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Background The clinical impact of addressing potential germline alterations from tumor-only next-generation sequencing (NGS) is not well characterized. Current guidelines for cancer genetic testing may miss clinically actionable germline changes, which may have important implications for cancer screening, treatment, and prevention. We examined whether increasing involvement of the clinical genetics service during somatic tumor-only NGS review at Molecular Tumor Board (MTB) increases the detection of germline findings. Methods In a retrospective evaluation of patients who underwent tumor-only NGS and were reviewed at MTB, we quantified genetic counseling (GC) referrals as well as germline testing uptake and results across three cohorts: before (C1) and after (C2) the addition of tumor-only NGS review and after (C3) instituting a formal process to coordinate NGS-based genetics referrals to preexisting oncology appointments. All statistical tests were two-sided. Results From 2013 to 2017, 907 tumor-only NGS reports were reviewed at MTB (nC1 = 281, nC2 = 493, nC3 = 133); gastrointestinal (22.5%), lung (19.7%), genitourinary (14.8%), and breast (14.1%) were the most common index cancers. GC visits due to MTB increased with each successive cohort (C1 = 1.1%, C2 = 6.9%, C3 = 13.5%; P for trend [ P trend] <.001), as did germline testing (C1 = 0.7%, C2 = 3.2%, C3 = 11.3%; P trend <.001). Diagnosis of germline pathogenic variants increased with each successive cohort (C1 = 1.4%, C2 = 2.0%, C3 = 7.5%; P trend =.003) and with germline pathogenic variants found by MTB review (C1 = 0.4%, C2 = 0.4%, C3 = 2.3%; P trend =.12). Conclusions Both review of tumor-only NGS by genetics and the institution of a process coordinating GC with oncology appointments increased the discovery of germline pathogenic variants from tumor-only NGS testing. Furthermore, this process identified germline pathogenic variant carriers who would not have otherwise met standard criteria for germline testing. [ABSTRACT FROM AUTHOR]

Background Exposure to ionizing radiation has been linked to myelodysplastic syndromes (MDS); it is not clear whether therapeutic radiation doses used for prostate cancer pose an increased MDS risk. Methods We performed a retrospective cohort study of prostate cancer patients diagnosed between 1986 and 2011 at Cleveland Clinic, comparing those who underwent definitive treatment with radical prostatectomy (RP) to radio-therapy either external beam radiotherapy (EBRT) or prostate interstitial brachytherapy (PI) and to population- based registries. Competing risk regression analyses were used to determine the cumulative risk of developing MDS. All statistical tests were two-sided. Results Of 10924 patients, 5119 (47%) received radiation (n = 2183 [43%] in EBRT group and n = 2936 [57%] in PI group) and 5805 (53%) were treated with RR Overall, 31 cases of MDS were observed, with age-adjusted incidence rates no higher than in population-based registries. In univariate analyses, advancing age (hazard ratio [HR] = 1.14; 95% confidence interval [CI] -- 1.09 to 1.20; P< .001) and radiotherapy exposure (HR = 3.44; 95% CI = 1.41 to 8.37; P= .007) were statistically significantly associated with development of MDS. In multivariable analyses, although advanced age (HR = 1.13; 95% CI= 1.06 to 1.19; P< .001) remained statistically associated with MDS, radiation did not, although a small non-statistically significant trend existed for PI-treated patients. MDS rates were no higher than in population-based registries. Conclusions With relatively short follow-up, prostate cancer patients definitively treated with radiation did not appear to have a statistically increased risk of subsequent MDS. [ABSTRACT FROM AUTHOR]

Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy. [ABSTRACT FROM AUTHOR]

The American Association of Blood Banks requires routine culture of hematopoietic progenitor cells prior to bone marrow transplantation. We sought to evaluate the cost of that requirement and the incidence and clinical significance of positive cultures. We performed a retrospective analysis of transplant recipients at our institution. Of the 605 patients for whom 1,934 consecutive cultures of harvests were done between December 1992 and February 1996, 11 had positive cultures. Six patients received a culture-positive harvest with no adverse effects. The total cost of cultures was $35,660 (U.S. $). In North America and worldwide in 1995, routine culture of harvests would have prevented 7.9 and 18.9 cases of bacteremia, respectively, at a cost of $95,000 per bacteremia prevented. We conclude that routine culture of hematopoietic progenitor cells yields low rates of positivity and that infusion of contaminated harvests rarely results in clinically adverse outcomes. [ABSTRACT FROM PUBLISHER]