Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy

Abstract

Most patients with ovarian cancer experience recurrence and develop resistance to platinum-based agents. The diagnosis of platinum resistance based on the platinum-free interval is not always accurate and timely in clinical settings. Herein, we used laser ablation inductively coupled plasma mass spectrometry to visualize the platinum distribution in the ovarian cancer tissues at the time of interval debulking surgery after neoadjuvant chemotherapy in 27patients with advanced high-grade serous ovarian cancer. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum throughout the tumor and adjacent stroma. The type A patients treated post-surgery with platinum-based adjuvant chemotherapy showed significantly shorter periods of recurrence after the last platinum-based chemotherapy session (p = 0.020) and were diagnosed with “platinum-resistant recurrence”. Moreover, type A was significantly correlated with worse prognosis (p = 0.031). Post-surgery treatment with non-platinum-based chemotherapy could be effective for the patients classified as type A. Our findings indicate that the platinum resistance can be predicted prior to recurrence, based on the platinum distribution; this could contribute to the selection of more appropriate adjuvant chemotherapy, which may lead to improves prognoses.

LA-ICP-MS analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma

“…However, we found no correlation between tissue or serum Pt levels and age, gender, histological subtype, tumor pathological stage, renal clearance or the type of Pt agent. These findings are consistent with the literature, as none of the aforementioned parameters had an impact on tissue Pt levels of NSCLC or gastric cancer patients [14,35]. Moreover, although cisplatin and carboplatin levels have not been directly compared in PM tissues yet, as they show equivalent survival rates, it is presumable that they have similar biological activities in PM [50].…”

“…We found that tissue Pt levels (full, tumorous and non-tumorous areas) showed correlation neither with the apoptotic rate of tumor cells (as determined by TUNEL labeling) nor with the patients' OS. These findings are in contrast to the literature, as high intratumoral Pt level was identified as a favorable prognostic factor in different tumor types [14,15,34,35]. Moreover, in a recent study on cisplatin-treated NSCLC ex vivoexplant cultures, Ki67 labeling (cell proliferation) and PARP expression (cell death) also correlated with intratumoral Pt levels [15].…”

Laser ablation‐inductively coupled plasma‐mass spectrometry analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma

“…We found that tissue Pt levels (full, tumourous and nontumourous areas) did not show correlation with either the apoptotic rate of tumour cells (as determined by TUNEL labelling) or the patients' OS. These findings are in contrast to the literature, as high intratumoural Pt level was identified as a favourable prognostic factor in different tumour types 14,15,42,43 . Moreover, in a recent study on cisplatin‐treated NSCLC ex vivo explant cultures, Ki67 labelling (cell proliferation) and poly‐ADP‐ribose polymerase (PARP) expression (cell death) also correlated with intratumoural Pt levels 15 .…”

“…These findings are in contrast to the literature, as high intratumoural Pt level was identified as a favourable prognostic factor in different tumour types. 14,15,42,43 Moreover, in a recent study on cisplatin-treated NSCLC ex vivo explant cultures, Ki67 labelling (cell proliferation) and poly-ADP-ribose polymerase (PARP) expression (cell death) also correlated with intratumoural Pt levels. 15 Our results indicate, that in addition to inadequate penetration into the tumour tissue, 13 other types of resistance mechanisms may also play a key role in the limited effectiveness of Pt agents in PM patients.…”

“…These findings are consistent with the literature, as none of these parameters had an impact on tissue Pt levels of NSCLC or gastric cancer patients. 14,43 Moreover, although cisplatin and carboplatin levels have not been directly compared in PM tissues yet, as they show equivalent survival rates, it is presumable that they have similar biological activities in PM. 58 As expected, serum Pt concentrations negatively correlated with the elapsed time between the last CHT cycle and sample collection.…”