D.M. Boruta

Endometrial cancer: A review and current management strategies: Part I

Endometrial carcinoma is the most common gynecologic malignancy. A thorough understanding of the epidemiology, pathophysiology, and management strategies for this cancer allows the obstetrician-gynecologist to identify women at increased risk, contribute toward risk reduction, and facilitate early diagnosis. The Society of Gynecologic Oncologys Clinical Practice Committee has reviewed the literature and created evidence-based practice recommendations for diagnosis and treatment. This article examines: • Risk factors, including genetic predisposition • Diagnostic and metastatic evaluation • Surgical management of early and advanced cancer, including lymphadenectomy in early cancer.

Defining prognostic variables in recurrent endometrioid endometrial cancer: a 15-year single-institution review.

Objective: This study aimed to examine the pattern of recurrence in patients with endometrioid endometrial cancer and to identify clinically important prognostic factors in the recurrent population. Methods: With institutional review board approval, a retrospective review identified 1061 patients who underwent primary surgery and treatment of endometrioid endometrial cancer at our institution from 1994 to 2007. Of this cohort, 77 (7.2%) patients developed a recurrence. Clinical factors were recorded, and Spearman correlation coefficients and &khgr;2 test were used to determine associations between groups. Kaplan-Meier survival estimates and Cox proportional-hazards model were used to determine how prognostic variables affected survival after recurrence (RS) and overall survival (OS). Results: Of 77 patients, site of recurrence was not available in 5 patients. The distribution of recurrence in the remaining 72 patients was as follows: isolated vaginal 18% (13/72), nonvaginal pelvic 12% (9/72), distant 31% (22/72), abdominal 24% (17/72), and nodal 15% (11/72). There was an overrepresentation of advanced stage (P < 0.001) and high-grade (P < 0.003) at presentation in the recurrent group. Median OS was 3.4 years and median RS was 1.3 years. Low-grade tumors, early stage, and those with less than 50% myometrial invasion were associated with a significant OS and RS advantage. Age-adjusted isolated vaginal recurrence presented with a 1.2-year RS survival advantage (P < 0.03). An age-adjusted Cox proportional hazard ratio model incorporating significant prognostic variables demonstrated that the only independent variable associated with worse OS and RS was increased histologic grade with a hazard ratio of 2.31 (95% confidence interval, 1.25-3.97) for RS and 2.44 (95% confidence interval, 1.41-4.62) for OS. Conclusions: Those patients with high-grade histology at the time of initial diagnosis manifest a decreased OS and RS, suggesting that the intrinsic biology of the tumor has the greatest prognostic importance.

Patient, treatment and discharge factors associated with hospital readmission within 30 days after surgery for vulvar cancer

OBJECTIVESnThe majority of hospital readmissions are unexpected and considered adverse events. The goal of this study was to examine the factors associated with unplanned readmission after surgery for vulvar cancer.nnnMETHODSnPatient demographic, treatment, and discharge factors were collected on 363 patients with squamous cell carcinoma in situ or invasive cancer who underwent vulvectomy at our institution between January 2001 and June 2014. Clinical variables were correlated using χ2 test and Students t-test as appropriate for univariate analysis. Multivariate analysis was then performed.nnnRESULTSnOf 363 eligible patients, 35.6% had in situ disease and 64.5% had invasive disease. Radical vulvectomy was performed in 39.1% and 23.4% underwent lymph node assessment. Seventeen patients (4.7%) were readmitted within 30days, with length of stay ranging 2 to 37days and 35% of these patients required a re-operation. On univariate analyses comorbidities, radical vulvectomy, nodal assessment, initial length of stay, and discharge to a post acute care facility (PACF) were associated with hospital readmission. On multivariate analysis, only discharge to a PACF was significantly associated with readmission (OR 6.30, CI 1.12-35.53, P=0.04). Of those who were readmitted within 30days, 29.4% had been at a PACF whereas only 6.6% of the no readmission group had been discharged to PACF (P=0.003).nnnCONCLUSIONSnReadmission affected 4.7% of our population, and was associated with lengthy hospitalization and reoperation. After controlling for patient comorbidities and surgical radicality, multivariate analysis suggested that discharge to a PACF was significantly associated with risk of readmission.

A SNaPshot of potentially personalized care: Molecular diagnostics in gynecologic cancer

BACKGROUNDnGenetic abnormalities underlie the development and progression of cancer, and represent potential opportunities for personalized cancer therapy in Gyn malignancies.nnnMETHODSnWe identified Gyn oncology patients at the MGH Cancer Center with tumors genotyped for a panel of mutations by SNaPshot, a CLIA approved assay, validated in lung cancer, that uses SNP genotyping in degraded DNA from FFPE tissue to identify 160 described mutations across 15 cancer genes (AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, IDH1, KIT, KRAS, MAP2KI, NOTCH1, NRAS, PIK3CA, PTEN, TP53).nnnRESULTSnBetween 5/17/10 and 8/8/13, 249 pts consented to SNaPshot analysis. Median age 60 (29-84) yrs. Tumors were ovarian 123 (49%), uterine 74(30%), cervical 14(6%), fallopian 9(4%), primary peritoneal 13(5%), or rare 16(6%) with the incidence of testing high grade serous ovarian cancer (HGSOC) halving over time. SNaPshot was positive in 75 (30%), with 18 of these (24%) having 2 or 3 (n=5) mutations identified. TP53 mutations are most common in high-grade serous cancers yet a low detection rate (17%) was likely related to the assay. However, 4 of the 7 purely endometrioid ovarian tumors (57%) harbored a p53 mutation. Of the 38 endometrioid uterine tumors, 18 mutations (47%) in the PI3Kinase pathway were identified. Only 9 of 122 purely serous (7%) tumors across all tumor types harbored a drugable mutation, compared with 20 of 45 (44%) of endometrioid tumors (p<0.0001). 17 pts subsequently enrolled on a clinical trial; all but 4 of whom had PIK3CA pathway mutations. Eight of 14 (47%) cervical tumors harbored a drugable mutation.nnnCONCLUSIONnAlthough SNaPshot can identify potentially important therapeutic targets, the incidence of drugable targets in ovarian cancer is low. In this cohort, only 7% of subjects eventually were treated on a relevant clinical trial. Geneotyping should be used judiciously and reflect histologic subtype and available platform.

Paradigm shift in the management of high-intermediate risk stage I endometrial cancer.

5103 Background: Recent randomized trials have suggested that high-intermediate risk endometrial cancer patients may safely be treated with adjuvant vaginal brachytherapy (VBT) rather than external beam radiotherapy (EBRT). The purpose of this study was to determine how this paradigm shift might impact clinical outcomes.nnnMETHODSnAll women with stage IA grade 3, stage IA with endocervical gland extension and grade 1-2, or stage IB grade 1-2 endometrioid carcinoma (FIGO 2009 system) treated from 2005 to 2010 at our institution were retrospectively identified. Data was extracted from computerized medical records. Group A consisted of 49 patients in the 1st half of the study and Group B 40 pts in the 2nd half.nnnRESULTSn89 pts underwent abdominal (65%) or minimally invasive (35%) hysterectomy. Group A was more likely to not be surgically staged (28% v 8%; P = 0.02) or have pelvic lymphadenectomy (PLN) only (55% v 33%; P = 0.05). Group B had a much higher rate of both PLN and para-aortic lymphadenectomy (PAALN; 59% v 18%; P < 0.001). Postoperatively, Group A was more likely to receive either EBRT (23% v 0%; P < 0.001) or no radiotherapy (33% v 8%; P = 0.01). Group B more frequently received only VBT (92% v 44%; P < 0.001). 2 of 4 patients with positive/equivocal cytology were the only ones to receive postoperative cytotoxic chemotherapy (6 cycles of paclitaxel and carboplatin). 5 of 89 (6%) patients (3 Group A, 2 Group B) relapsed during the follow-up interval (median 2 years): 2 having positive cytology that did not receive chemotherapy relapsed in the lung and the peritoneum, respectively; 1 staged with PLN only who received postoperative pelvic EBRT relapsed in the para-aortic nodes; 2 relapsed at the vaginal apex, neither of whom had received postoperative radiation.nnnCONCLUSIONSnThe paradigm shift favoring postoperative VBT cancer is effective at preventing local relapse while avoiding long-term toxicity in women with high-intermediate risk stage I endometrial cancer. Comprehensive PLN and PAALN is integral to this approach by excluding nodal disease. Peritoneal washings, although no longer part of the formal staging system, should be collected and may suggest the need for cytotoxic chemotherapy when positive.