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  • Fig Impact of low muscle attenuation at iframe

    2022-04-24

    Fig. 2. Impact of low muscle attenuation at diagnosis on mortality risk (cox regression).
    p ΒΌ 0.004) (Fig. 4). In a multivariable model, the following indices remained predictive of better survival; administration of radio-therapy as part of neoadjuvant therapy, normal muscle attenuation at baseline, amd preservation of muscle during therapy. No other factors remained significant (Table 3).
    Discussion
    We found that low muscle attenuation or radiodensity at diag-nosis, along with further muscle depletion during chemotherapy was associated with a higher risk of death in patients with BRPC. Furthermore, we highlighted the extent of cancer cachexia and sarcopenia at diagnosis for patients with BRPC.
    While previous studies showed that cancer cachexia affects between 40 and 80% of patients with pancreatic cancer, we believe that this Veratridine is the first study to evaluate the incidence using the Fearon classification [11] in a BRPC cohort.. We have shown that cancer cachexia is an early feature of the disease. Despite this, we did not
    find an association between cachexia at diagnosis and resectability, treatment tolerance, treatment delivery or overall survival. This is consistent with the findings of a recent study which evaluated the impact of baseline body composition on survival in nearly 800 patients with untreated pancreatic cancer [15]. They also reported that sarcopenia and depletion of adipose tissue stores were early features of the disease, but did not impact survival.
    While sarcopenia and cachexia at diagnosis were not associated with treatment outcome, low muscle attenuation at the time of diagnosis was found to double mortality risk. A previous cohort study of Japanese pancreatic cancer patients found that low muscle attenuation prior to neoadjuvant chemotherapy was not signifi-cant, however post treatment muscle attenuation was a negative prognostic indicator [16]. In fact, muscle attenuation may be su-perior to mass measure in predicting functional and strength assessment [17]. Muscle attenuation or radiodensity is reduced by adipose tissue infiltration of muscle, a known consequence of ag-ing. Increased accumulation of Veratridine lipid within muscle has also been
    Please cite this article as: Griffin OM et al., Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer, Pancreatology, https://doi.org/10.1016/j.pan.2019.07.039
    O.M. Griffin et al. / Pancreatology xxx (xxxx) xxx 5
    Fig. 3a. Impact of Fat-free Mass Loss (kg) during chemotherapy (Cox regression analysis).
    demonstrated in patients with increased inflammation associated with cachexia [18]. Transcriptomic analysis of rectus abdominal muscle biopsies taken from patients with pancreatic cancer at the time of resection highlighted that sarcopenia and myosteatosis are distinct biological profiles; increased inflammation and decreased muscle synthesis were observed in sarcopenia while disruption of oxidative phosphorylation and lipid accumulation were seen in patients with low muscle radiodensity [19]. Unlike most studies evaluating muscle radiodensity in pancreatic cancer patients to date, we measured muscle attenuation in muscle only by isolating and measuring intra-muscular adipose tissue separately. This approach was also adopted in a recent Dutch cohort study evalu-ating pancreatic cancer patients who underwent surgery where low muscle attenuation at diagnosis was also associated with reduced survival [20].
    Only three studies have sought to quantify body composition change during neoadjuvant chemotherapy for pancreatic cancer to date. The first study evaluated body composition change in 89 patients who received neoadjuvant Gemcitabine combined with Cisplatin followed by short-course radiotherapy and concurrent Gemcitabine as part of a phase II study [21]. The majority (64%) achieved resectability following treatment. A significant loss of skeletal muscle, visceral and subcutaneous adipose tissue were observed, and degree of muscle loss correlated with disease-free survival, while visceral adipose loss was associated with overall and progression-free survival. Another study from that institution longitudinally evaluated 127 patients who achieved resectability following neoadjuvant therapy [22]. Similar to our work, a combi-nation of chemotherapy regimens was used. Unlike their earlier findings only minimal changes in body composition during neo-adjuvant therapy were observed. In contrast, post-operative
    skeletal muscle increase during the first year following resection was associated with improved survival. More recently, a retro-spective cohort of 193 patients who were treated across 4 in-stitutions over 3 year period were evaluated [23]. Nearly two thirds of patients received Folfirinox chemotherapy, and the majority (71%) achieved resectability. A significant loss of both visceral and subcutaneous adipose tissue was observed while skeletal muscle increased. An increase in skeletal muscle during neoadjuvant chemotherapy was associated with resectability.