BackgroundPhase II studies have shown that the combination of capecitabine and irinotecan (the XELIRI regimen) is active in metastatic colorectal cancer (MCRC). There are, however, no data about the use of the XELIRI regimen in the neoadjuvant treatment.MethodsPatients with unresectable liver-only metastases of MCRC with ≤ 75 years of age were randomised to either the XELIRI (irinotecan 250 mg/m2 given on day one and capecitabine 1000 mg/m2 twice daily from day 2–15, every 21 days) or the FOLFIRI arm (irinotecan 180 mg/m2, 5-FU 400 mg/m2, LV 200 mg/m2, 5-FU 2400 mg/m2 (46-h infusion) – all given on day one, every 14 days). Primary end points were objective response rate (ORR) and rate of radical (R0) surgical resection. Secondary end points were progression-free survival (PFS), overall survival (OS) and safety.ResultsAltogether 87 patients were enrolled (41 pts in the XELIRI and 46 pts in the FOLFIRI arm). The median age was 63 years (63 years in the XELIRI and 62 years in the FOLFIRI arm) (p = 0.33). ORR was 49% in the XELIRI and 48% in the FOLFIRI arm (p = 0.76). The rate of radical R0 resection was 24% in both arms of patients. At the end of treatment, 37% of patients in the XELIRI and 26% of patients in the FOLFIRI arm were without evidence of the disease (CR+R0 resection) (p = 0.56). There were no statistical differences in grade 3 or 4 adverse events between both arms: diarrhoea 7% vs. 6%, neutropenia 5% vs. 13%, ischemic stroke 0 vs. 2%, acute coronary syndrome 2% vs. 4%, respectively. At the median follow up of 17 (range 1–39) months, the median PFS was 10.3 months in the XELIRI and 9.3 months in the FOLFIRI arm (p = 0.78), the median OS was 30.7 months in the XELIRI arm and 16.6 months in the FOLFIRI arm (p = 0.16).ConclusionThe XELIRI regimen showed similar ORR as the FOLFIRI regimen in the neoadjuvant treatment of patients with MCRC. In addition, the XELIRI regimen showed similar PFS and OS with acceptable toxicity compared to the FOLFIRI regimen.Trial RegistrationCurrent Controlled Trials ISRCTN19912492

BackgroundThe aim of the study was to analyze the overall survival (OS) and progression free survival (PFS) of patients with high grade and advanced stage epithelial ovarian cancer (EOC) with at least 60 months of follow-up treated in a single gynecologic oncology institute. We compared primary debulking surgery (PDS) versus neoadjuvant chemotherapy plus interval debulking surgery (NACT + IDS) stratifying data based on residual disease with the intent to identify the rationale for therapeutic option decision and the role of laparoscopic evaluation of resectability for that intention.Patients and methodsThis is observational retrospective study on consecutive patients with diagnosis of high grade and International Federation of Gynecology and Obstetrics (FIGO) stage III/IV EOC referred to our center between January 2008 and May 2012. We selected only patients with a follow-up of at least 60 months. Primary endpoint was to compare PDS versus NACT + IDS in term of progression free survival (PFS) and overall survival (OS). Secondary endpoints were PFS and OS stratifying data according to residual disease after surgery in patients receiving PDS versus NACT + IDS. Finally, through Cox hazards models, we tested the prognostic value of different variables (patient age at diagnosis, residual disease after debulking, American Society of Anesthesiologists (ASA) stage, number of adjuvant-chemotherapy cycles) for predicting OS.ResultsA total number of 157 patients were included in data analysis. Comparing PDS arm (108 patients) and NACT + IDS arm (49 patients) we found no significant differences in term of OS (41.3 versus 34.5 months, respectively) and PFS (17.3 versus 18.3 months, respectively). According to residual disease we found no significant differences in term of OS between NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0 or residual disease = 1, as well as no significant differences in PFS were found comparing NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0; contrarily, median PFS resulted significantly lower in PDS patients receiving optimal debulking (residual disease = 1) in comparison to NACT + IDS patients receiving complete debulking (residual disease = 0). PDS arm was affected by a significant higher rate of severe post-operative complications (grade 3 and 4). Diagnostic laparoscopy before surgery was significantly associated with complete debulking.ConclusionsWe confirm previous findings concerning the non-superiority of NACT + IDS compared to PDS for the treatment of EOC, even if NACT + IDS treatment was associated with significant lower rate of post-operative complications. On the other hand, selecting patients for NACT + IDS, based on laparoscopic evaluation of resectabilty prolongs the PFS and does not worse the OS compared to the patients not completely debulked with PDS.

Background High-grade serous ovarian cancer is a detrimental disease. Treatment options in patients with a recurrent disease are dependent on BRCA1/2 mutation status since only patients with known BRCA mutation are eligible for treatment with poly(ADP-ribose) polymerase inhibitors (PARPi). The aim of this study was to compare concordance of BRCA mutation analyses from cytological samples (CS) with BRCA mutation analyses from histological formalin fixed paraffin embedded (FFPE) samples. Methods Mutation analysis of BRCA1 and BRCA2 genes was performed in 44 women diagnosed with primary or recurrent high-grade ovarian cancer from three different samples: blood, cytological sample (ascites, pleural effusion and enlarged lymph nodes) and tumor tissue. Results from all three samples were compared. Results Among 44 patients, there were 15 germline mutations and two somatic mutations. A 100% concordance was found between cytological and histologic samples. Conclusion There is a 100% concordance in BRCA mutation testing between cytological and histologic samples. BRCA mutation testing from CS could replace testing from FFPE tissue in clinical decision making in ovarian cancer patients. Trial registration The study was retrospectively registered at ISRCTN registry on 24/11/2015 - ISRCTN42408038 .

BackgroundThe aim of the study was to establish whether there are different clinical entities of primary pulmonary choriocarcinoma (PPC) that deserve different diagnostic approach and the most optimal treatment.Patients and methodsA systematic review with PubMed search was conducted to identify studies that reported cases of PPC. The eligibility criteria were histological diagnosis of pulmonary choriocarcinoma and thorough examination of the reproductive organs to exclude potential primary choriocarcinoma in the gonads. Furthermore, to illustrate the review we additionally present a patient referred at our institution.Results55 cases (17 men) were included in the review with a median age of 34 years. Women with the history of gestational event showed better survival outcome than women without the history of gestational event. Patients treated with combined modality treatment (surgery and chemotherapy) survived longer than the patients without combined modality treatment. Furthermore, multivariate analysis of prognostic factors showed that the combined modality treatment had independent prognostic significance. Size of the tumour showed significant prognostic influence in univariate and multivariate analysis.ConclusionsPPC is an extreme rarity with variable clinical characteristics and outcome. It is important to capture and treat patients in the early stages of the disease. Women with the history of gestational event may show better survival, therefore genetic examination could help us to predict patient’s prognosis. Surgery followed by adjuvant chemotherapy appears to represent the best treatment for PPC.

In this association study the authors compared the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism in females and males with premature myocardial infarction (MI). I/D ACE gene polymorphism was tested in 738 subjects: 302 patients with MI (151 men and 151 women) and 436 healthy subjects (207 men and 229 women). In women the ACE-DD genotype was not associated with MI (OR 1.1, 95% CI 0.6-2.1, p=0.6), whereas the ACE-DD genotype conferred a 2-fold independent risk for MI in men (95% CI=1.2-3.4; p=0.013) after adjustment for cardiovascular risk factors. The authors found evidence for the sex difference in the effect of the ACE-DD genotype on MI risk. The ACE-DD genotype conferred a 2-fold independent risk for premature MI in males.

In the last ten years, clinical oncology has been revolutionized by the introduction of oncological immunotherapy, mainly in the form of immune checkpoint inhibitors (ICIs) that transformed the standard of care of several advanced solid malignancies. Using ICIs for advanced gynecological cancers has yielded good results, especially for endometrial cancer. In ovarian or cervical cancer, combining ICIs with other established agents has shown some promise. Concurrently with the clinical development of ICIs, biomarkers that predict responses to such therapy have been discovered and used in clinical trials. The translation of these biomarkers to clinical practice was somewhat hampered by lacking assay standardization and non-comprehensive reporting of biomarker status in trials often performed on a small number of gynecological cancer patients. We can expect increased use of ICIs combined with other agents in gynecological cancer in the near future. This will create a need for reliable response prediction tools, which we believe will be based on biomarker, clinical, and tumor characteristics. In this article, we review the basic biology of ICIs and response prediction biomarkers, as well as the latest clinical trials that focus on subgroup effectiveness based on biomarker status in gynecological cancer patients.

OPINION investigated maintenance olaparib in platinum-sensitive relapsed ovarian cancer patients without a germline BRCAm.• In this primary analysis, median PFS was 9.2 months overall, demonstrating clinical benefit versus historical controls.• Median PFS was prolonged across predefined biomarker subgroups based on BRCAm and HRD status.• The safety profile of maintenance olaparib was generally consistent with previous reports.• Our findings support maintenance olaparib as a standard of care in PSROC, irrespective of BRCAm or HRD status.

Background Osteopontin (sOPN) is a promising blood tumour marker for detecting epithelial ovarian cancer (EOC). However, other clinical uses of sOPN as a tumour marker in EOC are still lacking. Since sOPN concentrations in serum are not associated with those in ascites, we compared clinical value of sOPN concentrations in the two body fluids. Patients and methods The study included 31 women with advanced EOC and 34 women with benign gynaecological pathology. In the EOC group, serum for sOPN analysis was obtained preoperatively, after primary debulking surgery and after chemotherapy. In the control group, serum was obtained before and after surgery. Ascites and peritoneal fluid were obtained during surgery. sOPN concentrations were determined by flow cytometry bead-based assay. Results The sensitivity and specificity of sOPN in detecting EOC was 91.2% and 90.3% (cut-off = 47.4 ng/ml) in serum, and 96.8% and 100% (cut-off = 529.5 ng/ml) in ascites. Kaplan-Meier analysis showed a significant association between higher serum sOPN concentration and overall survival (p = 0.018) or progression free survival (p = 0.008). Higher ascites sOPN concentrations were associated with suboptimally debulked tumour and unresectable disease. Higher serum sOPN concentrations were associated with refractory disease or incomplete response to platinum-based chemotherapy. Conclusions The study showed that ascites sOPN level mirrors present disease and is superior to serum level for diagnostic purposes and surgical planning, although the end result of treatment is the response of the whole body in fighting the disease. The preoperative sOPN concentration in serum thus better reflects disease outcome.