1.1–6.1, p = 0.03) and NCT-S interval per week increase (OR 1.1, 95% CI 1.03–1.09, p < 0.001) as well as NCT-S >29 weeks (OR 6.1, 95% CI 2.02–18.50, p < 0.001) were predictive of increased pCR rate. Multivariate Cox regression showed that age, pCR and NCT-S >29 weeks were significantly predictive of OS, while gender, race, facility type, tumor grade, cT, cN stage, single vs. multiple chemotherapy agents and NRT were not.. Conclusion: NCT-S interval >29 weeks and pCR were independent predictors of better OS in pancreatic cancer patients. NRT predicted increased pCR but not OS in the multivariate analysis. Further studies are needed to optimize multimodality regimens that best improve OS.

Association of proteinuria, hypertension, and hand-foot-skin reaction with efficacy of apatinib in gastric cancer: Results from the post-marketing study (Ahead-G201).

73 Background: Ahead-G201 is an ongoing open-label, multicenter, post-marketing Phase IV trial assessing safety and efficacy of apatinib in 2000+ patients (pts) with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction. Proteinuria (PTN), hypertension (HTN) and hand-foot-skin reaction (HFSR) are common adverse events (AEs) related to anti-angiogenesis drugs. Methods: As of 2017/7/10, 1037 and 820 pts were evaluable for safety and survival. Clinical outcomes were compared between pts with and without PTN / PTN / HFSR using Kaplan–Meier methods and multivariate Cox regression model. Results: 200 (19.3%), 194 (18.8%) and 115 (11.1%) pts had PTN, HTN and HFSR, respectively. Similar mean daily dosage was found between pts with and without PTN, HTN or HFSR (from 520.6 to 551.0 mg/day). Pts developed PTN / HTN / HFSR had longer median medication durations (57 vs. 33 / 55 vs. 35 / 65 vs. 36 days; p&lt;0.001). However, there was no significant difference in tumor response and progression free survival (PFS) between pts with and without PTN/HTN/HFSR (Table). Only pts had HFSR showed significantly longer overall survival (OS) (8.38 vs. 5.95 months; p=0.0003). After adjusted for baseline and treatment characteristics, presence of HFSR was found to be independently associated with prolonged OS (HR: 1.82 [95%CI, 1.25–2.66]). Conclusions: Occurrence of HFSR is an independent predictor of better OS. Prior analysis based on Phase II and III indicated the relationship between HTN and prolonged OS, which needs to be further analyzed. Clinical trial information: NCT02426034. [Table: see text]

A novel morphologic and metabolic feature fused treatment response evaluation pipeline for pancreatic adenocarcinoma patients.

311 Background: Adaptive radiation therapy for pancreatic adenocarcinoma (PA) relies on accurate treatment response assessment. Traditional RECIST criteria poorly characterize tumors with complex morphological features, while PET imaging inefficiently detects tumors with intrinsically low standardized uptake value (SUV). Here, we performed regional comparisons of 3D intact PA surfaces pre and post chemoradiotherapy (CRT) utilizing surface measurements containing both morphological and metabolic features to better assess response. Methods: Twenty-one locally advanced PA patients with pre- and 6-8 week post-CRT 18F FDG-PET/CT scans were evaluated. Boundaries of initial and post-CRT tumors were manually defined on respective CT images. On each of the tumors, 3D meshes were generated, followed by surface based registration to achieve vertex-wise correspondence. For each surface vertex, a multivariate vector was formed from two components: anatomic (deformation tensors resulted from surface registration), and metabolic (regional SUV obtained from radius to surface projections). To assess tumor response, paired mahabanobis distance (Mdist) between pre- and post-CRT tumor surfaces with previously formed multivariate vectors were calculated for each patient. Mdist was evaluated using Cox analysis correlated with overall survival (OS) and compared with measurements based on serum CA19-9, volume, SUVmax and SUVmean. Results: Among all the tested parameters, Mdist is the best predictor of OS, with a hazard ratio of 0.437 (p = 0.036). Post-CRT versus pre-CRT ratios based on volume and SUVmax both reached borderline significance (p = 0.0769 and 0.0799, respectively), while CA19-9 and SUVmean failed in predicting OS in our small cohort of patients. Conclusions: We introduced a PET/CT-based novel morphologic and metabolic pipeline for post-CRT response evaluation in locally advanced PA. The fused Mdist outperformed traditional morphologic, metabolic, and physiological measurements in OS prediction. The presented fused model may serve as a new biomarker to better characterize the heterogeneity of tumor response to CRT and a predictive marker for surgical resection.

HE4 and eIF3a Expression Correlates with Surgical Outcome and Overall Survival in Ovarian Cancer Patients with Secondary Cytoreduction.

For recurrent ovarian cancer (ROC), secondary cytoreductive surgery (SCS) is recommended as one optional treatment. However, little is known about the expression and clinical significance of biomarkers during SCS. Human epididymis protein 4 (HE4) is a clinical biomarker for ovarian cancer. Eukaryotic translation initiation factor 3a (eIF3a) is investigated extensively as a potential biomarker for malignancy. The purpose of this study was to investigate the expressions of HE4 and eIF3a at SCS, as well as their associations with surgical outcome and survival in ROC patients. Immunohistochemistry was performed to determine the expressions of HE4 and eIF3a in ovarian tumors taken from both initial and secondary cytoreductive surgery of 35 ROC patients. eIF3a levels were significantly increased at SCS, compared to those at initial cytoreductive surgery (ICS), while HE4 levels were similar. Both HE4 and eIF3a expressions were associated with surgical outcome, in terms of residual tumor. For ICS, patients with high HE4 expression achieved a higher incidence of optimal cytoreduction than those with low HE4 expression (81.0% vs. 33.3%, P = 0.015). A similar result happened in SCS, indicated by higher incidence of no residual tumor in patients with high HE4 expression (76.4% vs. 44.4%, P = 0.046). And high HE4 expression at SCS was more likely to enhance surgical outcome of SCS (77.8% vs. 29.4%, P = 0.038). Therefore, high HE4 expression at either surgery is a predictor of better overall survival (OS) (P = 0.011 and 0.002). Furthermore, patients with an elevated total score (TS) of HE4 between the two surgeries tended to have prolonged OS, compared to those with a non-elevated TS of HE4 (P = 0.076). For eIF3a, initial eIF3a expression was associated with secondary residual tumor (P = 0.035), and the difference in eIF3a expression between the two surgeries correlated with OS (P = 0.052). The expressions of HE4 and eIF3a in tumor specimens correlated with surgical outcome and predicted OS in ROC patients with SCS, thus meriting further investigation.

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status.

Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system. From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis. 137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143). The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

Challenging a dogma: five-year survival does not equal cure in all colorectal cancer patients

ABSTRACTBackground: The current study tried to evaluate the factors affecting 10- to 20- years’ survival among long term survivors (>5 years) of colorectal cancer (CRC).Methods: Surveillance, Epidemiology and End Results (SEER) database (1988-2008) was queried through SEER*Stat program.Univariate probability of overall and cancer-specific survival was determined and the difference between groups was examined. Multivariate analysis for factors affecting overall and cancer-specific survival was also conducted.Results: Among node positive patients (Dukes C), 34% of the deaths beyond 5 years can be attributed to CRC; while among M1 patients, 63% of the deaths beyond 5 years can be attributed to CRC. The following factors were predictors of better overall survival in multivariate analysis: younger age, white race (versus black race), female gender, Right colon location (versus rectal location), earlier stage and surgery (P <0.0001 for all parameters). Similarly, the following factors were predictors of better cancer-specific survival in multivariate analysis: younger age, white race (versus black race), female gender, Right colon location (versus left colon and rectal locations), earlier stage and surgery (P <0.0001 for all parameters).Conclusion: Among node positive long-term CRC survivors, more than one third of all deaths can be attributed to CRC.

Preoperative Prognostic Factors After Liver Resection for Non-Colorectal, Non-Neuroendocrine Liver Metastases and Validation of the Adam Score in an Asian Population.

Historically, the benefit of liver resection for non-colorectal, non-neuroendocrine (NCNN) liver metastases has been controversial. This study aims to determine the preoperative prognostic factors of liver resection for NCNN liver metastases and validate the Adam score in an Asian population. Consecutive patients who underwent liver resection for NCNN liver metastases were identified retrospectively from a prospective liver resection database of the single institution between 2001 and 2014. Univariate Cox regression models were used to identify associations with outcome variables. Recurrence-free interval and overall survival were determined using the Kaplan-Meier method and compared using log-rank test. Seventy-eight consecutive patients were identified, which met the study criteria. Univariate analysis demonstrated that adenocarcinoma histology of primary cancer, disease-free interval and number of nodules were significant predictors of survival. Four of the six components of Adam score were significant predictors of survival. These were the presence of extrahepatic metastases, R2 resection, disease-free interval and type of a primary tumour. The total Adam score was also a significant predictor of survival. Liver resection for NCNN liver metastases is a safe and viable treatment option in carefully selected patients. Significant preoperative prognostic factors include adenocarcinoma primary tumours, disease-free interval and number of nodules. The total Adam score was a good predictor of overall survival and can be used to risk stratify patients undergoing hepatic resection for NCNN liver metastases.

Lewis x Antigen is Associated to Head and Neck Squamous Cell Carcinoma Survival.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with poor prognosis without appropriate prognostic markers. Previous research shows that Lewis antigens have been involved in carcinoma dissemination and patients´ survival. Fucosyl and sialyltransferases are the enzymes implicated in the Lewis antigens synthesis. The purpose of this study was to evaluate the prognostic utility of Lewis antigens in HNSCC. We conducted a prospective research including histological samples from 79 patients with primary HNSCC. Lewis x and sialyl Lewis x expression were detected by immunohistochemistry; patient's data, progression free, and overall survival were documented. A statistical correlation study of antigenic expression and patients´ histopathological variables was performed. Cox regression models with internal validation procedures were employed to analyze survival data. By immunohistochemistry, Lewis x was detected in 34/79 (43%) tumor samples, while sialyl Lewis x only in 11/79 (14%). Lewis x expression showed a positive correlation with tumor differentiation and a better overall survival for Lewis x+patients was detected. Moreover, multivariate Cox's regression analysis showed that Lewis x is an independent predictor of better overall survival. The in silico analysis supported the presence of deregulated fucosyl (FUT4) and sialyltransferase (ST3GAL4) in the Lewis synthetic pathway related to patient survival. These results suggest that Lewis x expression is associated with a better outcome in patients with HNSCC.

Effects of Adjuvant Radiotherapy in Patients With Synovial Sarcoma.

To analyze the treatment outcomes and the effects of adjuvant radiotherapy (RT) in patients with synovial sarcoma (SS). The medical records of 103 patients treated with definitive surgery for SS, with/without RT, from August 1982 to July 2013 were reviewed retrospectively. The median age of the patients was 33 years (range, 5 to 72 y). The most frequent tumor location was the extremities (79 patients, 77%). Seventy-five patients (73%) received adjuvant RT and 26 (25%) did not. The median dose of adjuvant RT was 61.2 Gy (range, 45 to 66.6 Gy). The median follow-up period was 5.4 years (range, 0.2 to 31.0 y). The 5- and 10-year overall survival rates were 77 % and 65%, respectively. The progression-free survival (PFS) rates at 5 and 10 years were 52% and 43%, respectively. The most common site of initial failure was the lung (24 patients), followed by local recurrence (14 patients). The 5-year local-recurrence-free survival (LRFS) and distant-metastasis-free survival (DMFS) rates were 80% and 63%, respectively. On multivariate analysis, a mitosis count of <10 per 10 high-power fields (HPF) was a significant predictor of better overall survival, PFS, LRFS, and DMFS (P=0.004, <0.001, 0.025, and <0.001, respectively). Adjuvant RT was an additional prognostic factor for better PFS and LRFS (P=0.006 and 0.028, respectively). A positive/uncheckable resection margin was associated with poor prognosis for DMFS (P=0.011). There was no significant difference in LRFS between the higher and lower RT dose groups (<63 Gy group, 89%; ≥63 Gy group, 88%; P=0.772). The lung and primary site were frequent sites of failure in patients treated with definitive surgery for SS. Adjuvant RT improved LRFS and PFS. Frequent mitotic figures (≥10 mitoses per 10 HPF) were the worst prognostic factor for these patients.

Predictive value of neutrophil-to-lymphocyte ratio on pathological complete response in triple negative breast cancer.

e12012 Background: Immune response in Triple Negative Breast Cancer (TNBC) plays a critical role in pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Therefore, neutrophil to lymphocyte ratio (NLR) could be an interesting biomarker to evaluate systemic inflammation in TNBC. Our aim was to evaluate the effect of NLR, also progression free survival (PFS) and overall survival (OS) as secondary objectives. Methods: We reviewed 338 medical records of II-III CS TNBC patients treated with NAC, in the 2000-2014 period, at Instituto Nacional de Enfermedades Neoplasicas. Patients were grouped in NLR &lt; 3 and ≥3. Survival differences were assessed by log-rank test in the univariate analysis and prognostic factors were then investigated by Cox regression analysis. Results: Mean age was 47y [range:24-79], 54% were premenopausal, 90.9% had clinical T3-T4 tumor and 80.5% clinical nodal involvement. There were 44 and 294 pts with II and III CS, respectively. From 338 patients, 259 had NLR &lt; 3 and 79, ≥3. No significant clinical differences were noted between these groups, except a higher mean BMI among patients with NLR &lt; 3 (28 vs 26Kg/m2, p = 0.01). pCR rate was higher in NLR &lt; 3 patients (22% vs 15.2%, p &lt; 0.001) and partial response was reached on 70.7% and 62% of pts with NLR &lt; 3 and ≥3, respectively. At 5 year median follow-up, 5-year DFS was higher among patients with NLR &lt; 3 (47 vs 34%, HR = 0.69, 95%CI: 0.50-0.95, p = 0.02) and so was 5-year OS (55 vs 40%, HR: 0.61, CI95%: 0.43-0.85, p = 0.004). At multivariate analysis, premenopausal status, non-pCR and nodal involvement were associated with worse DFS. Otherwise, NLR &lt; 3 (HR: 0.61, 95%CI: 0.43-0.86, p = 0.005) and pCR were predictors of better OS, nonetheless nodal involvement had negative impact on OS. Conclusions: NLR is a valuable predictive biomarker of pCR and OS in TNBC patients. We report less pCR rates due to higher stages among peruvian population.