Purpose: The oligometastatic state is a proposed entity between localized cancer and widely metastatic disease, comprising an intermediate subset of metastatic cancer patients. Most data to support locally-directed treatment, such as stereotactic ablative radiotherapy (SABR), for oligometastases are from retrospective institutional reports. Following the success of a recently completed and reported phase II trial demonstrating important clinical outcomes, herein we review the current landscape of ongoing clinical trials in this context. Materials and methods: A review of currently activated and registered clinical trials was performed using the clinicaltrials.gov database from inception to February 2019. A search of actively recruiting trials, using the key words oligometastases, SABR, and various related terms was performed. Search results were independently reviewed by two investigators, with discrepancies settled by a third. Data abstracted from identified studies included study type, primary disease site, oncologic endpoints, and inclusion/exclusion criteria. Results: Of the initial 216 entries identified, 64 met our review eligibility criteria after full-text review. The most common study type was a phase II clinical trial ( n = 35, 55%) with other study designs ranging from observational registry trials to phase III randomized controlled trials (RCTs). A minority of trials were randomized in design ( n = 17, 27%). While most studies allowed for metastases from multiple primary disease sites ( n = 22, 34%), the most common was prostate ( n = 13, 15%), followed by breast, gastrointestinal, non-small cell lung cancer (NSCLC), and renal ( n = 6, 9% each). In studies with a solitary target site, the most common was liver ( n = 6, 9%) followed by lung ( n = 3, 5%). The most common primary endpoints were progression-free survival (PFS) ( n = 20, 31%) and toxicity ( n = 10, 16%). A combined strategy of systemic therapy and SABR was an emerging theme ( n = 23, 36%), with more recent studies specifically evaluating SABR and immunotherapy ( n = 9, 14%). Conclusion: The safety and efficacy of SABR as oligometastasis-directed treatment is increasingly being evaluated within prospective clinical trials. These data are awaited to compliment the abundance of existing observational studies and to guide clinical decision-making.
Artificial intelligence (AI)-based models have become a growing area of interest in predictive medicine and have the potential to aid physician decision-making to improve patient outcomes. Imaging and radiomics play an increasingly important role in these models. This review summarizes recent developments in the field of radiomics for AI in head and neck cancer. Prediction models for oncologic outcomes, treatment toxicity, and pathological findings have all been created. Exploratory studies are promising; however, validation studies that demonstrate consistency, reproducibility, and prognostic impact remain uncommon. Prospective clinical trials with standardized procedures are required for clinical translation.
SummaryTo obtain host iron, Staphylococcus aureus secretes siderophores staphyloferrin A (SA) or staphyloferrin B (SB), and accesses heme iron through use of ironregulated surface determinant proteins. While iron transport in S. aureus is well documented, there is scant information about proteins required to access iron from complexes in the cytoplasm. In vitro studies identified a pyridine nucleotide-disulfide oxidoreductase, named IruO, as an electron donor for the heme monooxygenases IsdG and IsdI, promoting heme degradation. Here, we show that an iruO mutant was not debilitated for growth on heme, suggesting involvement of another reductase. NtrA is an ironregulated nitroreductase and, as with the iruO mutant, a ntrA mutant grew on heme comparable with wild type (WT). In contrast, a iruO ntrA double mutant was severely debilitated for growth on heme, a phenotype that was complemented by expression of either iruO or ntrA in trans, demonstrating their overlapping role in heme-iron utilization. Contrasting the involvement of multiple reductases for heme iron utilization, ntrA was shown essential for iron utilization using SA, although not SB or other siderophores tested, and an iruO mutant was incapable of deferoxamine-mediated growth. Accordingly, virulence of WT S. aureus, but not an iruO mutant, was enhanced in mice receiving deferoxamine.
A single center, long-term experience documented by a prospectively maintained database shows that cryoablation is a viable salvage option for radio-recurrent prostate cancer as it provides durable biochemical disease-free survival with acceptable morbidity.
Background Cigarette smoking is carcinogenic and has been linked to inferior treatment outcomes and complication rates in cancer patients. Here, we report the results of an 18-month pilot smoking cessation program that provided free nicotine replacement therapy (nrt).Methods In January 2017, the smoking cessation program at our institution began offering free nrt for actively cigarette-smoking patients with cancer. The cost of 4 weeks of nrt was covered by the program, and follow-up was provided by smoking cessation champions.Results From January 2017 to June 2018, 8095 patients with cancer were screened for cigarette use, of whom 1135 self-identified as current or recent smokers. Of those 1135 patients, 117 enrolled in the program and accepted a prescription for nrt. The rates of patient referral and patients attending a referral appointment were significantly higher in 2018–2018 than they had been in 2015–2016 (100% vs. 80.3%, p < 0.001, and 27.6% vs. 11.3%, p < 0.001, respectively). Median follow-up was 9.0 months (25%–75% interquartile range: 5.7–11.6 months). Of the patients who accepted nrt and who also had complete data (n = 71), 25 (35.2%) reported complete smoking cessation, and 32 (45.1%) reported only decreased cigarette smoking. On univariable analysis, no factors were significantly predictive of smoking cessation, although initial cigarette use (>10 vs. ≤10 initial cigarettes) was significantly predictive of smoking reduction (odds ratio: 5.04; 95% confidence interval: 1.46 to 17.45; p = 0.011).Conclusions This pilot study of free nrt demonstrated rates of referral and acceptance of nrt that were improved compared with historical rates, and most referred patients either decreased their use of cigarettes or quit entirely.
Background Patients with high-risk prostate cancer are at increased risk of lymph node metastasis and are thought to benefit from whole pelvis radiotherapy (WPRT). There has been recent interest in the use of hypofractionated radiotherapy in treating prostate cancer. However, toxicity and cancer outcomes associated with hypofractionated WPRT are unclear at this time. This phase II study aims to investigate the impact in quality of life associated with hypofractionated WPRT compared to conventionally fractionated WPRT. Methods Fifty-eight patients with unfavourable intermediate-, high- or very high-risk prostate cancer will be randomized in a 1:1 ratio between high-dose-rate brachytherapy (HDR-BT) + conventionally fractionated (45 Gy in 25 fractions) WPRT vs. HDR-BT + hypofractionated (25 Gy in 5 fractions) WPRT. Randomization will be performed with a permuted block design without stratification. The primary endpoint is late bowel toxicity and the secondary endpoints include acute and late urinary and sexual toxicity, acute bowel toxicity, biochemical failure-, androgen deprivation therapy-, metastasis- and prostate cancer-free survival of the hypofractionated arm compared to the conventionally fractionated arm. Discussion To our knowledge, this is the first study to compare hypofractionated WPRT to conventionally fractionated WPRT with HDR-BT boost. Hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if demonstrated to be well-tolerated and effective. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04197141 on December 12, 2019.
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