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Given the abundance of new research, it can be challenging to stay current on the latest advancements and findings. Oncology Times is here to help with summaries of the newest studies to ensure you are up-to-date on the latest innovations in oncology practice.


Cost-effectiveness of MR imaging-guided strategies for detection of prostate cancer in biopsy-naive men


A diagnostic MRI followed by one of three MRI-guided biopsy strategies is a cost-effective method to detect prostate cancer, according to new data (Radiology 2017; doi:10.1148/radiol.2017162181). Researchers created a decision-analysis model for biopsy-naive men (age groups: 41-50 years, 51-60 years, and 61-70 years). Researchers compared MR-guided approaches to the current standard of transrectal ultrasound-guided biopsies. Net health benefit was the primary outcome measure and was determined by "quality-adjusted life years (QALYs) gained or lost by investing resources in a new strategy compared with a standard strategy at a willingness-to-pay threshold of $50,000 per QALY gained." The researchers found using MRI to help detect lesions and guide biopsies increased standardized quality-adjusted life years for patients and was cost-effective in 94.05 percent of simulations. Researchers reported that the benefits were consistent across age groups and could potentially change how doctors identify and sample cancer lesions. Study authors concluded that, "MR imaging-guided strategies for the detection of prostate cancer were cost-effective compared with the standard biopsy strategy in a decision-analysis model."


CDK4/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin E negative cancers


Treating patients with estrogen-positive breast cancer (ER+) poses two challenges: the inability to predict who will respond to standard therapies and adverse events leading to therapy discontinuation. A recent study revealed how the biomarkers retinoblastoma protein (Rb) and cytoplasmic cyclin E could indicate which patients will respond best to current first-line therapies (Nat Commun 2017; doi:10.1038/ncomms15916). Researchers also found that combining the current therapy with autophagy inhibitors will result in using one-fifth of the dosage of the standard treatment, which could significantly reduce associated side effects. Data collected through The Cancer Genome Atlas uncovered alterations in the CDK4/6/cyclin D pathway in approximately 35 percent of the patients, making them an ideal population for targeting CDK4/6. "This study addresses the current limitations of CDK4/6 inhibitor treatment and proposes a biomarker-driven clinical trial that evaluates the ability of autophagy inhibitors to improve the selectivity and efficacy of CDK4/6 inhibitors in clinic," investigators concluded.


Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase I-II study


The drug gilteritinib shows promise in its ability to target the Fms-like tyrosine kinase 3 (FLT3) gene mutation of acute myeloid leukemia (AML), according to new research (Lancet Oncol 2017; doi:10.1016/S1470-2045(17)30416-3). In this first-in-human study, AML patients who were refractory to induction therapy or had relapsed after achieving remission with previous treatment received the FLT3 inhibitor and researchers found that the drug was well-tolerated. Primary endpoints included safety, tolerability, and pharmacokinetics of gilteritinib. Study participants were assigned to one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). FLT3 mutation (FLT3mut+) was not an inclusion criteria, however, researchers required 10 or more patients with locally confirmed FLT3mut+ to be included at each dose level of the expansion cohorts. Investigators found that gilteritinib was well-tolerated and determined the maximum tolerated dose is 300 mg/day. This was established after two of three patients in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhea and grade 3 elevated aspartate aminotransferase). "These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase III trials," researchers concluded.


A pilot study of stereotactic body radiation therapy combined with cytoreductive nephrectomy for metastatic renal cell carcinoma


A new study suggests that nephrectomy can be effectively paired with stereotactic body radiation therapy (SBRT) for patients with advanced kidney cancer (Clin Can Res 2017; doi:10.1158/1078-0432.CCR-16-2946). In a single-arm feasibility study, 14 patients with metastatic renal cell carcinoma (mRCC) were treated with 15 Gray (Gy) SBRT followed 4 weeks later by cytoreductive nephrectomy. The objective of this study was to assess the safety and feasibility of this approach, as well as analyze the immunological impact of high-dose radiation. Patients' tumors were monitored for expression of immunomodulatory molecules and tumor-associated antigens. Nephrectomy paired with high-dose stereotactic radiation is a feasible, well-tolerated treatment option, according to researchers. They also found that tumors treated with SBRT had increased expression of the immunomodulatory molecule calreticulin as well as the tumor-associated antigens CA9, 5T4, NY-ESO-1, and MUC-1.


Secondhand smoke exposure among community-dwelling adult cancer survivors in the United States: 1999-2012


Recently published data revealed that secondhand smoke exposure among nonsmoking adult cancer survivors has declined (Cancer Epidemiol Biomarkers Prev 2017; doi:10.1158/1055-9965.EPI-16-0777). Investigators used interview and serum cotinine data for 686 nonsmoking adults with a history of cancer from 7 consecutive cycles of the National Health and Nutrition Examination Survey. The study defined exposure to secondhand smoke as a serum cotinine level between 0.05 ng/mL and 10 ng/mL. Among study participants, 28.26 percent (95% CI: 24.97%-31.55%) had been exposed to secondhand smoke. From 1999-2000 and 2011-2012, exposure to secondhand smoke among nonsmoking adult cancer survivors declined from 39.61 percent (95% CI: 27.88%-51.34%) to 15.68 percent (95% CI: 9.38%-21.98%). According to study data, rates of exposure were higher among those with a history of a smoking-related cancer and those living below the federal poverty level compared with those with other types of cancer and those with the highest incomes. "Fortunately, secondhand smoke exposure among nonsmoking cancer survivors in the U.S. is on the decline, although certain subgroups remain disproportionately burdened," authors concluded. "These findings highlight clinical and public health imperatives to target socioeconomically disadvantaged nonsmoking cancer survivors to reduce their secondhand smoke exposure.


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