Significant Independent Predictor Of Overall Survival Research Articles

Prognostic factors of adrenocortical carcinoma in children and adolescents: a population-based study.

Adrenocortical carcinoma (ACC) is an uncommon adrenal gland endocrine tumor that has a poor prognosis in children. We aimed toconducta population-based cohort study to predict overall survival (OS) in pediatric patients with ACC. We used the Surveillance, Epidemiology, and End Results (SEER) database to conduct a retrospective cohort research on pediatric patients diagnosed with ACC between 1975 and 2018.We examined demographic characteristics, tumor stage and size, treatment options, and survival results. Kaplane-Meier estimations were used to generate survival curves based on several parameters. To compare survival curves, the log-rank test was applied.Cox proportional-hazards regression was used to determine the variables related with OS. In addition, we created a nomogram to predict overall survival in pediatric ACC patients. A total of 143 pediatric ACC patients were identified. Females were the most impacted (60.8%). Overall 1year, 3year, and 5year survival rates were 75.0%, 57.6%, and 53.7% for all patients, respectively. In comparison to older patients (5-19years), younger patients (≤ 4years) were shown to have more positive characteristics, including a higher likelihood of local disease (29.4% vs. 14%, P < 0.001), tumors less than 10cm (23.1% vs. 14.7%, P < 0.001), and improved overall survival (5year OS 89.6% vs. 27.7%, P < 0.001). Age at diagnosis, SEER stage, and surgery were significant independent predictors of OS in this model, according to the results of Cox proportional hazard regression. After that, we developed a nomogram for predicting OS in children with ACC. Patients older than 4years old had a higher chance of dying. Furthermore, the higher the SEER stage, the higher the risk of death. Patients who do not have surgery have a worse survival rate than those who do. Our study revealed that age at diagnosis, SEER stage, and surgery were found to be the most important predictors of the overall survival of pediatric ACC. These findings contribute to the existing body of knowledge and emphasize the importance of continued research to advance our understanding of pediatric ACC and improve patient care.

Survival Predictive Nomograms for Non-Surgical Brain Metastases Patients From Non-Small Cell Lung Cancer Receiving Radiotherapy: A Population-Based Study.

A high number of Non-Small Cell Lung Cancer (NSCLC) patients with brain metastasis who have not had surgery often have a negative outlook. Radiotherapy remains a most common and effective method. Nomograms were developed to forecast the cancer-specific survival (CSS) and overall survival (OS) in NSCLC individuals with nonoperative brain metastases who underwent radiotherapy. Information was gathered from the Surveillance, Epidemiology, and End Results (SEER) database about patients diagnosed with NSCLC who had brain metastases not suitable for surgery. Nomograms were created and tested using multivariate Cox regression models to forecast CSS and OS at intervals of 1, 2, and 3years. The research involved 3413 individuals diagnosed with NSCLC brain metastases who had undergone radiotherapy but had not experienced surgery. These participants were randomly divided into two categories. The analysis revealed that gender, age, ethnicity, marital status, tumor location, tumor laterality, tumor grade, histology, T stage, N stage, chemotherapy, tumor size, lung metastasis, bone metastasis, and liver metastasis were significant independent predictors for OS and CSS. The C-index for the training set for predicting OS was .709 (95% CI, .697-.721), and for the validation set, it was .705 (95% CI, .686-.723), respectively. The C-index for predicting CSS was .710 (95% CI, .697-.722) in the training set and .703 (95% CI, .684-.722) in the validation set, respectively. The nomograms model, as suggested by the impressive C-index, exhibits outstanding differentiation ability. Moreover, the ROC and calibration curves reveal its commendable precision and distinguishing potential. For the first time, highly accurate and reliable nomograms were developed to predict OS and CSS in NSCLC patients with non-surgical brain metastases, who have undergone radiotherapy treatment. The nomograms may assist in tailoring counseling strategies and choosing the most effective treatment method.

Endometrial carcinoma: association between mutational status, sites of metastasis, recurrence, and correlation with overall survival.

To investigate the association between sites of endometrial carcinoma (EC) recurrence and metastases, mutational status, race, and overall survival (OS). This single-center retrospective study evaluated patients with biopsy-proven EC that underwent genomic molecular testing between January 2015 and July 2021. Association between genomic profile and sites of metastases or recurrence was performed using Pearson's chi-squared or Fisher exact test. Survival curves for ethnicity and race, mutations, sites of metastases or recurrence were estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard regression models were used. The study included 133 women [median age 64 years (IQR 57-69)]. The most common mutation was TP53 (65/105 patients, 62%). The most common site of metastasis was the peritoneum (35/43, 81%). The most common recurrence was in lymph nodes (34/75, 45%). Mutations of TP53 and PTEN were significantly associated with Black women (p = 0.048, p = 0.004, respectively). In the univariable Cox regression analyses, TP53 mutation and presence of recurrence or metastases to the peritoneum were associated with lower OS (HR 2.1; 95% CI 1.1, 4.3; p = 0.03/ HR 2.9; 95% CI 1.6, 5.4; p = 0.0004; respectively). On multivariable Cox proportional hazards model ER expression (HR 0.4; 95% CI 0.22, 0.91; p = 0.03), peritoneal recurrence or metastases (HR 3.55; 95% CI 1.67, 7.57; p = 0.001), and Black race (HR 2.2; 95% CI 1.1, 4.6; p = 0.03) were significant independent predictors of OS. The integration of EC mutational status and clinicopathological risk assessment demonstrated potential implications on the patterns of metastasis, recurrence, and OS.

Comparing T2-T3 staging of penile cancer according to the American Joint Committee on cancer 8th edition with two modified staging systems in predicting survival outcome: A single-center experience.

Penile cancer is a rare malignancy of the genitourinary tract. We aimed to validate the recent changes in the T2 and T3 stages of penile cancer in the American Joint Committee on Cancer (AJCC) 8th edition and to compare its predictive ability with two other modified staging systems for survival outcomes. This is a retrospective study of patients diagnosed with penile cancer from June 2015 to March 2020. The AJCC 8th edition and two other newly proposed systems by Li et al. and Sali et al. were used for staging the tumor. All variables were categorized and correlated with lymph node (LN) metastases and overall survival (OS). Fifty-four patients were eligible for this study. The mean age was 58 years (range 46-72 years). The tumor stage (P = 0.016), clinical LN stage (P = 0.001), the involvement of the spongiosa (P = 0.015) and the cavernosa (P = 0.002), lymphovascular invasion (LVI) (P = 0.000), and PNI (P = 0.021) were found to be the significant predictors of LN metastases. When the 5 year OS was compared between the T2 and T3 stages of the AJCC 8th edition, Li staging and the Sali staging systems, it was 91% and 50.1% (P = 0.001), 97.5% and 10.3% (P = 0.000), 94.4% and 14.7% (P = 0.000), respectively. The presence of LVI (P = 0.001) was the most significant independent predictor of OS. The recent changes in the AJCC 8th edition pertaining to the T2-T3 stage are relevant, although the other two newly proposed staging systems were more precise in predicting the survival outcomes.

Early detection of venous thromboembolism after the initiation of chemotherapy predicts a poor prognosis in patients with unresectable metastatic pancreatic cancer who underwent first-line chemotherapy with gemcitabine plus nab-paclitaxel.

BackgroundPancreatic cancer is associated with a high thromboembolism risk. We investigated the significance of early venous thromboembolism (VTE) detection in patients with unresectable metastatic pancreatic cancer (UR-MPC) who received first-line chemotherapy with gemcitabine plus nab-paclitaxel (GnP).MethodsThis single-center retrospective study enrolled 174 patients with UR-MPC who underwent GnP as a first-line chemotherapy from April 2017 to March 2020. The early detection of VTE (deep venous thrombosis and pulmonary thromboembolism) was defined as diagnosis by the first follow-up CT scan after the initiation of chemotherapy. We compared the patients with early detection of VTE (VTE (+) group) with the others (VTE (-) group). We examined overall survival (OS), progress free survival (PFS), severe adverse events, and predictors associated with OS using the Cox proportional hazards model.ResultsEarly detection of VTE was observed in 17 patients (9.8%). Thirteen patients were diagnosed with VTE at treatment initiation, and four patients were diagnosed after treatment initiation. The median time to diagnosis after treatment initiation was 55 days (range: 31–71 days). Only 3 patients were symptomatic. The VTE (+) group exhibited worse OS and PFS than the VTE (-) group (OS: 259 days vs. 400 days, P < 0.001; PFS: 120 days vs. 162 days, P = 0.008). The frequency of grade 3–4 adverse events was not significantly different. Although the performance status was poorer in the VTE (+) group, VTE was identified as a statistically significant independent predictor for OS in multivariate analyses (HR, 1.87; 95% CI, 1.02–3.44; P = 0.041).ConclusionsEarly VTE detection is a predictor of a poor prognosis in UR-MPC patients who receive GnP as first-line chemotherapy, suggesting that screening VTE for patients with UR-MPC is crucial, even if patients are asymptomatic.

Optimizing management of the elderly patient with glioblastoma: Survival prediction online tool based on BC Cancer Registry real-world data.

Glioblastoma (GBM) is associated with fatal outcomes and devastating neurological presentations especially impacting the elderly. Management remains controversial and representation in clinical trials poor. We generated 2 nomograms and a clinical decision making web tool using real-world data. Patients ≥60 years of age with histologically confirmed GBM (ICD-O-3 histology codes 9440/3, 9441/3, and 9442/3) diagnosed 2005-2015 were identified from the BC Cancer Registry (n = 822). Seven hundred and twenty-nine patients for which performance status was captured were included in the analysis. Age, performance and resection status, administration of radiation therapy (RT), and chemotherapy were reviewed. Nomograms predicting 6- and 12-month overall survival (OS) probability were developed using Cox proportional hazards regression internally validated by c-index. A web tool powered by JavaScript was developed to calculate the survival probability. Median OS was 6.6 months (95% confidence interval [CI] 6-7.2 months). Management involved concurrent chemoradiation (34%), RT alone (42%), and chemo alone (2.3%). Twenty-one percent of patients did not receive treatment beyond surgical intervention. Age, performance status, extent of resection, chemotherapy, and RT administration were all significant independent predictors of OS. Patients <80 years old who received RT had a significant survival advantage, regardless of extent of resection (hazard ratio range from 0.22 to 0.60, CI 0.15-0.95). A nomogram was constructed from all 729 patients (Harrell's Concordance Index = 0.78 [CI 0.71-0.84]) with a second nomogram based on subgroup analysis of the 452 patients who underwent RT (Harrell's Concordance Index = 0.81 [CI 0.70-0.90]). An online calculator based on both nomograms was generated for clinical use. Two nomograms and accompanying web tool incorporating commonly captured clinical features were generated based on real-world data to optimize decision making in the clinic.

Utility of Early Posttreatment PET/CT Evaluation Using FDG or 18F-FCH to Predict Response to 90Y Radioembolization in Patients With Hepatocellular Carcinoma.

BACKGROUND. Assessment of hepatocellular carcinoma (HCC) treatment response after transarterial radioembolization (TARE) is challenging, because response by conventional imaging criteria may not become apparent until 6 months after treatment. Though HCC exhibits variable avidity for FDG, some cases of HCC without avidity for FDG show avidity for 18F-fluorocholine (18F-FCH). OBJECTIVE. The purpose of this study was to evaluate the utility of early posttreatment evaluation by PET/CT using FDG or 18F-FCH to predict 6-month treatment response and survival after TARE in patients with HCC. METHODS. This retrospective study included 37 patients (mean age, 67 years; 34 men, three women) with documented HCC treated by TARE who underwent both pre-treatment FDG PET/CT and 18F-FCH PET/CT and early FDG PET/CT and/or 18F-FCH PET/CT 4-8 weeks after treatment; FDG PET/CT and 18F-FCH PET/CT examinations were performed on separate dates. Only one of 73 initially identified potentially eligible patients was excluded because of lack of HCC avidity for both FDG and 18F-FCH. Response assessment by modified RECIST (mRECIST) on multiphase CT or MRI was performed at 1 month and 6 months in 23 patients. Early responses seen on PET/CT and 1-month mRECIST response were assessed as predictors of 6-month mRECIST response. Univariable and multivariable predictors of overall survival (OS) were identified. RESULTS. On pretreatment PET/CT, 28 (76%) patients were FDG-positive (showed visual uptake on FDG PET/CT and tumor-to-normal liver ratio > 1.15), 15 (41%) were FCH-positive (showed visual uptake on 18F-FCH PET/CT), and six (16%) were both FDG-positive and FCH-positive. Twelve of 28 FDG-positive HCCs exhibited early response by FDG PET/CT; seven of 15 FCH-positive HCCs exhibited early response by 18F-FCH PET/CT. Twelve (52%) patients exhibited 6-month mRECIST response. Response seen on early posttreatment PET/CT exhibited 100% (12/12) sensitivity and 100% (11/11) specificity for 6-month mRECIST response, whereas 1-month mRECIST response exhibited 67% (8/12) sensitivity and 100% (11/11) specificity for 6-month mRECIST response. Response seen on early posttreatment PET/CT was a significant independent predictor of OS on univariable (hazard ratio [HR], 0.4; 95% CI, 0.2-0.9; p = .03) and multivariable (HR, 0.2; 95% CI, 0.1-0.8; p = .01) analyses. CONCLUSION. Early evaluation after TARE by PET/CT using FDG or 18F-FCH may pre dict 6-month response and OS in patients with HCC. CLINICAL IMPACT. Early posttreatment evaluation with PET/CT could help more reliably identify true nonresponders after TARE, which in turn could prompt early response-adapted therapeutic management.

Predicting Survival in Patients with Pancreatic Cancer by Integrating Bone Marrow FDG Uptake and Radiomic Features of Primary Tumor in PET/CT.

Simple SummaryFDG uptake of bone marrow (BM) is known to reflect the degree of host inflammatory response to cancer cells and showed significant association with survival in diverse kinds of cancers. The aim of this retrospective study was to evaluate the prognostic significance of FDG uptake of BM and to investigate whether integrating FDG uptake of BM and radiomic features of primary tumors could improve the prediction of overall survival (OS) in patients with pancreatic cancer. In multivariable survival analysis, along with total lesion glycolysis (TLG) and first-order entropy of primary tumor lesions, FDG uptake of BM was an independent predictor of OS. We designed a PET/CT scoring system based on the cumulative scores of tumor factors (TLG and first-order entropy) and host factors (FDG uptake of BM). This scoring system was able to stratify the patients with three distinct prognostic groups independent of clinical stage and treatment modality.The purpose of this study was to evaluate the prognostic significance of FDG uptake of bone marrow (BM SUV) and to investigate its role combined with radiomic features of primary tumors in improving the prediction of overall survival (OS) in patients with pancreatic cancer. We retrospectively enrolled 65 pancreatic cancer patients with staging FDG PET/CT. BM SUV and conventional imaging parameters of primary tumors including total lesion glycolysis (TLG) were measured. First-order and higher-order textural features of primary cancer were extracted using PET textural analysis. Associations of PET/CT parameters of bone marrow (BM) and primary cancer with OS were assessed. BM SUV as well as TLG and first-order entropy of pancreatic cancer were significant independent predictors of OS in multivariable analysis. A PET/CT scoring system based on the cumulative scores of these three independent predictors enabled patient stratification into three distinct prognostic groups. The scoring system yielded a good prognostic stratification based on subgroup analysis irrespective of tumor stage and treatment modality. BM SUV was an independent predictor of OS in pancreatic cancer patients. The PET/CT scoring system that integrated PET/CT parameters of primary tumors and BM can provide prognostic information in pancreatic cancer independent of tumor stage and treatment.

Cumulative Burden of Postoperative Complications in Patients Undergoing Surgery for Primary Retroperitoneal Sarcoma.

Correlations between postoperative complications and oncological outcomes have been reported in several malignancies, but their impact in retroperitoneal sarcoma (RPS) is unclear. Our study aimed to evaluate the association between postoperative complications and prognosis in patients with RPS. Patients undergoing surgery for primary RPS from 2008 to 2019 at a sarcoma center were evaluated. The cumulative burden of postoperative complications was quantified using the Comprehensive Complication Index (CCI), and associations with local recurrence (LR), distant metastases (DM) and overall survival (OS) were assessed. Data were available for 191 patients, of whom 160 (82.9%) developed at least one postoperative complication, with a median CCI of 20.9 (interquartile range 8.7-33.5). After postoperative deaths were excluded (n = 3, 1.6%), the remaining patients were divided into those with a CCI of 0-20.9 (n = 97) and > 20.9 (n = 91). Patients with a CCI >20.9 had significantly shorter OS than those with a CCI of 0-20.9 (43.3% vs. 69.5% at 5 years; p = 0.005), and this difference remained significant after multivariable adjustment for patient- and treatment-related factors [hazard ratio (HR) 2.31, 95% confidence interval (CI) 1.30-4.09; p = 0.004]. However, CCI > 20.9 was not found to be a significant independent predictor of either LR (HR 1.30, 95% CI 0.76-2.23; p = 0.333) or DM (HR 1.08, 95% CI 0.61-1.93; p = 0.786). Increasing complication burden, as quantified by the CCI, is a significant independent predictor of OS; however, there is no evidence of a significant association with either LR or DM, which may be more related to tumor biological factors.

Sarcopenia with inflammation as a predictor of survival in patients with head and neck cancer

ObjectiveAlthough both sarcopenia and systemic inflammation affect the outcomes of head and neck cancer (HNC) patients, the association between sarcopenia and systemic inflammation and the combined prognostic effect of these factors in HNC patients remain unknown. This study aimed to evaluate the effect of sarcopenia with systemic inflammation on survival and disease control in HNC patients. MethodsWe retrospectively reviewed medical records of HNC patients treated between 2009 and 2016. The skeletal muscle area was measured using a single computed tomography image slice at the level of the third cervical vertebra. A prognostic score (SPLR) was developed based on sarcopenia and the platelet-lymphocyte ratio (PLR), and its prognostic value was evaluated. ResultsOverall, 164 patients were enrolled. In the multivariate analysis, sarcopenia was significantly associated with poor overall survival (OS) (p < 0.01). However, neither sarcopenia nor a high PLR was an independent prognostic factor for disease-free survival (DFS) or locoregional recurrence-free survival (LRFS). A high PLR was an independent predictor for sarcopenia (p < 0.01). A high SPLR was associated with older age, lower serum hemoglobin, and lower body mass index (all p < 0.05). Multivariate analysis revealed that SPLR was a significant independent predictor of OS, DFS, and LRFS (all p < 0.05). ConclusionsSystemic inflammation is significantly associated with sarcopenia. The survival and oncological effects of sarcopenia were enhanced when PLR was high. Thus, the combination of these two parameters may be useful for identifying HNC patients at a risk of poor survival outcomes.

Prognostic value and association of sarcopenic obesity and systemic inflammatory indexes in patients with hepatocellular carcinoma following hepatectomy and the establishment of novel predictive nomograms.

The specific impacts of sarcopenic obesity (SO) on hepatocellular carcinoma (HCC) and the association between SO and systemic inflammation remain unclear. This study aimed to investigate the prognostic value and association of SO and systemic inflammation with outcomes after hepatectomy for HCC and develop novel nomograms based on SO and inflammatory indexes for survival prediction. We retrospectively enrolled 452 patients with HCC who underwent radical hepatectomy between January 2012 and March 2015 in Fujian Provincial Hospital as the training cohort. In addition, 275 patients during the same period were enrolled as the external validation cohort. Patients were classified into different groups according to the presence of sarcopenia and obesity. Different inflammation indexes were evaluated to select the best predictor of overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate logistic regression were performed to investigate the associations between inflammatory indexes and SO. The inflammatory indexes with the highest predictive values and SO were selected for subgroup analyses to establish a novel classification system: the SOLMR grade. SOLMR grades identified in the multivariate Cox analysis were selected to construct novel nomograms for OS and RFS. SO (P<0.001) was an independent risk factor for OS and RFS. The lymphocyte-monocyte ratio (LMR) had the highest areas under the receiver operating characteristic (ROC) curves (AUCs) for OS (P<0.001) and RFS (P<0.001) and was identified as an independent factor of SO (P=0.001). SO and the LMR were selected to establish the SOLMR grade. Multivariate Cox analysis revealed that SOLMR grade was a significant independent predictor of OS (P<0.001) and RFS (P<0.001). Nomograms based on SOLMR grades were generated and accurately predicted 1-, 3- and 5-year OS and RFS in HCC patients. The C-index of the novel nomograms was higher than those of the other conventional staging systems (P<0.001). Both SO and the LMR were independent risk factors for OS and RFS in HCC patients after hepatectomy. The LMR was an independent factor of SO. The novel nomograms developed from the SOLMR grading system combining SO with the LMR provide good prognostic estimates of the outcomes of HCC patients.

1560P Sarcopenia and sarcopenic obesity in pancreatic ductal adenocarcinoma (PDAC) patients undergoing surgery after neoadjuvant therapy (NAT): Prevalence and clinical implications

Body anthropometry may be markedly affected by NAT for PDAC. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher morbidity and mortality. The present study evaluated the impact of sarcopenia/sarcopenic obesity and changes in body composition (BC) following NAT on surgical and survival outcomes in patients (pts) undergoing surgery for PDAC. PDAC pts with available CT-scans (both at diagnosis and preoperatively) undergoing surgical resection after NAT at two academic medical institutions from 2013 to 2015 were retrospectively assessed. BC was estimated by analyzing axial L3 CT images before and after NAT. Data were correlated with overall survival (OS) using a Cox regression model. Kaplan-Meier curves were compared with Log-Rank test. The final cohort consisted of 108 pts, with a median age of 63 years and a median follow-up of 16 months. Ninety-one pts (89.8%) received FOLFIRINOX. Sarcopenia and sarcopenic obesity were found at diagnosis in 41.7% and 16.7% of pts, respectively. After NAT, all body compartments significantly changed (p < 0.001); the prevalence of sarcopenia and sarcopenic obesity decreased to 30.5% and 10.2%, respectively, after NAT. These BC phenotypes were associated with a higher overall complications rate after surgery (69.7% vs. 30.3%, p = 0.027 and 81.8% vs. 18.2% %, p = 0.048, respectively). Particularly, cardiac complications were related to sarcopenia (9% vs. 0%, p = 0.028) and pts that developed postoperative complications had higher preoperative total adipose tissue (300 vs. 229 cm2, p > 0.05). With regards to OS, sarcopenic obesity at baseline (HR 3.45, p = 0.023) was found to be a significant independent predictor for OS at multivariate analysis. Our data provide evidence that BC impacts on both surgical and survival outcomes in PDAC pts undergoing NAT before resection. The associations with worse clinical outcomes emphasize the role of a careful nutritional evaluation, as well as the need to develop appropriate evidence-based nutritional interventions during NAT.

Superior therapy response predictions for patients with glioblastoma (GBM) using Cellworks Singula: MyCare-009-03.

2519 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of GBM patients remains relatively poor. Therapy selection is often based on information considering only a single aberration and ignoring other patient-specific omics data which could potentially enable more effective treatment selection. The Cellworks Singula™ report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a superior predictor of progression-free survival (PFS) and overall survival (OS) compared to PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 109 GBM patients aged 17 to 83 years treated with PPT. Patient omics data was available from TCGA. Singula uses PubMed to generate protein interaction network activated and inactivated disease pathways. We simulated PPT for each patient and calculated the quantitative drug effect on a composite GBM disease inhibition score based on specific phenotypes while blinded to clinical response. Univariate and multivariate proportional hazards (PH) regression analyses were performed to determine if Singula provides predictive information for PFS and OS, respectively, above and beyond age and PPT. Results: In univariate analyses, Singula was a significant predictor of both PFS (HR = 4.130, p &lt; 0.000) and OS (HR = 2.418, p &lt; 0.0001). In multivariate PH regression analyses, Singula (HR = 4.033, p &lt; 0.0001) remained an independent predictor of PFS after adjustment for PPT (p = 0.1453) and patient age (p = 0.4273). Singula (HR = 1.852, p = 0.0070) was also a significant independent predictor of OS after adjustment for PPT (p = 0.4127) and patient age (p = 0.0003). Results indicate that Singula is a superior predictor of both PFS and OS compared to PPT. Singula provided alternative therapy selections for 29 of 52 disease progressors detected by Cellworks. Conclusions: Singula is a superior predictor of PFS and OS in GBM patients compared to PPT. Singula can identify non-responders to PPT and provide alternative therapy selections.

Superior therapy response predictions for patients with low-grade glioma (LGG) using Cellworks Singula: MyCare-009-04.

2569 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of LGG patients remains relatively poor. Therapy selection is often based on information considering only a single aberration and ignoring other patient-specific omics data which could potentially enable more effective treatments. The Cellworks Singula report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a superior predictor of progression-free survival (PFS) and overall survival (OS) compared to PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 137 LGG patients aged 14 to 73 years treated with PPT. Patient omics data was available from TCGA. Singula uses PubMed to generate protein interaction network activated and inactivated disease pathways. We simulated the PPT for each patient and calculated the quantitative drug effect on a composite LGG disease inhibition score based on specific phenotypes while blinded to clinical response. Univariate and multivariate proportional hazards (PH) regression analyses were performed to determine if Singula provides predictive information for PFS and OS, respectively, above and beyond age and PPT. Results: In univariate analyses, Singula was a significant predictor of both PFS (HR = 3.587, p &lt; 0.0001) and OS (HR = 3.044, p = 0.0007). In multivariate PH regression analyses, Singula (HR = 3.707, p &lt; 0.0001) remained an independent predictor of PFS after adjustment for PPT (p = 0.3821) and patient age (p = 0.0020). Singula (HR = 2.970, p = 0.0013) was also a significant independent predictor of OS after adjustment for PPT (p = 0.0540) and patient age (p &lt; 0.0001). Results indicate that Singula is a superior predictor of both PFS and OS compared to PPT. Singula provided alternative standard of care therapy selections for all 34 disease progressors. Conclusions: Singula is a superior predictor of PFS and OS in LGG patients compared to PPT. Singula can correctly identify non-responders to PPT and provide alternative therapy selections.

Sarcopenia and sarcopenic obesity in pancreatic ductal adenocarcinoma (PDAC) patients undergoing surgery after neoadjuvant therapy (NAT): Clinical implications.

e16769 Background: Nutritional status may be markedly affected by NAT for PDAC. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher morbidity and mortality. The present study assessed the impact of sarcopenia/sarcopenic obesity and changes in body composition (BC) following NAT on surgical and survival outcomes in patients (pts) undergoing surgery for PDAC. Methods: PDAC pts with available CT-scans (both at diagnosis and preoperatively) undergoing surgical resection after NAT at two academic medical institutions from 2013 to 2015 were retrospectively evaluated. BC was assessed by analyzing axial L3 CT images before and after NAT. Data were correlated with overall survival (OS) using a Cox regression model. Kaplan-Meier curves were compared with Log-Rank test. Results: The final cohort consisted of 108 pts, with a median age of 63 years and a median follow-up of 16 months. Ninety-one pts (89.8%) received FOLFIRINOX. Sarcopenia and sarcopenic obesity were found at diagnosis in 41.7% and 16.7% of pts, respectively. After NAT, all body compartments significantly changed (p &lt; 0.001); the prevalence of sarcopenia and sarcopenic obesity decreased to 30.5% and 10.2%, respectively, after NAT. These BC phenotypes were related to a higher overall complications rate after surgery (69.7% vs. 30.3%, p = 0.027 and 81.8% vs. 18.2% %, p = 0.048, respectively). Particularly, cardiac complications were associated with sarcopenia (9% vs. 0%, p = 0.028) and pts that developed postoperative complications had higher preoperative total adipose tissue (300 vs. 229 cm2, p &gt; 0.05). With regards to OS, sarcopenic obesity at baseline (HR 3.45, p = 0.023) was found to be a significant independent predictor for OS at multivariate analysis. Conclusions: Our data provide evidence that BC impacts on both surgical and survival outcomes in PDAC pts undergoing NAT before resection. The associations with worse clinical outcomes emphasize the role of nutritional evaluation, as well as the need to develop appropriate evidence-based nutritional interventions during NAT.

Risk scoring based on expression of long non‑coding RNAs can effectively predict survival in hepatocellular carcinoma patients with or without fibrosis.

Patients with hepatocellular carcinoma (HCC) have different prognoses depending on whether or not they also have fibrosis. Since long non-coding RNAs (lncRNAs) affect tumor formation and progression, the present study aimed to investigate whether their expression might help predict the survival of patients with HCC. Expression profiles downloaded from The Cancer Genome Atlas database were examined to identify lncRNAs differentially expressed (DElncRNAs) between HCC patients with or without fibrosis. These DElncRNAs were then used to develop a risk scoring system to predict overall survival (OS) or recurrence-free survival (RFS). A total of 142 significant DElncRNAs were identified using data from 135 patients with fibrosis and 72 without fibrosis. For HCC patients with fibrosis, a risk scoring system to predict OS was constructed based on five lncRNAs (AL359853.1, Z93930.3, HOXA-AS3, AL772337.1 and AC012640.3), while the risk scoring system to predict RFS was based on 12 lncRNAs (PLCE1-AS1, Z93930.3, LINC02273, TRBV11-2, HHIP-AS1, AC004687.1, LINC01857, AC004585.1, AP000808.1, CU638689.4, AC090152.1 and AL357060.1). For HCC patients without fibrosis, the risk scoring system to predict OS was established based on seven lncRNAs (LINC00239, AC104971.4, AP006285.2, HOXA-AS3, AC079834.2, NRIR and LINC01929), and the system to predict RFS was based on five lncRNAs (AC021744.1, NRIR, LINC00487, AC005858.1 and AC107398.3). Areas under the receiver operating characteristic curves for all risk scoring systems exceeded 0.7. Uni- and multivariate Cox analyses showed that the risk scoring systems were significant independent predictors of OS for HCC patients with fibrosis, or of OS and RFS for HCC patients without fibrosis, after adjusting for clinical factors. Functional enrichment analysis suggested that, depending on the risk scoring system, highly associated genes were involved in pathways mainly associated with the cell cycle, chemokines, Th17 cell differentiation or thermogenesis. The findings of the present study indicate that risk scoring systems based on lncRNA expression can effectively predict the OS of HCC patients with fibrosis as well as the OS or RFS of HCC patients without fibrosis.

Impact of Immune Checkpoint Inhibitors with or without a Combination of Tyrosine Kinase Inhibitors on Organ-Specific Efficacy and Macrovascular Invasion in Advanced Hepatocellular Carcinoma

Introduction: The tumor microenvironments of different organs often differ and thus may affect the immunotherapy response. Objective: This study elucidated that the efficacy of programmed cell death protein-1 (PD-1) inhibitors varies across different metastatic sites among individuals with advanced hepatocellular carcinoma (HCC). Methods: We retrospectively analyzed treatment outcomes in advanced HCC patients receiving PD-1 inhibitors with or without a combination of tyrosine kinase inhibitors (TKIs). Both the overall response rate (ORR) and organ-specific response rate (OSRR) were assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. A survival analysis and its predictors were determined using a multivariate analysis. Results: We analyzed 42 advanced HCC patients (median age: 58.0 years; 78.6% males). Thirty (71.4%) patients were sorafenib-experienced and 27 (64.3%) were administered a combination of TKIs. The ORR was 14.3% and the disease control rate was 33.3%. The median overall survival (OS) and progression-free survival (PFS) were 12.0 and 2.9 months, respectively. The OSRRs were 14.7, 23.8, 28.6, and 50.0% for the liver, lungs, lymph nodes, and vascular response, respectively. The multivariate analysis indicated that the vascular response was significantly associated with PFS. ECOG performance status was a significant independent predictor of OS. Conclusions: PD-1 inhibitors improved OS and PFS in advanced HCC patients. Their efficacies varied among the metastatic locations regardless of the combination of TKIs; in particular, a higher response in vascular metastases was correlated with a longer PFS. PD-1 inhibitors may deliver a synergistic benefit in patients undergoing traditional therapy and progression in other organs in vascular responders.

Postoperative adjuvant therapy for patients with loco-regionally advanced oral squamous cell carcinoma who are at high risk of recurrence

Extranodal extension (ENE) of lymph node metastasis and the presence of a positive or close margin (PCM) are major risk factors for head and neck squamous cell carcinoma recurrence. This retrospective multicentre cohort study compared the prognostic impact of postoperative radiotherapy (RT) and concurrent chemoradiotherapy (CCRT) in oral squamous cell carcinoma (OSCC) patients at high risk of recurrence. One hundred and eighteen patients with PCM and/or ENE who underwent definitive surgery plus either adjuvant RT or CCRT using cisplatin for OSCC were investigated. The cohort-wide 5-year loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates (the main outcome measures) were 54.3%, 35.8%, and 43.2%, respectively. Multivariate analysis showed that age ≥64 years (hazard ratio (HR) 0.584), cT3–4 stage (HR 1.927), ≥4 metastatic lymph nodes (HR 1.912), and PCM (HR 2.014) were significant independent predictors of OS. Moreover, postoperative CCRT with cisplatin was associated with a significantly improved LRC rate, but not with improved DFS or OS rates, compared to postoperative RT (HR 0.360). Given that CCRT with cisplatin does not significantly improve survival, additional clinical trials will be required to validate new regimens that further improve the outcomes of patients with loco-regionally advanced OSCC going forward.

CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients

BackgroundThe evaluation for surgical resectability of pancreatic ductal adenocarcinoma (PDAC) patients is not only imaging-based but highly subjective. An objective method is urgently needed. We report on the clinical value of a phenotypic circulating tumor cell (CTC)-based blood test for a preoperative prognostic assessment of tumor metastasis and overall survival (OS) of PDAC patients. MethodsVenous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs were differentiated into epithelial (E), mesenchymal and hybrid (H) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification. FindingsA validated multivariable model consisting of disjunctively combined CTC phenotypes: “H-CTC≥15.0 CTCs/2ml OR E-CTC≥11.0 CTCs/2ml” generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889–1.000) and specificity of 0.886 (95% CI 0.765–0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E-CTC < 11.0 CTCs/2 ml was 16.5 months and for E-CTC ≥ 11.0 CTCs/2 ml was 5.5 months (HR = 0.050, 95% CI 0.004–0.578, P = .016). These OS results were consistent with the outcome of the metastatic analysis. InterpretationOur work suggested that H-CTC is a better predictor of metastasis and E-CTC is a significant independent predictor of OS. The CTC phenotyping model has the potential to be developed into a reliable and accurate blood test for metastatic and OS assessments of PDAC patients. FundNational Natural Science Foundation of China; Zhejiang Province Science and Technology Program; China Scholarship Council.

PS1500 HEALTHCARE RESOURCE UTILIZATION (HCRU) IN PATIENTS (PTS) WITH NEWLY DIAGNOSED (ND) ACUTE MYELOID LEUKEMIA (AML) TREATED IN THE CONNECT® MDS/AML DISEASE REGISTRY

Background:Treatment (Tx) options for pts with ND AML include high‐intensity (HI) chemotherapy (7+3 regimen) followed by consolidation therapy or allogeneic stem cell transplantation, low/intermediate‐intensity (LI) therapies (low‐dose cytarabine or hypomethylating agents), best supportive care (BSC), or no Tx. While several studies have examined HCRU and costs among pts with ND AML, these studies focused on claims data, and few studies have examined HCRU based on Tx regimen received.Aims:To examine HCRU in ND AML pts receiving different Tx modalities in the Connect® MDS/AML Disease Registry (NCT01688011).Methods:Pt demographics, disease characteristics, and Tx information were reported by sites at screening and every 3 months for AML pts enrolled from December 2013 to December 2018 in the Connect® MDS/AML Disease Registry, a large, US, multicenter, prospective observational cohort study of pts with ND AML (aged ≥55 yrs) or myelodysplastic syndromes (aged ≥18 yrs). HCRU was assessed in ND AML pts according to Tx groups defined as HI, LI, BSC, or no Tx initiated ≤45 days post‐diagnosis. Unplanned hospitalizations due to disease or Tx‐related complications were assessed at 3 and 6 months post‐enrollment. Response to Tx was analyzed in the HI and LI groups only. Number of transfusion episodes was calculated 6 months post‐enrollment and at each month in the HI and LI groups.Results:A total of 510 AML pts, treated at 22 academic and 92 community/government centers, were included in the analysis. Median age was 70 years (range 55–92), 63% were male, and 84% were white. 98 (19.2%) pts received BSC/no Tx, 186 (36.5%) received LI therapy, and 226 (44.3%) received HI therapy. The percentage of pts with ≥1 hospitalization was similar between the HI and LI groups (59.3% vs 53.8%), but was lower in the BSC/no Tx group (24.5%; P &lt; 0.05). During months 1–3 post‐enrollment, pts in the HI group spent a mean of 15.9 days in hospital versus 8.9 days in the LI group and 10.3 in the BSC/no Tx group; this decreased in all Tx groups to 11.6, 8.2, and 6.5 days, respectively during months 4–6 post‐enrollment. Mean monthly transfusion burden over the first 6 months in the HI and LI groups was 4.9 versus 2.8 transfusion episodes/month (P &lt; 0.01). During month 1 post‐enrollment, mean transfusion episodes in the HI group was 8.8 versus 3.2 in the LI group (P &lt; 0.01). Over the 6‐month study period, the transfusion rate decreased in both groups (P &lt; 0.01). Transfusion rates in the HI and LI groups were similar after Month 4 (Figure), coinciding with the end of consolidation chemotherapy in the HI group. In logistic regression analyses, pts in the HI group were more likely to achieve complete remission (CR) versus pts in the LI group, after adjusting for age, comorbidities, and disease risk (odds ratio 5.2, 95% CI 2.0–13.5; P &lt; 0.01). Mortality rates were significantly higher in the LI group versus the HI group at 60 (P &lt; 0.05) and 180 days (P &lt; 0.01), but not at 30 days. Median overall survival (OS) was longer in the HI group (21 months; 95% CI 16–32) versus the LI group (9 months; 95% CI 6–11; P &lt; 0.01); however, Tx group was not a significant independent predictor of OS in multivariate analysis.Summary/Conclusion:These findings highlight the level of HCRU in ND AML pts treated with different intensity therapies. While HCRU was highest in the HI group and may be secondary to cytopenia‐related complications associated with HI regimens, pts in this group were significantly more likely to achieve CR, have improved OS, and lower mortality rates at 60‐ and 180‐day landmarks.image