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Background Ovarian carcinosarcoma (OCS) is an uncommon, biphasic and highly aggressive ovarian cancer type, which has received relatively little research attention. Methods We curated the largest pathologically confirmed OCS cohort to date, performing detailed histopathological characterisation, analysis of features associated with survival and comparison against high-grade serous ovarian carcinoma (HGSOC). Results Eighty-two OCS patients were identified; overall survival was poor (median 12.7 months). In all, 79% demonstrated epithelial components of high-grade serous (HGS) type, while 21% were endometrioid. Heterologous elements were common (chondrosarcoma in 32%, rhabdomyosarcoma in 21%, liposarcoma in 2%); chondrosarcoma was more frequent in OCS with endometrioid carcinomatous components. Earlier stage, complete resection and platinum-containing adjuvant chemotherapy were associated with prolonged survival; however, risk of relapse and mortality was high across all patient groups. Histological subclassification did not identify subgroups with distinct survival. Compared to HGSOC, OCS patients were older (P P = 0.025), demonstrated lower chemotherapy response rate (P = 0.001) and had significantly poorer survival (P Conclusion OCS represents a distinct, highly lethal form of ovarian cancer for which new treatment strategies are urgently needed. Histological subclassification does not identify patient subgroups with distinct survival. Aggressive adjuvant chemotherapy should be considered for all cases, including those with early-stage disease.

BACKGROUND: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. METHODS: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). RESULTS: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. CONCLUSIONS: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients. ispartof: BRITISH JOURNAL OF CANCER vol:119 issue:9 pages:1075-1085 ispartof: location:England status: published

BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC).METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA.RESULTS: We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 μg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients.CONCLUSIONS: Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.British Journal of Cancer advance online publication, 30 March 2017; doi:10.1038/bjc.2017.86 www.bjcancer.com.

Background: Maintenance monotherapy with the poly(ADP-ribose) polymerase inhibitor olaparib significantly prolongs progression-free survival over placebo in patients with platinum-sensitive relapsed serous ovarian cancer, with greatest benefit seen in patients with a BRCA1/2 mutation (BRCAm). Preservation of health-related quality of life (HRQoL) is important during maintenance therapy; we evaluated the effect of olaparib on HRQoL in this Phase II trial (NCT00753545, Study 19). Methods: Patients received olaparib 400 mg b.i.d. (capsules) or placebo until progression. Patient-reported HRQoL and disease-related symptoms were evaluated using the FACT-Ovarian (FACT-O) questionnaire (completed at baseline and every 28 days until progression), the FACT/NCCN Ovarian Symptom Index (FOSI) and the Trial Outcome Index (TOI). TOI of the FACT-O was the primary measure. Results: Overall, 265 women were randomised to maintenance olaparib (n=136) or placebo (n=129). Compliance for HRQoL assessment was high (∼80% over time). Most patients in both arms reported a best response of ‘no change' on TOI (81%) and other HRQoL measures. There were no statistically significant differences in time to worsening or improvement rates of TOI, FOSI and FACT-O scores in the overall, BRCAm and germline BRCAm populations. Conclusions: Maintenance treatment with olaparib was well tolerated and had no adverse impact on HRQoL in this study of patients with platinum-sensitive relapsed serous ovarian cancer who had responded to their most recent platinum-based therapy (partial or complete response). Interpretation of the HRQoL results in this population may differ from patients who have not responded to their most recent platinum-based therapy.

BACKGROUND: Ovarian cancer is frequently advanced at presentation when treatment is rarely curative. Response to first-line platinum-based chemotherapy significantly influences survival, but clinical response is unpredictable and is frequently limited by the development of drug-resistant disease. METHODS: We used qRT–PCR analysis to assess intertumour differences in the expression of fibroblast growth factor 1 (FGF1) and additional candidate genes in human ovarian tumours (n ¼187), and correlated individuality in gene expression with tumour histology, chemotherapy response and survival. We used MTT assays to assess platinum chemosensitivity in drug-sensitive and drug-resistant ovarian cell lines. RESULTS: Marked intertumour differences in gene expression were observed, with each tumour having a unique gene expression profile. Nine genes, including FGF1 (P ¼1.7 � 10 � 5 ) and FGFR2 (P ¼0.003), were differentially expressed in serous and nonserous tumours. MDM2 (P ¼0.032) and ERBB2 (P ¼0.064) expression was increased in platinum-sensitive patients, and FGF1 (adjusted logrank test P ¼0.006), FGFR2 (P ¼0.04) and PDRFRB expression (P ¼0.037) significantly inversely influenced progression-free survival. Stable FGF1 gene knockdown in platinum-resistant A2780DPP cells re-sensitised cells to both cisplatin and carboplatin. CONCLUSION: We show for the first time that FGF1 is differentially expressed in high-grade serous ovarian tumours, and that individuality in FGF1 expression significantly influences progression-free survival and response to platinum-based chemotherapy.

Background: To determine (a) the cause of an improvement in survival from oropharyngeal squamous cell carcinoma (OSCC) in South East Scotland and (b) whether this improvement was human papillomavirus (HPV) and p16 subtype-dependent. Methods: Clinicopathological characteristics and outcome data for patients referred with OSCC from 1999 to 2001 (Cohort-1) and 2003 to 2005 (Cohort-2) were obtained. Molecular HPV detection and immunohistochemistry for p16 were performed from paraffin blocks. Results: Cohort-1 and Cohort-2 contained 118 and 136 patients, respectively. Kaplan–Meier analysis revealed significantly improved survival in Cohort-2 (P