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Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献3.
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Shane S. Bush NAN Policy Planning Committee 《Archives of clinical neuropsychology》2005,20(8):997-1007
Independent forensic neuropsychological examinations are performed by neuropsychologists who are hired as independent contractors by third parties to make determinations regarding neuropsychological functioning. The responsibilities of neuropsychologists when performing independent or court-ordered forensic examinations differ from those of clinical examinations. Because neuropsychological training typically occurs in clinical contexts, the transition to forensic contexts may result in uncertainty about how to negotiate the unique responsibilities of the forensic examiner role. Neuropsychologists are responsible for maintaining the highest standards of professional practice when performing independent and court-ordered forensic examinations. To reach and maintain the highest standards of practice, neuropsychologists must understand the unique relationships with retaining parties and examinees and strive to maintain true independence and objectivity. Although a true neuropsychologist-patient relationship is not considered to exist within the context of a forensic neuropsychological evaluation, neuropsychologists have ethical responsibilities to both the retaining party and the examinee. 相似文献
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Azra M. Sehic Lillian W. Gaber Shane Roy III Paula M. Miller Stephen B. Kritchevsky Robert J. Wyatt 《Pediatric nephrology (Berlin, Germany)》1997,11(4):435-437
Based upon the percentage of cases of IgA nephropathy (IgAN) in biopsy series, a lower prevalence has been assumed for African-Americans
compared with Americans of European descent. This may be due to a racial difference in the basic underlying pathology of IgAN
or to racial differences in patterns of referral and biopsy selection practices. Over the past decade (1985 – 1994), we have
found similar incidences of IgAN in Caucasian and African-American children from Shelby County, Tennessee. The incidence was
3.0 cases per million per year for Caucasian and 5.7 cases per million per year for African-American children. IgAN may be
more common in African-American children than previously appreciated. Population-based incidence studies will be necessary
to determine whether or not our experience has become a more widespread phenomenon.
Received August 21, 1996; received in revised form and accepted December 18, 1996 相似文献