Plasma nucleosome levels might predict response to therapy in patients with advanced non-small-cell lung cancer.
BACKGROUND
Recent progress in the field of anticancer drug discovery has created many options for improving the survival of patients with cancer. However, more effective diagnostic tools indicating early therapeutic efficacy or disease progression are still needed to improve the management of patients with inoperable cancer.


METHODS
Plasma nucleosome levels were quantified in 134 patients with advanced non-small-cell lung cancer before the first cycle of chemotherapy. It was also evaluated before the second and third cycles of chemotherapy in 42 patients receiving first-line chemotherapy. Nucleosomes were correlated with response to therapy as assessed by computed tomography after the third therapy cycle.


RESULTS
Patients who went into remission had significantly lower nucleosome levels before therapy cycles 2 and 3 than patients with no change or progression. High levels and insufficient decreases in nucleosome levels during the course of chemotherapy indicated poor outcome. Nucleosome levels before the second cycle detected poor response to therapy with a sensitivity and specificity of 69.2% and 75%, respectively (area under the receiver operating characteristic [ROC] curve, 0.816). Early prediction of disease progression was achieved with a sensitivity and specificity of 85.7% and 92.9%, respectively, for nucleosome levels before cycle 2 (area under the ROC curve, 0.930).


CONCLUSIONS
The monitoring of plasma nucleosome levels during the course of first-line chemotherapy could identify patients who are likely to have insufficient response to therapy and disease progression at an early stage. This might help in individualizing treatment and could lead to better management of advanced-stage lung cancer.
Kumar
Sachin
S
Department of Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Guleria
Randeep
R
Singh
Vikas
V
Bharti
Alok C
AC
Mohan
Anant
A
Das
Bhudev C
BC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000378:metabolism*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012074:Remission Induction / Q000379:methods; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009707:Nucleosomes