Monitoring the Response of PD-L1 Expression to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Nonsmall-Cell Lung Cancer Xenografts by Immuno-PET Imaging.

Accumulating evidence has suggested that the tumor microenvironment of nonsmall-cell lung cancer (NSCLC) may be impacted by chemotherapy, radiotherapy, or epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). PD-L1 is an important biomarker in the tumor microenvironment that can predict patient response to immunotherapies. Therefore, it is highly desirable to achieve a real-time, noninvasive assessment of PD-L1 expression, which can provide critical information for recruiting patients as well as monitoring therapeutic efficacy. We herein studied the EGFR-TKI-induced effects on PD-L1 levels in NSCLC tumor models using immuno-PET imaging with 89Zr-Df-KN035, an imaging tracer previously established by our group. A549 human NSCLC xenografts were established in BALB/c nude mice and treated with different doses of an EGFR-TKI gefitinib. PET imaging with 89Zr-Df-KN035 was performed before and after the treatment to evaluate PD-L1 expression, which was further verified by immunohistochemical staining. Our results demonstrate that 89Zr-Df-KN035 can specifically evaluate PD-L1 levels in NSCLC tumor models. Compared to the untreated control, the high dose of gefitinib inhibited tumor growth and lowered the tumor uptake of 89Zr-Df-KN035. In comparison, the low dose of gefitinib did not affect tumor growth, although the extensive tumor necrosis also led to the lower uptake of 89Zr-Df-KN035. In conclusion, our results demonstrate that immuno-PET imaging with 89Zr-Df-KN035 is a promising tool to noninvasively monitor PD-L1 expression in NSCLC treated with EGFR-TKIs and can be used to optimize treatment plans for immunotherapy.

Posttraumatic growth and psychological distress in Chinese early-stage breast cancer survivors: a longitudinal study.

OBJECTIVE: To describe the dynamic changes in posttraumatic growth (PTG) and psychological distress in hospitalized early-stage breast cancer (BC) survivors over a 6-month period. METHODS: A longitudinal study design was adopted. The PTG inventory (PTGI) and distress management screening measure were used 3 months after diagnosis, then again at 6 and 9 months after diagnosis. For baseline data, 155 BC patients who were receiving chemotherapy were selected from four first-class tertiary hospitals in Beijing from April 2010 to March 2011 using a purposive sampling method. Of these, 120 BC patients completed the follow-up investigation. A repeated measures analysis of variance, followed by least significant difference post-hoc analysis, was used to compare PTG and psychological distress. RESULTS: The total score of the PTGI was 62.72 ± 14.66 in BC survivors at 3 months after diagnosis.There was a weak negative relationship between PTG and psychological distress (r = ­0.282, p<0.001).PTG increased and psychological distress decreased from 3 to 9 months after diagnosis. The PTGI scores were 63.24 ± 14.21, 68.26 ± 15.29, and 70.29 ± 16.07 at 3, 6, and 9 months after diagnosis, respectively, with distress thermometer scores of 3.62 ± 1.98, 2.59 ± 2.00, and 2.51 ± 1.00, respectively. CONCLUSIONS: At 3 months after diagnosis, BC survivors develop PTG at a low level while they are receiving chemotherapy. PTG showed a weak negative association with psychological distress. The level of PTG shows an increasing tendency, whereas the degree of psychological distress exhibits a downward trend in the 9 months after diagnosis.