Molecular classification of cancers with an uncertain diagnosis as candidates for immunotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23183-e23183
Author(s):  
Afsaneh Barzi ◽  
Harris S Soifer ◽  
Mason Israel ◽  
Catherine A. Schnabel

e23183 Background: FDA approvals of immunotherapy checkpoint inhibitors (CPIs) are based on organ site and thus cancers of unknown primary or with uncertain tumor type diagnoses have limited access to these revolutionary treatments. The 92-gene assay (CancerTYPE ID) is a validated gene expression classifier of 50 tumor type/subtypes for metastatic patients, six of which (lung adenocarcinoma, lung squamous cell, head & neck squamous cell, urinary bladder, kidney, and melanoma) have FDA-approved indications for CPIs. Study objectives were to analyze the distribution of the 6 tumor types with available CPIs in a large dataset of clinical cases and report patient and disease characteristics for this subset. Methods: A de-identified database was created under an IRB approved protocol that contains pathology and molecular information from consecutive cases submitted for clinical testing with the 92-gene assay. The distribution of molecular diagnoses was analyzed based on biopsy site, age, and gender. Chi-squared tests were used to compare between subgroups. Results: A total of 24,484 patients were available for analysis. Median age was 66y and 46% were male. The assay rendered a molecular diagnosis with an approved CPI in 27% (N = 6536) of cases. The most common biopsy sites were lymph node (23%), lung (15%) and liver (12%). Lung adenocarcinoma (31%) was the most common molecular diagnoses, followed by urinary bladder (20%), and head & neck squamous (16%). The proportion of melanoma molecular diagnoses decreased with age (11% in < 40y vs 4-6% across other age groups, p < 0.001), whereas the proportion of urinary bladder molecular diagnoses increased from 15% in < 40y to 23% in patients > 65y (p < 0.001). Women had a higher proportion of lung adenocarcinoma molecular diagnoses (36% vs 28% in men; p < 0.001), while kidney molecular diagnoses were more common in men (14% vs 8% in women; p < 0.001). Conclusions: These findings highlight the utility of molecular classification to identify metastatic cancers with unknown or uncertain tumor type diagnoses that are eligible for CPI. In addition, there was a significant difference in the distribution of 92-gene molecular diagnoses by age and gender among cancers susceptible to CPI.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15700-e15700
Author(s):  
Andrew Eugene Hendifar ◽  
Harris S Soifer ◽  
Mason Israel ◽  
Catherine A. Schnabel

e15700 Background: Histological diagnosis of metastatic neuroendocrine tumors (NET) can be straightforward, but identification of the specific NET tumor type/subtype is often challenging based on morphology alone. Accurate identification of tumor type/subtype in NETs of unknown primary has implications for grading, staging, and treatment decision-making as availability of targeted therapies increases. The 92-gene assay (CancerTYPE ID) is a validated gene expression classifier of 50 tumor type/subtypes (including 7 NET subtypes) for patients with unknown/uncertain diagnoses. In this study, 92-gene assay results from cases submitted for clinical testing with molecular diagnoses of NET were evaluated. Methods: A de-identified database was created under an IRB approved protocol that contains clinical and molecular information from consecutive cases submitted for clinical testing with the 92-gene assay with sufficient tissue for testing. In this analysis, patient demographics and distribution of molecular diagnoses were analyzed based on biopsy site, age, and gender. Chi-squared tests were used to compare between subgroups. Results: Analysis included 24,484 patients. Median age was 65y (51% female). The 92-gene assay rendered a molecular diagnosis of NET in 6.3% of cases (n = 1551). Small/large cell lung carcinoma (50%) was the most common NET molecular diagnosis, followed by GI carcinoid (14%), islet cell (14%), Merkel cell (10%), and lung carcinoid (9%). In liver biopsies (39% of cases), all 7 NET subtypes were identified by the 92-gene assay. The proportion of molecular diagnoses classified as small/large cell lung NET increased with age, from 25% in < 40y to 45% in 40-65y and 55% in > 65y, and the proportion of islet cell NET decreased with age (p < 0.0001). Men had a higher proportion of molecular diagnoses that were small/large cell lung NET (53%) vs women (46%; p < 0.0001). Conclusions: These findings highlight the utility of molecular classification to identify distinct NET tumor types/subtypes to improve diagnostic precision and treatment decision-making. In addition, significant differences in the distribution of molecular diagnoses of NET subtype by age and gender were identified.


Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1447 ◽  
Author(s):  
Lindsay M. Wong ◽  
Neil Shende ◽  
Wei Tse Li ◽  
Grant Castaneda ◽  
Lauren Apostol ◽  
...  

The intra-tumor microbiota has been increasingly implicated in cancer pathogenesis. In this study, we aimed to examine the microbiome in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and determine its compositional differences with relation to age and gender. After grouping 497 LUAD and 433 LUSC patients by age and gender and removing potential contaminants, we identified differentially abundant microbes in each patient cohort vs. adjacent normal samples. We then correlated dysregulated microbes with patient survival rates, immune infiltration, immune and cancer pathways, and genomic alterations. We found that most age and gender cohorts in both LUAD and LUSC contained unique, significantly dysregulated microbes. For example, LUAD-associated Escherichia coli str. K-12 substr. W3110 was dysregulated in older female and male patients and correlated with both patient survival and genomic alterations. For LUSC, the most prominent bacterial species that we identified was Pseudomonas putida str. KT2440, which was uniquely associated with young LUSC male patients and immune infiltration. In conclusion, we found differentially abundant microbes implicated with age and gender that are also associated with genomic alterations and immune dysregulations. Further investigation should be conducted to determine the relationship between gender and age-associated microbes and the pathogenesis of lung cancer.


2019 ◽  
Vol 3 (2) ◽  

Radiographic Mandibular Indices serve as easy and relatively cheap tools for evaluating bone mineralization. Objectives: To examine the effect of age and gender on three mandibular indices: the panoramic mandibular index (PMI), the mandibular ratio (MR) and the mandibular cortical index (MCI), among Libyan population. Methods: The three indices were measured on 317 digital (OPGs) of adult humans (155 males, 162 females). The sample was divided into six age groups (from 18-25 years through 56-65 years). The measurements were analyzed for interactions with age and sex, using SPSS (Statistical Package for Social Studies) software version no. 22. The tests employed were two way ANOVA, the unpaired T-test and chi-square test. Results: The mean PMI fluctuated between 0.37 s.d. 0.012 and 0.38 s.d. 0.012. among the sixth age groups. One-way ANOVA statistical test revealed no significant of age on PMI. On the other hand gender variation has effect on PMI, since independent sample t-test disclosed that the difference between the male and female PMI means statistically significant. ANOVA test showed that the means of MR among age groups showed a negative correlation i.e. MR mean declined from 3.01 in 18-25 age groups to 2.7 in 55-65 age groups. In contrary, the gender showed no effect on MR according two sample t-test at p> 0.05. In regards with MCI, statistical analysis showed that it affected by age that is C1 was decreasing by age while C2 and C3 were increased by age. Using chi square test the result indicated that there is a significant difference among the different age group and the two genders in MCI readings. Conclusion: PMI was influenced significantly by age but minimally by the gender. MR is not affected by gender but has a negative correlation with age. MCI is affected by both age and gender


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Suju Wang ◽  
Wenyang Hao ◽  
Chunxiao Xu ◽  
Daofeng Ni ◽  
Zhiqiang Gao ◽  
...  

Objective(s). The purpose of this study was to explore the effectiveness of wideband acoustic immittance (WAI) in the diagnosis of otosclerosis by comparing the differences in the energy reflectance (ER) of WAI between patients with otosclerosis and age- and gender-matched normal hearing controls in the Chinese population. Methods. Twenty surgically confirmed otosclerotic ears were included in the otosclerotic group. The ER of WAI at ambient and peak pressures, resonance frequency, and 226-Hz tympanogram were collected prior to surgery using a Titan hearing test platform (Interacoustics A/S, Middelfart, Denmark). All diagnoses of otosclerosis in the tested ear were confirmed by surgery after the measurements. Thirteen normal adults (26 ears) who were age- and gender-matched with the otosclerotic patients were included as the control group. Results. At peak pressure, the ERs of otosclerotic patients were higher than those of the control group for frequencies less than 4,000Hz and were lower for frequencies greater than 4,000Hz. In addition, within the analyzed frequencies, the differences observed at 2,520Hz was statistically significant (p<0.05/16=0.003, Bonferroni corrected). At ambient pressure, the differences observed at 1,260 and 6,350Hz were statistically significant (p<0.05/16=0.003, Bonferroni corrected). Although the differences between the otosclerotic and control groups exhibited similar trends to those in studies implemented in Caucasian populations, the norms in the present study in the control group were different from those in the Caucasian populations, suggesting racial differences in WAI test results. Regarding the middle ear resonance frequency, no significant difference was observed between the two groups (P>0.05). Conclusion. WAI can provide valuable information for the diagnosis of otosclerosis in the Chinese population. Norms and diagnostic criteria corresponding to the patient’s racial group are necessary to improve the efficiency of WAI in the diagnosis of otosclerosis.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Hamed Mahmoud Shatla ◽  
Mariam Fathy Abdel Maksoud ◽  
Raghda Mohamed Hesham Zaitoun ◽  
Alaa Rabie Abdel Baset Mahmoud

Abstract Objective To measure the level of hair Mg, as well as its level in serum, in patients with epilepsy and compare them to the levels found in non-epileptic age and gender matched children, and to explore any potential correlation between either serum or hair level of magnesium and seizure characteristics in children with idiopathic epilepsy. Methods An observational cross-sectional study including 50 children with idiopathic epilepsy and 100 non-epileptic age and gender matched control subjects. Cases were subjected to full history taking, examination and measurements of serum and hair levels of magnesium, control subjects only had their serum and hair level of magnesium measured as for the cases. Results The mean serum magnesium was 29.11 ± 13.42 ug/ml for cases and 27.67 ± 7.24 ug/ml for controls and the median hair level of magnesium was 42.22 ug/g with IQR of 25.9 - 56.82 for cases and 38.6 ug/g with IQR of 25.21 - 61.25 for controls. No statistically significant difference was observed between both groups as regards either serum or hair magnesium levels. No statistically significant correlation was observed between either hair or serum levels of magnesium and seizure characteristics though the correlations were nearing statistical significance for the hair magnesium content. Conclusion Hair magnesium level may be better correlated to seizure characteristics and control than serum levels in patients with epilepsy.


2021 ◽  
Vol 17 ◽  
Author(s):  
Seyed Mostafa Seyedmardani ◽  
Saeed Abkhiz ◽  
Azadeh Megrazi ◽  
Aarefeh Jafarzade ◽  
Golshan Kamali Zonouz

Background : Fibromyalgia syndrome (FMS) is defined as widespread and persistent pain in the musculoskeletal system. There are limited reports regarding the prevalence of fibromyalgia syndrome in patients with advanced kidney failure undergoing regular hemodialysis. Therefore, this study aimed to evaluate the prevalence of fibromyalgia syndrome and its risk factors in a large proportion of patients under the hemodialysis condition. Materials and Methods: In this cross-sectional study, 293 patients who were admitted to the hemodialysis ward were evaluated for fibromyalgia syndrome in an educational hospital. The questionnaire was designed according to symptom severity score (SS score) and widespread pain index (WPI) criteria. The correlation between FMS and various variables, including demographic, clinical, and biochemistry biomarkers, was also precisely calculated by logistic regression. Data were analyzed using SPSS v.17 statistics software. Results: The results showed that, of 293 hemodialysis patients, 130 patients (44.4%) had fibromyalgia, the mean age of patients with and without fibromyalgia was 61.09 ± 15.36 and 53.49 ± 15.38 years old, respectively (P = 0.001). Moreover, there was a significant difference in terms of gender among patients with fibromyalgia syndrome (P = 0.001). To note, there was no significant relationship between the kidney failure etiopathogenesis, duration of dialysis, body mass index (BMI), Kt/v index, history of peritoneal dialysis, and laboratory parameters with fibromyalgia in hemodialysis patients (P > 0.05). However, our findings revealed that both age and gender could be considered as the predictor variables associated with fibromyalgia in patients undergoing hemodialysis. Conclusion: Taken together, in this study, we found that age and gender would be the critical factors in terms of the fibromyalgia syndrome in patients undergoing hemodialysis.


2016 ◽  
Vol 8 (3) ◽  
pp. 11
Author(s):  
Fereshteh Heydari ◽  
Shohreh Farahani

<p>This study was conducted to compare with the executive function of ADHD versus normal male and female children. To obtain this objective, 30 ADHD children referring a private psychological center for the first time who had taken no medication for this disorder, and 30 normal children from one of the schools of District 14 in Tehran were selected randomly who were of the same age and gender of ADHD children. Wisconsin test was used as a measurement tool. Results showed that there is a significant difference between the average scores of the executive function of normal and ADHD children as well as average scores of the executive function of normal boys and ADHD children at the 0.01 level. In addition, there was a significant difference between the average scores of the executive function of normal girls and ADHD girls at the 0.05 level according to which null hypothesis is rejected. Therefore, ADHD children are of lower executive and cognitive function compared to normal children and have extensive cognitive deficits. Therefore, they require medications along with special training and rehabilitation.</p>


2019 ◽  
Vol 13 (1) ◽  
pp. 170-176
Author(s):  
Hisayoshi Tachihara ◽  
Junichiro Hamada

Background: The rib cage, such as the thoracic spine and ribs, influences glenohumeral mobility and the development of shoulder disorders. Objective: To evaluate movements of the ribs, thoracic vertebrae during bilateral arm elevation and to clarify the characteristic influences of age and gender. Methods: Subjects comprised 33 healthy individuals divided into a young group (10 males, 7 females; mean age, 25 years) and a middle-aged group (8 males, 8 females; mean age, 52 years). Chest CT was performed with two arm positions: arms hanging downwards; and arms elevated at 160°. Images were three-dimensionally reconstructed to evaluate rib movement, extension angle of thoracic vertebrae. Results: Maximal movement was observed at the fifth rib, and rib movement decreased with increasing distance from the fifth rib in both the groups. In males, movement of the second to fourth ribs was smaller in the middle-aged group than in the young group (p < 0.05). Movement of the first to ninth ribs was smaller in females than in males (p < 0.05). No significant difference in the extension angle of the thoracic vertebrae was found. Conclusion: Fifth rib movement is the largest among all ribs during bilateral arm elevation. Reduction of upper rib movement initially arises as an age-related degradation in males. Women exhibit less rib movement during bilateral arm elevation.


2020 ◽  
Vol 56 (1) ◽  
pp. 15
Author(s):  
Husin Thamrin ◽  
Khafidhotul Ilmiah ◽  
Ni Wajan Tirthaningsih

Colorectal cancer has became burden in the world.The latest study shows that colorectal cancer is the third most common cancer in men and second most common cancer in women globally. There are difference characteristic of epidemiology in every countries. Moreover, there is no study that represents epidemiology of colorectal cancer in Indonesia yet, especially in East Java. The aim of this study was to describe colorectal tumor profile by age and gender in Gastroentero-Hepatology Center, Dr Soetomo Hospital. This study has received a certificate of Ethical Clearance No.273/Panke.KKE/IV/2015, a descriptive retrospective study. We collected data using medical records, and patients who have been colonoscopy examination and suspected colorectal tumor were included. There were 201 patients, divided to 100 males and 101 females. The peak of incidence was on 51-60 years old group, but on the 31-40 years old incidence of colorectal tumor was increased. The youngest patient was 17 years old. And tumors are more likely develop in distal area, especially in rectum. This study shows a different characteristic profile of colorectal tumor, where tumor is developed at young people and there is no significant difference between male and female for the incidence.


Author(s):  
Anuja Jha ◽  
Manju Agrawal ◽  
Arvind Neral ◽  
Rajesh Hishikar ◽  
Basant Maheshwari

Background: Empirically chosen antibiotics based on the local resistance pattern of uropathogens remain the principle treatment of urinary tract infections (UTI).Methods: Antibiogram of most frequent uropathogen was determined. Based on the antibiogram result, authors compared effectiveness of drugs recommended for UTI by National centre for disease control (NCDC), India, and assessed age and gender based variability in the effectiveness of these drugs.Results: 1278 urine samples were accounted, of which 405 samples showed significant growth. E. coli was the most common uropathogen (n=146, 36%) followed by enterococcus species (31%) and Klebsiella pneumoniae (10%). Using McNemar’s test authors found that nitrofurantoin (90% sensitivity) was statistically the most effective drug among drugs recommended by NCDC for uncomplicated cystitis. Furthermore, authors used Fisher’s exact test on adults and paediatrics and found that significant difference in effectiveness was observed for nitrofurantoin (p-value <0.001) and cotrimoxazole (p-value 0.034). Using logistic regression, authors found that with age, effectiveness of ciprofloxacin and cotrimoxazole deteriorate significantly (p-value 0.021 and 0.002 respectively). Additionally, authors observed that cotrimoxazole has significantly better efficacy in males compared to females (p-value 0.022).Conclusions: In accordance with present study, nitrofurantoin can be used as first line treatment for uncomplicated cystitis. Age and gender should be considered while prescribing empirical treatment for UTI. Periodic surveillance should be carried out to identify the on-going pattern of antibiogram to update the guideline for empirical therapy.


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