Cachexia Worsens Prognosis in Patients with Resectable Pancreatic Cancer

Bachmann, Jeannine; Heiligensetzer, Mathias; Krakowski-Roosen, Holger; Büchler, Markus W.; Friess, Helmut; Martignoni, Marc E.

doi:10.1007/s11605-008-0505-z

Cited by 351 publications

(284 citation statements)

References 36 publications

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“…Outcome results in this analysis indicate that the median difference in survival in BRPC and LAPC patients is separated by a mere six months, like other findings in the current literature (35,70,71). Our study specifically included patients with only borderline resectable and locally advanced disease, which correlates with IIA, IIB, and III AJCC stages.…”

Section: Discussionsupporting

confidence: 66%

“…The next best option is to use data from multiple studies using percentile based summative values. The literature currently uses a plethora of cohort-specific values, including using the lowest median, tertile, quartile, quintile, or standard deviation (19)(20)(21)23,24,27,28,(33)(34)(35)(36)(37)(38) in the study cohort. We validated our cohort's cutoff, by performing ROC curve analysis with regards to acute radiotoxicities which correlates to approximately a TPA of 500.…”

Section: Discussionmentioning

confidence: 99%

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Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

Jin¹,

Mellon²,

Frakes³

et al. 2018

J. Gastrointest. Oncol.

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Background: Total psoas area (TPA), a marker of sarcopenia, has been used as an independent predictor of clinical outcomes in gastrointestinal (GI) cancers as a proxy for frailty and nutritional status. Our study aimed to evaluate whether TPA, in contrast to traditional measurements of nutrition like body mass index (BMI) and body surface area (BSA), was predictive of outcomes in borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients receiving stereotactic body radiation therapy (SBRT). Methods: Retrospective analysis of an institutional review board approved database of 222 BRPC and LAPC treated with SBRT from 2009-2016 yielded 183 patients that met our selection criteria of pre-SBRT computed tomography (CT) imaging with an identifiable L4 vertebra. Once the L4 vertebral level was identified, the bilateral psoas muscles were manually contoured. This area was normalized by patient height, with units described in mm 2 /m 2 . Receiver operating characteristic (ROC) curves were generated for TPA, BMI, and BSA to elicit clinically relevant cutoffs. Regression and Kaplan-Meier analyses were used to correlate toxicity with survival functions.Results: Low TPA (OR =1.903, P=0.036) was predictive of acute toxicities, and only TPA was predictive of Grade 3 or higher acute toxicities (OR =10.24, P=0.007). Both findings were independent of tumor resectability. Pain (P=0.003), fatigue (P=0.040), and nausea (P=0.039) were significantly associated with low TPA. No association was identified between any measurement of nutritional status and the development of late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median =21.98 months) than their LAPC (median =16.2 months) counterparts (P=0.002), independent of nutritional status. Conclusions: TPA measurement is readily available and more specific than BMI or BSA as a predictor of acute radiotoxic complications following SBRT in BRPC/LAPC patients. A TPA of <500 mm 2 /m 2 is a clinically relevant cutoff that can direct physicians to address expected complications of pain, fatigue, and nausea. However, tumor resectability remains as the only predictor of overall survival in this cohort.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

Jin¹,

Mellon²,

Frakes³

et al. 2018

J. Gastrointest. Oncol.

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“…PDAC is also among the deadliest forms of cancer, with a 93% mortality rate in 5 years following diagnosis 33, 34, 35, 36. Current approaches to treating PDAC include cytotoxic chemotherapy, ionizing radiation, and surgical resection 37, 38.…”

Section: Discussionmentioning

confidence: 99%

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

Michaelis

Zhu

Burfeind

et al. 2017

J cachexia sarcopenia muscle

110

161

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BackgroundCachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC‐associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRASG12D P53R172H Pdx‐Cre+/+ (KPC) mouse.MethodsMale and female C57BL/6 mice were inoculated subcutaneously, intraperitoneally, or orthotopically with KPC tumour cells. We performed rigorous phenotypic, metabolic, and behavioural analysis of animals over the course of tumour development.ResultsAll routes of administration produced rapidly growing tumours histologically consistent with moderate to poorly differentiated PDAC. The phenotype of this model was dependent on route of administration, with orthotopic and intraperitoneal implantation inducing more severe cachexia than subcutaneous implantation. KPC tumour growth decreased food intake, decreased adiposity and lean body mass, and decreased locomotor activity. Muscle catabolism was observed in both skeletal and cardiac muscles, but the dominant catabolic pathway differed between these tissues. The wasting syndrome in this model was accompanied by hypothalamic inflammation, progressively decreasing brown and white adipose tissue uncoupling protein 1 (Ucp1) expression, and increased peripheral inflammation. Haematological and endocrine abnormalities included neutrophil‐dominant leukocytosis and anaemia, and decreased serum testosterone.ConclusionsSyngeneic KPC allografts are a robust model for studying cachexia, which recapitulate key features of the PDAC disease process and induce a wide array of cachexia manifestations. This model is therefore ideally suited for future studies exploring the physiological systems involved in cachexia and for preclinical studies of novel therapies.

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“…There is a vast array of published studies showing reduced survival in weight-losing cancer patients and in those with cachexia. Studies have consistently demonstrated that the prognosis for cancer patients with weight loss is worse than that for weight-stable patients (33)(34)(35)(36) . Table 1 summarises the available evidence for reduced survival in a variety of cancers which report hazard ratios of death ranging from 1·63 to 4·2 (37,38) .…”

Section: Malnutrition Cancer Cachexia and Survivalmentioning

confidence: 99%

Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later

et al. 2016

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An awareness of the importance of nutritional status in hospital settings began more than 40 years ago. Much has been learned since and has altered care. For the past 40 years several large studies have shown that cancer patients are amongst the most malnourished of all patient groups. Recently, the use of gold-standard methods of body composition assessment, including computed tomography, has facilitated the understanding of the true prevalence of cancer cachexia (CC). CC remains a devastating syndrome affecting 50-80 % of cancer patients and it is responsible for the death of at least 20 %. The aetiology is multifactorial and complex; driven by pro-inflammatory cytokines and specific tumour-derived factors, which initiate an energy-intensive acute phase protein response and drive the loss of skeletal muscle even in the presence of adequate food intake and insulin. The most clinically relevant phenotypic feature of CC is muscle loss (sarcopenia), as this relates to asthenia, fatigue, impaired physical function, reduced tolerance to treatments, impaired quality of life and reduced survival. Sarcopenia is present in 20-70 % depending on the tumour type. There is mounting evidence that sarcopenia increases the risk of toxicity to many chemotherapy drugs. However, identification of patients with muscle loss has become increasingly difficult as 40-60 % of cancer patients are overweight or obese, even in the setting of metastatic disease. Further challenges exist in trying to reverse CC and sarcopenia. Future clinical trials investigating dose reductions in sarcopenic patients and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms.

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Cachexia Worsens Prognosis in Patients with Resectable Pancreatic Cancer

Cited by 351 publications

References 36 publications

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later

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