scholarly journals PD-L1 and Tumor Mutational Burden Are Not Predictive of Thrombosis in a Cohort of 1,221 Patients with Solid Organ Malignancies

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1055-1055
Author(s):  
Rajat Thawani ◽  
Thomas Kartika ◽  
Benjamin Elstrott ◽  
Elizabeth Batiuk ◽  
Lilian Chen ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subgroup Analysis ◽  
Clinical Samples ◽  
Solid Organ ◽  
Primary Malignancy ◽  
Thrombotic Risk ◽  
Mutational Burden ◽  
Multivariable Logistic Regression ◽  
Tumor Mutational Burden ◽  
Solid Organ Malignancy

Abstract Introduction: Malignancy is a well-known risk factor for thrombosis. While many clinical risk factors for cancer-associated thrombosis have been described, it remains unknown how certain tumor specific observations (such as programmed death ligand 1 expression (PD-L1) and tumor mutational burden (TMB)) correspond to thrombotic risk. To determine the relationship between PD-L1 and TMB quantification and thrombosis in patients with solid tumors, we evaluated a large cohort of clinical samples from an NCI designated cancer center, correlating tissue sample pathology with the development of venous or arterial thromboembolism. Methods: We performed a retrospective cohort study of patients between the ages of 18-89 who underwent histopathologic examination and next generation sequencing for a diagnosis of a solid organ malignancy at the Knight Cancer Institute between June 2019 and Feb 2021. Medical records were reviewed to document clinical and demographic information as well as for the development of thrombosis after cancer diagnosis. Multivariable logistic regression was performed to assess if PD-L1 expression and TMB are independent predictors of thrombosis. Subgroup analysis was then performed to evaluate whether this relationship differed by the organ of the primary malignancy. All analyses were conducted in R (R Core Team 2019). Results: We identified 1,221 patients with solid organ malignancies (mean age 62, 53.6% male). The most common malignancies in the cohort were lung cancer (13.8%), pancreatic cancer (12.3%) and colon cancer (12.3%). Thrombotic events occurred in 206 patients (16.8%) after diagnosis of their malignancy (100 deep vein thrombosis, 42 pulmonary embolism, 46 visceral vein thromboses, 6 superficial vein thromboses, and 11 arterial events). The mean time from initial biopsy to thrombosis was 224 days. TMB (mean 8.5 mutations/Mb) was evaluated in all patients in the cohort, while PD-L1 expression testing (mean 23.0%) was available for 255 patients. On multivariable logistic regression adjusting for age and patient sex, neither TMB (ORadj: 0.97, CI: 0.92-1.03) nor PD-L1 expression (ORadj 1.00, CI: 1.00-1.02) were significant predictors of thrombotic events. Subgroup analysis by primary malignancy type did not demonstrate any specific primary sites for which TMB or PD-L1 were predictive of thrombosis. Discussion: Our analysis found no predictive relationship between TMB and PD-L1 expression with thrombotic events in patients with solid organ malignancy. Further analysis is needed to determine if specific treatment protocols, such as the use of immunotherapy in patients with varying levels of PD-L1 and TMB, alter thrombosis risk. Disclosures Shatzel: Aronora Inc,: Consultancy.

Outcomes of cancer patients with takotsubo cardiomyopathy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18101-e18101
Author(s):  
Achuta Kumar Guddati ◽  
Gagan Kumar ◽  
Iuliana Shapira ◽  
Parijat Saurav Joy
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Logistic Regression Analysis ◽  
Takotsubo Cardiomyopathy ◽  
Primary Diagnosis ◽  
Multivariable Logistic Regression Analysis ◽  
Solid Organ ◽  
Multivariable Logistic Regression

e18101 Background: Chemotherapy induced cardiomyopathy is an important complication of some chemotherapeutic agents. The stress of a cancer diagnosis and ongoing chemotherapy may contribute to cardiac morbidity in these patients. The burden of Takotsubo Cardiomyopathy (TCP) in cancer patients is unknown. The incidence of TCP and related outcomes in cancer patients was investigated in this study. Methods: The 2007-2013 National Inpatient Sample (NIS) was analyzed for patients with a prior and new diagnosis of TCP with and without malignancy. Risk factors for mortality were adjusted for associated conditions by multivariable logistic regression analysis. Results: From 2007 through 2013, an estimated 122,750 adults were admitted with a diagnosis of TCP. In 2013, the incidence of admissions in US of patients with coexisting TCP and malignancy was 1.13%. Admissions in 34,957 patients were for a primary diagnosis of TCP with 91.7% females; overall, 665 (2.1%) had solid organ cancer, 237 (0.74%) had hematological malignancy and 354 (1.11%) had metastatic cancer. Patients admitted for TCP with coexisting malignancy had a significantly higher mortality (13.8% vs. 2.9%, p < 0.0001), length of stay (7 vs. 4 days, p < 0.0001) and total charges ($29291 vs. $ 36231, p < 0.0001), compared to those with no malignancy. In patients with a primary diagnosis of TCP and without any underlying malignancy, males had a higher mortality (4.02% vs. 1.03%, p < 0.0001) whereas there was no gender difference in mortality in those with coexisting malignancy (6.25% vs 6.45%, p = 0.965). On multivariable logistic regression analysis, risk factors associated with mortality were solid cancer (OR 3.43, p = 0.008), stroke (OR 18.33, p < 0.0001), venous thromboembolic disease (OR 4.52, p = 0.004), malnutrition (OR 2.41, p = 0.006) and heart failure (OR 1.918, p = 0.004). Conclusions: Outcomes are significantly worse in patients with TCP and solid malignancy. Hence, this patient population must be regarded as high-risk and early diagnostic consideration for TCP is warranted. Early intervention may help lower mortality, decrease resource utilization and reduce the health care costs in these patients.

scholarly journals OA05 Tumor Mutational Burden Standardization Initiative: Establish a Consistent Methodology for TMB Measurement in Clinical Samples

2018 ◽  
Vol 13 (12) ◽  
pp. S1045-S1046
Author(s):  
A. Stenzinger ◽  
J. Allen ◽  
J. Maas ◽  
M. Stewart ◽  
D. Merino ◽  
...  
Keyword(s):  
Clinical Samples ◽  
Mutational Burden ◽  
Tumor Mutational Burden

The prognostic role of microsatellite status, tumor mutational burden, and protein expression in CRC.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 572-572 ◽  
Author(s):  
Sarit Schwartz ◽  
Yuan Tian ◽  
Fabiola Cecchi ◽  
Andrew Nguyen ◽  
Yeoun Jin Kim ◽  
...  
Keyword(s):  
Protein Expression ◽  
Treatment Options ◽  
Molecular Profiling ◽  
Clinical Samples ◽  
Rank Test ◽  
P16 Protein ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Patient Subgroups ◽  
P16 Expression

572 Background: Comprehensive molecular profiling of CRC can inform treatment decisions by identifying patient subgroups at varying risks of death. Microsatellite instability (MSI) is prognostic in CRC and is used to select patients for immunotherapy. High tumor mutational burden (TMB) is associated with genomic instability and is prognostic in melanoma. Expression of p16 protein is prognostic in many tumor types. We used proteomic and genomic profiling to measure MSI, TMB and p16 in CRC tumors and to assess associations with patient survival. Methods: In archived clinical samples of CRC, 76 proteins were quantitated with mass spectrometry-based proteomics. MSI was measured by WGS and RNA-seq; unstable loci were quantified in tumor and normal samples. Cutoffs were derived via ROC analysis: high TMB was defined as > 4.5 somatic mutations per megabase; p16 as > 108 amol/ug. Patients were grouped by microsatellite status (MSI vs. microsatellite stable [MSS]), TMB (high vs. low), and p16 protein expression level. Survival curves were compared with the Mantel-Cox log-rank test. Results: Of 145 samples, 39 (27%) had high TMB and 29 (20%) had MSI. Patients with MSI tumors had longer OS than patients with MSS tumors (HR: 0.096; p = 0.003). Similarly, patients with high TMB had longer OS than those with low TMB (HR: 0.076; p < 0.001). High p16 expression was prognostic of poor survival (HR: 2.874; p = 0.019). Among patients with MSS tumors or low TMB, those with low p16 levels had longer OS than patients with high p16 (HR: 0.257; p = 0.002 and HR: 0.249; p = 0.002, for MSS and low TMB, respectively). A combination of MSS, low TMB, and low p16 also differentiated between long and short survivors (HR: 0.249; p = 0.002). These associations remained after adjustment for tumor sidedness. Further analyses of clinical correlates will be presented. Conclusions: A combination of MSS, low TMB and low p16 expression characterized a subset of patients with longer survival. This is important because patients with MSS tumors have limited treatment options but may respond to CDK4/6 inhibitors due to low p16 expression. Molecular profiling of CRC may identify patient subgroups with a relatively poor prognosis who could benefit from personalized therapy.

scholarly journals Tumor mutational burden (TMB) standardization initiative: Establishing a consistent methodology for TMB measurement in clinical samples

2018 ◽  
Vol 29 ◽  
pp. viii45 ◽  
Author(s):  
A. Stenzinger ◽  
J. Allen ◽  
J. Maas ◽  
M. Stewart ◽  
D. Merino ◽  
...  
Keyword(s):  
Clinical Samples ◽  
Mutational Burden ◽  
Tumor Mutational Burden

scholarly journals Characteristics of genomic alterations in Chinese cholangiocarcinoma patients

2020 ◽  
Vol 50 (10) ◽  
pp. 1117-1125
Author(s):  
Guoping Jiang ◽  
Wu Zhang ◽  
Ting Wang ◽  
Songming Ding ◽  
Xiaoliang Shi ◽  
...  
Keyword(s):  
Genomic Alteration ◽  
Molecular Evidence ◽  
Cancer Genes ◽  
Primary Malignancy ◽  
Exact Test ◽  
Mutational Burden ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Tumor Mutational Burden ◽  
Formalin Fixed

Abstract Objective Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Here, we aimed to identify the genomic profile of CCA and provided molecular evidence for further biomarker development. Methods The formalin-fixed paraffin-embedded and matching blood samples were sequenced by deep sequencing targeting 450 cancer genes and genomic alteration analysis was performed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher’s exact test. Results The most commonly altered genes in this cohort were TP53 (41.27%, 26/63), KRAS (31.75%, 20/63), ARID1A and IDH1 (15.87%, 10/63, for both), SMAD4 (14.29%, 9/63), FGFR2 and BAP1 (12.70%, 8/63, for both), and CDKN2A (11.11%, 7/63). BAP1 mutations were significantly correlated with the CCA subtype. LRP2 mutations were significantly associated with the younger intrahepatic CCA (iCCA) patients, while BAP1 was associated with iCCA patients aged 55–65 years old. BAP1 and LRP2 mutations were associated with TMB. Conclusions Most Chinese CCA patients were 50–70 years old. BAP1 and LRP2 mutations were associated with the age of iCCA patients.

scholarly journals Tumor mutational burden standardization initiatives: Recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions

2019 ◽  
Vol 58 (8) ◽  
pp. 578-588 ◽  
Author(s):  
Albrecht Stenzinger ◽  
Jeffrey D. Allen ◽  
Jörg Maas ◽  
Mark D. Stewart ◽  
Diana M. Merino ◽  
...  
Keyword(s):  
Treatment Decisions ◽  
Clinical Samples ◽  
Mutational Burden ◽  
Tumor Mutational Burden

scholarly journals Effect of prostatic apex shape (Lee types) and urethral sphincter length in preoperative MRI on very early continence rates after radical prostatectomy

2021 ◽  
Author(s):  
Mike Wenzel ◽  
Felix Preisser ◽  
Matthias Mueller ◽  
Lena H. Theissen ◽  
Maria N. Welte ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Radical Prostatectomy ◽  
Regression Models ◽  
Urethral Sphincter ◽  
Anatomical Characteristics ◽  
Logistic Regression Models ◽  
Pad Test ◽  
Type D ◽  
Multivariable Logistic Regression ◽  
Type C

Abstract Purpose To test the effect of anatomic variants of the prostatic apex overlapping the membranous urethra (Lee type classification), as well as median urethral sphincter length (USL) in preoperative multiparametric magnetic resonance imaging (mpMRI) on the very early continence in open (ORP) and robotic-assisted radical prostatectomy (RARP) patients. Methods In 128 consecutive patients (01/2018–12/2019), USL and the prostatic apex classified according to Lee types A–D in mpMRI prior to ORP or RARP were retrospectively analyzed. Uni- and multivariable logistic regression models were used to identify anatomic characteristics for very early continence rates, defined as urine loss of ≤ 1 g in the PAD-test. Results Of 128 patients with mpMRI prior to surgery, 76 (59.4%) underwent RARP vs. 52 (40.6%) ORP. In total, median USL was 15, 15 and 10 mm in the sagittal, coronal and axial dimensions. After stratification according to very early continence in the PAD-test (≤ 1 g vs. > 1 g), continent patients had significantly more frequently Lee type D (71.4 vs. 54.4%) and C (14.3 vs. 7.6%, p = 0.03). In multivariable logistic regression models, the sagittal median USL (odds ratio [OR] 1.03) and Lee type C (OR: 7.0) and D (OR: 4.9) were independent predictors for achieving very early continence in the PAD-test. Conclusion Patients’ individual anatomical characteristics in mpMRI prior to radical prostatectomy can be used to predict very early continence. Lee type C and D suggest being the most favorable anatomical characteristics. Moreover, longer sagittal median USL in mpMRI seems to improve very early continence rates.

scholarly journals Comparison of laparoscopic and hand-assisted laparoscopic nephrectomy for inflammatory renal disease: which is the preferred approach?

2021 ◽  
Vol 13 ◽  
pp. 175628722098404
Author(s):  
Xudong Guo ◽  
Hanbo Wang ◽  
Yuzhu Xiang ◽  
Xunbo Jin ◽  
Shaobo Jiang
Keyword(s):  
Logistic Regression ◽  
Renal Disease ◽  
Complication Rate ◽  
Adverse Outcomes ◽  
Laparoscopic Nephrectomy ◽  
Multivariable Logistic Regression Analysis ◽  
Invasive Approach ◽  
Intraoperative Complication ◽  
Multivariable Logistic Regression ◽  
Significant Difference

Aims: Management of inflammatory renal disease (IRD) can still be technically challenging for laparoscopic procedures. The aim of the present study was to compare the safety and feasibility of laparoscopic and hand-assisted laparoscopic nephrectomy in patients with IRD. Patients and methods: We retrospectively analyzed the data of 107 patients who underwent laparoscopic nephrectomy (LN) and hand-assisted laparoscopic nephrectomy (HALN) for IRD from January 2008 to March 2020, including pyonephrosis, renal tuberculosis, hydronephrosis, and xanthogranulomatous pyelonephritis. Patient demographics, operative outcomes, and postoperative recovery and complications were compared between the LN and HALN groups. Multivariable logistic regression analysis was conducted to identify the independent predictors of adverse outcomes. Results: Fifty-five subjects in the LN group and 52 subjects in the HALN group were enrolled in this study. In the LN group, laparoscopic nephrectomy was successfully performed in 50 patients (90.9%), while four (7.3%) patients were converted to HALN and one (1.8%) case was converted to open procedure. In HALN group, operations were completed in 51 (98.1%) patients and conversion to open surgery was necessary in one patient (1.9%). The LN group had a shorter median incision length (5 cm versus 7 cm, p < 0.01) but a longer median operative duration (140 min versus 105 min, p < 0.01) than the HALN group. There was no significant difference in blood loss, intraoperative complication rate, postoperative complication rate, recovery of bowel function, and hospital stay between the two groups. Multivariable logistic regression revealed that severe perinephric adhesions was an independent predictor of adverse outcomes. Conclusion: Both LN and HALN appear to be safe and feasible for IRD. As a still minimally invasive approach, HALN provided an alternative to IRD or when conversion was needed in LN.

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