scholarly journals Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1021
Author(s):  
Justin W. Gorski ◽  
Zhuwei Zhang ◽  
J. Robert McCorkle ◽  
Jodi M. DeJohn ◽  
Chi Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Receptor ◽  
Debulking Surgery ◽  
Chemotherapy Sensitivity ◽  
Interval Debulking Surgery ◽  
Cancer Tumor ◽  
B Cell Receptor Signaling ◽  
Serous Epithelial Ovarian Cancer ◽  
Tumor Organoids

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC50 values were determined. One organoid line, UK1254, was predicted to be resistant to carboplatin based on its EC50 value (50.2 µM) being above clinically achievable Cmax. UK1254 had a significantly shorter PFS than the rest of the subjects (p = 0.0253) and was treated as a platinum-resistant recurrence. Subsequent gene expression analysis revealed extensively interconnected, differentially expressed pathways related to NF-kB, cellular differentiation (PRDM6 activation), and the linkage of B-cell receptor signaling to the PI3K–Akt signaling pathway (PI3KAP1 activation). This study demonstrates that patient-derived tumor organoids can be developed from patients at the time of primary or interval debulking surgery and may be used to predict clinical platinum sensitivity status or to investigate drivers of carboplatin resistance.

scholarly journals Interval debulking surgery for advanced epithelial ovarian cancer

2013 ◽  
Author(s):  
Siriwan Tangjitgamol ◽  
Sumonmal Manusirivithaya ◽  
Malinee Laopaiboon ◽  
Pisake Lumbiganon ◽  
Andrew Bryant
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Debulking Surgery ◽  
Interval Debulking Surgery ◽  
Advanced Epithelial Ovarian Cancer

Interval Debulking Surgery After Neodjuvant Chemotherapy Vs Primary Debulking Surgery For Stage Iii Epithelial Ovarian Carcinoma

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 15-15
Author(s):  
BM Ahmed ◽  
AT Amin ◽  
MK Khallaf ◽  
A Ahmed Refaat ◽  
SA Sileem
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Disease Free Survival ◽  
Figo Stage ◽  
Stage Iii ◽  
Debulking Surgery ◽  
Free Survival ◽  
Primary Debulking Surgery ◽  
Interval Debulking Surgery ◽  
Disease Free

Introduction: Ovarian cancer is the most lethal gynecologic malignancy and is the fifth most common cause of cancer-related death among women. Approach to FIGO stage III epithelial ovarian cancer remains challengeable. This study aims to evaluate the outcome of interval debulking surgery (IDS) vs. primary debulking surgery (PDS) for FIGO stage III epithelial ovarian cancer. Materials and Methods: During a period of six years (January 2014 to December 2019), we analyzed the patients for eligibility criteria, which were: (1) FIGO stage III epithelial ovarian cancer. (2) The age of 18 years or more (3) Patients underwent either PDS or IDS and received chemotherapy at South Egypt Cancer Institute. We divided them into two groups: (1) Those received three cycles of neoadjuvant chemotherapy and then underwent IDS plus three additional cycles of adjuvant chemotherapy and (2) Those who have PDS followed by six cycles of chemotherapy. Results: This study includes 380 eligible patients. The first group included 226 patients (59.47%) underwent PDS then 6 cycles of chemotherapy, while the group of IDS included 154 patients (40.53%). The treatment modality was not significant for overall survival (OS); however disease-free survival (DFS) was significantly reduced after IDS when compared to PDS (median DFS: 33 months; 95% CI 30.23-35.77 vs. 45 months; 95% CI 41.25-48.75 respectively; p= .000). Moreover, in subgroup analysis, OS and DFS were significantly dropped after IDS in elderly patients, patients with bad performance status, sub-optimal cytoreduction as well as high grade and undifferentiated tumors when compared to those who underwent PDS. Conclusion: Although treatment modality may not impact overall survival (OS), however, PDS results in a better disease-free survival than IDS. Moreover, IDS results in a significant drop in OS and DFS in special patients subgroups when compared to PDS. Therefore patients selection should be considered.

Patterns of Recurrence and Clinical Outcome of Patients With Stage IIIC to Stage IV Epithelial Ovarian Cancer in Complete Response After Primary Debulking Surgery Plus Chemotherapy or Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery: An Italian Multicenter Retrospective Study

2016 ◽  
Vol 27 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Angiolo Gadducci ◽  
Stefania Cosio ◽  
Valentina Zizioli ◽  
Sara Notaro ◽  
Roberta Tana ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Retrospective Study ◽  
Neoadjuvant Chemotherapy ◽  
Clinical Outcome ◽  
Epithelial Ovarian Cancer ◽  
Recurrence Rate ◽  
Complete Response ◽  
Debulking Surgery ◽  
Primary Debulking Surgery ◽  
Interval Debulking Surgery

ObjectiveThe objective of this retrospective study was to assess the clinical outcome of patients with advanced epithelial ovarian cancer in complete response after primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (IDS]).MethodsThe authors reviewed the hospital records of 384 patients who underwent PDS (n = 322) or IDS (n = 62) and who were in complete response after primary treatment.ResultsOptimal (residual disease [RD] < 1 cm) and complete (no gross RD) cytoreduction rates were higher after IDS than after PDS (71.0% vs 55.9%;P= 0.001 and 51.6% vs 35.7%, respectively;P= 0.02). Tumor recurred in 73.0% of the 322 complete responders after PDS versus 87.1% of the 62 complete responders after IDS (P= 0.01). The IDS group showed a higher recurrence rate within 6 months (11.3% vs 3.1%:P= 0.01) and a trend to higher recurrence rate between 6 and 12 months (30.6% vs 19.9%). Tumor recurred in 57.4% of the 115 completely cytoreduced patients after PDS versus 87.5% of the 32 completely cytoreduced patients after IDS (P= 0.001). The IDS group showed a trend to higher recurrence rate within 6 months (6.2% vs 1.7%) and a higher recurrence rate between 6 and 12 months (37.5% vs 15.6%;P= 0.01). Two-year, 5-year, and 7-year progression-free survival were 65.8%, 40.8%, and 39.3% for completely cytoreduced patients after PDS versus 43.8%, 12.5%, and 12.5% for completely cytoreduced patients after IDS (P= 0.001); and 2-year, 5-year, and 7-year overall survival were 96.4%, 69.3%, and 50.4% for the former versus 87.1%, 41.8%, and 32.6% for the latter (P= 0.001).ConclusionsThe clinical outcome of completely cytoreduced patients was significantly better for PDS group than for IDS group, and therefore, the achievement of no gross RD after surgery seemed to have a different prognostic relevance for the 2 groups.

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