scholarly journals Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4842
Author(s):  
Hidetaka Suzuki ◽  
Shuichi Mitsunaga ◽  
Masafumi Ikeda ◽  
Takao Aoyama ◽  
Kazumi Yoshizawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Group Performance ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Pancreatic Disease ◽  
High Serum ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.

scholarly journals Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer

2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Weekly Schedule ◽  
Dose Reductions

Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan–Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. Results: A total of 73 patients (median age: 73 years; range: 66–93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. Conclusion: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.

Abstract PO-001: Increased growth differentiation factor 15 serum levels in pancreatic cancer patients

2020 ◽  
Author(s):  
Veronica R. Placencio-Hickok ◽  
Arsen Osipov ◽  
Sejal Mehta ◽  
Subhash D. Katewa ◽  
Jiping Zha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

Clinical significance of serum alkaline phosphatase level in advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 183-183 ◽  
Author(s):  
I. Ohno ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
S. Shimizu ◽  
H. Takahashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Prognostic Factor ◽  
Performance Status ◽  
Elevated Serum ◽  
Advanced Pancreatic Cancer ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Bile Stasis ◽  
Low Serum

183 Background: Alkaline phosphatase (ALP) is an enzyme that is elevated by various hepatobiliary diseases. Generally its elevation is thought to indicate bile stasis. There are some reports that show ALP is an important prognostic factor for several cancers such as colon, lung, and gastric cancer. Often it is speculated that ALP elevation indicates bile stasis caused by liver metastasis. However, the significance of ALP elevation in advanced pancreatic cancer (APC) patients is not well evaluated. The aim of this study was to determine the significance of elevated serum ALP as a prognostic factor in patients with APC even without jaundice and liver metastasis. Methods: Serum ALP levels were measured in 393 patients with APC receiving gemcitabine monotherapy before treatment, and according to those levels, patients were subgrouped (ALP<upper normal limit (UNL), UNL-500 U/L, 501-700 U/L, 701-1000 U/L, 1000U/L < ALP). The clinical data of each group were analyzed to see characteristics of elevated ALP patients. The relationship between ALP level and survival, response were also examined. Results: The elevated ALP group included poor performance status (PS>1) patients (41.3%, p=0.001), and associated with low serum albumin (3.31±0.38, p<0.01). The elevated ALP group (median survival time (MST) 112 days) showed significantly worse prognosis and lower disease control rate compared to the normal ALP group (MST 217days) (p<0.001, p<0.001). Multivariate analysis revealed ALP (p<0.001), CRP (p<0.001), ascites (p<0.001), distant metastasis (p=0.003), white blood cell count (p=0.005), PS (p=0.020), AST (p=0.020), and ALT (p=0.020) were independent prognostic factors. Similar results were seen in liver metastasis free patients without jaundice. Conclusions: Elevated serum ALP level correlated with poor performance status and low serum albumin. ALP was also the independent prognostic factor in liver metastasis free APC patients without jaundice. No significant financial relationships to disclose.

Characterization of patients with high serum level of IL-6 in advanced pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 197-197
Author(s):  
Tomofumi Miura ◽  
Shuichi Mitsunaga ◽  
Satoshi Shimizu ◽  
Izumi Ohno ◽  
Hideaki Takahashi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Advanced Pancreatic Cancer ◽  
Disease Status ◽  
High Serum ◽  
Related Factor ◽  
Related Factors ◽  
Reactive Protein ◽  
Treatment Naïve

197 Background: IL-6 is a key mediator of cancer cachexia. The degree of cachexia affects serum IL-6 level in pancreatic cancer (PC) and is varied according to disease progression. The study population to characterize advanced PC patients with high IL-6 level needs the homogeneity in disease status. This study was aimed to identify IL-6-related factors in patients who were scheduled to undergo first-line chemotherapy for treatment-naïve advanced PC. Methods: Patients with treatment-naïve advanced PC were eligible for inclusion in this study. Patients with obvious infection or biliary drainage were excluded. Serum IL-6 levels and clinical parameters (e.g. symptoms, body composition) were prospectively collected. A high IL-6 level was defined as a value greater than the median value in all of the analyzed patients, and analyses were performed to identify risk factors for high IL-6 levels. Results: Eighty patients were analyzed. A multivariate analysis determined that the following parameters were associated with high IL-6: the presence of liver metastasis [Odds ratio (OR): 4.8, p < 0.01], fatigue (OR 3.4, p = 0.02), high carcinoembryonic antigen (CEA) levels (OR: 6.9, p = 0.03), anemia (OR: 9.5, p = 0.01), and high C-reactive protein (CRP) levels (OR: 12.4, p = 0.02). A decreased skeletal muscle mass tended to be frequently observed in patients with high IL-6 levels. Conclusions: High serum IL-6 related the presence of liver metastasis, severe fatigue, high CEA, high CRP and anaemia. Additionally, skeletal muscle loss might be the IL-6 related factor.

scholarly journals Digital Detection of Sarcopenia in Pancreatic Cancer: Additional Utilization to Plan Patient Management

2021 ◽  
Author(s):  
Mustafa Jalal ◽  
Jennifer A Campbell ◽  
Jonathan Wadsley ◽  
Andrew D Hopper
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Skeletal Muscle Index ◽  
Ecog Ps ◽  
Cancer Network

Abstract Purpose: The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting ‘digital sarcopenia’ is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC).Methods: Patients diagnosed with LAPC referred for endoscopic ultrasound guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) was noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. Results: In total 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received BSC only. The prevalence of sarcopenia (p=0.0003), age ≥ 75 years old (p=0.03) and ECOG-PS 2-3 (p=0.01) were significantly higher in the patents receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. Conclusion: Our study has shown that digital skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

Clinical significance of elevation of the serum IL-6 level in patients with advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 181-181
Author(s):  
S. Mitsunaga ◽  
M. Ikeda ◽  
K. Nakachi ◽  
I. Ohno ◽  
S. Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Volume ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Japanese Version ◽  
Serum Levels ◽  
Ecog Performance Status ◽  
Reactive Protein ◽  
Treatment Naïve ◽  
Median Change

181 Background: IL-6, one of the pro-inflammatory cytokines, is a recognized mediator of cachexia and cancer cell invasion. It has been reported that elevation of the serum IL-6 level may be associated with deterioration of the clinical condition and tumor progression in advanced pancreatic cancer (PC) patients. The aim of this study was to clarify the clinical features of increased serum IL-6 levels in patients with advanced PC receiving chemotherapy. Methods: Patients with treatment-naïve unresectable PC and no obvious infectious conditions were eligible for this study. Serum levels of IL-6 were measured by an electrochemiluminescence assay. Symptoms were rated numerically from 0 to 10 using the Japanese version of the M. D. Anderson Symptom Inventory. Tumor volume was calculated as the sum of the long diameters of the tumors. The measurements were performed before chemotherapy and at one month after the start of chemotherapy. Results: A total of 87 patients (male/female: 41/46; ECOG performance status: 0/1/2: 59/26/1; media age: 66 years) were enrolled; all patients were administered systemic chemotherapy (gemcitabine [GEM]/GEM+S-1/GEM+other/S-1: 52/11/9/15). The median serum level of IL-6 was 1.3 pg/mL before chemotherapy (at baseline) and 1.8 pg/mL at one-month after the start of chemotherapy. The median change of IL-6 from the baseline was +0.18 pg/mL. Patients with increase of the serum IL-6 level by more than 0.18 pg/mL were assigned to the elevated IL-6 group (n=42; median change in IL-6: +1.66 pg/mL). The elevated IL-6 group showed more sadness (p=0.019), numbness (p=0.008), and gain of body weight (p=0.016) at the baseline as compared to the non-IL-6-elevated group (n=42; median change in IL-6: -0.27 pg/mL). Comparison of the elevated and non-IL-6-elevated groups revealed a greater degree of increase in the tumor volume (p=0.015), deterioration of nausea (p=0.046) and vomiting (p=0.028), neutrophilia (p=0.004), and elevation of the serum C-reactive protein (p=0.011) in the elevated IL-6 group than in the non-IL-6-elevated group. Conclusions: Elevation of the serum IL-6 level may be associated withsymptom deterioration, increase of the tumor mass, and inflammatory reaction in patients with advanced PC. No significant financial relationships to disclose.

scholarly journals Computed Tomographic Sarcopenia in Pancreatic Cancer: Further Utilization to Plan Patient Management

2021 ◽  
Author(s):  
Mustafa Jalal ◽  
Jennifer A. Campbell ◽  
Jonathan Wadsley ◽  
Andrew D. Hopper
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Skeletal Muscle Index ◽  
Computed Tomographic ◽  
Ecog Ps

Abstract Purpose The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting ‘computed tomographic sarcopenia’ is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC). Methods Patients diagnosed with LAPC referred for endoscopic ultrasound-guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) were noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. Results In total, 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received best supportive care (BSC) only. The prevalence of sarcopenia (p = 0.0003), age ≥ 75 years old (p = 0.03), and ECOG-PS 2–3 (p = 0.01) were significantly higher in the patients receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. Conclusion Our study has shown that computed tomographic skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

High Levels of Growth Differentiation Factor 15 in Patients with Congenital Dyserythtopoietic Anemia Type I

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3456-3456
Author(s):  
Hannah Tamary ◽  
Hanna Shalev ◽  
Galit Avraham ◽  
Meira Zoldan ◽  
Itai Levi ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Elevated Serum ◽  
Serum Levels ◽  
High Serum ◽  
Type I ◽  
Soluble Transferrin Receptor ◽  
Ineffective Erythropoiesis ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
A Minor

Abstract Growth differentiation factor 15 (GDF15) is a member of the TGF-beta superfamily of cytokines previously found to suppress hepcidin in primary human hepatocytes. GDF15 is secreted from human erythroblasts, and extremely high serum levels are present in β-thalassemia patients (Tanno et al., Nat. Med. 2007, 13, 1096–1101). To determine if elevated GDF15 levels are unique for thalassemia or more generally associated with iron-loading related to ineffective erythropoiesis, we determined the GDF15 levels, as well as, serum hepcidin (Swinkels DW et al, PLoS ONE PLoS ONE. 2008;3:e2706), ferritin, erythropoietin (EPO) and soluble transferrin receptor (sTfR) in patients with the congenital dyserythropoietic anemia type I (CDA I). Seventeen Israeli Bedouins with CDA I were studied, all homozygous for the founder R1040W mutation in the CDAN1 gene. All of the patients studied were young adults with a mean age of 29 years. Two patients previously underwent splenectomy, and one patient is currently transfusion-dependent. For comparison, ten healthy volunteers (HV) were studied. The mean level of GDF15 in CDA I patients was significantly elevated [10,239 ± 3,049 pg/ml (range 5,530–17,008) compared to 269 ± 238 pg/ml in healthy controls; p = 1.5×10−10]. Consistent with a previous study of dyserythropoietic anemia patients, significantly higher levels of soluble transferrin receptor were detected among the CDA I population (sTfR; CDA I, 86.4 ± 14.0 nmol/L; HV, 21.4 ± 6.2 nmol/L, p = 7.4×10−15). Serum EPO levels were also elevated (EPO; CDA I, 118 ± 59 IU/dL; HV, 2.0 ± 1.5 IU/dL, p = 2.3×10−7). For iron analyses, three patients with extensive transfusion histories were excluded. Among the remaining 14 patients, iron overload was demonstrated by elevated serum ferritin (CDA I, 916 ± 507 ng/ml; HV, 72 ± 60 ng/ml, p = 1.4×10−5). Despite the significant elevation in iron stores, significantly elevated levels of hepcidin 25 (Hep25) were not detected in the CDA I patients. Instead, a minor decrease in serum Hep25 levels were detected (Hep25; CDA I, 3.3 ± 2.8 nM; HV, 4.1 ± 3.0 nM, p = 0.27). Correlation analyses were performed between the iron parameters (Ferritin and Hep25) and GDF15, sTfR, or EPO levels. Only GDF15 demonstrated a significant positive correlation with ferritin and significant inverse correlations with Hep25 and the Hep25/Ferritin ratio. Weaker correlations with EPO were identified. Unexpectedly, the correlation trends for sTfR were opposite those of GDF15 in this group. These results demonstrate that GDF15 is immensely over-expressed in CDA I, and further suggest this cytokine contributes to hepcidin dysregulation and secondary hemochromatosis in humans with ineffective erythropoiesis.

Association of interleukin-6 levels and neutropenia during gemcitabine monotherapy for advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 178-178 ◽  
Author(s):  
H. Okuyama ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
I. Ohno ◽  
S. Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Inflammatory Cytokines ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Severe Neutropenia ◽  
Ecog Performance Status ◽  
Tnf Α ◽  
Low Serum ◽  
Pro Inflammatory Cytokines

178 Background: Neutropenia is an important dose-limiting toxicity of gemcitabine (GEM) in patients with advanced pancreatic cancer (PC). Serum haptoglobin, regulated by pro-inflammatory cytokines, is a predictor of neutropenia in PC patients under treatment with GEM. We conducted this study with the aim of identifying the association between serum levels of haptoglobin and cytokines and the risk of development of neutropenia in advanced PC patients receiving GEM therapy. Methods: Serum levels of haptoglobin and pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-2β, IL-6, IL-8, IL-10, IL-12, TNF-α) were measured in 55 patients with advanced PC. All patients (median age: 67 years, male/female: 26/29, ECOG performance status: 0/1/2: 32/21/2,) received GEM monotherapy as the initial treatment for PC. The severity of neutropenia within the first 90 days of the GEM treatment was graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Categorical or and noncategorical data were compared using Student's t test. Multivariate regression analysis was performed using logistic regression modeling. The significance level was set at p<0.05. Results: Grade 0 to 2 (G0/1/2) and grade 3 to 4 (G3/4) neutropenia were observed in 32 patients (58.2%) and 23 patients (41.8%), respectively. The G3/4 neutropenia group showed low serum levels of haptoglobin (mean 144.4 mg/dl vs. 186.7 mg/dl, p=0.097), IL-1β (mean 0.07 pg/ml vs. 0.24 pg/ml, p=0.044), IL-6 (mean 1.13 pg/ml vs. 6.43 pg/ml, p=0.002), IL-8 (mean 18.4 pg/ml vs. 44.8 pg/ml, p=0.015), and TNF-α (mean 6.28 pg/ml vs. 8.86 pg/ml, p=0.017) as compared to the G0/1/2 neutropenia group. Multivariate analysis revealed that only low serum IL-6 was significantly associated with the development of G3/4 neutropenia (OR=0.081, p=0.0011). Conclusions: Low serum IL-6 level was associated with severe neutropenia. Thus, circulating IL- 6 levels may be a predictor of the development of severe neutropenia in advanced PC patients receiving GEM therapy. No significant financial relationships to disclose.

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