Extensive Surgical Staging Research Articles

Lymph Node Staging with a Combined Protocol of 18F-FDG PET/MRI and Sentinel Node SPECT/CT: A Prospective Study in Patients with FIGO I/II Cervical Carcinoma.

Lymph node metastasis (LNM) is present in a minority of patients with early stages of cervical carcinomas. As conventional imaging including PET/CT has shown limited sensitivity, systematic lymphadenectomies are often conducted for staging purposes. Therefore, the aim of this prospective study was to analyze the impact of 18F-FDG PET/MRI in addition to sentinel lymph node (SLN) biopsy on lymph node (LN) status. Methods: Forty-two women with an initial diagnosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IA-IIB cervical carcinoma were included between March 2016 and April 2019. Each patient underwent preoperative whole-body 18F-FDG PET/MRI and SLN imaging with SPECT/CT after intracervical injection of 99mTc-labeled nanocolloid. Systematic lymphadenectomy and SLN biopsy served as the reference standard. Staging using PET/MRI was performed by nuclear medicine and radiology experts working in consensus. Results: One patient was excluded from surgical staging because of liver metastases newly diagnosed on PET/MRI. The overall prevalence of LNM in the remaining 41 patients was 29.3% (12/41). Five of 12 patients with LNM had solely small metastases with a maximum diameter of 5 mm. The consensus interpretation showed PET/MRI to have a specificity of 100% (29/29; 95% CI, 88.3%-100%) for LNM staging but a low sensitivity, 33.3% (4/12; 95% CI, 12.8%-60.9%). LN size was the most important factor for the detectability of metastases, since only LNMs larger than 5 mm could be identified by PET/MRI (sensitivity, 57.1% for >5 mm and 0% for ≤5 mm). Paraaortic LNM was evaluated accurately in 3 of the 4 patients with paraaortic LN metastasis. SLNs were detectable by SPECT/CT in 82.9% of the patients or 69.0% of the hemipelves. In cases with an undetectable SLN on SPECT/CT, the malignancy rate was considerably higher (31.2% vs. 19.3%). The combination of PET/MRI and SLN SPECT/CT improved the detection of pelvic LNM from 33.3% to 75%. Conclusion:18F-FDG PET/MRI is a highly specific N-staging method and improves LNM detection. Because of the limited sensitivity in frequently occurring small LNMs, PET/MRI should be combined with SLN mapping. The proposed combined protocol helps to decide whether extensive surgical staging is necessary in patients with FIGO I/II cervical cancer.

Incidence of omental metastasis in uterine serous carcinoma: study protocol for a systematic review and meta-analysis

IntroductionUterine serous carcinoma accounts for only about 10% of all endometrial cancers but this subtype is the most common amongst non-endometrioid endometrium cancers and contributes to more than half of...

Trends in the surgical management of malignant ovarian germcell tumors

ObjectiveTo evaluate trends in the surgical management of young women and pediatric patients with malignant ovarian germ cell tumors (MOGCTs) and associated survival outcomes. Materials and methodsUsing the Surveillance, Epidemiology, and End Results database we identified patients under 40 years who underwent surgery between 1994 and 2014. The Joinpoint Regression Program was employed to investigate the presence of temporal trends and calculate average annual percent change (AAPC) rates. For analysis purposes two age groups were formed; pediatric/adolescent (≤21 yrs) and young adult (22–40 yrs). Histology was categorized into dysgerminoma, immature teratoma, yolk-sac tumor, mixed germ cell tumor and other histology. Cancer specific survival was compared using log-rank tests. ResultsA total of 2238 patients were identified, with median age 21 years. Only 12.4% underwent hysterectomy. One third underwent omentectomy, and one half underwent lymphadenectomy (LND). A decrease in the rate of omentectomy (AAPC: −2.15, 95% CI: −3.4, −0.9) and hysterectomy (AAPC: −3.31, 95% CI: −6.1, −0.4) was observed. There was no change in the rate of LND (AAPC: 0.17, 95% CI: −0.7, 1.1). Pediatric patients were less likely to undergo omentectomy (30.2% vs 35.5%, p < 0.001), hysterectomy (3.5% vs 22%, p < 0.001) and LND (45.6% vs 54.7%, p < 0.001). There were no apparent survival differences according to the performance of hysterectomy, omentectomy or LND, when stratified by early (stage I) and advanced stage (II–IV), (p > 0.05). ConclusionsPediatric patients with MOGCTs undergo less extensive surgical staging. A trend towards less extensive surgical procedures for young women over time was observed, without an apparent detrimental effect on cancer specific survival.

L1CAM Predicts Adverse Outcomes in Patients with Endometrial Cancer Undergoing Full Lymphadenectomy and Adjuvant Chemotherapy.

L1 cell adhesion molecule (L1CAM) has been established as an important predictor of poor survival of early-stage endometrial cancer patients. We investigated whether L1CAM remains a significant predictor of poor survival of patients with advanced-stage endometrial cancer undergoing extensive surgical staging and adjuvant chemotherapy. We prepared tissue microarray (TMA) from surgical tissue specimens of 161 endometrial cancer patients who underwent full lymphadenectomy combined with adjuvant chemotherapy for patients at risk for recurrence, and evaluated expression of L1CAM using immunohistochemistry. The correlation between L1CAM positivity and clinicopathological factors and the prognostic significance of L1CAM expression was investigated. Among 161 cases who had a follow-up duration of over 3years, 48 cases (29.8%) showed positive staining for L1CAM. L1CAM positivity was significantly correlated with non-endometrioid histology (p < 0.0001), vascular invasion (p = 0.0157), and positive cytology (p = 0.005), and was a significant predictor of poor survival among advanced-stage patients, but not early-stage patients in our cohort. L1CAM-positive patients showed a higher recurrence rate and frequency of distant failure than L1CAM-negative patients. Multivariate analysis revealed that para-aortic lymph node metastasis (PANM) and L1CAM positivity were independent predictors of poor survival. Overall survival can be stratified into three groups by the combination of PANM and L1CAM positivity. L1CAM is an independent predictor of poor survival in endometrial cancer patients undergoing full lymphadenectomy and adjuvant chemotherapy, thus indicating that L1CAM can be clinically used as a biomarker to identify those patients at increased risk of recurrence.

Role of imaging in the routine management of endometrial cancer.

Endometrial cancer is the most common gynecologic cancer in women today. It is surgically staged, and while surgery is the primary treatment modality, the identification of disease extent-in particular extrauterine spread-prior to surgery is important to optimize treatment decision making. Ultrasound and MRI are useful for evaluating the extent of local disease, while CT and PET are used for detecting lymph node or distant metastases. Diffusion-weighted MRI has also been used for detecting small metastatic deposits in lymph nodes and omentum. Extrauterine soft tissue involvement can be detected by ultrasound, CT, MRI, and PET. Recently, intraoperative visualization techniques, such as sentinel lymph node mapping, are increasingly used to avoid extensive surgical staging without compromising treatment. Imaging is also used for planning adjuvant treatment and detection of postoperative residual disease in high-risk patients, monitoring and detecting recurrent disease, and in post-treatment surveillance of asymptomatic patients with high risk of relapse.

Nuclear β-catenin localization and mutation of the CTNNB1 gene: a context-dependent association

Although the majority of low-grade, early-stage endometrial cancer patients have good survival with surgery alone, patients who recur tend to do poorly. Identification of patients at high risk of recurrence who would benefit from adjuvant treatment or more extensive surgical staging would help optimize individualized care of endometrial cancer patients. CTNNB1 (encodes β-catenin) mutations identify a subset of low-grade, early-stage endometrial cancer patients at high risk of recurrence. Mutation of CTNNB1 exon 3 is classically associated with translocation of the β-catenin protein from the membrane to the nucleus and activation of Wnt/β-catenin signaling. Given the clinical utility of identifying endometrial carcinomas with CTNNB1 mutation, the purpose of this study was to determine if immunohistochemistry could act as a surrogate for CTNNB1 gene sequencing. Next-generation sequencing was performed on 345 endometrial carcinomas. Immunohistochemical localization of β-catenin was determined for 53/63 CTNNB1 exon 3 mutant tumors for which tissue was available and a subset of wild-type tumors. Nuclear localization of β-catenin had 100% specificity in distinguishing CTNNB1 mutant from wild type, but sensitivity was lower (84.9%). Nearly half of CTNNB1 mutant cases had only 5–10% of tumor cells with β-catenin nuclear localization. The concordance between pathologists blinded to mutation status in assessing nuclear localization was 100%. The extent of β-catenin nuclear localization was not associated with specific CTNNB1 gene mutation, tumor grade, presence of non-endometrioid component, or specific concurrent gene mutations in the tumor. For comparison, nuclear localization of β-catenin was more diffuse in desmoid fibromatosis, a tumor also associated with CTNNB1 mutation. Thus, nuclear localization of β-catenin assessed by immunohistochemistry does not detect all endometrial cancers with CTNNB1 gene mutation. The extent of nuclear localization may be tumor type dependent. For endometrial cancer, immunohistochemistry could be an initial screen, with CTNNB1 sequencing employed when nuclear localization of β-catenin is absent.

Staging with Unilateral Salpingo-Oophorectomy and Expert Pathological Review Result in No Recurrences in a Series of 81 Intestinal-Type Mucinous Borderline Ovarian Tumors

Objective: Recent studies suggest that mucinous borderline ovarian tumors (MBOTs) belong to a high-risk group that is more likely to develop an invasive recurrence. The objective is to determine these risk factors. Methods: A monocentric retrospective review of all consecutive patients with intestinal-type MBOT diagnosed between 1993 and 2013. All tumors were evaluated by one pathologist without knowledge of clinical outcome. Extensive surgical staging and pathological tumor sampling (1 block/cm diameter in tumors <10 cm and 2 blocks/cm diameter in tumors >10 cm) were performed in all cases. Results: A total of 81 patients were included. Patients with micro-invasion were also included. None of the patients recurred. No bilateral tumors, nor tumors with International Federation of Gynecology and Obstetrics stage II or higher, were diagnosed. Median follow-up was 87 months. Conclusions: In our series of pure intestinal-type MBOT, including micro-invasion, no recurrences were observed. Given the heterogeneity of these tumors staging with at least unilateral salpingo-oophorectomy, extensive pathological sampling, and expert pathological review are of paramount importance to be able to diagnose a pure intestinal-type MBOT and excluding gastrointestinal mucinous tumors and more important, excluding an invasive focus, defining a mucinous ovarian carcinoma. When these conditions are fulfilled, the prognosis of pure intestinal-type MBOT is excellent.

Failure to recognize preoperatively high-risk endometrial carcinoma is associated with a poor outcome

ObjectiveTo evaluate the misdiagnosis between endometrial biopsy and definitive surgical pathology and to assess whether the failure in recognizing preoperatively high-risk endometrial carcinoma (EC) can impact oncological outcomes. Study designA retrospective study was conducted to evaluate patients with EC diagnosed by preoperative endometrial biopsy who subsequently underwent surgical staging between 2006 and 2013 at our institution. In patients with a surgical diagnosis of high-risk EC, histotype and grade change between the endometrial biopsy and surgical specimen (discordance diagnosis) were evaluated and correlated to survival outcomes. Cox's regression model for multivariable analysis was used to evaluate the effect of several variables (age, stage, discordance in diagnosis, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy) on the survival rate. ResultsData from 447 patients were reviewed. Among 109 women with surgical diagnosis of high-risk EC, 35 (32.1%) were preoperatively misdiagnosed. Of these 35 women, 24 (68.6%) cases were upgraded to grade 3, and 11 (3.4%) were upgraded to serous or clear cell type in the definitive specimen. The 5-year overall survival (OS; 70.2 vs. 86.8%; p=0.029), disease-specific survival (DSS; 72.5 vs. 88.2%; p=0.039) and recurrence free survival (RFS; 62.6 vs. 82.5%; p=0.024) were significantly lower in the high-risk EC patients who were preoperatively undiagnosed in the endometrial biopsy compared with patients with an appropriate preoperative histological diagnosis. Controlling for age, stage, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy, multivariable analysis revealed that discordance in diagnosis was associated with poorer survival outcomes. ConclusionFailure to recognize preoperatively high-risk ECs is associated with worse outcomes.

Robotic surgical staging for endometrial and cervical cancers in medically ill patients

ObjectivesPatients with high anesthesiological risk due to old age, obesity and severe co-morbidities alone or in combination are considered as poor candidates for extensive surgical staging procedures, especially if through minimally invasive approach. We aimed to evaluate the feasibility and safety of robotic surgical staging of endometrial and cervical cancers in the medically ill patient. MethodsBetween 07-2007 and 12-2012, consecutive patients scheduled for staging for endometrial or cervical cancer were directed towards robotic staging and divided into two groups according to their starting score in the American Society for Anaesthesiologists (ASA): Group 1 (ASA 1–2) and Group 2 (ASA ≥3). ResultsOverall, 169 (71.9%) patients had ASA 1–2 whereas 66 (28.1%) had ASA ≥3. ASA ≥3 were older (p<0.0001) with a greater proportion of co-morbidities (p<0.0001), as well as of Class II (4.7% vs 19.7%; p=0.0007) and Class III obesity (2.4% vs 31.8%; p<0.0001). No differences were found between groups in terms of operative time, blood loss, intra- and post-operative complications, conversion rate and hospitalization. No differences were recorded either in terms of staging procedures performed or in terms of number of pelvic (p=0.72) and para-aortic (p=0.86) lymph nodes retrieved. ConclusionsDespite theoretical concerns about the performance of robotic surgery in patients with high anesthesiological risk, our experience showed that robotics is a feasible, safe and viable option for the management of endometrial and cervical cancers also in this more vulnerable group of patients.

Recent advances in research on epigenetic alterations and clinical significance of para-aortic lymphadenectomy in endometrial cancer: an introduction

Endometrial cancer is the most frequent cancer of the female reproductive organs in industrialized countries. In 2012, the numbers of new cases and deaths from endometrial cancer in the US were estimated to be 47,130 and 8,010, respectively [1]. The incidence of endometrial cancer is also increasing steadily in Japan, where the estimated number of new cases in 2007 was 9,104 [2] and the number of deaths in 2011 was 2,034 [3]. Endometrial cancer is a surgically staged disease and post-operative therapy is offered to patients with a high risk of recurrence according to the extent and aggressiveness of the tumor. Current topics in endometrial cancer include: the therapeutic significance of lymphadenectomy, the role of epigenetic alterations, and revision of the International Federation of Gynecology and Obstetrics staging criteria (FIGO 2008) for this disease. There was a paradigm shift in the treatment strategy for endometrial cancer after the introduction of a surgical staging system (FIGO 1988) that replaced the older clinical staging system. The newer paradigms of extended-surgical staging containing lymphadenectomy with more restricted use of adjuvant therapy and the older paradigm of simple hysterectomy bilateral salpingo-oophorectomy with more frequent use of adjuvant radiotherapy need to be compared prospectively in terms of survival benefits, quality of life, and cost of treatment [4]. Several issues regarding surgical staging need to be clarified. They include: how should suitable patients for complete lymphadenectomy be selected and what is the optimal extent of lymphadenenctomy? The therapeutic significance of lymphadenectomy has long been a matter of great debate. In 1964, Lewis suggested a therapeutic effect of pelvic lymphadenectomy in nodepositive patients [5]. He employed pelvic lymphadenectomy because endometrial cancer often recurred at the pelvic side wall after conventional hysterectomy and bilateral salpingo-oophorectomy, which suggested inadequate primary surgery. Retrospective studies suggest a therapeutic significance for lymphadenectomy, which is a function of removed lymph node count (thoroughness) and area of dissection (pelvic only versus pelvic and para-aortic lymphadenectomy) [6–8]. However, two prospective randomized controlled trials (RCTs) that intended to prove the therapeutic role of pelvic lymphadenectomy failed to show any survival advantage of pelvic lymphadenectomy versus no lymphadenectomy [9, 10]. However, there has been some criticism about the design of these trials because para-aortic lymphadenectomy was not included in the study arm. A retrospective cohort study which compared pelvic lymphadenectomy with combined pelvic and paraaortic lymphadenectomy revealed survival improvement in the pelvic and para-aortic lymphadenectomy group if this treatment was offered to intermediate-/high-risk endometrial cancer patients [11]. Based on these findings, discussions have begun about the design of future clinical trials to validate the therapeutic significance of lymphadenectomy. Topics for discussion include the eligibility of patients (all patients or selected patients at some risk of nodal metastasis), extent of lymphadenectomy (area: pelvic alone versus pelvic plus para-aortic, thoroughness: number of nodes removed), and type of experimental design (RCT versus cohort study). The difficulties and pitfalls of RCTs for validating surgical procedures have often been addressed [12–16]. These include the participating surgeons’ expertise in experimental N. Sakuragi (&) Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, North 15, West 7, Kitaku, Sapporo 060-8638, Japan e-mail: sakuragi@med.hokudai.ac.jp

Endometrial cancer: prognostic significance of risk classification based on pre-intraoperative findings

The aim of this study was to determine whether a pre-intraoperative prognostic classification of endometrial cancer (EC) patients may accurately predict prognosis. Prognostic factors achievable before and during surgery (histotype, grade, myoinvasion, cervical spread, abdominal spread) were utilized to classify patients in low-risk (endometrial adenocarcinoma, grade 1-2, myoinvasion <50%, no evidence of abdominal spread), and in intermediate/high risk (serous papillary and clear cell, grade 3, myoinvasion >50%, cervical invasion, abdominal spread). Risk classification obtained pre-intraoperatively was compared with the classification obtained from definitive surgical-pathological assessment in 130 consecutive patients with EC treated with surgery. Pre-intraoperative risk assessment correctly identified risk classification in 125 (96%) patients; sensitivity, specificity, PPV and NPV were 98%, 94%, 94%, and 98%, respectively. Median follow-up was 38 months (range 6-93), and 14 (10%) patients relapsed (median time 14 months, range 3-60). Relative risk of relapse was higher in intermediate/high-risk patients with both classifications (pre-intraoperative RR 3.37, CI 0.99-11.5; surgical-pathological RR 4.56, CI 1.2-17.3). As regards survival 11 patients have died, 6 due to endometrial cancer and 5 due to intercurrent disease. Five-years DFS according to pre-intraoperative assessment was 89% and 71% for low-risk and intermediate high-risk patients (p = 0.028), respectively; according to definitive assessment was 91% and 70% for low-risk and intermediate/high-risk patients (p = 0.009), respectively. This classification, giving an accurate risk and prognostic estimate with parameters routinely utilized in clinical practice, may help the surgeon when undertaking the decision to perform limited or extended surgical staging according to tumor and patient characteristics.

Is Lymphadenectomy Justified in Endometrial Cancer?

Endometrial cancer has in the meantime become the most frequent malignant tumor of the female genital tract. With a 5-year survival rate of 82% for all stages and more than 90% for the most common stage I, it is a carcinoma with an excellent prognosis. Against this background and in light of the results of recent studies, the value of extensive surgical staging including pelvic and para-aortic lymphadenectomy beyond the standard therapy of hysterectomy with bilateral adnexectomy must be questioned.

Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass

ObjectiveWomen presenting with a large or complex ovarian cyst are referred to extensive surgical staging to ensure the correct diagnosis and treatment of a possible epithelial ovarian cancer. We hypothesized that measurement of the biomarkers HE4 and CA-125 preoperatively would improve the assignment of these patients to the correct level of care.MethodsPatients diagnosed with a cystic ovarian mass and scheduled for an operation at our center of excellence for ovarian cancer surgery from 2001 to 2010 were prospectively included (n=394) and plasma was collected consecutively. Cut-off for HE4 was calculated at 75% specificity (85 pM and 71.8 pM for post and premenopausal women). For CA-125, 35 U/mL cut-off was used. The study population included women with malignant (n=114), borderline (n=45), and benign (n=215) ovarian tumors.ResultsReceiver operator characteristic (ROC) area under the curve (AUC) in the benign versus malignant cohorts was 86.8% for CA-125 and 84.4% for HE4. Negative predictive value was 91.7% when at least one of the biomarkers was positive, with only early stage epithelial ovarian cancer showing false negative results. Sensitivity at set specificity (75%) was 87% for risk of ovarian malignancy algorithm (ROMA) in the postmenopausal cohort (cut-off point, 26.0%) and 81% in the premenopausal cohort (cut-off point, 17.3%). ROC AUC in the benign versus stage I epithelial ovarian cancer was only 72% for HE4 and 76% for CA-125.ConclusionIn our study, population HE4 did not outperform CA-125. Based on our data a prospective trial with patients already diagnosed with an ovarian cyst may be conducted.

Evaluation of Src Tyr419 as a predictive biomarker in a neoadjuvant trial using dasatinib in resectable malignant pleural mesothelioma.

7042 Background: Preclinical studies in malignant pleural mesothelioma (MPM) have shown that dasatinib, a multitargeted Src kinase/PDGFR inhibitor, has antitumor activity. We designed a novel biomarker-based neoadjuvant trial using dasatinib in resectable MPM. Methods: Untreated MPM patients undergo extended surgical staging (ESS) with multiple biopsies along the future surgical incision line to account for tumor heterogeneity. If deemed a surgical candidate for either P/D or EPP, patients receive 4 weeks of oral dasatinib (70 mg BID) followed by P/D or EPP. If a radiographic response is seen, an additional 2 years of dasatinib maintenance after adjuvant radiotherapy and chemotherapy is given. Serum/blood/platelets/pleural effusion are collected for exploratory analysis of peripheral surrogate biomarkers. Primary endpoint is biomarker modulation of Src Tyr419 in tumor tissue. Secondary endpoints: response, survival, safety/toxicity, and peripheral biomarker modulation. Results: 15 patients enrolled on the trial (4/08–1/10) have successfully completed ESS, neoadjuvant dasatinib, and P/D (n=10) or EPP (n=5). 13 epitheliod and 2 biphasic histology, 12 men: 3 women. The dasatinib main side effects were grade 1-2: anemia, nausea, vomiting, anorexia, fatigue, and anxiety. Grade 3 toxicities included fluid retention, infection (pneumonia), and hypoxia. There are no grade 4-5 toxicities. Post-surgical grade 3 toxicity included anemia, arrhythmia, HTN, and pleural effusion; 1 grade 4 episode of hyperglycemia. After 4 weeks of neoadjuvant dasatinib therapy, there was 1 PD, 12 SD and 2 minor responses. In the initial analysis of Src Tyr419 in 13 patients, higher baseline levels of p-Src Tyr419 predicted for an improved PFS with dasatinib therapy (p=0.008). Also, patients who had significant modulation of p-Src Tyr419 after dasatinib therapy had improved PFS (p=0.008). Conclusions: There is preliminary evidence that a subgroup of MPM patients gain clinical benefit from dasatinib therapy and that baseline p-Src Tyr419 levels in MPM tumor tissue may be predictive of PFS. This is the first targeted therapy neoadjuvant trial to potentially identify a predictive biomarker in MPM. No significant financial relationships to disclose.

Phase I trial of neoadjuvant dasatinib in patients with resectable malignant pleural mesothelioma

7580 Background: The optimal multi-modality treatment for resectable malignant pleural mesothelioma (MPM) remains unknown. We designed a biomarker-based neoadjuvant trial from our preclinical studies showing that dasatinib, a multi-targeted Src kinase inhibitor, has activity against MPM and target specificity to Src Tyr419. Methods: Untreated MPM patients underwent extended surgical staging (ESS) with multiple biopsies to account for tumor heterogeneity, lymph node status and to rule out sarcomatoid features. If deemed a surgical candidate for either pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP), patients received 4 weeks of oral dasatinib (70 mg BID) followed by P/D or EPP. If either a radiographic or molecular response (de-phosphorylation of Src Tyr419 in tumor) is achieved, an additional 2 years of dasatinib maintenance after adjuvant radiotherapy and systemic chemotherapy is given. The primary endpoint of this trial was biomarker modulation of Src Tyr419. Secondary endpoints included response, survival, safety/toxicity, and biomarker modulation in tumor/serum/platelets/pleural effusion. The total planned sample size is 24 to detect a 50% reduction in positive p-Src Tyr419 expression with 80% power, one-sided 10% type I error rate, and 10% inevaluable rate. Results: To date, ten patients have registered on the trial (4/08 - 12/08); six have successfully completed the ESS, neoadjuvant dasatinib, and P/D (n=3) or EPP (n=3). Two patients are still receiving neoadjuvant dasatinib; and 2 patients were deemed to not be surgical candidates due to a rapid decline in PS and one was found to have bilateral mesothelioma. The main side effects to dasatinib were grade 1–2: anemia, nausea, vomiting, anorexia, electrolyte abnormalities, fatigue, and anxiety. Grade 3 toxicities included hyperkalemia (1), infection - pneumonia (1), and hypoxia (1). There were no grade 4–5 toxicities. Post-surgical grade 3 toxicity included anemia, electrolyte abnormalities, arrhythmia, HTN, and pleural effusion; one grade 4 episode of hyperglycemia was seen. Conclusions: This study demonstrates that biomarker-based neoadjuvant MPM trials with novel agents are feasible. Updated clinical and translational correlative results will be presented. No significant financial relationships to disclose.

Alveolar soft part sarcoma of the cervix: case report and literature review

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy typically found in the extremities or chest of young adults. We present a case of an alveolar soft part sarcoma arising in the endocervix of a 38-year-old premenopausal woman. This cancer was treated by extrafascial hysterectomy. No evidence of metastatic disease was found after extensive surgical staging. Since treatment, she has since remained disease-free for more than 5 years without additional therapy. This is the second case of ASPS arising in the endocervix of which we are aware. Our observations suggest simple hysterectomy suffices for optimal clinical management of cervical ASPS and that surgical staging of this disease offers little prognostic benefit.

The risk of less extensive surgical staging in endometrial cancer

16587 Background: To evaluate the risk of nodal metastases in endometrial cancer. Methods: Demographic, clinico- pathologic, treatment and surgery information were obtained from the Surveillance, Epidemiology and End Results Program of the National Cancer Institute between 1988 and 2001 on all patients with endometrial cancer who underwent a lymphadenectomy. Kaplan-Meier and Cox regression analyses were used for analyses. Results: Of 15,283 women diagnosed with endometrial cancer, the median age at diagnosis was 64 years (range 22–99). The majority (79.8%) of patients were Caucasian; 6.3% were Hispanic, 5.9% African-American, and 5.7% were Asian. 12,067 had stage I-II disease and 3,216 had stage III-IV disease. 13,419 patients had endometrioid, 1,483 papillary serous, and 381 had clear cell carcinoma. Grade 1, 2, and 3 disease was found in 26.3%, 37.0%, and 30.8%, respectively. 37.6% of women received adjuvant radiation. 13.1% of women with stage I-IV disease had lymph node metastasis. The survival of patients with nodal metastasis was 53.2% vs. 91.4% with negative lymph nodes (p<0.001). In a subset of patients with similar eligibility criteria based on the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) clinical trial (stage IC grade 1 and all grade 2 disease), 10% of these patients had nodal metastasis. After excluding patients with stage IV disease, the risk of nodal metastasis was 6.0%. Of those with grade 2 cancers, the risk of nodal metastasis was 10.8%. In multivariate analysis, age, race, stage, grade, primary surgery, histology, and nodal metastasis all remained as significant independent prognostic factors for survival. Conclusions: In the overall study group, patients with endometrial cancer have a 10% risk of nodal metastases. The information obtained from lymphadenectomy can potentially circumvent or guide adjuvant therapy. No significant financial relationships to disclose.

Stage II endometrial carcinoma: Limiting post-operative radiotherapy to the vaginal vault in node-negative tumors

Objective. To evaluate the outcomes of patients with node-negative stage II endometrial cancer who received vault brachytherapy without external beam pelvic radiotherapy (EBRT). Methods. A retrospective review of all stage II endometrioid type endometrial cancer patients referred to Cancer Care Manitoba was undertaken between October 1995 and March 2001. Forty-nine patients were identified with disease confined to the uterus, but not all patients received extended surgical staging (ESS) with pelvic lymphadenectomy. These patients were evaluated for recurrence and morbidity data. Results. Twenty node-negative stage II cancers were identified. Three were treated without adjuvant treatment, 12 received vault brachytherapy and 5 received more conventional treatment with EBRT and vault brachytherapy. No recurrences or deaths occurred in these patients. Mean follow-up was 40 months. No surgical complications were encountered in this group and no morbidity from radiotherapy was observed. Conclusions. Limiting adjuvant treatment to vault brachytherapy for node-negative stage II endometrial cancer results in less morbidity and excellent survival and is worthy of further investigation.

Low risk endometrial cancer: a study of pelvic lymph node metastasis.

The aim of our study was to find preoperative or intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy. A retrospective review of the medical records of 107 patients with endometrioid adenocarcinoma, FIGO grade 1 or 2 tumor, myometrial invasion <or=50%, and no intraoperative evidence of macroscopic extrauterine spread was performed. Clinicopathologic risk factors were analyzed with Fisher 's exact test with regards to pelvic lymph node metastasis. The median age of the patients was 54 years. Pelvic lymph node metastasis was observed in five of 107 patients (4.7%), where two patients with small tumors of 2 cm or less had positive pelvic lymph nodes. The presence of positive pelvic lymph nodes did not correlate with depth of invasion, histologic grade, cervical invasion, peritoneal cytology, menopausal status, preoperative serum CA125 level, or primary tumor diameter. Only lymphvascular space involvement (P < 0.0001) was significantly correlated to pelvic lymph node metastasis. We suggest that all patients with endometrial cancer who are taken to the operating room for primary therapy should be prepared to undergo extended surgical staging, except when clinical or operative factors increase patients' morbidity.

Low risk endometrial cancer: A study of pelvic lymph node metastasis

The aim of our study was to find preoperative or intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy. A retrospective review of the medical records of 107 patients with endometrioid adenocarcinoma, FIGO grade 1 or 2 tumor, myometrial invasion ≤50%, and no intraoperative evidence of macroscopic extrauterine spread was performed. Clinicopathologic risk factors were analyzed with Fisher ′s exact test with regards to pelvic lymph node metastasis. The median age of the patients was 54 years. Pelvic lymph node metastasis was observed in five of 107 patients (4.7%), where two patients with small tumors of 2 cm or less had positive pelvic lymph nodes. The presence of positive pelvic lymph nodes did not correlate with depth of invasion, histologic grade, cervical invasion, peritoneal cytology, menopausal status, preoperative serum CA125 level, or primary tumor diameter. Only lymphvascular space involvement (P &lt; 0.0001) was significantly correlated to pelvic lymph node metastasis. We suggest that all patients with endometrial cancer who are taken to the operating room for primary therapy should be prepared to undergo extended surgical staging, except when clinical or operative factors increase patients' morbidity.