clinical benefit and risk of death with endocrine therapy in ovarian cancer a comprehensive review and meta analysis

Abstract Background Steroid hormones promote epithelial ovarian cancer (EOC) growth and their receptor expression is associated with disease outcome. Hormone therapy is frequently used in pretreated EOC, but the magnitude of activity overall and by specific agents or tumor characteristics is unknown. Methods Clinical Benefit Rates (CBR) and deaths from clinical trials of endocrine agents were meta-analyzed. Summary estimates of CBR (SCBR) and Odd Ratio for death (SOR) were calculated according with type of drug, ER and PgR status, platinum resistance, line of therapy, tumor grade and tamoxifen dose. Results Fifty-three trials in 2490 patients were analyzed. Overall, SCBR was 41% (95%CI, 0.34–0.48) for any endocrine treatment, 43% (95%CI, 0.30–0.56) for tamoxifen, 39% (95%CI, 0.29–0.50) for aromatase inhibitors and 37% (95%CI, 0.26–0.48) for progestins. The SCBR for ER + and/or PgR + tumors was 46% (95%CI, 0.34–0.57) versus 37% (95%CI, 0.27–0.48) in tumors with unknown receptors and 55% in platinum sensitive (95%CI, 0.28–0.80) versus 40% (95%CI, 0.29–0.51) in platinum resistant tumors The SOR for death calculated from 6 out of 9 randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy (SOR = 0.69, 95%CI, 0.50–0.97), with a possible tendency for a greater effect in first line and low grade tumors. The overall quality of the RCTs was low. Conclusions The activity of endocrine therapy in advanced EOC is worth considering and seems to support large properly designed randomized trials in the first treatment of hormone sensitive EOC

the science behind vitamins and natural compounds for breast cancer prevention getting the most prevention out of it

Summary This review highlights the role of vitamins and natural compounds in breast cancer prevention, with a particular focus on Vitamin D. In the last decades, both encouraging and discouraging results about the association between antioxidant supplementation and cancer have been reported to public and scientific community. Their safe and favorable toxicity profile makes them suitable to be investigated in a preventive setting. However, a recent large meta-analysis showed that treatment with beta carotene, vitamin A, and vitamin E may increase mortality, whereas the potential roles of vitamin C and selenium on mortality need further study. Likewise, folate levels were not associated with reduced breast cancer risk in a recent meta-analysis. Several studies have shown that a high proportion of women at-risk for breast cancer or affected by the disease have deficient vitamin D levels, i.e., 250H-

Economic Impact of Inter-Regional Health Mobility In The Oldest European Administrative Region: A Starting Point For Changing Organizational Model?

Objectives: The aim of this study is to evaluate the inter-regional mobility expenditures, with particular reference to oncology, in Liguria Region. Study design: A descriptive analysis of inter-regional mobility expenditures from 2008 to 2015 was carried out. Methods: The analysis involved a detailed assessment of global balance of interregional health mobility by means the DRGs; the flow of specialist outpatient and pharmaceutical was also used. Results: Since 2008 until 2012 an increase of negative balance of global healthcare expenditure in Liguria Region was observed [34.7 \u20ac mill (2008) and 62.3 \u20ac mill (2012)]; subsequently a quite stable trend was recorded between 2012 and 2015 [ranging between 59.8 \u20ac mill (2013) and 63.2 \u20ac mill (2014)]. The passive mobility was 15.1% on the total spending for hospital acute care in 2012 and a similar value was detected in 2015 (15.2%). The higher costs for passive mobility were attributable to the surgical DRGs (69.4% in 2012 and 69.8% in 2015) with a double estimate of the expenditure in comparison with medical ones (2012: 99.4 \u20ac mill vs 43.8 \u20ac mill, \u394= 55.6 \u20ac mill; 2015: 96.6 \u20ac mill vs 41.9 \u20ac mill, \u394= 54.7 \u20ac mill). The highest cost sources in the process of passive mobility are the surgical areas, particularly the surgical hospitalizations for orthopaedic and cardiologic interventions. The spending analysis for oncologic DRG, divided into surgical and medical for passive and active mobility, showed that the surgical DRG determined a negative balance of 3.8 \u20ac mill in 2012 and 4.3 \u20ac mill in 2015, while the medical DRG showed a positive balance of 0.5 \u20ac mill in 2012 and 0.7 \u20ac mill in 2015. Conclusions: Our evaluation highlights that the inter-regional mobility for hospital acute care is the most relevant issue for the economic regional balance and reveals an important flow of patients moving from Liguria Region to neighbouring regions. As the equity of access and distribution of the supply of care remains a priority of Regional Health System, the active mobility in oncologic field could be a marker of quality health planning

Case report: Variable response to immunotherapy in ovarian cancer: Our experience within the current state of the art

: Despite recent advances in ovarian cancer (OC) treatment, including the introduction of bevacizumab and PARP-inhibitors, OC remains a lethal disease. Other therapeutic options are being explored, such as immunotherapy (IT), which has been proved effective in many solid tumors. Findings about tumor-infiltrating cytotoxic and regulatory T cells, together with the expression of PD-1 on immune cells and of PD-L1 on tumor cells, gave the rationale for an attempt to the use of IT also in OC. We treated two patients with avelumab, an anti-PD-L1 monoclonal antibody, after the first line of chemotherapy: Patient A underwent 19 cycles of maintenance therapy with avelumab with a disease-free interval of 12 months, whereas patient B showed a slight progression of disease after only eight cycles. A higher PD-L1 expression in tumor cells of patient A was detected. She also underwent a genomic assessment that described the presence of a high Tumor Mutational Burden (TMB) and a status of Loss of Heterozygosity (LoH). This different response to the same treatment puts in evidence that some genomic and immune features might be investigated

Hormonal Therapy and Chemoprevention.

Hormone replacement therapy (HRT) can increase the quality as well as the length of life, but a prolonged use can also increase the risk of breast cancer. The combination of HRT and a selective estrogen receptor modulator (SERM) such as tamoxifen may retain the benefits while reducing the risks of either agent. A post hoc analysis of the Italian Tamoxifen Prevention Study showed a borderline significant reduction of breast cancer among women who were on HRT continuously and tamoxifen as compared with continuous HRT users who received placebo. Recent studies suggest that the standard dose of tamoxifen may be reduced to one-quarter (i.e., 10 mg every other day) without loss of its beneficial biological effects. Since the endometrial effect of tamoxifen seems to be both dose and time dependent, a dose reduction could substantially reduce the risk of endometrial cancer while retaining its preventive efficacy. On the other hand, the addition of HRT containing progestins could also minimize the risk of endometrial cancer associated with tamoxifen. Moreover, estrogen should reduce the incidence of vasomotor and urogenital symptoms, which are a major reason for tamoxifen withdrawal in prevention studies. Notably, in the National Surgical Adjuvant Breast Project (NSABP) P-1 trial, women ages 50 or younger had no increased incidence of adverse events, including endometrial cancer and venous thromboembolic events. One possible explanation for the lack of toxicity in premenopause is the presence of adequate circulating estrogen levels which prevent tamoxifen to act as an estrogen agonist at these target tissues. Moreover, data from the current Italian tamoxifen prevention trial indicate that the compliance was substantially higher for de novo and current HRT users as compared to women who never received HRT during the study. The combination of HRT and tamoxifen at low doses could thus reduce the risks and side effects while retaining the benefits of either agent

Prognostic significance of VEGF after twenty-year follow-up in a randomized trial of fenretinide in non-muscle-invasive bladder cancer

Non-muscle-invasive bladder cancer (NMIBC) may progress to muscle-invasive disease, but no effective preventive treatments are available. In addition, no reliable prognostic biomarkers have been identified. We assessed the long-term effect of the oral retinoid fenretinide and the prognostic value of circulating VEGF levels. We updated through the Tumor Registry the vital status of 99 patients with resected Ta/T1 bladder tumors who were recruited in a randomized trial of 2 years of fenretinide or no treatment in 1993-1994. Serum VEGF levels measured at baseline and 12 months were available in a subgroup of 62 patients. After a median of 20.5 years, 54 subjects died, 35 of any cancer and 14 of bladder cancer. Neither overall survival (OS), nor cancer survival (CS) or bladder cancer survival (BCS) was affected by fenretinide (log-rank P 65 0.2). DNA aneuploidy in bladder washing was associated with shorter OS (P =0.02), CS (P =0.05), and BCS (P = 0.09). Subjects with baseline VEGF levels in the top quintile ( 65350 pg/mL) had a significantly shorter OS (P =0.01), CS (P = 0.02), and BCS (P= 0.008). The trend across quintiles of VEGF was significant for BCS (P =0.007). Multivariate analyses showed that, in addition to smoking status, VEGF level in the top quintile was an independent prognostic factor for OS (HR =2.7; 95% CI, 1.1-6.5), CS (HR = 3.3; 95% CI, 1.1-9.4) and BCS (HR =8.9; 95% CI,1.3-61). Fenretinide did not affect the long-term outcome of patients with NMIBC. High serum VEGF level was a significant predictor of overall and cancer death and may help to identify high-risk subjects who may benefit from a preventive therapy. Cancer Prev Res; 9(6); 437-44

Adherence to Guidelines among Italian Urologists on Imaging Preoperative Staging of Low-Risk Prostate Cancer: Results from the MIRROR (Multicenter Italian Report on Radical Prostatectomy Outcomes and Research) Study

Objective. A number of evidence-based guidelines for diagnosis and management of prostate cancer have been published. The aim of this study is to evaluate the adherence of Italian urologists to the guidelines concerning the preoperative imaging staging of prostate cancer. Methods. In October 2007 a multicentric observational perspective study called Multicentric Italian Report on Radical prostatectomy Outcome and Research (MIRROR) was started in 135 Italian urology centers. Recruitment was closed in December 2008 and 2,408 cases were collected. In this paper we have taken into consideration all examinations carried out for preoperative imaging staging, evaluating compliance with the recommendations in the American Urological Association (AUA) and European Association of Urology (EAU) guidelines. Results. Five hundred sixty-seven (53.34%) patients were not managed according to the EAU guidelines concerning T-staging, 545 (51.27%) concerning N-staging and 757 (71.21%) concerning M-staging. According to AUA guidelines, we also analyzed patients with a Gleason grade of biopsy specimens of 7: 238 (57.35%) of these patients had undergone testing for T staging, 244 (57.35%) for N-staging and 322 (77.60%) for M-staging. Conclusions. The compliance of Italian urologists with the guidelines is low, leading to an inappropriate increase in cost of care and unnecessary anxiety for the patients

Comparisons between glucose analogue 2-deoxy-2-((18)F)fluoro-D-glucose and (18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

To compare 2-deoxy-2-((18)F)fluoro-D-glucose((18)F-FDG) and (18)F-sodium ((18)F-NaF) positron emission tomography/computed tomography (PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases