Dobson SR, McNeil S, Dionne M, et al.
Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial.
JAMA. 2013; 309(17):1793-802 [PubMed]

IMPORTANCE: Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible.
OBJECTIVE: To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses.
DESIGN, SETTING, AND PATIENTS: Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%).
INTERVENTION: Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. MAIN OUTCOMES AND MEASURES: Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months.
RESULTS: The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36.
CONCLUSIONS AND RELEVANCE: Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00501137.

Sachan R, Gupta P, Patel ML, et al.
Cervical tuberculosis masquerading as cancer cervix: a report of three cases.
Indian J Tuberc. 2013; 60(1):46-9 [PubMed]

Tuberculosis is still frequently observed in third world countries like Africa and Asia. Here we report three cases of genital tuberculosis with variable presentations. First case was a lady of reproductive age group who presented with polymenorrhea and post-coital bleeding with unhealthy cervix. Histopathology of cervical tissue revealed tubercular cervicitis. Second and third cases presented with different complaints like discharge per vaginum, post-coital bleeding and pain in lower abdomen with growth over the cervix. Cervical biopsy was inconclusive of tuberculosis but endometrial tissue sampling for TB PCR was positive. This shows that newer diagnostic marker test can help us to detect secondary genital tuberculosis.

Renshaw AA, Elsheikh TM
Assessment of manual workload limits in gynecologic cytology: reconciling data from 3 major prospective trials of automated screening devices.
Am J Clin Pathol. 2013; 139(4):428-33 [PubMed]

Previous prospective studies have shown different results when comparing automated and manual screening of gynecologic cytology. The results of 3 large prospective studies were reviewed and relative sensitivity used as a gold standard. No significant differences could be shown in relative sensitivity between the ThinPrep Imaging System and the FocalPoint GS Imaging System (P > .05). When manual screening was restricted to less than 6 hours per day, 50 or fewer slides per day, and at least 6 minutes per slide (<10 slides/h), the relative sensitivity for automation was significantly lower for atypical squamous cells of undetermined significance and above (ASC+) (0.81; 95% confidence interval [CI], 0.79-0.83) than when manual screening was not restricted (1.07; 95% CI, 1.03-1.10). All 3 sites that screened 10 or more slides per hour manually had a relative sensitivity for automation that was significantly higher for high-grade squamous intraepithelial lesions and above (HSIL+) than for the remaining groups who screened less than 10 slides per hour (1.40 [95% CI, 1.22-1.60] vs 0.97 [95% CI, 0.95-1.00]). These results suggest that location finding of abnormalities (ASC+) may be more strongly associated with time spent screening per day, whereas classification/interpretation skills (HSIL+) may depend on time spent on an individual case. There is no evidence that automated screening devices are more sensitive than manual screening performed at lower well-defined workloads. More restricted workloads (≤41 slides/d, ≤4.5 h/d) for manual screening may perform significantly better than automated screening devices as measured by histologic cervical intraepithelial neoplasia 2 and above.

Carrigg A, Teschendorf C, Amaro D, et al.
Examination of sources of diagnostic error leading to cervical cone biopsies with no evidence of dysplasia.
Am J Clin Pathol. 2013; 139(4):422-7 [PubMed]

At our institution, 17% of cervical conization specimens are reported as negative for dysplasia or malignancy. To identify sources of error, we reviewed 53 negative conization specimens and their prior and follow-up cytology, biopsy, and endocervical curettage specimens. Examination of deeper-level sections and p16 immunostaining were performed on all conization specimens and selected biopsy specimens. Dysplasia was detected in 26% (14/53) of conization specimens. Twenty-eight percent (15/53) of cones were truly negative, and the presurgical material had been overcalled as high-grade squamous intraepithelial lesions (HSIL). Forty-five percent (24/53) of cones were truly negative and HSIL was confirmed in the presurgical material. Of these, 11% (6/53) showed subsequent evidence of residual dysplasia and 26% (14/53) were negative on further follow-up. Deeper-level sections, p16 immunostains, and consensus review may help identify squamous dysplasia in conization specimens and may prevent the overdiagnosis of HSIL on cervical biopsies.

Aich RK, Dasgupta S, Chakraborty B, et al.
Primary fallopian tube carcinoma with metastasis in the contralateral ovary.
J Indian Med Assoc. 2012; 110(7):494-5, 498 [PubMed]

Primary malignant neoplasm of the fallopian tube is one of the rarest gynaecological malignancies and a pre-operative diagnosis is often missed due to its diagnostic confusion with the tubo-ovarian mass, hydrosalpinx, ectopic pregnancy and ovarian malignancy. Transcoelomic, lymphatic, transluminal and haematogenous spread may occur to the other abdominal and pelvic organs as well as to the distant sites. Though the body of the uterus, ovaries and the contralateral fallopian tube are frequently involved, in the present case the contralateral ovary was the only site of involvement which is very unusual.

Rai B, Patel FD, Chakraborty S, et al.
Bladder-rectum spacer balloon in high-dose-rate brachytherapy in cervix carcinoma.
Int J Radiat Oncol Biol Phys. 2013; 85(5):e217-22 [PubMed]

PURPOSE: To compare bladder and rectum doses with the use of a bladder-rectum spacer balloon (BRSB) versus standard gauze packing in the same patient receiving 2 high-dose-rate intracavitary brachytherapy fractions.
METHODS AND MATERIALS: This was a randomized study to compare the reduction in bladder and rectum doses with the use of a BRSB compared with standard gauze packing in patients with carcinoma of the cervix being treated with high-dose-rate intracavitary brachytherapy. The patients were randomized between 2 arms. In arm A, vaginal packing was done with standard gauze packing in the first application, and BRSB was used in the second application. Arm B was the reverse of arm A. The International Commission for Radiation Units and Measurement (ICRU) point doses and doses to 0.1-cm(3), 1-cm(3), 2-cm(3), 5-cm(3), and 10-cm(3) volumes of bladder and rectum were compared. The patients were also subjectively assessed for the ease of application and the time taken for application. Statistical analysis was done using the paired t test.
RESULTS: A total of 43 patients were enrolled; however, 3 patients had to be excluded because the BRSB could not be inserted owing to unfavorable local anatomy. Thus 40 patients (80 plans) were evaluated. The application was difficult in 3 patients with BRSB, and in 2 patients with BRSB the application time was prolonged. There was no significant difference in bladder doses to 0.1 cm(3), 1 cm(3), 2 cm(3), 5 cm(3), and 10 cm(3) and ICRU bladder point. Statistically significant dose reductions to 0.1-cm(3), 1-cm(3), and 2-cm(3) volumes for rectum were observed with the BRSB. No significant differences in 5-cm(3) and 10-cm(3) volumes and ICRU rectum point were observed.
CONCLUSION: A statistically significant dose reduction was observed for small high-dose volumes in rectum with the BRSB. The doses to bladder were comparable for BRSB and gauze packing. Transparent balloons of variable sizes are recommended for patients with a less spacious vaginal cavity.

Hasan TN, Shafi G, Syed NA, et al.
Methanolic extract of Nigella sativa seed inhibits SiHa human cervical cancer cell proliferation through apoptosis.
Nat Prod Commun. 2013; 8(2):213-6 [PubMed]

Nigella sativa (NS), also known as black cumin, has long been used in traditional medicine for treating various cancer conditions. In this study, we sought to investigate the potential anti-cancer effects of NS extract using SiHa human cervical cancer cells. NS showed an 88.3% inhibition of proliferation of SiHa human cervical cancer cells at a concentration of 125 microL/mL methanolic extract at 24 h, and an IC50 value 93.2 microL/mL. NS exposure increased the expression of caspase-3, -8 and -9 several-fold. The analysis of apoptosis by Dead End terminal transferase-mediated dUTP-digoxigenin end labeling (TUNEL) assay was used to further confirm that NS induced apoptosis. Thus, NS was concluded to induce apoptosis in SiHa cell through both p53 and caspases activation. NS could potentially be an alternative source of medicine for cervical cancer therapy.

Bishayee K, Ghosh S, Mukherjee A, et al.
Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: signal cascade and drug-DNA interaction.
Cell Prolif. 2013; 46(2):153-63 [PubMed]

OBJECTIVES: Small aromatic compounds like flavonoids can intercalate with DNA molecules bringing about conformational changes leading to reduced replication and transcription. Here, we have examined one dietary flavonoid, quercetin (found in many fruit and vegetables), for possible anti-cancer effects, on HeLa cells originally derived from a case of human cervical cancer.
MATERIAL AND METHODS: By circular dichroism spectroscopy we tested whether quercetin effectively interacted with DNA to bring about conformational changes that would strongly inhibit proliferation and migration of the HeLa cells. Cytotoxic effects of quercetin on cancer/normal cells, if any, were determined by MTT assay and such depolarization of mitochondrial membrane potential, as a consequence of quercetin treatment, and accumulation of reactive oxygen species (ROS) also were studied, by FACS analysis and expression profiles of different anti- and pro-apoptotic genes and their products were determined.
RESULTS: Quercetin intercalated with calf thymus cell DNA and HeLa cell DNA and inhibition of anti-apoptotic AKT and Bcl-2 expression were observed. Levels of mitochondrial cytochrome-c were elevated and depolarization of mitochondrial membrane potential occurred with increase of ROS; upregulation of expression of p53 and caspase-3 activity were also noted. These alterations in signalling proteins and externalization of phosphotidyl serine residues were involved with initiation of apoptosis. Reduced AKT expression suggested reduction in cell proliferation and metastasis potential, with arrest of the cell cycle at G2/M.
CONCLUSION: Quercetin would have potential for use in cervical cancer chemotherapy.

Laz TH, Rahman M, Berenson AB
Human papillomavirus vaccine uptake among 18- to 26-year-old women in the United States: National Health Interview Survey, 2010.
Cancer. 2013; 119(7):1386-92 [PubMed] Article available free on PMC after 01/04/2014

BACKGROUND: Human papillomavirus (HPV) vaccine uptake among young adult women has been reported to be very low. The authors conducted this study to provide an update on HPV vaccine uptake among 18- to 26-year-old women.
METHODS: The authors used the National Health Interview Survey 2010 data to estimate HPV vaccine coverage and their correlates.
RESULTS: Overall, 22.7% of women initiated (≥1 dose) and 12.7% completed the vaccine (≥3 doses). Thus, about 56% of women who initiated the vaccine completed it. Multivariate logistic regression analyses showed that younger age, unmarried status, Papanicolaou test, influenza vaccine, lifetime vaccines, and HPV vaccine awareness were positively associated with receiving ≥1 and ≥3 doses. In addition, uninsured women were less likely to receive ≥1 dose (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.28-0.84), and blacks (OR, 0.48; 95% CI, 0.23-0.99) and women with a family income <100% of the federal poverty level (OR, 0.40; 95% CI, 0.21-0.73) were less likely to receive ≥3 doses. Furthermore, based on vaccine initiators, blacks were less likely than whites to complete the vaccine (OR, 0.29; 95% CI, 0.16-0.55). Two thirds of unvaccinated women were not interested in future vaccination. Among those who were interested, >76.4% preferred to receive it free or at a lower cost, whereas 20% would pay the full cost of the vaccine.
CONCLUSIONS: One in 8 women completed the 3-dose HPV vaccine. Educational and vaccine financing programs are needed to improve the uptake among low-income minority women who are at increased risk for cervical cancer.

Postawski K, Przadka-Rabaniuk D, Piersiak T
8-oxo-7,8-dihydroguanine level - the DNA oxidative stress marker - recognized by fluorescence image analysis in sporadic uterine adenocarcinomas in women.
Ginekol Pol. 2013; 84(1):44-50 [PubMed]

OBJECTIVES: In the case of carcinogenesis in human endometrium no information exists on tissue concentration of 8-oxo-7,8-dihydroguanine, the DNA oxidative stress marker This was the main reason to undertake the investigation of this DNA modification in human uterine estrogen-dependent tissue cancers.
MATERIAL AND METHODS: In order to estimate the level of oxidative damage, 8-oxo-7,8-dihydroguanine was determined directly in cells of tissue microscope slides using OxyDNA Assay Kit, Fluorometric. Cells were investigated under confocal microscope. Images of individual cells were captured by computer-interfaced digital photography and analyzed for fluorescence intensities (continuous inverted 8-bit gray-scale = 0 [black]-255 [white]). Fluorescence scores were calculated for each of 13 normal endometrial samples and 31 uterine adenocarcinoma specimens. Finally the level of the oxidative stress marker was also analyzed according to histological and clinical features of the neoplasms.
RESULTS: The obtained data revealed that: 8-oxo-7,8-dihydroguanine levels were higher in uterine adenocarcinomas than in normal endometrial samples (48,32 vs. 38,64; p<0,001); in contrast to normal endometrium there was no correlation between age and DNA oxidative modification content in uterine cancer; highest mean fluorescence intensity was recognized in G2 endometrial adenocarcinomas; level of 8-oxo-7,8-dihydroguanine does not depend on Body Mass Index (BMI) and cancer uterine wall infiltration or tumor FIGO stage.
CONCLUSIONS: Our study indicates that accumulation of the oxidized DNA base may contribute to the development of endometrial neoplasia, however oxidative DNA damage does not seem to increase with tumor progression.

Hamed AH, Shepard MK, Maglinte DD, et al.
Neoadjuvant chemotherapy followed by simultaneous robotic radical trachelectomy and reversal of tubal sterilization in stage IB2 cervical cancer.
JSLS. 2012 Oct-Dec; 16(4):650-3 [PubMed] Article available free on PMC after 01/04/2014

INTRODUCTION: The aim of this study was to report a case of cervical cancer stage IB2 treated with neoadjuvant chemotherapy, followed by simultaneous robotic-assisted radical trachelectomy and reversal of tubal sterilization. Case Description: This case occurred in a university hospital involving a 31-y-old woman with stage IB2 cervical cancer treated using neoadjuvant chemotherapy, robotic surgery, and tubal anastomosis to determine cancer disease status and achieve restoration of tubal patency.
DISCUSSION: A successful radical trachelectomy with patent tubes was done bilaterally. Cancer and fertility procedures can be simultaneously implemented and achieved.

Nezhat FR, Denoble SM, Cho JE, et al.
Safety and efficacy of video laparoscopic surgical debulking of recurrent ovarian, fallopian tube, and primary peritoneal cancers.
JSLS. 2012 Oct-Dec; 16(4):511-8 [PubMed] Article available free on PMC after 01/04/2014

BACKGROUND AND OBJECTIVE: Studies on the role of laparoscopy in secondary or tertiary cytoreduction for recurrent ovarian cancer are limited. Our objective is to describe our preliminary experience with laparoscopic secondary/tertiary cytoreduction in patients with recurrent ovarian, fallopian, and primary peritoneal cancers.
METHODS: This is a retrospective analysis of a prospective case series. Women with recurrent ovarian, fallopian tube, or primary peritoneal cancers deemed appropriate candidates for laparoscopic debulking by the primary surgeon(s) were recruited. The patients underwent exploratory video laparoscopy, biopsy, and laparoscopic secondary/tertiary cytoreduction between June 1999 and October 2009. Variables analyzed include stage, site of disease, extent of cytoreduction, operative time, blood loss, length of hospital stay, complications, and survival time.
RESULTS: Twenty-three patients were recruited. Only one surgery involved conversion to laparotomy. Seventeen (77.3%) of the patients had stage IIIC disease at the time of their initial diagnosis, and 20 (90.9%) had laparotomy for primary debulking. Median blood loss was 75 mL, median operative time 200 min, and median hospital stay 2 d. No intraoperative complications occurred. One patient (4.5%) had postoperative ileus. Eighteen (81.8%) of the patients with recurrent disease were optimally cytoreduced to 1cm. Overall, 12 patients have no evidence of disease (NED), 6 are alive with disease (AWD), and 4 have died of disease (DOD), over a median follow-up of 14 mo. Median disease-free survival was 71.9 mo.
CONCLUSIONS: In a well-selected population, laparoscopy is technically feasible and can be utilized to optimally cytoreduce patients with recurrent ovarian, fallopian, or primary peritoneal cancers.

Kanbayashi Y, Hosokawa T, Kitawaki J, Taguchi T
Statistical identification of predictors for paclitaxel-induced peripheral neuropathy in patients with breast or gynaecological cancer.
Anticancer Res. 2013; 33(3):1153-6 [PubMed]

AIM: The aim of this study was to identify predictors for paclitaxel-induced peripheral neuropathy (PIPN).
PATIENTS AND METHODS: We conducted a retrospective analysis of 227 patients who had been treated with paclitaxel at a single institution between January 2008 and July 2011. At the time of chemotherapy completion, the severity of PIPN was graded on a scale of 0-5, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Multivariate-ordered logistic regression analysis was employed to examine the relationship between various predictive factors and the occurrence of PIPN.
RESULTS: Diabetes mellitus [odds ratio (OR)=0.070], age (OR=1.991), co-administration of neurotropin (OR=3.654), co-administration of opioids (OR=0.312), co-administration of vitamin B12 (OR=2.554), co-administration of antidepressant (OR=4.754) and co-administration of gabapentinoids (OR=14.620), were significantly associated with reduction of or less serious PIPN.
CONCLUSION: Our study indicates that PIPN may be alleviated by co-administration of opioids.

Tsubamoto H, Kawaguchi R, Ito K, et al.
Phase II study of carboplatin and weekly irinotecan combination chemotherapy in recurrent ovarian cancer: a Kansai clinical oncology group study (KCOG0330).
Anticancer Res. 2013; 33(3):1073-9 [PubMed]

BACKGROUND: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of irinotecan plus carboplatin chemotherapy in patients with epithelial ovarian cancer (EOC).
PATIENTS AND METHODS: Patients with either radiologically- or serologically-recurrent EOC were administered intravenous irinotecan (60 mg/m(2); days 1 and 8) and carboplatin area under the curve of 5 mg/ml/min (day 1), repeated every 21 days. The primary end-point was response rate (RR), while the secondary end-points were adverse events and progression-free survival (PFS).
RESULTS: Between 2005 and 2009, 40 patients (median age=59 years) with EOC were enrolled. Intention-to-treat analysis showed an RR of 43% [95% confidence interval (CI)=27-58%]. For patients with a platinum-free interval (PFI) of <6 months, overall RR based on RECIST was 21% (95% CI=0-43%) and median PFS was 3.7 months (95% CI=2.5-7.7 months), while those in patients with PFI ≥6 months were 52% (95% CI=31-74%) and 9.1 months (95% CI=7.9-11.2 months), respectively. Grade 3/4 toxicity encountered during the first cycle included G3/G4 neutropenia in 65% of patients (12/14), G3/G4 thrombocytopenia in 48% (18/1), G3 febrile neutropenia in 5% (2), G3 nausea in 5% (2), G3 diarrhea in 5% (2), and G3 fatigue in 5% of patients (2).
CONCLUSION: This carboplatin plus irinotecan combination demonstrated a modest activity in recurrent EOC. However, considering its hematological toxicities, the regimen should be further investigated to establish the feasibility of the modified dose for platinum-sensitive disease.

Santeufemia DA, Lumachi F, Basso SM, et al.
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy as salvage treatment for a late wound recurrence of endometrial cancer.
Anticancer Res. 2013; 33(3):1041-4 [PubMed]

Endometrial cancer (EC) is usually diagnosed at an early stage, when surgery-alone may be curative, but 20-25% of patients with EC have higher-risk early-stage disease requiring radiation therapy alone or in combination with chemotherapy, in addition to surgery. Most EC relapses are either pelvic or distant metastases and occur within the first three years after hysterectomy. Laparotomy wound recurrences of EC are extremely rare, and only a few cases have been previously reported. We describe the unusual case of a late wound recurrence from an EC surgically removed 10 years previously which was successfully treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) after response to a hormonal therapy. Ten years after abdominal hysterectomy and bilateral salpingo-oophorectomy, on computed tomographic (CT) scan, a 70-year-old woman exhibited an abdominal mass of 3.5 cm, strictly adherent to the abdominal rectal muscle. CT-guided biopsy revealed estrogen- and progesterone receptor-positive metastasis from EC and the patient was treated with megestrole acetate. The whole body (18)F-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET)/CT showed a marked metabolic response at the single metastatic site, with no further metastases, and the patient underwent surgical resection of the mass followed by immediate HIPEC perfusion with cisplatin. No residual macroscopic disease was present at the end of surgery and no complications occurred during the hospital stay. At 12-month follow-up, the patient is alive without evidence of disease. Although this approach is still being investigational for peritoneal recurrence of EC, our report confirms its feasibility and its promising results in highly selected patients.

Jung PS, Kim DY, Kim MB, et al.
Progression-free survival is accurately predicted in patients treated with chemotherapy for epithelial ovarian cancer by the histoculture drug response assay in a prospective correlative clinical trial at a single institution.
Anticancer Res. 2013; 33(3):1029-34 [PubMed]

This study aimed to prospectively correlate clinical outcomes of advanced epithelial ovarian cancer (AEOC), with the results of in vitro chemosensitivity testing of taxol and carboplatin using the in vitro histoculture drug response assay (HDRA). A total of 104 patients with AEOC were treated with combination chemotherapy of taxol and carboplatin after primary cytoreductive surgery between 2007 and 2012 at the Asan Medical Center, Seoul, Korea. To compare chemosensitivity in the HDRA with clinical response, all patients were first categorized into two groups as either sensitive to both taxol and carboplatin (SS), or not sensitive to one or both drugs (R) based on HDRA results. The recurrence rate was much lower in the SS group compared to the R group; 29.2% vs 69.8%, respectively (p=0.02). The SS group had a significantly longer progression-free survival compared to the R group, 34.0 months vs 16.0 months, respectively (p=0.025). These results demonstrate that the HDRA prospectively correlates to clinical outcome from chemotherapy and that treatment regimens can be individualized based on the HDRA.

Paulsson G, Andersson S, Sorbe B
A population-based series of ovarian carcinosarcomas with long-term follow-up.
Anticancer Res. 2013; 33(3):1003-8 [PubMed]

AIM: The aim of the present study was to evaluate a consecutive series of ovarian carcinosarcomas with regard to prognosis, treatment and prognostic factors.
PATIENTS AND METHODS: A consecutive series of 81 ovarian carcinosarcomas from two well-defined geographic regions were studied with regard to survival, type of primary and adjuvant therapy and prognostic factors. All patients but one underwent primary surgery and some patients also received adjuvant chemotherapy (platinum-based) alone or in combination with radiotherapy. Univariate and multivariate Cox proportional regression analysis was used. Survival was analyzed by the Kaplan-Meier technique and differences were assessed by the log-rank test.
RESULTS: The mean age of the patients was 73 years. Fifty-one patients received adjuvant chemotherapy and nine patients pelvic irradiation. The 5-year overall survival rate was 10%. Adjuvant therapy (any type) and six completed cycles of chemotherapy were highly significant factors with regard to improved overall survival rate. The only significant tumor-associated prognostic factor was the International Federation of Gynecology and Obstetrics (FIGO) grade of the tumor. FIGO stage, site of metastatic spread, tumor size, histology, DNA ploidy, and tumor necrosis were non-significant factors. Therapy was rather well-tolerated and 29 patients (57%) completed at least six cycles of adjuvant chemotherapy.
CONCLUSION: Adjuvant and completed chemotherapy according to the treatment plan were the most important prognostic factors. FIGO grade (grade 3 vs. 1-2) of the epithelial component of the tumor was also a significant prognostic factor in multivariate Cox analysis.

Zou B, Li QQ, Zhao J, et al.
β-Elemene and taxanes synergistically induce cytotoxicity and inhibit proliferation in ovarian cancer and other tumor cells.
Anticancer Res. 2013; 33(3):929-40 [PubMed]

β-Elemene, originally derived from plants, has been recently investigated as a new anticancer agent. The purpose of this study was to explore the efficacy and mechanisms of action of the combined use of β-elemene plus a taxane as an antitumor therapeutic strategy for ovarian cancer and other carcinomas. The interaction of β-elemene with paclitaxel or docetaxel produced additive to moderately synergistic effects against the platinum-resistant ovarian cancer cell line A2780/CP70 and its parental cell line A2780, and showed moderately synergistic activity against PC-3 prostate cancer cells. In addition, the co-administration of β-elemene and a taxane at low-micromolar concentrations dramatically increased the rate of micronucleus formation and the percentage of mitotic arrest in both ovarian cancer cell lines, as compared with treatment with either agent alone. The highest synergy towards the ovarian cancer cells was observed with β-elemene plus docetaxel. Consistent with these data, treatment of A2780/CP70 cells with β-elemene plus a taxane strikingly reduced cell viability and increased cell apoptosis, as assessed by annexin V binding. Moreover, β-elemene plus docetaxel induced elevated levels of caspase-9 and p53 proteins in A2780/CP70 cells, and the combination of β-elemene plus a taxane caused marked cell-cycle arrest at the G2/M phase in these cells. One possible mechanism to account for the enhanced cytotoxic efficacy of this combination treatment is a β-elemene-induced increase in taxane influx into cancer cells. These observations indicate that combination therapy with β-elemene and taxanes has synergistic antitumor activity against ovarian and prostate carcinomas in vitro. This promising new therapeutic combination warrants further pre-clinical exploration for the treatment of chemoresistant ovarian cancer and other types of tumors.

Shah MM, Zerlin M, Li BY, et al.
The role of Notch and gamma-secretase inhibition in an ovarian cancer model.
Anticancer Res. 2013; 33(3):801-8 [PubMed]

BACKGROUND: The Notch pathway is dysregulated in ovarian cancer. We sought to examine the role of Notch and gamma-secretase (GS) inhibition in ovarian cancer.
MATERIALS AND METHODS: Established ovarian cancer cell lines were used. Quantitative polymerase chain reaction (qPCR) was used to determine the relative expression of Notch receptor and ligands. Effects of GS inhibition on proliferation, colony formation, and downstream effectors were examined via methylthiazole tetrazolium (MTT) and Matrigel assays, and qPCR, respectively. In vivo experiments with a GS inhibitor and cisplatin were conducted on nude mice. Tumors were examined for differences in microvessel density, proliferation, and apoptosis.
RESULTS: Notch3 was the most up-regulated receptor. The ligands JAGGED1 and DELTA-LIKE4 were both up-regulated. GS inhibition did not affect cellular proliferation or anchorage-independent cell growth over placebo. The GS inhibitor Compound-E reduced microvessel density in vivo.
CONCLUSION: GS inhibition does not directly affect cellular proliferation in ovarian carcinoma, but Notch pathway blockade may result in angiogenic alterations that may be therapeutically important.

Hong DG, Park NY, Chong GO, et al.
Laparoscopic transperitoneal infrarenal para-aortic lymphadenectomy in patients with FIGO stage IB1-II B cervical carcinoma.
JSLS. 2012 Apr-Jun; 16(2):229-35 [PubMed] Article available free on PMC after 01/04/2014

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the safety, feasibility, and clinical outcomes of laparoscopic transperitoneal infrarenal para-aortic lymphadenectomy in patients with FIGO stage IB1-IIB cervical carcinoma.
METHODS: Between August 1999 and April 2009, we performed 59 laparoscopic transperitoneal lymphadenectomies; specifically, 12 procedures were performed up to the level of the left renal vessels, and 47 procedures were performed up to the level of the inferior mesenteric artery. We retrospectively analyzed the pathology reports and clinical data and compared the 2 groups. The data were analyzed with a nonparametric Mann-Whitney test, Kaplan-Meier log-rank test, and Pearson's correlation analysis.
RESULTS: The 2 groups did not significantly differ with respect to histologic type (P = .093), clinical stage (P = .053), tumor size (P = .383), time interval to start adjuvant therapy postoperatively (P = .064), and type of adjuvant therapy (P = .407). The blood loss (P = .131), operative time (P = .200), mean hospital stay (P = .417), and postoperative self-voiding (P = .306) did not significantly differ between the groups, with the exception of the number of harvested lymph nodes (P = .001). The disease-free survival was better in the group that underwent infrarenal para-aortic lymphadenectomy than the group that did not (P = .017); however, the 2 groups did not differ with respect to overall survival (P = .115).
CONCLUSION: We suggest that laparoscopic transperitoneal infrarenal lymphadenectomy for cervical cancer is feasible and safe. The rate of positive lymph nodes in infrarenal lymphadenectomy is very rare in patients with locally advanced cervical carcinoma. Infrarenal lymphadenectomy in patients with cervical cancer did not provide additional survival benefits in this study.

Johansson C, Schwartz S
Regulation of human papillomavirus gene expression by splicing and polyadenylation.
Nat Rev Microbiol. 2013; 11(4):239-51 [PubMed]

Human papillomaviruses (HPVs) are small DNA tumour viruses that are present in more than 99% of all cervical cancers. The ability of these viruses to cause disease is partly attributed to the strict coordination of viral gene expression with the differentiation stage of the infected cell. HPV gene expression is regulated temporally at the level of RNA splicing and polyadenylation, and a dysregulated gene expression programme allows some HPV types to establish long-term persistence, which is a risk factor for cancer. In this Review, we summarize the role of splicing and polyadenylation in the regulation of HPV gene expression and discuss the viral and cellular factors that control these processes.

Durowade KA, Osagbemi GK, Salaudeen AG, et al.
Prevalence and risk factors of cervical cancer among women in an urban community of Kwara State, north central Nigeria.
J Prev Med Hyg. 2012; 53(4):213-9 [PubMed]

BACKGROUND: Cervical cancer is the second most common malignancy in women worldwide with a high incidence in under-developed countries and Nigeria is one of these countries. This study aimed at screening for cervical cancer using Papanicolaou smear and to identify risk factors for cervical cancer among women in Olufadi community, Kwara State, North-central Nigeria.
METHODS: This was a cross-sectional study involving the screening of women aged 25-64 years for cervical cancer using Papanicolaou smear. Respondents were selected through systematic random sampling of households. Interviewer- administered questionnaire and clinical report form were also used to collect data. In addition, Pap smear samples were taken. Data was analyzed using SPSS version 15.
RESULTS: Only 10 (5.0%) respondents had positive cytology result, while the rest were normal. Of the 10 positive cytology results, 1 (10.0%) was high grade squamous intraepithelial lesion (HGSIL) while the remaining 9 (90.0%) were low grade squamous intraepithelial lesion (LGSIL) which corresponds to 0.5% and 4.5% of the total respondents respectively. Risk factors for cervical cancer identified included coitarche, tobacco smoking, number of sexual partners and family history of cervical cancer.
CONCLUSION: The findings from this study attest to the increasing burden of cervical cancer. The high number of positive results obtained from the study coupled with the presence of risk factors was an indication of how useful regular screening will be in the early detection of cervical cancer.

Huang CY, Ho CM, Chen YL, et al.
Impact of lymphadenectomy in uterine endometrioid carcinoma.
Eur J Surg Oncol. 2013; 39(4):350-7 [PubMed]

AIMS: To investigate the role of lymphadenectomy in uterine endometrioid carcinoma based on the 2009 FIGO staging system.
METHODS: Using an institution-maintained cancer registry database, all patients who were treated surgically for endometrial cancer from 1991 to 2008 in two medical centers were analyzed. Kaplan-Meier and Cox proportional hazards methods were used to determine the role of lymphadenectomy.
RESULTS: From 961 women with uterine endometrioid carcinoma, 680 underwent lymphadenectomy and 281 did not. Young age, early-stage disease, low-grade tumor, and lymphadenectomy were favorable independent prognostic factors. The five-year disease-specific survival (DSS) of stages IA, IB, II, and III, and the two-year DSS of stage IV patients who underwent lymphadenectomy were 97.8%, 88.3%, 91.5%, 70.5%, and 32.1%, respectively, compared to 98.7%, 70.0%, 73.3%, 42.9%, and 16.6% in those without lymphadenectomy (p > 0.05 for stage IA; p < 0.01 for stages IB-IV, log-rank test). In high-risk patients (i.e., poorly-differentiated, outer-half myometrial invasion, and stages II-IV), more extensive lymph node resection was associated with an improved five-year DSS, from 71.3% (1-10 nodes removed) and 85.3% (11-20 nodes removed) to 86.8% (>20 nodes removed) (p = 0.02, log-rank test). For stage IIIC-IV patients with nodal metastasis, the extent of node resection also significantly improved the five-year DSS, from 34.4% (1-10 nodes removed) and 62.4% (11-20 nodes removed) to 79.6% (>20 nodes removed) (p = 0.04, log-rank test).
CONCLUSIONS: Lymphadenectomy improves the survival of patients with uterine endometrioid carcinoma stage IB to stage IV. The extent of lymphadenectomy also improves the survival of high-risk patients and those with nodal disease.

Kalin A, Merideth MA, Regier DS, et al.
Management of reproductive health in Cowden syndrome complicated by endometrial polyps and breast cancer.
Obstet Gynecol. 2013; 121(2 Pt 2 Suppl 1):461-4 [PubMed]

BACKGROUND: Cowden syndrome is an autosomal-dominant condition associated with mutations in the tumor suppressor gene PTEN. Gynecologic malignancies are common with a 5-10% risk of endometrial cancer and 25-50% risk of breast cancer.
CASE: A 37-year-old woman with a history of breast cancer, other neoplasms, and multiple skin lesions was diagnosed with Cowden syndrome after a germline PTEN mutation was identified. The endometrium had high glucose uptake on positron emission tomography scan and was irregularly thickened on ultrasonography; biopsy revealed endometrial polyps and simple hyperplasia. Fifteen months later, hysteroscopy again confirmed numerous benign endometrial polyps.
CONCLUSION: Recurrent, multiple endometrial polyps portend a high risk of endometrial cancer in women with Cowden syndrome. Monitoring for malignancy and consideration of hysterectomy after childbearing is completed is warranted.

Ciszek B, Heimrath J, Ciszek M
The application of human papilloma virus genotyping for the identification of neoplasm lesions in the cervix of women with abnormal cytology smears.
Adv Clin Exp Med. 2012 Nov-Dec; 21(6):759-66 [PubMed]

BACKGROUND: A connection between infections with a highly oncogenic type of human papilloma virus and the development of cervical intraepithelial neoplasia and preinvasive cervical cancer has been proven both experimentally and clinically. The period after which persistent virus infection will lead to the development of precancerous and invasive lesions is dependent on, among others, the HPV genotype. The oncogenic types of human papilloma virus destabilize the genome of an infected cell and thus initiate the carcinogenesis process.
OBJECTIVES: The aim of this work was to analyze the frequency of occurrence of different oncogenic HPV genotypes among women with abnormal cytological smears and the correlation of this data with the degree of cervical intraepithelial neoplasia exacerbation.
MATERIAL AND METHODS: The sample consisted of 75 women of child-bearing age (16-43 years old) with an abnormal cytological smear and positive test identifying an infection with an oncogenic type of human papilloma virus. In every case histopathological verification, aimed at excluding pathologies in the endocervix, was conducted using a colposcopy with guided biopsy and cervix abrasion.
RESULTS: The authors found that the frequency of occurrence of different HPV genotypes of the groups of cytological diagnoses ASC-US, LSIL and HSIL do not differ statistically (p = 0.57). However, what is noteworthy is the more common occurrence of HPV 16 in type LSIL lesions (45.45%) and HPV 18 of a more advanced type HSIL (37.50%) pathology. Through the verification of the cytology results with histopathological diagnosis of the above groups the authors obtained statistically significant differences (p < 0.001) of individual pathological states. When regarding cytological HSIL diagnosis, CIN 1 was never diagnosed, while in other cytological groups cervical intraepithelial neoplasia of a low degree constituted over 40%. Analogically about 40% of HSIL diagnoses after histopathological verification turned out to be cancer of a pre-invasive state (CIS/AIS), the presence of which was not revealed by ASC-US and LSIL. What is more, CIN2/3 diagnosis was less frequent in the ASC-US cytological group than in the other two groups. While analyzing a share of other than HPV 16 and HPV 18 oncogenic types of human papilloma virus, the authors found that the most common were HPV 31, 45 and 33. In CIN 1 and CIN 2 their share was over 60%. In CIS/AIS type pathologies, no other types of human papilloma virus than HPV 16 and HPV 18 were shown.
CONCLUSIONS: Positive results of DNA HR HPV testing of women with abnormal cytology results identified a risk group for the development of cervical cancer. No statistically significant differences of the frequency of HPV 16 and HPV 18 type occurrences were found in analyzed groups with cytological and histopathological diagnoses.

Al-Loh S, Al-Hussaini M
Undifferentiated endometrial carcinoma: a diagnosis frequently overlooked.
Arch Pathol Lab Med. 2013; 137(3):438-42 [PubMed]

Undifferentiated endometrial carcinoma (UEC) is a relatively uncommon neoplasm with only few studies published thus far. It has always been a diagnostic challenge because of the lack of proper definition cited in most of the standard textbooks. Recently however, a few studies have highlighted the clinicopathologic features of UEC. The distinctive morphology of UEC was noted by the group from MD Anderson Cancer Center, which enabled them to establish the defining criteria. It appears to be more aggressive than endometrial endometrioid adenocarcinoma, FIGO (International Federation of Gynecology and Obstetrics) grade 3, its main differential diagnosis. Proper recognition of this entity is important owing to its aggressive behavior.

Sangkomkamhang US, Lumbiganon P, Laopaiboon M, Mol BW
Progestogens or progestogen-releasing intrauterine systems for uterine fibroids.
Cochrane Database Syst Rev. 2013; 2:CD008994 [PubMed]

BACKGROUND: Uterine fibroids are the most common premenopausal benign uterine tumours. Fibroids can cause symptoms including heavy menstrual bleeding, pelvic pressure and pain. Progestogens can be administered by various routes. Intramuscular injection of depot medroxyprogesterone acetate (DMPA) has dual actions (stimulatory or inhibitory) on fibroid cell growth. Progestogen-releasing intrauterine systems (IUS) decrease menstrual blood loss associated with fibroids by inducing endometrial atrophy and reduction of uterine fibroid size. Currently, their effectiveness for the treatment of uterine fibroids has not been evaluated.
OBJECTIVES: To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.
SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Specialised Register (inception to 17 August 2012), CENTRAL (inception to 17 August 2012) and Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, MEDLINE (inception to 17 August 2012), Ovid EMBASE (1 January 2010 to 17 August 2012), Ovid PsycINFO (inception to 17 August 2012), CINAHL database, and trials registers for ongoing and registered trials.
SELECTION CRITERIA: All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.
DATA COLLECTION AND ANALYSIS: We assessed all potentially eligible studies identified as a result of the search strategy. Two review authors extracted data from each included study using an agreed form and assessed the risk of bias. We resolved discrepancies through discussion.
MAIN RESULTS: This review included three studies. However, data for progestogen-releasing intrauterine systems were available from only one study that compared 29 women with a levonorgestrel (LNG)-IUS versus 29 women with a combined oral contraceptive (COC) for treating uterine fibroids. There was a significant reduction of menstrual blood loss (MBL) in women receiving the LNG-IUS compared to the COC using the alkaline hematin test (mean difference (MD) 77.5%, 95% CI 71.3% to 83.67%, 58 women) and a pictorial assessment chart (PBAC) (MD 34.5%, 95% CI 14.9% to 54.1%, 58 women). The reduction in uterine fibroid size was significantly greater in the leuprorelin group at 16 weeks compared to the progestogen lynestrenol group (MD -15.93 mm, 95% CI -18.02 to -13.84 mm, 46 women). There was no RCT evaluating the effect of DMPA on uterine fibroids.
AUTHORS' CONCLUSIONS: Progestogen-releasing intrauterine systems appear to reduce menstrual blood loss in premenopausal women with uterine fibroids. Oral progestogens did not reduce fibroid size or fibroid- related symptoms. However, there was a methodological limitation and the one included study with data had a small sample size. This evidence is insufficient to support the use of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.

Al Rawahi T, Lopes AD, Bristow RE, et al.
Surgical cytoreduction for recurrent epithelial ovarian cancer.
Cochrane Database Syst Rev. 2013; 2:CD008765 [PubMed]

BACKGROUND: The standard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy. Most women with primary ovarian cancer achieve remission on this combination therapy. For women achieving clinical remission after completion of initial treatment, most (60%) with advanced epithelial ovarian cancer will ultimately develop recurrent disease. However, the standard treatment of women with recurrent ovarian cancer remains poorly defined. Surgery for recurrent ovarian cancer has been suggested to be associated with increased overall survival.
OBJECTIVES: To evaluate the effectiveness and safety of optimal secondary cytoreductive surgery for women with recurrent epithelial ovarian cancer. To assess the impact of various residual tumour sizes, over a range between 0 cm and 2 cm, on overall survival.
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to December 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For databases other than MEDLINE, the search strategy has been adapted accordingly.
SELECTION CRITERIA: Retrospective data on residual disease, or data from randomised controlled trials (RCTs) or prospective/retrospective observational studies that included a multivariate analysis of 50 or more adult women with recurrent epithelial ovarian cancer, who underwent secondary cytoreductive surgery with adjuvant chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm.
DATA COLLECTION AND ANALYSIS: Two review authors (KG, TA) independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis.
MAIN RESULTS: There were no RCTs; however, we found nine non-randomised studies that reported on 1194 women with comparison of residual disease after secondary cytoreduction using a multivariate analysis that met our inclusion criteria. These retrospective and prospective studies assessed survival after secondary cytoreductive surgery in women with recurrent epithelial ovarian cancer.Meta- and single-study analyses show the prognostic importance of complete cytoreduction to microscopic disease, since overall survival was significantly prolonged in these groups of women (most studies showed a large statistically significant greater risk of death in all residual disease groups compared to microscopic disease).Recurrence-free survival was not reported in any of the studies. All of the studies included at least 50 women and used statistical adjustment for important prognostic factors. One study compared sub-optimal (> 1 cm) versus optimal (< 1 cm) cytoreduction and demonstrated benefit to achieving cytoreduction to less than 1 cm, if microscopic disease could not be achieved (hazard ratio (HR) 3.51, 95% CI 1.84 to 6.70). Similarly, one study found that women whose tumour had been cytoreduced to less than 0.5 cm had less risk of death compared to those with residual disease greater than 0.5 cm after surgery (HR not reported; P value < 0.001).There is high risk of bias due to the non-randomised nature of these studies, where, despite statistical adjustment for important prognostic factors, selection is based on retrospective achievability of cytoreduction, not an intention to treat, and so a degree of bias is inevitable.Adverse events, quality of life and cost-effectiveness were not reported in any of the studies.
AUTHORS' CONCLUSIONS: In women with platinum-sensitive recurrent ovarian cancer, ability to achieve surgery with complete cytoreduction (no visible residual disease) is associated with significant improvement in overall survival. However, in the absence of RCT evidence, it is not clear whether this is solely due to surgical effect or due to tumour biology. Indirect evidence would support surgery to achieve complete cytoreduction in selected women. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

Galaal K, van der Heijden E, Godfrey K, et al.
Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma.
Cochrane Database Syst Rev. 2013; 2:CD006812 [PubMed]

BACKGROUND: Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of women with advanced uterine carcinosarcoma is poor with a pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence.
OBJECTIVES: To evaluate the effectiveness and safety of adjuvant radiotherapy and/or systemic chemotherapy in the management of uterine carcinosarcoma.
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), 2012, Issue 10, MEDLINE and EMBASE up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma.
DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy were pooled in random-effects meta-analyses.
MAIN RESULTS: Three trials met the inclusion criteria and these randomised 579 women, of whom all were assessed at the end of the trials. Two trials assessing 373 participants with stage III to IV persistent or recurrent disease, found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide, after adjustment for performance status (HR = 0.75, 95% confidence interval (CI): 0.60 to 0.94 and HR = 0.72, 95% CI: 0.58 to 0.90 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, where significantly more women experienced these ailments in the combination therapy group than the Ifosamide group (RR = 3.53, 95% CI: 1.33 to 9.37).In one trial there was no statistically significant difference in the risk of death and disease progression in women who received whole body irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI: 0.48 to 1.05 and HR = 0.79, 95% CI: 0.53 to 1.18 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, where significantly less women experienced these morbidities in the whole body irradiation group than the chemotherapy group (RR= 0.02, 95% CI: 0.00 to 0.16) for haematological morbidity and all nine women in the trial experiencing neuropathy morbidity were in the chemotherapy group).
AUTHORS' CONCLUSIONS: In advanced stage metastatic uterine carcinosarcoma as well as recurrent disease adjuvant combination, chemotherapy with ifosfamide should be considered. Combination chemotherapy with ifosfamide and paclitaxel is associated with lower risk of death compared with ifosfamide alone. In addition, radiotherapy to the abdomen is not associated with improved survival.

Shylasree TS, Bryant A, Athavale R
Chemotherapy and/or radiotherapy in combination with surgery for ovarian carcinosarcoma.
Cochrane Database Syst Rev. 2013; 2:CD006246 [PubMed]

BACKGROUND: Ovarian carcinosarcoma, also known as malignant mixed Mullerian tumour, is a rare malignant gynaecological tumour constituting about 1% or less of all ovarian cancers. In over 80% of cases, there is extra-ovarian intra-abdominal spread at diagnosis. The primary treatment has traditionally been surgical cytoreduction followed by radiotherapy and chemotherapy or chemotherapy alone. Regimes have included cisplatin alone; a combination of doxorubicin, ifosfamide, dacarbazine, cyclophosphamide, taxol; and various other combinations. The effectiveness of these various regimens appears to be mixed. Therefore, there is a need to clarify if there is an optimum neoadjuvant or adjuvant therapy after surgical cytoreduction for this rare tumour. Also, it is important to address quality of life (QoL) issues related to treatment, particularly toxicity, as the overall prognosis appears to be poor.
OBJECTIVES: To assess the effectiveness and safety of various adjuvant and neoadjuvant chemotherapy and radiotherapy options or chemotherapy alone in combination with surgery in the management of ovarian carcinosarcoma.
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to February 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field.
SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that compared neoadjuvant or adjuvant chemotherapy and radiotherapy, or chemotherapy alone, in women with ovarian carcinosarcoma (malignant mixed Mullerian sarcoma of the ovary). We also reviewed non-randomised studies (NRS) for discussion in the absence of RCTs.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed.
MAIN RESULTS: The search strategy identified 297 unique references of which all were excluded.
AUTHORS' CONCLUSIONS: We found no evidence to inform decisions about neoadjuvant and adjuvant chemotherapy and radiotherapy regimens, or chemotherapy alone, for women with ovarian carcinosarcoma. Ideally, an RCT that is multicentre or multinational, or well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances, are needed to compare treatment modalities and improve current knowledge. Further research in genetic and molecular signalling pathways might improve understanding of this tumour subtype.