Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women.

PURPOSE: BRCA gene mutations (BRCAm) have an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. METHODS: This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). RESULT: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. CONCLUSION: The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. TRIAL REGISTRATION: Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Germline mutations in Black patients with ovarian, fallopian tube and primary peritoneal carcinomas.

OBJECTIVE: Routine genetic testing for ovarian cancer and identification of germline mutations can help improve early detection of cancer as well as guide treatment. Knowledge of genetic counseling and referral rates for genetic testing has been lower for Black patients, compared to White patients. We aimed to describe the demographics and presence of germline mutations in Black individuals with ovarian, fallopian tube or peritoneal carcinoma at two large academic institutions. METHODS: Fifty-one Black patients with invasive epithelial ovarian, fallopian tube, or primary peritoneal carcinoma were identified via institutional tissue banks over a 20-year time-period. Germline DNA was sequenced using BROCA, a targeted capture and parallel sequencing assay that identified pathogenic germline mutations in ovarian carcinoma susceptibility genes. RESULTS: Germline mutations in ovarian cancer susceptibility genes were found in 25.5% of women, most commonly BRCA1 and BRCA2. This mutation frequency mirrors those previously described among predominantly White populations. Our data suggests there may be an advantage in survival among those with germline mutations, although this was not statistically significant. CONCLUSIONS: Given similar frequencies of germline mutations between Black and White patients with ovarian cancer, we conclude that there are not major differences in the genetic predisposition to ovarian carcinoma. Equitable access to genomic advancements including germline and tumor sequencing would facilitate equal access to PARP inhibitors, the standard of care for patients with BRCA mutated advanced ovarian cancer.

Referral patterns for genetic counselling of women diagnosed with tubo-ovarian or peritoneal high-grade serous carcinoma (HGSC) within the Auckland Gynaecological Oncology Centre.

BACKGROUND: Germline BRCA1/2 mutations account for approximately 15% of invasive ovarian carcinomas. Referral of all women with non-mucinous epithelial tubo-ovarian and peritoneal cancer, especially high-grade serous carcinoma (HGSC) to genetic services for genetic counselling and subsequent BRCA testing, has become standard of care in many countries. Publicly funded BRCA testing was restricted to women ≤70 years old with HGSC in New Zealand for most of our study period. Referral rates of women with HGSC for BRCA mutation testing in New Zealand have not previously been reported. AIMS: To determine the proportion of eligible patients with tubo-ovarian or peritoneal HGSC referred to Auckland Gynaecologic Oncology Centre who were referred for genetic counselling. To determine the number of patients who underwent BRCA1/2 genetic testing and the rate of germline BRCA mutations. METHODS: Eligible cases were identified from Auckland Gynaecologic Oncology multidisciplinary meetings database from 1 January 2012 to 31 December 2014. Genetic referrals sent were checked against the genetic services database to ensure that referrals were received. Genetic counselling clinic attendance, uptake and results of genetic testing were also collected. RESULTS: One hundred and four eligible patients were identified with 58 patients referred. Referral rates increased from 37.5% in 2012 to 64.3% in 2014. Of the 58 patients referred, 53 attended genetic counselling, and 49 underwent BRCA mutation testing, of whom 10 (20.4%) tested positive for a germline BRCA mutation. CONCLUSION: Overall, 55.8% of eligible patients were referred for genetic testing; however, referral rates increased with time. This BRCA mutation-positive rate is comparable with current international data.

Disease mapping of zero-excessive mesothelioma data in Flanders.

PURPOSE: To investigate the distribution of mesothelioma in Flanders using Bayesian disease mapping models that account for both an excess of zeros and overdispersion. METHODS: The numbers of newly diagnosed mesothelioma cases within all Flemish municipalities between 1999 and 2008 were obtained from the Belgian Cancer Registry. To deal with overdispersion, zero inflation, and geographical association, the hurdle combined model was proposed, which has three components: a Bernoulli zero-inflation mixture component to account for excess zeros, a gamma random effect to adjust for overdispersion, and a normal conditional autoregressive random effect to attribute spatial association. This model was compared with other existing methods in literature. RESULTS: The results indicate that hurdle models with a random effects term accounting for extra variance in the Bernoulli zero-inflation component fit the data better than hurdle models that do not take overdispersion in the occurrence of zeros into account. Furthermore, traditional models that do not take into account excessive zeros but contain at least one random effects term that models extra variance in the counts have better fits compared to their hurdle counterparts. In other words, the extra variability, due to an excess of zeros, can be accommodated by spatially structured and/or unstructured random effects in a Poisson model such that the hurdle mixture model is not necessary. CONCLUSIONS: Models taking into account zero inflation do not always provide better fits to data with excessive zeros than less complex models. In this study, a simple conditional autoregressive model identified a cluster in mesothelioma cases near a former asbestos processing plant (Kapelle-op-den-Bos). This observation is likely linked with historical local asbestos exposures. Future research will clarify this.

Escalation of socioeconomic disparities among patients with colorectal cancer receiving advanced surgical treatment.

BACKGROUND: As tumor burden increases in colorectal cancer, treatment complexity progresses from colectomy to hepatectomy and lastly to cytoreductive surgery with heated intraperitoneal chemotherapy (CRS-HIPEC). The aim of this study was to evaluate whether disparities exist in the access to progressively more complex surgical treatment options. METHODS: Patients undergoing surgery for colorectal cancer were grouped by treatment type: group 1 (n = 224) underwent colectomy for nonmetastatic disease, group 2 (n = 112) underwent hepatectomy for liver metastasis, and group 3 (n = 112) underwent CRS-HIPEC for carcinomatosis. RESULTS: Whites were predominant in the HIPEC group (71.4 %) compared to the hepatectomy (67.9 %) and colectomy (57.6 %) groups (p = 0.025). The majority of the privately insured patients were in the HIPEC group (70.5 %) compared to the hepatectomy (56.2 %) and colectomy (30.4 %) groups (p < 0.0001). Distance traveled to the hospital was farthest on average in the HIPEC group (104.6 ± 258.3 km) compared to the hepatectomy (29.0 ± 28.0 km) or colectomy (26.4  ± 66.2 km) group (p < 0.0001). Mean household income also varied between the three groups, with HIPEC patients earning $56,957 (±24,124), hepatectomy patients earning $56,999 (±28,588), and colectomy patients earning ($51,518 ± 24,201) (p = 0.0503) on average per year. The HIPEC cohort contained a higher proportion of English speakers (90.2 %) than the other groups (hepatectomy 87.9 %, colectomy 85.3 %); however, this difference was not statistically significant (p = 0.43). CONCLUSIONS: CRS-HIPEC is not accessed equally across all socioeconomic groups. Patients undergoing HIPEC were most often white, English speaking, and privately insured; had a higher mean income; and had traveled the greatest distances on average to access surgical care.

Primary peritoneal carcinoma in complete remission: a case report.

Primary peritoneal carcinoma (PPCa) is a relatively uncommonly diagnosed tumor. It has a similar presentation to ovarian cancer. PPCa has a poor prognosis with survival ranging from 12-18 months. PPCa spreads mainly transperitoneally, but lymphatic and hematological metastases have also been reported. It is a diagnosis of exclusion made after pathological report. Here, a case of a 71-year-old female who presented with early satiety, fatigue, weight loss and left cervical lymphadenopathy and was diagnosed with metastatic PPCa, is reported. The patient was treated with chemotherapy and achieved a complete remission. The management of this rare tumor is discussed herein.

Incidence of ovarian, peritoneal, and fallopian tube carcinomas in the United States, 1995-2004.

OBJECTIVE: The objective of this analysis was to describe the distribution of pelvic carcinomas in the United States by demographic, pathologic, and clinical features. METHODS: Carcinomas of the ovary (n = 112,541), peritoneum (n = 6,458), and fallopian tube (n = 3,479) were identified through 24 population-based registries in the United States during the period 1995 to 2004. Age-adjusted incidence rates were calculated per million population using counts derived from the 2000 U.S. census. RESULTS: The age-adjusted incidence rate for ovarian carcinoma (119.9 per million) was substantially higher than for peritoneal (6.78 per million) or fallopian tube (3.72 per million) carcinomas. White women had the highest rates for all three malignancies. Rates for peritoneal carcinoma were lowest among Black women (2.88 per million) and rates for fallopian tube carcinoma were lowest among Hispanic women (2.45 per million). Serous carcinomas were the most commonly diagnosed histologic type for all anatomic sites. Peritoneal carcinomas were diagnosed at later ages (mean, 67 years) and more advanced stages (85% regional/distant) compared with fallopian tube carcinomas (mean, 64 years; 62% regional/distant) and ovarian carcinomas (mean, 63 years; 76% regional/distant). Incidence for all three pelvic carcinomas was lowest in the South. Time trend analyses between 1973 and 2005 exhibited a significant decline in ovarian carcinoma incidence and rises in the rates of peritoneal and fallopian tube cancers. CONCLUSIONS: Similarities in the incidence patterns for ovarian, peritoneal, and fallopian tube carcinomas support the likelihood of a common molecular pathogenesis.

Peritoneal carcinoma in women with genetic susceptibility: implications for Jewish populations.

Women from families with multiple cases of breast and ovarian cancer, specifically those who carry cancer-associated mutations of BRCA1 or BRCA2 are at increased life-time risk for peritoneal carcinoma, even after previous surgery to remove the ovaries, fallopian tubes and uterus. Hereditary breast-ovarian cancer (HBOC) syndrome and the associated BRCA1 and BRCA2 mutations are particularly prevalent in women of Jewish lineage, and specific BRCA1 and BRCA2 germline mutations have been linked with peritoneal carcinoma and HBOC syndrome in Jewish populations, especially those of Ashkenazi descent. This review presents the currently available data and looks forward toward further and better understanding of peritoneal carcinoma in women with inherited susceptibility. Over 90% of peritoneal cancer in patients from HBOC syndrome kindreds and associated with BRCA1 and BRCA2 mutations are serous carcinomas, which is equivalent with the proportion of ovarian cancers that are serous carcinomas in similar patients. The best indications are that while many peritoneal carcinomas in genetically susceptible women may arise directly from malignant transformation of the peritoneum, others might represent metastases from primary ovarian or fallopian tube carcinomas. Although the incidence of borderline ovarian tumors may not be increased in HBOC syndrome kindreds and those who carry cancer-associated BRCA1 and BRCA2 mutations, these individuals could be susceptible to malignant transformation of borderline lesions of the ovaries and peritoneum. Moreover, recent reports raise the question of possibly increased risk in Jewish carriers of germline BRCA1 mutations for uterine papillary serous carcinoma, which could be the source of metastasis to the peritoneum in some cases. The penetrance of cancer-associated BRCA1 mutations for ovarian cancer is estimated to be 11%-54%, and for BRCA2 mutations the penetrance for ovarian cancer is 11%-23%. So far, available screening methods appear to be insufficient for early detection of many ovarian cancers. Prophylactic oophorectomy has been found to reduce the risk for ovarian cancer in women from HBOC kindreds and those who carry cancer-associated BRCA1 and BRCA2 mutations, leaving a residual risk for peritoneal carcinomatosis of well less than 5%. Therefore, surgical removal of the ovaries, fallopian tubes and uterus, after child-bearing has been completed and by early in the fifth decade of life, are appropriate prophylactic procedures in women whose genetic susceptibility puts them at increased risk for cancers of mullerian tract origin, including ovarian and fallopian tube carcinomas and possibly serous carcinoma of the uterus. Hysterectomy, as well as salpingo-oophorectomy, removes the gynecologic organs targeted for malignant transformation in genetically susceptible women and simplifies decisions regarding hormone replacement therapy and chemical prophylaxis and treatment of breast cancer. Unless a transabdominal operative approach is otherwise indicated, laparoscopic-assisted transvaginal techniques are well suited for intra-abdominal exploration, cytology, biopsies and prophylactic salpingo-oophorectomy and hysterectomy in women with hereditary susceptibility to gynecologic cancer.

Endometriosis in multiparous women.

The incidence of endometriosis in the general population has been reported to range from 4% to 32%. A more realistic figure is probably 7.5%. An incidence of 7.4% was found in 42 of 566 multiparous women undergoing tubal sterilization at Baylor College of Medicine, Houston. Twelve of the 42 (29%) were less than five months postpartum. Hispanics had an incidence of endometriosis similar to that of whites and blacks. Indigent status had no bearing on the presence of endometriosis. A higher incidence of spontaneous abortion was found in patients with endometriosis, but the difference was not statistically significant.

PIP: Patients undergoing laparoscopic tubal sterilization at Baylor College of Medicine in Houston from 1985-1986 constituted a study group for collecting data on the incidence and demographics of endometriosis in women who present for care not associated with gynecologic symptoms. A lesion was not considered to be an endometriosis implant unless it was highly typical -- brown, black or blue, and circumscribed by fibrosis. Laparoscopy was performed with a single-puncture technique. The entire pelvis, including the cul-de-sac and ovarian fossae, was observed for evidence of pelvic disease, including adhesions and endometriosis. 566 women underwent laparoscopy and pelvic evaluation; endometriosis was identified in 42 women. 28 of the 42 cases were minimal, 10 mild, and 4 moderate. 16 of 42 patients (38%) with endometriosis as compared to 235 of 524 (44.8%) without endometriosis complained of dysmenorrhea. The mean age, gravidity, and parity did not differ in endometriosis patients as compared to the other women. 80.4% of the women were indigent. Neither race nor indigent status differed in endometriosis patients as compared to the other women. 12 of the 42 patients with endometriosis were less than 5 months postpartum; 14 of the 42 patients with endometriosis were current oral contraceptive users (33.3%) as compared to 222 of the 524 (42.4%) without endometriosis. Current OC use appeared to be protective, but statistical significance was lacking. While spontaneous abortions were more common in patients with endometriosis, statistical significance also was lacking. In sum, a 7.4% incidence of endometriosis was found in multiparous fertile women.