236 Predictors of ICI renal toxicity: a pathological approach

BackgroundInflammatory response in unintended tissues and organs associated with the use of immune checkpoint inhibitors also known as immune related adverse events (irAEs) is a management challenge, and renal irAEs are associated with increased patient morbidity and mortality. The most common renal toxicity is acute interstitial nephritis (AIN), characterized by infiltration of renal tissue with immune cells, and may be analogous to kidney transplant rejection. Using both clinical variables and tissue findings we evaluated a large cohort of ICI cases to determine predictors of renal response and overall survival.MethodsWe retrospectively reviewed all patients treated with ICI (August 2007 to August 2020) at MD Anderson Cancer Center. A total of 38 patients with biopsy confirmed AIN and available tissue were identified. All slides were reviewed by two board certified renal pathologists and the severity of inflammation and chronicity was graded using transplant rejection BANFF criteria. Patients were categorized as renal responders if creatinine improved or returned to baseline after treatment and non-responders if it did not. Fisher’s exact tests for categorical variables and t-test/ANOVA or the counterparts of the non-parametric approaches (Wilcoxon rank-sum or Kruskal-Wallis) for continuous variables were used to compare patient‘s characteristics between groups. The distribution of overall survival (OS) was estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups.ResultsBased on the detailed pathological findings, patients with increased interstitial fibrosis were less likely to have renal response with treatment compared to patients with less fibrosis, (p < 0.05). Inflammation, tubulitis, number of eosinophils and neutrophils had no impact on renal response. Patients with response within 3 months of AKI treatment had a superior OS in comparison to patients who responded late (12-month OS rate: 77% vs 27%, p < 0.05). Notably, patients who received concurrent ICI and achieved renal response within 3 months had the best OS while those who did not receive concurrent ICI nor achieved renal response had worst OS (12-month OS rate: 100% (renal response and concurrent ICI) vs 72% ( renal response with no concurrent ICI), vs 27% ( no renal response and nonconcurrent ICI) (p < 0.05).ConclusionsThis is the first analysis of ICI induced nephritis where a detailed pathological and clinical evaluation was performed to predict renal response. Our findings highlight the importance of early diagnosis and treatment of ICI-AIN while continuing concurrent ICI therapy.Ethics ApprovalThis retrospective study was approved by the institutional review board at The University of Texas MD Anderson Cancer Center, and the procedures followed were in accordance with the principles of the Declaration of Helsinki.

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Maintenance immunosuppressive therapy with resumption of immune checkpoint inhibitor treatment to reduce recurrence of immune-mediated colitis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2642 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2642-2642

Author(s):

Hamzah Abu-Sbeih ◽

Fangwen Zou ◽

Barbara Dutra ◽

Mehmet Altan ◽

Jennifer Leigh McQuade ◽

...

Keyword(s):

Overall Survival ◽

Immunosuppressive Therapy ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Cancer Center ◽

Adequate Treatment ◽

Univariate Logistic Regression Analysis ◽

Immune Mediated ◽

Md Anderson ◽

Current Guidelines

2642 Background: Immune-mediated colitis (IMC) may limit immune checkpoint inhibitors (ICI) treatment. Current guidelines recommend consideration of resuming ICI when IMC symptoms subside to ≤ grade 1. We aimed to investigate the effect of maintenance immunosuppressive therapy (IST) on the outcome of IMC in patients who resume ICI therapy. Methods: We retrospectively studied patients who resumed ICI therapy after adequate treatment of IMC from March 2015 to June 2020 at MD Anderson Cancer Center. Relevant demographic, oncologic, and ICI data were collected and analyzed. Univariate logistic regression analysis was conducted to assess risk factors of IMC recurrence. Results: We included 102 patients with a median age of 61 years. 66% were males and 97% were Caucasians. 48 patients (47%) received IST maintenance in conjunction with ICI resumption and 54 patients did not. Symptoms of IMC recurred in 28 patients, 8 (17%) in the concurrent IST group and 20 (37%) in the other group. Compared to no concurrent IST group, patients on concurrent IST were more likely to have received combined ICI regimen (60% vs 41%, p = 0.003) and more initial ICI doses (9 vs 5 doses, p = 0.030). Concurrent IST group had significantly longer ICI treatment duration on resumption (72 vs 62 days, p = 0.023), more ICI resumed doses (5 vs 4 doses, p = 0.038), and lower IMC recurrence (17% vs 37%, p = 0.027). Patient who received more IST doses, both therapeutic and prophylactic, had lower rate of IMC recurrence (OR 0.72, p = 0.012; table). IST maintenance treatment (OR 0.34, p = 0.024) was associated with lower IMC recurrence rate after ICI resumption. Vedolizumab was the predominant IST used. Overall survival was comparable among the two groups (p = 0.934). Conclusions: Concurrent IST treatment with ICI resumption after IMC was associated with significantly lower IMC recurrence and more extended ICI treatment while reserving similar overall survival to patients without IST maintenance therapy. Future prospective randomized trial of concurrent IST is still merited for further clarification.[Table: see text]

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Impact of use of phosphodiesterase type 5 inhibitors (PDE5-I) after radical prostatectomy (RP) on biochemical recurrence-free (BCRF) and overall survival (OS): A retrospective study from the Northwestern University SPORE in prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.27 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 27-27 ◽

Cited By ~ 1

Author(s):

Arden B. Roston ◽

Irene B. Helenowski ◽

William Catalona ◽

Robin Leikin ◽

Michael Gurley ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Biochemical Recurrence ◽

Retrospective Cohort ◽

Clinical Stage ◽

Categorical Variables ◽

Rank Test ◽

Cancer Center ◽

Continuous Variables ◽

Phosphodiesterase Type 5 Inhibitors

27 Background: The correlation between PDE5-I use to improve erectile function post RP and BCRF and OS on prostate cancer (PCa) patients (pts) has yielded conflicting results among prior retrospective cohort studies (Michl, 2015). Recent data suggests that these drugs may have an impact on immunity that may explain possible benefits. This study’s purpose was to determine whether PDE5-I use affects BCRF and OS for pts treated with RP for PCa. Methods: This is an IRB approved retrospective cohort study analyzing a subset of pts consented to the SPORE in PCa at Northwestern University’s Lurie Cancer Center. Inclusion criteria included men diagnosed with PCa and treated with RP with curative intent between 2003-2015. Study population (n = 2,410) showed 834 (34.6%) received a PDE5-I post-RP, while 1,576 (65.4%) did not. Pts were grouped based on PDE5-I use and no PDE5-I use after RP. A PDE5-I user must have filled at least 2 prescriptions or completed at least 2 inpatient administrations of a PDE5-I. Continuous variables were summarized by descriptive statistics and differences between groups were assessed via the Wilcoxon rank sum test. Categorical variables were reported by frequencies and percentages and compared via Fisher’s exact test. OS and BCRF survival were summarized for 10-yr rates using Kaplan-Meier estimates. The difference in BCRF and OS between groups was evaluated via log-rank test. Results: Mean age at RP was 60, and 90.95 % were Caucasian. Except for pairwise comparisons for significance of Gleason 3+3 vs. 3+4 histology with higher prevalence of 3+4 in the PDE5-I group (p = 0.0004) and a higher percent of clinical stage T2b-c than T2a in the no PDE5-I group (p = 0.01), no differences were noted in demographics. The 10-yr BCRF survival among PDE5-I users was 92.53% compared to 79.63% among non-users after RP (p < 0.0001). The 10-yr OS rate among PDE5-I users was 97.22% compared to 92.69% among non-users (p = 0.008). Conclusions: This retrospective analysis suggests that PDE5-I use improves biochemical recurrence free survival and overall survival in pts treated with RP for PCa.

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Bortezomib-Containing Regimens (BCR) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.1846.1846 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1846-1846

Author(s):

Victor H Jimenez-Zepeda ◽

Peter Duggan ◽

Paola Neri ◽

Nizar J Bahlis

Keyword(s):

Overall Survival ◽

Research Funding ◽

Clinical Characteristics ◽

Progression Free Survival ◽

Categorical Variables ◽

Rank Test ◽

Cancer Center ◽

Fisher Exact Test ◽

Free Survival ◽

The Impact

Abstract Introduction In patients not eligible for transplant due to age and/or co-morbidities, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor proven to be efficacious in myeloma, have been reported. Based on these findings, we aimed to evaluate the impact of different bortezomib combinations for the treatment of non transplant-eligible MM. Methods All- consecutive patients treated with bortezomib-containing regimens (BCR) at Tom Baker Cancer Center (TBCC) from 01/2006 to June/2015 were evaluated. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results 113 consecutive patients with MM received BCR. Thirty-three patients were treated with cyclophosphamide, bortezomib and dexamethasone (CyBorD), 41 with bortezomib, melphalan and prednisone (VMP) and 39 with bortezomib and dexamethasone (VD). Clinical characteristics are shown in Table 1. At the time of analysis, 20, 17 and 18 patients in the CyBorD, VMP and VD groups are still alive and 14, 33 and 30 have already progressed, respectively. ORR and VGPR rates were 93.9%/75.7%, 80%/53% and 76%/48% (p=0.001) for patients treated with CyBorD, VMP and VD, respectively. Median OS was NR for CyBorD, compared to 41months and 37 months for VMP and VD patients (p=0.6). Median PFS was 16.7 months for CyBorD compared to 17.5 months and 11 months for VMP and VD (P=0.6), respectively. The rate of treatment discontinuation and median number of cycles were: 9%, 26% and 12.8% and 6, 7.5 and 4 cycles for CyBorD, VMP and VD patients, respectively. Patients were to receive 6-9 cycles of treatment and the regimen could be continued to a maximum of 2 years at the discretion of the treating hematologist based on tolerability and response. Nine patients (27%) in the CyBorD group and 17 (41.4%) and 4 (10%) in the VMP and VD group received maintenance treatment. Median OS and PFS was longer for the group receiving maintenance (62 months vs 32 months and 23 months vs 10 months, p=0.007). In conclusion, bortezomib containing regimens are efficacious in the treatment of non-transplant eligible MM. Patients receiving maintenance appeared to exhibit longer PFS and OS. Very elderly patients should be subjected to frailty and comorbidity indexes aiming to decrease toxicity and prolong survival. Table 1. Clinical Characteristics Characteristic CyBorD, n=33 VMP, n=41 VD, n=39 Age (median) 58 58 58 GenderMaleFemale 20 (60.6%)13 (39.4%) 22 (53.6%)19 (46.4%) 26 (66.6%)13 (33.4%) Hb (g/L) 107 110 103 Calcium (µmol/L) 2.4 2.35 2.31 Creatinine (µmol/L) 115.5 103 108 B2microglobulin (µmol/L) 4.1 3.42 5.9 Albumin (g/L) 31 31 30 Stage IStage IIStage III 6 (12.1%)14 (42.4%)13 (45.5%) 9 (21.9%)19 (46.3%)13 (31.8%) 4 (10.2%)16 (41%)18 (48.8%) LDH (IU/L) 185 179 174 BMPC (%) 31 30 33.5 Heavy chain:IgGIgAFLC onlyIgDIgMBiclonal 2247000 19148000 21107010 Light chain:KappaLambdaBiclonal 16170 29120 24150 High riskStandard risk 5 (15%) 28 6 (14.6%)35 8 (20%)31 Ab: BMPC: Bone marrow plasma cells. Figure 1. Overall survival for patients receiving CyBorD, VMP and VD Figure 1. Overall survival for patients receiving CyBorD, VMP and VD Figure 2. Progression-Free survival for patients receiving CyBorD, VMP and VD Figure 2. Progression-Free survival for patients receiving CyBorD, VMP and VD Figure 3. OS for patients receiving CyBorD, VMP and VD maintenance Figure 3. OS for patients receiving CyBorD, VMP and VD maintenance Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; J&J: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

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MO153RENAL FUNCTIONS OUTCOME IN METASTATIC NON SMALL LUNG CARCINOMA PATIENTS: THE RISK OF AKI IN FIRST LINE THERAPY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.0031 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Francesco Trevisani ◽

Federico Di Marco ◽

Francesco Fiorio ◽

Monica Cattaneo ◽

Erika Rijavec ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Combined Therapy ◽

Overweight And Obesity ◽

Categorical Variables ◽

Rank Test ◽

First Line ◽

Metastatic Nsclc ◽

Platinum Based Chemotherapy

Abstract Background and Aims The optimal use of immune and target therapies, the optimal use of standard chemotherapy (CT) is of paramount importance, especially for patients affected by chronic kidney disease (CKD) who require dose adjustment according to the glomerular filtration rate (GFR) to avoid acute kidney injury (AKI) establishment. Immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy (CT) are options for the palliative treatment of metastatic non-small cell lung cancer (NSCLC). Recently, CT in combination with immune-checkpoint inhibitors has become the treatment of choice for this setting of patients. Therefore, it is fundamental to investigate the potential nephrotoxic effects of both treatments and their potential additive effects on renal function. Aim of our study was to compare the nephrotoxic effect of both ICIs and CT (cisplatin and carboplatin-based) in a consecutive cohort of patients affected by metastatic NSCLC. Method A consecutive cohort of 126 patients treated in first-line for NSLCL was enrolled in a single tertiary Hospital between 2018 and 2020. Inclusion criteria were: age (> 18 years old), eGFR (> 15 ml/min/1.73), histological diagnosis of metastatic NSCLC. Each patient underwent immunotherapy or CT according to clinical conditions, comorbidities and programmed death ligand 1 (PD-L1) expression status. eGFR (using CKD-EPI formula 2009) was detected at baseline and after each cycle of immunotherapy or CT (using cisplatin or carboplatin) in order to determine the correct renal status using the K-DIGO 2012 guidelines for AKI stages and CKD classes. Pts were subdivided into CKD categories G according to their eGFR values before and after the treatment. AKI onset was evaluated by rise in creatine levels according to K-DIGO criteria. Clinical stage according to cTNM (AJCC TNM system-2019) was collected at baseline before the first treatment. Comorbidities (e.g., diabetes, blood hypertension, overweight and obesity) were also included. Comparison between numerical variables was performed using linear regressions; between groups using Kruskal-Wallis rank sum test for numerical variables and Pearson’s Chi square test for categorical variables. Log rank test was used to test differences between groups in terms of AKI onset during the therapy. Results Clinical and pathological characteristics are reported in table 1. From the analysis, no significative differences were detected between Immunotherapy and CT group for age, gender, basal serum creatinine, basal eGFR, basal BMI, diagnosis of diabetes, hypertension, basal CKD G group or overall AKI onset. Treatment cycles were significantly different between the two groups (p<0.001) with a short median number of cycles for the CT group. No significative difference in terms of decay of eGFR calculated as final-basal values was detected (p=0.8). AKI onset over cycles was significantly different between the two groups (p=0.02), observing a higher risk of developing earlier AKI for CT group (cisplatin or carboplatin) (13,9%) with respect to immunotherapy (7,4%) (figure 1 and 2). Conclusion Our study highlights that both cisplatin and carboplatin-based CT displays an augmented incidence of AKI development after a lower number of therapy cycles in respect of immunotherapy. The nephrotoxic effects of combined therapy for NSLCL should be always evaluated by nephrologist during the treatment of NSLCL patients to avoid an augmented risk of AKI derived from the combination of immunotherapy and CT in first line.

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Obesity Is Poor Prognostic Factor in Lower Risk Myelodysplastic Syndrome

Blood ◽

10.1182/blood.v118.21.5018.5018 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5018-5018

Author(s):

Asmita Mishra ◽

Dana E Rollison ◽

Najla H Al Ali ◽

Maria Corrales-Yepez ◽

Pearlie K Epling-Burnette ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Myelodysplastic Syndrome ◽

Lower Risk ◽

Cox Regression ◽

Cancer Center ◽

Kaplan Meier ◽

Baseline Characteristics ◽

Md Anderson ◽

The Impact

Abstract Abstract 5018 Background: Obesity was associated with a more than 2-fold greater risk of myelodysplastic syndrome (MDS) in a recent epidemiological study (Ma et al, Am J Epidemiol. 2009 June 15; 169(12): 1492–1499). The impact of obesity on outcome of disease in patients with an established diagnosis of MDS has not been studied. We examined the prognostic value of obesity in a large cohort of lower risk MDS patients treated at the Moffitt Cancer Center (MCC). Methods: Data were collected retrospectively from the Moffitt Cancer Center (MCC) MDS database and individual charts reviewed. The primary objective was to evaluate the impact of obesity on overall survival (OS) in lower risk patients with MDS. Patients with low or intermediate-1 (int-1) risk disease by International Prognostic Scoring System (IPSS) were included. Obesity was defined as a body mass index (BMI) ≥ 30 (Standard definition) measured at time of referral to MDS program at MCC. Patients were divided into two groups according to BMI ≥ 30 or BMI < 30. All analyses were conducted using SPSS version 19.0. Chi square and independent t-test were used to compare baseline characteristics between the 2 groups for categorical and continuous variables, respectively. The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Cox regression was used for multivariable analysis. Results: Between January 2001 and December 2009, 479 low/int-1 IPSS risk MDS patients were included. Among those, 132 (27.6%) had BMI ≥ 30 and 325 (67.8%) had BMI <30; BMI was missing in 22 patients (4.6%). The baseline characteristics between the two groups were comparable. No difference was noted in mean age, WHO subtype, karyotype, MD Anderson risk model group, red blood cell transfusion dependency (RBC-TD), or serum ferritin (Table-1). The median OS was 59 mo (95%CI 48–70) in patients with BMI <30 compared to 44 (95%CI 38–50) in patients with BMI ≥ 30. (p=0.03). There was no difference in rate of AML transformation according to BMI, 12.9% and 15.7% respectively for BMI ≥ 30 and BMI <30. (P=0.3). In Cox regression analysis obesity predicted inferior OS (Hazard ratio (HR) 1.7 (95%CI 1.15–2.4) (P=0.007) after adjustment for age, MD Anderson risk group, serum ferritin, RBC-TD, use of hypomethylating agents and tobacco use. Conclusion: Our data suggest that obesity is an independent adverse prognostic factor for OS in patients with lower risk MDS. Obesity may be associated with other comorbidities and metabolic dearrangements that contribute to the pathogenesis of the underlying disease. Disclosures: No relevant conflicts of interest to declare.

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Enhancing risk stratification in primary mediastinal nonseminomatous germ cell tumors (PMNSGCT): A 27-year experience at a tertiary cancer center.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.373 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 373-373

Author(s):

Andrea Necchi ◽

Salvatore Lo Vullo ◽

Patrizia Giannatempo ◽

Elena Farè ◽

Daniele Raggi ◽

...

Keyword(s):

Overall Survival ◽

Risk Stratification ◽

Elevated Serum ◽

Germ Cell Tumors ◽

Good Prognosis ◽

Rank Test ◽

Cancer Center ◽

High Survival ◽

Prognostic Impact ◽

Final Histology

373 Background: Mediastinal GCTs and PMNSGCTs poorly benefit from CT and half of patients (pts) still die for disease. Enhancing the risk stratification may result in tailoring a personalized treatment strategy since diagnosis. Methods: Between 1985 and 2012, 87 pts with PM-GCT were treated at our center. Of them, pure seminomatous histology was excluded. Cox proportional hazards regression analysis was conducted to examine the prognostic impact of these candidate factors on overall survival (OS): type of 1st-line CT (high [HDCT] vs conventional dose [CDCT]), post-CT surgery, type of baseline elevated serum tumor marker (STM), presence of lung or liver-bone-brain metastases (LBB), STM response (still elevated vs normal or normalized), and histology (viable cancer [VC] vs necrosis/teratoma [NT]). OS curves were compared by Kaplan Meier method with the log-rank test. Results: The study included 68 cases with PMNSGCT. Median age was 28.5 yrs (IQR: 23-35). 12 pts (17.7%) presented with mediastinal syndrome, 23 (33.8%) had lung and 7 (10.3%) LBB metastases. 12 pts received upfront HDCT and 45 pts (66.2%) underwent post-CT surgery. The final model of poor prognostic factors included no surgery (HR: 8.74, 95%CI, 1.77-43.01), surgery + VC (HR: 6.97, 95%CI, 1.46-33.30), and lung metastases (HR: 2.92, 95%CI, 0.99-8.64). The model demonstrated moderate discriminatory ability for OS (c-statistic=0.68). A risk stratification model based on the combination of these factors and accounting for a 50% five-year survival cutoff identified 2 groups (poor prognosis, N=28 vs good prognosis, N=26) with distinct overall survival curves (p<0.001). Pre-operative STM and final histology were not associated (p=0.574 at Chi squared test). 5-yr OS after receiving 2nd line CT (n=25) was 18.7% (95%CI, 7.9-44.5). Results are limited by small numbers. Conclusions: Pts with PMNSGCT classified as having a good prognosis in this model had a fairly high survival estimate, while a strategy of consolidation CT for pts with poorest risk features warrants investigation, once the model is confirmed. The effect of surgery on survival was independent of post-CT STM, which also poorly predicted final histology.

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Subset of patients with unfavorable T1N2-3M0 gastric cancer for whom surgery alone is the standard treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.105 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 105-105

Author(s):

Yukio Maezawa ◽

Tsutomu Sato ◽

Toru Aoyama ◽

Kazuki Kano ◽

Kenki Segami ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Standard Treatment ◽

Stage Ii ◽

Rank Test ◽

Cancer Center ◽

Tumor Diameter ◽

Significant Difference ◽

Macroscopic Tumor

105 Background: ACTS-GC trial demonstrated that S-1 is effective as adjuvant chemotherapy for Japanese patients who have undergone curative D2 gastrectomy for gastric cancer and were diagnosed with pathological stage II disease. However, stages T1N2M0 and T1N3M0, which are classified as part of Stage II, were excluded from the ACTS-GC trial. The aim of the present study was to identify the unfavorable subset of patients with T1N2M0 and T1N3M0 gastric cancer for whom surgery alone is the standard treatment. Methods: The present study examined 59 patients who were diagnosed with T1N2M0 or T1N3M0 gastric cancer at Kanagawa Cancer Center and Yokohama City University Hospital between January 2000 and June 2010. Univariate and multivariate analyses were performed to identify risk factors for overall survival using a Cox proportional hazards model. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter. A macroscopic tumor diameter greater than 30mm was regarded as a critical point of classification considering the survival. Mulitivariate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 60.0% in patients with a macroscopic tumor diameter < 30mm, and 84.6% in those with a macroscopic tumor diameter > 30mm (P = 0.027). Conclusions: Among T1N2M0 and T1N3M0 gastric cancer patients for whom surgery alone is the standard treatment, having a small T1N2-3 tumor of less than 30 mm in diameter was the sole risk factor for gastric cancer survival. These tumors might be another target for adjuvant chemotherapy.

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Analysis of Immune-Related Signatures Related to CD4+ T Cell Infiltration With Gene Co-Expression Network in Pancreatic Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.674897 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhen Tan ◽

Yubin Lei ◽

Bo Zhang ◽

Si Shi ◽

Jiang Liu ◽

...

Keyword(s):

Overall Survival ◽

Molecular Mechanisms ◽

Cox Regression ◽

Risk Groups ◽

Gene Signature ◽

Gene Expression Omnibus ◽

Ductal Adenocarcinoma ◽

Rank Test ◽

Cancer Center ◽

Cox Regression Analysis

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most invasive solid malignancies. Immunotherapy and targeted therapy confirmed an existing certain curative effect in treating PDAC. The aim of this study was to develop an immune-related molecular marker to enhance the ability to predict Stages III and IV PDAC patients.MethodIn this study, weighted gene co-expression network (WGCNA) analysis and a deconvolution algorithm (CIBERSORT) that evaluated the cellular constituent of immune cells were used to evaluate PDAC expression data from the GEO (Gene Expression Omnibus) datasets, and identify modules related to CD4+ T cells. LASSO Cox regression analysis and Kaplan–Meier curve were applied to select and build prognostic multi-gene signature in TCGA Stages III and IV PDAC patients (N = 126). This was followed by independent Stages III and IV validation of the gene signature in the International Cancer Genome Consortium (ICGC, N = 62) and the Fudan University Shanghai Cancer Center (FUSCC, N = 42) cohort. Inherited germline mutations and tumor immunity exploration were applied to elucidate the molecular mechanisms in PDAC. Univariate and Multivariate Cox regression analyses were applied to verify the independent prognostic factors. Finally, a prognostic nomogram was created according to the TCGA-PDAC dataset.ResultsA four-gene signature comprising NAPSB, ZNF831, CXCL9 and PYHIN1 was established to predict overall survival of PDAC. This signature also robustly predicted survival in two independent validation cohorts. The four-gene signature could divide patients into high and low-risk groups with disparity overall survival verified by a Log-rank test. Expression of four genes positively correlated with immunosuppression activity (PD-L1 and PD1). Immune-related genes nomogram and corresponding calibration curves showed significant performance for predicting 3-year survival in TCGA-PDAC dataset.ConclusionWe constructed a novel four-gene signature to predict the prognosis of Stages III and IV PDAC patients by applying WGCNA and CIBERSORT algorithm scoring to transcriptome data different from traditional methods of filtrating for differential genes in cancer and healthy tissues. The findings may provide reference to predict survival and was beneficial to individualized management for advanced PDAC patients.

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The Impact of 20q Deletion on Clinical Presentation, Treatment Response and Survival in Patients with Acute Myeloid Leukemia (AML): The University of Texas MD Anderson Cancer Center Experience

Blood ◽

10.1182/blood.v126.23.1369.1369 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1369-1369

Author(s):

Jad Chahoud ◽

Hagop M. Kantarjian ◽

Farhad Ravandi ◽

Koji Sasaki ◽

Guillermo Garcia-Manero ◽

...

Keyword(s):

Overall Survival ◽

Treatment Response ◽

Research Funding ◽

Objective Response ◽

Normal Karyotype ◽

Prognostic Indicators ◽

Cancer Center ◽

Cytogenetic Abnormalities ◽

Md Anderson ◽

The Impact

Abstract Background: Karyotype classification is one of the strongest independent prognostic indicators in AML. The majority of recurring chromosomal aberrations are associated with an individual prognosis, other less frequent like the Del (20q), have been minimally evaluated and classified as intermediate risk in AML. Multiple studies established isolated 20q deletion as a good prognostic marker in MDS, with lower AML transformation rates and longer median overall survival (OS) in comparison with complex 20q deletion. Objective: The aim of this study is to determine the frequency and the impact on outcome of 20q deletion alone or with additional cytogenetic abnormalities in adult patients with AML. Patients and Methods: AML patients with chromosome 20 abnormalities were identified between 2000 and 2012 through the MD Anderson Cancer Center AML database (n=1741). Collected data included baseline demographics, number and type of additional cytogenetic abnormalities, disease characteristics, treatment and outcome. OS was defined as time from hematological diagnosis to death or last follow-up and relapse-free survival (RFS) was measured from time of hematological response to relapse. The Kaplan-Meier product limit method was used to estimate overall survival and the log-rank tests were employed for statistical comparisons between the OS curves. Results: From a total of 1741 adult AML patients, we identified 35 with Del (20q), representing 2% of our cohort. The distribution of cytogenetic abnormalities was as follows: isolated Del (20q) in 5 (14%), +8 in 3 (9%), +8 complex in 2 (6%), -5 complex in 8 (23%), -7 complex in 5 (14%), -7 not complex in 1 (3%), -5 and -7 complex in 6 (17%), other complex in 1 (3%), and other not complex in 4 (11%). Patients with Del (20q) were older (p=0.04), with lower bone marrow blast numbers (p<0.001), and lower WBC (p=0.001) compared to patients without Del (20q) (Table 1). Median RFS and OS for patients with Del (20q) were 16.8 and 7.5 months (mos), respectively. Objective response rates were 43% and 65% for patients with and without Del (20q), respectively (p=0.04) and the CR rates were 36% and 58%, respectively (p=0.01). Significant benefit was observed for OS in patients without Del (20q) (13.5 mos; 95% CI, 13.45-13.49; p=0.011), but not in RFS (19.52 mos; 95% CI, 19.48-19.55; p=0.376) in comparison with patients with Del (20q) (16.8 mos; 95% CI, 16.41-17.23; and 7.5 mos; 95% CI, 7.26-7.73). Patients with Del (20q) were compared to the remaining patients with leukemia classified as unfavorable cytogenetic status; the median survival for Del (20q) patients was similar by OS (OS 6.9 mos, 95% CI, 6.82-6.91). On the other hand, patients with Del (20q) had a significantly decreased overall survival (7.5 mos; 95% CI, 7.26-7.73, p=0.002) in comparison to patients with normal karyotype (17.7 mos; 95% CI, 17.64-17.71). No difference in survival was observed between patients with isolated Del (20q) and those with additional cytogenetic abnormalities: the median OS were 5 and 7.5 mos, respectively (p=0.964) (Figure 1). Conclusion: Our data demonstrated that Del (20q) occurs in 2% of previously untreated AML patients, with around 63% of these patients showing complex karyotype. Patients with Del (20q) have lower response rate and worse outcome, similar to patients with unfavorable cytogenetics. Table 1. Clinical descriptors, hematologic parameters and outcome of each set of patients Del 20qin Karyotype All othersnon-Del 20q P N = 35 N = 1706 Age (y), median (range) 65 (35-83) 61 (12-89) 0.04 Baseline hematologic data median (range) WBC × 109/L 2.7 (0.7-32.6) 5.8 (0.3-433) 0.001 Hemoglobin, g/dL 8.1 (5.6-14.2) 8.7 (2-93.3) 0.29 Platelet count, × 109/L 40 (7-254) 49 (2-676) 0.21 Neutrophil 29 (4-88) 16 (0-94) <0.001 PB blasts 9 (0-50) 16 (0-99) 0.02 BM blasts 30 (7-98) 47 (0-99) <0.001 Treatment Response and Survival Prior Chemo/XRT 7 301 0.72 CR 13 (37%) 990 (58%) 0.01 CRp 3 (9%) 88 (5%) 0.03 Cri 0 18 (1%) - RFS median, mo (95% CI) 17.22 (16.81-17.62) 25.59 (25.56-25-62) 0.55 OS median, mo (95% CI) 7.49 (7.26-7.73) 13.47 (13.45-13.49) 0.01 Disclosures Chahoud: American Society of Hematology (ASH): Other: 2015 HONORS Award recipient. Off Label Use: Inotuzumab.. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

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ABO blood group and survival in pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.380 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 380-380

Author(s):

Christina Wai ◽

Karthik Devarajan ◽

John Parker Hoffman

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Neoadjuvant Therapy ◽

Blood Group ◽

Blood Groups ◽

Prognostic Indicators ◽

Rank Test ◽

Cancer Center ◽

Abo Blood Group ◽

Survival Difference

380 Background: ABO blood group has been shown to be a risk factor in many gastrointestinal cancers. Recent studies have shown that patients with non-O blood groups have a higher risk of pancreatic adenocarcinoma compared to those with blood group O. Based on this finding, we were interested in seeing if a particular ABO blood group would have an impact on survival outcomes in pancreatic cancer. Methods: A retrospective chart review of 236 pancreatic patients who underwent surgical resection at a major cancer center from January 1998 to July 2011 was performed. Data were collected for demographics, ABO blood group, Rh factor, CA 19-9 level, use of neoadjuvant therapy, pathological stage, surgical margins and peritoneal washings. Overall survival (OS) was compared amongst the different blood groups. Results: There were 118 male and 118 female patients. The median age at diagnosis was 68. Of the 236 patients, 80 (33.9%) were blood group O, 108 (45.8%) were blood group A, 32 (13.6%) were blood group B and 16 (6.8%) were blood group AB. For all patients, there was no statistically significant association between ABO blood group and OS (log rank test p = 0.7). Furthermore, no survival difference was seen between O and non-O blood groups when the data was stratified by stage and neoadjuvant therapy. Conclusions: Like other GI malignancies, ABO groups have been shown to be linked to the risk of pancreatic cancer. The mechanism by which this occurs is not completely clear. In our analysis of ABO blood groups, they were not shown to be prognostic indicators. There does not appear to be a difference in overall survival between patients with O blood group and those with non-O blood groups.

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