Therapeutic value of selective lymphadenectomy in interval debulking surgery for stage IIIc and IV epithelial ovarian cancer
17
Citation
21
Reference
10
Related Paper
Citation Trend
Abstract:
Objective
The role of selective lymphadenectomy at the time of interval debulking surgery in patients with advanced ovarian cancer remains a topic of debate. This study aimed to evaluate the value of selective lymphadenectomy during interval debulking surgery in patients with radiologic evidence of lymph node metastasis at initial diagnosis that ultimately become negative on imaging after neoadjuvant chemotherapy.Methods
A retrospective analysis including patients with stage IIIC–IV epithelial ovarian cancer and suspicious pelvic or para-aortic lymph node metastasis by imaging at diagnosis that resolved after neoadjuvant chemotherapy. The study was conducted from January 1996 to June 2016 with R0 interval debulking surgery. The patients with disease progression after neoadjuvant chemotherapy were excluded. Suspicious metastatic lymph nodes at initial diagnosis by computed tomography/magnetic resonance imaging were excised by selective lymphadenectomy. Survival curves were constructed by the Kaplan-Meier method, and a multivariate analysis was performed using Cox regression.Results
There were a total of 330 patients included in the analysis. Selective lymphadenectomy of suspicious nodes (Group 1) was performed in 145 patients. Systematic lymphadenectomy (Group 2) was performed in 118 patients. Sixty-seven patients did not undergo lymphadenectomy (Group 3). There were no significant differences in clinicopathologic features among the groups. Median progression-free survival was 28, 30.5, and 22 months in Groups 1, 2, and 3, respectively (log-rank, p=0.049). No-lymphadenectomy was an independent factor affecting progression-free survival (Cox analysis, HR=1.729, 95% CI 1.213 to 2.464, p=0.002), with no difference between Groups 1 and 2 (Cox analysis, HR=1.097, 95% CI 0.815 to 1.478, p=0.541). Median overall survival was 50, 59, and 57 months in Groups 1, 2, and 3, respectively (Cox analysis, p=0.566). Patients who underwent selective lymphadenectomy had lower 1-year frequencies of lower extremity lymphedema and lymphocysts than those with systematic lymphadenectomy (6.2% vs 33.1%, p<0.001, and 6.2 % vs 27.1%, p<0.001, respectively).Conclusions
Extent of lymphadenectomy (systematic or selective) had no significant impact on progression-free survival or overall survival. In addition, the risks of lower extremity lymphedema and lymphocysts were lower in patients who underwent selective lymphadenectomy.Keywords:
Debulking
Lymphadenectomy
Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt, the value of debulking surgery after induction chemotherapy has not yet been defined. In this randomized study we investigated the effect on survival of debulking surgery.
Debulking
Induction chemotherapy
Cite
Citations (13)
Ovarian cancer is the leading cause of morbidity/mortality from gynecologic malignancy.Early detection of disease is difficult due to the propensity for ovarian cancer to disseminate throughout the peritoneum.Currently, there is no single accurate test to detect primary or recurrent ovarian cancer.We report a novel clinical strategy using PPF: a multimodal, PET and optical, folate receptor (FR)-targeted agent for ovarian cancer imaging.The capabilities of PPF were evaluated in primary human ovarian cancer cells, in vivo xenografts derived from primary cells and ex vivo patient omemtum, as the heterogeneity and phenotype displayed by patients is retained.Primary cells uptake PPF in a FR-dependent manner demonstrating approximately a 5-to 25-fold increase in fluorescence.By both PET and fluorescence imaging, PPF specifically delineated FR-positive, ovarian cancer xenografts, with similar tumor-to-background ratios of 8.91±0.91 and 7.94±3.94,and micro-metastatic studding (<1mm), which demonstrated a 3.5-fold increase in PPF uptake over adjacent normal tissue.Ex vivo patient omentum demonstrated selective uptake of PFF by tumor deposits.The ability of PPF to identify metastatic deposits <1mm could facilitate more complete debulking (currently, optimal debulking is <10mm residual tumor), by providing a more sensitive imaging strategy improving treatment planning, response assessment and residual/recurrent disease detection.Therefore, PPF is a novel clinical imaging strategy that could substantially improve the prognosis of patients with ovarian cancer by allowing pre-, post-and intra-operative tumor monitoring, detection and possibly treatment throughout all stages of therapy and tumor progression.
Debulking
Primary tumor
Ex vivo
Tumor Debulking
Cite
Citations (24)
Debulking
Cite
Citations (0)
Debulking
Cite
Citations (0)
Abstract Survival of ovarian cancer patients is directly related to the amount of residual disease present after debulking surgery. In 80% of the cases, extensive microscopic cancer remains even after the patient is deemed optimally debulked. Hence, detection of sub-mm cancer clusters during tumor excision is a critical unmet need. Recent studies have shown that reducing the dimensions of residual cancer to less than 1 mm significantly improves clinical outcomes. In the present study we evaluate the performance of a fluorescent, molecular imaging agent, LUM015 (Lumicell, Wellesley, MA), which is activated by cathepsin enzymes in the tumor, and a wide-field-of-view imaging device (Lumicell) to detect sub-mm residual cancer clusters in an mouse model for ovarian cancer. In this study, we generated orthotopic ovarian cancer mouse models(n=10) with well characterized serous ovarian cancer cell lines, CP70 and SKOV3. Once the tumor disseminated, the imaging agent LUM015 (3.52 mg/kg) was injected via the tail vein, and after 6 hours, the mice were euthanized. Tumor debulking was performed throughout the abdominal cavity. After debulking, the whole abdominal wall was dissected in 4 quadrants, organs were harvested and all were imaged with the LUM device. Features exhibiting high fluorescence were marked and dissected, prepared into slides, and stained with hematoxylin and eosin for pathologic correlation with LUM015 fluorescence imaging. In 36 tissues from orthotopic ovarian cancer mouse models, LUM015 imaging system could detect the tumor presence with 100% of sensitivity and 60% of specificity. We demonstrated that the imaging system can detect sub-mm cancer clusters that could not be identified with visual inspection. With a cathepsin activated fluorescence imaging molecule (LUM015) and a wide-field-of-view imaging device, we detected microscopic residual ovarian cancer tumors in orthotopic xenograft models after debulking grossly with high sensitivity. Translation of this imaging technology into the clinical setting may help to detect microscopic residual tumor features during the debulking operation in ovarian cancer. Citation Format: Youngjeong Na, Tim Kwok, Christopher Awtrey, David B. Strasfeld, Jorge M. Ferrer, David Lee, Michael J. Birrer. Identification of microscopic ovarian tumor foci utilizing a novel imaging device in a murine ovarian cancer model, an opportunity to improve optimal cytoreduction. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2056. doi:10.1158/1538-7445.AM2014-2056
Debulking
Ovarian tumor
Minimal Residual Disease
Abdominal cavity
Tumor Debulking
Cite
Citations (0)
Debulking
Cite
Citations (0)
Debulking
Neoadjuvant Therapy
Cite
Citations (8)
Debulking
Cite
Citations (0)
Debulking
Cite
Citations (6)
Objective
The role of selective lymphadenectomy at the time of interval debulking surgery in patients with advanced ovarian cancer remains a topic of debate. This study aimed to evaluate the value of selective lymphadenectomy during interval debulking surgery in patients with radiologic evidence of lymph node metastasis at initial diagnosis that ultimately become negative on imaging after neoadjuvant chemotherapy.Methods
A retrospective analysis including patients with stage IIIC–IV epithelial ovarian cancer and suspicious pelvic or para-aortic lymph node metastasis by imaging at diagnosis that resolved after neoadjuvant chemotherapy. The study was conducted from January 1996 to June 2016 with R0 interval debulking surgery. The patients with disease progression after neoadjuvant chemotherapy were excluded. Suspicious metastatic lymph nodes at initial diagnosis by computed tomography/magnetic resonance imaging were excised by selective lymphadenectomy. Survival curves were constructed by the Kaplan-Meier method, and a multivariate analysis was performed using Cox regression.Results
There were a total of 330 patients included in the analysis. Selective lymphadenectomy of suspicious nodes (Group 1) was performed in 145 patients. Systematic lymphadenectomy (Group 2) was performed in 118 patients. Sixty-seven patients did not undergo lymphadenectomy (Group 3). There were no significant differences in clinicopathologic features among the groups. Median progression-free survival was 28, 30.5, and 22 months in Groups 1, 2, and 3, respectively (log-rank, p=0.049). No-lymphadenectomy was an independent factor affecting progression-free survival (Cox analysis, HR=1.729, 95% CI 1.213 to 2.464, p=0.002), with no difference between Groups 1 and 2 (Cox analysis, HR=1.097, 95% CI 0.815 to 1.478, p=0.541). Median overall survival was 50, 59, and 57 months in Groups 1, 2, and 3, respectively (Cox analysis, p=0.566). Patients who underwent selective lymphadenectomy had lower 1-year frequencies of lower extremity lymphedema and lymphocysts than those with systematic lymphadenectomy (6.2% vs 33.1%, p<0.001, and 6.2 % vs 27.1%, p<0.001, respectively).Conclusions
Extent of lymphadenectomy (systematic or selective) had no significant impact on progression-free survival or overall survival. In addition, the risks of lower extremity lymphedema and lymphocysts were lower in patients who underwent selective lymphadenectomy.Debulking
Lymphadenectomy
Cite
Citations (17)