Prognostic significance of human papilloma virus (HPV) in penile cancer: A National Cancer Database (NCDB) study.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 5-5
Author(s):  
Adithya Chennamadhavuni ◽  
Josiah An ◽  
Sarah L. Mott ◽  
Rohan Garje

5 Background: HPV is associated with 30 - 50% of penile cancers, with some studies showing improved outcomes in these patients. This study evaluated the effect of HPV infection on penile cancer outcomes. Methods: The national cancer database (NCDB) was utilized to identify HPV tested penile cancer patients at the time of diagnosis from 2004 – 2016. Chi-squared tests and Cox regression models were used in analysis. Results: Out of 486 patients with penile squamous cell cancer, 139 (29%) were HPV +ve, and 347 (71%) were HPV -ve. Greater than 50% of HPV +ve were < 65 years old, Caucasian, from low-income areas ( < $48,000), and had public or no insurance. Similar incidence patterns were noted in HPV- ve patients. 77% pts who were HPV +ve had a moderate to poorly differentiated tumor. Most HPV +ve presented with early-stage cancer, and 12% were stage IV at diagnosis. 5-year overall survival (OS) was better among HPV +ve 62% vs. 50% in HPV -ve patients. Multivariable analysis (MVA) shows superior survival among patients with age < 65 years, low comorbidity score (0-1), and earlier stage at diagnosis. Patients with HPV +ve adjusted for age, comorbidities, stage, and treatment showed significantly improved survival. HPV -ve patients had 1.49 times increased risk of death compared to HPV +ve. Conclusions: HPV positive penile cancer is associated with significantly improved survival independent of age, comorbidities, stage, and treatment modality. This study reiterates the prognostic significance of HPV status and testing for HPV status at diagnosis should be a standard practice. [Table: see text]

Open Heart ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. e001229
Author(s):  
Rowlens M Melduni ◽  
Waldemar E Wysokinski ◽  
Zhenzhen Wang ◽  
Bernard J Gersh ◽  
Samuel J Asirvatham ◽  
...  

ObjectivePrevious studies have postulated a causal role of patent foramen ovale (PFO) in the aetiology of embolic stroke in the general population. We hypothesised that the presence of concomitant PFO and atrial fibrillation (AF) will add incremental risk of ischaemic stroke to that linked to AF alone.MethodsWe analysed data on 3069 consecutive patients (mean age 69.4±12.2 years; 67.1% men) undergoing transoesophageal echocardiography-guided electrical cardioversion (ECV) for AF between May 2000 and March 2012. PFO was identified by colour Doppler and agitated saline contrast study. All patients were followed up after ECV for first documentation of ischaemic stroke. Outcomes were compared using Cox regression models.ResultsThe prevalence of PFO was 20.0% and the shunt direction was left-to-right in the majority of patients (71.4%). Patients with PFO had a higher frequency of obstructive sleep apnoea (21.7% vs 17.1%, p=0.01) and higher mean peak left atrial appendage emptying velocity (38.3±21.8 vs 36.1±20.4 cm/s; p=0.04) compared with those without PFO. Otherwise, baseline characteristics were similar between groups. During a mean follow-up period of 7.3±4.6 years, 214 patients (7.0%) had ischaemic stroke. Multivariable analysis showed no significant association between PFO and ischaemic stroke (HR, 0.82 (95% CI 0.57 to 1.18)). PFO shunt direction was strongly associated with stroke: HR, 1.91 (95% CI 1.16 to 3.16) for right-to-left shunt and HR, 0.58 (95% CI 0.36 to 0.93) for left-to-right shunt.ConclusionsThe presence of concurrent PFO in this largely anticoagulated group of patients with AF was not associated with increased risk of ischaemic stroke.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6004-6004 ◽  
Author(s):  
D. Rischin ◽  
R. Young ◽  
R. Fisher ◽  
S. Fox ◽  
Q. Le ◽  
...  

6004 Background: Previous studies have reported that in patients with oropharyngeal cancer (OPC) the presence of human papilloma virus (HPV) is associated with an improved prognosis. We sought to determine the prognostic importance of HPV and p16 in patients with OPC treated with concurrent chemoradiation on a large international phase III trial. Methods: Patients with previously untreated Stage III or IV head and neck squamous cell cancer were randomized to receive definitive radiotherapy concurrently with either cisplatin or cisplatin plus tirapazamine. In this substudy, analyses were restricted to patients with OPC who received > 60 Gy and did not have major radiation deviations predicted to impact on tumor control. HPV 16/18 were detected by in situ hybridization and scored as detected or undetected. p16 was detected by immunohistochemistry. Nuclear and cytoplasmic staining intensity of tumor cells was scored as grade 0–3, with grade 2 and 3 called positive. Log rank and Cox regression used for survival analyses. p values were 2-sided . Results: 384 out of 861 patients had OPC and met the eligibility criteria. Slides were available for HPV assay in 195 and for p16 in 186, and for both in 173. 54/195 (28%) were HPV positive, 107/186 (58%) were p16 positive. HPV pos tumors were associated with better 2-year overall survival (OS) (94 v 77%, p = 0.007) and better failure-free survival (FFS) (86 v 75%, p = 0.035) compared to HPV neg tumors. Similarly p16 pos tumors were associated with better 2-year OS (92 v 75%, p = 0.004) and FFS (87 v 72%, p = 0.003) compared to p16 neg . After adjustment for stage, Hb and ECOG PS, HPV pos had better OS than HPV neg (HR 0.29, p = 0.018), and p16 pos had better OS than p16 neg (HR 0.39, p = 0.013). When the HPV and p16 results were combined the relative HRs for OS were: HPVpos/p16pos 0.35 (45 patients, 26% of cases), HPVpos/p16neg 0 (3pts, 2%), HPVneg/p16pos 0.73 (58pts, 33%), HPVneg/p16neg 1.79 (67 pts, 39%). Conclusions: Our results confirm the prognostic significance of tumor HPV status in oropharyngeal cancer treated with chemoradiation, but also show that p16 identifies a larger group with an improved prognosis. The HPV neg/p16 pos population has a better prognosis compared to patients with HPV neg/p16 neg tumors. No significant financial relationships to disclose.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi114-vi114
Author(s):  
Josiah An ◽  
Adithya Chennamadhavuni ◽  
Sarah Mott ◽  
Rohan Garje

Abstract BACKGROUND Glioblastoma is one of the most aggressive and commonly encountered brain tumors. Standard of care includes surgical resection with adjuvant or concurrent chemoradiation which is predominantly based on adult clinical trials. Our study objective was to assess whether survival differed in AYA compared to older adults. METHODS The National Cancer Database was used to identify patients with at least surgically resected glioblastoma from 2004 to 2016. Cox regression models were utilized to estimate the effect of treatment on overall survival (OS) while accounting for immortal time bias (3-months) and clustering within facility. RESULTS Among 51,718 patients with glioblastoma identified, 2,930 patients were AYA. Multivariable analysis (MVA) shows OS was significantly higher in AYA, female, non-white, high income, unilateral cancer patients with private insurance receiving treatments in high volume facilities. OS among AYA patients was significantly lower in surgery + (radiation or chemotherapy: S+(RT or CT) group compared to surgery only (S) (HR=1.33, 95% CI 1.06–1.65), but no significant survival difference between surgery + chemoradiation (S+C+RT) groups and surgery only (HR=0.97, 95% CI 0.83–1.14). Median survival is ~28 months in AYA among S and S+C+RT groups whereas significantly lower survival (median OS ~18 months) is seen in S+RT or CT. Non-AYA patients were at 2 times increased risk of death compared to AYA patients who received the same type of treatment. CONCLUSIONS In conclusion, AYA population has more than twice the median OS in comparison to non-AYA patients. Worse overall survival was seen among S+RT or CT in comparison to S and S+RT+CT in AYA group. For patients needing either chemotherapy or radiation with surgery, possibly a trimodal approach might provide better survival advantage. Prospective studies are needed to further explore optimal treatment modalities in this unique population.


2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Maria Lukács Krogager ◽  
Peter Søgaard ◽  
Christian Torp‐Pedersen ◽  
Henrik Bøggild ◽  
Gunnar Gislason ◽  
...  

Background Hyperkalemia can be harmful, but the effect of correcting hyperkalemia is sparsely studied. We used nationwide data to examine hyperkalemia follow‐up in patients with hypertension. Methods and Results We identified 7620 patients with hypertension, who had the first plasma potassium measurement ≥4.7 mmol/L (hyperkalemia) within 100 days of combination antihypertensive therapy initiation. A second potassium was measured 6 to 100 days after the episode of hyperkalemia. All‐cause mortality within 90 days of the second potassium measurement was assessed using Cox regression. Mortality was examined for 8 predefined potassium intervals derived from the second measurement: 2.2 to 2.9 mmol/L (n=37), 3.0 to 3.4 mmol/L (n=184), 3.5 to 3.7 mmol/L (n=325), 3.8 to 4.0 mmol/L (n=791), 4.1 to 4.6 mmol/L (n=3533, reference), 4.7 to 5.0 mmol/L (n=1786), 5.1 to 5.5 mmol/L (n=720), and 5.6 to 7.8 mmol/L (n=244). Ninety‐day mortality in the 8 strata was 37.8%, 21.2%, 14.5%, 9.6%, 6.3%, 6.2%, 10.0%, and 16.4%, respectively. The multivariable analysis showed that patients with concentrations >5.5 mmol/L after an episode of hyperkalemia had increased mortality risk compared with the reference (hazard ratio [HR], 2.27; 95% CI, 1.60–3.20; P <0.001). Potassium intervals 3.5 to 3.7 mmol/L and 3.8 to 4.0 mmol/L were also associated with increased risk of death (HR, 1.71; 95% CI, 1.23–2.37; P <0.001; HR, 1.36; 95% CI, 1.04–1.76; P <0.001, respectively) compared with the reference group. We observed a trend toward increased risk of death within the interval 5.1 to 5.5 mmol/L (HR, 1.29; 95% CI, 0.98–1.69). Potassium concentrations <4.1 mmol/L and >5.0 mmol/L were associated with increased risk of cardiovascular death. Conclusions Overcorrection of hyperkalemia to levels <4.1 mmol/L was frequent and associated with increased all‐cause and cardiovascular mortality. Potassium concentrations >5.5 mmol/L were also associated with an increased all‐cause and cardiovascular mortality.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9021-9021 ◽  
Author(s):  
I. D. Schnadig ◽  
E. K. Fromme ◽  
C. L. Loprinzi ◽  
J. A. Sloan ◽  
M. Mori ◽  
...  

9021 Background: Physician-reported performance status (PS) is an important prognostic factor in advanced malignancies and is a commonly used stratification variable in cancer clinical trials. However, the extent, predictors, and prognostic importance of disagreement in PS assessment between physicians and patients have not been examined. Methods: Using NCCTG clinical trials from 1987–1990 (J Clin Oncol 19(15):3539–3546, 2001), we analyzed the difference and agreement of PS (ECOG and Karnofsky [KPS]) and nutritional status assessments reported by physicians and patients individually. The degree of disagreement was analyzed using paired t-test. Overall mortality was estimated by Kaplan-Meier method. The effect of disagreement on overall survival was analyzed by Cox regression. Independent predictors of disagreement were identified by logistic regression. Results: 1,636 patients with advanced lung and colorectal cancer had a median survival of 9.8 months (95% CI, 9.4 to 10.4). Percent agreement between patients and physicians about KPS, ECOG PS, and appetite/nutritional status was 32.9%, 43.4% and 42.0% respectively. Physicians were more likely to rate patients better than individual patients were to rate themselves: ECOG (Mean 0.91 vs 1.30, p<.0001), KPS (Mean 83.3 vs. 81.7, p<0.0001), appetite/nutritional status (Mean 1.6 vs. 2.1, p<0.0001). Inability to work, depression and less than a high school education were independently associated with disagreement. An increased risk of death was observed for patient and physician disagreement on KPS (HR=1.15, 95% CI, 1.03 to 1.27 p=0.01) and appetite/nutritional status (HR=1.39, 95% CI, 1.26 to 1.54 p<0.0001). Conclusions: Patients and physicians frequently disagree about patient PS, with physicians tending to rate patients higher than patients do themselves. Baseline patient demographic factors that independently predict disagreement have been identified. Disagreement confers an increased risk of death in the setting of advanced malignancies. These findings illustrate limitations of physician-only assessed PS. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4052-4052
Author(s):  
Joanna Alyse Young ◽  
Sally Jeanne Trufan ◽  
William Mills Worrilow ◽  
Laura W. Musselwhite ◽  
Reza Nazemzadeh ◽  
...  

4052 Background: ASCC incidence is rising. There are limited data on the relationships between sociodemographic & clinicopathological features and outcomes of ASCC pts. Methods: Pts diagnosed with ASCC between 2004 and 2016 were retrospectively reviewed. Data obtained from the NCDB were used to examine the impact of sociodemographic status on clinicopathological features and outcomes. Pts were categorized based on low (median < $38,000) or high (≥$68,000) income and low ( > 21% with no high school diploma) or high ( < 7% with no high school diploma) education areas based on zip code at time of diagnosis. Logistic regression and chi-square were used to examine differences between groups. Results: In total, 44,084 pts with ASCC were identified: median age, 59 yrs, 86% white; 11% black; 64% female. Most pts (84%) resided in metro areas; 29.7% vs 19.8% lived in high vs low income areas; 22.9% vs 17.8% lived in high vs low education areas. Seven percent were uninsured, 50% had government (Gov), and 43% had private insurance. Male gender (HR 1.62, CI 1.41-1.85, p < 0.001), low income area (HR 1.28, CI 1.19-1.37, p = 0.014), and insurance status (Gov, HR 1.55, CI 1.32-1.82, p < 0.001 and uninsured, HR 1.37, CI 1.37-1.85, p = 0.039) were associated with a higher risk of death. After adjusting for age, sex, race, stage, grade, insurance status, and comorbidity, pts from low income/education (n = 6695) vs high income/education (n = 4316) areas had a 33 % increased risk of death (HR: 1.33, p < 0.001). Pts with stage IV ASCC in the low income/education (n = 227) vs high income/education (n = 295) groups had worse overall survival (mOS, 1.4 vs 1.9 yrs, p < 0.020). Of the 44,084 pts, 5461 (12.4%) had confirmed HPV status. Of these, 2658 (48.7%) were HPV+ (high risk subtypes) and 2803 (51.3%) were HPV-. Compared to the HPV- pts, HPV+ pts were more likely to be women (71.8% vs 67.8%, p = 0.001), have stage 3 (38.1% vs 33.6%) or 4 (7.9% vs 5.9%, p < 0.001) cancer, and have poorly differentiated (29.5% vs 25.6%, p < 0.001) tumors. There were no significant differences in race, education, income, metro area, insurance status, or comorbidity between the HPV+ and HPV- pts. Moreover, HPV status did not impact OS (HR 0.92, CI 0.81-1.04, p = 0.195). Conclusions: HPV status was not correlated to income, education or insurance status, and did not impact OS in ASCC pts. Male gender and insurance status were associated with increased risk of death. Pts living in low income and low education areas were associated with worse survival.


2005 ◽  
Vol 23 (7) ◽  
pp. 1473-1482 ◽  
Author(s):  
Derek L. Dai ◽  
Magdalena Martinka ◽  
Gang Li

Purpose Akt is a serine/threonine kinase that leads to stimulation of cell cycle progression, cell proliferation, and inhibition of apoptosis. To investigate the role of Akt in melanoma pathogenesis, we examined the expression of phospho-Akt (p-Akt; Ser-473) in melanocytic lesions at different stages and analyzed the correlations between the p-Akt expression level and clinicopathologic factors and patient survival. Patients and Methods We evaluated the p-Akt expression in 12 cases of normal nevi, 58 cases of dysplastic nevi, 170 cases of primary melanomas, and 52 cases of melanoma metastases using tissue microarray and immunohistochemistry. Results Strong p-Akt expression was observed in 17%, 43%, 49%, and 77% of the biopsies in normal nevi, dysplastic nevi, primary melanoma, and melanoma metastases, respectively. Significant differences for p-Akt staining pattern were observed between normal nevi and primary melanomas (P < .05), and between primary melanomas and melanoma metastases (P < .001). Furthermore, our Kaplan-Meier survival curves showed that strong p-Akt expression is inversely correlated with both overall and disease-specific 5-year survival of patients with primary melanoma (P < .05 for both). Strikingly, our multivariate Cox regression analysis revealed that p-Akt is an independent prognostic factor in low-risk melanomas (thickness ≤ 1.5 mm; relative risk, 6.44; 95% CI, 1.28 to 32.55; P = .018). Conclusion The expression of p-Akt increases dramatically with melanoma invasion and progression and is inversely correlated with patient survival. In addition, p-Akt may serve as an independent prognostic marker and help to identify those patients with low-risk melanomas who are at increased risk of death.


Heart ◽  
2019 ◽  
Vol 106 (6) ◽  
pp. 467-473 ◽  
Author(s):  
Laurie W Geenen ◽  
Vivan J M Baggen ◽  
Robert M Kauling ◽  
Thomas Koudstaal ◽  
Karin A Boomars ◽  
...  

ObjectiveDespite its predictive value for mortality in various diseases, the relevance of growth differentiation factor-15 (GDF-15) as prognostic biomarker in pulmonary hypertension (PH) remains unclear. This study investigated the association between GDF-15 and outcomes in adults with PH.MethodsThis is a single-centre prospective observational cohort study. All adults with PH were included at the day of their diagnostic right heart catheterisation between 2012 and 2016. PH due to left heart disease was excluded. Venous blood sampling was performed and included GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements. Kaplan-Meier curves and Cox regression analysis were used to investigate the association between GDF-15 and a composite endpoint of death or lung transplantation. We adjusted for age and NT-proBNP in multivariable analysis. Reference values were established by GDF-15 measurements in healthy controls.ResultsGDF-15 was measured in 103 patients (median age 59.2 years, 65% women, 51% pulmonary arterial hypertension). GDF-15 was elevated in 76 patients (74%). After a median follow-up of 3.4 (IQR 2.3–4.6) years, 32 patients (31.1%) reached the primary endpoint. Event-free survival 2 years after diagnosis was 100% in patients with normal GDF-15 versus 72.4% in patients with elevated GDF-15 (p=0.007). A significant association was found between GDF-15 and the primary endpoint (HR per twofold higher value 1.77, 95% CI 1.39 to 2.27, p<0.001), also after adjustment for age and NT-proBNP (HR 1.41, 95% CI 1.02 to 1.94, p=0.038).ConclusionsHigh GDF-15 levels are associated with an increased risk of death or transplant in adults with PH, independent of age and NT-proBNP. As non-specific biomarker, GDF-15 could particularly be useful to detect low-risk patients.


2021 ◽  
pp. 174749302110062
Author(s):  
Thiago Cerqueira-Silva ◽  
Beatriz MM Gonçalves ◽  
Camila B Pereira ◽  
Louise M Porto ◽  
Maria EL Marques ◽  
...  

Background and Aims Chagas disease is a common cause of heart failure (HF) and death in developing countries. Although stroke is known to occur in these patients, an accurate estimate of stroke incidence is lacking. We aimed to determine the incidence of stroke and death in patients with HF, comparing Chagas and non-Chagas etiologies. Methods Cohort of stroke-free patients with HF (Framingham criteria) followed in a university-based outpatient clinic in Brazil. Baseline characteristics included sociodemographic, risk factor assessment, echocardiographic and electrocardiographic findings. Chagas disease was defined by appropriate serologic tests. Cause-specific Cox regression was used to search for predictors of stroke or death as separate outcomes. Results We studied 565 patients with HF between January 2003 and December 2018, mean age 54.3 ± 12.9 years, 305 (54.0%) females, 271/535 (50.7%) with Chagas disease. Chagas patients were older (55.5 vs. 53.1 years), more frequently women (60.5% vs. 47.3%), less frequently harbored coronary artery disease (14.5% vs. 34.1%) when compared to non-Chagas patients. Echocardiography showed more severe disease among non-Chagas patients [median left ventricle ejection fraction (LVEF) 37.3% vs. 47.0%]. Over a mean 42.9 (±34.4) months, we followed 404 (71.5%) patients, completing 1442 patient-years of follow-up. Stroke incidence was higher in Chagas when compared to non-Chagas patients (20.2 vs. 13.9 events per 1000 patient-years), while death rate was similar (41.6 vs. 43.1 deaths per 1000 patient-years). In the multivariable analysis for stroke outcome adjusted for LVEF and arrhythmias, cause-specific hazard ratio (CSHR) for Chagas was 2.54 (95% confidence interval 1.01–6.42, p = 0.048). Chagas disease was also associated with increased risk of death (CSHR 1.83; 95% confidence interval 1.04–3.24, p = 0.037). Conclusion Chagas disease is associated with increased risk of stroke and death when compared to other etiologies of HF, independently of HF severity or cardiac arrhythmias, suggesting other factors contribute to increased stroke risk and mortality in Chagas disease. Early prevention and treatment of Chagas disease is imperative to reduce a later risk of stroke in endemic areas.


2021 ◽  
pp. 019459982110045
Author(s):  
Evan J. Patel ◽  
Jamie R. Oliver ◽  
Adam S. Jacobson ◽  
Zujun Li ◽  
Kenneth S. Hu ◽  
...  

Objective Assess the testing rates and prognostic significance of human papilloma virus (HPV) status in hypopharynx malignancies. Study Design Historical cohort study. Setting National Cancer Database. Methods Review of the National Cancer Database was conducted between 2010 and 2017 for squamous cell carcinomas (SCCs) of the hypopharynx. We investigated how often the tumors were tested for HPV and whether it was associated with survival outcomes. Results A total of 13,269 patients with hypopharynx malignancies were identified. Most cases were not tested for HPV status (n = 8702, 65.6%). Of those tested, 872 (19.1%) were positive for HPV and 3695 (80.9%) were negative. The proportion of nonoropharyngeal SCCs tested for HPV increased nearly every year during the study, with roughly one-third of cases (31.9%) being tested in 2017. In the facilities classified as high-testing centers of nonoropharyngeal SCCs of the head and neck, 18.7% of hypopharyngeal tumors were HPV positive. HPV-negative status was associated with worse survival on multivariable analysis. In propensity score–matched analysis controlling for all factors significant in multivariable regression, 2-year survival remained higher in the HPV-positive cohort (77.7% vs 63.1%, P < .001). Conclusions HPV-positive tumors constitute a sizable minority of hypopharynx tumors and are associated with improved survival. Expansion of HPV testing to hypopharynx malignancies may be warranted.


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