Significant Predictor Of Poor Overall Survival Research Articles

Prognostic role of the systemic immune-inflammation index and pan-immune inflammation value for outcomes of breast cancer: a systematic review and meta-analysis.

This review examined the literature for evidence on the prognostic ability of systemic immune-inflammation index (SII) and pan-immune inflammation value (PIV) for predicting overall survival (OS) and disease-free survival (DFS) in breast cancer patients. PubMed, Embase, Scopus, and Web of Science were searched with Google Scholar for gray literature. All types of studies reporting the association between SII or PIV and OS or DFS of breast cancer were eligible. 13 studies on SII and 4 studies on PIV were included. Meta-analysis showed that a high SII was a significant predictor of OS (HR: 1.97 95% CI: 1.54, 2.52 I2=76%) and DFS (HR: 2.07 95% CI: 1.50, 2.86 I2=79%) in breast cancer patients. These results did not change on sensitivity analysis and were more or less stable on multiple subgroup analyses. Pooled analysis showed that high PIV was also a significant predictor of poor OS (HR: 2.63 95% CI: 1.46, 4.74 I2=71%) and DFS (HR: 1.64 95% CI: 1.23, 2.17 I2=0%) in breast cancer patients. High SII and PIV can predict poor OS and DFS in breast cancer patients. High heterogeneity and the observational nature of data are important limitations of the review. Further studies are needed specifically on PIV to increase the strength of the evidence.

Favorable Outcomes with Low Dose Anti Thymocyte Globulin Based Graft Versus Host Disease Prophylaxis after Mismatched Unrelated Donor Allogenic Hematopoietic Cell Transplantation

DISCUSSION INTRODUCTION Anti thymocyte globulin (ATG) based Graft versus Host disease (GVHD) prophylaxis is widely used for unrelated donor allogeneic hematopoietic cell transplantation (HCT) although the optimal dose remains unclear. Recently, registry based and single centre retrospective analyses have suggested superior outcomes with the PTCy based GVHD prophylaxis regimens when compared to ATG based regimens in mismatched unrelated donor (MMUD) allogeneic HCT, however, these studies all used doses of ATG ≥ 5mg/kg. Outcomes following MMUD allogeneic HCT with lower dose ATG based GVHD prophylaxis regimens have not been extensively studied. Thus, we analysed outcomes of HLA 9/10 MMUD allogeneic HCTs using two low dose ATG based regimens as GVHD prophylaxis at our centre. All adult patients undergoing standard of care allogenic hematopoietic cell transplant at The Ottawa Hospital from January 1 st 2015- December 31, 2022 were included. Data regarding demographics, HLA mismatched allele, conditioning regimen, dose of ATG, time to engraftment, and rates of acute and chronic GVHD was collected. The primary outcome evaluated was overall survival (OS) and secondary outcomes were GVHD-free relapse-free survival (GRFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). Survival outcomes were analyzed using Kaplan Meier analysis. Predictors of survival were identified using Cox-proportional hazards regression model. 77 patients (Males 62.3% (n=48); Median age - 50 years) underwent allogeneic HCT from MMUD. Most common indication for transplant was MDS/AML in 66.2% (n=51) followed by ALL in 11.3% (n=9) patients. Most frequently mismatched locus was HLA A in 37.7% (n= 29) followed by HLA B in 14.3% (n=11). Myeloablative conditioning regimen was received by 76.6% (n=59) while reduced intensity regimens were used in 23.4% (n=18) patients. Rabbit ATG was part of the GVHD prophylaxis regimen in all patients with majority (81%; n=63) receiving 2.5mg/kg and remaining 18.2% (n=14) receiving 4.5mg/kg of the drug. Grade II-IV acute GVHD occurred in 24.7% (n=19) while chronic GVHD occurred in 32.5% (n= 25) patients. After a median follow up of 21 months, relapse occurred in 28.6% (n=22) patients. Two year OS (Fig 1), and GRFS of the whole cohort were 60.6% and 45.3% respectively. 2-year incidence of non-relapse mortality (NRM) and cumulative incidence of relapse (CIR) were 16.9% and 18.2% respectively. Dose of ATG (2.5 mg/kg vs 4.5 mg/kg) was not a predictor of outcomes in either univariate and multivariate analyses. Age more than 50 years, primary diagnosis of lymphoma, reduced intensity conditioning and mismatch in loci other than HLA C were significant predictors of poor OS after univariate analysis. Only primary diagnosis of lymphoma (Hazard Ratio (HR) - 7.76; p=0.045) and mismatch in loci other than HLA C (HR - 9.53; p=0.03) were significant predictors of poor OS after multivariate analysis. When compared to published single centre and registry-based studies using ATG doses ≥ 5 mg/kg, GVHD prophylaxis using ATG doses ≤4.5 mg/kg seems to provide improved outcomes in patients undergoing allogeneic HCT from mismatched unrelated donors (Table 1). Our findings suggest that further studies are needed directly comparing lower dose ATG based regimens to PTCy based regimens to determine the ideal GVHD prophylaxis regimen for patients undergoing allogeneic HCT from HLA mismatched unrelated donors.

Impact of Early Hospitalization, Medical Comorbidities and Allogeneic Stem Cell Transplantation on Survival in Acute Myeloid Leukemia Patients Treated with Venetoclax Based Therapy - a Single Institution Experience from an Academic Center

Introduction: Bcl-2 inhibitor Venetoclax (Ven) in combination with hypomethylating agents (HMA) has improved response rates (RR), and median overall survival (OS) in Acute Myeloid Leukemia (AML) patients who are elderly and/or ineligible for intensive therapies. However, observed outcomes in patients treated in off-trial setting may be inferior (Winters, et al 2019). While disease markers that predict poor RR are well described, patient factors that could impact the inferior outcomes in the real-world setting have not been fully understood. We investigated the impact of incremental age, early hospitalization, comorbidity burden, along with other disease and treatment variables, on survival. Patients and methods: After IRB approval, all consecutive patients with AML and high-risk myelodysplastic syndromes (MDS) who were treated with Ven based regimen between 2017 and 2021 were reviewed. Descriptive statistics are reported. Kaplan-Meir analysis was used to estimate survival, and cox-proportional hazards was used to investigate survival association with variables. Overall survival (OS) was calculated from the time of initiation of venetoclax to the date of last follow up or death. Disease related data, effect of Incremental age, number of medical co-morbid conditions, unplanned early hospitalization (EH) rates within 30 days (EH30) and 90 days (EH90), causes of hospitalization, transfusion needs, and other treatment related adverse events were captured. Factors that impacted EH and overall survival were investigated. Results: Baseline characteristics are outlined in Table 1. A total of 89 subjects with AML and MDS-EB2 who received Ven based therapy were identified. All but 3 received HMA/Ven combination. Forty-nine (55%) received HMA/Ven in first line (FL) and 40(45%) in second line (SL) or later, of whom 12(30%) were treated in post- transplant (ASCT) relapse. Median age was 72 and 64, and median follow up was 21 months (95% CI, 9,27) and 22 months (95% CI, 9,32), respectively, for FL and SL. By ELN criteria high risk patients were 77% and 57% in FL and SL cohorts, respectively. Sixty percent and 40% patients had EH30 and 52%, and 35% patients had EH90 in FL and SL cohorts, respectively. Presence of ≥2 comorbidities significantly predicted EH90 (p=0.04). Most common cause of EH was neutropenic fever and sepsis. In 20 patients where data was available, median pRBC units received were 6(range 1-32), and 10(range 0-50), and median platelet units were 8(range 0-42), and 1 (range 0-73), in FL and SL cohorts, respectively. Table 2 summarizes survival outcomes by important variables. Median OS is 6 months (95% CI, 4,10), and 8 months (95% CI, 4,11) for the entire FL and SL groups. Within the SL group, median OS was significantly worse at 4 months (95% CI 0,8) Vs 11 months (95% CI, 4,13) for those who previously received an ASCT vs those who did not (p=0.02). In FL patients, increasing age (10 vs 5 months, p=0.03) and poor therapy response (11 vs 2 months, p<0.0001) had significant impact on survival, while in SL group TP53mut (13 vs 4 months, p=0.04) and poor response (8 vs 2.5 months p=0.04) were significant predictors of poor OS. On multivariate analysis (MVA), only TP53mut (p=0.04), and response (p=0.003) retained significant impact on OS in both FL and SL cohorts. While EH90 and presence of ≥2 comorbidities also trended towards lower survival, they did not reach statistical significance. Incremental age had no impact on OS in MVA. Following remission, ASCT Vs no-ASCT resulted in an improved survival, with a median OS of 15 months (95%CI 0,19) vs 5 months (95% CI 3,9), p=0.09; and NR (95% CI 3, NR months) Vs 6 months (95% CI 4, 8), p=0.04, In both FL and SL cohorts respectively. Conclusions: We comprehensively evaluated disease and patient factors, and their impact on hospitalization, and on OS in AML patients during Ven based therapy. EH and transfusions were common, without an impact on OS. Age had no impact on EH or OS, but comorbidity burden increased EH risk. High risk disease and poor response to therapy resulted in poor OS. ASCT was crucial for prolonged OS in both FL and SL cohorts. One likely cause of inferior OS noted in FL patients could be the lower rate of ASCT. Our results could provide better understanding to optimize Ven based therapy, and improve early treatment related toxicities in the real-world setting. Quality of life and health care utilization burden associated with this regimen needs to be studied systematically. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prognostic Value of Geriatric Nutritional Risk Index for Patients with Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

The purpose of this review was to collate evidence on the prognostic ability of the geriatric nutritional risk index (GNRI) for predicting overall survival (OS) and disease-free survival (DFS) in non-small cell lung cancer (NSCLC). The datasets of PubMed, Scopus, Embase, CENTRAL, and Google Scholar were searched up to 24 May 2022 for English-language studies reporting the association between GNRI and OS or DFS in NSCLC patients. Eleven studies with 2865 patients were included. We noted that low GNRI was a significant predictor of poor OS (HR: 1.96 95% CI 1.66, 2.30 I2 = 0% p < 0.00001) and poor DFS (HR: 1.74 95% CI: 1.36, 2.23 I2 = 34% p < 0.0001) in NSCLC patients. The results did not change on sensitivity analysis. There was no evidence of publication bias. Most results were significant on subgroup analysis based on study location, tumor stage, therapy type, sample size, and GNRI cut-off. Data indicate that GNRI has good prognostic ability in patients with NSCLC. Individuals with low GNRI are at an increased risk of poor OS and DFS. GNRI could be incorporated as a simple, easy-to-use tool for the initial stratification of patients thereby allowing focused treatment plans.

Prognostic factors in diffuse leptomeningeal glioneuronal tumor (DLGNT): a systematic review

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, first described by the WHO Classification of Central Nervous System Tumors in 2016. The clinical course is variable. Most tumors have low-grade histological findings although some may have more aggressive features. The goal of this systematic review was to identify prognostic factors for poor overall survival (OS). We performed a systematic review using three databases (PubMed, Google Scholar, and Embase) and the following search terms: diffuse leptomeningeal glioneuronal tumor, DLGNT, DLMGNT. Statistical analysis was performed using Statistica 13.3. We included 34 reports in our review comprising 63 patients, published from 2016 to 2022. The median OS was 19months (range: 12-51months). Using multivariable Cox survival analysis, we showed that Ki-67 ≥ 7%, age > 9years, symptoms of elevated intracranial pressure (ICP) at admission, and the presence of contrast-enhancing intraparenchymal tumor are associated with poor OS. Receiver operating characteristic (ROC) analysis identified Ki-67 ≥ 7% as a significant predictor of poor OS. Signs or symptoms of increased ICP with imaging findings of diffuse leptomeningeal enhancement should raise suspicion for DLGNT. In our systematic review, Ki-67 ≥ 7% was the most important prognostic factor for OS in DLGNT. The presence of intraparenchymal tumor with contrast enhancement was thought to represent disease progression and, together with patient age, was associated with poor OS.

Prognostic Impact of Radiological Splenic Artery Involvement in Pancreatic Ductal Adenocarcinoma of the Body and Tail.

Splenic artery (SpA) involvement heralds poor prognosis in pancreatic ductal adenocarcinoma (PDAC) of the body and tail but is not included in the resectability criteria. This study evaluated the prognostic impact of radiological SpA involvement in PDAC of the body and tail. Preoperative computed tomography images of patients who underwent distal pancreatectomy for resectable PDAC of the body and tail (n = 242) at our hospital between 2004 and 2018 were graded according to splenic vessel involvement status as clear, abutment, or encasement. Clinicopathological prognostic factors and overall survival (OS) and recurrence-free survival (RFS) rates were compared between the three groups. The prognostic value of radiological involvement status was assessed using Harrell's concordance statistic (C-index) and time-dependent receiver-operating characteristic curve analysis and compared with pathological findings. The diagnostic concordance rate was 0.87 (weighted κ statistic). Prognosis worsened with progression from clear, abutment, to encasement status. SpA encasement (hazard ratio [HR] 1.97, p = 0.04) predicted poor OS in multivariate Cox hazard regression analysis. SpA abutment (HR 1.77, p = 0.017) and encasement (HR 1.86, p = 0.034) independently predicted poor RFS. Splenic vein abutment and encasement were not significant predictors of poor OS or RFS. SpA encasement without adjuvant chemotherapy had the poorest prognosis because of early distant metastasis. The prognostic value was higher for radiological SpA involvement than for pathological SpA invasion. Radiological SpA involvement status is a meaningful and reproducible prognostic indicator that can be used preoperatively for determining the treatment strategy in PDAC of the body and tail.

Factores pronósticos de eficacia y seguridad que afectan a la supervivencia global de los pacientes con cáncer de próstata metastásico sometidos a tratamiento con [177Lu]Lu-PSMA-617: estudio en un único centro

BackgroundDetermining the efficacy, safety, and prognostic factors affecting overall survival (OS) among metastatic prostate cancer patients undergoing PSMA-targeted radioligand therapy (PRLT). MethodIn this retrospective study, from November 2016 and December 2019, 43 heavily pretreated (90.7% on 1st line androgen deprivation therapy (ADT), 53.5% on 2nd line ADT, 58.1% on docetaxel) metastatic prostate cancer patients with median age of 71 years (range: 51-88 years) were enrolled. Treatment cycles were repeated every 8 weeks (range: 6-12 weeks). To evaluate the biochemical response after each cycle, prostate specific antigen (PSA) levels were measured and analyzed according to the Prostate Cancer Working Group 3 (PCWG3) criteria cutoffs. Possible adverse events after therapy were retrospectively classified according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. Kaplan-Meier and multivariable Cox proportional hazard regression analyses were used to identify factors associated with OS. ResultsA total of 112 cycles of PRLT with a median of 3 cycles (range: 1-6) and median administered activity per cycle of 6.29 GBq (range: 4.45-7.7 GBq) were used. PSA decline was observed in 65.1% of patients, and best PSA decline of ≥50% and ≥90% were achieved in 39.5% and 23.3% of patients, respectively. Major (grade III) anemia and thrombocytopenia occurred in 11.6% and 7% of patients, respectively. Median OS and median PSA progression-free survival were 52 and 20 weeks, respectively. In univariate analysis, baseline hemoglobin <11.2 g/dL, baseline platelets count ≥327,000/μL, PSA decline <20.94% after first cycle of therapy, Eastern Cooperative Oncology Group (ECOG) >2, baseline PSA ≥115 ng/ml, cumulative dose of 177Lu-PSMA <12.95 GBq, initial alkaline phosphatase ≥196.5 U/L, initial lactate dehydrogenase ≥380 U/L and superscan pattern in bone scintigraphy were associated with worse OS. In multivariable Cox regression analysis, higher baseline platelet count, lower baseline hemoglobin, superscan pattern, and lower cumulative dose of 177Lu-PSMA remained significant predictors of poor OS. ConclusionPRLT with 177Lu-PSMA is well-tolerated and effective in metastatic prostate cancer patients who have no other treatment options available. The novel prognostic markers found in this study (high platelet count, superscan pattern) were associated with poor overall survival.

The role of stereotactic body radiotherapy in switching systemic therapy for patients with extracranial oligometastatic renal cell carcinoma.

Targeting oligometastatic lesions with metastasis-directed therapy (MDT) using stereotactic-body radiotherapy (SBRT) may improve treatment outcomes and postpone the need for second-line systemic therapy (NEST). We looked at the results of oligometastatic renal cell carcinoma (RCC) patients who had five or fewer lesions and were treated with SBRT. We examined the treatment outcomes of 70 extracranial metastatic RCC (mRCC) patients treated at two oncology centers between 2011 and 2020. The clinical parameters of patients with and without NEST changes were compared. The prognostic factors for overall survival (OS), progression-free survival (PFS), and NEST-free survival were evaluated. Median age was 67years (range 31-83years). Lung and bone metastasis were found in 78.4% and 12.6% of patients, respectively. With a median follow-up of 21.1months, median OS was 49.1months and the median PFS was 18.3months. Histology was a prognostic factor for OS, BED, and treatment switch for PFS in univariate analysis. In multivariate analysis, the significant predictor of poor OS was clear cell histology, and a lower BED for PFS. Following SBRT for oligometastatic lesions, 19 patients (27.2%) had a median NEST change of 15.2months after MDT completion. There were no significant differences in median OS or PFS between patients who had NEST changes and those who did not. No patient experienced grade ≥ 3 acute and late toxicities. The SBRT to oligometastatic sites is an effective and safe treatment option for ≤ 5 metastases in RCC patients by providing favorable survival and delaying NEST change.

The Modified Glasgow Prognostic Score and Prognostic Nutritional Index as Prognostic Markers in Patients With Metastatic Breast Cancer Treated With Eribulin.

To examine the role of the Modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) as prognostic markers for patients with metastatic breast cancer (MBC). We investigated the associations of clinico-pathological factors with time-to-treatment failure (TTF) and overall survival (OS) in 110 patients with MBC treated with eribulin. C-Reactive protein >1 mg/dl, albumin <3.5 g/dl, mGPS=2, and PNI <40 were significant predictors of shorter TTF in univariate analyses. PNI <40 remained a significant and independent predictor of shorter TTF in multivariate analyses. De novo tumor, visceral metastases, C-reactive protein >1 mg/dl, albumin <3.5 g/dl, mGPS=2, and PNI <40 were significant predictors of poor OS at the univariate level. A PNI <40 was a significant and independent predictor of poor OS in multivariate analyses. PNI is a reliable predictor of TTF and OS in patients with MBC treated with eribulin.

Association between contrast enhancement on contrast-enhanced CT and lenvatinib effectiveness in hepatocellular carcinoma.

The aim of the present study was to investigate whether the degree of contrast enhancement on contrast-enhanced (CE)-CT can predict the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). A total of 67 consecutive patients with LEN-treated HCC were retrospectively analysed. In the pretreatment CE-CT, the CT values were measured using a region of interest within the main nodule and the liver parenchyma in the arterial phase, and the macroscopic degree of contrast enhancement of the tumour area was quantified by calculating the enhancement ratio (ER) of the liver parenchyma. The associations of pretreatment ER with progression-free survival (PFS) and overall survival (OS) were then investigated. There were 20, 27 and 20 patients in the ER ≥1.5, 1.0≤ ER <1.5 and ER <1.0 groups, respectively. There was no significant difference in the PFS and OS among the three ER groups (PFS, P=0.63; OS, P=0.455). The ER <1.0 group had significantly more patients with larger tumour diameters, Barcelona Clinic Liver Cancer (BCLC) stage C with extrahepatic metastases, and higher des-γ-carboxy prothrombin values compared with the ER ≥1.0 group, suggesting that ER <1.0 reflected more aggressive types of HCC. The multivariate analysis revealed tumour size and α-fetoprotein as independent predictors of shorter PFS. Albumin-bilirubin grade 2 and BCLC stage C were significant predictors of poor OS, whereas the ER was confirmed as a non-significant predictor of both PFS and OS. Only non-alternating LEN and transarterial therapy (AT) were identified as independent predictors of unfavourable OS in patients with BCLC stage B HCC. Therefore, LEN has a strong therapeutic effect on HCC, regardless of the degree of contrast enhancement. Furthermore, AT may prolong the OS of LEN-treated patients with BCLC stage B HCC, regardless of tumour vascularity.

Efficacy, safety and prognostic factors affecting overall survival among metastatic prostate cancer patients undergoing treatment with 177Lu-PSMA-617: A single center study

BackgroundDetermining the efficacy, safety, and prognostic factors affecting overall survival (OS) among metastatic prostate cancer patients undergoing PSMA-targeted radioligand therapy (PRLT). MethodIn this retrospective study, from November 2016 and December 2019, 43 heavily pretreated (90.7% on 1st line androgen deprivation therapy (ADT), 53.5% on 2nd line ADT, 58.1% on docetaxel) metastatic prostate cancer patients with median age of 71 years (range: 51−88 years) were enrolled. Treatment cycles were repeated every 8 weeks (range: 6–12 weeks). To evaluate the biochemical response after each cycle, prostate specific antigen (PSA) levels were measured and analyzed according to the Prostate Cancer Working Group 3 (PCWG3) criteria cutoffs. Possible adverse events after therapy were retrospectively classified according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. Kaplan-Meier and multivariable Cox proportional hazard regression analyses were used to identify factors associated with OS. ResultsA total of 112 cycles of PRLT with a median of 3 cycles (range: 1–6) and median administered activity per cycle of 6.29 GBq (range: 4.45–7.7 GBq) were used. PSA decline was observed in 65.1% of patients, and best PSA decline of ≥50% and ≥90% were achieved in 39.5% and 23.3% of patients, respectively. Major (grade III) anemia and thrombocytopenia occurred in 11.6% and 7% of patients, respectively. Median OS and median PSA progression-free survival were 52 and 20 weeks, respectively. In univariate analysis, baseline hemoglobin <11.2 g/dL, baseline platelets count ≥327,000/μL, PSA decline <20.94% after first cycle of therapy, Eastern Cooperative Oncology Group (ECOG) >2, baseline PSA ≥ 115 ng/mL, cumulative dose of 177Lu-PSMA <12.95 GBq, initial alkaline phosphatase ≥196.5 U/L, initial lactate dehydrogenase ≥380 U/L and superscan pattern in bone scintigraphy were associated with worse OS. In multivariable Cox regression analysis, higher baseline platelet count, lower baseline hemoglobin, superscan pattern, and lower cumulative dose of 177Lu-PSMA remained significant predictors of poor OS. ConclusionPRLT with 177Lu-PSMA is well-tolerated and effective in metastatic prostate cancer patients who have no other treatment options available. The novel prognostic markers found in this study (high platelet count, superscan pattern) were associated with poor overall survival.

An Ara-C, Daunorubicin, and Etoposide microRNA (ADEmiR) Score As a Prognostic Tool to Predict AML Treatment Outcomes

Introduction: Ara-C (cytarabine), daunorubicin, and etoposide (ADE) remain key chemotherapies used in remission induction and consolidation therapy of pediatric acute myeloid leukemia (pAML). However, multiple drug resistance is a major cause of therapeutic failure in pAML. Several ADE-significant pharmacokinetic/pharmacodynamic (PK/PD) genes have been identified. However, it is unknown which microRNAs (miRNA) have a significant impact on the regulation of gene (mRNA) expression levels involved in ADE's pharmacology and the treatment outcomes of pAML patients. Methods: pAML patients with available bone marrow mRNA and miRNA expression levels from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were included in the analysis. For step 1, we assembled a list of significant PK/PD genes (n=67) to ADE. In step 2, correlation analyses between mRNA expression levels of target PK/PD genes and miRNA expression levels were performed using mRNA-seq and miRNA-seq data from the TARGET database. miRNA-mRNA pairs with significant anti-correlation for expression levels using Spearman's rho (FDR &amp;lt; 0.05) were included for further analysis. In step 3, the least absolute shrinkage and selection operator (LASSO) was used to fit the Cox regression model with overall survival (OS) as the outcome variable on miRNAs with significant negative correlation with PK/PD genes from step 2. A thousand bootstraps of LASSO Cox regression were performed to identify miRNAs represented in at least 75% of the models. Coefficients from select miRNAs were used to generate a miRNA signature equation for the ADE response (ADEmiR) score. In step 4, patients were classified into low or high score groups according to the median value from the ADEmiR score, and analysis was performed for association with event-free survival (EFS), OS, minimal residual disease after the end of induction 1 (MRD1), and complete remission after the end of induction1 (CR1). Lastly, multivariate analysis was conducted using confounding factors such as age, clinically identified risk groups, FLT3 mutation status, and white blood cell count (WBC). The ADEmiR score equation was then validated using miRNA expression levels data from 164 adult AML patients from The Cancer Genome Atlas (TCGA) database. Results: 219 patients were identified with a mean age of 10±6 years, and 54% were male. Within TARGET cohort, the high ADEmiR score group was associated with significantly inferior EFS (HR=3.26, p&amp;lt;0.001) and OS (HR=6.51, p&amp;lt;0.001) (Figure 1), higher MRD1 (44% vs. 22%, p=0.0054) and a greater proportion of patients not achieving CR1 (29% vs. 12%, p=0.0037) (Figure 2). In a multivariate Cox regression model that included ADEmiR score, age, clinically identified risk groups, FLT3 mutation status, and WBC, the high ADEmiR score group remained significantly worse for EFS (HR=2.54, p&amp;lt;0.001) and OS (HR=5.85, p&amp;lt;0.001) (Table 1). Among clinically identified risk groups, the high ADEmiR score remained a significant predictor of poor OS in the low-risk group (HR=4.80, p&amp;lt;0.001), the standard-risk group (HR=7.00, p&amp;lt;0.001), and the high-risk (HR=9.03, p=0.035) (Figure 3). The ADEmiR score was further validated in the TCGA cohort with consistent results showing the high ADEmiR score group was associated with inferior OS (HR=1.97, p&amp;lt;0.001) (Figure 1). In a multivariate Cox regression of the TCGA cohort, the high ADEmiR score group stayed significant with worse OS (HR=1.61, p=0.024). In the clinically identified risk groups of the TCGA cohort, the high ADEmiR score was associated with poor OS in both intermediate-risk (HR=1.71, p=0.033) and poor-risk groups (HR=2.66, p=0.037) with a trend in the low-risk group (HR=2.10, p=0.2) (Figure 4). Conclusions: The ADEmiR signature scoring system utilizing miRNA could serve as a prognostic tool to predict treatment outcomes in AML patients receiving ADE. Ongoing studies conducted by our group are focused on validating the ADEmiR score in other cohorts as well as its integration with our other gene-expression based prognostic tools such as ADE-Response Score (ADE-RS), and pediatric leukemic stem cell (pLSC6) score to predict optimal ADE treatment outcomes in pediatric AML. Disclosures No relevant conflicts of interest to declare.

Impact of Age on the Outcomes of HCT for AML in CR1: Promising Therapy for Older Adults

Background Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The only curative therapy remains an allogeneic hematopoietic stem cell transplant (HCT), yet it is complicated by non-relapse mortality (NRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in a large cohort of patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1). Methods HCT recipients 60 years or older with AML in CR1 reported to the CIBMTR were included. Cox models were used to compare rates of overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM), relapse, acute GHVD, chronic GVHD in 3 separate age groups: 60-64 years vs. 65-70 years vs. 70+ years (Figure 1A). Results 1,327 patients undergoing HCT from 2007-2017 were included. The three age cohorts (60-64; 65-69; 70+) were comparable in demographic and disease characteristics, except the older cohort had more males, more de novo AML, and a higher incidence of measurable residual disease (MRD) pre-HCT. Fewer had sibling donors and more were performed in recent years. With median follow-up of nearly 3 years, patients aged 60-64 had significantly better OS, DFS and lower NRM than those aged 65-69 and 70+. Those aged 65-69 and 70+ had similar outcomes (Figure 1). Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p=0.026). NRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥ 3. Conditioning intensity was not a significant predictor of outcomes with HR for OS for 60-69 cohort of 0.46 for RIC and 0.49 for MAC (p=0.38). There was no difference in the relapse rate, incidence of G3/4 acute GVHD, or incidence of moderate-severe chronic GVHD across the age cohorts. Poor risk cytogenetics, presence of MRD prior to HCT, cord blood as graft source, and transplant prior to 2016 were significant predictors of poor OS. Discussion In this large retrospective series of HCT for AML in CR1, age had a small effect OS and NRM after accounting for other predictors. High-risk features such as poor cytogenetics and presence of MRD prior to HCT were significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection. Table Disclosures Kebriaei: Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Jazz: Consultancy; Amgen: Other: Research Support; Kite: Other: Served on advisory board; Pfizer: Other: Served on advisory board. Weisdorf:FATE Therapeutics: Consultancy; Incyte: Research Funding.

Impact of sidedness of colorectal cancer on tumor immunity

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

Comparison of the prognostic values of 18F-fluorodeoxyglucose parameters from colon and non-colon sites of involvement in diffuse large B-cell lymphoma of the colon

We examined the prognostic values of 18F-fluorodeoxyglucose (18F-FDG) parameters from colon, non-colon, and total lesions in patients with diffuse large B-cell lymphoma (DLBCL) of the colon. Positron emission tomography/computed tomography (PET/CT) in 50 patients was retrospectively analyzed for maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). During follow-up, 13 patients showed progression and 9 died from disease. Receiver operating characteristics (ROC) curve analysis showed that non-colon and total lesion MTV and TLG and colon lesion SUVmax were associated with progression or death. Significant univariate predictors of poor event-free survival (EFS) included stage III-IV, greater International Prognostic Index (IPI) score, no resection, high non-colon lesion SUVmax, MTV and TLG, and high total lesion MTV and TLG. Univariate predictors of poor overall survival (OS) included stage III–IV, greater IPI score, no resection, high non-colon lesion MTV and TLG, high total lesion MTV, and low colon lesion SUVmax. Multivariate analysis revealed that high non-colon lesion TLG was independently associated with poor EFS and OS. Low colon lesion SUVmax was also independently associated with poor OS. In a subgroup with colon-dominant involvement (n = 35), non-colon lesion MTV and TLG were associated with events and non-colon lesion MTV was associated with patient death. Univariate analysis showed that high non-colon lesion MTV was a significant predictor of poor EFS and OS, while non-colon lesion TLG was a significant predictor of poor OS. Thus, volumetric FDG parameters of non-colon lesions offered significant prognostic information in patients with DLBCL of the colon.

Prognostic and Clinicopathological Value of Programmed Cell Death Ligand1 Expression in Patients With Small Cell Lung Cancer: A Meta-Analysis

Background: Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule expressed by cancer cells. Previous studies have demonstrated the prognostic role of PD-L1 expression in patients with small cell lung cancer (SCLC), where the results were inconsistent. Therefore, we conducted a meta-analysis to identify the prognostic impact of PD-L1 on SCLC.Methods: We searched the PubMed, Embase, ISI Web of Science, and Cochrane Library databases for articles published before and on March 2nd, 2020. Data of PD-L1 expression in tumor cells detected using immunohistochemistry methods were extracted for analysis. Pooled hazard ratios (HRs) with confidence intervals (CIs) and odds ratios (ORs) with 95% CIs were calculated to assess the correlations among PD-L1, overall survival (OS), and clinicopathological factors.Results: Nine studies of 921 patients published between 2015 and 2019 were included in this meta-analysis. The pooled data (HR = 0.91, 95% CI = 0.46–1.80, p = 0.787) indicated that PD-L1 expression is not a significant predictor of poor OS. Moreover, the results also revealed that PD-L1 expression is not significantly associated with gender (OR = 1.12, 95% CI = 0.73–1.74, p = 0.601), age (OR = 1.15, 95% CI = 0.58–2.30, p = 0.683), pN stage (OR = 0.65, 95% CI = 0.24–1.72, p = 0.381), pT stage (OR = 1.16, 95% CI = 0.26–5.23, p = 0.847), serum lactate dehydrogenase level (OR = 1.06, 95% CI = 0.13–8.43, p = 0.958), or performance status (OR = 0.69, 95% CI = 0.24–1.95, p = 0.479). No significant publication bias was detected in this meta-analysis.Conclusions: This meta-analysis suggests that PD-L1 expression is not a significant prognostic factor of poor survival in SCLC. Because of significant variations, high-quality studies are needed to validate our results.

A 5-Gene Ara-C, Daunorubicin and Etoposide (ADE) Drug Response Score As a Prognostic Tool to Predict AML Treatment Outcome

Introduction: Cytarabine, daunorubicin and etoposide (ADE) are commonly used for remission and intensification of pediatric acute myeloid leukemia (AML). However, development of drug resistance is a major cause of treatment failure. In this study, we performed a comprehensive evaluation of expression levels of genes of pharmacological significance (pharmacokinetic /pharmacodynamic) to ADE and derived a drug response score predictive of treatment outcomes in pediatric AML patients. Methods: This study included 163 cases (median age=8.79 year, range= (0.013-21.1)) with AML enrolled in the multicenter AML02 clinical trial (ClinicalTrials.gov Identifier: NCT00136084) with Affymetrix U133A microarray gene expression and clinical data available. We used a penalized LASSO regression algorithm (glmnet R-package) to fit a cox regression model on diagnostic leukemic cell gene expression levels of 66 genes of pharmacological significance to ADE. We performed 1000 bootstraps of LASSO regression with event free survival (EFS) as the outcome variable and the five genes represented in at least 95% of the models were included to build an ADE-Response Score (ADE-RS) equation. Patients were classified into low or high score groups using recursive portioning implemented in Rpart-R package and evaluated for association with minimal residual disease after induction I (MRD1), EFS and overall survival (OS). ADE response score equation was further validated using RNA-Seq gene-expression data obtained from diagnostic samples of 432 pediatric AML patients enrolled in Children's Oncology Group (COG) AAML0531 and AAML03P1 treatment protocols. Results: After applying LASSO regression, we defined the equation: ADE-RS = (0.128 x DCTD) - (0.0993 x TOP2A) + (0.212 x ABCC1) - (0.113 x MPO) - (0.126 x CBR1) to develop ADE-response score (ADE-RS), followed by classifying patients into low (60%; 98 patients) or high (40%; 65 patients) score groups. Patients in the high ADE-RS group had significantly worse EFS (HR=4.07(2.43-6.84), P &amp;lt; 0.0001; Figure 1A) and OS (HR= 4.54(2.42-8.49), P&amp;lt;0.0001) and higher proportion of MRD1 positive patients (P=0.014; Figure 1B) compared to patients in the low ADE-RS group. These results were validated in an independent COG cohort, where patients in the high score group demonstrated higher MRD1 positivity (P=0.0005; Figure 1D) and inferior EFS (HR=1.32(1.01-1.73), P=0.044; Figure 1C). We recently developed a six-gene leukemic stem cell score (pLSC6 score) that was associated with risk-groups (P&amp;lt;0.00001) and outcome (oral presentation ASH2018, Under-review, Leukemia). We further integrated pLSC6 and ADE-RS and observed significantly better prediction of treatment outcomes in AML02, COG and TCGA cohorts. Based on pLSC6 and ADE-response scores, patients were classified into three groups; 1) Low/Low:pLSC6/ADE-RS; for patients with low pLSC6 and low ADE-RS. 2) Low/High:pLSC6/ADE-RS: for patients in low pLSC6 and high ADE-RS or vice versa.3) High/High:pLSC6/ADE-RS: for patients in high pLSC6 and high ADE-RS. In all study cohorts, patients in low/low pLSC6-ADE-RS group demonstrated better outcomes compared to the low-high and the high/high score groups (EFS in AML02 cohort; Figure 1E and OS; Figure 1F). In a multivariable cox-regression models that included pLSC6-ADE response score groups, MRD1 status, risk groups, WBC at diagnosis and age in AML02 cohort, high pLSC6-ADE score group was found significantly associated with poor EFS (HR=6.02(2.71-13.2), P&amp;lt;0.00001; Figure 1G) and was the only significant predictor of poor OS (HR=8.3(2.9-23.99), P&amp;lt;0.00001; Figure 1H) Discussion: In this study, we defined a pharmacological response score focused on key genes of PK/PD significance to ADE. We further integrated LSC score with the ADE response score to improve our ability to predict treatment outcome in AML patients across different clinical trials. ADE-RS was composed of five genes: DCTD, which is a deaminase, involved in ara-C inactivation; CBR1, a carbonyl reductase involved in inactivation of daunorubicin (DNR); MPO, myeloperoxidase, an etoposide activator; ABCC1, an efflux transporter of DNR and etoposide; and TOP2A, DNA topoisomerase II alpha, which is a target for DNR and etoposide. Integrated pLSC6 and ADE-RS has a potential to predict treatment outcomes using diagnostic gene expression levels and accordingly develop treatment strategies to improve treatment outcome. Figure 1 Disclosures Gruber: Bristol-Myers Squibb: Consultancy. Rubnitz:AbbVie: Research Funding.

Prognostic Significance of Sarcopenia With Inflammation in Patients With Head and Neck Cancer Who Underwent Definitive Chemoradiotherapy.

Purpose: With growing evidence that inflammation and low muscularity play a role in the survival of cancer patients, we evaluated the prognostic implications of sarcopenia with systemic inflammation in patients who underwent definitive chemoradiotherapy (CCRT) for locally advanced head and neck cancer.Materials and Methods: We analyzed 221 patients with head and neck cancer who received definitive CCRT between 2006 and 2015. The skeletal muscle area was measured using a single computed tomography image slice at the level of the third lumbar vertebra (L3). Sarcopenia was defined as an L3 muscle index of <49 cm2/m2 for men and <31 cm2/m2 for women.Results: Patients with sarcopenia (n = 106) exhibited higher neutrophil/lymphocyte ratios (NLRs) than those without (n = 115); the former also had an inferior 3-year overall survival (OS) rate (62%) than the latter (76%, p = 0.037). Among patients with sarcopenia, those who also had high NLRs (n = 51) showed significantly poorer OS and progression-free survival (PFS). In the multivariate analysis, sarcopenia plus a high NLR remained the most significant predictor of poor OS and PFS. Patients with sarcopenia required more frequent interruption of RT; patients whose RT was interrupted for ≥5 days showed inferior disease control and OS.Conclusions: Sarcopenia accompanied by systemic inflammation at initial diagnosis is associated with significantly inferior OS and PFS. Additionally, patients with sarcopenia required RT interruption more frequently. Intensive nutritional support and additional treatment methods are required for these patients while undergoing RT.

Radiotherapy alone and with concurrent chemotherapy for nasopharyngeal carcinoma: A retrospective study.

We sought to evaluate clinical outcomes and toxicities of radiation therapy (RT) alone compared to RT with concurrent chemotherapy (CCT) for nasopharyngeal carcinoma (NPC) treatment.We conducted a retrospective review of consecutive patients with biopsy-proven nonmetastatic NPC who underwent RT at our institution. From May 2001 to April 2015; 62 newly diagnosed NPC patients were treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) with or without CCT. The patients were classified as follows: 8% stage I, 15% stage II, 32% stage III, and 45% stage IVA/IVB. A total of 76% of tumors were World Health Organization types II or III. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS) were analyzed.The median follow-up period for living patients was 53 months. The median actual delivered dose was 70 Gy with a range of 28 to 70 Gy in fraction sizes of 2 Gy. The estimated 5-year OS, PFS, LRPFS, and DMFS rates were 72.7%, 59.8%, 77.9%, and 84.2%, respectively. The use of CCT was a predictive factor of significantly better OS and PFS, whereas stage IV was a significant predictor of poor OS and PFS. The most severe acute toxicities included Grade 3 mucositis in 56% and Grade 3 dermatitis in 8%. Subset analysis revealed that Grade 2 xerostomia was significantly lower in the IMRT (23%) group than in the 3D-CRT (52%) group (P = .02).RT yielded favorable outcomes. CCT was associated with longer PFS and OS than RT alone.

Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis in Head and Neck Squamous Cell Carcinoma

We aimed to investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis in patients with head and neck squamous cell carcinoma (HNSCC) and integrate it into a multivariate prognostic model. A retrospective review of magnetic resonance imaging findings was conducted in patients with pathologically confirmed HNSCC between June 2012 and December 2015. For each tumor, six histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC (ADC10, ADC50, and ADC90); mean ADC values (ADCmean); kurtosis; and skewness. The clinical variables included age, sex, smoking status, tumor volume, and tumor node metastasis stage. The association of these histogram and clinical variables with overall survival (OS) was determined. Further validation of the histogram parameters as independent biomarkers was performed using multivariate Cox proportional hazard models combined with clinical variables, which was compared to the clinical model. Models were assessed with C index and receiver operating characteristic curve analyses for the 12- and 36-month OS. Ninety-six patients were eligible for analysis. Median follow-up was 877 days (range, 54-1516 days). A total of 29 patients died during follow-up (30%). Patients with higher ADC values (ADC10 > 0.958 × 10-3 mm2/s, ADC50 > 1.089 × 10-3 mm2/s, ADC90 > 1.152 × 10-3 mm2/s, ADCmean > 1.047 × 10-3 mm2/s) and lower kurtosis (≤0.967) were significant predictors of poor OS (P < .100 for all). After adjusting for sex and tumor node metastasis stage, the ADC90 and kurtosis are both significant predictors of OS with hazard ratios = 1.00 (95% confidence interval: 1.001-1.004) and 0.58 (95% confidence interval: 0.37-0.90), respectively. By adding the ADC parameters into the clinical model, the C index and diagnostic accuracies for the 12- and 36-month OS showed significant improvement. ADC histogram analysis has incremental prognostic value in patients with HNSCC and increases the performance of a multivariable prognostic model in addition to clinical variables.