The Scarface Score: Deciphering Response to DNA Damage Agents in High-Grade Serous Ovarian Cancer-A GEICO Study.

Genomic Instability (GI) is a transversal phenomenon shared by several tumor types that provide both prognostic and predictive information. In the context of high-grade serous ovarian cancer (HGSOC), response to DNA-damaging agents such as platinum-based and poly(ADP-ribose) polymerase inhibitors (PARPi) has been closely linked to deficiencies in the DNA repair machinery by homologous recombination repair (HRR) and GI. In this study, we have developed the Scarface score, an integrative algorithm based on genomic and transcriptomic data obtained from the NGS analysis of a prospective GEICO cohort of 190 formalin-fixed paraffin-embedded (FFPE) tumor samples from patients diagnosed with HGSOC with a median follow up of 31.03 months (5.87-159.27 months). In the first step, three single-source models, including the SNP-based model (accuracy = 0.8077), analyzing 8 SNPs distributed along the genome; the GI-based model (accuracy = 0.9038) interrogating 28 parameters of GI; and the HTG-based model (accuracy = 0.8077), evaluating the expression of 7 genes related with tumor biology; were proved to predict response. Then, an ensemble model called the Scarface score was found to predict response to DNA-damaging agents with an accuracy of 0.9615 and a kappa index of 0.9128 (p < 0.0001). The Scarface Score approaches the routine establishment of GI in the clinical setting, enabling its incorporation as a predictive and prognostic tool in the management of HGSOC.

Breast cancer during pregnancy: results of maternal and perinatal outcomes in a single institution and systematic review of the literature.

To compare the maternal and the perinatal variables of the patients with pregnancy associated breast cancer (PABC) and the pregnant patients without breast cancer (PNABC), we retrospectively included 13 PABC cases and 66.265 PNABC patients. The PABC patients presented a lower mean gestational age at their delivery and had higher induction of labour and prematurity rates. A diagnosis was performed before stage III in 77% of the cases. The overall survival was 90%; moreover, we collected 16 manuscripts when gathering data from 1581 patients with PABC. The mean follow-up time was 70 ± 8 months. The mean maternal age at diagnosis was 34 years old. Most of the patients were at their second trimester of pregnancy. The gestational age at delivery was 35 weeks. A mastectomy was the most frequently used surgical approach. PABC should be managed by a multidisciplinary team, ensuring there is a rigorous oncological treatment, with foetal well-being. IMPACT STATEMENT What is already known on this subject? The malignant breast tumours diagnosed during pregnancy, or 1 year after a delivery are increasing, there is evidence supporting the treatment during a pregnancy with maternal and foetal safety. A PABC should be managed by a multidisciplinary team in a referral centre, ensuring that there is a rigorous oncological treatment with foetal well-being. What do the results of this study add? Our results show that the PABC patients in our centre had a mean maternal age older than the PNABC women, as well as a higher percentage of the induction of labour and prematurity. 48 Cancer was usually diagnosed in early stages, and the most common type was ductal infiltrating, with positive hormonal receptors. For those patients continuing their pregnancies, a mastectomy plus a lymphadenectomy was the most frequent chemotherapy, and was usually administered in the third trimester of pregnancy. What are the implications of these findings for future clinical practice and/or further research? Moreover, the number of publications concerning PABC has grown, series are still scarce. We understand the limitations of the low number of the cases on our population, but this study is the first which compare the PABC with the PNABC patients, allowing to describe and compare the obstetrical and perinatal variables. Finally, we consider it is of a paramount importance to create an international database to register in a prospective way all of the cases of PABC to increase our knowledge in this field.

Maternal and perinatal outcomes in pregnancy-associated melanoma. Report of two cases and a systematic literature review.

OBJETIVES: Melanoma is one of the most frequent malignancies during gestation. However, oncological and perinatal management is still challenging. Our first objective is to describe the cases of pregnancy-associated melanoma (PAM) diagnosed in our centre between January-2004 and May-2015. Secondly, to perform a systematic review of the published articles analysing the maternal-perinatal outcomes of patients diagnosed with PAM. DESIGN, POPULATION AND METHODS: Obstetrical, oncological and perinatal variables were recorded in the case series. For the systematic review we include all published articles assessing the obstetric and neonatal outcomes in PAM cases in Pubmed, Web of Knowledge and Cochrane Library. The search was restricted to articles published in English, between January-2004 and May-2015. Study characteristics, oncological and maternal-perinatal variables were recorded in the systematic review. RESULTS: Two patients were found: the first case presents a newly diagnosed metastatic melanoma at 26-weeks of gestation with fatal maternal and neonatal outcome. The second case presents a patient with metastatic melanoma who got pregnant during her treatment. For the systematic review we found 25 articles, providing data from 489 patients. Maternal-perinatal outcomes, including termination of pregnancy rates, vary depending on the country, gestational age and tumour stage at diagnosis. PAM is usually detected at advanced stages, even with metastasis affecting the placenta and the foetus. CONCLUSIONS: When diagnosed at early stages, melanoma does not seem to alter the evolution of gestation, whereas patients with advanced stages of melanoma frequently deliver prematurely, by caesarean section, with lower neonatal weight, higher neonatal morbidity and mortality rates.

"The impact of debulking surgery in patients with node-positive epithelial ovarian cancer: Analysis of prognostic factors related to overall survival and progression-free survival after an extended long-term follow-up period".

OBJECTIVE: to estimate the prognostic factors associated with survival and progression free survival (PFS) in patients with node-positive epithelial ovarian cancer (EOC) after an extended long-term follow-up period. METHODS: Data was provided by the Tumor Registry of the Mayo Clinic, Scottsdale, Arizona on 116 node-positive EOC patients who underwent primary cytoreductive surgery observed over the period 1996-2014. RESULTS: At censoring date, 21 patients were alive (18%), 95 dead (82%), 18 without evidence of disease (NED) (15 alive, 3 dead) and 76 with evidence of disease (ED) (2 alive, 74 dead). Twenty-nine ED patients (38.2%) experienced a recurrence within 2 years, 53 patients (69.7%) before 5 years. No recurrences were recorded after 10 years. The median follow-up in alive patients was 169.8 months (1.20-207.9 months), 34.9 months (0.30-196.2 months) in dead patients, 128.4 months for NED patients (72.8-202.5 months) and 34.6 months (0.1-106.9 months) in ED patients. Multivariate analysis showed an increased risk of dead in patients with age ≥ 60 years (HR: 3.20; p < 0.002), stage IVA/B (compared with stage IIIA1/2, HR: 4.31; p < 0.001 and stage IIIB/C, HR: 5.31; p < 0.010) and incomplete surgery (compared with complete surgery, HR: 3.10; 95% CI, 1.41-6.77; p < 0.003) and a decreased PFS in stage IVA/B (compared with stages IIIB/C; p = 0.003 and stage IIIA; p = 0.000) and residual volume after surgery >0.6 cm (compared with residual disease <0.5 cm; p < 0.023). CONCLUSIONS: prognostic factors for an extended long-term PFS are similar as those for survival, because after 17-year follow-up period, the majority of alive patients are NED patients.

Peritoneal carcinomatosis: A malignant disease with an embryological origin?

INTRODUCTION: In 1931, Simpson et al. coined the term "peritoneal carcinomatosis" to describe the regional spread of ovarian tumors as localized or extended with involvement of the peritoneal serous membrane and neighboring anatomical structures. Research into the origin of peritoneal carcinomatosis is based on two phases in a woman's life: EMBRYO DEVELOPMENT: During week 3, the bilaminar disc becomes a trilaminar disc called the mesoderm. Inside the lateral plate mesoderm, the coelomic cavity is divided into 2 layers: the parietal (somatic) mesoderm, which gives rise to the parietal peritoneum and pleural surfaces; and the visceral (splanchnic) mesoderm, which gives rise to the visceral peritoneum, visceral surface of the pleura, gonadal stroma, and the muscular layer of the hollow viscera and its mesenteries. TUMOR SPREAD: Transcoelomic metastasis and metaplasia of pluripotent stem cells in the peritoneum was involved in the pathogenesis of ovarian cancer. This involvement takes the form of a synchronous malignant transformation at multiple foci and may cause intraperitoneal field cancerization. Pluripotent stem cells play a role both in the development of the embryonic peritoneum and in the spread of transcoelomic tumors. Consequently, knowledge of the origin of these cells (embryonic or current) could be extremely useful. The many markers that act during the embryonic period can affect descendants, that is, cells are already marked before specification and differentiation are activated. Thus, programmed activation could be attributed to genetic and epigenetic changes.

International Federation of gynecology and obstetrics staging classification for cancer of the ovary, fallopian tube, and peritoneum: estimation of survival in patients with node-positive epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to determine the survival of patients with node-positive epithelial ovarian cancer according to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. MATERIALS AND METHODS: We performed a retrospective chart review. Data from all consecutive patients with node-positive epithelial ovarian cancer (stages IIIC and IV) who underwent cytoreductive surgery at the Mayo Clinic from 1996 to 2000 were reassessed to evaluate the prognostic significance of the new FIGO stages. Multivariate Cox regression was performed, and Kaplan-Meier survival curves constructed. RESULTS: The distribution of the restaged patients was as follows: IIIA1, 23 patients (IIIA1i, 9 patients; and IIIA1ii, 14 patients); IIIA2, 3 patients; IIIB, 4; IIIC, 67 patients; IVA, 4 patients; and IVB, 15 patients. In the univariate analysis, the relative risk for positive nodes greater than 10 mm on the longer axis was 2.57 and 3.00 for patients with microscopic peritoneal disease, compared with patients with microscopic positive nodes. However, the difference was not statistically significant. Moreover, the univariate analyses revealed statistically significant differences for 2014 FIGO stages (IIIA, IIIB, IIIC, and IVA-B), anatomical sites of peritoneal metastases, and disease staged at IIIC because of the presence of omental metastases. Multivariate analysis showed that survival was higher in patients restaged to IIIA-B than in those restaged to IIIC and IV (hazard ratios, 2.75 and 3.16, respectively; P = 0.002). The hazard ratio for patients with abdominal peritoneal metastases was 2.76 compared with patients with pelvic peritoneal metastases (P = 0.001). CONCLUSIONS: The current 2014 FIGO staging system for ovarian cancer successfully correlates survival, anatomical location of peritoneal metastases, and extra-abdominal lymph node metastases.