Implementación de la biopsia selectiva del ganglio centinela en pacientes con cáncer de mama tratadas en hospitales comarcales de la Comunidad Autónoma de Cantabria

Objective

To evaluate the results of sentinel lymph node (SLN) biopsy in women with breast cancer treated in hospitals without a nuclear medicine unit.

Subjects and methods

Eighty-eight patients with early-stage breast cancer treated in two district hospitals between February 2007 and July 2010 were included. The day before surgery a lymphoscintigraphy was performed in the specialized hospital. Intraoperative localization of the SLN was accomplished by the combined use of a hand-held gamma probe and a manual gamma-camera.

Results

Surgical localization of the SLN was successful in 97.7% of the patients. The mean number of lymph nodes excised by each procedure and each surgical team was 2.1±1.4 and 2.5±1.2. Axillary lymph node dissection was performed in 27.2% of the patients. There was one false-negative result and one false-positive result.

Conclusion

The implementation of SLN biopsy in district hospitals provides similar results to those obtained in the supervising hospital.     

Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: A SEER analysis

Objective

The aims of this study are to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from women with high grade papillary serous ovarian carcinoma when compared by stage as well as to identify any associated clinico-pathologic factors.

Methods

The Surveillance, Epidemiology, and End Results (SEER) Program data for all 18 registries from 1998 to 2009 was reviewed to identify women with OCS and high grade papillary serous carcinoma of the ovary. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan–Meier method. Factors predictive of outcome were compared using the Cox proportional hazard model.

Results

The final study group consisted of 14,753 women. 1334 (9.04%) had OCS and 13,419 (90.96%) had high grade papillary serous carcinoma of the ovary. Overall, women with OCS had a worse five-year, disease specific survival rate, 28.2% vs. 38.4% (P < 0.001). This difference persisted for each FIGO disease stages I–IV, with five year survival consistently worse for women with OCS compared with papillary serous carcinoma. Over the entire study period, after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, lymph node dissection, and history of secondary malignancy after the diagnosis of ovarian cancer, carcinosarcoma histology was associated with decreased cancer-specific survival.

Conclusions

OCS is associated with a poor prognosis compared to high grade papillary serous carcinoma of the ovary. This difference was noted across all FIGO stages.     

Contemporary analysis of pelvic and para-aortic metastasis in endometrial cancer using the SEER registry

Objective

To determine the incidence of regional lymph node involvement for early-stage endometrial cancer by using the Surveillance, Epidemiology, and End Results (SEER) registry.

Methods

In a retrospective study, data were analyzed from patients who were diagnosed with stage IA–IIB endometrioid adenocarcinoma and were treated between 1998 and 2003. The incidence of pelvic and para-aortic lymph node involvement was determined.

Results

Data were analyzed from 4052 patients. Incidences of pelvic and para-aortic lymph node metastases were: 1% and 0% in stage IA, grade 1 disease; 2% and 0% in IA, grade 2; 2% and 1% in IA, grade 3; 2% and 0% in IB, grade 1; 3% and 1% in IB, grade 2; 3% and 2% in IB, grade 3; 7% and 3% in IC, grade 1; 8% and 5% in IC, grade 2; 12% and 8% in IC, grade 3; 7% and 3% in IIA, grade 1; 10% and 4% in IIA, grade 2; 10% and 5% in IIA, grade 3; 8% and 4% in IIB, grade 1; 13% and 8% in IIB, grade 2; and 19% and 12% in IIB, grade 3.

Conclusion

Incidences of pelvic and para-aortic metastases were lower than previously reported. Patients at higher stages and grades had a 10% or higher risk of lymph node involvement and might benefit from aggressive therapy.     

Surgery for early stage cervical cancer: How radical should it be?

Objective

Less radical or non radical surgery for early-stage cervical cancer has been proposed to reduce morbidity while maintaining oncologic outcomes. Given that a standardized approach to conservative surgery is not yet available, we have summarized the literature on less radical surgery to better inform clinical practice.

Methods

MEDLINE R and MEDLINE in-process and non-indexed citations were searched from inception to April 14, 2013 to identify all English-language articles evaluating less-radical or non radical surgery for invasive cervical carcinoma. Articles including patients with squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma were included and a narrative review of the literature is presented.

Results

Radical surgery is associated with significant adverse effects in terms of urinary function, sexual function, and body image. Radical trachelectomy is an accepted fertility-sparing option, but still leads to morbidity from parametrectomy. The importance of the parametrectomy in patients with small early-stage tumors has been questioned recently, and many studies have found simple hysterectomy and simple trachelectomy can be safe in appropriately selected patients. Cone biopsy may be a fertility-sparing option in those patients with a very low risk of parametrial involvement. Neoadjuvant chemotherapy is also being investigated as a method to reduce the need for radical surgery. Sentinel lymph node biopsy is discussed as a method to reduce the morbidity while increasing the sensitivity of pelvic lymph node assessment in women with early cervical cancers. Finally, the treatment of early adenocarcinoma is addressed.

Conclusions

It appears many women with early-stage cervical cancer can be treated less radically than has been done in the past. Large prospective trials are underway to further define candidates for less-radical surgery.     

Tumor size,depth of invasion,and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: A SEER analysis

Objectives

The objective of this investigation was to evaluate the risk of nodal metastasis in patients with endometrial cancer, using the Mayo criteria, in a population-based analysis.

Materials and methods

Data from the SEER registry was reviewed for endometrial cancer cases diagnosed between 1988 and 2010. Patients were considered at low-risk for nodal metastasis if their tumors were histologic grade 1 or 2, myometrial invasion was less than 50%, and tumor size equal to or less than 2 cm. Patients not meeting these criteria were considered at high-risk for nodal involvement.

Results

The final study group consisted of 19,329 women with surgically staged endometrial cancer. Of these, 1035 (5.3%) had lymph node involvement. Based on Mayo criteria, 4095 (21.1%) patients were found to be at low-risk and 15,234 (78.9%) at high-risk for nodal metastasis. Low-risk features were associated with a 1.4% risk for lymph node metastasis, compared to 6.4% in patients with high-risk features (p < 0.001). When myometrial invasion was removed from the analysis, low-risk pathologic features were associated with a 2.4% risk of lymph node metastasis, compared to 10.4% in patients with high-risk features (p < 0.001).

Conclusions

In a population-based analysis, women with low-risk endometrial cancer, as defined by the Mayo criteria, have a low rate of lymph node metastasis.     

Primeros resultados de la disección del ganglio centinela en los carcinomas epidermoides vulvares

Objective

The aim was to analyse our first results in the sentinel lymph node procedure in vulvar cancer, as regards the detection rate, false negative cases and relation with cancer recurrence or not.

Material and methods

Retrospective study of first 9 cases of sentinel lymph node detection in vulvar squamous cell carcinoma, between June 2004 and December 2007.

Results

We identified the sentinel node in 8 out of 9 patients (88% detection rate). There were no false negative cases, giving a negative predictive value of 100%. Only one patient with a negative sentinel node died of vulvar cancer. She also had Fanconi anaemia.

Conclusions

Sentinel lymph node detection in patients with squamous cell carcinoma of the vulva is feasible, and can be an alternative to conventional inguinofemoral lymphadenectomy.     

Pattern analysis of regional spread and therapeutic lymph node dissection in cervical cancer based on ontogenetic anatomy

Objective

In cervical cancer lymph node dissection is applied for regional tumor staging. Up to now, the use of (chemo)radiation in the nodal positive patient has prevented the exact pattern analysis of regional tumor spread and the evaluation of the therapeutic role of lymph node dissection. New surgical techniques founded on ontogenetic instead of functional anatomy for the treatment of cervical cancer dispensing with adjuvant radiotherapy offer the possibility to accurately determine the topography of regional lymph node metastases which is the prerequisite for optimized diagnostic and therapeutic lymph node dissection.

Methods

Patients with cervical cancer FIGO stages IB-IIB were treated with total mesometrial resection (TMMR) and lymph node dissection after exposing the ontogenetic visceroparietal compartments of the female pelvis. Resected lymph nodes were allocated to regions topographically defined by the embryonic development of the iliac, lumbar and mesenteric lymph systems prior to histopathological assessment.

Results

71 of 305 treated patients had lymph node metastases. Topographic distribution of these metastases at primary surgery and analysis of pelvic failures showed a spatial pattern related to the ontogenesis of the abdominopelvic lymphatic system. Five-year locoregional tumor control probability was 96% (95% CI: 94-98) for the whole group and 87% (95% CI: 77-97) for nodal positive patients.

Conclusions

The pattern of regional spread in cervical cancer can be comprehended and predicted from ontogenetic lymphatic compartments. In patients with early cervical cancer lymph node dissection based on ontogenetic anatomy achieves high regional tumor control without adjuvant radiation.     

PET/CT in the staging of patients with a pelvic mass suspicious for ovarian cancer

Objective

To prospectively assess the value of PET/CT for staging, diagnosis and operability of ovarian cancer, with special attention to the peritoneal spread.

Methods

From June 2009 to March 2011, 69 patients with suspicion of having an ovarian cancer underwent an ¹⁸ F-FDG PET/CT. To identify the diagnostic value of PET/CT, the results were compared with the findings at diagnostic laparoscopy and/or debulking surgery.

Results

There were 56 patients with malignant tumors and 13 with benign tumors. We observed a sensitivity and specificity of 93% and 77%, respectively for malignant tumors with PET/CT. CT alone had a sensitivity and specificity of 96% and 38%, respectively. The overall FIGO classification evaluation for PET/CT and CT were the same. For the evaluation of metastases, the sensitivity of PET/CT was worse, while the specificity was better than CT. Retroperitoneal lymph node metastases were diagnosed better with PET/CT, while there was no difference for peritoneal spread and for the intestines. PET/CT detected another unknown primary tumor in 3 (4.3%) cases.

Conclusion

PET/CT is better than CT in detecting retroperitoneal lymph node metastases, but not for peritoneal metastases.     

The role of preoperative ultrasound evaluation of inguinal lymph nodes in patients with vulvar malignancy

Objectives

Inguinal lymphadenectomy in vulvar malignancies is associated with significant morbidity, especially in patients over 70 years old. Under certain conditions, surgical guidelines recommend biopsy and evaluation of the sentinel node in early vulvar cancer. The purpose of our study is to evaluate ultrasonography as a predictor of inguinal lymph node involvement.

Methods

A retrospective study was performed with 60 patients who had vulvar malignancies (92% of which were squamous cell carcinomas) and who were treated at our hospital between 2002 and 2012. The patients ranged in age from 35 to 89 years, with a median age of 76 years. In total, 118 groin scans were retrospectively evaluated for sonographic evidence of lymph node involvement (i.e., absence of fatty hilum, irregular shape, cortical region diameter and vascularization pattern). The results were then compared with histopathologically confirmed lymph node status.

Results

Histopathologically confirmed lymph node status was available for 107 of the inguinal nodes examined by ultrasound, and lymph node metastases were found in 38 (35.5%) cases. The presence or absence of inguinal lymph node metastases was correctly identified by sonography in 92 (86.0%) of the scanned areas. Sensitivity was 76.3%, specificity was 91.3%, and positive and negative predictive values were 82.9% and 87.5%, respectively.

Conclusions

Ultrasonography of the inguinal lymph nodes showed a relatively high sensitivity and specificity for predicting inguinal tumor metastases. However, our results indicate that surgical lymph node staging is still needed to precisely determine inguinal lymph node status in vulvar cancer, especially because a missed lymph node-metastasis is often fatal.     

Incidence of metastasis in the circumflex iliac nodes distal to the external iliac nodes in ovarian cancer

Objective

The circumflex iliac nodes distal to the external iliac nodes (CINDEINs) are included in the regional lymph nodes that are commonly dissected during systematic lymphadenectomy for ovarian cancer. Because in recent years CINDEIN dissection has been reported as a significant risk factor for postoperative lower limb lymphedema, we investigated the validity of omitting the CINDEIN dissection by evaluating the distribution pattern of positive lymph nodes in ovarian cancer, in order to improve postoperative quality of life (QOL).

Methods

We performed a retrospective chart review of 142 patients with ovarian cancer who had undergone systematic lymphadenectomy between 1995 and 2010. We assessed the distribution pattern of lymph node metastasis and the presence of CINDEIN metastasis according to the pT classification (pT1, pT2, and pT3).

Results

Of the 142 patients, 71, 21, and 50 were classified into pT1, pT2, and pT3, respectively. The lymph nodes most frequently involved were the para-aortic lymph nodes superior to the mesenteric artery (14%), followed by the obturator nodes (11%), the internal iliac nodes (9.4%), and the common iliac nodes (7.4%). Although the frequency of CINDEIN metastasis was 5.3% (6 of 114 cases with CINDEIN dissection), no metastasis to the CINDEINs was observed in pT1 patients.

Conclusions

It may be acceptable to omit CINDEIN dissection during surgery for pT1 ovarian cancer in view of postoperative QOL.     

Clinical significance of tumor volume in endometrial cancer: A Japan–Korea cooperative study

Objective

The aim of this study was to elucidate the significance of tumor volume as a risk factor for predicting lymph node metastasis.

Methods

We applied the tumor volume index to the data that were collected for 327 Korean patients with endometrial cancer who underwent preoperative assessment including magnetic resonance imaging (MRI) and subsequent surgery including systematic lymphadenectomy. The volume index, which we previously reported in the literature, was defined as the product of maximum longitudinal diameter along the uterine axis, maximum anteroposterior diameter in a sagittal section image, and maximum horizontal diameter in a horizontal section image according to MRI data, from 425 Japanese women with endometrial cancer. Relationships between lymph node metastasis and results of preoperative examinations including volume index were analyzed by logistic regression analysis.

Results

The prevalence of affected lymph nodes was 14.2%. Multivariate analysis showed that high-grade histology assessed by endometrial biopsy [odds ratio (OR); 2.9, 95% confidence interval (CI): 1.4–6.4], volume index (OR; 2.4, 95% CI: 1.1–5.3), node enlargement assessed by MRI (OR; 4.2, 95% CI: 1.4–13.2), and high serum cancer antigen (CA)125 level (OR; 3.6, 95% CI: 1.6–8.1) were significantly and independently related to lymph node metastasis. When volume index was excluded from the analysis, myoinvasion assessed by MRI was an independent risk factor for lymph node metastasis as well as high-grade histology, node enlargement, and high serum CA125 level.

Conclusion

Volume index is compatible with myometrial invasion as a factor for predicting lymph node metastasis in endometrial cancer.     

Is venous thromboprophylaxis necessary in patients undergoing minimally invasive surgery for a gynecologic malignancy?

Objectives

Current recommendations for the use of venous thromboprophylaxis in patients undergoing minimally invasive surgery (MIS) for a gynecologic malignancy are derived from patients undergoing open surgery. Our objective was to determine the 30-day prevalence of symptomatic venous thromboembolism (VTE) after laparoscopic gynecologic oncology procedures in patients who received no thromboprophylaxis.

Methods

Between January 2006 and September 2013, women who underwent MIS for endometrial, cervical or ovarian cancer at a single institution were included. Data on patient demographics, diagnosis, comorbidities, perioperative characteristics, use of thromboprophylaxis, and diagnosis of VTE were collected retrospectively.

Results

Of the 419 patients who underwent MIS for a gynecologic cancer, 352 (84%) received no VTE prophylaxis. At least a total laparoscopic hysterectomy (simple or radical) or pelvic lymph node dissection was performed in 95% of these patients. The median length of surgery was 137 min and 95% of patients were discharged home within 1 day of surgery. The rate of VTE in the 352 untreated patients was 0.57% (1 pulmonary embolism and 1 deep vein thrombosis). There were no VTE diagnosed within 30 days of surgery in the 67 patients who received anticoagulant thromboprophylaxis.

Conclusion

The rate of VTE is low in patients undergoing minimally invasive surgery for a gynecologic malignancy despite no VTE prophylaxis. The benefits of routine use of VTE prophylaxis in this population are questionable.     

Recurrencias loco-regionales en pacientes con cáncer de mama invasivo que presentan 3 ganglios positivos o menos. ¿Está indicada la radioterapia?

Introduction

There is international consensus on the role of regional lymph node radiotherapy in patients with early stage breast cancer and four or more positive lymph nodes. However, the decision is less clear when fewer than four affected lymph nodes are affected. As our hospital does not systematically carry out adjuvant radiotherapy in regional lymph nodes in patients with three or fewer positive lymph nodes, we assessed locoregional recurrence in this group of patients during the first 5 years after treatment.

Material and Methods

We performed a retrospective study based on a 5-year follow-up after the end of treatment. Data were obtained from the patients’ clinical histories. Outcomes were compared with those reported by Overgaard et al in a subgroup of patients with three or fewer affected lymph nodes receiving radiotherapy in the regional lymph nodes.

Results

No locoregional recurrence was detected up to 5 years after treatment. No significant differences were found between our patients and those of Overgaard (p = 0.5412).

Conclusion

In view of the obtained results it does not seem necesary to treat with radiotherapy on lymph node chains to all early stage breast cancer patiens with three or fewer affected lymph nodes.     

Impact of sentinel lymph node biopsy on the therapeutic management of early-stage endometrial cancer: Results of a retrospective multicenter study

Objective

The aim of this study is to assess the impact of sentinel lymph node (SLN) mapping and ultrastaging on the therapeutic management of early-stage endometrial cancer.

Methods

This retrospective multicenter study covered the period from January 2000 through December 2012 and included 304 women with presumed low- or intermediate-risk endometrial cancer. Node staging, histology results, and the effects of both on therapeutic management were assessed in two groups: those who underwent the SLN mapping and ultrastaging procedure and those treated in accordance with French guidelines.

Results

The SLN procedure detected metastatic lymph nodes in three times more women than lymphadenectomy did (16.2% versus 5.1%, p = 0.03). Specifically, it found 7 macrometastases (5.1%) and 15 micrometastases (11%); 11 of the latter (8.1%) were detected by serial sectioning and immunohistochemistry (IHC), that is, pathologic ultrastaging. The SLN biopsy false-negative rate was 0% (95% CI: 0–1.6%). This ultrastaging enabled us to modify the adjuvant therapy for half the patients. Women with micrometastases detected by the SLN procedure were treated with external beam radiotherapy (EBRT), while those whose SLN biopsies were negative received vaginal brachytherapy (VBT) or clinical follow-up. SLN biopsies had no impact on recurrence-free survival.

Conclusion

SLN mapping and ultrastaging improved staging and made it possible to adapt adjuvant therapy to risk of recurrence.     

Follicle-stimulating hormone polypeptide modified nanoparticle drug delivery system in the treatment of lymphatic metastasis during ovarian carcinoma therapy

Objective

Traditional chemotherapy drugs have an obvious drawback of nonspecific biodistribution in treating ovarian cancer. Follicle-stimulating hormone receptor (FSHR), a G-protein coupled receptor which is mainly expressed in reproductive system, is an important drug target in developing novel therapeutics.

Methods

Using a polypeptide of follicle-stimulating hormone (named as FSHP), a conjugated nanoparticle, FSHP-NP was developed to target FSHR in lymphatic metastasis of ovarian cancer. FSHP-NP was tested for recognition specificity and uptake efficiency on FSHR-expressing cells. A paclitaxel (PTX)-loaded FSHP-NP (FSHP-NP-PTX) was further developed and its anti-tumor effect was determined in vivo and in vitro.

Results

Taking NuTu-19 cells as an example, FSHP-NP-PTX displayed significantly stronger anti-cell proliferative and anti-tumor effects in a dose- and time-dependent manner when compared with free PTX or naked PTX-loaded nanoparticles (NP-PTX) in vitro. In vivo examinations showed that the size and weight of the lymph nodes were reduced in the FSHP-NP-PTX group.

Conclusion

FSHR as a novel therapeutic target in ovarian cancer and delivery of PTX via conjugated nanoparticle (FSHP-NP) might represent a new therapeutic approach in ovarian cancer.     

Synchronous primary cancers of the endometrium and ovary in young women: A Korean Gynecologic Oncology Group Study

Objective

Some authors have recommended the use of diagnostic laparoscopy as a pretreatment assessment step for conservative hormonal treatment in young women with endometrial cancer. The aim of this study was to determine the incidence of synchronous primary cancer of the endometrium and ovary in young women.

Methods

The medical records of 3240 patients with endometrial cancer who underwent primary surgery between 1995 and 2010 were collected from 7 institutions and were retrospectively reviewed. Low-risk endometrial cancer was defined as tumors without myometrial invasion; normal or benign-looking ovaries; normal CA-125; grade 1 endometrioid histology; and early stage endometrial cancer on pretreatment assessment.

Results

Fifteen percent (471/3240) were younger than 40 years of age. The incidence of synchronous ovarian cancer in young women with endometrial cancer was 4.5% (21/471). In patients with low-risk endometrial cancer, synchronous cancers were not identified.

Conclusion

The incidence of synchronous ovarian malignancies in young women with endometrial cancer was quiet low (4.5%), unlike previous studies have revealed (11–29%). Therefore, diagnostic laparoscopy is not mandatory in patients with low-risk early stage endometrial cancer selected for conservative treatment to confirm the absence of ovarian malignancy.     

Preoperative pelvic lymphoscintigraphy is of limited usefulness for sentinel lymph node detection in cervical cancer

Objectives

To analyze concordance between preoperative lymphoscintigraphy and intraoperative lymphatic mapping (ILM) for sentinel lymph node identification using technetium 99m-labeled-dextran 500 (99m-Tc) and patent blue dye in patients with early cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy, as well as to evaluate sentinel lymph node (SLN) detection.

Study design

Forty-seven patients underwent surgical treatment for cervical cancer. For SLN identification, 99m-Tc and blue patent were injected into the cervix on the eve and day of surgery, respectively. Preoperative pelvic lymphoscintigraphy was performed in all patients after 99m-Tc injection. Concordance between preoperative lymphoscintigraphy and ILM was evaluated.

Results

Of the 56 patients who underwent preoperative lymphoscintigraphy, 43 (81.13%) had at least one lymph node identified. Bilateral lymph nodes were identified in 21 (37.5%) patients. Sentinel lymph nodes detected on ILM had been previously found on preoperative lymphoscintigraphy in 66.7%, 67.2% and 0% in the right, left and central locations, respectively. In 14 patients (25%), only one lymph node was identified on preoperative lymphoscintigraphy, but more than one sentinel lymph node was detected on intraoperative mapping. In nine (16.1%) patients, lymphoscintigraphy showed only unilateral lymph nodes, but ILM identified bilateral sentinel lymph nodes.

Conclusion

The combination of patent blue and radionuclide techniques produced excellent results for SLN detection in cervical cancer. Preoperative lymphoscintigraphy does not offer any advantage over ILM for SLN identification.     

Outcomes of patients with low-risk endometrial cancer surgically staged without lymphadenectomy based on intra-operative evaluation

Objective

The objective of the study was to evaluate clinical outcomes in patients with stage I endometrial cancer undergoing surgical management without lymphadenectomy based on intra-operative assessment for low-risk disease.

Methods

Between 2000 and 2009, a total of 179 patients were surgically staged without lymphadenectomy for low-risk stage I endometrial cancer. Low-risk cancer was defined by intra-operative criteria based on both gross and frozen tissue microscopic evaluation: 1) G1 or G2 endometrioid histology; 2) myoinvasion < 50%; 3) no cervical disease, and 4) no intra-abdominal metastasis. Records were reviewed for postoperative complications, pathological diagnoses, adjuvant radiation treatment, cancer recurrence, and mortality.

Results

Morbidity, cancer recurrence, and disease-specific mortality were low. Postoperative complications occurred in 5 patients (2.8%). Nine patients (5.0%) were offered adjuvant radiation for higher risk disease diagnosed on final pathology. Radiation morbidity was minimal: grade 1 vaginal toxicity in 2 patients. Three patients (1.7%) experienced recurrent cancer with mean time to recurrence of 43.7 months. Five year overall survival was 95.8%. The five year probability of disease-specific death was 1.1%.

Conclusion

In an institution with reliable capability of pathological frozen tissue diagnosis, omission of lymph node dissection is a reasonable option in the surgical management of those patients with low-risk disease diagnosed by intra-operative factors.     

Inhibition of epithelial ovarian cancer by Minnelide,a water-soluble pro-drug

Objective

Minnelide is a water-soluble pro-drug of triptolide, a natural product. The goal of this study was to evaluate the effectiveness of Minnelide on ovarian cancer growth in vitro and in vivo.

Methods

The effect of Minnelide on ovarian cancer cell proliferation was determined by real time electrical impedance measurements. Multiple mouse models with C200 and A2780 epithelial ovarian cancer cell lines were used to assess the efficacy of Minnelide in inhibiting ovarian cancer growth.

Results

Minnelide decreased cell viability of both platinum sensitive and resistant epithelial ovarian cancer cells in vitro. Minnelide with carboplatin showed additive effects in vitro. Minnelide monotherapy increased the survival of mice bearing established ovarian tumors. Minnelide, in combination with carboplatin and paclitaxel, improved overall survival of mice.

Conclusions

Minnelide is a promising pro-drug for the treatment of ovarian cancer, especially when combined with standard chemotherapy.