scholarly journals Incidence and frequency of cancer cachexia during chemotherapy for advanced pancreatic ductal adenocarcinoma

2020 ◽  
Vol 28 (11) ◽  
pp. 5271-5279 ◽  
Author(s):  
Shuichi Mitsunaga ◽  
Eiji Kasamatsu ◽  
Koji Machii
Keyword(s):  
Overall Survival ◽  
Weight Loss ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cachexia ◽  
Ductal Adenocarcinoma ◽  
Cancer Therapies ◽  
First Line ◽  
Timing Of Onset ◽  
Line Chemotherapy

Abstract Purpose Cachexia influences the patient’s physical wellbeing and quality of life, and the patient’s ability to tolerate their cancer therapies, especially cytotoxic chemotherapy. The purpose of this study was to investigate the frequency and timing of onset of cancer cachexia during chemotherapy and its association with prognosis and toxicity in patients with pancreatic ductal adenocarcinoma (PDAC). Methods We performed a retrospective study in patients who underwent first-line chemotherapy after diagnosis of advanced PDAC between 6 June 2008 and 31 March 2017. Base cachexia (weight loss up to 6 months before starting first-line chemotherapy) and follow-up cachexia (after starting first-line chemotherapy) were defined as weight loss > 2% with a body mass index (BMI) < 20 kg/m2 or weight loss > 5%. Results A total of 150 patients were registered. The median age and BMI were 65 years and 21.7 kg/m2, respectively. Base cachexia occurred in 50% of patients. Follow-up cachexia occurred in 32% within 12 weeks of starting first-line chemotherapy, reaching 64% at 1 year. Overall survival was not significantly different between patients with and without follow-up cachexia, regardless of whether cancer cachexia occurred within 12, 24, or 48 weeks of starting first-line treatment. Appetite loss, fatigue, nausea, and diarrhea were more frequent in patients with follow-up cachexia than in those without follow-up cachexia. Conclusion Follow-up cachexia had an early onset, but was not a prognostic factor for overall survival in patients with PDAC. Some adverse events tended to be more frequent in patients with follow-up cachexia than in those without follow-up cachexia.

Homologous recombination deficiency (HRD): A biomarker for first-line (1L) platinum in advanced pancreatic ductal adenocarcinoma (PDAC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4132-4132 ◽  
Author(s):  
Wungki Park ◽  
Winston Wong ◽  
Kenneth H. Yu ◽  
Anna M. Varghese ◽  
Nadeem Riaz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ductal Adenocarcinoma ◽  
Clinical Implications ◽  
Genomic Profiling ◽  
First Line ◽  
Biomarker Validation ◽  
Definition Of ◽  
Platinum Chemotherapy ◽  
Prospective Database

4132 Background: HRD is an emerging biomarker for platinum therapy in PDAC. The clinical implications regarding differences in outcome between germline and somatic HRD in advanced PDAC treated with 1L platinum is unexplored. Methods: We evaluated overall survival (OS) for advanced PDAC (stage III/IV) based on their pathogenic germline (gHRD) and somatic HRD (sHRD) using integrated genomic profiling from MSK-IMPACT and 1L platinum use. HRD defined by pathogenic alterations from the following genes: BRCA1/2, PALB2, ARID1A/B/2, ATR, ATRX, ATM, BAP1, RAD50/51C/D, BRIP1, NBN, CHECK1/2, FANCA/C, CDK12, and MRE11. Results: Advanced PDAC patients (n=461) treated at MSK enrolled in a prospective database, were evaluated. Median follow-up was 27.6 months (95% CI, 24.6-30.6). Both germline and somatic profilings were available for n=350 (76%) but only somatic profiling was available for n=111 (24%). We identified n=52 patients with gHRD (11.3%), n=42 patients with sHRD (9.1%), and 48 patients with somatic VUS for HRD genes. From all 461 patients, the OS was not different between 1L non-platinum vs. 1L platinum groups (19 M vs. 19.3 M), regardleess of their HRD status. (Table) The OS was superior for gHRD vs. non-gHRD (28.7 M vs. 18.2 M), regardless of 1L treatment choice. However, similar significant OS superiority was neither observed in sHRD vs. non-sHRD, nor in VUS sHRD vs. non-VUS sHRD. In a subgroup analysis of 1L platinum treated patients, the OS was superior in gHRD vs. non-gHRD (NR vs. 17.9 M); however, there was no OS difference between sHRD and non-sHRD. Conclusions: In advanced PDAC patients, only gHRD predicted better overall survival for first-line platinum chemotherapy. These findings emphasize the importance of germline mutation testing of HRD in PDAC. Biomarker validation and functional definition of HRD such as loss of heterozygosity analysis is underway. [Table: see text]

scholarly journals The systemic activin response to pancreatic cancer: Implications for effective cancer cachexia therapy

2018 ◽  
Author(s):  
Xiaoling Zhong ◽  
Marianne Pons ◽  
Christophe Poirier ◽  
Yanlin Jiang ◽  
Jianguo Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Weight Loss ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Conditioned Medium ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Cancer Cachexia ◽  
Dominant Negative ◽  
Prolonged Survival ◽  
Ductal Adenocarcinoma

AbstractPancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy with high rates of cachexia. Serum activin correlates with PDAC cachexia and mortality, while activin administration causes cachexia in mice. We studied activin in human tumors and in mice with orthotopic or genetic PDAC. Cachexia severity correlated with activin expression in tumor lines. Activins were expressed in both cancer and tumor stromal cells, but also in organs in murine PDAC cachexia. Tumor cells expressed activin-βA, or Inhba, while organs expressed both activin-βA and activin-βB, or Inhbb. PDAC elicits activin expression; PDAC conditioned medium induced activin and atrophy of myotubes. Treatment with the activin trap, ACVR2B/Fc, reduced cachexia and prolonged survival in mice with activin-low tumors, and reduced cachexia in activin-high tumors, without affecting activin expression in organs. Mice expressing dominant negative ACVR2B in muscle were protected for weight loss but not survival. Overall our results indicate that PDAC induces a systemic activin response, leading to cachexia, and that activin targets might include organs beyond muscle. Targeting of both tumor-derived and host-derived activins could improve cachexia therapy.

scholarly journals 18F-FDG PET/CT imaging biomarkers for early and late evaluation of response to first-line chemotherapy in patients with pancreatic ductal adenocarcinoma

2021 ◽  
pp. jnumed.121.261952
Author(s):  
Matthias R. Benz ◽  
Wesley R. Armstrong ◽  
Francesco Ceci ◽  
Giulia Polverari ◽  
Timothy R. Donahue ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Fdg Pet ◽  
Ct Imaging ◽  
Ductal Adenocarcinoma ◽  
Imaging Biomarkers ◽  
First Line ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Line Chemotherapy

scholarly journals A retrospective cohort study to investigate the incidence of cancer-related weight loss during chemotherapy in gastric cancer patients

2020 ◽  
Vol 29 (1) ◽  
pp. 341-348 ◽  
Author(s):  
Masaru Fukahori ◽  
Masayuki Shibata ◽  
Satoshi Hamauchi ◽  
Eiji Kasamatsu ◽  
Koji Machii
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Weight Loss ◽  
Cohort Study ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
First Line ◽  
Line Chemotherapy

Abstract Purpose This study aimed to evaluate cancer-related weight loss (WL) after the start of first-line chemotherapy as a surrogate marker for cancer cachexia in patients with advanced gastric cancer. We investigated the incidence of WL and the relationship between WL and overall survival (OS) or adverse events. Methods We conducted a retrospective cohort study in 131 patients with advanced gastric cancer who received first-line systemic chemotherapy between September 1, 2010, and August 31, 2016, at Kurume University Hospital and Shizuoka Cancer Center Hospital. WL was defined in this study as weight loss of > 5% or weight loss of > 2% with a body mass index of < 20 kg/m2 within the last 6 months after the start of chemotherapy. Results Median age and median Eastern Cooperative Oncology Group performance status of the patients participating in this study were 68 years old and 0, respectively. Incidence of WL was 53% at the first 12 weeks after starting first-line chemotherapy, and increased to 88% after 48 weeks. Overall survival rates were significantly associated with WL at 12, 24, and 48 weeks. Appetite loss and fatigue were more frequent and more severe in patients with WL. Conclusion WL was especially observed in more than half the patients within 12 weeks after starting chemotherapy. WL appeared to relate to adverse events or reduced survival. These results suggest the importance of monitoring WL or providing nutritional support at the beginning of chemotherapy.

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