Additional file 1: Figure S1. of Associations and prognostic implications of Eastern Cooperative Oncology Group performance status and tumoral LINE-1 methylation status in stage III colon cancer patients

Survival analyses using RFS from the date of chemotherapy. (A) Survival analyses show that low LINE-1 methylation status was closely associated with shorter RFS times (P = 0.040). (B) There was no significant difference in RFS according to the performance status (PS). (C) Survival analysis stratified by combinatory PS and LINE-1methyaltion statuses. The difference was significant between PS(0)/LINE-1(high) and PS(1)/LINE-1(low) (P = 0.021). (D) Survival analysis using the TNR value in higher BMI score patients. (TIF 3476 kb

Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index

<div><p>Introduction</p><p>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.</p><p>Methods</p><p>We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm²/m² (male) and < 33.9 cm²/m² (female) using ROC curve.</p><p>Results</p><p>Among 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (<i>P</i>< 0.001), decreasedBMI and SMI during chemotherapy (<i>P</i> = 0.002, <i>P</i> = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (<i>P</i>< 0.001) and decreased SMI (<i>P</i> = 0.001), the OS of female patients was influenced with overweight at diagnosis (<i>P</i> = 0.006), decreased BMI (<i>P</i> = 0.032) and decreased SMI (<i>P</i> = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (<i>P</i> = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; <i>P</i> = 0.002).</p><p>Conclusions</p><p>Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.</p></div

ROC curve ofsarcopenia for both genders.

<p>ROC curve ofsarcopenia for both genders.</p

Clinical characteristics by gender.

<p>LAPC, locally advanced pancreatic cancer; MPC, metastatic pancreatic cancer; ECOGPS, Eastern Cooperative Oncology Group performance status;BMI, body mass index; SMI, skeletal muscle index; SD, standard deviation.</p><p>^†Sarcopenia: males< 42.2 cm²/m², females< 33.9 cm²/m².</p><p>^<i>a</i><i>P</i>values were calculated using theFisher’s exact test.</p><p>^<i>b</i><i>P</i>values were calculated using theIndependent t-test.</p><p>Clinical characteristics by gender.</p

Correlation of BMI and SMI at diagnosis.

<p>BMI, body mass index; SMI, skeletal muscle index; HR, hazard ratio; OS, overall survival.</p><p>^<i>a</i><i>P</i>values were calculated using the Cox-proportional hazard model, adjusted with gender, age, extent of disease, and PS.</p><p>^<i>b</i><i>P</i>values were calculated using the Cox-proportional hazard model, adjusted with age, extent of disease, and PS.</p><p>^<i>c</i><i>P</i>values were calculated within nonsarcopenia group.</p><p>^<i>d</i><i>P</i>values were calculated within sarcopenia group.</p><p>Correlation of BMI and SMI at diagnosis.</p

Computed tomography images of the region of the third lumbar vertebra, with skeletal muscle highlighted in blue (-29 to 150 Hounsfield units).

<p>The blue line on the three-dimensionally reconstructed image on the left indicates the level of the third lumbar vertebra, which is shown in the axial view on the right.</p

Correlation of changesin BMI and SMI.

<p>BMI, body mass index; SMI, skeletal muscle index; HR, hazard ratio; OS, overall survival</p><p>^<i>a</i><i>P</i>values were calculated using the Cox-proportional hazard model, adjusted with gender, age, extent of disease, PS, BMI at diagnosis, and sarcopenia.</p><p>^<i>b</i><i>P</i>values were calculated using the Cox-proportional hazard model, adjusted withage, extent of disease, PS, BMI at diagnosis, and sarcopenia.</p><p>^<i>c</i><i>P</i>values were calculated within maintained SMI group.</p><p>^<i>d</i><i>P</i>values were calculated within decreased SMI group.</p><p>Correlation of changesin BMI and SMI.</p

Survival according to change in body mass indexand skeletal muscle index.

<p>BMI decreased by more than 1 kg/m² and SMI decreased by more than 2 cm²/m² were strongly related to worseoutcome. Decrease of BMI (A) for the entire patients (HR 1.452; <i>P</i> = 0.002); (B) for the male patients (HR 1.218; <i>P</i> = 0.142); (C) for the female patients (HR 1.464; <i>P</i> = 0.032). Decrease of SMI (D) for the entire patients (HR 1.390;<i>P</i> = 0.004); (E) for the male patients (HR 1.560; <i>P</i> = 0.001); (F) for the female patients (HR 1.521; <i>P</i> = 0.014).</p

Changes in body composition during first line chemotherapy by gender.

<p>BMI, body mass index; SMI, skeletal muscle index; SD, standard deviation.</p><p>^†Change in BMI: maintained ≥ -1 kg/m², decreased < -1 kg/m².</p><p>^‡Change in SMI: maintained ≥ -2 cm²/m²; decreased < -2 cm²/m².</p><p>^<i>a</i><i>P</i> values were calculated using theFisher exact test.</p><p>^<i>b</i><i>P</i>values were calculated using theIndependent t-test.</p><p>Changes in body composition during first line chemotherapy by gender.</p

Factors associated with overall survival.

<p>LAPC, locally advanced pancreatic cancer; MPC, metastatic pancreatic cancer; PS, performance status;BMI, body mass index; SMI, skeletal muscle index; OS, overall survival; HR, hazard ratio; CI, confidential interval.</p><p>^†Controlled: complete response, partial response, and stable disease.</p><p>Factors associated with overall survival.</p