MP24-16 PSOAS MUSCLE VOLUME IS A PREDICTIVE MARKER OF APPETITE LOSS IN PROSTATE CANCER PATIENTS TREATED WITH ENZALUTAMIDE

e16500 Background: Obesity has been reported to have an influence on prostate cancer incidence and its aggressive phenotype but this remains controversial. Body mass index (BMI) is useful marker of obesity but it does not represent body fat percentage precisely. The relationship between body composition and the efficacy of androgen deprivation therapy (ADT) has not well been studied. Here, we investigated whether body composition features including the psoas muscle may be predictive factors of ADT. Methods: This study enrolled hormone-sensitive metastatic prostate cancer patients who were treated with primary ADT from April 2006 to August 2009 in Kyushu University Hospital, and who underwent a CT scan prior to primary ADT for calculating body fat percentage, psoas muscle ratio (psoas muscle, cm3/height, cm2), and BMI. Results: Of the 178 patients enrolled, 60 patients died during follow-up. Median follow-up was 32 months, and progression-free survival (PFS) and overall survival (OS) were 28 and 80 months, respectively. Multivariate analysis revealed that the psoas muscle ratio was correlated with OS (hazard ratio [HR]: 0.448; 95% CI = 0.206–0.922; P= 0.028). Conclusions: This study demonstrated that higher psoas muscle ratio predicts longer OS among non-localized prostate cancer patients treated with primary ADT. [Table: see text]

Download Full-text

Association of "DNA damage signature" with poor outcome in early prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.13 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 13-13

Author(s):

Mahesh Iddawela ◽

Carmel Pazaro ◽

Mitchell Lawrence ◽

Luc Furic ◽

Renea Taylor ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Damage ◽

Cancer Patients ◽

Prognostic Marker ◽

Disease Free Survival ◽

Predictive Marker ◽

Parp Inhibitors ◽

The Cancer Genome Atlas ◽

Early Prostate Cancer ◽

Poor Outcome

13 Background: Whole genome and matching normal tissue analyses in prostate cancer patients have shown that widespread genomic changes occur in multiple distant regions of the genome simultaneously (Baca et al., Cell. 2013). The inherent genomic instability in prostate cancers causes activation of pathways involved in DNA damage, which could be a prognostic and potentially predictive marker for treatment with agents impacting DNA repair (e.g. PARP inhibitors). Using a published dataset, a “DNA damage signature” was generated to test its role as a potential prognostic marker. Methods: A 10-gene signature was generated, using the top 9 genes (MXD3, ZMYND19, BANF1, TOMM40, UBE2S, SNRPF, RPP21, CDK2AP2 and H2AFX) correlated with H2AFX expression, which is known to be unregulated upon DNA damage. TP53 was added due to its significant role in this pathway. This signature was then assessed in The Cancer Genome Atlas dataset (TCGA, unpublished data at NCI) as a discovery set and then validated in the MSK dataset (Taylor et al., 2010) using mutation, copy number, mRNA and proteomic data. Results: Genes in the signature were altered in 31% (77/246) of patients, by amplification and over expression compared to normal. The most frequent alterations were found in TP53 (15%), MXD3 (7%), BANF1 (7%), UBE28 (7%) and CDK2AF2 (7%). Analysis of protein changes associated with alteration in genomic signature showed upregulation of FOXO3, BCL2L1, BAK1 and PCNA (P<0.05). There were significant correlations between the signature and Gleason score (p=0.0015), PTEN (p=0.003) & RAD51 gene expression (p<0.001), but not with ERG,PSA, PIK3CA or BRCA2. Patients with alterations were associated with poor disease free survival (DFS) (p=0.002). When expression was assessed in the validation set, 73%(62/85) samples showed altered gene signatures and those with alterations also had poor DFS (p=0.003). Conclusions: The DNA damage signature can be used to define a group of patients with poor outcome and has the potential to be used as prognostic marker in treatment decisions in early prostate cancer patients.

Download Full-text

Can serum IL-6 levels predict sarcopenia and poor outcome in relapsed/refractory gynecologic cancer patients?

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2592 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2592-2592

Author(s):

Tomoyuki Yoshikawa ◽

Masashi Takano ◽

Kazuya Kudoh ◽

Morikazu Miyamoto ◽

Tadashi Aoyama ◽

...

Keyword(s):

Skeletal Muscle ◽

Serum Level ◽

Cancer Patients ◽

Cancer Cachexia ◽

Gynecologic Cancer ◽

Psoas Muscle ◽

Muscle Volume ◽

Rank Test ◽

Gynecologic Cancers ◽

Psoas Major Muscle

2592 Background: Cancer cachexia occurs in more than half of cancer patients and can be the primary cause of death for at least 20% of all patients. Cancer cachexia also lowers quality of life in cancer survivors due to a severe loss of skeletal muscle mass. Although a multitude of cytokines have been implicated in facilitating a cachectic state, the correlation of serum IL-6 and cancer-induced muscle wasting in gynecologic cancer patients has not been elucidated. Methods: The correlation between serum level of IL-6 and skeletal muscle volume in the patients with gynecologic cancers that received multiple lines of therapy was retrospectively evaluated. We used the psoas muscle index [PMI (cm2/m2)], the psoas major muscle area at the fifth lumber level divided by the height squared, measured using digital axial CT images, for the value of skeletal muscle volume. The level of IL-6 cut-off for elevation was defined as more than 12.0 pg/mL. The comparison of the survival distributions from the day of IL-6 measuaments was made using a log-rank test. Results: A total of 74 cases were assessed for the serum IL-6 and PMI: 32 cases with Mullerian cancers, 24 cases with endometrial cancers, 13 cases with cervical cancers, and 5 patients with others. The group with elevated IL-6 were associated with the lower PMI (t-test, p = 0.0154). The patients with IL-6 elevation had significantly worse survival compared with those with normal IL-6 (1y-OS; 31% vs. 80%, p < 0.0001). In 28 patients with more than two-point measurements of IL-6, the patients with the decrease to the level of IL-6 cut-off had favorable survival compared with those without the decrease (6m-OS; 100% vs. 52%, p = 0.0069). Conclusions: Serum level of IL-6 could be a sentinel biomarker for cancer-induced sarcopenia in the patients with gynecologic cancers. Additionally, IL-6 could be a biomarker to determine further continuation of aggressive chemotherapy for the patients that had received multiple lines of chemotherapy.

Download Full-text