P. Sukumvanich

Sentinel lymph node biopsy in early-stage cervical cancer: Utility of intraoperative versus postoperative assessment

OBJECTIVE To determine the diagnostic accuracy of sentinel lymph node (SLN) detection using lymphoscintigraphy, intraoperative blue dye, and radiocolloid in patients with early-stage cervical cancer. METHODS Intra-cervical injection of technetium-99 sulfur colloid and lymphoscintigraphy were performed preoperatively. Isosulfan blue was injected intra-cervically immediately prior to surgery. SLNs were excised and examined intraoperatively (imprint cytology and frozen section) and postoperatively (H and E histology and immunohistochemistry (IHC) for cytokeratin). RESULTS Thirty eight patients were evaluable. Laparoscopy and laparotomy were performed in 28.9% and 71.1%, respectively. Subjects had squamous cell carcinoma (n=26), adenocarcinoma (n=10) or adenosquamous (n=2) histologies. 55.3% had cervical tumors <2 cm. The overall SLN detection rate was 92.1%. The external iliac region just distal to the common iliac bifurcation was the most common SLN location. A mean of 2.1 SLNs were detected per patient with bilateral SLNs observed in 47.4%. On final pathology, metastatic nodal disease was identified in 15.7% of patients. Of these, 83.3% were detected in the SLNs. Sensitivity of SLN detection of metastasis was 100% for patients with cervical tumors <2 cm. However intraoperative evaluation by imprint cytology and frozen section correctly identified lymph node metastasis in only 33.3%. CONCLUSIONS SLN detection is feasible and accurately reflects pelvic nodal basin status when performed in early-stage cervical cancer patients. However, while current intraoperative pathology techniques for assessing nodal metastases reliably detect metastases larger than 2 mm, they lack sufficient sensitivity to detect micrometastasis and isolated tumor cells.

Three-dimensional High Dose Rate Intracavitary Image-guided Brachytherapy for the Treatment of Cervical Cancer Using a Hybrid Magnetic Resonance Imaging/Computed Tomography Approach: Feasibility and Early Results

AIMS To evaluate the feasibility and outcome of image-guided brachytherapy (IGBT) for treating cervical cancer using magnetic resonance imaging (MRI)-based planning for the first fraction followed by computed tomography (CT)-based planning for subsequent fractions. MATERIALS AND METHODS Forty-four patients with cervical cancer were treated with three-dimensional high dose rate IGBT. The brachytherapy dose was 5.0-6.0 Gy × five fractions. All but five patients received concurrent weekly cisplatinum at 40 mg/m(2). All patients received external beam radiotherapy (EBRT) with a median dose of 45Gy over 25 fractions. Total doses for the high-risk clinical target volume (HRCTV) and organs at risk, including the rectum, bladder and sigmoid, from EBRT and brachytherapy were summated and normalised to a biologically equivalent dose of 2Gy per fraction (EQD(2)). At 3 months after therapy, any early response was assessed with positron emission tomography (PET)/CT imaging. RESULTS The mean D(90) for the HRCTV was 83.3 (3.0) Gy. The mean 2 cm (3) dose to the bladder, rectum and sigmoid colon organs was 79.7 (5.1), 57.5 (4.4) and 66.8 (5.7) Gy, respectively. All but one (2.3%) patient had a complete response. Follow-up PET/CT was carried out in 41 (93.0%) patients, of whom 38 (92.5%) had a complete response. Of the 38 patients with a complete response on PET/CT, two had local recurrences at 6 and 8 months, respectively. Actuarial 2 year local control, disease-specific and overall survival rates were 88, 85 and 86%, respectively. CONCLUSION This is the first report of three-dimensional high dose rate IGBT for the treatment of cervical cancer using a hybrid MRI/CT approach. Early results have shown the feasibility of this approach with excellent local control. Additional studies are needed to assess long-term outcomes of local control and associated morbidities.

Survival advantage associated with multimodal therapy in women with node‐positive (stage‐IIIC) uterine papillary serous carcinoma: a National Cancer Database study

Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer. Adjuvant chemotherapy (CT) has become standard care in treatment of women with advanced‐stage UPSC, but the role of consolidative radiotherapy (RT) is unclear. This study aims to evaluate survival outcomes of multimodal therapy.

The Role of High-Risk Human Papilloma Virus Testing in the Surveillance of Cervical Cancer After Treatment.

CONTEXT Cervical cancer affects 12 000 women in the United States annually. However, despite its prevalence, there remains no good methodology to detect its recurrence. OBJECTIVE To identify the role of cervicovaginal high-risk human papilloma virus (hr-HPV) testing in predicting cervical cancer recurrence. DESIGN This is a retrospective study of patients who underwent hr-HPV testing as part of their routine surveillance for cervical cancer. Standard statistical analyses, including χ² test and multivariable logistic regression, were performed with IBM SPSS 19.0. RESULTS A total of 133 patients were identified, of whom 107 (80%) had squamous cell carcinoma. Ninety patients (68%) had bulky disease and were treated primarily with chemoradiation and brachytherapy. Of patients whose disease recurred, 5 patients (42%) had tested positive for hr-HPV during their surveillance period, compared to 13 patients (11%) for whom disease did not recur (relative risk: 3.88, P = .002). On multivariate logistic regression, hr-HPV status remained significantly predictive of disease recurrence (odds ratio: 12.3, P = .02, 95% confidence interval: 1.5-99.6). Using 2 × 2 table analysis, we found that while cervicovaginal cytology has limited specificity (5.7%) in predicting recurrence, the combination of cytology with hr-HPV testing increases the specificity of testing to 89.3%. CONCLUSIONS Persistence of hr-HPV is a risk factor for disease recurrence. High-risk-HPV testing is not routinely used during surveillance for cervical cancer, but this study suggests that large, prospective trials investigating the role of hr-HPV testing in cervical cancer surveillance are needed.

Abstract 10: Comparison of outcomes in patients undergoing rectosigmoid resection: End colostomy versus reanastomosis

9: Identification of molecular markers for targeted treatment of uterine sarcoma J. Shank, J. Rhode, J. Liu. University of Michigan, Ann Arbor, MI, USA, Monarch Womens Cancer Center, Salt Lake City, UT, USA Objectives: Uterine sarcomas are rare and aggressive tumor types. Patients diagnosed with this disease often have poor clinical outcomes, despite multi-modal therapy. Because uterine sarcomas are not common, investigations into novel therapeutics for this disease have been limited. The aim of our study was to identify the expression of therapeutic targets using tissue microarrays in order to direct the exploration of molecularly targeted treatment. Methods: Tumor tissue was collected from 36 patients with uterine sarcomas (6 endometrial stromal sarcomas [ESS], 7 leiomyosarcomas [LMS], and 23 carcinosarcoma [CS]) who were evaluated at a single cancer center between 1996 and 2004. Tissue microarrays were constructed and expression of several molecular markers that are associated with targeted therapeutics in current use for other tumor types was assessed. Expression of VEGF, EGRF, c-Kit and HER-2 was investigated using immunohistochemistry. Immunostaining was evaluated by a gynecologic pathologist. Clinical outcomes including demographic data, treatment modalities received, and overall survival were recorded. Results: The mean age of patients included in this study was 63 (range 35–91). Expression of VEGF, EGFR, c-KIT, and HER-2 was detected in 81%, 81%, 72%, and 14% of all uterine sarcomas examined respectively. VEGF was expressed in 17% of ESS (1/6), 86% of LMS (6/ 7), and 96% of CS (22/23). EGFR was expressed in 50% of ESS (3/6), 86% of LMS (6/7), and 87% of CS (20/23). Expression of c-KIT was seen in 50% of ESS (3/6), 57% of LMS (4/7), and 83% of CS (19/23). HER-2 expression was minimal in all tumor types (ESS 17% [1/6], no expression in any LMS samples, and CS 7% [4/23]). Conclusions: Our data suggests that anti-angiogenic therapy may have activity in uterine leiomyosarcomas and carcinosarcomas. Targeted therapy for EGFR may have significant effects in patients with LMS and CS. This finding may justify using monoclonal antibodies against EGFR (such as cetuximab) or small molecule inhibitors of EGFR (such as gefitinib) in patients with LMS and CS. c-KIT also may be a potential target in CS and further studies with imatinib may be justified. HER-2 is a poor therapeutic target in all three types of uterine sarcomas. These results provide rationale for the use of targeted therapy to improve outcomes for uterine sarcoma

Pregnancy Related Breast Carcinoma: Comparison of Receptor Status with Age-Matched Controls.

Pregnancy related breast cancer (PRBC) is defined as breast cancer that is diagnosed during a pregnancy or within 1 year post-partum. These are generally considered as biologically aggressive tumors but the recent data suggests their prognosis to be similar to that of non-pregnant patients matched for age and stage. In the last few years, gene-expression profiling has been used to define breast cancer molecular classes with prognostic significance. The determination of tumor molecular class by immunohistochemistry is a reasonable alternative to molecular profiling. Therefore, we used immunohistochemical surrogate markers, estrogen receptors (ER), progesterone receptors (PR) and HER2 to determine breast cancer molecular classes in PRBC and compared them to age matched controls. ER and PR were scored using a semi-quantitative H-score like method that take into account both intensity and percentage cellular staining, and the score has a dynamic range of 0-300. An ER and PR score >10 was considered a positive result. An ER/PR score of 200 or higher in a tumor was considered as strongly positive for the hormone receptor. HER2 was considered positive only if 3+ by IHC or unequivocally amplified by FISH. The tumors were classified as luminal A (LUMA), Luminal B (LUMB), Triple Negative (TN), ERBB2, Luminal A-HER2 Hybrid (LAHH), and Luminal B-HER2 Hybrid (LBHH). The immunohistochemical criteria, prevalence of molecular subtypes in PRBC and age matched controls (age less than 40 years) is shown in the table below. Statistical analysis was performed using SPSS software version 16.0. Chi-square test was performed to compare the differences in percentages between PRBC and the non-pregnant control group. A p-value Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6012.