John H. Shepherd

Diagnostic Performance of Nanoparticle-Enhanced Magnetic Resonance Imaging in the Diagnosis of Lymph Node Metastases in Patients With Endometrial and Cervical Cancer

PURPOSE Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node-specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria. METHODS Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria. Lymph node sampling was performed in all patients. RESULTS Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 of 44 patients (25%). On a node-by-node basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by size criteria were 29%*, 99%, 56%, and 96%, and by USPIO criteria (reader 1/reader 2) were 93%/82%* (*P = .008/.004), 97%/97%, 61%/59%, and 100%/99%, respectively (where [*] indicates the statistical difference of P = x/x between the two results marked by the asterisk). On a patient-by-patient basis, sensitivity, specificity, PPV, and NPV by size criteria were 27%*, 94%, 60%, and 79%, and by USPIO criteria (reader 1/reader 2) were 100%/91%* (*P = .031/.06), 94%/87%, 82%/71%, and 100%/96%, respectively. The kappa statistic was 0.93. CONCLUSION Lymph node characterization with USPIO increases the sensitivity of MRI in the prediction of lymph node metastases, with no loss of specificity. This may greatly improve preoperative treatment planning.

Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment

PURPOSE Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. PATIENTS AND METHODS Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. RESULTS Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls. CONCLUSION Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.

Radical vaginal trachelectomy as a fertility‐sparing procedure in women with early‐stage cervical cancer—cumulative pregnancy rate in a series of 123 women

Objective  To analyse the fertility rates, complications and recurrences in a group of women who have undergone radical vaginal trachelectomy and pelvic lymphadenectomy for early‐stage cervical cancer.

Radical trachelectomy in early stage carcinoma of the cervix: outcome as judged by recurrence and fertility rates

The recurrence and fertility rates in 30 women undergoing radical trachelectomy for early stage invasive cervical cancer at St Bartholomews and Royal Marsden Hospital were reviewed. There were no recurrences, and the mean follow up was 23 months (range 1–64 months). Of 13 women trying to have a baby, eight had conceived with a total of 14 pregnancies and nine live births. Two were still trying and three were experiencing sub‐fertility. There were seven premature deliveries and one late miscarriage. Six of the preterm births and the late miscarriage were associated with prelabour spontaneous rupture of membranes. This conservative yet locally radical procedure for a highly selected group of women who wished to preserve their fertility appears to offer a safe alternative to radical hysterectomy in early invasive cervical cancer.

Natural history and prognosis of untreated stage I epithelial ovarian carcinoma

PURPOSE The aim of this study was to investigate the independent significance of prognostic factors in stage I invasive epithelial ovarian cancer (EOC). PATIENTS AND METHODS Between 1980 and 1994, all patients with stage I EOC (borderline tumors excluded) following surgical resection were entered onto this study. No patient received adjuvant therapy and patients were monitored as follows: years 1 to 2-physical examination and serum CA125 every 3 months and computed tomographic (CT) scan every 6 months; years 3 to 5-physical examination and serum CA125 every 6 months and CT scan yearly; years 5 to 10-annual physical examination and serum CA125, with CT scan if clinically indicated. RESULTS A total of 194 patients entered the study. The median patient age was 54 years (range, 15 to 83), and the median follow-up duration 54 months (range, 7 to 157). Five-year survival rates were as follows: stage IA, 93.7%; stage IB, 92%; and stage IC, 84%. Multivariate analysis using Coxs regression identified grade (P < .001), presence of ascites (P = .05), and surface tumor (P < .01) as independent poor prognostic factors. International Federation of Gynecology and Obstetrics (FIGO) substage did not appear to have independent prognostic significance. Intraoperative capsule rupture was not found to be prognostically significant. The impact of pre-operative rupture remains unclear. CONCLUSION This is an important series, as no patient received adjuvant therapy, and represents the natural history of surgically resected stage I EOC.

Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group

PURPOSE We have examined the role of an increase in cisplatin dose-intensity in patients with advanced epithelial ovarian cancer by means of single-agent carboplatin therapy. PATIENTS AND METHODS Two hundred twenty-seven patients were randomized to treatment and eligible for analysis. The dose of carboplatin was calculated according to the Calvert formula. One hundred seventeen patients received carboplatin at an area under the concentration time curve (AUC) of 6 for six courses, administered every 28 days, and 110 patients received carboplatin at an AUC of 12 for four courses, administered every 28 days. Patients were eligible provided they had not received prior chemotherapy or radiotherapy and had International Federation of Gynecology and Obstetrics stages II to IV or relapsed stage I epithelial ovarian cancer. RESULTS The planned total-dose increase was 33% for the patients treated with carboplatin AUC 12, but the received percentage total-dose increase was 20%. There were no differences in progression-free or overall survival between the two treatment arms; the overall survival rate at 5 years was 31% and 34% of patients treated at AUCs 6 and 12, respectively. There was significantly more toxicity associated with carboplatin AUC 12, which resulted in more treatment delays and/or dose reductions (52% v 18%; P < .001). CONCLUSION We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs. Nonhematologic toxicities were not clinically significant. Carboplatin offers an opportunity to intensify cisplatin therapy, but a greater than two-fold increase in dose-intensity probably needs to be achieved before significant effects on survival will be produced and hematologic support will be required.

The role of vaginal scan in measurement of endometrial thickness in postmenopausal women

Summary. Transvaginal ultrasound scanning was performed on 111 postmenopausal women. Of these women, 103 had postmenopausal bleeding, and eight were undergoing hysterectomy. Of the 103 women with bleeding, 93 had dilatation and curettage (D&C) and 10 patients were treated conservatively with a repeat scan in six months. A correlation of ultrasound findings and endometrial histopathology was possible in 94 patients. In 59 of these (63%) the endometrium was atrophic and the ultrasound endometrial thickness was 5 mm or less. In 29 (31%) patients the endometrial histology was abnormal and ultrasound endometrial thickness was greater than 5 mm. In six patients the endometrium was atrophic, but the ultrasonic endometrial thickness was apparently greater than 5 mm due to intracavity fluid. We suggest that an endometrial thickness of 5 mm is an appropriate cut‐off level for conservative management of patients with postmenopausal bleeding, or in screening for endometrial carcinoma.

Evaluation of endometrial carcinoma on magnetic resonance imaging

Our aims were to assess diagnostic performance of T2-weighted (T2W) and dynamic gadolinium-enhanced T1-weighted (T1W) magnetic resonance imaging (MRI) in the preoperative assessment of myometrial and cervical invasion by endometrial carcinoma and to identify imaging features that predict nodal metastases. Two radiologists retrospectively reviewed MR images of 96 patients with endometrial carcinoma. Tumor size, depth of myometrial and cervical invasion, and nodal enlargement were recorded and then correlated with histology. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the identification of any myometrial invasion (superficial or deep) were 0.94, 0.50, 0.93, 0.55 on T2W and 0.92, 0.50, 0.92, 0.50 on dynamic T1W, and for deep myometrial invasion were 0.84, 0.78, 0.65, 0.91 on T2W and 0.72, 0.88, 0.72, 0.88 on dynamic T1W. The sensitivity, specificity, PPV and NPV for any cervical invasion (endocervical or stromal) were 0.65, 0.87, 0.57, 0.90 on T2W and 0.50, 0.90, 0.46, 0.92 on dynamic T1W, and for cervical stromal involvement were 0.69, 0.95, 0.69, 0.95 on T2W and 0.50, 0.96, 0.57, 0.95 on dynamic T1W. Leiomyoma or adenomyosis were seen in 73% of misdiagnosed cases. Sensitivity and specificity for the detection of nodal metastases was 66% and 73%, respectively. Fifty percent of patients with cervical invasion on MRI had nodal metastases. In conclusion, MRI has a high sensitivity for detecting myometrial invasion and a high NPV for deep invasion. MRI has a high specificity and NPV for detecting cervical invasion. Dynamic enhancement did not improve diagnostic performance. MRI may allow accurate categorization of cases into low- or high-risk groups ensuring suitable extent of surgery and adjuvant therapy

Radical trachelectomy: a way to preserve fertility in the treatment of early cervical cancer

In the Centenary year of Wertheims hysterectomy for the treatment of invasive cervical cancer, it is appropriate to look at less radical methods of managing early stage disease. Radical trachelectomy with pelvic lymphadenectomy is a conservative but locally radical procedure, preserving the corpus uteri and therefore fertility potential. The first 10 cases in a pilot study are presented. One patient has required post‐operative radiotherapy and another a completion radical hysterectomy. Three live births by caesarean section and three other pregnancies have resulted. Careful selection within strict criteria may allow this more conservative approach without compromising cure. These procedures should be carried out in referral centres with continuing follow up and review.

Natural History of Stage IV Epithelial Ovarian Cancer

PURPOSE In this report we present the natural history, prognostic factors, and therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS We reviewed 192 patients with stage IV EOC as defined in 1985 by the International Federation of Gynecology and Obstetrics. RESULTS The site of stage IV-defining disease was cytologically positive pleural effusion in 63 patients, liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other sites in 15 patients, and disease at multiple stage IV-defining metastatic sites in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25 patients (14.8%) were left with only microscopic residual disease or less than 2 cm of macroscopic residual disease. The overall response rate to chemotherapy was 56%; the complete response rate was 18%. The median progression-free survival was 7.1 months, and the median overall survival was 13.4 months. The median overall survival of patients with positive pleural effusions only was 13.4 months as compared with 10.5 months for patients with visceral disease only, but this difference was not statistically significant. The 5-year survival rate was 7.6%, with only six patients surviving more than 5 years. Univariate and multivariate analysis showed that two parameters were associated with a shorter survival time: visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION Patients with stage IV EOC initially respond to chemotherapy as often as those with less advanced disease, but the long-term prognosis is very poor. The size of residual disease is not a prognostic factor in this group of patients, and, therefore, the role of debulking surgery in these patients needs to be reconsidered.