Real-world outcome analysis of EGFR-mutated lung adenocarcinoma with brain metastases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13588-e13588
Author(s):  
Feng-Che Kuan ◽  
Wei-Hsun Yang ◽  
Hung-Yi Lai ◽  
Chun-Chieh Huang ◽  
Cheng-Ta Yang ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lung Adenocarcinoma ◽  
Egfr Mutations ◽  
Outcome Analysis ◽  
P Value ◽  
Research Database ◽  
Poor Prognostic Factor ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Egfr Mutated

e13588 Background: BM represent a common problem in EGFR-mutated lung adenocarcinoma. The updated Lung-molGPA elucidates the survival in patients with non-small-cell lung cancer and BM by incorporating the effect of EGFR gene alterations. However, the nature history and differences of prognostic implication between common and uncommon EGFR mutations remain unsolved. Methods: By retrospective analysis of Chang-Gung Research Database (CGRD), patients with EGFR-mutated lung adenocarcinoma and BM were included into analysis of PFS and OS. EGFR mutations were categorized into exon 19 deletions (Del19), exon 21 Leu858Arg substitution (L858R) and uncommon mutations. Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models was performed to estimate adjusted hazard ratios (HR) and 95% confidence interval (CI). The p-value was set to be statistically significant at 0.05 or less. Results: From April 1, 2014 to June 30, 2015, 269 out of 818 patients with EGFR-mutated lung adenocarcinoma and BM were included, of which 115 patients with Del19, 131 patients with L858R, and 23 patients with uncommon EGFR mutations. The baseline characteristics were balanced in age, gender, KPS, ECM, number of BM, and timing of BM. In comparison with those with L858R, uncommon mutations is a poor prognostic factor for PFS (HR 2.24, 95% CI: 1.34-3.75, p = 0.002). The median PFS of Del 19, L858R, and uncommon EGFR mutations were 10.4, 10.0, and 3.2 months, respectively (log-rank p = 0.03). Besides, the median OS of Del 19, L858R, and uncommon EGFR mutations were 18.1, 17.4, and 12.5 months, respectively (log-rank p = 0.05). In comparison with those treated with gefitinib, afatinib treatment is a good prognostic factor for PFS and OS (PFS, HR 0.57, 95% CI: 0.35-0.94, p = 0.03; OS, HR 0.48, 95% CI: 0.26-0.91, p = 0.03). The median PFS of those treated with sequential WBRT, concurrent WBRT and TKI alone were 11.0, 8.5, and 10.3, respectively (log-rank p = 0.63). In addition, the median OS of those treated with sequential WBRT, concurrent WBRT and TKI alone were 18.7, 15.2, and 18.2 months, respectively (log-rank p = 0.50). Conclusions: Among patients with EGFR-mutated adenocarcinoma, common and uncommon EGFR mutations have distinct natural history and prognostic implications in patients with BM.

MCRS1 EXPRESSION MORE IN TUMOR PART AND SERVES AS A POOR PROGNOSTIC FACTOR IN EXTRAHEPATIC CHOLANGIOCARCINOMA

2021 ◽  
pp. 72-75
Author(s):  
Hung-Chune Maa ◽  
Pham van Tuyen ◽  
Yen-Lin Chen ◽  
Yao-Nan Yuan
Keyword(s):  
Prognostic Factor ◽  
Large Scale ◽  
Surgical Margin ◽  
P Value ◽  
Extrahepatic Cholangiocarcinoma ◽  
Poor Prognostic Factor ◽  
Kaplan Meier ◽  
Survival Plot

INTRODUCTION:Microporous protein 1 (MCRS1) acts as a cancer gene. MCRS1 is associated with poor prognosis in several types of cancer including colorectal cancer, hepatocellular carcinoma, glioma, and non-small cell lung cancer. In the current study, we are trying to shed light on the role of MCRS1 in the extrahepatic cholangiocarcinoma. METHODS: We retrospectively selected 13 patients who diagnosed extrahepatic cholangiocarcinoma. All clinical charts and histopathology reports were reviewed for and recoded for age, gender, tumor size, surgical margin status, lymph node metastasis, distant metastasis and TMN staging. All patients were followed for 1~10 years. The median follow-up period was 3.2 years. RESULTS: The expression level of MCRS1 showed signicantly higher in tumor part than non-tumor part. In the Kaplan-Meier survival plot , the high MCRS1 expression group showed poor survival probability with p value of 0.020. The Hazard ratio of MCRS1 showed 8.393 folds in high MCRS1 expression group when compared with low expression group with the borderline p value of 0.05. CONCLUSION:MCRS1 serves as a poor prognostic factor. Further analysis, no correlation was found in proliferation, apoptosis, angiogenesis and EMT markers. The reason may be the sample size and large-scale study in the future is mandatory

Real-world evidence: Molecular subtype and its prognostic implications of Lung-molGPA in EGFR-mutated adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21621-e21621
Author(s):  
Feng-Che Kuan ◽  
Chung-Sheng Shi ◽  
Wei-Hsun Yang ◽  
Hung-Yi Lai ◽  
Chun-Chieh Huang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Egfr Mutations ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Real World Evidence ◽  
Prognostic Implications ◽  
Egfr Mutated ◽  
Exon 19

e21621 Background: EGFR mutations are heterogenous but all carry the same weight in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Methods: Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 256 patients were included with a median overall survival (OS) of 17.2months. Patients with Lung-molGPA scores of 1, 1.5-2.0, 2.5-3.0, and 3.5-4.0 had median OS of 5.9,11.5, 17.2, and 23.4months, respectively (p < 0.001). In multivariate analysis of OS, only age (³70 versus < 70 years, HR:1.71, 95% CI:1.25-2.35, p < 0.001), KPS ( < 70 versus ³70, HR:1.71, 95% CI:1.26-2.31, p < 0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p = 0.037) remained statistically significant. In patients with a Lung-molGPA score £2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.9vs 12.8vs 4.5months, p = 0.021) and prognostic implications (Leu858Arg versus exon 19 deletions, HR: 1.85, 95% CI: 1.20-2.84, p = 0.005; other versus exon 19 deletions, HR:2.18, 95% CI:1.11-4.26, p = 0.023). Conclusions: Different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

scholarly journals Title: Lung-molGPA in EGFR-mutated Adenocarcinoma: Prognostic Implications of Molecular Subtypes and Targeted Therapies

2020 ◽  
Author(s):  
Feng-Che Kuan ◽  
Chung-Sheng Shi ◽  
Wei-Hsun Yang ◽  
Meng-Hung Lin ◽  
Hung-Yi Lai ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Molecular Subtypes ◽  
Egfr Mutations ◽  
Rare Mutations ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Cox Proportional Hazard Models ◽  
Prognostic Implications ◽  
Egfr Mutated ◽  
Exon 19

EGFR mutations are heterogenous but all carry the same weighting in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 256 patients were included with a median overall survival (OS) of 17.2 months. In multivariate analysis of OS, only age (70 versus &amp;lt;70 years, HR:1.71, 95% CI:1.25-2.35, p&amp;lt;0.001), KPS (&amp;lt;70 versus 70, HR:1.71, 95% CI:1.26-2.31, p&amp;lt;0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p=0.037) remained statistically significant. In patients with a Lung-molGPA score 2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.8 vs 12.4 vs 12.1 months, p=0.021). In conclusion, different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

Germline BRCA1/2, PALB2, and ATM mutations in 3,030 patients with pancreatic adenocarcinoma: Survival analysis of carriers and noncarriers.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 280-280
Author(s):  
Pashtoon Murtaza Kasi ◽  
Fergus Couch ◽  
William R Bamlet ◽  
Chunling Hu ◽  
Steven Hart ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Pancreatic Adenocarcinoma ◽  
Final Analysis ◽  
Parp Inhibitors ◽  
P Value ◽  
Pathogenic Variants ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Before And After ◽  
Brca1 Brca2

280 Background: Patients with pancreatic adenocarcinoma (PDAC) can have mutations in breast cancer associated genes ( BRCA1/2) and other homologous recombination (HR) pathway genes. The therapeutic significance of these mutations for PDAC patients is not yet established. We performed a comprehensive survival analysis of 3,030 unselected PDAC patients comparing non-carriers and carriers of BRCA1/2, PALB2, and ATM mutations. Methods: We analyzed germline DNA samples and outcomes from confirmed PDAC patients recruited from 1999-2014 into the Mayo Clinic SPORE in Pancreatic Cancer registry. A total of 3,046 genomic DNA samples were analyzed by next generation sequencing. All pathogenic variants were validated by Sanger sequencing. Survival analysis of PDAC patients with and without BRCA1, BRCA2, PALB2, or ATM germline mutations was performed using the Kaplan-Meier method and log-rank tests. Hazard ratios (HR) were calculated using Cox proportional hazard modeling adjusted for co-variates including age, sex, and stage. A p-value < 0.05 was considered statistically significant. Pre- and post-FOLFIRINOX eras were defined as before and after June 1, 2011. Results: A total of 139 (4.6%) patients were noted to have deleterious mutations in BRCA1, BRCA2, PALB2, or ATM genes. After exclusion of patients with missing data, final analysis was restricted to 2,452 PDAC patients. Overall survival was slightly better (14.2 months versus 11.3 months) in patients with mutations as compared to those without mutations, although this finding was not statistically significant (p = 0.07). When stratified by FOLFIRINOX era, 40 patients with these mutations in the post-FOLFIRINOX era had better outcomes than 668 non-carriers (adjusted HR 0.62; 95% CI 0.43-0.89; p = 0.0062). Conclusions: Deleterious germline BRCA1/2, PALB2, and ATM mutations were seen in approximately 5% of patients with PDAC. Post-FOLFIRINOX era patients with these mutations had improved outcomes, possibly secondary to exposure to DNA-damaging chemotherapies. Germline screening of PDAC patients and development of trials incorporating this information (e.g., PARP inhibitors) has potential value for PDAC patients.

D2-40-positive lymphatic vessel invasion is not a poor prognostic factor in stage I lung adenocarcinoma

2013 ◽  
Vol 63 (4) ◽  
pp. 201-205 ◽  
Author(s):  
Kei Shimizu ◽  
Kazuhito Funai ◽  
Haruhiko Sugimura ◽  
Keigo Sekihara ◽  
Akikazu Kawase ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lung Adenocarcinoma ◽  
Lymphatic Vessel ◽  
Lymphatic Vessel Invasion ◽  
Stage I ◽  
Poor Prognostic Factor ◽  
Vessel Invasion

scholarly journals Association between type 2 diabetes and osteoporosis risk: A representative cohort study in Taiwan

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254451
Author(s):  
Hsin-Hui Lin ◽  
Hsin-Yin Hsu ◽  
Ming-Chieh Tsai ◽  
Le-Yin Hsu ◽  
Kuo-Liong Chien ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Anatomical Therapeutic Chemical ◽  
Osteoporotic Fractures ◽  
Research Database ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Event Rates ◽  
Osteoporosis Risk

Although previous studies have investigated the relationship between fracture risk and type 2 diabetes (T2D), cohort studies that estimate composite osteoporosis risk are lacking. This retrospective cohort study sought to determine the risk of osteoporosis in Taiwanese patients with T2D. Patients diagnosed with T2D between 2002 and 2015 identified through the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia were included. A total of 1690 men and 1641 women aged ≥40 years linked to the National Health Insurance Research Database (NHIRD) were followed up to the end of 2015 to identify the incidences of osteoporosis through ICD9-CM codes for osteoporosis or osteoporotic fractures or usage of anti-osteoporotic agents according to Anatomical Therapeutic Chemical codes determined from NHIRD. The person year approach and Kaplan–Meier analysis were then used to estimate the incidences and cumulative event rates, whereas the Cox proportional hazard model was used to calculate adjusted hazard ratios (HR) for osteoporosis events. A total of 792 new osteoporosis events were documented over a median follow-up duration of 13.6 years. Participants with T2D had higher osteoporosis risk [adjusted HR: 1.37, 95% confidence interval (CI): 1.11–1.69] compared with those without T2D. Subgroup analyses revealed that age had a marginally significant effect, indicating that T2D had a more pronounced effect on osteoporosis risk in younger population (<65 years old). No difference was found between patients stratified according to sex. In conclusion, T2D was significantly associated with increased osteoporosis risk, especially in younger participants.

scholarly journals Influence of Sex on Survival Rates of HPV Positive Oropharyngeal Cancers

2021 ◽  
Author(s):  
Sally H Preissner ◽  
Susanne Nahles ◽  
Saskia Preissner ◽  
Max Heiland ◽  
Benedicta Beck-Broichsitter ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Survival Rates ◽  
Dorsal Surface ◽  
Hpv Infection ◽  
Malignant Neoplasms ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Hpv Status ◽  
Icd 10 ◽  
Male Patients

Abstract The role of human papillomavirus (HPV) status for the prognosis of oropharyngeal cancers (OPCs) is discussed controversially. Here, we present an analysis of about 144,969 head and neck cancer cases (ICD-10 codes: C00-C13) with a sub-cohort of 62,775 tumor cases of the oropharynx (C02, C09, C10). To this end, de-identified data from electronic health records (EHRs) of about 40 health care organizations from 30 different countries were used. Odds ratios (ORs), hazard ratios (HRs) and Kaplan-Meier analyses were used to compare outcomes between different cancer entities of neoplasms of the dorsal surface, of the tongue (C02), of tonsils (C09) and of the oropharynx (C10) of females and males with and without HPV infection. To avoid the bias from different age-distributions, the cohorts were balanced using propensity score matching.The 5-year survival rate for HPV positive patients is somewhat better than for HPV negative patients but for age- and sex-balanced cohorts there remains no significant advantage for HPV positive patients (HR 1.126 (0.897-1.413). Looking at the different entities and HPV status for age-matched male and female patients separately, HPV is a significantly positive prognostic factor for females in all entities, whereas for male patients it is only a positive prognostic factor for malignant neoplasms of oropharynx (C10) (HR 1.077 (0.602-1.926)).

Immune-related adverse events (irAEs) among urothelial carcinoma (UC) patients treated with PD-1 VS PD-L1 inhibitors: A real-world observational study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17017-e17017
Author(s):  
Saby George ◽  
Elizabeth Bell ◽  
Nicole Engel-Nitz ◽  
John C White ◽  
Lincy S. Lal ◽  
...  
Keyword(s):  
Observational Study ◽  
Real World ◽  
A Priori ◽  
P Value ◽  
Research Database ◽  
Limited Information ◽  
Kaplan Meier ◽  
New Treatment ◽  
Lower Incidence Rate ◽  
Time To Onset

e17017 Background: Anti-PD-1/PD-L1 agents are US FDA-approved for patients with advanced or metastatic UC, but limited information exists on real world irAEs among this patient population. We examined the rates and time to onset of select irAEs in UC patients receiving PD-L1s vs PD-1s in the real world. Methods: This observational study included US commercial and Medicare Advantage health plan members from Optum Research Database with UC and treated with a PD-1 or PD-L1 agent between 01-Sep-14 and 30-Apr-19. Baseline characteristics were assessed ≤ 6-months prior to the first claim for anti-PD-1/PD-L1. 21 irAEs were chosen a priori based on the ASCO clinical guideline on irAE management, clinical input, frequency, and cost of treatment. Patients were followed for newly occurring irAEs, based on claims ICD codes, during the PD-1/PD-L1 therapy and up to 180 days after if no new treatment, study period end, death, or disenrollment. Kaplan-Meier method was utilized to calculate time to onset of irAEs. Results: The study included 240 patients receiving PD-L1s and 317 receiving PD-1s. Baseline demographics were similar (Table). The most common irAEs were 1) thyroid disorders, 2) impaired ventricular function with heart failure and vasculitis, 3) rash, and 4) nephritis. UC patients receiving PD-L1s had a lower rate of irAEs vs PD-1s, mainly driven by lower rates of hematologic and endocrine toxicities (Table). UC patients receiving a PD-L1 also had longer time to irAE onset (p-value = 0.05). Conclusions: UC patients receiving PD-L1s had a lower incidence rate of irAEs and longer time to irAE onset than patients on PD-1s. Findings suggest patients receiving PD-1s may require more intense monitoring for irAEs than patients taking PD-L1s. [Table: see text]

Significance of scores generated by a cancer therapy matching engine for patient outcomes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15099-e15099
Author(s):  
Eden Romm ◽  
Emiliya Davtyan ◽  
Kevin Bush ◽  
Ramsay Sutton ◽  
Itamar Patek ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Progression Free Survival ◽  
Sampling Bias ◽  
P Value ◽  
Cancer Drugs ◽  
Sequencing Data ◽  
Ampullary Adenocarcinoma ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Suitable Treatment

e15099 Background: Oncologists need effective precision medicine tools to navigate the myriad of therapeutic options to best address each patient’s unique tumor profile. Described here is a digital solution, which analyzes tumor data (NGS, other), scores and ranks known and novel matching combinations of cancer drugs with molecular-level precision for decision support. Methods: All data was acquired through the published supplement of the I-PREDICT study (NCT 02534675). Patients with available progression-free survival (PFS) and sequencing data who received <3 matched non-experimental cancer drugs in combination were evaluated (n=77). To determine each patient’s score (represented as %), the system used expert-curated content integrated within an artificial intelligence (AI) reasoning framework that computed how well the therapy each patient received matched their tumor’s genomic profile. The dataset was binarized at 36 possible thresholds, which split the data into higher vs. lower score bins. Relationship with PFS and the degree of separation between bins were evaluated with Kaplan-Meier plots and assessed in terms of p-value, hazard ratios and related confidence intervals (Table). To prevent sampling bias at high and low thresholding extremes of this dataset, a limit was imposed of >25 patients per bin. Results: Significant separation between high and low scoring bins was observed in >73% of evaluable thresholds. The mean p-value was 0.044 (range, 0.011-0.13). The hazard ratio was consistently ̃2 (mean, 1.81, range, 1.50-2.08). A similar level of statistical significance was observed for all thresholds up to and including bracketing of 60% (Table). Despite the small size of this dataset and the disparity between sample counts per bin seen at the end of the range, significant p-values of <0.05 were achieved. Ex., a 68-year-old female with an ampullary adenocarcinoma harboring ERBB2, CDK6 and other alterations, received a combination of pertuzumab and trastuzumab scoring 56%. The PFS was 745+ days. However, had palbociclib, ribociclib, or abemaciclib been added to this combination, the resulting 3-drug options would have scored even higher due to also targeting CDK6. Conclusions: Our study indicates that therapies with higher scores were predictive of better PFS, while lower scores were predictive of worse PFS. The results will be validated on larger datasets but are already demonstrative of the utility of this system in providing digital guidance to oncologists in selecting the most suitable treatment. [Table: see text]

scholarly journals The Temporal Relationship between Selected Mental Disorders and Substance-Related Disorders: A Nationwide Population-Based Cohort Study

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Mu-Lin Chiu ◽  
Chi-Fung Cheng ◽  
Wen-Miin Liang ◽  
Pen-Tang Lin ◽  
Trong-Neng Wu ◽  
...  
Keyword(s):  
Mental Disorders ◽  
Personality Disorders ◽  
Large Scale ◽  
Later Life ◽  
Population Based ◽  
Research Database ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Taiwan National Health Insurance ◽  
Substance Related Disorders

Introduction. Previous studies have examined the association between specific mental disorders, particularly mood and anxiety disorders, and substance-related disorders; but the temporal link between them remains unclear. This study aimed to examine whether individuals with specific mental disorders, including affective psychoses, neurotic disorders, schizophrenia, personality disorders, and adjustment reaction, have higher risks for subsequently developing substance-related disorders compared to those without. Methods. A large-scale study with longitudinal data was conducted using the Taiwan National Health Insurance Research Database (NHIRD) consisting of 2,000,118 patients’ medical records from 2000 to 2009. A total of 124,423 people diagnosed with selected mental disorders and the same number of people without the diagnoses of the selected disorders were identified between January 1, 2001, and December 31, 2006, and followed up for the diagnoses of substance-related disorders till the end of 2009. We estimated the risk for subsequently developing substance-related disorders among patients with the selected mental disorders compared to those without by using Cox proportional hazard models. The cumulative incidence of substance-related disorders was calculated using the Kaplan-Meier method. Results. The risk for developing substance-related disorders in patients with selected mental disorders is about 5 times (HR=5.09, 95% CI: 4.74-5.48) higher than those without after adjusting for potential confounding variables. From the multivariate analyses of subsamples stratified by age, sex, and urban and income levels, we found all adjusted hazard ratios were significantly higher than 1.0, ranging from 2.12 (95% CI: 1.72-2.62) to 14.55 (95% CI: 7.89-26.83). For children and adolescents aged 10-19 years, those with specific mental disorders had 14.55-fold higher risk for developing substance-related disorders in later life compared to their counterparts. Furthermore, patients with personality disorders had the highest risk (HR=25.05). Conclusions. The earlier onset of the selected mental disorders is a potential risk for developing substance-related disorders in later life, particularly for personality disorders. Health professionals should pay more attention to this at-risk population, especially to adolescents with mental disorders.

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