scholarly journals Clinical Relevance of Serum Kyn/Trp Ratio and Basal and IFNγ-Upregulated IDO1 Expression in Peripheral Monocytes in Early Stage Melanoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Annabel Meireson ◽  
Liesbeth Ferdinande ◽  
Marc Haspeslagh ◽  
Benjamin Hennart ◽  
Delphine Allorge ◽  
...  
Keyword(s):  
Clinical Relevance ◽  
Immune Escape ◽  
Early Stage ◽  
Disease Stage ◽  
Rank Test ◽  
First Year ◽  
Ido1 Expression ◽  
Treatment Naïve ◽  
Melanoma Patients

Immune escape is an early phenomenon in cancer development/progression. Indoleamine 2,3-dioxygenase 1 (IDO1) is a normal endogenous mechanism of acquired peripheral immune tolerance and may therefore be tumor-promoting. This study investigated the clinical relevance of IDO1 expression by immune cells in the lymph nodes and blood and of the serum kynurenine/tryptophan (Kyn/Trp) ratio in 65 systemic treatment naïve stage I-III melanoma patients. Blood samples were collected within the first year of diagnosis. Patients had a median follow-up of 61 months. High basal IDO1 expression in peripheral monocytes and low IFNγ-induced IDO1 upregulation correlated with worse outcome independent from disease stage. Interestingly studied factors were not interrelated. During follow-up, the risk of relapse was 9% (2/22) in the subgroup with high IFNγ-induced IDO1 upregulation in monocytes. In contrast, if IDO1 upregulation was low, relapse occurred in 30% (3/10) of patients with low basal IDO1 expression in monocytes and in 61.5% (8/13) in the subgroup with high basal IDO1 expression in monocytes (Log-Rank test, p=0.008). This study reveals some immune features in the blood of early stage melanoma that may be of relevance for disease outcome. These may offer a target for sub-stratification and early intervention.

Characterisation of macular neovascularisation in geographic atrophy

2021 ◽  
pp. bjophthalmol-2021-318820
Author(s):  
Riccardo Sacconi ◽  
Maria Brambati ◽  
Alexandra Miere ◽  
Eliana Costanzo ◽  
Vittorio Capuano ◽  
...  
Keyword(s):  
Fundus Autofluorescence ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
First Year ◽  
Age Related ◽  
Treatment Naïve ◽  
Type 3 ◽  
Endothelial Growth Factor

AimTo characterise macular neovascularisation (MNV) developing in eyes affected by geographic atrophy (GA).MethodsIn this multicentric longitudinal study involving three retina referral centres, patients previously affected by GA who developed an active MNV were included. Patients were investigated using structural optical coherence tomography (OCT), fundus autofluorescence, OCT-angiography and dye angiographies. Patients were treated with ProReNata antivascular endothelial growth factor (VEGF) injections and were revaluated after treatment.ResultsAmong 512 patients previously diagnosed with GA, 40 eyes of 40 patients (mean age 80.8±7.9 years, mean GA area 8.73±7.39 mm2) presented with treatment-naïve exudative MNV (accounting for an estimated prevalence of 7.81%; 5.49 to 10.13, 95% CIs) and thus were included in the analysis. 67.5% of MNVs were classified as type 2 MNV, 25% as type 1, 2.5% as type 3 and 5% as mixed phenotype. In 92.5% of cases, active MNV in GA showed subretinal hyperreflective material with or without evidence of subretinal/intraretinal hyporeflective exudation. During a mean follow-up of 28±25 months, patients were treated with 6.6±6.3 anti-VEGF injections, with 2.9±1.4 injections in the first year of treatment. No patient developed GA enlargement in the area of MNV.ConclusionsMNVs in GA showed different features and therapeutic response in comparison to previously reported features of MNV in age-related macular degeneration (AMD) without GA. For these reasons, the combined phenotype (ie, GA with neovascular AMD) should be considered as a distinct entity in the research and clinical setting.

scholarly journals The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4157
Author(s):  
Giovanni Paolino ◽  
Veronica Huber ◽  
Serena Camerini ◽  
Marialuisa Casella ◽  
Alberto Macone ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Extracellular Vesicles ◽  
Ad Hoc ◽  
Early Stage ◽  
Disease Onset ◽  
Protein Composition ◽  
Disease Stage ◽  
Biological Macromolecules ◽  
Healthy Donors ◽  
Melanoma Patients

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is fundamental to increasing survival and therapeutic adjustment. In stages II–IV especially, additional indications for adjuvant therapy purposes after resection and for treatment of metastatic patients are urgently needed. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) derived from the plasma of stage 0–I, II and III–IV melanoma patients (n = 38) could reflect disease stage. The subpopulation of sEV expressing CD81 EV marker (CD81sEV) was captured by an ad hoc immune affinity technique from plasma depleted of large EV. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA was detectable in patients with respect to healthy donors (HD). Moreover, a higher C18:0/C18:1 ratio, as a marker of cell membrane fluidity, distinguished early (stage 0–I) from late (III–IV) stages’ CD81sEV. Proteomics detected increases in CD14, PON1, PON3 and APOA5 exclusively in stage II CD81sEV, and RAP1B was decreased in stage III–IV CD81sEV, in comparison to HD. Our results suggest that stage dependent alterations in CD81sEV’ FA and protein composition may occur early after disease onset, strengthening the potential of circulating sEV as a source of discriminatory information for early diagnosis, prediction of metastatic behavior and following up of melanoma patients.

scholarly journals Lung Cancer in Homeless People: Clinical Outcomes and Cost Analysis in a Single Institute

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Koung Jin Suh ◽  
Ki Hwan Kim ◽  
Jin Lim ◽  
Jin Hyun Park ◽  
Jin-Soo Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Medical Center ◽  
Homeless People ◽  
Stage Iv ◽  
Disease Stage ◽  
Curative Surgery ◽  
Early Stage Disease ◽  
Outpatient Visits

Introduction. To characterize the demographic and clinical features, outcomes, and treatment costs of lung cancer in homeless people. Methods. Medical records of 22 homeless patients with lung cancer at Seoul National University Boramae Medical Center in Seoul, South Korea, were retrospectively analyzed. Results. All patients were men (median age, 62 years). Most patients (78%) had advanced disease (stage IIIB, n=2; stage IV, n=15). Seven died during initial hospitalization (median survival, 1.5 months). Six were lost to follow-up after initial outpatient visits or discharges from initial admission (median follow-up, 13 days). Only 4 received appropriate treatment for their disease and survived for 1, 15, 19, and 28 months, respectively. Conversely, 4 of 5 patients with early stage disease (stage I, n=4; stage IIA, n=1) received curative surgery (median follow-up 25.5 months). The median treatment cost based on 29 days of hospitalization and 2 outpatient visits was $12,513, constituting 47.3% of the 2013 per capita income. Inpatient treatment accounted for 90% of the total costs. The National Health Insurance Service paid 82% of the costs. Conclusion. Among the homeless, lung cancer seems to be associated with poor prognosis and substantial costs during a relatively short follow-up and survival period.

Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naïve to anti-PD-1 therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9534-9534 ◽  
Author(s):  
Mohammed M. Milhem ◽  
Georgina V. Long ◽  
Christopher J. Hoimes ◽  
Asim Amin ◽  
Christopher D. Lao ◽  
...  
Keyword(s):  
Disease Stage ◽  
Open Label ◽  
Stage Iiic ◽  
Kaplan Meier ◽  
Unresectable Stage ◽  
Treatment Naïve ◽  
Phase 1B ◽  
Grade 3 ◽  
Post Hoc

9534 Background: SD-101 is a synthetic CpG TLR9 agonist. Pembrolizumab is a PD-1 inhibitor. SYNERGY-001/KEYNOTE-184 assesses the safety and preliminary efficacy of the combination of SD-101 and pembrolizumab in patients naïve to anti-PD-1/L1 therapy with unresectable stage IIIC-IV melanoma. Methods: SD-101 was evaluated as 2 mg/lesion injected into 1 to 4 lesions and 8 mg/lesion in 1 lesion as 4 weekly doses followed by 7 doses Q3W. Pembrolizumab was administered as 200 mg IV Q3W. CT scans were performed every 9 weeks. Responses were assessed per investigator using RECIST v1.1. Responses and post-hoc Kaplan-Meier analyses of PFS in the ITT population were compared for patients who received 2 mg/lesion with 8 mg/lesion. Results: 86 patients (2 mg: N = 45; 8 mg: N = 41) have been enrolled with similar baseline characteristics: median age = 66 years; male = 67%; ECOG stage 0 = 67%; disease stage: IIIC = 21%; IVM1a/b = 50%; IVM1c = 28%; LDH ≤ ULN = 71%; treatment naïve = 73%. Median follow up to date is 8.1 months in 2 mg group and 8.3 months in 8 mg group. SD-101 safety profile comprises flu-like symptoms with most frequent grade ≥3 SD-101-related AEs of headache (7%), fatigue (7%), malaise (5%), myalgia (4%), and chills (4%). Immune-related AEs were reported in 19%. ORR in 2 mg group = 71% (95% CI: 57, 82) (CR: 13%) and in 8 mg group = 49% (95% CI: 33, 65) (CR: 7%) with responses in both injected and non-injected lesions, including visceral. DOR = not reached (NR) in either group. ORR by baseline PD-L1 expression in 62 patients, 53% of whom were PD-L1 positive: 2 mg = 80%/79% (PD-L1 positive/negative); 8 mg = 62%/40% (PD-L1 positive/negative). PFS was higher in 2 mg group with median PFS in 2 mg = NR (95% CI: Not estimable [NE], NE) and in 8 mg = 10.4 months (95% CI: 4.2, NE), HR = 0.45 (95% CI: 0.21, 0.98), p = 0.036. 6 month PFS rate in 2 mg = 81% and in 8 mg = 60%. 6 month OS rate in 2 mg = 98% and in 8 mg = 92%. Conclusions: The TLR9 innate immune stimulant, SD-101, in combination with pembrolizumab has been well-tolerated, and is showing promising high response rates and PFS, regardless of PD-L1 expression, particularly in patients who received 2 mg SD-101. Clinical trial information: NCT02521870.

Patterns in progression from early stage melanoma to late stage melanoma: Implications for survivorship follow up.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24055-e24055
Author(s):  
Benjamin Switzer ◽  
David James Savage ◽  
Jung Min Song ◽  
Carolyn Stanek ◽  
Pauline Funchain
Keyword(s):  
Disease Progression ◽  
Metastatic Disease ◽  
De Novo ◽  
Early Stage ◽  
Stage Iv ◽  
Symptomatic Disease ◽  
Stage Ia ◽  
Melanoma Patients ◽  
Stage Iv Melanoma

e24055 Background: Despite an encouraging 99% five-year survival in patients diagnosed with early-stage melanoma, a higher proportion of fatal melanomas initially present with thin ( < 1mm) rather than thick ( > 4mm) melanoma.1 Therefore, early-stage melanoma survivorship remains a topic of high interest. We examined a cohort of early-stage melanomas which progressed to stage IV to inform survivorship and risk-stratification approaches in this large, understudied population. Methods: From a retrospective single-center study of 880 consecutive melanoma patients from 2016-2020, we identified new, non- de novo diagnoses of stage IV melanoma which progressed from an initial early-stage (IA-IIA) diagnosis. Descriptive data were collected via chart review on demographics, clinical features, presentation at time of progression, and follow up prior to progression. Results: A total of 50 patients met the inclusion criterion of an initial stage IA-IIA diagnosis with subsequent progression to stage IV melanoma. Primary early stage melanomas were diagnosed an average of 6.1 years prior to metastatic disease progression, with 46% (n = 23) diagnosed within 3 years, 22% (n = 11) between 4-6 years, 12% (n = 6) between 7-10 years, 8% (n = 4) between 10-12 years, and 12% (n = 6) beyond the 12 year mark from their initial early-stage diagnosis. Average age at time of diagnosis was 57.7 (median 60, range 21-68), and 62% (n = 31) were male. The two most common early-stage diagnostic sites were lower extremities (27.5%, n = 14) and back (23.5%, n = 12). The two most common sites of metastatic disease were lung (46%, n = 23) and brain (28%, n = 14). A total of 30% (n = 15) and 34% (n = 17) of this cohort maintained follow up with oncology and dermatology, respectively, prior to their stage IV diagnosis. Symptomatic disease lead to 80% (n = 40) of stage IV diagnoses, while 14% (n = 7) were diagnosed through routine oncologic or dermatologic follow up, and the final 6% were diagnosed incidentally. Conclusions: Early stage melanoma patients who develop stage IV disease exhibit wide ranges in onset of disease progression, thus survivorship plans for this group could include a combination of early provider screening and patient education for later presentations of metastatic disease. Due to relatively common metastatic involvement of the lung and brain, a high suspicion to screen for metastatic disease with symptoms involving these organs may be appropriate.

Symptoms of fatigue and depression in ischemic heart disease are driven by personality characteristics rather than disease stage: a comparison of CAD and CHF patients

2008 ◽  
Vol 15 (5) ◽  
pp. 583-588 ◽  
Author(s):  
Otto R.F. Smith ◽  
Susanne S. Pedersen ◽  
Ron T. Van Domburg ◽  
Johan Denollet
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Early Stage ◽  
Multivariable Analysis ◽  
Type D Personality ◽  
Ischemic Heart ◽  
Disease Stage ◽  
Type D ◽  
The Impact

Background Symptoms of fatigue and depression are prevalent across stages of ischemic heart disease (IHD). We examined (i) the effect of both the IHD stage and type-D personality on fatigue and depressive symptoms at 12-month follow-up, and (ii) whether the effect of type-D personality on these symptoms is moderated by IHD stage. Methods Two different samples of patients were included to represent IHD stage: 401 percutaneous coronary intervention patients (early-stage IHD) and 105 ischemic chronic heart failure patients (end-stage IHD) completed the DS14 Type-D Scale at baseline. Logistic regression analysis was used to examine the impact of IHD stage and type-D personality on fatigue and depression at follow-up. Results Disease stage was neither associated with symptoms of fatigue ( P = 0.99) nor depression ( P = 0.29) at 12 months. In contrast, type-D personality was shown to predict both symptoms of fatigue [odds ratio (OR) = 2.96; 95% confidence interval (CI): 1.92–4.58, P < 0.001] and depression (OR = 4.91; 95% CI: 3.16–7.65, P < 0.001) at follow-up; the effect of type-D personality on these symptoms was not moderated by disease stage. In multivariable analysis, type-D remained a significant predictor of symptoms of fatigue (OR = 3.14; 95% CI: 1.98–4.99, P < 0.001) and depression (OR = 5.90; 95% CI: 3.60–9.67, P < 0.001), also after controlling for symptom levels at baseline. Conclusion Type-D personality but not disease stage predicted symptoms of fatigue and depression at 12-month follow-up.

scholarly journals CyTOF reveals phenotypically-distinct human blood neutrophil populations differentially correlated with melanoma stage

2019 ◽  
Author(s):  
Yanfang Peipei Zhu ◽  
Tobias Eggert ◽  
Daniel J. Araujo ◽  
Pandurangan Vijayanand ◽  
Christian H. Ottensmeier ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Disease Stage ◽  
Positive Trend ◽  
List Type ◽  
Functional Evaluation ◽  
Blood Neutrophil ◽  
Key Points ◽  
Treatment Naïve ◽  
Melanoma Patients

ABSTRACTUnderstanding neutrophil heterogeneity and its relationship to disease progression has become a recent focus of cancer research. Indeed, several studies have identified neutrophil subpopulations associated with pro- or anti-tumoral functions. However, this work has been hindered by the lack of widely-accepted markers with which to define neutrophil subpopulations. To identify markers of neutrophil heterogeneity in cancer, we utilized single-cell cytometry by time-of-flight (CyTOF) coupled with high-dimensional analysis on blood samples from treatment-naïve, melanoma patients. Our efforts allowed us to identify 7 blood-neutrophil clusters, including 2 previously identified individual populations. Interrogation of these neutrophil subpopulations revealed a positive trend between specific clusters and disease stage. Finally, we recapitulated these 7 blood-neutrophil populations via flow cytometry and found that they exhibit diverse capacities for phagocytosis and reactive oxygen species (ROS) production in vitro. In summary, our data provide a refined consensus on neutrophil-heterogeneity markers, enabling a prospective functional evaluation in patients with solid tumors.KEY POINTSCyTOF analysis reveals 7 blood neutrophil clusters correlating with melanoma stage in treatment-naïve patients.Neutrophil clusters by unbiased-calling are recapitulated by flow cytometry and harbor diverse phagocytic and ROS-producing capacities.

First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7500-7500 ◽  
Author(s):  
Ian Flinn ◽  
Richard van der Jagt ◽  
Julie E. Chang ◽  
Peter Wood ◽  
Tim E. Hawkins ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Duration Of Response ◽  
Treatment Naïve

7500 Background: BRIGHT, a phase 3, open-label, noninferiority study comparing efficacy and safety of bendamustine plus rituximab (BR) vs rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP) in treatment-naive patients (pts) with indolent non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL), showed that the complete response rate for first-line BR was statistically noninferior to R-CHOP/R-CVP ( Blood 2014). Pts were monitored for ≥5 years (yr) to assess the overall effect of BR or R-CHOP/R-CVP in a controlled clinical setting. This analysis reports the time-to-event variables of the 5-yr follow-up (FU) study. Methods: Pts with iNHL or MCL randomized to 6-8 cycles of BR or R-CHOP/R-CVP underwent complete assessments at end of treatment, then were monitored regularly. Progression-free survival (PFS), event-free survival (EFS), duration of response (DOR) and overall survival (OS) were compared using a stratified log-rank test. Results: Of 447 randomized pts, 224 received BR, 104 R-CHOP, and 119 R-CVP; 419 entered the FU. The median FU time was 65.0 and 64.1 months for BR and R-CHOP/R-CVP, respectively. The 5-yr PFS rate was 65.5% (95% CI 58.5-71.6) and 55.8% (48.4-62.5), and OS was 81.7% (75.7-86.3) and 85% (79.3-89.3) for BR and R-CHOP/R-CVP, respectively. The hazard ratio (95% CI) for PFS was 0.61 (0.45-0.85; P= .0025), EFS 0.63 (0.46-0.84; P= .0020), DOR 0.66 (0.47-0.92; P= .0134), and OS 1.15 (0.72-1.84; P= .5461) comparing BR vs R-CHOP/R-CVP. Similar results were found in iNHL [PFS 0.70 (0.49-1.01; P= .0582)] and MCL [PFS 0.40 (0.21-0.75; P= .0035)], with the strongest effect in MCL. Use of R maintenance was similar, 43% in BR and 45% in R-CHOP/R-CVP. B was included as second-line in 27 (36%) of the 75 pts requiring therapy who originally received R-CHOP/R-CVP. Comparable safety profiles with expected adverse events were observed in the FU study in BR vs R-CHOP/R-CVP. Conclusions: The long-term FU of the BRIGHT study has confirmed that PFS, EFS, and DOR were significantly better for BR, and OS was not statistically different between BR and R-CHOP/R-CVP. The safety profile was as previously reported. Clinical trial information: NCT00877006.

Correlates of anxiety and depression in chronic lymphocytic leukemia (CLL) survivors.

2018 ◽  
Vol 36 (7_suppl) ◽  
pp. 153-153 ◽  
Author(s):  
AnnaLynn Williams ◽  
Rina Yarosh ◽  
Jackson Clark ◽  
Carla Casulo ◽  
Paul M. Barr ◽  
...  
Keyword(s):  
Active Surveillance ◽  
Early Stage ◽  
Performance Status ◽  
Lymphocytic Leukemia ◽  
Older Age ◽  
Disease Stage ◽  
Anxiety And Depression ◽  
Poor Performance Status ◽  
Treatment Naïve ◽  
Time Since Diagnosis

153 Background: CLL is an indolent lymphoma effecting aging populations. Early stage patients are assigned to active surveillance and only 10% of patients require treatment at diagnosis. Active surveillance for CLL may increase susceptibility to anxiety and depression, resulting in enhanced comorbidities and reduced quality of life. However, little is known about the prevalence and risk factors of anxiety and depression in CLL. Methods: 125 CLL patients that were treatment naïve (n = 86) or previously chemotherapy-treated (n = 39) completed anxiety and depression questionnaires (State Trait Anxiety Index (STAI) and Center for Epidemiologic Studies Depression (CES-D)). Multivariable linear regression was used to examine associations with STAI/CES-D score. Logistic regression was used to examine clinically meaningful anxiety and depression, using validated cut points of 40 for the STAI and 16 (or on antidepressants) for the CES-D. All models included treatment status (treatment naïve vs. treated), age, gender, ECOG grade, time since diagnosis, education, & disease stage. Results: Patients had a median age of 65, were mostly male (60.8%), Caucasian (96%), well educated (55% ≥ college), and had low stage CLL (66% stage 0) and good performance status (67% ECOG 0). 20 and 24% of patients had clinically meaningful anxiety or depression (11% had both). Treatment and time since diagnosis were not associated with anxiety or depression. Older age was associated with better STAI and CES-D scores (STAI β = -0.34 (95%CI -0.52, -0.17) CES-D β = -0.27 (95%CI -0.42, -0.12)), and each 1 year increase in age was associated with a 9% decrease in odds of anxiety and a 7% decrease in odds of depression (OR 0.91(95%CI 0.86, 0.96) OR 0.93 (95%CI 0.88, 0.98) respectively). An ECOG grade of 3 or 4 was a significant predictor of increased depression risk (OR 2.84 (95%CI 1.03, 7.82)) and worse CES-D scores (β = 4.69 (95%CI 8.09, 1.29)) but not of anxiety. Conclusions: Anxiety and depression are common among CLL patients. Poor performance status was associated with more depression while older age was associated with less anxiety and depression. Future studies should investigate potential interventions for anxiety and depression in younger CLL patients.

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