Volume-based predictive biomarkers of sequential FDG-PET/CT for sunitinib in cancer of unknown primary: identification of the best benefited patients.
OBJECTIVE
To test the performance of sequential18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in predicting survival after sunitinib therapies in patients with cancer of unknown primary (CUP).


METHODS
CUP patients were enrolled for sequential PET/CT scanning for sunitinib and a control group. Univariate and multivariate analysis were applied to test the efficacy of sunitinib therapy in CUP patients. Next, sequential analyses involving PET/CT parameters were performed to identify and validate sensitive PET/CT biomarkers for sunitinib therapy. Finally, time-dependent receiver operating characteristic (TDROC) analyses were performed to compare the predictive accuracy.


RESULTS
Multivariate analysis proved that sunitinib group had significantly improved survival (p < 0.01) as compared to control group. After cycle 2 of therapy, multivariate analysis identified volume-based PET/CT parameters as sensitive biomarkers for sunitinib (p < 0.01). TDROC curves demonstrated whole-body total lesion glycolysis reduction (Δ WTLG) and follow-up WTLG to have good accuracy for efficacy prediction. This evidence was validated after cycle 4 of therapy with the same method.


CONCLUSIONS
Sunitinib therapy proved effective in treatment of CUP. PET/CT volume-based parameters may help predict outcome of sunitinib therapy, in which Δ WTLG and follow-up WTLG seem to be sensitive biomarkers for sunitinib efficacy. Patients with greater reduction and lower WTLG at follow-up seem to have better survival outcome.
Department of Orthorpedic Oncology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.|Department of Pathology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Yifei
Y
Ma
Department of Orthorpedic Oncology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Wei
W
Xu
Department of Geriatrics, Tianjin Medical University General Hospital, Laboratory of Neuro-Trauma and Neurodegenerative Disorder, Geriatrics Institute, Tianjin, 300352, China.
Ruojing
R
Bai
Department of Neuro-oncology, Neurosurgery Institute, Beijing, 100000, China.
Yiming
Y
Li
Department of Pathology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China. yuhongyucz@aliyun.com.
Hongyu
H
Yu
Department of PET/CT Radiology, Panorama Medical Imaging Center, Shanghai, China.|Department of PET/CT Radiology Center, Number 85 Hospital of PLA, 1328 Huashan Road, Shanghai, 200004, China.
Chunshan
C
Yang
Department of PET/CT Radiology Center, Number 85 Hospital of PLA, 1328 Huashan Road, Shanghai, 200004, China.
Huazheng
H
Shi
Department of PET/CT Radiology Center, Number 85 Hospital of PLA, 1328 Huashan Road, Shanghai, 200004, China.
Jian
J
Zhang
Department of Stomatology, The First People's Hospital of Shangqiu, Shangqiu, 476100, Henan Province, China.
Jidong
J
Li
Department of Radiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Chenguang
C
Wang
Department of Orthorpedic Oncology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China. jianruxiao83@163.com.
Jianru
J
Xiao
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015415:Biomarkers; D002681:China / Q000453:epidemiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality*; D017063:Outcome Assessment, Health Care / Q000379:methods; D018579:Patient Selection; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods / Q000706:statistics & numerical data*; D015995:Prevalence; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D000077210:Sunitinib; D015996:Survival Rate; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D015415:Biomarkers; D007211:Indoles; D011758:Pyrroles; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000077210:Sunitinib
Cancer of unknown primary; Sunitinib; Survival prediction; Volume-based PET/CT parameters