A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer

ContextMolecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.ObjectiveTo perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC).Evidence acquisitionThe review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446–52) and American Urology Association (AUA) criteria.Evidence synthesisIn total, 42 studies and 30 407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n = 12 141), prospective registries (n = 17 053), and prospective and post hoc randomized trial analyses (n = 1213). In 32 studies (n = 12 600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n = 8543). GC use changed the management in active surveillance (number needed to test [NNT] = 9) and postprostatectomy (NNT = 1.5–4) settings in five studies (n = 4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state.ConclusionsConsistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making.Patient summaryIn this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.     

Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance)

Annals of Surgical Oncology - De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete...     

Clinical utility of the AJCC 8th edition pT1 subclassification and impact on practice patterns in stage I seminoma

BackgroundThe American Joint Committee on Cancer 8^th edition staging guidelines for testicular cancer established a 3 cm cutoff to subclassify stage T1 seminomas (<3 cm = pT1a and ≥3 cm = pT1b). The efficacy of this cutoff in predicting metastatic disease and impact on treatment patterns have not been studied.MethodsWe retrospectively reviewed patients with pT1 testicular seminoma in the National Cancer Database from 2004 to 2016. Receiver operating curves were used to determine the efficacy of the 3 cm tumor cutoff in identifying metastatic disease, and multivariable regression was used to compute the effect of tumor size on the rate of adjuvant therapy among Stage I patients.ResultsA total of 10,134 patients with pT1 seminoma were evaluated. The current size cutoff of 3 cm for subclassification did not exhibit high discrimination in identifying metastatic disease (area under receiver operating curve: 0.546). Surveillance has grown as the preferred treatment after orchiectomy ?32.1% in 2004 to 81.2% in 2015. However, the rate of adjuvant therapy for pT1, Stage I seminomas associated positively with tumor size even with adjustment for year of diagnosis. For tumors above 3 cm, the odds ratio stabilized around 1.9. By using the 3 cm cutoff to guide adjuvant therapy, up to 85% of T1b patients may be overtreated.ConclusionThe 3 cm cutoff for subclassification of Stage I seminoma does not predict metastatic recurrence but is associated with increased receipt of adjuvant therapy. A 3 cm cutoff and the pT1a/b classification may therefore contribute to overtreatment in many young patients with a long life expectancy for whom minimizing adverse effects should be prioritized.     

Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal.

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.     

Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.     

Epidemiology of chronic suppurative otitis media and deafness in a rural area and developing an intervention strategy

Of 613 children evaluated in a village in Haryana 94 (15.3%) were observed to have chronic suppurative otitis media (CSOM). Fifty eight (61.7%) children had hearing impairment. CSOM contributed to 71.6% of the hearing impaired (58/81). On analysis of association of CSOM with literacy and socio-economic status of mothers, and age, sex, and upper respiratory tract infections (URI) in children positive correlation was observed only with URIs (P<0.001). Literacy and socio-economic status of the mothers did not correlate significantly with knowledge about treatment seeking, and ear cleaning practices, probably due to the narrow range of incomes and literacy levels. An intervention program consisting of play, demonstrations, health charts and slogans, and aural cleaning and antibiotic drops was introduced.     

Carcinoma of the maxillary antrum — A 10 year experience

A retrospective analysis was performed of 250 cases of carcinoma of the maxillary antrum seen over a 10 years period (1975–1984). 98.24% patients were seen in T3 and T4 stages (UICC 1985). 40.7% patients presented with clinically palpable nodes. 42.9% patients were treated by radical radiation and 18.6% by a combination of preoperative radiation followed by surgery. Rest 38.5% patients were treated with palliative intention. Three year disease free survival was 39.58% with radiation alone and 51.91% with combined modality treatment which includes patients salvaged by surgery. Failures were mainly at the local site, 75.86% with radiation alone and 60% with combined modality treatment. Combined modality treatment, preferably preoperative radiation followed by radical surgery, gives the best results in the management of carcinoma of the maxillary antrum.     

Anatomic Location of the Tongue Base Neurovascular Bundle

Knowledge of the location of the hypoglossal/lingual artery neurovascular bundle (HLNVB) is essential in performing tongue base resections for neoplasm and for obstructive sleep apnea. Transoral and transcervical resections of the tongue base may be performed with greater exposure and certainty when the relationship of the HLNVB to local landmarks is understood; knowledge of the HLNVB allows resection of a larger amount of contralateral tongue base during partial glossectomy without violating the contralateral remnant tongue's blood supply. Ten cadaver heads were dissected to determine the position of the HLNVB with respect to soft tissue and bony landmarks at the tongue base. Our results indicate the position of the tongue base HLNVB is significantly inferior and lateral, that is, 2.7 cm inferior and 1.6 cm lateral to the foramen cecum, 0.9 cm superior to the hyoid bone, and 2.2 cm medial to the mandible. This inferolateral location allows the potential for aggressive tongue base resection without neurovascular compromise.