title: Tumor cavitation: impact on objective response evaluation in trials of angiogenesis inhibitors in non-small-cell lung cancer.
abstract: OBJECTIVE
  We have observed cavitation of lesions in clinical trials of an angiogenesis inhibitor combined with chemotherapy for non-small-cell lung cancer (NSCLC). We hypothesized that cavitation might alter response assessment in such clinical trials.
  
  
  METHODS
  We performed a retrospective radiologic review of patients with NSCLC enrolled onto three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials of platinum-based chemotherapy with or without a small-molecule angiogenesis inhibitor (vascular endothelial growth factor receptor inhibitor [VEGFRI]). Response was assessed both by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and a novel alternate method in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. Rates of cavitation were documented.
  
  
  RESULTS
  Marked cavitation of pulmonary lesions was seen in 24% of 33 patients treated with VEGFRI combined with platinum-based chemotherapy but in none of 18 patients treated with platinum-based chemotherapy alone. Use of the alternate method for response assessment resulted in an alteration of response assessment, time to best response, duration of response, and time of disease progression in a minority of patients compared with RECIST.
  
  
  CONCLUSIONS
  Cavitation of target and nontarget lesions is common in NSCLC patients treated with VEGFRIs and platinum-based chemotherapy. Impact on response and time to event outcomes occurred but seems to be less common. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions, potentially altering outcomes of key efficacy parameters in clinical trials. This should be prospectively assessed in clinical trials of angiogenesis inhibitors.
authors.affiliation: Cancer Research UK Clinical Centre, Southampton General Hospital, Southampton, United Kingdom. S.J.Crabb@soton.ac.uk
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Crabb
authors.forename: Demetris
authors.initials: D
authors.lastname: Patsios
authors.forename: Eric
authors.initials: E
authors.lastname: Sauerbrei
authors.forename: Peter M
authors.initials: PM
authors.lastname: Ellis
authors.forename: Andrew
authors.initials: A
authors.lastname: Arnold
authors.forename: Glenwood
authors.initials: G
authors.lastname: Goss
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Jean
authors.initials: J
authors.lastname: Powers
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
authors.forename: Scott A
authors.initials: SA
authors.lastname: Laurie
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care / Q000379:methods; D017239:Paclitaxel / Q000008:administration & dosage; D011859:Radiography; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D000093542:Gemcitabine
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine