Predictor Of On Overall Survival Research Articles

The log odds of positive neck lymph nodes is a superior lymph node predictor for overall survival in head and neck cancer: a population-based analysis in Germany

BackgroundThis population-based study investigated the influence of different lymph node (LN) classifications on overall survival (OS) in head and neck cancer (HNC).Methods401 patients (median age: 57 years; 47% stage IV) of the Thuringian cancer registries with diagnosis of a primary HNC receiving a neck dissection (ND) in 2009 and 2010 were included. OS was assessed in relation to total number of LN removed, number of positive LN, LN ratio, and log odds of positive LN (LODDS).ResultsMean number of LODDS was 0–0.96 ± 0.57. When limiting the multivariate analysis to TNM stage, only the UICC staging (stage IV: HR 9.218; 95% CI 2.721–31.224; p < 0.001) and LODDS > – 1.0 (HR 2.120; 95% CI 1.129–3.982; p = 0.019) were independently associated with lower OS.ConclusionLODDS was an independent and superior predictor for OS in HNC in a population-based setting with representative real-life data.

Combining liquid biopsy and functional imaging analysis in metastatic castration-resistant prostate cancer helps predict treatment outcome.

Plasma tumour DNA (ptDNA) is a potential early noninvasive biomarker of treatment outcome in metastatic castration‐resistant prostate cancer (mCRPC). Herein, we investigated whether pretreatment ptDNA levels reflect metabolic tumour burden in mCRPC and better predict treatment outcome in combination with functional imaging. Targeted next‐generation sequencing was performed to estimate the ptDNA fraction from 102 mCRPC patients receiving abiraterone or enzalutamide. The maximum standardized uptake value (SUVmax), total lesion activity (TLA) and metabolic tumour volume (MTV) were evaluated on 18F‐fluorocholine positron emission tomography/computed tomography. We assessed a Weibull multiple regression model to determine the combined impact of clinical, molecular and imaging characteristics on overall survival (OS) and progression‐free survival (PFS), and to obtain prognostic scores. A significant association was seen between ptDNA and SUVmax, MTV and TLA. For survival analysis, patients were randomly allocated into a training (n = 68) and a validation (n = 34) set. In the training set, multivariable analyses showed that ptDNA, MTV and serum lactate dehydrogenase together with visceral metastasis were independent predictors of both OS and PFS. Prognostic scores were generated, with the identification of three groups of patients with significantly different median OS (29.2, 15.9 and 8.7 months) and PFS (13.3, 7.7 and 3.2 months) probabilities. The differences in median survival between risk groups were confirmed in the validation cohort for both OS and PFS. In our study, we showed that integrating plasma DNA analysis with functional imaging may improve prognostic risk stratification and treatment selection in mCRPC.

Chemoembolization Plus Microwave Ablation vs Chemoembolization Alone in Unresectable Hepatocellular Carcinoma Beyond the Milan Criteria: A Propensity Scoring Matching Study.

PurposeTransarterial chemoembolization (TACE) is recommended in patients with unresectable HCC beyond the Milan criteria (MC). However, the long-term efficacy of TACE remains unsatisfactory. Percutaneous microwave ablation (MWA) is a curative therapy for early-stage HCC that provides better local tumor control than TACE; however, MWA is limited for large or multifocal lesions. We aimed to compare treatment efficacy and downstaging rate following combined TACE-MWA and TACE alone in patients with unresectable HCC beyond the MC.Patients and MethodsPatients with unresectable HCC beyond the MC who underwent either TACE-MWA (n=91) or TACE alone (n=140) at four medical institutions were included. Potential influencing factors on overall survival (OS) and progression-free survival (PFS) were included in the Cox regression analysis. Propensity-score matching of patients treated with TACE-MWA and TACE alone was performed. Differences in OS and PFS were compared with the Log rank test. Patients who met the University of California, San Francisco criteria were eligible for assessment of the probability of downstaging within the MC. Downstaging rate was compared between the two groups.ResultsIn multivariate analysis, treatment with TACE alone was an independent predictor of poor PFS (P=0.011) and OS (P<0.001). Both PFS (P=0.043) and OS (P=0.002) were significantly higher in patients treated with TACE-MWA than those treated with TACE alone. The downstaging rate was higher in patients treated with TACE-MWA than those treated with TACE alone (P=0.039).ConclusionCompared with TACE alone, TACE-MWA may offer a survival benefit in terms of OS and PFS in HCC patients beyond the MC. Additionally, TACE-MWA may provide higher probability of downstaging within the MC than TACE alone, thereby increasing the possibility of liver transplantation.

Combination of the ratio between metastatic and harvested lymph nodes and negative lymph node count as a prognostic indicator in advanced gastric cancer: a retrospective cohort study.

The aim of our study was to examine the impact of the combination of the ratio between metastatic and harvested lymph nodes (RML) and negative lymph node (NLN) count on overall survival (OS) in patients with advanced gastric cancer (GC). The clinicopathological data of 2,952 advanced GC patients who received curative resection between 1994 and 2015 were collected. They were divided into four groups according to the RML: 0, 0-0.1, 0.1-0.4, and >0.4. We distinguished survival differences through Kaplan-Meier analysis among the subgroups to investigate the impacts of the RML on OS in advanced GC patients. OS was examined according to clinicopathological variables. Spearman's correlation coefficient was used to assess the relationships between the RML and metastatic lymph node (MLN) count and NLN count. A total of 1,182 patients were enrolled into the study. The median follow-up time was 39 months (interquartile range 20 to 68 months). The 5-year OS rate of all 1,182 GC patients was 54.4%. Kaplan-Meier survival analysis showed that the median OS declined significantly with increasing RML (5-year survival rate 81.2% vs. 69.1% vs. 42.8% vs. 13.1%, P<0.001). As the NLN count increased, the survival rate of GC patients increased (5-year survival rate 12.8% vs. 25.2% vs. 60.2%, P<0.05). The RML, not NLN count, was identified as an independent factor for OS (P<0.001) through multivariate analysis. Spearman correlation analysis suggested that the RML was positively correlated with the number of MLNs (ρ=0.973, P<0.001) and inversely associated with the NLN count (ρ=-0.513, P<0.001). The RML is an independent prognostic predictor of OS in advanced GC patients, and the NLN count may serve as a supplementary strategy for the present tumor-node-metastasis (TNM) classification to further improve the prognostic prediction efficiency. The combination of the RML and NLN count should be an important predictor for current clinical applications.

MP45-19 EVALUATION OF THE UTILITY OF LYMPH-VASCULAR INVASION AS AN INDEPENDENT PROGNOSTIC PREDICTOR OF OVERALL SURVIVAL FOR PATIENTS WITH RENAL CELL CARCINOMA THAT UNDERGO NEPHRECTOMY

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance I (MP45)1 Sep 2021MP45-19 EVALUATION OF THE UTILITY OF LYMPH-VASCULAR INVASION AS AN INDEPENDENT PROGNOSTIC PREDICTOR OF OVERALL SURVIVAL FOR PATIENTS WITH RENAL CELL CARCINOMA THAT UNDERGO NEPHRECTOMY Nikola Rakic, Ivan Rakic, Jacob Keeley, Nicholas Corsi, Chandler Bronkema, Marcus Jamil, Akshay Sood, Giacomo Novara, Mani Menon, Craig Rogers, and Firas Abdollah Nikola RakicNikola Rakic More articles by this author , Ivan RakicIvan Rakic More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Chandler BronkemaChandler Bronkema More articles by this author , Marcus JamilMarcus Jamil More articles by this author , Akshay SoodAkshay Sood More articles by this author , Giacomo NovaraGiacomo Novara More articles by this author , Mani MenonMani Menon More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002066.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymph-vascular invasion (LVI) is recognized as an adverse pathological feature in patients with renal cell carcinoma (RCC). However, its impact on overall survival (OS) is not clear, and scarcely addressed in literature. Our aim was to assess the prognostic ability of LVI as a predictor of OS in RCC patients using a large, North American cohort. METHODS: We included 45,036 cM0 RCC patients, diagnosed between 2010 and 2015, that underwent partial or radial nephrectomy within the National Cancer Database. Kaplan-Meier curves and long-rank test were used to depict and compare survival curves. Cox regression analysis tested the relationship between LVI and OS, after accounting for the following covariates: age, Charlson Comorbidity Index status, pathological tumor stage, number of nodes removed, number of positive nodes, pathological nodal status (LNI), and pathological LVI status. RESULTS: Median age (IQR) was 60 (52-68), and most patients had pT1 stage (70.0%). Nodal status was pN0, pN1, and pNx in 14.0%, 3.7%, and 82.3%, respectively. Overall, 7.7% of patients had LVI. Median (IQR) follow-up of the cohort was 38 months (20-59). At 5-years, OS was 59.8% in patients with LVI vs. 85.1% in patients without LVI (p-value<.0001). When patients were stratified based on nodal stage, these rates were 55.8% vs. 77.2% in pN0 patients, (p<0.0001) and 34.1% vs. 39.7% in pN1 patients (p<0.0001). LVI was an independent predictor of higher overall risk of mortality (hazard ratio [HR]: 1.53, 95% CI: 1.36–1.71, p<.001). Other covariates that had a detrimental prognostic impact included pN1 disease (HR: 2.08), Fuhrman grade 3 disease (HR: 1.30), Fuhrman grade 4 disease (HR: 2.54), a pT2 disease (HR: 1.40) and pT3/4 disease (HR: 1.92). (all p-value<0.0001) CONCLUSIONS: Our findings highlight the detrimental impact of LVI on OS in a large nationwide cohort. To the best of our knowledge, this is the first validation of the prognostic ability of LVI in RCC patients on a nationwide level, as virtually all previous studies were institutional. Besides, we observed a synergistic impact for LVI in the presence of pN1, as these patients fare worse than those who have pN1 disease without LVI. Our findings highlight an important utility that LVI can provide in deciding a patient’s prognosis after nephrectomy, and further exploration should examine exactly what its role may become. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e811-e811 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nikola Rakic More articles by this author Ivan Rakic More articles by this author Jacob Keeley More articles by this author Nicholas Corsi More articles by this author Chandler Bronkema More articles by this author Marcus Jamil More articles by this author Akshay Sood More articles by this author Giacomo Novara More articles by this author Mani Menon More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement Loading ...

PD51-12 WHOLE-PELVIS COMPARED TO BLADDER-ONLY RADIATION THERAPY PROLONGS OVERALL SURVIVAL IN MUSCLE-INVASIVE BLADDER CANCER PATIENTS: RESULTS FROM A CANADIAN MULTI-CENTER COLLABORATIVE STUDY

You have accessJournal of UrologyBladder Cancer: Invasive III (PD51)1 Sep 2021PD51-12 WHOLE-PELVIS COMPARED TO BLADDER-ONLY RADIATION THERAPY PROLONGS OVERALL SURVIVAL IN MUSCLE-INVASIVE BLADDER CANCER PATIENTS: RESULTS FROM A CANADIAN MULTI-CENTER COLLABORATIVE STUDY Ronald Kool, Gautier Marcq, Ionut Busca, Hamidreza Abdi, Rodney Breau, Mark Dawidek, Peter Black, Gagan Fervaha, Robert Siemens, Nimira Alimohamed, Claudio Jeldres, Michael Uy, Bobby Shayegan, Jonathan Izawa, Michael Kim, Girish Kulkarni, and Wassim Kassouf Ronald KoolRonald Kool More articles by this author , Gautier MarcqGautier Marcq More articles by this author , Ionut BuscaIonut Busca More articles by this author , Hamidreza AbdiHamidreza Abdi More articles by this author , Rodney BreauRodney Breau More articles by this author , Mark DawidekMark Dawidek More articles by this author , Peter BlackPeter Black More articles by this author , Gagan FervahaGagan Fervaha More articles by this author , Robert SiemensRobert Siemens More articles by this author , Nimira AlimohamedNimira Alimohamed More articles by this author , Claudio JeldresClaudio Jeldres More articles by this author , Michael UyMichael Uy More articles by this author , Bobby ShayeganBobby Shayegan More articles by this author , Jonathan IzawaJonathan Izawa More articles by this author , Michael KimMichael Kim More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , and Wassim KassoufWassim Kassouf More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002078.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous randomized data failed to show a clear oncological benefit of whole-pelvis (WP-RT) compared to bladder-only radiation (BO-RT) in highly selected patients with non-metastatic muscle-invasive bladder cancer (MIBC) undergoing chemoradiation. Our objective was to evaluate the impact of WP-RT vs. BO-RT on overall survival (OS) in an unselect population of MIBC patients treated with RT-based bladder preserving therapy. METHODS: We conducted a collaborative Canadian study of 943 non-metastatic MIBC patients (cT2-4b, cN0-3, M0) who underwent bladder-preserving RT-based therapy with curative intent (≥40Gy) at 10 academic centers across Canada. Baseline clinico-pathological characteristics and follow-up data were collected. Kaplan-Meier survival estimates were performed. A multivariable Cox regression model was used to explore independent predictors of OS. RESULTS: Median age was 77 years [IQR 68-82], 694 (74%) patients were males. A total of 719 patients (76%) were cT2, 220 (24%) cT3-4b, 90 (10%) were N+, and 188 (20%) had concomitant CIS. WP-RT was delivered to 552 (52%) patients. At 3 months post RT, 71% had a complete response (CR). Median follow-up was 54 months (95% CI 49-58) and 439 patients (46.6%) died. Median time to death was 52 months (95% CI 44-66). On multivariable analysis, WP-RT was associated with prolonged OS (HR 0.61, p<0.001), independently of age (HR 1.03, p=0.004), ECOG (HR 1.80, p<0.001), high cT stage (HR 1.39, p=0.035), presence of hydronephrosis (HR 1.59, p=0.007) and CR (HR 0.55, p<0.001). CONCLUSIONS: WP-RT is associated with improved OS in MIBC patients undergoing bladder-preserving therapy. Prospective trials are needed to validate these findings, as RT-based therapy is increasingly utilized in patients with higher risk MIBC. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e910-e910 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ronald Kool More articles by this author Gautier Marcq More articles by this author Ionut Busca More articles by this author Hamidreza Abdi More articles by this author Rodney Breau More articles by this author Mark Dawidek More articles by this author Peter Black More articles by this author Gagan Fervaha More articles by this author Robert Siemens More articles by this author Nimira Alimohamed More articles by this author Claudio Jeldres More articles by this author Michael Uy More articles by this author Bobby Shayegan More articles by this author Jonathan Izawa More articles by this author Michael Kim More articles by this author Girish Kulkarni More articles by this author Wassim Kassouf More articles by this author Expand All Advertisement Loading ...

MM-220: The Predictive Role of the Pretreatment Neutrophil/Lymphocyte, Lymphocyte/Monocyte, and Platelet/Lymphocyte Ratios in Multiple Myeloma Patients: A Single-Center Experience

Context The biological behavior of multiple myeloma is determined by genetics and the marrow microenvironment. Inflammatory cells are the major sources of cytokines in MM-infiltrated bone marrow, and they can mediate immune suppression in MM. The current risk stratification for myeloma patients is mainly based on tumor biology, tumor burden, and patient characteristics. No factors related to inflammatory microenvironment have been enrolled. Objective Evaluate the prognostic value of cellular components of the systemic inflammatory response, including NLR, LMR, and PLR, on overall survival (OS) in MM patients. Design A retrospective study, including 190 MM patients who presented at our center during 2008–2019. Setting It was carried out in Oncology Center, Mansoura University (OCMU). Patients 190 patients with MM, with F/M (38.4%/61.6%) and mean age 57.22 ± 9.87 years. Interventions The patients were subjected to full laboratory and radiological assessments. Treatment was according to institute guidelines, dividing patients into transplant fit and unfit. Main Outcome Measures We determined the optimum cutoff points for the NLR, LMR, and PLR as predictors for OS based on the receiver operating characteristic (ROC) curve. Based on the cutoff values, the patients were categorized into the groups as follows: high-NLR group (≥1.99) and low-NLR group ( Results In this study, OS was significantly improved in patients without renal impairment (P=0.002), serum albumin >3.5 mg/dl (P=0.006), LDH ULN (P=0.215), PLR Conclusion Neutrophil/lymphocyte ratio and lymphocyte/monocyte ratio can be used in daily practice as a predictor for survival in multiple myeloma.

Prognostic significance of the postoperative prognostic nutritional index in patients with glioblastoma: a retrospective study

BackgroundThe prognostic nutritional index (PNI) reflects immunonutritional status. We evaluated the effects of postoperative PNI and perioperative changes in the PNI on overall survival (OS) in glioblastoma (GBM) patients.MethodsDemographic, laboratory, and clinical data were retrospectively collected from 335 GBM patients. Preoperative and postoperative PNIs were calculated from serum albumin concentration and lymphocyte count, which were measured within 3 weeks before surgery and 1 month after surgery. Patients were classified into high (n = 206) or low (n = 129) postoperative PNI groups according to the postoperative PNI cutoff value and further classified into four groups according to the cutoff values of the preoperative and postoperative PNIs, as follows: Group HH (both high PNIs, n = 92), Group HL (high preoperative and low postoperative PNI, n = 70), Group LH (low preoperative and high postoperative PNI, n = 37), and Group LL (both low PNIs, n = 136).ResultsThe median OS was significantly longer in the high postoperative PNI (PNI ≥ 50.2) group than the low postoperative PNI (PNI < 50.2) group (24.0 vs. 15.0 months, p < 0.001). In multivariate analysis, high postoperative PNI was a significant predictor of OS. OS was significantly longer in Group HH than in Group LL and seemed longer in Group HH than in Group HL and in Group LH than in Group LL. OS was not different between Groups HH and LH or between Groups HL and LL.ConclusionsHigh postoperative PNI was associated with improved OS and perioperative changes in PNI may provide additional important information for prognostic prediction in GBM patients.

Prediction of overall survival in patients across solid tumors following atezolizumab treatments: A tumor growth inhibition-overall survival modeling framework.

The objectives of the study were to use tumor size data from 10 phase II/III atezolizumab studies across five solid tumor types to estimate tumor growth inhibition (TGI) metrics and assess the impact of TGI metrics and baseline prognostic factors on overall survival (OS) for each tumor type. TGI metrics were estimated from biexponential models and posttreatment longitudinal data of 6699 patients. TGI‐OS full models were built using parametric survival regression by including all significant baseline covariates from the Cox univariate analysis followed by a backward elimination step. The model performance was evaluated for each trial by 1000 simulations of the OS distributions and hazard ratios (HR) of the atezolizumab‐containing arms versus the respective controls. The tumor growth rate estimate was the most significant predictor of OS across all tumor types. Several baseline prognostic factors, such as inflammatory status (C‐reactive protein, albumin, and/or neutrophil‐to‐lymphocyte ratio), tumor burden (sum of longest diameters, number of metastatic sites, and/or presence of liver metastases), Eastern Cooperative Oncology Group performance status, and lactate dehydrogenase were also highly significant across multiple studies in the final multivariate models. TGI‐OS models adequately described the OS distribution. The model‐predicted HRs indicated good model performance across the 10 studies, with observed HRs within the 95% prediction intervals for all study arms versus controls. Multivariate TGI‐OS models developed for different solid tumor types were able to predict treatment effect with various atezolizumab monotherapy or combination regimens and could be used to support design and analysis of future studies.

Systemic Inflammation Response Index is an Independent Prognostic Indicator for Patients with Renal Cell Carcinoma Undergoing Laparoscopic Nephrectomy: A Multi-Institutional Cohort Study.

BackgroundWe conducted a multicenter clinical study to examine the prognostic value of the systemic inflammation response index (SIRI) in renal cell carcinoma (RCC) patients.MethodsWe collected patients who underwent nephrectomy from 2014 to 2019 at three centers (343 in the training group and 100 in the validation group). SIRI was created based on hemoglobin and lymphocyte to monocyte ratio (LMR). Kaplan–Meier curves and receiver operating characteristic (ROC) curves were used to analyze the effect of LMR, hemoglobin and SIRI on overall survival (OS) and cancer-specific survival (CSS) effects.ResultsIn both the training and validation groups, SIRI was a better predictor of OS and CSS than LMR and hemoglobin. A total of 192 (56.0%) patients were included in grade 1, 108 (31.5%) in grade 2, and 43 (12.5%) in grade 3 based on SIRI in the training group. Higher SIRI was associated with worse prognosis. Multivariate cox regression analysis showed that SIRI was an independent prognostic risk factor for OS (grade 3 vs grade 1: HR=4.93; 95% CI 2.21–11.00, p < 0.001) and CSS (grade 3 vs grade 1: HR=6.29; 95% CI 2.28–17.39, p < 0.001) in patients with RCC. In addition, SIRI-based prognostic nomograms were able to better predict OS and CSS in RCC patients.ConclusionSIRI is an independent prognostic factor for patients undergoing laparoscopic nephrectomy for RCC, and a prognostic nomogram covering SIRI can better predict survival of RCC patients.

A novel ferroptosis-related 12-gene signature predicts clinical prognosis and reveals immune relevancy in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is still highly aggressive and lethal even with various therapeutic approaches. As the kidney is an iron metabolism-related organ, exploring and assessing the clinical value of ferroptosis, an iron-dependent regulated cell death, is practical and important.MethodsPrognostic ferroptosis-related differentially expressed genes (DEGs) were identified from the KIRC cohort in the cancer genome atlas (TCGA) database, from which a prognostic signature was established using Lasso-penalized Cox regression analysis. Each patient in the KIRC cohort and the E-MTAB-1980 cohort (from the ArrayExpress database) was assigned a calculated signature-correlated risk score and categorized to be either in the high- or low-risk group divided by the median risk score in the KIRC cohort. Then, the independent prognostic value of the signature was further assessed by Kaplan-Meier (K-M) survival, time-dependent receiver operating characteristic (ROC) and Cox regression analyses based on overall survival (OS) in both cohorts. Finally, risk-related DEGs were identified in both cohorts and subjected to enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and immune infiltration.ResultsAmong 60 ferroptosis-related genes, 32 prognostic DEGs were identified, from which we constructed a prognostic 12-gene signature with CARS1, HMGCR, CHAC1, GOT1, CD44, STEAP3, AKR1C1, CBS, DPP4, FANCD2, SLC1A5 and NCOA4. Patients in both cohorts were divided into high- and low-risk groups, which were visually distributed in two sets and had positive-risk-related mortality. The K-M survival and the ROC curves validated that the signature has prognostic value with P < 0.05 and area under the curve > 0.7 in both cohorts, respectively. Multivariate Cox regression further confirmed the risk score as an independent prognostic predictor for OS. Commonly enriched terms in GO and KEGG not only showed a high iron correlation but also, interestingly, immune relevance of 3 immune cells (macrophages, mast cells and regulatory T cells) and 1 immune-related function (antigen processing cell co-stimulation).ConclusionWe established a novel 12 ferroptosis-related-gene signature that was proven to be an independent prognostic predictor for OS and inferred to be related to tumour immunity in ccRCC; however, the underlying mechanism is still poorly characterized and needs further exploration.

The Role of Upfront Autologous Hematopoietic Cell Transplantation in the Treatment of Mantle Cell Lymphoma, a Population Based Study Using the National Cancer Data Base (NCDB)

Introduction: There are no prospective randomized data supporting the use of upfront consolidative autologous stem cell transplant (ASCT) in newly diagnosed mantle cell lymphoma (MCL) patients (pts). The aim of this population-based study in MCL pts is to better define the impact of frontline ASCT on overall survival (OS), and to identify factors influencing treatment selection.Methods: Using the National Cancer Data Base (NCDB), we identified pts with newly diagnosed MCL treated from 2004-2012 with multi-agent chemo alone or in combination with consolidative ASCT as part of first line treatment. Univariable and multivariable Cox proportional hazards regression analyses were used to identify predictors for treatment selection and OS, including age, gender, race, stage, Charlson-Deyo comorbidity index (CDCI), income, education, insurance, treatment facility type, distance to treatment facility and year of diagnosis. Income was recorded as quartiles of median annual household income and education as percentage of persons with less than high school education in pts' residence census. Including these same factors, a propensity score matched analysis (PSMA) was performed to further account for confounding variables.Results: We identified 16,035 MCL pts with known survival times. The following groups were excluded: no chemo (n=3,193), chemo status/type unknown (n=1,056), chemo contraindicated (n=199), single-agent chemo (n=983), received allogeneic SCT (n=79) or ASCT data missing (n=235). The final analysis included 10,290 pts. Median age was 65 years (range 20-90); 66% were > 60 years, 73% male, 93% Caucasian, and 78% had stage III-IV. CDCI was 0 in 79%, 1 in 16% and ≥2 in 5%. Forty percent of pts were treated at academic institutions and 49% travelled >11.5 miles to receive treatment. Medicare was the most common insurance type (48%), followed by private (43%) and Medicaid (4%). Median follow up was 34 months (interquartile range (IQR) 16-60). Median OS for the entire cohort was 64 months; 5- and 10-year OS rates were 52% and 33%, respectively. Seventeen percent of the pts (n=1774) underwent upfront ASCT, and there was a trend of increased use from 2004-2012 (11.9% in 2004 and 21.2% in 2012) that resulted in an annual increase of 1.2% (p<0.001). 31% of pts ≤60 and 25% of pts ≤70 years received ASCT. For the ASCT group, median age was 58 years (IQR 52-64; range 23-77); 89 pts (5%) were ≥70 years of age. Predictors for ASCT use included (p<0.001 for each): stage III-IV (odds ratio (OR) 2.4), having private insurance (OR 2.71), higher education (OR 2.1), no transition of care (diagnosis and treatment done at the same facility) (OR 3.15), longer distance (> 11.5 miles) to treatment facility (OR 1.73) and year of diagnosis ≥2009 (OR 1.62) (Figure 1). Median follow up was 44 months (IQR 28-69) for ASCT group and 31 months (IQR 14-58) for chemo only group. Five and 10-year OS rates for ASCT and chemo group were 77%, 57%, 47% and 28%, respectively. After adjusting for other covariates, the use of ASCT was associated with superior OS (HR: 0.46; 95% CI 0.41-0.52; p<0.001). Other factors associated with superior OS were: female gender (HR 0.92, p=0.01), income (HR 0.92, p<0.001), private insurance (HR 0.71, p<0.001), no transition of care (HR 0.82, p<0.001) and diagnosis year ≥2009 (HR 0.91, p=0.005). Predictors for inferior OS were: age >60 (HR 1.62, p<0.001), African American race (HR 1.23, p=0.009), stage III-IV (HR 1.58, p<0.001) and CDCI ≥2 (HR 2.0, p<0.001). Using a subset of 1582 pts treated with ASCT and 1582 matched controls treated with chemo only, PSMA confirmed the OS benefit associated with ASCT (HR 0.5; CI 0.44-0.57, p<0.001). This OS benefit was observed in both younger (≤60 years: HR 0.44, CI 0.37-0.53, p<0.001) and older pts (>60 years: HR 0.59, CI 0.46-0.68; p<0.001) (Figure 2).Conclusion: In this large MCL cohort, the use of upfront consolidative ASCT was associated with superior OS when compared to chemo alone. Less than one third of young MCL pts treated with multi-agent chemo received consolidative ASCT, and this was influenced by sociodemographic factors with patterns favoring pts with higher education and private insurance. While one caveat in interpreting this retrospective study is that ASCT may have been preferentially applied to pts who responded to induction therapy, these data suggest clinical efficacy of ASCT in MCL. Prospective randomized trials are needed for further validation. [Display omitted] DisclosuresMajhail:Sanofi: Honoraria; Anthem, Inc.: Consultancy.

Impact of Comorbidities and Concomitant Medications on Survival of Patients with Chronic Lymphocytic Leukemia: Analysis of an Unselected Patient Population from East Bohemia

Introduction: Chronic lymphocytic leukemia (CLL) is a disease with an extremely variable clinical course. Biological features of CLL with impact on prognosis have been well defined over the last decades, but there is little data on how comorbidities of CLL patients (pts) may influence overall survival. Importantly, most of the studies on this topic included selected patient populations from secondary or tertiary centers with significant bias caused by high proportion of referred patients with unfavourable disease course.Aims: to evaluate impact of major comorbidities on overall survival (OS) in an unselected CLL population.Patients and methods: We performed a retrospective analysis of 202 pts (median age, 69 years, 60% males), who were diagnosed with CLL according to NCI-WG and IWCLL criteria in the Hradec Králové district (population 162,820 as of December 2011) between January 1st, from 1999, and December 31st, 2013. Influence of four major comorbidities (ischemic heart disease [IHD], diabetes mellitus [DM] on therapy, chronic obstructive pulmonary disease [COPD] and second primary malignancy [SPM]) as well as number of concomitant medications as an indicator of total comorbidity burden were evaluated using Kaplan-Meier curves and log-rank test: Multivariate analysis was performed using the Enter methodResults: Basic characteristics are listed in Table 1. A total of 37 pts (18%) had IHD, 30 (15%) had DM, 18 (9%) had COPD and 26 (13%) had SPM. Only IHD had major impact on OS (p=0.0005, Fig.1) in univariate analysis. Using receiver operator curve (ROC) analysis, it was determined that the optimal cut-off associated with shorter OS was ≥ 4 concomitant medications (p=0.029, Fig.2). Cox regression analysis included the following variables which proved significant in univariate analysis: Rai modified risk, age, IHD, number of concomitant medications, and year of diagnosis (1999-2005 vs. 2006-2013). High or intermediate modified Rai risk (p<0.0001), age ≥ 70 (p<0.0001), year of diagnosis 2006-2013 (p= p<0.0001) were significant predictors of shorter OS and there was a trend towards for pts IHD (p= 0.059) in multivariate analysis, the cumulative number of the 4 major comorbidities did not have statistically significant impact on OS.Conclusion: Our results indicate that ischemic heart disease and number of concomitant medications are significantly associated with shorter overall survival in patients with CLL. Supported by program PROGRES Q40/08 and by DRO (UHHK, 00179906) from Ministry of Health, Czech Republic. [Display omitted] DisclosuresVodarek:Janssen: Consultancy, Honoraria, Other: Travel grants ; Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants ; Servier: Consultancy, Honoraria, Other: Travel grants . Simkovic:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau. Motyckova:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding, Speakers Bureau. Belada:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants , Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau. Smolej:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau.

The prognostic significance of lymphovascular tumor invasion in localized high-grade osteosarcoma: Outcomes of a single institution over ten years.

e22013 Background: Lymphovascular tumor invasion (LVI) has shown evidence of an association with worse survival in high-grade osteosarcoma. The purpose of this investigation was to prognosticate LVI as a predictor of survival in these patients. Methods: This study was a retrospective review of high-grade, localized osteosarcoma patients diagnosed over a consecutive ten-year period. Cox proportional hazards regression was used to assess the prognostic significance of LVI on overall survival (OS). Results: A total of 42 cases met inclusion criteria with a median follow-up of 64 months (range, 6-158 months). LVI was present in 21.4% (n = 9) cases. The five and ten-year probabilities of OS in LVI (+) were 40% and 20%, respectively, compared to LVI (-) with five and ten-year estimates of 93% and 81%, respectively (p &lt; 0.001). After controlling for confounding variables, advanced age at diagnosis (HR, 1.134; 95% CI, 1-1.2; p = 0.01) and LVI (HR, 21.768; 95% CI, 3-135; p = 0.001) were found to be significantly negative predictors of OS. Using a competing risk analysis and Gray's test of equality, LVI (+) and LVI (-) were not statistically different with respect to cumulative incidence of recurrence (p = 0.8118), though were highly significant for cumulative incidence of mortality over time (p = 0.0029). Conclusions: The presence of LVI in the setting of high-grade, localized osteosarcoma is associated with greater rates of mortality and tumor recurrence and portends a dismal prognosis.

Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection.

Simple SummaryKRAS mutational heterogeneity between primary colorectal cancer and liver metastases may present a challenge in assessing prognostic information prior to the multimodal treatment. Aim of our study is to assess the incidence of KRAS discordance in a single-center series by comparing primary colorectal tumor specimens with the corresponding liver metastasis. Mutation analyses in all patients were performed at the same institution. Impact of discordance on overall survival and risk factors associated with discordance were analyzed. Our study showed that KRAS discordance was observed in 15.9% of patients. In patients with wild-type colorectal primary tumors, subsequent acquisition of mutation in the corresponding liver metastasis was associated with worse overall survival and was significantly more frequently found in patients with multiple liver metastases. These results suggested that, in the era of precision medicine, the possibility of KRAS discordance should be taken into account within the multidisciplinary management of patients with metastatic colorectal cancer.If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

Impact of Lymphovascular Invasion on Overall Survival in Patients With Prostate Cancer Following Radical Prostatectomy: Stage-per-Stage Analysis.

The detrimental impact of lymphovascular invasion (LVI) in prostate cancer (PCa) on biochemical recurrence has been described; the impact of LVI on overall survival (OS) remains unclear. This investigation sought to evaluate the impact of LVI on OS in patients with PCa. We examined men with nonmetastatic PCa treated with radical prostatectomy between 2010 and 2015. Only men with documented LVI status were included (n=232,704). Patients were stratified according to final pathologic T stage (pT2, pT3a, and pT3b). Of the 232,704 patients who met inclusion criteria, 17,758 (8%) were found to have LVI on final pathology. Overall, 174,838 (75%), 40,281 (17%), and 17,585 (8%) patients had pT2, pT3a, and pT3b disease, respectively. Median follow-up was 42.7 months (27.1-58.7). At 5 years, the OS in LVI versus non-LVI patients was 94% versus 95% in pT2 (P=.0004), 92% versus 95% in pT3a (P < .0001), and 86% versus 92% in pT3b (P < .0001). On multivariable analysis, LVI status was not an independent predictor of OS in pT2 disease (hazard ratio, 1.12; 95% confidence interval [CI], 0.93-1.36; P=.2). In pT3a and pT3b disease, presence of LVI had 1.2-fold (95% CI, 1.03-1.44; P=.02) and 1.4-fold (95% CI, 1.20-1.59; P < .001) higher overall mortality than their counterparts without LVI. Our report demonstrates the detrimental impact of LVI on OS in locally advanced PCa (pT3a and higher). This information may prove valuable when risk stratifying based on final pathology.

Clinicopathological predictors of survival in resected primary lung adenocarcinoma

AimsPrimary lung adenocarcinoma consists of a spectrum of clinical and pathological subtypes that may impact on overall survival (OS). Our study aims to evaluate the impact of adenocarcinoma subtype and...

Impact of high-intensity local treatment on overall survival in stage IV upper tract urothelial carcinoma

ObjectivesTo investigate the impact of high-intensity local treatment (LT) on overall survival (OS) in patients with stage IV upper tract urothelial carcinoma (UTUC). Patients and methodsWithin the National Cancer Database, we identified 7,357 patients diagnosed with stage IV UTUC from 2004 to 2015. Patients who underwent high-intensity LT, defined as radical surgery of the primary tumor, were compared with those who did not. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Weighted survival analyses were used to test the association between high-intensity LT and OS. Multivariable Cox model was used to assess for independent predictors of OS. Sensitivity analysis was used to account for possible biases. ResultsAmong stage IV patients, 10.6% (n = 779) had locally advanced disease (T4), 32.6% (n = 2,399) had node-positive disease (N+) and 56.8% (N = 4,179) had distant metastases (M+). Fewer than half of the patients underwent high-intensity LT (n = 2,908, 39.5%) while the remainder did not. On IPTW-adjusted survival analysis, high-intensity LT was associated with a prolonged OS (11.17 months [IQR, 5.19 to 24.28] months vs. 6.18 months [IQR, 2.27 to 14.49], P ≤ 0.001). A similar benefit was seen on adjusted survival analyses for each stage IV subgroup, defined according to TNM characteristics. The survival benefit was confirmed at sensitivity analysis. ConclusionHigh-intensity LT in balanced cohorts of patients with stage IV UTUC is associated with prolonged OS including those with locally advanced (T4), node-positive (N+) or distant metastases (M+).

Combining molecular and functional imaging in metastatic castration-resistant prostate cancer (mCRPC).

141 Background: Recently, plasma tumour DNA (ptDNA) has been identified as a potential early noninvasive biomarker of treatment response in mCRPC patients ( Conteduca, Br J Cancer 2020). In this study, we sought to determine whether pre-treatment ptDNA could accurately reflect metabolic tumor burden in mCRPC and if it could be in combination with functional imaging could provide better prognostication. Methods: Between October 2011 and June 2016, 102 plasma samples from mCRPC patients treated with abiraterone or enzalutamide were collected. Targeted next-generation sequencing was performed to determine baseline ptDNA fraction. Maximum standardized uptake value (SUVmax), total lesion activity (TLA), and metabolic tumour volume (MTV) were calculated on 18F-fluorocholine positron emission tomography/computed tomography. A Weibull multiple regression model was adopted to evaluate the combined impact of clinical, molecular and imaging features on overall survival (OS) and to obtain a prognostic score. Each variable was allotted a “partial score” that depended on the size of the regression coefficient. Total scores ranged between 0 and 5.85 and assigned patients to 3 different risk groups according to 18-months survival probability: group I, &gt;70%; group II 30%-70%; and group III, &lt;30%. We estimated OS probabilities by the exponential model and by the Kaplan-Meier method. Results: We observed a significant association between ptDNA levels dichotomized as below or above median plasma tumor fraction (low ptDNA≤0.188 versus high ptDNA&gt;0.188) and median SUVmax (p&lt;0.0001), MTV (p=0.0005) and TLA (p&lt;0.0001). Patients were randomly divided into a training set (n=68) and a validation set (n=34). In the training cohort, we performed a multivariable analysis showing that visceral metastasis, serum LDH, MTV and ptDNA were independent predictors of OS [HR=2.64, 95%CI 1.32-5.26, p=0.006; HR=3.69, 95%CI 1.98-6.87, p&lt;0.0001; HR=1.91, 95%CI 1.13-3.21, p=0.015; and HR=2.64, 95%CI 1.32-5.26, p=0.003, respectively]. In the training set, median OS was significantly different among the 3 risk groups (risk group I, 29.2 months [95% CI, 18.3 to 37.0 months]; risk group II, 15.9 months [95% CI, 10.6 to 24.0 months]; and risk group III, 8.7 months [95% CI, 6.3 to 15.4 months]; p&lt;0.0001). Similar results were observed in the validation set groups (risk group I, 23.4 months [95% CI, 8.1 to 38.5 months]; risk group II, 13.3 months [95% CI, 3.7 to 18.0 months]; and risk group III, 7.3 months [95% CI, 2.6 to 11.8 months]; p=0.001). Conclusions: Integrating plasma DNA analysis with functional imaging may improve prognostic risk stratification and treatment selection in mCRPC patients. A larger prospective evaluation is now warranted.

Survival and Prognostic Nomogram for Primary Gastrointestinal Melanoma (PGIM): A Population-based Study.

Primary gastrointestinal mucosal melanoma (PGIM) is an aggressive and rare disease, commonly with poor prognosis. We aimed to determine the clinical risk and prognosis of this rare entity. Patients (n=962) with PGIM documented in the Surveillance, Epidemiology, and End Results database between 1975-2016 were included. Prognostic factors on overall survival (OS) and cancer-specific survival (CSS) were identified. A nomogram was constructed to predict the OS of PGIM patients. Primary site, summary stage, and therapeutic method were all independent predictors of OS and CSS, and age was the only factor significantly associated with OS. Independent prognostic factors of OS were selected to develop a predictive nomogram. The Harrell's C-index of the nomogram was 0.712, the area under the curve (AUC) was 0.746, 0.758, 0.810 for the 1-, 3-, and 5-year OS, respectively, and calibration plots were in good agreement. Several prognostic factors of PGIM were demonstrated and a practical nomogram model was created in this study.