scholarly journals BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups

2014 ◽  
Vol 211 (4) ◽  
pp. 669-683 ◽  
Author(s):  
Marie-Luise Berres ◽  
Karen Phaik Har Lim ◽  
Tricia Peters ◽  
Jeremy Price ◽  
Hitoshi Takizawa ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
High Risk ◽  
Somatic Mutation ◽  
Risk Groups ◽  
Low Risk ◽  
Braf V600e ◽  
Increased Risk ◽  
Clinical Risk Groups ◽  
Myeloid Neoplasia

Langerhans cell histiocytosis (LCH) is a clonal disorder with elusive etiology, characterized by the accumulation of CD207+ dendritic cells (DCs) in inflammatory lesions. Recurrent BRAF-V600E mutations have been reported in LCH. In this study, lesions from 100 patients were genotyped, and 64% carried the BRAF-V600E mutation within infiltrating CD207+ DCs. BRAF-V600E expression in tissue DCs did not define specific clinical risk groups but was associated with increased risk of recurrence. Strikingly, we found that patients with active, high-risk LCH also carried BRAF-V600E in circulating CD11c+ and CD14+ fractions and in bone marrow (BM) CD34+ hematopoietic cell progenitors, whereas the mutation was restricted to lesional CD207+ DC in low-risk LCH patients. Importantly, BRAF-V600E expression in DCs was sufficient to drive LCH-like disease in mice. Consistent with our findings in humans, expression of BRAF-V600E in BM DC progenitors recapitulated many features of the human high-risk LCH, whereas BRAF-V600E expression in differentiated DCs more closely resembled low-risk LCH. We therefore propose classification of LCH as a myeloid neoplasia and hypothesize that high-risk LCH arises from somatic mutation of a hematopoietic progenitor, whereas low-risk disease arises from somatic mutation of tissue-restricted precursor DCs.

Hematopoietic Stem Cells and Circulating Myelomonocytic Precursors With BRAF-V600E Are Identified In High-Risk Patients and Define LCH As a Myeloid Neoplasia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 103-103
Author(s):  
Karen Phaik-Har Lim ◽  
Tricia L Peters ◽  
Marie-Luise Berres ◽  
Jeremy Price ◽  
Hitoshi Takizawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
High Risk ◽  
Hematopoietic Stem Cells ◽  
Somatic Mutation ◽  
Peripheral Blood ◽  
Risk Groups ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Hematopoietic Stem ◽  
Myeloid Neoplasia

Abstract Background Langerhans Cell Histiocytosis (LCH) is a clonal lymphoproliferative disorder characterized by inflammatory lesions with characteristic CD207+ dendritic cells (DCs). LCH has variable clinical presentations ranging from single lesions to potentially fatal multi-system “High Risk” disease. The etiology of LCH remains elusive, with debate of LCH as an inflammatory versus malignant disorder unresolved. The first recurrent somatic genetic mutation in LCH, BRAF-V600E, was recently reported in 57% of LCH lesions (Badalian-Very et al., 2010). In this study, we investigate the clinical significance of BRAF-V600E and identify cells carrying the mutation to determine the origins of LCH. Methods Lesions, peripheral blood, peripheral monocyte/dendritic cell populations, and hematopoietic stem cells were genotyped for the BRAF-V600E mutation with real-time PCR. The presence of the BRAF-V600E mutation was correlated with clinical variables and analyzed with standard statistical methods. Colony-forming unit assays were used to test the hematopoietic potential of CD34+ cells purified from bone marrow aspirate. Results Lesions from 100 patients with LCH were genotyped, and 64% percent carried the V600E mutation, which localized to the infiltrating CD207+ DCs. In 16 patients with more than one lesion, BRAF status remained fixed, suggesting somatic mutation is an early event. BRAF-V600E did not define specific clinical risk groups or impact overall survival, but it was associated with approximately two-fold higher risk of relapse (p=0.04). Furthermore, the cellular compartment carrying the mutation correlated with disease severity: The ability to detect BRAF-V600E in circulating mononuclear cells defined High-Risk LCH with 100% sensitivity/87%specificity. The ability to detect BRAF-V600E in circulating blood cells in patients with High-Risk LCH defined clinically detectable disease with 97% sensitivity/100% specificity. Analysis of sorted populations localized the BRAF-V600E to CD11c+ and CD14+ fractions in peripheral blood, and to CD34+ cells in bone marrow. Potential of the CD34+ hematopoietic stem cells with the BRAF-V600E mutation to differentiate into myeloid precursors was verified with in vitrocolony-forming unit assays. Conclusions The molecular foothold of BRAF at the base of LCH pathogenesis will allow therapeutic strategies to move beyond empiric observation to risk-stratified and targeted approaches. Furthermore, effectiveness of therapy may be tested by following BRAF-V600E in peripheral blood cells as a marker of residual disease. We hypothesize that High-Risk LCH arises from somatic mutation of an immature myelomonocytic precursor cell, where Low-Risk disease arises from somatic mutation of tissue-restricted DC precursors. We therefore propose classifying LCH as a bone fide myeloid neoplasia in which BRAF-V600E expression in precursor versus mature dendritic cells defines clinically distinct risk-groups. Disclosures: No relevant conflicts of interest to declare.

The Glasgow whipple risk score to predict pancreas-specific complications after pancreaticoduodenectomy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 394-394
Author(s):  
Lavanniya Kumar Palani Velu ◽  
Vishnuvardhan Chandrabalan ◽  
Ross Carter ◽  
Colin McKay ◽  
Donald McMillan ◽  
...  
Keyword(s):  
High Risk ◽  
Serum Amylase ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Prolonged Stay ◽  
Increased Risk ◽  
Clinically Significant ◽  
Serum Crp

394 Background: Pancreas-specific complications (PSC), comprising postoperative pancreatic fistula, post-pancreatectomy haemorrhage, and intra-abdominal collections, are drivers of morbidity following pancreaticoduodenectomy (PD). Intra-operatively derived pancreatic gland texture is a major determinant of postoperative PSC. We have previously demonstrated that a postoperative day 0 (PoD0) serum amylase ≥ 130 IU/L is an objective surrogate of pancreatic texture, and is associated with PSC. We sought to refine the PSC risk prediction model by including serial measurements of serum C-reactive protein (CRP). Methods: 230 consecutive patients undergoing PD between 2008 and 2014 were included in the study. Routine serum investigations, including amylase and CRP were performed from the pre-operative day. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP associated with clinically significant PSC. Results: 95 (41.3%) patients experienced a clinically significant PSC. ROC analysis identified post-operative day 2 (PoD2) serum CRP of 180 mg/L as the optimal threshold (P=0.005) associated with clinically significant PSC, a prolonged stay in critical care (P =0.032), and a relaparotomy (P = 0.045). Patients with a PoD0 serum amylase ≥ 130 IU/L who then developed a PoD2 serum CRP ≥ 180 mg/L had a higher incidence of postoperative complications. Patients were categorised into high, intermediate and low risk groups based on PoD0 serum amylase and PoD2 serum CRP. Patients in the high risk group (PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l) had significantly higher incidence of PSC, a return to theatre, prolonged lengths stay (all P≤ 0.05) and a four-fold increase in perioperative mortality compared patients in the intermediate and low risk groups (7 deaths in the high risk group versus 2 and nil in the intermediate and low risk groups respectively). Conclusions: A high risk profile, defined as PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l, should raise the clinician’s awareness of the increased risk of clinically significant PSC and a complicated postoperative course following pancreaticoduodenectomy.

scholarly journals Serbian lymphoma study group: Demografic characteristics of 257 patients with follicular lymphoma

2015 ◽  
Vol 72 (6) ◽  
pp. 483-488
Author(s):  
Olivera Simonovic ◽  
Lana Macukanovic-Golubovic ◽  
Bosko Andjelic ◽  
Darko Antic ◽  
Biljana Mihaljevic
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Treatment Decision ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Prognostic Groups

Background/Aim. Follicular lymphoma (FL) is a B-cell tumor usually with indolent clinical course, yet in some cases the course of the disease can be very aggressive. The aim of the re-search was to determine distribution of patients into prognostic groups based on the International Prognostic Index (IPI) and Folicular Lymphoma International Prognostic Index (FLIPI) criteria, as well as to determine the importance of classifying patients into the prognostic groups, since this could potentially have the influence on selection of the treatment modality. Methods. The retrospective study was performed on 257 patients with follicular lymphoma diagnosed between January 2000 and April 2011. Results. Based on the IPI score, 153 (59.53%) patients had low risk, 57 (22.18%) low intermediate risk, 15 (5.84%) high intermediate risk, 9 (3.50%) high risk, whereas the classification of 23 patients diagnosed with FL remained with unknown risk according to the IPI. Based on the FLIPI prognostic index, 113 (43.97%) patients had low risk, 70 (27.24%) intermediate risk and 51 (19.84%) high risk, whereas the classification of 23 (8.95%) patients remained unknown. On the basis of the FLIPI 2 prognostic index, 48 (18.68%) patients had low risk, 145 (56.42%) intermediate risk and 41 (15.95%) high risk. The classification into prognostic groups for 23 (8.95%) patients remained unknown. According to the IPI, FLIPI and FLIPI 2 there were the patients that required treatment in all the risk groups. Conclusion. The FLIPI and FLIPI 2 effectively identify patients at high risk, thus helping in treatment decision for each single patient.

scholarly journals Identification of a Nine Immune-Related lncRNA Signature as a Novel Diagnostic Biomarker for Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Mengqin Yuan ◽  
Yanqing Wang ◽  
Qinqian Sun ◽  
Shiyi Liu ◽  
Shu Xian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Risk Score ◽  
Prognostic Value ◽  
Expression Profiles ◽  
Risk Groups ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Potential Biomarker ◽  
Increased Risk

Hepatocellular carcinoma (HCC) ranks fifth among common cancers and is the second most common cause of cancer-related mortality worldwide. This study is aimed at identifying an immune-related long noncoding RNA (lncRNA) signature as a potential biomarker with prognostic value to improve early diagnosis and provide potential therapeutic targets for HCC patients. The subjects of this study were HCC samples with complete transcriptome data and clinical information downloaded from The Cancer Genome Atlas (TCGA) database. We then extracted the immune-related mRNA and lncRNA expression profiles. Based on the expression profiles of immune-related lncRNAs, we identified a nine-lncRNA signature that was related to the progression of HCC. The risk score was calculated based on the expression level of the nine lncRNAs of each sample, which divided patients into high-risk and low-risk groups. We found that the increased risk score was associated with a poor prognosis of HCC patients. To assess the accuracy of the survival model, we calculated a receiver operating characteristic (ROC) for validation. The curve showed that the area under the curve (AUC) for the risk score was 0.792. Besides, both principal component analysis (PCA) and gene set enrichment analysis (GSEA) were further used for functional annotation. We found that the distribution patterns were different between the low-risk and high-risk groups in PCA, and the underlying mechanism by which the nine lncRNAs promoted the progression of HCC involved an abnormal immune status. Finally, we analyzed the infiltration of twenty-nine kinds of immune cells and the activation of immune function in HCC using the ssGSEA algorithm. The results showed that aDCs, iDCs, macrophages, Tfh, Th1, Treg, and NK cells were correlated with the progress of HCC patients. And the immune functions including APC costimulation, CCR, check point, HLA, MHC class I, and Type II IFN responses were also significantly different between the high-risk and low-risk groups. In conclusion, our study identified a nine-lncRNA signature with potential prognostic value for patients with HCC, which could be used as a new biomarker for the diagnosis and immunotherapy of HCC.

External validation of two predictive scores of chemotherapy toxicities among older patients with solid cancer, from ELCAPA prospective cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12050-12050
Author(s):  
Maxime Frelaut ◽  
Philippe Caillet ◽  
Stephane Culine ◽  
Elena Paillaud ◽  
Christophe Tournigand ◽  
...  
Keyword(s):  
High Risk ◽  
Prospective Cohort ◽  
Older Patients ◽  
Risk Groups ◽  
Low Risk ◽  
Solid Cancer ◽  
Cancer Type ◽  
Severe Toxicity ◽  
Increased Risk ◽  
Grade 3

12050 Background: Severe chemotherapy toxicities are frequent among older patients, and may have a major impact on mortality, comorbidities, and quality of life. Two scores were developed to predict severe toxicities: Chemotherapy Risk Assessment Scale for High-age patients (CRASH) score, and Cancer and Aging Research Group Study (CARG) score. The main objective of the present study was to evaluate the predictive value of both scores on an external cohort. Secondary objective was to identify individual predictive factors of severe chemotherapy toxicities. Methods: The Elderly Cancer Patients (ELCAPA) survey consists in a prospective cohort including patients aged 70 years or older referred for a geriatric assessment (GA) before anticancer treatment, such as chemotherapy for solid cancer. CARG and CRASH score were retrospectively collected. Main endpoint was grade 3/4/5 toxicities for CARG-score, hematologic grade 4/5 and non-hematologic grade 3/4/5 toxicities for CRASH-score. Calibration and discrimination (Area Under ROC Curve, AUC) were evaluated. Results: From July 2010 to March 2017, 248 patients were included. Among them, 150 (61%) experienced severe toxicity as defined in CARG study, and 126 (51%) as defined in CRASH study. There was no increased risk of toxicity in intermediate and high risk groups of CARG-score compared to low risk group (OR = 0.3, IC95% [0.1 – 1.4], p= 0.1; and OR = 0.4, IC95%[0.1 – 1.7], p= 0.2 respectively, AUC-ROC = 0.55). Similarly, there was no more risk of severe toxicities in intermediate low, intermediate high, and high risk groups compared to low risk groups of CRASH combined score (respectively OR = 1, IC95% [0.3 – 3.6], p= 0.99; OR = 1, IC95% [0.3 – 3.4], p= 0.9; OR = 1.5, IC95% [0.3 – 8.1], p= 0.67; AUC-ROC = 0.52). A multivariate predictive model including cancer type, performance status (PS 0 vs. PS 1-2), number of severe comorbidities (Cumulative Illness Rating Scale for Geriatrics, CIRS-G, ≥1 grade 3 or 4 comorbidity), body mass index (BMI > 25 kg/m² protective vs. normal BMI), and Chemotox score (1 vs. 0) had an AUC of 0.78. Conclusions: Neither CARG nor CRASH score was predictive of severe chemotherapy toxicities in the ELCAPA cohort. There is a need to identify new predictors of chemotherapy toxicity in older patients with solid cancers.

scholarly journals Age dependence of modern clinical risk groups for localized prostate cancer – a population-based study

2019 ◽  
Author(s):  
Minh-Phuong Huynh-Le ◽  
Tor Åge Myklebust ◽  
Christine H. Feng ◽  
Roshan Karunamuni ◽  
Tom Børge Johannesen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Clinical Risk ◽  
High Risk Disease ◽  
Clinical Risk Groups

AbstractBackgroundOptimal prostate cancer (PCa) screening strategies will focus on men most likely to have potentially-lethal, localized disease. Age-specific incidence rates (ASIRs) for clinical risk groups could guide risk-stratified screening.ObjectiveDetermine ASIRs and proportions of PCa diagnoses in Norway for modern risk-group and Gleason score categories.Design, Setting, and ParticipantsAll men diagnosed with PCa in Norway in 2014-2017 (n=20,356).Outcome Measurements and Statistical AnalysisPatients were assigned to clinical risk groups: low, favorable-intermediate, unfavorable-intermediate, high, regional, and metastatic, using Gleason score and clinical stage. Associations were assessed between age and (1) Gleason score (including Gleason 3+4 and 4+3) and (2) PCa risk group. Risk-group ASIRs were calculated by multiplying the overall Norwegian ASIR by the proportions observed for each category.ResultsOlder age was significantly associated with higher Gleason score and more advanced disease. For example, among men aged 55-59, 65-69, 75-79, and 85-89 years, the percentage with Gleason 8-10 disease was 16.5%, 23.4%, 37.2%, and 59.9%, respectively (p<0.001); the percentage with at least high-risk disease was 29.3%, 39.1%, 60.4%, and 90.6%, respectively. Corresponding percentages for low-risk PCa were 24.0%, 17.9%, 10.2%, and 4.1% (p<0.001). The respective maximum ASIRs (per 100,000 men) for low-risk, favorable-intermediate-risk, unfavorable-intermediate-risk, high-risk, regional, and metastatic disease were: 157.1, 183.8, 194.8, 408.3, 172.3, and 330.0; incidence for low-risk and favorable-intermediate-risk PCa peaked before age 70, while more advanced categories peaked after 70. At age 75-79 years, the ASIR of high-risk disease was approximately 6 times greater than at 55-59 years.ConclusionsRisk of clinically-significant, localized PCa increases with age. Healthy older men may be among those most likely to benefit from PCa screening.

Prediction of Survival in Patients with Myelodysplastic Syndrome According to WHO Classification-Based Prognostic Scoring System (WPSS).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4617-4617
Author(s):  
Jun Ho Jang ◽  
Kihyun Kim ◽  
Chul W. Jung ◽  
Keon Woo Park
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Risk Scores ◽  
The Mean ◽  
Very High

Abstract Background Based upon the classification of FAB criteria, International Prognostic Scoring System(IPSS) has been a standard prognostic model to predict survival and progression in MDS. In 2000, the WHO has formulated a new classification of myelodysplastic syndrome(MDS). The aim of this study was to evaluate the prognostic value of WHO classification-based prognostic scoring system(WPSS) in MDS. Patients and methods One hundred forty-nine patients who were diagnosed as having de novo MDS at the Division of Hematology-Oncology, Samsung medical center, Seoul, Korea, between Dec. 1994 and Feb. 2007, were evaluated retrospectively for clinical and hamatologic features at diagnosis, transfusion dependence, overall survival(OS), and progression to leukemia(LFS). Risk group stratifications in MDS patients were done according to IPSS and WPSS. Results 18 patients(12.1%), 93 patients (62.4%), 29 patients(29%) and 9 patients(6%) had IPSS risk scores of low, intermediate-1(Int-1), intermediate-2(Int-2) and high, respectively. According to WPSS risk scores, 8 patients(5.4%), 30 patients(20.1%), 41 patients(27.5%), 57 patients(38.3%) and 13 patients(8.7%) were classified to very low, low, intermediate, high and very high risk group, respectively. In IPSS, median OSs of low, Int-1, Int-2 and high subgroup were 65.2, 32.9, 14.3 and 9.1 months respectively (p<0.001). According to WPSS, median OSs of very low, low, intermediate, high and very high risk subgroup were not reached, 55.4, 27.4, 19.0 and 6.2 months respectively (p<0.001). Between subgroups classified according to WPSS, significant differences in OS were noted in low vs. intermediate risk group (p=0.047), in intermediate vs. high risk group (p=0.046) and in high vs. very high risk group(p=0.003) but statistically not significant difference in OS was observed between very low and low risk group (p=0.08). The mean and median OS of the lowest risk group(low risk) in IPSS are 65.33 and 55.43 months, respectively. The mean and median OS of the lowest risk group(very low risk) in WPSS are 102.8 months and not reached, respectively. Conclusion These data show that WPSS with five risk groups might provide more refined prognostic stratifications of MDS than IPSS with four risk groups. Especially, new prognostic system appears to discriminate a subset of patients with very low risk, who could have long term survival.

Plasma Biomarker Profiling In Langerhans Cell Histiocytosis: Risk-Stratifying The Inflammatory Storm

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2854-2854
Author(s):  
Miguel Dario Cantu ◽  
Tricia L Peters ◽  
Karen Phaik-Har Lim ◽  
Albert Shih ◽  
Rikhia Chakraborty ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Langerhans Cell Histiocytosis ◽  
Risk Groups ◽  
Langerhans Cell ◽  
Response To Therapy ◽  
Low Risk ◽  
Clinical Risk ◽  
Clinical Risk Groups ◽  
Single Lesion

Abstract Introduction Despite indistinguishable histology and the common feature of Birbeck granules in lesion biopsies, clinical presentation of patients with Langerhans Cell Histiocytosis (LCH) is highly variable, from single lesion cured by curretage, to multi-system disease requiring aggressive chemotherapy or stem cell transplant. Risk stratification for Langerhans Cell Histiocytosis has historically assigned clinical risk groups based on anatomic location and extent of LCH lesions, which is the basis for dose and duration of chemotherpy on recent Histiocyte Society trials. In this study, we test the hypothesis that distinct subgroups of patients with LCH may be identified by relative levels of circulating biomarkers. Methods Pre-therapy plasma was collected on 97 patients with LCH (82 Pediatric: 17 High-Risk, 23 Multisystem/Multifocal “Non-risk”, 42 Single Lesion “Non-risk”; 15 Adult: 5 High-Risk, 5 Multisystem/Multifocal “Non-risk”, 5 Single Lesion “Non-risk”) and 49 control subjects (32 Pediatric, 17 Adult). Quantitative levels of plasma proteins (158 analytes) was determined by multiplex analysis with Millipore MagPix kits and the Luminex plate reader. Data were analyzed with both unsupervised and supervised methodologies. Results Consensus clustering with non-negative matrix factorization (NMF) clusters identified three groups which were analyzed along with clinical categories. Significant clinical variables included age (adult samples clustered in NMF group 1) and LCH risk category (High-Risk LCH samples clustered in NMF group 3). Samples from patients with the BRAF-V600Emutation or relapse within 1 year did not cluster into any NMF group with signifiance. Additionally, supervised analysis identified specific molecules that were significantly differentially expressed between different clinical categories after multiple testing correction (FDR<0.10): Pediatric LCH vs Adult LCH (72 molecules significant, largest differences in MMP-3, MMP-2 and osteopontin); Pediatric Control vs Pediatric LCH (66 molecules significant, largest differences in SDF-1a, IL-20, MIP-1d, FGF-2 and sIL-4R); Pediatric Low-Risk vs Pediatric High-Risk (47 molecules significant, largest differences in sTNF-R11, sTNF-RI, I-309, sIL2Ra and osteopontin). While previous studies have analyzed expression differences of cytokines in LCH lesions and plasma, in this study the most striking differences are between control vs LCH samples are chemokine molecules. The largest differences between Low-Risk and High-Risk LCH patients include inflammatory cytokines and receptors. Conclusions Despite mounting evidence supporting pathogenesis of LCH as a myeloid neoplasia arising from immature dendritic cell precursors, these results are consistent with exuberant chemokine and cytokine expression in patients with active LCH, supporting a potential role for inflammation in pathogenesis. This study demonstrates the feasibility of identifying novel LCH sub-groups according to plasma protein profiles with unsupervised analysis, and significant differences can be detected in protein levels between clinical risk groups. Future studies will validate the clinical utility of plasma biomarkers in diagnosis, risk-stratification and determining response to therapy. Finally, feasibility of collecting plasma compared to viable lesions makes plasma studies ideal for prospective collection and analysis in cooperative group studies. Disclosures: No relevant conflicts of interest to declare.

Predicting cumulative incidence of chemotherapy toxicity in older patients with cancer: Korean Cancer Study Group prospective cohort study (KCSG) PC 13-09.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21539-e21539 ◽  
Author(s):  
Jee Hyun Kim ◽  
Jin Won Kim ◽  
Se Hyun Kim ◽  
Yun-Gyoo Lee ◽  
In Gyu Hwang ◽  
...  
Keyword(s):  
High Risk ◽  
Geriatric Assessment ◽  
Cumulative Incidence ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Prediction Tool ◽  
Chemotherapy Toxicity ◽  
Increased Risk ◽  
Line Chemotherapy

e21539 Background: Older adults have increased risk of developing chemotherapy toxicity. Currently available prediction tools do not provide information on cumulative risk and none are from Asia. Methods: Patients with histologically confirmed solid cancer aged ≥70 years were prospectively enrolled from 17 centers and underwent geriatric assessment before starting their 1st line chemotherapy. Chemotherapy toxicity prediction model was built for adverse events (AEs) ≥G3, among geriatric assessment, laboratory and clinical variables. Model discrimination values were evaluated using c-statistics compared with actual cumulative incidence of AE ≥G3 in each cycle. Results: 301 patients were enrolled with a median age of 75 years (range 70-93). Primary site included colorectal (28.9%), lung (24.6%), hepato-biliary-pancreatic (22.3%), stomach (10.6%) and others (13.6%). Median chemotherapy cycle was 4 (2-7 cycles). During first line chemotherapy, 53.8% of patients experienced AEs ≥G3. Six variables significantly associated with occurrence of AEs ≥ G3 were serum protein < 6.7 g/dL, no dose reduction at first cycle, suffering from psychological stress or acute disease in the past 3 months, water consumption of less than 3 cups per day, not being able to obey command of 'Grab a piece of paper in your hand', and self-perception of ‘not in good health’. Model with all six variables was selected with the highest mean value of c statistics (0.646) and prediction tool indicated score ranging from 0 to 8 points. Patients were classified to 4 risk groups; 61 (21.0%), 143 (49.3%), 66 (22.8%), and 20 (6.9%) in low (0, 1 point), medium-low (2, 3), medium-high (4, 5), and high risk group (6, 7, 8). Predicted cumulative incidence of AEs ≥G3 was discriminated according to risk groups; low risk group: 13%, 19%, 27%, 30%, 30% in cycle 1, cycle 2, cycle 3, cycle 4, cycle 5, medium-low risk: 17%, 37%, 48%, 56%, 60%, medium-high risk: 26%, 44%, 50%, 68%, 75%, and high risk: 45%, 62%, 87%, 94%, 94%. Conclusions: Novel prediction tool could identify those at high risk of developing AEs ≥G3 after chemotherapy, which provided information on cumulative incidence in each cycle.

PET Parameters are Useful in Predicting Endometrial Cancer Risk Classes and Prognosis

2020 ◽  
Author(s):  
Adnan Budak ◽  
Emrah Beyan ◽  
Abdurrahman Hamdi Inan ◽  
Ahkam Göksel Kanmaz ◽  
Onur Suleyman Aldemir ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Myometrial Invasion ◽  
Risk Groups ◽  
Total Sample ◽  
Tumor Stage ◽  
Low Risk ◽  
Tumor Diameter ◽  
Grade 3 ◽  
Fdg Pet Ct

Abstract Aim We investigate the role of preoperative PET parameters to determine risk classes and prognosis of endometrial cancer (EC). Methods We enrolled 81 patients with EC who underwent preoperative F-18 FDG PET/CT. PET parameters (SUVmax, SUVmean, MTV, TLG), grade, histology and size of the primary tumor, stage of the disease, the degree of myometrial invasion (MI), and the presence of lymphovascular invasion (LVI), cervical invasion (CI), distant metastasis (DM) and lymph node metastasis (LNM) were recorded. The relationship between PET parameters, clinicopathological risk factors and overall survival (OS) was evaluated. Results The present study included 81 patients with EC (mean age 60). Of the total sample, 21 patients were considered low risk (endometrioid histology, stage 1A, grade 1 or 2, tumor diameter < 4 cm, and LVI negative) and 60 were deemed high risk. All of the PET parameters were higher in the presence of a high-risk state, greater tumor size, deep MI, LVI and stage 1B-4B. MTV and TLG values were higher in the patients with non-endometrioid histology, CI, grade 3 and LNM. The optimum cut-off levels for differentiating between the high and low risk patients were: 11.1 for SUVmax (AUC = 0.757), 6 for SUVmean (AUC = 0.750), 6.6 for MTV(AUC = 0.838) and 56.2 for TLG(AUC = 0.835). MTV and TLG values were found as independent prognostic factors for OS, whereas SUVmax and SUVmean values were not predictive. Conclusions The PET parameters are useful in noninvasively differentiating between risk groups of EC. Furthermore, volumetric PET parameters can be predictive for OS of EC.

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