scholarly journals The Path of Most Resistance: A Rare Instance of Metastatic Pancreatic Adenocarcinoma Identified Within Skeletal Muscle

Cureus ◽  
2021 ◽  
Author(s):  
Caitlin E Harmon ◽  
Sanjay P Lamsal ◽  
Taylor S Harmon ◽  
Khaled Mohamed ◽  
Travis E Meyer
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Adenocarcinoma ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Rare Instance

scholarly journals Clinical significance of skeletal muscle density and sarcopenia in patients with pancreatic cancer undergoing first-line chemotherapy: a retrospective observational study.

2020 ◽  
Author(s):  
In-Ho Kim ◽  
Moon Hyung Choi ◽  
In Seok Lee ◽  
Tae Ho Hong ◽  
Myung Ah Lee
Keyword(s):  
Skeletal Muscle ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Pancreatic Adenocarcinoma ◽  
Cox Regression ◽  
First Line ◽  
Poor Overall Survival ◽  
Skeletal Muscle Index ◽  
Muscle Density ◽  
Metastatic Pancreatic Adenocarcinoma

Abstract Background To investigate the clinical impact of sarcopenia and skeletal muscle density among patients with metastatic pancreatic adenocarcinoma who underwent palliative first line gemcitabine-based chemotherapy. Methods A total of 330 patients with metastatic pancreatic adenocarcinoma who were treated with palliative first line gemcitabine-based chemotherapy between January 2010 and March 2017 were included in this study. Sarcopenia and skeletal muscle density status were identified by L3 vertebra level skeletal muscle index in cm 2 /m 2 and muscle attenuation in Hounsfield units using computed tomography. Results A skeletal muscle index to skeletal muscle density comparison revealed a positive correlation (R 2 = 0.058, P<0.001). Kaplan–Meier analysis showed that low skeletal muscle density was associated with poor overall survival. Multivariate analysis using Cox regression showed that low skeletal muscle index and low skeletal muscle density were poor prognostic factors for overall survival, respectively. Co-presence of low skeletal muscle index and low skeletal muscle density had more powerful prognostic implication for overall survival. Grade 3 or higher toxicity of chemotherapy was more frequently observed in patients with low skeletal muscle index and low skeletal muscle density. Overall survival was not associated with skeletal muscle density status among patients who were chemotherapy responders (complete or partial responses). However, among non-responders (stable or progressive disease), low skeletal muscle density groups had significantly poorer overall survival than did the high skeletal muscle density groups. Conclusions Sarcopenia and skeletal muscle density status can be considered a prognostic factor in patients with metastatic pancreatic adenocarcinoma who receive palliative first line gemcitabine-based chemotherapy. Severe chemotherapy toxicity occurred in the sarcopenia and low skeletal muscle density groups. Our data suggest that comprehensive assessment of skeletal muscle parameters may be more useful prognostic factors.

scholarly journals Clinical significance of skeletal muscle density and sarcopenia in patients with pancreatic cancer undergoing first-line chemotherapy : a retrospective observational study.

2020 ◽  
Author(s):  
In-Ho Kim ◽  
Moon Hyung Choi ◽  
In Seok Lee ◽  
Tae Ho Hong ◽  
Myung Ah Lee
Keyword(s):  
Skeletal Muscle ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Pancreatic Adenocarcinoma ◽  
Cox Regression ◽  
First Line ◽  
Poor Overall Survival ◽  
Skeletal Muscle Index ◽  
Muscle Density ◽  
Metastatic Pancreatic Adenocarcinoma

Abstract Background: To investigate the clinical impact of sarcopenia and skeletal muscle density among patients with metastatic pancreatic adenocarcinoma who underwent palliative first line gemcitabine-based chemotherapy.Methods: A total of 330 patients with metastatic pancreatic adenocarcinoma who were treated with palliative first line gemcitabine-based chemotherapy between January 2010 and March 2017 were included in this study. Sarcopenia and skeletal muscle density status were identified by L3 vertebra level skeletal muscle index in cm2/m2 and muscle attenuation in Hounsfield units using computed tomography.Results: A skeletal muscle index to skeletal muscle density comparison revealed a positive correlation (R2 = 0.058, P<0.001). Kaplan–Meier analysis showed that the low skeletal muscle density was related to poor overall survival. Multivariate analysis using Cox regression showed that low skeletal muscle index and low skeletal muscle density were poor prognostic factors for overall survival, respectively. Co-presence of low skeletal muscle index and low skeletal muscle density had more powerful prognostic implication for overall survival. Grade 3 or higher toxicity of chemotherapy was more frequently observed in patients who have a low skeletal muscle index and low skeletal muscle density. Overall survival was not related to skeletal muscle density status among patients who were chemotherapy responders (complete or partial responses). However, among non-responders (stable or progressive disease), low skeletal muscle density groups had significantly poorer overall survival in comparison with high skeletal muscle density groups.Conclusions: Sarcopenia and skeletal muscle density status can be considered a prognostic factor in patients with metastatic pancreatic adenocarcinoma who received palliative first line gemcitabine-based chemotherapy. Severe chemotherapy toxicity occurred in the sarcopenia and low skeletal muscle density groups. Our data suggest that a comprehensive assessment of skeletal muscle parameters may be more useful prognostic factors.

scholarly journals Clinical significance of skeletal muscle density and sarcopenia in patients with pancreatic cancer undergoing first-line chemotherapy: a retrospective observational study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
In-Ho Kim ◽  
Moon Hyung Choi ◽  
In Seok Lee ◽  
Tae Ho Hong ◽  
Myung Ah. Lee
Keyword(s):  
Skeletal Muscle ◽  
Prognostic Factors ◽  
Pancreatic Adenocarcinoma ◽  
Cox Regression ◽  
First Line ◽  
Poor Overall Survival ◽  
Cross Sectional ◽  
Skeletal Muscle Index ◽  
Muscle Density ◽  
Metastatic Pancreatic Adenocarcinoma

Abstract Background To investigate the clinical impact of sarcopenia and skeletal muscle density (SMD) among patients with metastatic pancreatic adenocarcinoma who underwent palliative first line gemcitabine-based chemotherapy. Methods A total of 330 patients treated with first line gemcitabine-based chemotherapy between January 2010 and March 2017 were included. CT scans before chemotherapy and after 8±2 weeks were evaluated. The L3 skeletal muscle index (SMI) was used to detect sarcopenia and calculated as the total area of the L3 skeletal muscle divided by the height-squared (cm2/m2). SMD was quantified as the mean muscle radiation attenuation of the muscle cross-sectional area across the L3 vertebral body level and was assessed between − 29 and + 150 Hounsfield units. Results A SMI to SMD comparison revealed a positive correlation (R2 = 0.058, P < 0.001). Compared with high SMD, the risks of low SMI were 1.516 (95% confidence interval [CI]: 1.164–1.973) among patients with low SMD. Kaplan–Meier analysis showed that the low SMD was related to poor overall survival (OS, median, 6.1 versus [vs.] 7.9 months, P = 0.010). Multivariate analysis using Cox regression showed that low SMI (hazard ratio [HR]: 1.35, 95% CI: 1.03–1.78, P = 0.032) and low SMD (HR: 1.45, 95% CI: 1.09–1.93, P = 0.011) were poor prognostic factors for OS, respectively. Co-presence of low SMI and low SMD had more powerful prognostic implication for OS (HR: 1.58, 95% CI: 1.12–2.23, P = 0.010). Grade 3 or higher toxicity of chemotherapy was more frequently observed in patients who have a low SMI (43% vs. 59%, P = 0.019) and low SMD (44% vs. 60%, P = 0.023). OS was not related to SMD status among patients who were chemotherapy responders (complete or partial responses). However, among non-responders (stable or progressive disease), low SMD groups had significantly poorer OS in comparison with high SMD groups (median, 5.6 vs 7.4 months, P = 0.006). Conclusions Sarcopenia and SMD status can be considered a prognostic factor in patients with metastatic pancreatic adenocarcinoma who received palliative first line gemcitabine-based chemotherapy. Severe chemotherapy toxicity occurred in the sarcopenia and low SMD groups. Our data suggest that a comprehensive assessment of skeletal muscle parameters may be more useful prognostic factors.

scholarly journals Clinical significance of skeletal muscle density and sarcopenia in patients with pancreatic cancer undergoing first-line chemotherapy : a retrospective observational study.

2021 ◽  
Author(s):  
In-Ho Kim ◽  
Moon Hyung Choi ◽  
In Seok Lee ◽  
Tae Ho Hong ◽  
Myung Ah Lee
Keyword(s):  
Skeletal Muscle ◽  
Prognostic Factors ◽  
Pancreatic Adenocarcinoma ◽  
Cox Regression ◽  
First Line ◽  
Poor Overall Survival ◽  
Cross Sectional ◽  
Skeletal Muscle Index ◽  
Muscle Density ◽  
Metastatic Pancreatic Adenocarcinoma

Abstract Background: To investigate the clinical impact of sarcopenia and skeletal muscle density (SMD) among patients with metastatic pancreatic adenocarcinoma who underwent palliative first line gemcitabine-based chemotherapy.Methods: A total of 330 patients treated with first line gemcitabine-based chemotherapy between January 2010 and March 2017 were included. CT scans before chemotherapy and after 8±2 weeks were evaluated. The L3 skeletal muscle index (SMI) was used to detect sarcopenia and calculated as the total area of the L3 skeletal muscle divided by the height-squared (cm2/m2). SMD was quantified as the mean muscle radiation attenuation of the muscle cross-sectional area across the L3 vertebral body level and was assessed between -29 and +150 Hounsfield units. Results: A SMI to SMD comparison revealed a positive correlation (R2 = 0.058, P<0.001). Compared with high SMD, the risks of low SMI were 1.516 (95% confidence interval [CI]: 1.164-1.973) among patients with low SMD. Kaplan–Meier analysis showed that the low SMD was related to poor overall survival (OS, median, 6.1 versus [vs.] 7.9 months, P=0.010). Multivariate analysis using Cox regression showed that low SMI (hazard ratio [HR]: 1.35, 95% CI: 1.03–1.78, P=0.032) and low SMD (HR: 1.45, 95% CI: 1.09–1.93, P=0.011) were poor prognostic factors for OS, respectively. Co-presence of low SMI and low SMD had more powerful prognostic implication for OS (HR: 1.58, 95% CI: 1.12–2.23, P=0.010). Grade 3 or higher toxicity of chemotherapy was more frequently observed in patients who have a low SMI (43% vs. 59%, P=0.019) and low SMD (44% vs. 60%, P=0.023). OS was not related to SMD status among patients who were chemotherapy responders (complete or partial responses). However, among non-responders (stable or progressive disease), low SMD groups had significantly poorer OS in comparison with high SMD groups (median, 5.6 vs 7.4 months, P=0.006).Conclusions: Sarcopenia and SMD status can be considered a prognostic factor in patients with metastatic pancreatic adenocarcinoma who received palliative first line gemcitabine-based chemotherapy. Severe chemotherapy toxicity occurred in the sarcopenia and low SMD groups. Our data suggest that a comprehensive assessment of skeletal muscle parameters may be more useful prognostic factors.

Biologically optimized schedule of gemcitabine and nab-paclitaxel regimen in metastatic pancreatic adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4168-TPS4168
Author(s):  
Laith I. Abushahin ◽  
Anne M. Noonan ◽  
John L. Hays ◽  
Pannaga G. Malalur ◽  
Ashish Manne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Dose Intensity ◽  
Standard Of Care ◽  
Significance Level ◽  
Pancreatic Cancer Cells ◽  
Metastatic Pancreatic Adenocarcinoma

TPS4168 Background: Metastatic pancreatic adenocarcinoma has a poor prognosis, and improvements in therapy have been challenging. Alongside efforts in developing novel agents, there is a need to optimize and maximize the benefit of currently approved drugs. Gemcitabine + nab-paclitaxel is a frequently used regimen for pancreatic adenocarcinoma. Nab-paclitaxel is albumin–bound chemotherapy; hence the role of albumin uptake is critical for its effect. Caveolae are small membrane invaginations essential for transendothelial albumin uptake. Cav-1 is the principal structural component of caveolae. Williams and colleagues have published a series of preclinical studies demonstrating that tumor cell-specific Cav-1 expression directly correlates with albumin and albumin-bound chemotherapy uptake and subsequent apoptotic response in tumor cells. In vitro studies showed that exposure of pancreatic cancer cells to Gemcitabine resulted in up-regulation of Cav-1 peaking 48 hours after gemcitabine exposure. This Cav-1 up-regulation correlated with increased temporal albumin cellular uptake. In addition, Williams and colleagues noted that exposure of pancreatic cancer cell lines to Gemcitabine resulted in a time–specific re-entry of cells into the G2/M phase (nab-paclitaxel cytotoxicity phase) between 48-60 hours after gemcitabine treatment. Collectively this data suggest that infusing nab-paclitaxel after 48 hours of gemcitabine infusion would be optimal for both increased uptake as well as increased susceptible tumor cells. We had previously shown this effect on multiple cell lines as well as mouse models. Methods: This is a phase II trial; patients will receive a standard of care chemotherapy regimen consisting of FDA-approved Gemcitabine + nab-paclitaxel with modification of the schedule to deliver nab-paclitaxel 48 hours (2 days) after gemcitabine infusions. The primary endpoint is ORR, with a null hypothesis of 20% vs. a target of 35%. Employing a 2-stage design (minimax) and assuming 80% power and a 0.05 significance level, a total of 53 patients will be required. In the first stage, if at least 7/31 patients respond to therapy, an additional 22 patients will be added for a total of 53 patients. The study will be terminated early if ≤ six patients respond in the first stage. Observation of response in at least 16/53 patients would be required to warrant further investigation of this infusion schedule of combination therapy. The secondary endpoints include the safety of the regimen schedule, Relative dose intensity, disease control rate, PFS, and OS. The trial opened to enrollment in June 2020 and is accepting patients. Clinical trial information: NCT04115163.

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