Association Between Changes in Body Composition and Neoadjuvant Treatment for Pancreatic Cancer.

Published on Sep 1, 2018in JAMA Surgery13.625
· DOI :10.1001/JAMASURG.2018.0979
Marta Sandini15
Estimated H-index: 15
(University of Milano-Bicocca),
Manuel Patino11
Estimated H-index: 11
(Harvard University)
+ 20 AuthorsCarlos Fernandez-del Castillo101
Estimated H-index: 101
(Harvard University)
Importance Sarcopenia and sarcopenic obesity have been associated with poor outcomes in unresectable pancreatic cancer (PC). Neoadjuvant treatment (NT) is used increasingly to improve resectability; however, its effects on fat and muscle body composition have not been characterized. Objectives To evaluate whether NT affects muscle mass and adipose tissue in patients with borderline resectable PC (BRPC) and locally advanced PC (LAPC) and determine whether there were potential differences between patients who ultimately underwent resection and those who did not. Design, Setting, and Participants In this retrospective cohort study conducted at 4 academic medical centers, 193 patients with BRPC and LAPC undergoing surgical exploration after NT who had available computed tomographic scans (both at diagnosis and preoperatively) and confirmed pancreatic ductal adenocarcinoma were evaluated. The study was conducted from January 2013 to December 2015. Data analysis was performed from September 2016 to May 2017. Measurement of body compartments was evaluated with volume assessment software before and after NT. A radiologist blinded to the patient outcome assessed the areas of skeletal muscle, total adipose tissue, and visceral adipose tissue through a standardized protocol. Exposures Receipt of NT. Main Outcomes and Measures Achievement of pancreatic resection at surgical exploration after the receipt of NT. Results Of the 193 patients with complete radiologic imaging available after NT, 96 (49.7%) were women; mean (SD) age at diagnosis was 64 (11) years. Most patients received combined therapy with fluorouracil, irinotecan, oxaliplatin, leucovorin, and folic acid (124 [64.2%]) and 86 (44.6%) received chemoradiotherapy as well. The median interval between pre-NT and post-NT imaging was 6 months (interquartile range [IQR], 4-7 months). All body compartments significantly changed. The adipose compound decreased (median total adipose tissue area from 284.0 cm 2 ; IQR, 171.0-414.0 to 250.0 cm 2 ; IQR, 139.0-363.0; P 2 ; IQR, 59.9-191.0 to 97.7 cm 2 ; IQR, 48.0-149.0 cm 2 ; P 2 ; IQR, 99.3-142.0 to 123 cm 2 ; IQR 104.8-152.5 cm 2 ; P  = .001). Surgical resection was achievable in 136 (70.5%) patients. Patients who underwent resection had experienced a 5.9% skeletal muscle area increase during NT treatment, whereas those who did not undergo resection had a 1.7% decrease ( P Conclusions and Relevance Patients with PC experience a significant loss of adipose tissue during neoadjuvant chemotherapy, but no muscle wasting. An increase in muscle tissue during NT is associated with resectability.
📖 Papers frequently viewed together
339 Citations
2,576 Citations
1,629 Citations
#1G. Carrara (UniSR: Vita-Salute San Raffaele University)H-Index: 3
#2Nicolò Pecorelli (UniSR: Vita-Salute San Raffaele University)H-Index: 20
Last. Marco Braga (UniSR: Vita-Salute San Raffaele University)H-Index: 43
view all 7 authors...
Summary Background & aims Recent studies report that muscle depletion can impair short and long-term results after abdominal surgery. The aim of the present study is to quantify sarcopenia rate in patients undergoing pancreatic resection for cancer and to identify possible determinants of muscle waste. Methods Total abdominal muscle area (TAMA) and visceral fat area (VFA) were measured by preoperative CT scan imaging at the level of the third lumbar vertebra in 273 patients undergoing pancreas r...
27 CitationsSource
#1Marta SandiniH-Index: 15
Last. Luca GianottiH-Index: 54
view all 8 authors...
Abstract Objective Complication rates after pancreatic resections remain high despite improvement in perioperative management. The effects of body composition and the relationship among different body compartments on surgical morbidity are not comprehensively investigated. The aim of this study was to assess whether the evaluation of different body compartments and their relationship was associated with the development of major postoperative complications after pancreatoduodenectomy (PD) for can...
61 CitationsSource
#1Cecilia GavazziH-Index: 23
#2Silvia ColatruglioH-Index: 3
Last. Rosalba MiceliH-Index: 63
view all 8 authors...
Abstract Background Weight loss is frequent in patients with gastrointestinal (GI) cancer. Nutritional status deteriorates throughout anti-cancer treatment, mostly after major surgery, increasing complications, reducing tolerance and worsening the final prognosis. Enteral nutrition is safe and effective in malnourished patients undergoing major GI surgery. Randomised trials aimed at investigating the effects of home enteral nutrition (HEN) in post-surgical patients with GI cancer are lacking. Th...
39 CitationsSource
#1Claudio BassiH-Index: 110
#2G. BalzanoH-Index: 8
Last. Marco RameraH-Index: 9
view all 4 authors...
Improving the quality and effectiveness of care is a key priority of any health policy. The outcomes of health care can be considered as indicators of effectiveness or quality. The scientific literature that evaluates the association between the volume of activity and the outcome of health interventions has greatly developed over the past decade, but, for practical reasons, ethical and social issues, a few randomized controlled studies were made to evaluate this association, although there are n...
13 CitationsSource
#1Yasunori NishidaH-Index: 4
#2Yuichiro KatoH-Index: 16
Last. Masaru KonishiH-Index: 44
view all 11 authors...
Background Postoperative pancreatic fistula (POPF) is a serious complication of pancreaticoduodenectomy (PD). Sarcopenia is a newly identified marker of frailty. We performed this study to assess whether preoperative sarcopenia has an impact on clinically relevant POPF formation.
62 CitationsSource
#1Michele Petruzzelli (Medical Research Council)H-Index: 16
#2Erwin F. WagnerH-Index: 131
Metabolic dysfunction contributes to the clinical deterioration observed in advanced cancer patients and is characterized by weight loss, skeletal muscle wasting, and atrophy of the adipose tissue. This systemic syndrome, termed cancer-associated cachexia (CAC), is a major cause of morbidity and mortality. While once attributed solely to decreased food intake, the present description of cancer cachexia is a disorder of multiorgan energy imbalance. Here we review the molecules and pathways respon...
159 CitationsSource
#1Nicolò Pecorelli (UniSR: Vita-Salute San Raffaele University)H-Index: 20
#2G. Carrara (UniSR: Vita-Salute San Raffaele University)H-Index: 3
Last. Marco Braga (UniSR: Vita-Salute San Raffaele University)H-Index: 43
view all 8 authors...
Background Analytical morphometric assessment has recently been proposed to improve preoperative risk stratification. However, the relationship between body composition and outcomes following pancreaticoduodenectomy is still unclear. The aim of this study was to assess the impact of body composition on outcomes in patients undergoing pancreaticoduodenectomy for cancer. Methods Body composition parameters including total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed by pr...
115 CitationsSource
#1Younak Choi (Seoul National University Hospital)H-Index: 7
#2Do-Youn Oh (Seoul National University Hospital)H-Index: 56
Last. Yung-Jue Bang (Seoul National University Hospital)H-Index: 107
view all 8 authors...
Introduction Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer.
124 CitationsSource
#1Katie E. Rollins (NIHR: National Institute for Health Research)H-Index: 16
#2Nilanjana Tewari (NIHR: National Institute for Health Research)H-Index: 7
Last. Dileep N. Lobo (NIHR: National Institute for Health Research)H-Index: 71
view all 8 authors...
Summary Background & aims Patients with pancreatic cancer have a poor prognosis, are often cachectic, and frequently demonstrate features of systemic inflammation, which may contribute to the phenomenon of myosteatosis. Analysis of body composition from CT scans has been used to study sarcopenia and its association with prognosis in a number of types of cancer, particular in combination with obesity. It has also been suggested that myosteatosis, defined as attenuated mean skeletal muscle Hounsfi...
118 CitationsSource
#1Amanda B. Cooper (Penn State Milton S. Hershey Medical Center)H-Index: 14
#2Rebecca Slack (University of Texas MD Anderson Cancer Center)H-Index: 25
Last. Matthew H.G. Katz (University of Texas MD Anderson Cancer Center)H-Index: 66
view all 17 authors...
Background Little is known about changes in body composition that may occur during neoadjuvant therapy for pancreatic cancer. This study was designed to characterize these changes and their potential relationships with therapeutic outcomes.
85 CitationsSource
Cited By48
Neoadjuvant treatment: A window of opportunity for nutritional prehabilitation in patients with pancreatic ductal adenocarcinoma
#1M.E. Phillips (University of Surrey)
#2M.D. Robertson (University of Surrey)
view all 5 authors...
Summary null null Background and aims null Patients with pancreatic cancer often experience significant deterioration in nutritional status over time. Malnutrition is complex and multifactorial, with malabsorption, pain, toxic dependencies, co-morbidities and malignant processes all playing a role. The aims of this systematic review were to assess nutritional changes over time and identify tolerance of nutritional intervention, thus identifying potential areas for further research to improve pat...
#1Mustafa Jalal (Royal Hallamshire Hospital)H-Index: 3
#2Jennifer A Campbell (Royal Hallamshire Hospital)H-Index: 4
Last. Andrew D. Hopper (Royal Hallamshire Hospital)H-Index: 19
view all 4 authors...
Purpose null 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). null Methods null Patients diagnosed with LAPC referred for endo...
#1Dong Woo ShinH-Index: 3
#2Minseok Albert Kim (Seoul National University Hospital)H-Index: 2
Last. Jin-Hyeok HwangH-Index: 31
view all 5 authors...
1 CitationsSource
#1Jian-Xian Lin (Fujian Medical University)H-Index: 22
#2Yi-Hui Tang (Fujian Medical University)H-Index: 1
Last. Felice BorghiH-Index: 9
view all 22 authors...
Summary null null Background null Body composition profiles influence the prognosis of several types of cancer; however, the role of body composition in patients with locally advanced gastric cancer (LAGC) after neoadjuvant treatment (NT) has not been well characterized. null null null Patients and methods null A total of 213 patients with LAGC who underwent gastrectomy after NT at a high-volume institution from southern China were comprehensively evaluated for primary analysis. Additionally, 17...
#1Joseph E. Rupert (IU: Indiana University)H-Index: 5
#2Ashok Narasimhan (IU: Indiana University)H-Index: 3
Last. Teresa A. ZimmersH-Index: 37
view all 15 authors...
Most patients with pancreatic adenocarcinoma (PDAC) suffer cachexia; some do not. To model heterogeneity, we used patient-derived orthotopic xenografts. These phenocopied donor weight loss. Furthermore, muscle wasting correlated with mortality and murine IL-6, and human IL-6 associated with the greatest murine cachexia. In cell culture and mice, PDAC cells elicited adipocyte IL-6 expression and IL-6 plus IL-6 receptor (IL6R) in myocytes and blood. PDAC induced adipocyte lipolysis and muscle stea...
3 CitationsSource
#1Calvin ColeH-Index: 7
#2John F. Bachman (URMC: University of Rochester Medical Center)H-Index: 3
Last. David C. Linehan (URMC: University of Rochester Medical Center)H-Index: 62
view all 11 authors...
BACKGROUND Skeletal muscle wasting (SMW) in cancer patients is associated with increased morbidity, mortality, treatment intolerance and discontinuation, and poor quality of life. This is particularly true for patients with pancreatic ductal adenocarcinoma (PDAC), as over 85% experience SMW, which is responsible for ~30% of patient deaths. While the established paradigm to explain SMW posits that muscle catabolism from systemic inflammation and nutritional deficiencies, the cause of death, and t...
PURPOSE OF REVIEW Cancer cachexia is a syndrome of loss of weight and muscle mass that leads to reduced strength, poor physical performance and functional impairment. Muscular fatigue is a distressing syndrome that patients with cachexia suffer from and can impair quality of life. Here, we review recent updates in muscular fatigue in cancer cachexia research with a focus on mechanisms, biomarkers and potential therapies. RECENT FINDINGS Both in mice and humans, research has shown that muscle fat...
3 CitationsSource
#1Fabio Casciani (UPenn: University of Pennsylvania)H-Index: 2
#2Maxwell T. Trudeau (UPenn: University of Pennsylvania)H-Index: 3
Last. Ronald R. SalemH-Index: 29
view all 55 authors...
Abstract Background The association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored. Methods In total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003–2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated ...
#1Powell-Brett S (University Hospitals Birmingham NHS Foundation Trust)
#2Rupaly PandeH-Index: 3
Last. Fujii T
view all 3 authors...
Improving outcomes among patients with resectable pancreatic cancer is one of the greatest challenges of modern medicine. Major improvements in survival will result from the development of novel therapies. However, optimising existing pathways, so that patients realise benefits of already proven treatments, presents a clear opportunity to improve outcomes in the short term. This narrative review will focus on treatments and interventions where there is a clear evidence base to improve outcomes i...
1 CitationsSource