Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor. METHODS: ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing. FINDINGS: 256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8-10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0-14·7) in the BRCA mutant subgroup, 5·7 months (5·3-7·6) in the LOH high subgroup, and 5·2 months (3·6-5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16-0·44, p<0·0001) and LOH high (0·62, 0·42-0·90, p=0·011) subgroups compared with the LOH low subgroup. The most common grade 3 or worse treatment-emergent adverse events were anaemia or decreased haemoglobin (45 [22%] patients), and elevations in alanine aminotransferase or aspartate aminotransferase (25 [12%]). Common serious adverse events included small intestinal obstruction (10 [5%] of 204 patients), malignant neoplasm progression (10 [5%]), and anaemia (nine [4%]). Three patients died during the study (two because of disease progression and one because of sepsis and disease progression). No treatment-related deaths occurred. INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. These results extend the potential usefulness of PARP inhibitors in the treatment setting beyond BRCA mutant tumours. FUNDING: Clovis Oncology, US Department of Defense Ovarian Cancer Research Program, Stand Up To Cancer-Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant, and V Foundation Translational Award.

Assessment of the Role of Intraoperative Frozen Section in Guiding Surgical Staging for Endometrial Cancer.

OBJECTIVE: The aim of this study was to assess the role of intraoperative frozen section (FS) in guiding decision making for surgical staging of endometrioid endometrial cancer (EC). METHODS: Medical records were collected retrospectively on 112 patients with endometrioid EC, who underwent total hysterectomy and bilateral salpingo-oophorectomy at the University of Arizona Medical Center from January 1, 2010, to December 31, 2014. Only patients with endometrioid adenocarcinoma, grade 1, less than 50% myometrial invasion, and tumor size less than 2 cm determined by intraoperative FS omitted lymphadenectomy; otherwise, surgical staging was performed with lymph node dissection. The FS results were compared with the permanent paraffin sections (PSs) to assess the diagnostic accuracy. RESULTS: The concordance rate of different variables between FS and PS in EC was 100%, 89.3% (100/112), 97.3% (109/112), and 95.5% (107/112), respectively, with respecting to histological subtype, grade, myometrial invasion, and tumor size. Diagnostic accurate rate of combined risk factors deciding surgical staging at the time of FS was 95.5% (107/112), and the discordance rate of all risk factors considered between FS and PS was 4.5%, resulting 3 cases (2.7%) undertreated and 2 cases (1.8%) overtreated. CONCLUSIONS: Despite nonideal FS evaluation, intraoperative FS diagnosis for EC is highly reliable by providing guidance for the intraoperative decisions of surgical staging at our institution, and such guidelines may be referenced by the institutions with sufficient gynecologic pathology expertise.

Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma.

Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (<2 cm) in extrauterine sites and without finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites including ovary and omentum and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence of serous tubal intraepithelial carcinoma or not are useful clinicopathologic features to determine primary cancer site, which helps in clinical management.

Tubal origin of ovarian endometriosis.

Endometriosis is a puzzling and debilitating disease that affects millions of women around the world. Ovary is the most common organ site involved by endometriosis. Despite various hypotheses about its cell of origin, uncertainty remains. On the basis of our clinicopathologic observations, we hypothesize that fallopian tube may contribute the histogenesis of ovarian endometriosis. To examine if the hypothesis, tubal origin of ovarian endometriosis, has scientific supporting evidence, we identified a set of novel genes, which are either highly expressed in the normal fallopian tube or in the endometrium through a gene differential array study. Among many differentially expressed genes, FMO3 and DMBT1 were selected as the initial biomarkers to test the hypothesis. These biomarkers were then validated in ovarian sections with foci of endometriosis by comparing their expression levels in the fallopian tube and the endometrium within the same patients with real-time PCR, western blot and immunohistochemistry analysis. FMO3 was highly expressed in the tubal epithelia while low in the paired endometrium. In contrast, DMBT1 was high in the endometrium but low in the fallopian tube. In 32 ovarian endometriosis cases analyzed by real-time PCR, 18 (56%) showed a high level of FMO3 and a low level of DMBT1 expression. However, 14 (44%) endometriosis cases showed a reversed expression pattern with these two markers. Results were similarly seen in the methods of western blot and immunohistochemistry. The findings suggest that approximately 60% of the ovarian endometriosis we studied may be derived from the fallopian tube, whereas about 40% of the cases may be of endometrial origin. The fallopian tube epithelia may represent one of the tissue sources contributing to ovarian endometriosis. Such novel findings, which require confirmation, may have a significant clinical impact in searching for alternative ways of prevention and treatment of endometriosis.

Secretory cell expansion with aging: risk for pelvic serous carcinogenesis.

OBJECTIVE: Recent advances suggest that precancerous lesions of pelvic serous carcinoma (PSC) originate from tubal secretory cells. The purpose of our study was to determine if increased number of secretory cells shows difference in age and location and to examine their association with serous neoplasia. MATERIALS AND METHODS: Three groups (benign control, high-risk, and PSC) of patients with matched ages were studied. The age data was stratified into 10-year intervals ranging from age 20 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data was analyzed by standard contingency table and Poisson distribution methods after age justification. RESULTS: We found that the absolute number of tubal secretory cells increased significantly with age within each age group. Age remained a significant risk factor for serous neoplasia after age adjustment. In addition, a dramatic increase of secretory cells was observed in high-risk and PSC patients. Further, secretory cell expansion (SCE) was more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and was significantly associated with serous neoplasia (p<0.001). CONCLUSIONS: These findings suggest that SCE could potentially serve as a sensitive biomarker for early serous carcinogenesis within the fallopian tube. Findings support a relationship between serous neoplasia and increased secretory to ciliated cell ratios. Findings also support a relationship between frequency of SCE and increasing age, presence of high-risk factors and co-existing serous cancers.

Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study.

PURPOSE: This study assessed the efficacy, safety, and pharmacokinetics of adavosertib in combination with four chemotherapy agents commonly used in patients with primary platinum-resistant ovarian cancer. PATIENTS AND METHODS: Women with histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer with measurable disease were enrolled between January 2015 and January 2018 in this open-label, four-arm, multicenter, phase II study. Patients received adavosertib (oral capsules, 2 days on/5 days off or 3 days on/4 days off) in six cohorts from 175 mg once daily to 225 mg twice daily combined with gemcitabine, paclitaxel, carboplatin, or pegylated liposomal doxorubicin. The primary outcome measurement was overall response rate. RESULTS: Three percent of patients (3/94) had confirmed complete response and 29% (27/94) had confirmed partial response. The response rate was highest with carboplatin plus weekly adavosertib, at 66.7%, with 100% disease control rate, and median progression-free survival of 12.0 months. The longest median duration of response was in the paclitaxel cohort (12.0 months). The most common grade ≥3 adverse events across all cohorts were neutropenia [45/94 (47.9%) patients], anemia [31/94 (33.0%)], thrombocytopenia [30/94 (31.9%)], and diarrhea and vomiting [10/94 (10.6%) each]. CONCLUSIONS: Adavosertib showed preliminary efficacy when combined with chemotherapy. The most promising treatment combination was adavosertib 225 mg twice daily on days 1-3, 8-10, and 15-17 plus carboplatin every 21 days. However, hematologic toxicity was more frequent than would be expected for carboplatin monotherapy, and the combination requires further study to optimize the dose, schedule, and supportive medications.

Incidence of Hypersensitivity Reactions to Carboplatin or Paclitaxel in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer With or Without BRCA1 or BRCA2 Mutations.

The association of BRCA mutation status with hypersensitivity reactions (HSRs) to carboplatin has gained interest in recent years, particularly in patients with ovarian, fallopian tube, and primary peritoneal cancer. The primary objective of this study is to determine whether the presence of BRCA mutations increased the likelihood of HSRs to carboplatin. The incidence of HSRs to paclitaxel and symptom grade based on the Common Terminology Criteria for Adverse Events, version 4.0, were explored as secondary endpoints. A retrospective chart review of patients with ovarian, fallopian tube, or primary peritoneal cancer at the University of Arizona Cancer Center who underwent treatment with carboplatin-containing regimens and received genetic testing was performed. Institutional review board approval was obtained for this study. Fisher's exact test was used to analyze the primary outcome. Out of 167 initial patients, 62 with germline test results constituted the evaluable sample. 15 of 62 (24.2%) BRCA-tested patients were treated with carboplatin monotherapy, while 44 of 62 (71.0%) patients were treated with paclitaxel-containing regimens. Hypersensitivity reactions occurred in 4 of 13 (30.8%) BRCA-mutated patients and 22 of 49 (44.9%) BRCA wild-type patients (p = .5291). Hypersensitivity reactions to paclitaxel occurred in 1 of 13 (7.7%) BRCA-mutated patients and 26 of 49 (53.1%) BRCA wild-type patients (p = .0039). Overall, there were 11 grade 1 reactions, 14 grade 2 reactions, and 16 grade 3 reactions to carboplatin. All reactions to carboplatin in BRCA-mutated patients were grade 1. All paclitaxel reactions manifested as grade 2. The sample size was the main study limitation. The presence of BRCA mutations was not statistically significantly associated with a higher incidence of HSRs to carboplatin, but was statistically significant with regards to paclitaxel.

Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer.

PURPOSE: Selective lymphadenectomy is widely accepted in the management of endometrial cancer. Purported benefits are individualization of adjuvant therapy based on extent of disease and resection of occult metastases. Our goal was to assess effects of the extent of selective lymphadenectomy on outcomes in women with apparent stage I endometrial cancer at laparotomy. PATIENTS AND METHODS: Patients with endometrial cancer who received primary surgical treatment between 1973 and 2002 were identified through an institutional tumor registry. Inclusion criteria were clinical stage I/IIA disease and procedure including hysterectomy and selective lymphadenectomy (pelvic or pelvic + aortic). Exclusion criteria included presurgical radiation, grossly positive lymph nodes, or extrauterine metastases at laparotomy. Recurrence and survival were analyzed using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: Among 509 patients, the median number of lymph nodes removed was 15 (median pelvic, 11; median aortic, three). Pelvic and aortic node metastases were found in 24 (5%) of 509 patients and 11 (3%) of 373 patients, respectively. Patients with poorly differentiated cancers having more than 11 pelvic nodes removed had improved overall survival (hazard ratio [HR], 0.25; P < .0001) and progression-free survival (HR, 0.26; P < .0001) compared with patients having poorly differentiated cancers with 11 or fewer nodes removed. Number of nodes removed was not predictive of survival among patients with cancers of grade 1 to 2. Performance of aortic selective lymphadenectomy was not associated with survival. Three (27%) of 11 patients with microscopic aortic nodal metastasis are alive without recurrence. CONCLUSION: These data add to the literature documenting the possible therapeutic benefit of selective lymphadenectomy in management of patients with apparent early-stage endometrial cancer.

MRI of ovarian torsion: Correlation of imaging features with the presence of perifollicular hemorrhage and ovarian viability.

PURPOSE: The purpose of our study is to test for: (a) correlation between the presence of a perifollicular T2-hypointense rim on MRI with the presence of perifollicular hemorrhage on histology; and (b) correlation between this finding and diminished ovarian viability after intra-operative detorsion. METHODS AND MATERIALS: Our IRB-approved, retrospective study evaluated 780 patients between August 2012 and February 2016 with ovarian torsion as a diagnostic consideration on the emergency department note. Patients were included if they had preoperative MRI and intraoperatively confirmed case of ovarian torsion. MRIs were retrospectively reviewed for presence of perifollicular T2 hypointense rim in the torsed ovary. Two arms of analysis were performed: (a) assessment of perifollicular hemorrhage on histological exam; and (b) assessment of ovarian viability after intra-operative detorsion. Sensitivity, specificity, positive predictive value, and negative predictive value of MRI for predicting ovarian viability in the setting of torsion was performed. κ test assessed level of agreement between readers. RESULTS: 24 patients included in one of the two arms; 20 in viability analysis and 12 in perifollicular hemorrhage analysis (8 in both). The presence of T2-hypointense rim on MRI demonstrated 88.9% sensitivity and 66.7% specificity for the diagnosis of perifollicular hemorrhage on histology, and 91.7% sensitivity and 100% specificity for predicting intraoperative viability. CONCLUSION: The presence of a perifollicular T2 hypointense rim on MRI in the setting of ovarian torsion correlates with perifollicular hemorrhage on histopathologic exam, and may also be a useful predictor of ovarian viability in patients presenting with ovarian torsion.

Struma ovarii simulating ovarian sertoli cell tumor: a case report with literature review.

Struma ovarii, as a monodermal variant of ovarian teratoma, constitutes about less than 3% of ovarian teratomas. It is difficult to be macroscopically recognized. Multiple appearances under microscope serve as another reason to mislead the accurate pathologic evaluation. Here, we report an unusual case of struma ovarii occurred in a 77 years old woman, which is currently known as the oldest age for this disease. The frozen section morphologically showed sex cord like elements and was suspicious for a sex-cord stromal tumor, probably a Sertoli cell tumor. Final pathological diagnosis was confirmed as struma ovarii based on the typical morphologic thyroid follicles and immunohistochemical staining results.

PAX8: a sensitive and specific marker to identify cancer cells of ovarian origin for patients prior to neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy followed by cytoreduction surgery has been used where an accurate cytologic or pathologic diagnosis is usually required before the initiation of neoadjuvant chemotherapy. However, it is difficult to make definitive diagnosis of presence of cancer cells, particularly gynecologic versus non-gynecologic origin, from those ascites specimens due to the absence of specific biomarkers of gynecologic cancers. In the present study, we evaluated if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant chemotherapy. METHODS: Two hundred and two cytology specimens including 120 pretreatment ovarian cancer samples, 60 benign controls, and 22 malignant non-gynecologic cases were studied. All cytology slides were morphologically reviewed in a blinded fashion without knowing corresponding pathology diagnosis, if present. A total of 168 cytology specimens with a cell block were stained with PAX8 and Calretinin. These included patients with potential for ovarian cancer neoadjuvant chemotherapy (n=96), metastatic cancers (n=22), and benign controls (n=50). RESULTS: Among the 96 ascitic samples prior to neoadjuvant chemotherapy, 76 (79%) showing morphologic features consistent with cancers of ovarian primary were all PAX+/Calretinin-. The remaining 20 (21%) cases were positive for adenocarcinoma, but morphologically unable to be further classified. Among the 22 metastatic cancers into the pelvis, one case with PAX8+/Calretinin- represented a renal cell carcinoma and the remaining 21 PAX8-/Calretinin- metastatic cancers were either breast metastasis (n=4) and the metastasis from gastrointestinal tract (n=17). Among the 50 benign control pelvic washing cases, 5 PAX8+/Calretinin-cases represented endosalpingiosis (n=4) and endometriosis (n=1), 25 PAX8-/Calretinin+cases showed reactive mesothelial cells, and the remaining 20 specimens with PAX8-/Calretinin- phenotype typically contained inflammatory or blood cells without noticeable diagnostic epithelia. CONCLUSIONS: PAX8 identifies all Müllerian derived benign or malignant epithelia. When combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas of ovarian origin, which will be ideal to be used for those patients with a possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy.

Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

PURPOSE: This phase I trial evaluated intraperitoneal (i.p.) pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer. EXPERIMENTAL DESIGN: Dose escalation of day 1 i.p. pemetrexed accrued three patients to each of five dose levels (60-1,000 mg/m(2)), along with day 2 i.p. cisplatin (75 mg/m(2)) and day 8 i.p. paclitaxel (60 mg/m(2)). The goals were to determine maximum tolerated dose (MTD), 18-month progression-free survival (PFS), and pharmacokinetics of i.p. pemetrexed. RESULTS: Cycles, given every 21 days, had an 80% 6-cycle completion rate. There was minimal grade III toxicity in the first 4 dose levels and remarkably an almost complete absence of peripheral neuropathy and alopecia. At the highest dose level, two of three patients experienced ≥ grade III and dose-limiting toxicity (DLT; hematologic, infection, gastrointestinal). There was a pharmacokinetic advantage for i.p. pemetrexed with an intraperitoneal:plasma area under the concentration-time curve ratio of 13-fold. Neither analysis of pharmacokinetic nor homocysteine levels explains the unexpected severity of toxicity in those two patients. On the basis of plasma C(24h) levels, the 42 cycles at ≥ 500 mg/m(2) i.p. pemetrexed without DLT, the MTD appears to be 500 mg/m(2). Median PFS is 30.1 months; 18-month PFS is 78.6% (median follow-up 22.4 months). CONCLUSIONS: This i.p.-only regimen in front-line ovarian cancer is feasible with PFS in line with recent literature. We suggest phase II trials of this regimen in this population with i.p. pemetrexed at 500 mg/m(2). The favorable toxicity profile at doses <1,000 mg/m(2), which needs to be confirmed, appears to compare well with standard combination i.v./i.p. platinum/taxane chemotherapy in this disease.

Ovarian cancer metastatic to the breast presenting as inflammatory breast cancer: a case report and literature review.

Background. Primary ovarian carcinoma with metastasis to the breast is rare, with only 39 cases reported in the current literature. Ovarian metastasis to the breast presenting as inflammatory breast carcinoma is even more infrequent, with only 6 cases reported.Case. We present a patient who developed metastatic inflammatory cancer of the breast from a stage IIIC papillary serous ovarian adenocarcinoma approximately 1 year after the original diagnosis. Pathologic analysis confirmed the origin of the tumor: a high-grade adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. In addition, the tumor was strongly positive on immunohistochemistry for CA-125, identical to the ovarian primary. The patient died of diffuse metastasis 5 months after the breast tumor was noted.Conclusion. Although ovarian metastasis to the breast presenting as inflammatory breast cancer is rare, it should be included in the differential diagnosis for any patient with a personal history of ovarian cancer. Accurate differentiation is necessary because treatment differs significantly for patients with ovarian metastasis to the breast, as compared with patients with primary inflammatory breast cancer. Ovarian metastasis to the breast confers a poor prognosis: patient survival ranged from 3 to 18 months, with a median survival of 6 months after the diagnosis of the breast metastasis.

The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer.

OBJECTIVE: The clinical significance and optimal management of patients with stage IIIA endometrial cancer are controversial. We sought to determine whether recurrence and survival of patients with stage IIIA endometrial cancer differ with surgical pathologic findings (positive peritoneal cytology versus positive adnexae or serosa) and adjuvant treatment. METHODS: Retrospective single institution analysis of patients surgically staged for IIIA endometrial cancer at Duke University Medical Center from 1973 to 2002. Stage IIIA patients were stratified into positive cytology alone (group IIIA1, n=37) and positive adnexae or uterine serosa (group IIIA2, n=20). Comparison was made with previously reported group of 467 patients with surgical stage I/II disease. Recurrence and survival were analyzed using Kaplan-Meier estimations and Cox proportional hazards model. RESULTS: Mean age of 57 patients with stage IIIA endometrial cancer was 63. Adjuvant therapies were administered to 89% patients (74% radiotherapy, 4% chemotherapy, 19% progestins). Five-year overall (OS) and recurrence-free disease-specific survival (RFDSS) were 64% and 76%, respectively. Survival was similar comparing IIIA1 (62%) and IIIA2 (68%, p=0.999). RFDSS by adjuvant therapy was: external beam radiotherapy 89% (n=10), intraperitoneal P32 84% (n=21), progestins 78% (n=9), none 75% (n=6). 61% recurrences included extrapelvic component. In multivariable analysis of stage I-IIIA patients (n=517), positive cytology but not adnexal/serosal metastasis was predictive of death (HR 1.70, 95% CI 1.06-2.73) and disease recurrence (HR 1.70, 95% CI 1.07-2.71). CONCLUSION: Among patients with stage IIIA endometrial cancer, metastasis to adnexae or serosa does not appear to confer worse prognosis than positive cytology alone. Positive cytology is an independent predictor of prognosis among patients with stage I-IIIA endometrial cancer. While optimal adjuvant therapy for these groups remains unclear, recurrence patterns suggest that systemic therapies are appropriate.

Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology.

OBJECTIVE: To determine whether pelvic lymph node count is associated with patterns of recurrence or survival in patients with FIGO stage I and II endometrial cancer. METHODS: Single institution retrospective study of 467 patients with FIGO stage I and II endometrial cancer treated with primary surgery including lymph node dissection. Analysis included pelvic lymph node count, histology, stage, age, race, BMI, year of surgery, depth of myometrial invasion, and adjuvant radiation. Kaplan-Meier life-tables were used to calculate survival; the Cox proportional hazards model was used to identify prognostic factors independently associated with survival. RESULTS: Mean pelvic lymph node count was 12.6 (SD +/- 8). Distant recurrence was associated with decreased pelvic lymph node count, high-risk histology, and postoperative pelvic radiation. Pelvic lymph node count was not associated with survival by univariate analysis, however, overall (OS) and progression-free (PFS) survival were significantly better with pelvic lymph node counts >or=12 among women with high-risk histology (P < 0.001), but not among women with low-risk histology. Multivariable Cox proportional hazards regression identified increasing age, non-Caucasian race, and high-risk histology as independent negative prognostic factors for both OS and PFI. Among patients with high-risk histology, pelvic lymph node count remained an independent prognostic factor for both overall (OS) and progression-free survival (PFS) in the model, with hazard ratios of 0.28 and 0.29, respectively, when >or=12 pelvic lymph nodes were identified. Pelvic lymph node count had no association with OS or PFS in women with low-risk histology. CONCLUSION: Pelvic lymph node count >or=12 is an important prognostic variable in patients with FIGO stage I and II endometrial cancer who have high-risk histology. Most likely, the association of survival and lymph node count in this group is the result of improved staging among patients with higher pelvic lymph node counts.

Delay in treatment of invasive cervical cancer due to intimate partner violence.

BACKGROUND: Intimate partner violence (IPV) is underreported and creates a complex psychosocial medium that adversely affects the health of its victims. We present the first case report in the literature, though likely not the first time, in which a patient delayed her cancer treatment due to domestic abuse and her disease progressed. CASE: A 41-year-old female with vaginal bleeding was diagnosed with cervical cancer. After several years of declining recommendations for treatment, she was questioned separate from her partner and she revealed a long-standing history of abuse. CONCLUSIONS: Physicians must be aware of the signs of spousal abuse to lessen negative impact on the treatment of their patients. Once domestic violence is discovered, there are many resources available to help patients with their needs.

Resection of lymph node metastases influences survival in stage IIIC endometrial cancer.

OBJECTIVE: Surgical staging of endometrial cancer identifies those patients with microscopic metastatic disease most likely to benefit from adjuvant therapy and may also confer therapeutic benefit. Our objective was to compare survival of patients who underwent resection of grossly positive lymph nodes (LN) to those with microscopically positive LN. METHODS: Patients had stage IIIC endometrial cancer with pelvic and/or aortic LN metastases and underwent surgery between 1973 and 2002. Exclusion criteria included pre-surgical radiation and second primary cancer. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Mean age of 96 patients with stage IIIC endometrial cancer was 64. There were 45 cases with microscopic LN involvement and 51 with grossly enlarged LN. Overall, 41% had disease in aortic LN, which in 18% represented isolated aortic LN metastasis. Adjuvant therapies were given to 92% of patients (85% radiotherapy, 10% chemotherapy, 10% progestins). Among those with grossly involved LN, 86% were completely resected. Five-year disease-specific survival (DSS) was 63% in 45 patients with microscopic metastatic disease compared to 50% in 44 patients with grossly positive LN completely resected and 43% in 7 with residual macroscopic disease. In multivariable analyses, gross nodal disease not debulked (HR=6.85, P=0.009), serosal/adnexal involvement (HR=2.24, P=0.036), diagnosis prior to 1989 (HR=4.33, P<0.001), older age (HR=1.09, P<0.001), and >2 positive lymph nodes (HR=3.12, P=0.007) were associated with lower DSS. CONCLUSION: Grossly involved LN can often be completely resected in patients with stage IIIC endometrial cancer. These retrospective data provide evidence suggestive of a therapeutic benefit for lymphadenectomy in endometrial cancer.