Faculty Bibliography

OBJECTIVE:To evaluate clinical outcomes of patients with BRCA-associated ovarian cancer who developed brain metastases (BM). METHODS:Patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) and BM, treated at a single institution from 1/1/2008-7/1/2018, were identified from two institutional databases. Charts and medical records were retrospectively reviewed for clinical characteristics and germline BRCA mutation status. Appropriate statistics were used. RESULTS:Of 3649 patients with EOC, 91 had BM (2.5%). Germline mutation status was available for 63 (69%) cases; 21 (35%) of these harbored a BRCA1/2 mutation (15 BRCA1, 6 BRCA2). Clinical characteristics were similar between groups. BM were diagnosed at a median of 31 months (95% CI, 22.6-39.4) in BRCA-mutated (mBRCA) and 32 months (95% CI, 23.7-40.3) in wild-type BRCA (wtBRCA) (p = 0.78) patients. Brain metastases were the only evidence of disease at time of BM diagnoses in 48% (n = 10) mBRCA and 19% (n = 8) wtBRCA (p = 0.02) patients. There was no difference in treatment of BM by mutation status (p = 0.84). Survival from time of BM diagnosis was 29 months (95%CI, 15.5-42.5) in mBRCA and 9 months (95% CI, 5.5-12.5) in wtBRCA patients, with an adjusted hazard ratio (HR) of 0.53, p = 0.09; 95% CI, 0.25-1.11. HR was adjusted for presence of systemic disease at time of BM diagnosis. CONCLUSION/CONCLUSIONS:This is the largest study to date comparing outcomes in patients with EOC and BM by mutation status. mBRCA patients were more likely to have isolated BM, which may be a factor in their long survival. This supports the pursuit of aggressive treatment for mBRCA EOC patients with BM. Additional studies examining the correlation of BRCA mutational status with BM are warranted.

Primary fallopian tube carcinoma is a rare and difficult to cure disease. It is often grouped under the epithelial ovarian cancer umbrella, together with primary ovarian and peritoneal carcinomas. More recent evidence has suggested that epithelial ovarian cancers originate from a fallopian tube precursor. The mainstay of treatment is surgical cytoreduction and platinum-based chemotherapy. There is much debate over the best timing for surgery and the best approach to delivering the chemotherapy: traditional intravenous once every 3 weeks regimen, versus intraperitoneal, versus dose-dense intravenous regimens. Although these debates continue, novel targeted therapies, including bevacizumab and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors, have emerged. PARP inhibitors are particularly efficacious in patients with BRCA1/2 gene mutations, and their use has been shown to prolong patient survival. This article reviews the pathologic etiology; describes the heredity, treatment challenges, and controversies; and summarizes novel therapies in primary fallopian tube carcinoma.

Objective/UNASSIGNED:To report characteristics of patients with low-grade endometrioid endometrial carcinoma (EC) who develop brain metastases. Methods/UNASSIGNED:We retrospectively identified all patients treated at our institution for FIGO grades 1/2 EC from 1/2000-12/2016, who developed brain metastases. Electronic medical records were reviewed, data abstracted. Overall survival (OS) was determined from time of brain metastases to death or last follow-up. Appropriate statistical tests were used. Results/UNASSIGNED: = .04) for best supportive care. Conclusion/UNASSIGNED:Brain metastases in low-grade EC is rare, prognosis generally poor. Compared to supportive care only, any treatment results in more favorable outcomes.

BACKGROUND:The optimal first-line chemotherapy for ovarian carcinosarcoma has not yet been determined. We therefore sought to determine the progression-free survival (PFS) and overall survival (OS) for patients with ovarian carcinosarcoma treated at our institution with different first-line chemotherapy regimens. METHODS:This single-institution, retrospective analysis included all patients with ovarian or primary peritoneal carcinosarcoma diagnosed from September 1996 to July 2017. Kaplan Meier analysis with a log-rank Mantel-Cox test was used to compare PFS and OS between treatment groups, and a p-value of < 0.05 was considered statistically significant. RESULTS:Thirty-one patients met inclusion criteria: two patients were stage IC, 5 were stage II, 21 were stage III, and 3 were stage IV. The median PFS and OS for all stages was 9.3 and 19.7 months respectively. Fifteen patients (48%) received carboplatin/paclitaxel as first therapy, 7 (23%) received ifosfamide/paclitaxel, 6 (19%) received a different regimen, and 3 (10%) did not receive chemotherapy. Patients treated with carboplatin/paclitaxel had a statistically significant longer PFS when compared to those receiving ifosfamide/paclitaxel (17.8 vs. 8.0 months, p = 0.025). OS was similar between all comparisons. CONCLUSIONS:In summary, in our cohort of ovarian carcinosarcoma patients, median PFS is longer in patients treated with carboplatin/paclitaxel compared to ifosfamide/paclitaxel. Overall survival was similar for all treatment groups, potentially due to subsequent treatment crossover. Given the rarity and aggressive nature of this tumor, further study into optimal first-line chemotherapy is warranted.

OBJECTIVE:Melanoma originating from gynecologic sites (MOGS), including the vulva, vagina, and cervix, is a rare and aggressive form of melanoma with poor long-term clinical outcome. The clinicopathologic features of vulvar and non-vulvar tumors remain relatively understudied, and in contrast to cutaneous melanomas at non-sun-exposed sites, MOGS typically do not harbor BRAF mutations. Thus, we sought to analyze the clinicopathologic and molecular features of MOGS. METHODS:A large retrospective cohort of patients with MOGS (n=59) at a single large academic institution over a 28-year period was identified. Associations among clinicopathologic characteristics were assessed via standard statistical approaches, and clinical outcome was examined using Cox regression analysis. Sanger sequencing was utilized to identify mutations in hotspot regions of BRAF, KIT, NRAS, and CTNNB1. RESULTS:Tumors involving the vagina and/or cervix (non-vulvar) are significantly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive resection margins, lymph node metastasis, and poor long-term clinical outcome (with increased risk of death due to disease). The aggressive clinical behavior of non-vulvar tumors is independent of advanced clinical stage and lymph node metastasis in multivariate analysis. Targeted molecular analysis confirms an overall low rate of oncogenic mutations in our MOGS cohort, although KIT mutations (particularly in exon 11) are relatively enriched. CONCLUSIONS:Overall, our results show that non-vulvar MOGS are aggressive tumors with poor long-term clinical outcome and indicate that few targeted therapeutic options are currently available to patients with MOGS.

OBJECTIVE:To determine the adherence to hematologic chemotherapy hold parameters for the carboplatin and dose-dense paclitaxel chemotherapy regimen in patients with ovarian, fallopian tube, or primary peritoneal cancers. METHODS:This is a quality assessment survey study. All 26 NCCN Member Institutions were contacted electronically. Hematologic chemotherapy hold parameter values (absolute neutrophil count [ANC] and platelet count) on days 1, 8, and 15 of each cycle were queried. These hold parameters were compared with published data supporting the use of dose-dense chemotherapy regimens in ovarian cancer. RESULTS:The overall survey response rate was 85% (22/26 sites). Of responders, 27% (6 sites) were fully adherent with all hematologic hold parameters and 64% (14 sites) used hold parameters that differed from the published protocol. Specifically, all of these sites use hold parameters higher than those recommended in the literature. Two centers did not have center-specific hold parameters. CONCLUSIONS:Carboplatin and dose-dense paclitaxel chemotherapy has been shown to increase progression-free survival and overall survival in patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancers. However, our study found that two-thirds of queried sites had hold parameters higher than those in the published protocol. Using more stringent hold parameters may lead to compromised clinical outcomes. Further research is necessary to determine the optimal strategy to increase individual site adherence to chemotherapy hematologic hold parameters as specified in published trials.

OBJECTIVE:To examine the association between race/ethnicity, perineal length and the risk of perineal laceration. METHODS:This is a prospective cohort study of a diverse group of women with singleton gestations in the third trimester of pregnancy. Perineal length was measured and mean values calculated for several racial/ethnic groups. Chi-squared analyses were used to examine rates of severe perineal laceration (third or fourth degree laceration) by race/ethnicity among women considered to have a short perineal length. Further, subgroup analyses were performed comparing nulliparas to multiparas. RESULTS:Among 344 study participants, there was no statistically significant difference in mean perineal length by race/ethnicity (White 4.0 ± 1.1 cm, African-American 3.7 ± 1.0 cm, Latina 4.1 ± 1.1 cm, Asian 3.8 ± 1.0 cm, and other/unknown 4.0 ± 0.9 cm). Considering parity, more multiparous Asian and African-American women had a short perineal length (20.7 and 23.5%, respectively, p = 0.05). Finally, the rate of severe perineal lacerations in our cohort was 2.6% overall, but was 8.2% among Asian women (p = 0.04). CONCLUSIONS:We did not find a relationship between short perineal length and risk of severe perineal laceration with vaginal delivery, or a difference in mean perineal length by maternal race/ethnicity. However, we did find that women of different racial/ethnic groups have varying rates of severe perineal laceration, with Asian women comprising the highest proportion.