title: Changes in the diffusion capacity for carbon monoxide and the development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma treated with everolimus.
abstract: OBJECTIVE
  The aim of the present study was to evaluate how treatment with everolimus changes readouts of the pulmonary function test (PFT) in patients with metastatic renal cell carcinoma (mRCC). We also attempted to determine whether changes of PFT or everolimus-associated non-infectious pneumonitis (NIP) might affect the efficacy of everolimus.
  
  
  METHODS
  The results of PFTs, radiological reports and medical records of 36 mRCC patients treated with everolimus after failure to vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) were reviewed.
  
  
  RESULTS
  Whereas 9 patients (30%) developed radiological changes consistent with everolimus-associated NIP (pneumonitis group), 27 were included in the non-pneumonitis group. The baseline value of the diffusing capacity for carbon monoxide divided by the alveolar volume (DLco/VA) was 90%. It decreased significantly as the duration of treatment increased (p<0.01). There was no significant difference in DLco/VA values between patients with and without NIP either at baseline (p=0.28) and 6 weeks after the initiation of everolimus therapy (p=0.18). The changes in DLco/VA between baseline and 6 weeks did not differ between the two groups (p=0.55). Time-dependent covariate Cox analysis, indicated that the decrease in DLco/VA was not correlated with the efficacy of everolimus in terms of progression-free survival (PFS; HR=1.0, p=0.94) and overall survival (OS; HR=0.98, p=0.18), whereas development of NIP was associated with worse PFS (HR=4.60, p=0.01).
  
  
  CONCLUSIONS
  Patients with mRCC who are receiving everolimus therapy display a reduction in DLco/VA over time. However, neither the baseline DLco/VA nor the change in DLco/VA over time can help predict either development of NIP or the efficacy of everolimus.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Hematology-Oncology, KEPCO Medical Center, Seoul, Republic of Korea.
authors.forename: Kwonoh
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Preventive Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea jaelyun@amc.seoul.kr.
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.affiliation: Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: In-Gab
authors.initials: IG
authors.lastname: Jeong
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Cheryn
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Bum-Sik
authors.initials: BS
authors.lastname: Hong
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Junhyuk
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Choung Soo
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Hanjong
authors.initials: H
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002248:Carbon Monoxide / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D000068338:Everolimus; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011014:Pneumonia / Q000139:chemically induced* / Q000503:physiopathology*; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects*; D012129:Respiratory Function Tests; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002248:Carbon Monoxide; D000068338:Everolimus; D020123:Sirolimus
keywords: Metastatic renal cell carcinoma; everolimus; pneumonitis; pulmonary function test