Summary Background Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in...

Background:Endometriosis-associated malignant transformation in abdominal surgical scar (EAMTAS) is a very rare and aggressive phenomenon. Our current article aims to provide a clinical overview, focusing on risk factors affecting survival.Methods:We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review based on prior reviews and case reports regarding the phenomenon published as abstracts in English, from January 1980 to November 2016. Overall, we identified 47 cases, and we included another case from our institution. We further contacted previous investigators to receive updated follow-up regarding their patients. We analyzed the data, focusing on risk factors that might affect overall survival.Results:All the patients reported in the literature had a uterine surgery, mainly caesarean section. The median time-lag from first surgery to the diagnosis of cancer was about 19 years. Clear-cell carcinoma (CCC) was the most prevalent histology (67%), followed by endometrioid adenocarcinoma (15%). Most of the patients were treated by extensive surgery and chemotherapy and/or radiation. Overall 5 years survival was about 40%. Median overall survival was 42 months (95% confidence interval of [18.7, 65.3]). Although our review is currently the largest in the literature, we cannot draw any statistical significant results due to the limited number of patients reported. According to univariate Cox-regression models, a tendency toward worse prognosis was shown for 3-year disease-free survival clear cell histologic-type (P = .169), and tumor diameter ≥8 cm in nonclear-cell histology, 18 months postdiagnosis (P = .06).Conclusion:EAMTAS is a rare and aggressive disease. It is mostly related to cesarean section scars and is diagnosed many years postsurgery. Clear-cell histology tends to endure from the worse prognosis. The treatment is mainly extensive surgery and adjuvant chemotherapy and/or radiotherapy.

Background. The neutrophil-to-lymphocyte ratio (NLR), an inflammation marker, is prognostic in several cancers. We assessed the association between the pretreatment NLR and outcome of patients with metastatic castrationresistant prostate cancer (mCRPC) treated with the CYP17 inhibitor ketoconazole.Methods. This was an international, retrospective study of 156 mCRPC patients treated with ketoconazole. The independent effect of the pretreatment NLR and factors associated with treatment outcome were determined by multivariate analysis.Results. Seventy-eight patients (50%) had a >50% decline in prostate-specific antigen (PSA). The median progression-free survival (PFS) time was 8 months. Excluded from the analysis were 23 patients without available data on their NLR and those with a recent health event or treat-

Describe the association between risk factors for renal cell carcinoma and the outcome of sunitinib treatment for metastatic disease.Explain the impact of active smoking on the outcome of sunitinib-treated metastatic renal cell carcinoma.Discuss obesity, hypertension, and diabetes in relation to the outcome of sunitinib-treated metastatic renal cell carcinoma. ABSTRACTBackground. Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development.Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC).Methods. An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors.Results. Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with

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Bisphosphonates may improve the RR, PFS and OS of sunitinib treatment in RCC with bone metastases.

Background: The objective of this study was to evaluate if hypothyroidism developing during sunitib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. Methods: Thirty-one consecutive patients with clear cell mRCC were retrospectively analyzed. Thyroid function was assessed prior to therapy, every 6 weeks during the first 6 months and every 2–4 months thereafter. Hypothyroidism was considered present if thyroid-stimulating hormone (TSH) exceeded the upper normal limit (UNL) with normal triiodothyronine (T3) and thyroxine (T4). Results: Hypothyroidism occurred in 16 patients (52%) within 3 months (range 0.7–22.9) of treatment initiation. Thyroid replacement corrected TSH below the UNL in 10 patients (63%). The distribution according to Motzer prognostic criteria revealed good prognosis in 16 patients (52%), intermediate in 9 (29%) and poor in 6 (19%). The hypothyroid patients tended to have longer progression-free survival (PFS; median 12.2 vs. 9.4 months; p = 0.234) and longer survival (median 22.4 vs. 13.9 months; p = 0.234) than the euthyroid patients. Clinical benefits were similar in both groups. Conclusions: Hypothyroidism that develops in mRCC patients treated with sunitinib is associated with a trend toward prolonged PFS and survival, with a similar clinical benefit rate.

OBJECTIVE To evaluate the prostate‐specific antigen (PSA) ‘flare’ phenomenon in patients with androgen‐independent prostate cancer (AIPC) treated with docetaxel, as flare is a known effect of androgen‐deprivation therapy in hormone‐dependent prostate cancer. PATIENTS AND METHODS The charts of 56 patients who received docetaxel‐based chemotherapy in three different centres from August 1999 to August 2007 were reviewed retrospectively. The biochemical response was characterized according to the Bubley criteria. There was an immediate PSA response (PSA decline ≥ 50%) in 23 (41%) patients, PSA stabilization (PSA decline < 50%) in 16 (29%) and PSA progression in nine (16%). There was also a fourth response, i.e. PSA flare, defined as an increase in PSA level with no symptomatic progression, after starting docetaxel‐based chemotherapy administered every 3 weeks. RESULTS Eight (14%) patients with PSA flare were identified; all had osseous disease and five had additional soft‐tissue disease. The PSA flare lasted a median (range) of 21 (21–42) days and it spread over a median of 1 (1–2) cycles. The temporary PSA surge exceeded baseline values by a median (range) of 61.5 (12–404)%. There was a subsequent PSA response in six of the eight patients and PSA stabilized in the remaining two. Patients with flare received a median of 8.5 (5–12) treatment cycles, vs a median of 8 (2–12) in the immediate PSA response group (P = 0.103, Student’s t‐test). The Response Evaluation Criteria in Solid Tumors criteria evaluation showed one patient with a partial response and six with stable disease. The median survival of patients with PSA flare was 12.5 months, while that of the immediate PSA responders was 20.1 months (not statistically significant, P = 0.168, log‐rank test). CONCLUSION Of patients with AIPC, 14% had an initial PSA flare after starting docetaxel‐based chemotherapy. The occurrence of PSA flare had no effect on treatment duration or outcome. With lack of clinical progression, docetaxel‐based chemotherapy should be administered for at least two 3‐week cycles before further decisions are made about efficacy.