Alex J. Crandon

Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors

Effective combination chemotherapy has improved the previously dismal prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young patients, conservative surgery with adjuvant chemotherapy has made the preservation of fertility possible, even in patients with advanced disease. The increase in cure rates has shifted the focus of recent studies to the long term menstrual, reproductive, and gynecologic outcomes in these patients.

Impact of Hemoglobin Levels Before and During Concurrent Chemoradiotherapy on the Response of Treatment in Patients with Cervical Carcinoma Preliminary Results

In patients undergoing radiation for cervical carcinoma, there is evidence that anemia is associated with an impaired outcome. For patients undergoing chemoradiation, there are no data available. The objective of this retrospective study was to examine the impact of anemia before and during chemoradiation in patients with cervical carcinoma.

SYNCHRONOUS 5-FLUOROURACIL, MITOMYCIN-C AND RADIATION THERAPY IN THE TREATMENT OF LOCALLY ADVANCED CARCINOMA OF THE CERVIX

Locally advanced carcinoma of the cervix has a poor prognosis with a high incidence of persistent or recurrent local disease contributing to distressing symptoms and poor survival. This has remained unaltered over the past 30 years in spite of the addition of other therapeutic modalities. Between 1983 and January 1986, 38 patients with locally advanced carcinoma of the cervix were treated with synchronous 5-fluorouracil, mitomycin-C, and radiotherapy. The results of this pilot study indicate both an improvement in pelvic control and in 3-year survival rate for the chemosensitized therapy compared to conventional radiotherapy alone (55% v 28%) using historical controls. Improved survival was only significant for bulky FIGO Stage IIb tumors. The toxicity of this combination was predominantly gastro-intestinal and led to modification of both radiation dose and technique with subsequent improvement in the incidence of side effects. The results suggest that the combination of synchronous chemotherapy with radiotherapy is an improved method of treatment for locally advanced carcinoma of the cervix and that a prospective randomized trial is now justified.

Prognostic Importance of Preoperative CA-125 in International Federation of Gynecology and Obstetrics Stage I Epithelial Ovarian Cancer: An Australian Multicenter Study

PURPOSE To evaluate the prognostic significance of preoperative CA-125 levels on overall survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer (EOC). PATIENTS AND METHODS Data from 518 patients with FIGO stage I EOC treated in seven gynecologic oncology centers throughout Australia between 1990 and 2002 were analyzed. Patients with borderline tumors and nonepithelial ovarian carcinomas were excluded, as were women in whom CA-125 had not been determined preoperatively. Preoperative CA-125 levels were studied in surgically staged and incompletely staged patients and compared with prognostic factors, such as substage, grade, and histologic type. Multivariate Cox models were calculated. RESULTS CA-125 levels more than 30 U/mL were associated with higher grade, substage 1B and 1C, nonmucinous histologic type, and older age. In univariate analysis, higher histologic grade, the absence of surgical staging, and preoperative CA-125 levels more than 30 U/mL were associated with impaired survival. Multivariate analysis identified histologic grade, preoperative CA-125, and surgical staging as independent predictors for survival. In the subgroup of completely surgically staged patients, the 5-year overall survival rate was 82% (95% CI, 76% to 88%) for patients with CA-125 levels more than 30 U/mL and 95% (95% CI, 90% to 99%) for patients with CA-125 levels of 30 U/mL or less (P = .028). In the group of incompletely staged patients, the 5-year survival rates were similar for patients with elevated and normal serum CA-125 levels. CONCLUSION Complete surgical staging, histologic grade, and preoperative serum CA-125 levels are independent prognostic factors and should be included in the decision making for chemotherapy.

Incidence Of Post‐Operative Deep Vein Thrombosis In Gynaecological Oncology

Using 125I‐fibrinogen scanning the incidence of post‐operative DVT amongst patients with gynaecological malignancy was shown to be 37,9% which is substantialy higher than the 10% to 15% expected in a general gynaecological population. Twenty per cent of the total group studied had isotopic evidence of bilateral venous thrombosis post‐operatively. The inaccuracy of clinical diagnosis was demonstrated, and also the need to investigate both limbs if thrombosis was suspected. The incidence of post‐operative DVT was found to be significantly lower in smokers (11.5%) compared with non‐smokers (68.4%) (p<0.00025).

Expression of MUC1 splice variants in benign and malignant ovarian tumours

MUC1 is expressed on the surface of ovarian cancer cells. Nine different splice variants of MUC1 have been described, but no study has reported on the expression of MUC1 isoforms in human ovarian cancer. Our study compares patterns of expression of MUC1 splice variants of malignant and benign ovarian tumours. Ovarian tissue samples were taken from patients with benign ovarian tumours (n = 34) and from patients who had surgery for primary (n = 47) or recurrent (n = 8) ovarian cancer. RT‐PCR for MUC1 splice variants A, B, C, D, X, Y, Z, REP and SEC was performed and their expression compared to clinical and histopathologic parameters. Variants A, D, X, Y and Z were more frequently expressed in malignant than in benign tumours. All primary ovarian cancer cases were positive for variant REP but negative for variant SEC. No significant association of the expression of MUC1 splice variants with the response to chemotherapy or patient survival could be demonstrated. Expression of MUC1 splice variants A, D, X, Y, Z and REP is associated with the presence of malignancy, whereas expression of MUC1/SEC is associated with the absence of malignancy.

Fertility and Ovarian Function After Conservative Surgery for Germ Cell Tumours of the Ovary

Malignant ovarian germ cell tumours (MOGCT) principally occur in girls and young women and are generally unilateral. Effective combination chemotherapy with conservative surgery has seen a dramatic improvement in survival rates. This increase has shifted the focus to long‐term fertility and reproductive outcome. The present study describes 45 patients with MOGCT treated with conservative surgery to preserve fertility, with or without the addition of chemotherapy. The age range was 10 to 32 years with a mean of 20 years. The majority of the subjects had Stage 1 tumours; 44 underwent unilateral salpingo‐oophorectomy and 1 patient ovarian cystectomy. Adjuvant chemotherapy was administered in 29 patients. Overall mean follow‐up was 58.7 months. There were 4 recurrences and 2 deaths. Survival of those with Stage 1 disease was 97% and for advanced stages 87%. During chemotherapy 50% became amenorrhoeic but 96% resumed normal menstrual function on completion. Seven healthy babies were recorded in the chemotherapy group and no documented birth defects occurred in any of these. There was no case of persistent infertility; 3 patients experienced temporary problems. It is concluded that conservative fertility‐sparing surgery is the treatment of choice in these young women and advanced disease is not necessarily a contraindication. The majority can anticipate normal menstrual function and fertility.

Nomograms to predict isolated loco-regional or distant recurrence among women with uterine cancer

OBJECTIVE While there is ample literature on prognostic factors for uterine cancer, currently there are nomeans to estimate an individuals risk for recurrence or to differentiate the risk of loco-regional recurrence from distant recurrence. We addressed this gap by developing nomograms to individualize the risk of recurrence. METHODS A total of 2097 consecutive patients who underwent primary surgery between 1997 and 2007 were included. Sixteen covariates were evaluated for their prognostic significance and modeled using multivariable competing risks regression to predict three-year outcomes as part of a nomogram. Each covariate in the nomogram is assigned a value, and a sum of these values form the overall risk score from which three-year incidence probabilities can be predicted for each individual. Predictive accuracy was assessed with concordance index and then corrected for optimism. RESULTS The median follow-up time (inter-quartile range, IQR) was 50.0 (28.3-77.5) months and 221 patients developed a recurrence (127 patients with isolated loco-regional recurrence, 94 patients with distant recurrence). The nomograms included the following covariates: age at diagnosis, FIGO stage (2009), grade, lymphovascular invasion, histological type, depth of myometrial invasion, and peritoneal cytology. Concordance indices for isolated loco-regional and distant recurrences were 0.73 and 0.86, respectively. CONCLUSIONS Our nomograms quantify an individual patients risk of isolated loco-regional and distant recurrence, using factors that are routinely collected. They may assist clinicians to assess an individuals prognosis, individualize treatment and also assist in the risk stratification in prospective randomized clinical trials evaluating the effectiveness of treatments for uterine cancer.

Pap smear screening history of women with squamous cell carcinoma and adenocarcinoma of the cervix

Background:  Since the introduction of the Pap smear screening, the incidence of squamous cell carcinoma (SCC) has decreased significantly, but the incidence of adenocarcinoma (AC) relative to SCC has increased.

Validation of the FIGO 2009 Staging System for Carcinoma of the Vulva

Background The previous (1988) International Federation of Gynecology and Obstetrics (FIGO) vulval cancer staging system failed in 3 important areas: (1) stage 1 and 2 disease showed similar survival; (2) stage 3 represented a most heterogeneous group of patients with a wide survival range; and (3) the number and morphology of positive nodes were not taken into account. Objective To compare the 1988 FIGO vulval carcinoma staging system with that of 2009 with regard to stage migration and prognostication. Methods Information on all patients treated for vulval cancer at the Queensland Centre for Gynecological Cancers, Australia, between 1988 to the present was obtained. Data included patients’ characteristics as well as details on histopathology, treatments, and follow-up. We recorded the original 1988 FIGO stage, reviewed all patients’ histopathology information, and restaged all patients to the 2009 FIGO staging system. Data were analyzed using the Kaplan-Meier method to compare relapse-free survival and overall survival. Results Data from 394 patients with primary vulval carcinoma were eligible for analysis. Patients with stage IA disease remained unchanged. Tumors formerly classified as stage II are now classified as stage IB. Therefore, FIGO 2009 stage II has become rare, with only 6 of 394 patients allocated to stage II. Stage III has been broken down into 3 substages, thus creating distinct differences in relapse-free survival and overall survival. Prognosis of patients with stage IIIC disease is remarkably poor. Conclusion The FIGO 2009 staging system for vulval carcinoma successfully addresses some concerns of the 1988 system. Especially, it identifies high-risk patients within the heterogeneous group of lymph node–positive patients.