title: An analysis of the relationship between metastases and cachexia in lung cancer patients.
abstract: Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co-occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P < 0.0001] treatment, respectively). The change in number of metastatic sites over time correlated with increasing weight loss (5.2%, 10.6%, 13.4%, and 13.4%, for an increase of 0, 1, 2, and ≥3 metastatic sites, from initial diagnosis to the endpoint; P < 0.0001). Patients with cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08-4.16; P < 0.0001). Tumors with mutated KRAS were associated with an increased risk of weight loss (11.4% weight loss in patients with mutated KRAS vs. 6.0% in patients with wild-type KRAS; P = 0.0011). Our findings suggest that the capabilities of lung cancer to metastasize and cause cachexia might be linked intrinsically and are independent of treatments administered. KRAS-mutated tumors were more commonly associated with cachexia.
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, New York.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Shiono
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Columbia University, New York, New York.
authors.forename: Kan
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Surgery, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Downey
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, New York.
authors.forename: Nikita
authors.initials: N
authors.lastname: Consul
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Columbia University, New York, New York.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Villanueva
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, New York.
authors.forename: Kristen
authors.initials: K
authors.lastname: Beck
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Columbia University, New York, New York.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Fenn
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Columbia University, New York, New York.
authors.forename: Donald
authors.initials: D
authors.lastname: Dietz
authors.affiliation: Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Clinical Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Radiology, Columbia University Medical Center, New York, New York.|Herbert Irving Comprehensive Cancer Center, New York, New York.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Divgi
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Columbia University, New York, New York.|Herbert Irving Comprehensive Cancer Center, New York, New York.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kalinsky
authors.affiliation: Department of Biostatistics, Columbia University, New York, New York.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Biostatistics, Columbia University, New York, New York.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anatomic Pathology, Weill Cornell Medical College, New York, New York.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Borczuk
authors.affiliation: Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan.|Department of Palliative Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York.
authors.forename: Balazs
authors.initials: B
authors.lastname: Halmos
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, New York. sa3141@cumc.columbia.edu.|Herbert Irving Comprehensive Cancer Center, New York, New York. sa3141@cumc.columbia.edu.
authors.forename: Swarnali
authors.initials: S
authors.lastname: Acharyya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002100:Cachexia / Q000453:epidemiology / Q000209:etiology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D016283:Proto-Oncogene Proteins p21(ras)
keywords: Cachexia; KRAS mutation; lung cancer; metastasis