The present study showed the longitudinal changes in body composition and the associations of these changes with clinical outcomes in patients with LAPC during the first-line FOLFIRINOX chemotherapy. The principal findings of this study are: (i) the patients with well-maintained SM during chemotherapy were associated with higher resectability and longer OS than those with low SM ratio, even though cRDI was not different. (ii) The AT change during chemotherapy was not correlated with clinical outcomes; however, significant decrease in AT ratio showed poor clinical outcomes.
A large proportion of patients with PC are affected by sarcopenia. Although sarcopenia at the time of diagnosis has been reported to be an independent prognostic factor of reduced survival in PC patients as well as in several cancers [5–10, 12–17], the underlying mechanism that links sarcopenia with poor survival has not been fully elucidated. SM accounts for 40–50% of the total body weight and has a high metabolic capacity [18]. Many studies have reported that sarcopenic patients at the time of diagnosis have poor long-term outcomes [19–21]. However, initial sarcopenia can be exaggerated by cancer burden due to depression, cancer-related gastrointestinal obstruction, or uncontrolled diabetes, especially in patients with PC [15, 16]. The inability to maintain SM causes progressive functional impairment and a decreased quality of life, which in turn increases morbidity and mortality [22, 23]. Considering the vicious cycle of sarcopenia and increased morbidity and mortality, it is necessary to maintain SM in patients with PC.
Further, the findings of our study suggest that AT loss was not significantly associated with prognosis. The significant fat loss is associated with decreased survival in patients with PC, and this finding is consistent with the previously published data [24]. Previous studies have shown that sarcopenia, sarcopenic obesity, and myosteatosis at the time of diagnosis are associated with decreased survival in patients with PC [25, 26]. However, owing to the complexity of PC, it is difficult to fully elucidate the underlying mechanisms associated with AT reduction and poor clinical outcomes.
Furthermore, a study has implicated tumor Fn14 (tumor necrosis factor receptor superfamily member 12A; TNFRSF12A) as an inducer of cachexia in mice models, and it was shown that the antibodies against Fn14 prevented tumor-induced cachexia and extended lifespan without chemotherapy [27]. This suggests that regardless of chemotherapy, survival time can be prolonged if cachexia and sarcopenia are prevented. Since it is difficult to recover completely with the conventional nutritional support, rehabilitation for maintaining SM has also been introduced [28]. As mentioned earlier, maintaining SM during chemotherapy has been linked to longer survival period and higher resectability. The efforts to maintain SM, including dietary or physical rehabilitation programs, concurrent administration of nutritional supplements, and/or drugs targeting chronic inflammation and cachexia may represent a critical adjuvant strategy during chemotherapy [29]. It has been shown that timely nutritional and metabolic support can increase the adherence and improve response to the chemotherapy [30]. Since the rehabilitation program for patients with PC have not yet been established, further research and discussion is needed.