Natural history of patients (pts) with advanced cholangiocarcinoma (CCA) with FGFR2 gene fusion/rearrangement or wild-type (WT) FGFR2.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4089-4089
Author(s):  
Rachna T. Shroff ◽  
Jessica Rearden ◽  
Ai Li ◽  
Susan Moran ◽  
Stacie Peacock Shepherd ◽  
...  
Keyword(s):  
Natural History ◽  
Advanced Disease ◽  
Late Onset ◽  
Stage Iv ◽  
Primary Objective ◽  
Initial Diagnosis ◽  
Wild Type ◽  
Real World Data ◽  
Comprehensive Genomic Profiling ◽  
History Of

4089 Background: CCA is a rare, heterogeneous malignancy with poor prognosis due to late onset of symptoms and relative resistance to available therapies. FGFR2 fusions are common, occurring in 10–16% of intrahepatic CCA (iCCA). There is increasing awareness of the importance of molecular profiling to inform treatment choices, although real-world data (RWD) are lacking on the natural history of pts with CCA and FGFR2 fusions/rearrangements receiving therapies for advanced disease. This retrospective, observational, natural history study used a nationwide (US-based) de-identified clinico-genomic database (CGDB) to compare overall survival (OS) in pts with advanced CCA and FGFR2 fusions/rearrangements vs. those with wild-type (WT) FGFR2. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine CCA CGDB (FH-FMI-CGDB). The data originated from approximately 280 US cancer clinics (̃800 sites of care). Pts were ≥18y of age, had chart-confirmed advanced CCA, comprehensive genomic profiling, and ≥2 visits within the Flatiron Health network since Jan 1, 2011. Primary objective: evaluate OS in pts with FGFR2 fusions/rearrangements and WT FGFR2 from the index date (date of diagnosis of advanced CCA) to date of death from any cause. A key secondary objective was to evaluate the influence of FGFR status on OS after adjusting for potential prognostic variables. Risk-set adjustment was used to account for left truncation for all time-to-event analyses. Results: As of May 2020, 571 pts from the CCA FH-FMI-CGDB met the inclusion criteria; 75 pts with FGFR2 fusions/rearrangements (median age 63y; 64% female; 95% iCCA; 68% stage IV at initial diagnosis), and 496 pts FGFR2 WT (median age 65y; 48% female; 74% iCCA; 55% stage IV at initial diagnosis). Median OS was numerically higher, but not statistically different, for pts with FGFR2 fusions/rearrangements vs FGFR2 WT (12.1m [95% CI 8.5−17.1] vs 7.1m [95% CI 5.7−8.8]; log rank p = 0.184). Median OS was also numerically higher, but not statistically different, for FGFR2 fusions/rearrangements vs FGFR WT in the subset of 437 pts with iCCA (12.1m [95% CI 8.4−17.1] vs 7.8m [95% CI 6.1−10.0]; log rank p = 0.375). FGFR2 status was not a significant factor contributing to OS in univariate, bivariate, or multivariate models after adjusting for potential prognostic covariates. Conclusions: This analysis of RWD did not demonstrate a clear survival advantage for pts with FGFR2 fusions/rearrangements vs FGFR2 WT CCA receiving therapies for advanced disease, although a non-significant trend towards longer OS was observed in pts with FGFR2 fusions/rearrangements. FGFR2 status was not a significant predictor of OS after adjusting for potential prognostic covariates. An additional sub-analysis is ongoing to determine OS from time of initiation of second-line therapy in pts with FGFR2 fusions/rearrangements.

Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
L Obici ◽  
R Mussinelli ◽  
M Basset ◽  
G Manfrinato ◽  
...  
Keyword(s):  
Natural History ◽  
Median Survival ◽  
Troponin I ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Wild Type ◽  
Staging Systems ◽  
Significant Difference ◽  
History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P<0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P<0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

scholarly journals Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System

2016 ◽  
Vol 68 (10) ◽  
pp. 1014-1020 ◽  
Author(s):  
Martha Grogan ◽  
Christopher G. Scott ◽  
Robert A. Kyle ◽  
Steven R. Zeldenrust ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Natural History ◽  
Risk Stratification ◽  
Cardiac Amyloidosis ◽  
Staging System ◽  
Wild Type ◽  
History Of

scholarly journals Natural history ofMycobacterium aviumcomplex lung disease in untreated patients with stable course

2017 ◽  
Vol 49 (3) ◽  
pp. 1600537 ◽  
Author(s):  
Ji An Hwang ◽  
Sunyoung Kim ◽  
Kyung-Wook Jo ◽  
Tae Sun Shim
Keyword(s):  
Body Mass Index ◽  
Natural History ◽  
Lung Disease ◽  
Body Mass ◽  
Initial Diagnosis ◽  
Acid Fast Bacilli ◽  
Sputum Conversion ◽  
History Of ◽  
Negative Sputum ◽  
Systemic Symptoms

Little is known about the long-term natural history ofMycobacterium aviumcomplex lung disease (MAC-LD) in untreated patients with stable course.The aim of this study was to investigate the natural course of untreated stable MAC-LD, with a focus on factors associated with clinical deterioration, spontaneous sputum conversion and prognosis.Of 488 patients diagnosed with MAC-LD between 1998 and 2011, 305 patients (62.5%) showed progressive MAC-LD resulting in treatment initiation within 3 years of diagnosis and 115 patients (23.6%) exhibited stable MAC-LD for at least 3 years with a median follow-up duration of 5.6 years. Patients with stable MAC-LD were more likely to have higher body mass index and less systemic symptoms at initial diagnosis compared with patients with progressive MAC-LD, while positive sputum acid-fast bacilli smear, fibrocavitary type and more extensive disease in radiological findings were more associated with progressive MAC-LD. Of the untreated patients with stable MAC-LD, 51.6% underwent spontaneous sputum conversion, with younger age, higher body mass index and negative sputum acid-fast bacilli smear at initial diagnosis found to be predictors of this occurrence.Advanced age, fibrocavitary type and abnormal pulmonary function were negative prognostic factors for survival in patients with stable MAC-LD.

Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas

2012 ◽  
Vol 83 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Haruki Koike ◽  
Fumiaki Tanaka ◽  
Rina Hashimoto ◽  
Minoru Tomita ◽  
Yuichi Kawagashira ◽  
...  
Keyword(s):  
Natural History ◽  
Late Onset ◽  
Familial Amyloid Polyneuropathy ◽  
History Of ◽  
Amyloid Polyneuropathy ◽  
Endemic Areas

The natural history of late-onset epilepsy secondary to vascular disease

1989 ◽  
Vol 80 (6) ◽  
pp. 524-526 ◽  
Author(s):  
D. R. Fish ◽  
D. H. Miller ◽  
R. C. Roberts ◽  
J. D. Blackie ◽  
R. W. Gilliatt
Keyword(s):  
Natural History ◽  
Vascular Disease ◽  
Late Onset ◽  
History Of

Natural history of late-onset GM2 gangliosidosis: Four years of data collected at NTSAD annual conferences

2020 ◽  
Vol 129 (2) ◽  
pp. S136
Author(s):  
Camille Rochmann ◽  
Pascal Minini ◽  
Julie Kissell ◽  
Gerald Cox ◽  
Florian Eichler ◽  
...  
Keyword(s):  
Natural History ◽  
Late Onset ◽  
Gm2 Gangliosidosis ◽  
History Of

The Natural History of Late Onset Tay-Sachs Disease

2012 ◽  
Vol 105 (2) ◽  
pp. S67
Author(s):  
Padmaja Yerramilli-Rao ◽  
Ourania Giannikopoulos ◽  
Kim Kublis ◽  
Jessica Pan ◽  
Florian Eichler
Keyword(s):  
Natural History ◽  
Late Onset ◽  
Tay Sachs Disease ◽  
History Of

Clinical outcome of sequential chemotherapy in metastatic and/or recurrent gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15521-e15521
Author(s):  
Y. Moon ◽  
S. Rha ◽  
H. Jeung ◽  
S. Shin ◽  
N. Yoo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Natural History ◽  
Performance Status ◽  
Stage Iv ◽  
Poor Performance ◽  
Median Number ◽  
Care Group ◽  
Metastatic Site ◽  
Stage Iv Gastric Cancer ◽  
History Of

e15521 Background: Little is known about data on subsequent chemotherapy (CTx) following 1st-line CTx in stage IV gastric cancer. The purpose of this study was to analyze the natural history of stage IV gastric cancer with sequential CTx Methods: A total of 532 patients (pts) with unresectable gastric adenocarcinoma were studied. They were managed with a strategy of maximal administration of CTx only if pts’ general conditions were allowed. Response evaluation was performed by RECIST every 2 cycles. Response of unmeasurable lesions was dichotomized only into stable disease or progressive disease. Results: When pts were divided into CTx group (460 of 532, 87%) and best supportive care group (BSC; 72 of 532, 13%) resulting from poor performance/pt's refusal/comorbidity (31/23/18), the former had younger age (p = 0.046), better performance (p < 0.001), and less advanced metastatic sites (p = 0.001) than the latter. Median overall survivals from diagnosis of unresectable cancer were 12.0/13.3/2.5 months for overall/CTx/BSC, respectively. 87%/47%/23% of the whole pts received 1st/2nd/3rd-line CTx, respectively. Median number of regimens delivered was 2. Maximally 5th-line CTx was given to 15 pts (3%). Response and disease control rates were 21.7%/12.5%/11.8% and 79.4%/56.3%/49.4% for 1st/2nd/3rd lines, respectively. Median progression-free and overall survivals from CTx were 5.5/3.4/2.5 months and 12.1/7.9/5.5 months for 1st/2nd/3rd lines, respectively. The most common cause of discontinuation of CTx was disease progression (68%/74%/70%) followed by pt's refusal (22%/13%/12%) for 1st/2nd/3rd lines, respectively. Prognosticators were performance status, histology, metastatic site, and CTx before 1st or 2nd line. Conclusions: When pts with unresectable gastric cancer were managed with a strategy of maximal administration of CTx, a considerable number of pts could receive 2nd or 3rd line CTx, showing modest activity. Performance status and metastatic site were consistent prognosticators even if lines changed. Our data on the natural history of stage IV gastric cancer with sequential CTx may suggest that clinical trials can be performed in a 2nd or 3rd line setting as well. No significant financial relationships to disclose.

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