Significant Prognostic Factors For Overall Survival Research Articles

Adult T-Cell Leukemia/Lymphoma: A Cohort of 41 Cases Recorded in the Brazilian T-Cell Project

Introduction:Adult T cell Leukemia/Lymphoma (ATLL) is a mature T-Cell-neoplasm related to human T-cell lymphotropic virus type 1 (HTLV-1) infection that shows variable clinical presentation and adverse prognosis with shorter overall survival (OS) when compared to other peripheral T-cell lymphomas (PTCL). Previous epidemiological studies estimated cumulative incidence in endemic regions around the world. In Brazil, mainly due to its vast dimension, data collection has limitations and is subject to bias. In April 2015 theBrazilianT-cell longitudinal project initiative was launched. One of the primary purposes was the collection of epidemiological and clinical data from the most frequent subtypes of newly diagnosed PTCL. Among them, 41 cases of ATLL were recorded. Objectives:The aim of this study is to describe clinical features, frequency and overall survival (OS) of 41 cases of ATLL registered in the ongoingBrazilianT-Cell Project. Methods:This is an ambispective observational study design collecting baseline characteristics, clinical features including date of diagnosis, clinical subtypes, B symptoms, performance status, Ann-Arbor staging, HTLV-1 status, number of sites, nodal and extra nodal presentation and types of skin lesions, peripheral blood counts and biochemical tests, front-line treatment and best response after first-line treatment. REDcap Platform has been used to collect and store data and for descriptive analysis the IBM-SPSS version 24 was applied. Kaplan-Meier method estimated the OS, whereas Log-Rank tests to compare its curves. OS period was calculated from diagnosis date until death or last seen date, and event was death by any cause. Results:Out of 281 cases of PTCL registered so far, 41 were ATLL cases. The median age was 50 years (34-88), 25 (64%) female; a higher incidence of lymphoma subtype was observed (46%), followed by acute (29%), chronic (17%) and smoldering (8%). Most of the patients (85%) had advanced-stage disease (III-IV, Ann-Arbor) and 56% had B symptoms (Table 1); 73% received chemotherapy with anthracycline-based regimens (46.5% CHOEP; 33.5% CHOP; 20% others) whereas 17% were managed with immunotherapy and antiviral therapy. The overall response rate was 30%; no response or progression 46%; stable disease 9% and 15% no data available yet (Table 2). Median follow-up was 13 months and 25 months for 41% of alive patients. Two year OS was 39% (95%CI: 23-55%) (Figure 1). Smoldering and Chronic subtypes showed better OS when compared with acute and lymphoma (100% smoldering, 86% chronic; 30% lymphoma type and 13% acuteP=0.04) (Figure 2). The multivariate Cox Regression analysis found male gender (HR 10.9 95%CI: 3.0-39.7, P<0.0001) and albumin (HR 0.23 Beta -1.45 95%CI: 0.10-0.55, P=0.001) as significant prognostic factors for OS. Discussion:ATLL prognosis remains poor regardless of the type of treatment regimen and may be associated with the high incidence of lymphoma and acute subtypes, as well as advanced stage disease presentation. Despite the high number of cases seen in southeastern region of Brazil, it is important to emphasize there are still limited data from other regions. Albeit the sample size is small, these findings confirmed literature review data so far, with poor overall survival in a short time and gender and albumin as predictors of OS in the multivariate analysis. Conclusion:This study highlights the poor prognosis associated with ATLL. Moreover, it seems relevant to expand this study to all Brazilian regions. Hence, the need for early diagnosis and new treatment strategies, able to reduce mortality is warranted, that could possibly change the nature and spectrum of disease. Disclosures Federico: Spectrum:Consultancy, Membership on an entity's Board of Directors or advisory committees;Sandoz:Consultancy, Membership on an entity's Board of Directors or advisory committees;Cephalon/Teva:Research Funding;Mundipharma s.r.l.:Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Millennium/Takeda:Research Funding;Roche:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda:Consultancy, Membership on an entity's Board of Directors or advisory committees.

Validation of Prognostic Radiomic Features From Resectable Pancreatic Ductal Adenocarcinoma in Patients With Advanced Disease Undergoing Chemotherapy.

Radiomic features in pancreatic ductal adenocarcinoma (PDAC) often lack validation in independent test sets or are limited to early or late stage disease. Given the lethal nature of PDAC it is possible that there are similarities in radiomic features of both early and advanced disease reflective of aggressive biology. To assess the performance of prognostic radiomic features previously published in patients with resectable PDAC in a test set of patients with unresectable PDAC undergoing chemotherapy. The pre-treatment CT of 108 patients enrolled in a prospective chemotherapy trial were used as a test cohort for 2 previously published prognostic radiomic features in resectable PDAC (Sum Entropy and Cluster Tendency with square-root filter[Sqrt]). We assessed the performance of these 2 radiomic features for the prediction of overall survival (OS) and time to progression (TTP) using Cox proportional-hazard models. Sqrt Cluster Tendency was significantly associated with outcome with a hazard ratio (HR) of 1.27(for primary pancreatic tumor plus local nodes), (Confidence Interval(CI):1.01 -1.6, P-value = 0.039) for OS and a HR of 1.25(CI:1.00 -1.55, P-value = 0.047) for TTP. Sum entropy was not associated with outcomes. Sqrt Cluster Tendency remained significant in multivariate analysis. The CT radiomic feature Sqrt Cluster Tendency, previously demonstrated to be prognostic in resectable PDAC, remained a significant prognostic factor for OS and TTP in a test set of unresectable PDAC patients. This radiomic feature warrants further investigation to understand its biologic correlates and CT applicability in PDAC patients.

Grade 4 Lymphopenia Induced by High Cardiac Radiation Exposure Predicted the Poor Prognosis in Left Non-Small Cell Lung Cancer Receiving Postoperative Radiotherapy

Aimed to investigate the correlation between grade 4 (G4) lymphopenia and cardiac dosimetric and the role of G4 lymphopenia in predicting prognosis in left non-small cell lung cancer (NSCLC) receiving postoperative radiotherapy (PORT). Between 2009 and 2018, the clinical characteristics and radiation parameters of patients with PORT for left NSCLC were reviewed retrospectively. Lymphopenia was graded according to the CTCAE 4.0. Absolute lymphocyte count (ALC) nadir < 0.2 × 103/ul was defined as grade 4 (G4) lymphopenia. Logistic regressions were performed to analyzed potential related factors of lymphopenia. The overall survival (OS) was measured from the date of RT started to the date of death from any cause or the follow-up date. Kaplan-Meier was performed to calculate survival, and log-rank test was used to compare survival between the G4 and non-G4 group. Two-sided p values < 0.05 were considered statistically significant. A total of 151 patients were reviewed in this study. The major patients were female (52.3%), age ≥ 60 (60.3%), former/current smoker (74.8%), lobectomy (79.5%), stage III (84.1%), postoperative chemotherapy (75.5%) and intensity-modulated radiotherapy (IMRT, 64.2%). The clinical characteristics (e.g. Cardiac disease, body mass index, baseline ALC) and radiation dosimetric (PTV dose, and Heart/Lung RT dosimetric) of G4 (18 pts., 11.9%) and non-G4 (133 pts., 88.1%) were well balanced. The median PTV dose was 60 Gy in G4, whereas it was 54 Gy in non-G4. However, the PTV of G4 was significantly larger than that of non-G4 (563.51 ± 276.07 vs. 395.86 ± 254.58, p = 0.005). Multivariate logistic regression indicated PTV volume (HR 1.00, p = 0.01), PTV dose (HR 1.08, p = 0.04), RT fraction size (HR 0.23, p = 0.02), and Heart V5 (HR 1.09, p = 0.03) were associated with G4 lymphopenia. The median survival time of the whole cohorts was 36.8 months, while it was 23.2 months in the G4 group and 37.5 months in the non-G4 group (p = 0.01). The 1- and 3-year survival in G4 were 77.8% and 33.3%, respectively, compared to 85.2% and 53.1%, respectively, in non-G4. Multivariate analysis revealed former/current smoker (HR 1.57, p = 0.04), postoperative chemotherapy (HR 0.58, p = 0.02) and G4 lymphopenia (HR 1.78, p = 0.04) were significant prognostic factors for OS. Grade 4 lymphopenia was common in left NSCLC patients with PORT and correlated with heart V5. Grade 4 lymphopenia could predict poor survival in this population.

Impact of sidedness of colorectal cancer on tumor immunity

BackgroundClinical and molecular characteristics differ between right-sided and left-sided colorectal cancer (CRC). This study aimed to clarify the correlation between CRC sidedness and tumor immunity.MethodsA total of 102 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of programmed cell death (PD)-1, PD1-ligand 1 (PD-L1), forkhead box P3 (Foxp3), transforming growth factor (TGF)-β, and indoleamine-pyrrole 2,3-dioxygenase (IDO) were examined using immunohistochemistry and the relationships between sidedness and several prognostic factors were examined.ResultsClinicopathological factors were not significantly different between right- and left-sided CRC. The tumor immunity-related molecule PD-L1 was more highly expressed in right-sided than in left-sided CRC (62.9% vs. 30.6%, p<0.01). No significant difference was found in overall survival (OS) and disease-free survival (DFS) by sidedness. PD-1 and Foxp3 expression were significant prognostic factors for OS. Lymph node metastasis (N), lymphatic invasion (ly), and PD-L1 expression were significant prognostic factors for DFS. In right-sided CRC, IDO-positive patients had a poor OS (p<0.05), and IDO was the only independent prognostic indicator for OS. N and venous invasion were identified as independent prognostic indicators for DFS. In left-sided CRC, univariate analysis identified PD-1, PD-L1, and Foxp3 expression as significant predictors of poor OS. Multivariate analysis confirmed PD-L1 expression as an independent prognostic indicator. N, ly, and PD-L1 expression levels were identified as significant predictors of poor DFS.ConclusionsThe prognostic factors were IDO in right-sided CRC and PD-L1 and Foxp3 in left-sided CRC. These findings indicated that tumor immunity might play different roles depending upon sidedness. Tumor location may be an important factor to consider when assessing immune response and therapeutic decisions in CRC patients.

The prognostic significance of inflammation-based scores in patients with ampullary carcinoma after pancreaticoduodenectomy

BackgroundGrowing evidence indicates that the systemic inflammatory response plays an important role in cancer development and progression. Several inflammatory markers have been reported to be associated with clinical outcomes in patients with various types of cancer. This study was designed to evaluate the prognostic value of inflammatory indexes in patients with ampullary cancer (AC) who underwent pancreaticoduodenectomy (PD).MethodsWe retrospectively reviewed the data of 358 patients with AC who underwent PD between 2009 and 2018. R software was used to compare the area under the time-dependent receiver operating characteristic (ROC) curves (AUROCs) of the inflammation-based indexes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI) and prognostic index (PI), in terms of their predictive value for survival. The survival differences of these indexes were compared by the Kaplan-Meier method and univariate and multivariate analyses were performed to determine the prognostic factors of disease-free survival (DFS) and overall survival (OS).ResultsThe estimated 1-, 2-, and 3-year OS and DFS rates were 83.9, 65.8, and 55.2% and 58.0, 42.8, and 37.8%, respectively, for the entire cohort. The survival differences were significant in terms of OS and DFS when patients were stratified by these inflammation-based indexes. The comparisons of the AUROCs of these inflammation-based indexes illustrated that NLR and PI displayed the highest prognostic value, compared to the other indexes. When NLR and PI were combined, NLR-PI showed even higher AUROC values and was identified as a significant prognostic factor for OS and DFS.ConclusionSpecific inflammatory indexes, such as NLR, PLR and dNLR, were found to be able to predict the OS or DFS of patients. As a novel inflammatory index, the level of NLR-PI, which can be regarded as a more useful prognostic index, exhibited strong predictive power for predicting the prognosis of patients with AC after the PD procedure.

Prognostic significance of sarcopenia in microsatellite-stable gastric cancer patients treated with programmed death-1 inhibitors.

Sarcopenia has been underscored as a significant predictor of poor prognosis in cancer patients undergoing immunotherapy with programmed death-1 (PD-1) inhibitors. We aimed to investigate the prognostic significance of computed tomography (CT)-determined sarcopenia in patients with microsatellite-stable (MSS) gastric cancer (GC) treated with PD-1 inhibitors. We retrospectively assessed patients with MSS GC who had been treated with PD-1 inhibitors from March 2016 to June 2019. Pre-treatment sarcopenic status was determined by analyzing L3 skeletal muscle index with abdominal CT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and the differences in survival probability according to sarcopenic status were compared using the log-rank test. Cox proportional hazards regression analyses were performed to identify predictors of PFS and OS. Of 149 patients with MSS GC (mean age, 57.0 ± 12.3years; 93 men), 79 (53.0%) had sarcopenia. Patients with sarcopenia had significantly shorter PFS than patients without sarcopenia (median, 1.4months vs. 2.6months; P = 0.026). Sarcopenia was independently associated with shorter PFS (adjusted hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.10-2.93; P = 0.020). Patients with sarcopenia had shorter OS than patients without sarcopenia (median, 3.6months vs. 4.9months; P = 0.052), but sarcopenia itself was not a significant prognostic factor for OS (adjusted HR, 1.01; 95% CI, 0.58-1.75; P = 0.974). CT-determined sarcopenia is an independent prognostic factor for PFS in patients with MSS GC treated with PD-1 inhibitors.

Preoperative sarcopenia is associated with poor overall survival in pancreatic cancer patients following pancreaticoduodenectomy.

To analyze the effect of preoperative body composition on survival in patients with pancreatic cancer following pancreaticoduodenectomy (PD). Between October 2005 and August 2018, 116 patients (68 men, 48 women, mean age 66.2 ± 11.9 years) diagnosed with pancreatic adenocarcinoma following PD were retrospectively enrolled. The preoperative CT on vertebral level L3 was assessed for total abdominal muscle area (TAMA), visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and mean skeletal muscle attenuation (SMD). The clinical data and pathological findings of tumors were collected. The impact of these factors on disease-free survival (DFS) and overall survival (OS) was evaluated by the Kaplan-Meier method and by univariable and multivariable Cox proportional hazards models. The 3-year DFS and OS rates were 8% and 25%, respectively. Of 116 patients, 20 (17.2%), 3 (2.6%), and 46 (39.7%) patients were classified as having sarcopenia, sarcopenic obesity, and myosteatosis, respectively. The VAT-TAMA ratio (1.2 ± 0.7 vs 0.9 ± 0.5, p = 0.01) and the visceral to subcutaneous adipose tissue area ratio (1.3 ± 0.7 vs 0.9 ± 0.5, p = 0.04) were higher in sarcopenic patients than in the nonsarcopenic group. Preoperative sarcopenia and sarcopenic obesity were associated with shorter OS (p = 0.012 and p = 0.041, respectively), but not shorter DFS. Myosteatosis was neither associated with DFS nor OS. On multivariable analysis, sarcopenia was the only significant prognostic factor for OS (p = 0.039). Preoperative sarcopenia assessed by CT is a poor prognostic factor for OS in pancreatic cancer patients after PD. • Sarcopenia and sarcopenic obesity can be evaluated by abdominal CT on L3 level. • Patients with diabetes mellitus (DM) had lower sex-standardized subcutaneous adipose tissue area index and skeletal muscle density and higher visceral to subcutaneous adipose tissue area ratio than did those without DM. • Preoperative sarcopenia, sarcopenic obesity, and new-onset diabetes mellitus may predict poor overall survival in pancreatic cancer patients following pancreaticoduodenectomy.

A Nomogram Based on Aspartate Aminotransferase/Alanine Aminotransferase (AST/ALT) Ratio to Predict Prognosis After Surgery in Gastric Cancer Patients.

Introduction:Using the TMN classification alone to predict survival in patients with gastric cancer has certain limitations, we conducted this study was to develop an effective nomogram based on aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio to predict overall survival (OS) in surgically treated gastric cancer.Methods:we retrospectively analyzed 190 cases of gastric cancer and used Cox regression analysis to identify the significant prognostic factors for OS in patients with resectable gastric cancer. The predictive accuracy of nomogram was assessed using a calibration plot, concordance index (C-index) and decision curve. This was then compared with a traditional TNM staging system. Based on the total points (TPS) by nomogram, we further divided patients into different risk groups.Results:multivariate analysis of the entire cohort revealed that independent risk factors for survival were age, clinical stage and AST/ALT ratio, which were entered then into the nomogram. The calibration curve for the probability of OS showed that the nomogram-based predictions were in good agreement with actual observations. Additionally, the C-index of the established nomogram for predicting OS had a superior discrimination power compared to the TNM staging system [0.794 (95% CI: 0.749-0.839) vs 0.730 (95% CI: 0.688-0.772), p < 0.05]. Decision curve also demonstrated that the nomogram was better than the TNM staging system. Based on TPS of the nomogram, we further subdivided the study cohort into 3 groups including low risk (TPS ≤ 158), middle risk (158 < TPS ≤ 188) and high risk (TPS > 188) categories. The differences in OS rate were significant among the groups.Conclusion:the established nomogram is associated with a more accurate prognostic prediction for individual patients with resectable gastric cancer.

Prognostic value of prognostic nutritional index in nasopharyngeal carcinoma: A meta-analysis containing 4511 patients.

The prognostic nutritional index (PNI) is an index reflecting the nutritional and inflammatory status of patients and is explored for prognosis in nasopharyngeal carcinoma (NPC). However, the data are conflicting. In the current study, a meta-analysis was performed to comprehensively clarify the association between PNI and prognosis of NPC. PubMed, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), and Wanfang database were searched up to July 25, 2020. Hazard ratio (HR) and with 95% confidence interval (CI) were calculated to assess the impact of PNI on the survival outcomes of patients with NPC. A total of 10 studies containing with 4511 patients were identified. The pooled results showed that NPC patients with a low PNI would have a worse overall survival (OS) (HR=1.89, 95%CI=1.59-2.25, p<0.001), distant metastasis-free survival (DMFS) (HR=2.01. 95%CI=1.66-2.43, p<0.001), progression-free survival (PFS) (HR=1.59, 95%CI=1.32-1.91, p<0.001), and locoregional recurrence-free survival (LRRFS) (HR=1.51, 95%CI=1.04-2.21, p=0.032). Subgroup analysis showed that the low PNI was still a significant prognostic factor for OS and DMFS. Our meta-analysis demonstrated that a low PNI was significantly correlated to poor OS, DMFS, PFS, and LRRFS in NPC. Therefore, we suggest PNI applied as an indicator for prediction of the short- and long- term survival outcomes in patients with NPC.

Prognostic value of automated bone scan index for predicting overall survival among bone metastatic castration resistant prostate cancer patients treated with radium-223.

IntroductionThe objective of this study was to evaluate automated bone scan index (aBSI) as a prognostic biomarker for overall survival (OS) in bone‐metastatic, castration‐resistant prostate cancer (mCRPC) patients treated with radium‐223 (Ra‐223).Materials and methodsWe identified 42 men treated with Ra‐223 for mCRPC. We investigated aBSI as an independent prognostic factor by multivariate analysis. Moreover, we evaluated the prognostic value of the aBSI after 12 weeks after the first cycle of Ra‐223 administration and aBSI change from baseline to after 12 weeks (ΔBSI).ResultsMedian baseline PSA and aBSI were 42.8 ng/mL and 1.5%, respectively. Median OS was 20.7 months. Multivariate analysis showed that baseline aBSI was a significant prognostic factor for OS. The aBSI at 12 weeks after first Ra‐223 administration also exhibited significant prognostic value for OS, while we found no evidence of prognostic value for ΔBSI.ConclusionsBaseline aBSI may be a significant prognostic factor for OS in bone‐metastatic CRPC patients treated with Ra‐223.

Prognosis and safety of radium-223 with concurrent abiraterone acetate or enzalutamide use for metastatic castration-resistant prostate cancer: Real-world data of Japanese patients.

ObjectivesTo evaluate the real‐world data on the efficacy and safety of a combination therapy with radium‐223 (Ra‐223) and second‐generation androgen‐receptor targeting agents (ARTAs), including abiraterone acetate (ABI) and enzalutamide (ENZ), among Japanese patients with bone metastatic castration‐resistant prostate cancer (CRPC).Patients and methodsWe retrospectively reviewed 79 patients with bone metastatic CRPC who were treated with Ra‐223. The number of patients with concurrent ARTA use was 24:17 receiving ABI and 7 receiving ENZ. We evaluated the overall survival (OS) according to ARTA use and compared the survival of patients treated with Ra‐223 with or without ARTA using multivariate analysis.ResultsThe median survival in the entire cohort was 23.5 months. The patients receiving Ra‐223 combined with ARTA showed a tendency of better OS than patients treated with Ra‐223 alone, although no significant difference was observed (median OS, 26.5 vs 23.5 months; P = .115). A multivariate analysis showed that the extent of disease on bone scan (EOD) scores and pain at baseline were significant predictors of OS. The concurrent use of bone‐modifying agents (BMAs) was not significant for favorable OS (P = .050). However, the concurrent use of second‐generation ARTA was not a significant factor for OS. Regarding safety, a bone fracture occurred in only one (4.2%) of 24 patients treated with combined Ra‐223 and ARTA therapy.ConclusionOur real‐world data analysis suggested that Ra‐223 combined with a second‐generation ARTA is well tolerated in Japanese patients. The EOD score and pain at baseline are significant prognostic factors for OS, but the concurrent use of second‐generation ARTA has no influence on OS among men treated with Ra‐223. The concurrent use of BMA yields a marginally favorable OS.

Unresectable Hepatocellular Carcinoma: Transcatheter Arterial Chemoembolization Combined With Microwave Ablation vs. Combined With Cryoablation.

Background: Transcatheter arterial chemoembolization (TACE) combined with ablation has been widely used for treating unresectable hepatocellular carcinoma (HCC). However, the technique with which TACE should be combined for it to be more effective remains unknown.Purpose: To retrospectively evaluate the efficacy and safety of TACE combined with microwave ablation (MWA) vs. TACE combined with cryoablation (CRA) in treating unresectable HCC.Materials and Methods: From January 2011 to December 2018, 108 patients diagnosed with unresectable HCC were divided into either the TACE-MWA group (n = 48) or TACE-CRA group (n = 60). Overall survival (OS) and time to progression (TTP) were compared between the two groups. To reduce potential bias, a propensity score matching (PSM) was performed. Complications were observed. Kaplan-Meier survival curves were constructed and compared using the log-rank test.Results : The baseline characteristics of the two groups were balanced. The median OS was 20.9 months (95% CI 14.3–27.6 months) in the TACE-MWA group and 13.0 months (95% CI 8.8–17.1 months) in the TACE-CRA group (P = 0.096). The median TTP was 8.8 months (95% CI 4.3–13.4 months) in the TACE-MWA group and 9.3 months (95% CI 7.1–11.5 months) in the TACE-CRA group (P = 0.675). After PSM, 48 patients remained in each group. The median OS in the TACE-MWA and TACE-CRA groups was 20.9 months (95% CI 14.3–27.6 months), and 13.5 months (95% CI 8.4–18.6 months, P = 0.100), respectively. The median TTP in the TACE-MWA and TACE-CRA groups was 8.8 months (95% CI 4.3–13.4 months), and 8.6 months (95% CI 3.1–14.2 months, P = 0.909), respectively. The overall incidence rate of ablation-related complications was lower in the TACE-MWA group than in the TACE-CRA group (66.7 vs. 88.3%, P = 0.006). Multivariate analysis showed that the presence of portal vein tumor thrombus (PVTT) and the maximum diameter of intrahepatic tumor were significant prognostic factors for OS and TTP.Conclusion: The efficacy of TACE-MWA and TACE-CRA in the treatment of unresectable HCC was comparable. TACE-MWA was more promising because of a lower complication rate, especially with regard to thrombocytopenia. Further prospective randomized controlled trials are required to validate our findings.

P-302 Prognostic factors in stage IV appendiceal adenocarcinoma

Appendiceal carcinomas (AC) account for 1-2% of colorectal cancers (CRC), but there is limited data to guide treatment. We sought to identify prognostic factors for overall survival (OS). We identified histologically confirmed cases of appendiceal adenocarcinomas with metastatic disease and information about OS diagnosed between 2004 and 2016 from the National Cancer Database (NCDB). Kaplan-Meier method and log-rank test were used to estimate and compare OS. Recursive partitioning analysis (RPA) analysis was performed on the entire cohort. 6,792 patients met our inclusion criteria: 5,742 patients underwent surgical resection of the primary tumor and 1,050 patients did not. Surgical status, age, comorbidity status, cancer center type, chemotherapy use, and income were significant prognostic factors for OS by RPA, in that order. Patients who underwent surgery, were younger than 75 years, were treated at an academic institution, and were from communities with median income >=$63,000 (N=1,309) had the best median OS of 60.8 months, followed by similar patients from communities with median income < 0.0001). For patients who did not undergo surgery, OS decreased by 6 months if they had comorbidities (11 vs. 17 months, p< 0.0001). Surgical status, age, comorbidity status, cancer center type, chemotherapy use, and income were significant prognostic factors for OS by RPA, in that order. The best OS was seen in patients who underwent surgery, were younger than 75 years, were treated at an academic institution, and from communities with median income >=$63,000.

P-298 Surgical resection of primary tumor as a prognostic factor in stage IV colon adenocarcinoma

Stage IV colon adenocarcinomas represent 22% of all colon cancer cases at diagnosis. There are some known prognostic factors such as left vs right sidedness, microsatellite instability, and KRAS and BRAF mutations. We seek to identify if surgical resection of the primary tumor is a prognostic factor for overall survival (OS). We identified histologically confirmed cases of colon adenocarcinomas with metastatic disease and information about surgery status and OS diagnosed between 2004 and 2016 from the National Cancer Database (NCDB). Kaplan-Meier method and log-rank test were used to estimate and compare OS. Recursive partitioning analysis (RPA) analysis was performed on the entire cohort. 169,001 patients met our inclusion criteria: 102,369 patients underwent surgical resection of the primary tumor and 66,632 patients did not. Surgical status, age, and sidedness were significant prognostic factors for OS by RPA, in that order. Patients who underwent surgery, younger than 75 years, with left-sided tumors had median OS of 30.7 months, compared with patients who did not undergo surgery, were younger than 75 years, with left-sided tumors had a median OS of 14.5 months (p< 0.0001). A similar improvement in OS was seen with patients with right-sided tumors. In the older than 75 years group, patients who underwent surgery had improved median OS of 10.2 months, compared with non-surgery patients who had median OS of 4.1 months (p< 0.0001). Surgical status, age, and sidedness were significant prognostic factors for OS, in that order. Patients who underwent surgery, were younger than 75 years, with left-sided tumors had the best OS.

Assessing the efficacy of repeat resections in recurrent glioblastoma: a systematic review.

The inevitable recurrence of glioblastoma (GBM) results in patients often undergoing multiple resections with questionable benefit to overall survival (OS). To systematically review and analyze prior studies examining the potential added benefit of repeat resection (RR) in recurrent GBM. We performed a PRISMA-compliant systematic review of literature published between 1969 to 2019 involving patients undergoing RR at GBM recurrence. The search yielded 3994 non-duplicate citations. Final abstraction included 43 articles, with 2 level II and 41 level III studies. The earliest paper we included was published in 1987 [1], and 35 identified papers (81.4%) were published within the last 10 years. The survival data of 9236 patients (55% male) were analyzed, with a median age of 56; 3726 patients underwent RR. In 31 studies with a comparable single-surgery-only cohort, 20 articles reported a statistically significant increase in OS with RR, 7 reported nonsignificant trends toward increased OS with RR, and 4 reported no significant increase in OS with RR. Twenty-two articles with multivariate analyses of Karnofsky performance scores and 17 articles with extent-of-resection reported these as significant prognostic factors of OS. In 26 studies, median OS among all patients was 17.85 months inclusive of median OS following RR totaling 9.6 months. Notably, in 10 studies with data on subsequent progressions (2+ recurrences), 6 studies reported significant increases in OS with subsequent repeat resection (sRR) compared to those not undergoing sRR. Recurrent GBM presents a treatment challenge. There appears to be an OS benefit for RR upon first recurrence as well as sRR. Such findings warrant further investigation of the potential benefits of continued surgical intervention after subsequent progressions of GBM.

Combined Analysis of Intragastric Malignant Exfoliation and Ca 72.4 Concentration in Stomach Adenocarcinoma: The “GL1 Ca 72.4” Parameter

Introduction/Objective: Differently from other digestive malignancies, gastric cancer (GC) pathobiology is still little known and understood. Recently, cytopathology and molecular biology on gastric juice/gastric lavage (GJ/GL) of GC patients have provided novel and interesting results in terms of screening, diagnosis, prognosis, and therapy. However, entertaining cytologic examination and molecular test as a unified solo-run test is previously unreported. Our aim was to assess the new parameter “GL Ca 72.4” for GC patients. Methods: Between April 2012 and July 2013, GJ/GL obtained from 37 surgical GC patients were tested for the presence/absence (GL1/GL0) of exfoliated malignant cells along with the intragastric concentration of Ca 72.4 (normal value <6.49 ng/mL: Ca 72.4n; elevated level ≥6.49 ng/mL: Ca 72.4+). Results: At a median follow-up of 79.3 months, all the GC alive patients were “GL0 Ca 72.4n.” The “GL1 Ca 72.4+” parameter, in comparison with GL0 Ca 72.4n, strongly correlated with deeper tumor invasion (p = 0.027), severe nodal metastasis (p = 0.012), worst metastatic node ratio (p = 0.041), higher number of metastatic lymph nodes (30 vs. 20 nodes, p = 0.014), angiolymphatic invasion (p = 0.044), advanced stage (p = 0.034), and adjuvant therapy (p = 0.044). The Kaplan-Meier model showed that GL1 Ca 72.4+ subjects had shorter overall survival (OS) than GL0 Ca 72.4n cases (9.7 vs. 43.2 months, respectively, p = 0.042). At univariate analysis, the GL1 Ca 72.4+ parameter resulted a significant prognostic factor for OS (p = 0.023). Conclusions: The combined cyto-molecular parameter “GL1 Ca 72.4+” appears to be a strong indicator of aggressive tumor behavior and a significant prognostic factor of poor survival for GC patients.

FACT physical wellbeing to independently predict overall survival in patients with acute myeloid leukemia.

7532 Background: Patient-reported outcomes (PROs) predict overall survival (OS) in solid cancer populations, but little evidence exists around the prognostic value of PROs in patients with hematologic malignancies. We investigated whether scales from the Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu) predicted OS beyond established prognostic factors. Methods: Data were from 317 AML patients unfit for intensive therapy from a clinical trial comparing Dacogen (decitabine) plus Talacotuzumab versus Dacogen (decitabine) alone (AML2002; NCT02472145). We used ridge-penalized Cox models to determine whether baseline (1st cycle) FACT-Leu scales predicted OS. FACT-Leu scales significant in these models and factors from a validated prognostic model, the AML composite model (AML-CL; covariates listed in Table), were entered into Cox proportional hazard models. Lastly, model selection procedures were run with 1000 bootstrapped samples using all variables. The inclusion frequency of each FACT-Leu scale in the final models was examined to evaluate prognostic value for OS (i.e., higher the % of inclusion, higher importance of the variable). Results: In the ridge-penalized Cox models, the Physical Wellbeing Scale (PWB), Trial Outcome Index (TOI), and FACT-Leu Total scales were significant predictors of OS. After adjusting for the AML-CL factors, an important difference (2 pts) in PWB score was associated with a 9% decline in OS. (Table) Model validity was evidenced as the PWB scale appeared in a large majority of selected models (90%-97%), while the TOI (45%-73%) and FACT-Leu Total (41%-71%) appeared less often. Conclusions: FACT-Leu scales, especially the PWB, were significant prognostic factors for OS among AML patients not suitable for intensive therapy. These results may indicate PROs' value as stratification factors in trials with AML patients and underscore the need to more systematically collect PRO data in routine care practice with AML patients. Clinical trial information: NCT02472145 . [Table: see text]

Identifying optimal candidates for liver resection or transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma.

BackgroundRecommended as the first-line treatment for advanced unresectable hepatocellular carcinoma (HCC), sorafenib has been shown to prolong median overall survival (OS) for patients. However, advanced HCC sees high heterogeneity across patient groups. Recently, a growing number of studies have indicated surgical resection and transarterial chemoembolisation (TACE) to perform well in patients with portal vein tumor thrombosis (PVTT). The aim of this study was to compare the outcomes of liver resection and TACE and to identify prognostic factors related to OS for BCLC stage C patients with performance status (PS) 1 who have a single tumor but no vascular invasion or extrahepatic spread.MethodsA total of 323 consecutive patients in BCLC stage C with PS 1 who had only one tumor and no vascular invasion or extrahepatic spread were enrolled in this retrospective study, regardless of tumor size. Survival analyses were performed using the Kaplan-Meier analysis, and statistical differences between the TACE and sorafenib groups were examined by the log-rank test. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS.ResultsBased on the Kaplan-Meier curves, patients treated with surgical resection showed a better OS than those who underwent TACE, with OS at 1, 3, and 5 years (85.7%, 48.8%, and 33.3% vs. 66.6%, 21.8%, and 13.4%, respectively; log-rank P<0.001). Univariate and multivariate analyses demonstrated that tumor size, albumin, bilirubin, Child-Pugh score, and treatment method were significant prognostic factors for OS. According to the subgroup analyses based on tumor size, there were significant differences in OS among overall subsets between patients who underwent hepatectomy and those who underwent TACE therapy.ConclusionsLiver resection had a better prognostic performance than TACE and should be put forward as an alternative treatment modality to TACE for BCLC stage C patients with PS 1 who have a single tumor and no vascular invasion or extrahepatic spread.

Identifying optimal candidates of transarterial chemoembolization (TACE) vs. sorafenib in patients with unresectable hepatocellular carcinoma.

BackgroundSorafenib has been recommended as the first-line treatment and shown to prolong median overall survival (OS) of patients with advanced unresectable hepatocellular carcinoma (HCC). Recently, a growing amount of research has supported the application of transarterial chemoembolization (TACE) in patients with advanced-stage HCC. The aim of this study was to compare the outcomes of TACE and sorafenib and identify the prognostic factors related to OS for Barcelona Clinic Liver Cancer (BCLC) stage C patients with PS 1 but without vascular invasion or extrahepatic spread.MethodsA total of 323 consecutive patients in BCLC stage C with PS 1 but without vascular invasion or extrahepatic spread were enrolled in this retrospective study. Survival analyses were performed using the Kaplan-Meier analysis, and the statistical differences between the TACE and sorafenib groups were examined by the log-rank test. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS.ResultsBased on the Kaplan-Meier curves, patients treated with TACE showed a better OS than those undergoing sorafenib, with respective OS at 1, 3, and 5 years (67.7%, 41.5%, 23.2% vs. 55.6%, 29.6%, 4.8%; log-rank P=0.002). The univariate analysis indicated that tumor size, tumor number, and treatment method, along with platelet (PLT), white blood cell (WBC), and α-fetoprotein (AFP) count, were associated with OS. The multivariate analysis demonstrated that tumor size, tumor number, and treatment method were significant prognostic factors for OS. According to the subgroups analyses based on the tumor size and tumor number, there were significant differences in OS among overall subsets between TACE and sorafenib therapy.ConclusionsTACE provided better prognostic performance than sorafenib and should be suggested as an alternative treatment modality to sorafenib for BCLC stage C patients with PS 1 but without vascular invasion or extrahepatic spread.

Primary Resistance to PD-1-Based Immunotherapy-A Study in 319 Patients with Stage IV Melanoma.

Background: Primary resistance to immunotherapy can be observed in approximately 40–65% of the stage IV melanoma patients treated with immune checkpoint inhibitors. A minority of the patients receive a second-line therapy, and the clinical benefit is small. Patients and methods: Stage IV melanoma patients treated with first-line PD-1-based immunotherapy between January 2015 and December 2018 were investigated. Primary resistance was defined as progressive disease (PD) at the time of the first tumor assessment after starting immunotherapy. Patients with complete response, partial response, and stable disease were classified as having disease control (DC). Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan–Meier estimator. Univariate and multivariate logistic regression analyses were performed to determine prognostic factors associated with OS. Results: Three hundred and nineteen patients were included, and 40% had primary resistance to immunotherapy. The median follow-up time was 22 months. Patients with primary resistance had 1-, 2-, and 3-year OS rates of 41%, 15%, and 10%, respectively, compared to 91%, 81%, and 65% for the patients who achieved DC. The following independently significant prognostic factors for OS were identified: protein S100B level and primary tumor localization. There was a statistically significant difference for OS (p < 0.0001) but not for PFS (p = 0.230) when analyzing risk groups formed with a combination of these two variables (low-, intermediate-, and high-risk subgroups). Conclusions: Melanoma patients with primary resistance to immunotherapy have a dismal prognosis. Response at the first tumor assessment after starting immunotherapy is a stronger prognostic factor for the further course of the disease than pretreatment risk factors.