OBJECTIVE:

Serous borderline tumor (SBT) is a unique histopathologic entity of the ovary, believed to be intermediate between benign cystadenoma and invasive low-grade serous carcinoma. While somatic mutations in the KRAS or BRAF, and rarely ERBB2, genes have been well characterized in SBTs, other genetic alterations have not been described. Toward a more comprehensive understanding of the molecular genetic architecture of SBTs, we undertook whole exome sequencing of this tumor type.

METHODS:

Following pathologic review and laser capture microdissection to enrich for tumor cells, whole exomes were prepared from DNA of two independent SBTs and subjected to massively parallel DNA sequencing.

RESULTS:

Both tumors contained an activating mutation of the BRAF gene. A total of 15 additional somatic mutations were identified, nine in one tumor and six in the other. Eleven were missense mutations and four were nonsense or deletion mutations. Fourteen of the 16 genes found to be mutated in this study have been reported to be mutated in other cancers. Furthermore, 12 of these genes are mutated in ovarian cancers. The FBXW7 and KIAA1462 genes are noteworthy candidates for a pathogenic role in serous borderline tumorigenesis.

CONCLUSIONS:

These findings suggest that a very small number of somatic genetic mutations are characteristic of SBTs of the ovary, thus supporting their classification as a relatively genetically stable tumor type. The mutant genes described herein represent novel candidates for the pathogenesis of ovarian SBT.

Despite the increasing availability of palliative care, oncology providers often misunderstand and underutilize these resources. The goals of palliative care are relief of suffering and provision of the best possible quality of life for both the patient and her family, regardless of where she is in the natural history of her disease. Lack of understanding and awareness of the services provided by palliative care physicians underlie barriers to referral. Oncologic providers spend a significant amount of time palliating the symptoms of cancer and its treatment; involvement of specialty palliative care providers can assist in managing the complex patient. Patients with gynecologic malignancies remain an ideal population for palliative care intervention. This review of the literature explores the current state of palliative care in the treatment of gynecologic cancers and its implications for the quality and cost of this treatment.

OBJECTIVE:

The aim of this multicenter, retrospective study was to evaluate the efficacy and the safety of single agent Trabectedin (ET-743, Yondelis®) in very heavily treated, relapsed ovarian cancer (ROC) patients.

PATIENTS AND METHODS:

Response to treatment was classified according to RECIST criteria. Progression-free (PFS), and overall survival (OS) were also assessed.

RESULTS:

98 patients were analyzed (originally 67 platinum sensitive, and 31 platinum refractory/resistant). Median number of previous regimens was 4 (range:1-6). In the whole population, overall response rate (ORR) was 27.5%; stable disease (SD) was observed in 33 patients (33.6%), and clinical benefit was achieved in 60 cases (61.2%). ORR was 38.6% in fully platinum sensitive population, and 26.1% in partially platinum sensitive patients. In platinum refractory/resistant disease, ORR was 12.9%. Overall, median PFS and OS were 5, and 13 months, respectively. Patients responding to Trabectedin showed a more favorable PFS (median= 9 months) than patients with SD (median=6 months), or progression (median=2 months). Median OS of responding patients was 18 months compared to 14 months in SD patients, and 9 months in progressing patients. Grade 3-4 neutropenia was observed in 17 (17.3%) patients. Transient and non-cumulative Grade 3-4 AST and ALT level elevation was found in 7 (7.1%), and 13 (13.3%) cases, respectively. There was 1 case of Grade 3, and 1 case of Grade 4 cardiac toxicity.

CONCLUSIONS:

Trabectedin, as single agent, retains its efficacy in terms of rate of ORR and clinical benefit in heavily treated ROC patients, especially in the group of platinum sensitive disease.

OBJECTIVE:

To evaluate which clinicopathologic factors influenced overall survival (OS) in endometrial carcinoma and to determine if the surgical effort to assess para-aortic (PA) lymph nodes (LNs) at initial staging surgery impacts OS.

METHODS:

All patients diagnosed with endometrial cancer from 1/1993-12/2011 who had LNs excised were included. PALN assessment was defined by the identification of one or more PALNs on final pathology. A multivariate analysis was performed to assess the effect of PALNs on OS. A form of recursive partitioning called classification and regression tree (CART) analysis was implemented. Variables included: age, stage, tumor subtype, grade, myometrial invasion, total LNs removed, evaluation of PALNs, and adjuvant chemotherapy.

RESULTS:

The cohort included 1920 patients, with a median age of 62 years. The median number of LNs removed was 16 (range, 1-99). The removal of PALNs was not associated with OS (P=0.450). Using the CART hierarchically, stage I vs. stages II-IV and grade 1-2 vs. grade 3 emerged as predictors of OS. If the tree was allowed to grow, further branching was based on age and myometrial invasion. Total number of LNs removed and assessment of PALNs as defined in this study were not predictive of OS.

CONCLUSION:

This innovative CART analysis emphasized the importance of proper stage assignment and a binary grading system in impacting OS. Notably, the total number of LNs removed and specific evaluation of PALNs as defined in this study were not important predictors of OS.

OBJECTIVE:

The aim of this study was to build a model to predict the risk of lymph node metastases (LNM) in women with low- or intermediate-risk endometrial cancer (EC) using histological and immunohistochemical markers.

METHODS:

Samples were collected from 68 women with low- or intermediate-risk EC. European Society of Medical Oncology (ESMO) risk group, lymphovascular space involvement (LVSI), immunostaining expressions of Estrogen receptor (ER) and Progesteron receptor (PR) were used to build a recursive partitioning model to predict final lymph node status.

RESULTS:

The number of women with final low- and intermediate risk EC was 34 (50%) each. LVSI was present in 7 women with low-risk (20%) and 28 (80%) with intermediate-risk EC. Nineteen women (28%) had LNM at final histology. A lower immunostaining of ER (p=0.02) and PR (p=0.03) was found in women with LNM compared with those without. Women were correctly classified by the model in 87% of cases; among the 56 women without LNM that were predicted, 48 (86%) had no LNM at final histology. Among the 12 women with LNM predicted, 11 (92%) had LNM at final histology.

CONCLUSIONS:

Our results show that lymph node status can be predicted with a relatively high accuracy in women with low- or intermediate-risk EC. This can help physicians to better adapt surgical staging and adjuvant therapies.

OBJECTIVE:

Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer.

METHODS:

Chromosomal copy numbers at 3q26 (3q), 5p15 (5p), 20q13 (20q) and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ≥3 or ≥4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2+ and/or HSIL.

RESULTS:

The median number of cells with ≥3 signals increased with the severity of cervical lesion for each genomic locus (p-trend<0.02 for each locus). ROC analysis for the number of cells with ≥3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q, 5p, 20q and cen7, respectively, for the detection of CIN2+ and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes.

CONCLUSIONS:

Chromosomal gains at 3q, 5p, 20q and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.

OBJECTIVE:

Based on previous studies, standard gynecological screening consisting of annual transvaginal ultrasonography (TVU) was added with endometrial sampling in women with Lynch Syndrome (LS). The aim of this study was to evaluate the additional value of endometrial sampling in detecting (pre)malignancies of the endometrial tissue in women with LS or first-degree relatives.

METHODS:

All women above 30years of age with LS or first-degree relatives at 50% risk of LS are offered annual gynecological screening in our family cancer clinic. Endometrial screening results from January 2003-December 2007 (period I: standard screening by transvaginal sonography and serum CA125) were compared with screening results from January 2008-June 2012 (period II: standard screening added with endometrial sampling).

RESULTS:

Seventy five women (300 patient years) were screened annually. There were 266 screening visits, 117 in period I and 149 in period II. In period I, four premalignant endometrial lesions were detected and one endometrial carcinoma (FIGO stage IB). In period II, two premalignancies were found. None of the lesions would have been missed without standard endometrial sampling. No interval endometrial cancers were detected in this study.

CONCLUSION:

In this study, annual endometrial screening seems an effective screening tool in the detection of premalignancies and early endometrial cancer in women with LS. Adding standard endometrial sampling to annual TVU has no additional value in the early detection of (pre)malignant endometrial lesions in women with LS in this study.

OBJECTIVE:

To determine if early palliative care intervention in patients with recurrent, platinum-resistant ovarian cancer is potentially cost saving or cost-effective.

METHODS:

A decision model with 6 month time horizon evaluated routine care versus routine care plus early referral to a palliative medicine specialist (EPC) for recurrent platinum-resistant ovarian cancer. Model parameters included rates of inpatient admissions, emergency department (ED) visits, chemotherapy administration, and quality of life (QOL). From published ovarian cancer data, we assumed baseline rates over the final 6 months: hospitalization 70%, chemotherapy 60%, ED visit 30%. Published data from a randomized trial evaluating EPC in metastatic lung cancer were used to model odds ratios (OR) for potential reductions in hospitalization (OR 0.69), chemotherapy (0.77), and emergency department care (OR 0.74) and improvement in QOL (OR 1.07). The costs of hospitalization, ED visit, chemotherapy, and EPC were based on published data. Ranges were used for sensitivity analysis. Effectiveness was quantified in quality adjusted life years (QALYs); survival was assumed equivalent between strategies.

RESULTS:

EPC was associated with a cost savings of $1,285 per patient over routine care. In sensitivity analysis incorporating QOL, EPC was either dominant or cost-effective, with an incremental cost-effectiveness ratio (ICER) < $50,000/QALY, unless the cost of outpatient EPC exceeded $2,400. Assuming no clinical benefit other than QOL (no change in chemotherapy administration, hospitalizations or ED visits), EPC remained highly cost-effective with ICER $37,440/QALY.

CONCLUSION:

Early palliative care intervention has the potential to reduce costs associated with end of life care in patients with ovarian cancer.

OBJECTIVE:

Radical trachelectomy is a standard treatment for selected patients with early-stage cervical cancer. Outcomes are well established for vaginal radical trachelectomy (VRT), but not for abdominal radical trachelectomy (ART).

METHODS:

We searched MEDLINE, EMBASE, and CINAHL (October 1997 through October 2012) using the terms: uterine cervix neoplasms, cervical cancer, abdominal radical trachelectomy, vaginal radical trachelectomy, fertility sparing, and fertility preservation. We included original articles, case series, and case reports. Excluded were review articles, articles with duplicate patient information, and articles not in English.

RESULTS:

We identified 485 patients. Ages ranged from 6 to 44 years. The most common stage was IB1 (331/464; 71%), and the most common histologic subtype was squamous cell carcinoma (330/470; 70%). Operative times ranged from 110 to 586 minutes. Blood loss ranged from 50 to 5,568 mL. Three intraoperative complications were reported. Forty-seven patients (10%) had conversion to radical hysterectomy. One hundred fifty-five patients (35%) had a postoperative complication. The most frequent postoperative complication was cervical stenosis (n=42; 9.5%). The median follow-up time was 31.6 months (range, 1-124). Sixteen patients (3.8%) had disease recurrence. Two patients (0.4%) died of disease. A total of 413 patients (85%) were able to maintain their fertility. A total of 113 patients (38%) attempted to get pregnant, and 67 of them (59.3%) were able to conceive.

CONCLUSION:

ART is a safe treatment option in patients with early-stage cervical cancer interested in preserving fertility.