A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer

BackgroundIn vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.MethodsFrom 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate.ResultsOf 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24–18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84–5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8–258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1–4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced.ConclusionsThe addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy.Trial RegistrationClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00745134","term_id":"NCT00745134"}}NCT00745134.     

肿瘤学实践技能改善活动:提高肿瘤学医师的诊疗水平

美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)是全球领先的肿瘤专业学术组织,学会宗旨是预防癌症及改善癌症诊疗服务.肿瘤学实践技能改善活动(Quality Oncology Practice Initiative,QOPI)始于2002年,是在ASCO健康服务委员会的指导下,以临床实践为基础的医疗质量改善活动,其目标是帮助肿瘤科医师通过自我检查和改善,促进其诊疗水平的提高.     

Evaluation of Targeted Next-Generation Sequencing for the Management of Patients Diagnosed with a Cancer of Unknown Primary

BackgroundCancer of unknown primary (CUP) comprises a heterogeneous collection of malignancies that are typically associated with a poor prognosis and a lack of effective treatment options. We retrospectively evaluated the clinical utility of targeted next-generation sequencing (NGS) among CUP patients to assist with diagnosis and identify opportunities for molecularly guided therapy.Patients and MethodsPatients with a CUP at Moffitt Cancer Center who underwent NGS between January 1, 2014 and December 31, 2019, were eligible for study inclusion. Next-generation sequencing results were assessed to determine the frequency of clinically actionable molecular alterations, and chart reviews were performed to ascertain the number of patients receiving molecularly guided therapy.ResultsNinety-five CUP patients were identified for analysis. Next-generation sequencing testing identified options for molecularly guided therapy for 55% (n = 52) of patients. Among patients with molecularly guided therapy options, 33% (n = 17) were prescribed a molecularly guided therapy. The median overall survival for those receiving molecularly guided therapy was 23.6 months. Among the evaluable patients, the median duration of treatment for CUP patients (n = 7) receiving molecular-guided therapy as a first-line therapy was 39 weeks. The median duration of treatment for CUP patients (n = 8) treated with molecularly guided therapy in the second- or later-line setting was 13 weeks. Next-generation sequencing results were found to be suggestive of a likely primary tumor type for 15% (n = 14) of patients.ConclusionNext-generation sequencing results enabled the identification of treatment options in a majority of patients and assisted with the identification of a likely primary tumor type in a clinically meaningful subset of patients.     

Home parenteral nutrition: does affiliation with a national support and educational organization improve patient outcomes?

BACKGROUND: For patients receiving home parenteral nutrition (HPN), catheter-related bloodstream infection (CRBSI) and reactive depression may significantly impact quality-of-life. This study evaluated the influence of patient affiliation with a national organization promoting HPN education and peer support on these outcome variables. METHODS: Using a case-control design, we compared 2 groups of affiliated patients with nonaffiliated controls, who were matched for diagnosis, HPN duration, sex, and age. Group 1 data were obtained from patients in large HPN medical practice programs. Group 2 data were obtained from patients in small medical practices with a small number of HPN patients. All participants were evaluated by structured interviews every 6 months over 18 months. RESULTS: In both data collection groups, affiliated patients (A) had significantly higher (mean +/- SD) quality-of-life scores compared with nonaffiliated patients (NA): (Gr 1: A, 19.8 +/- 4.7 versus NA, 17.6 +/- 5.6, p = .05; Gr 2: A, 20.4 +/- 5.2 versus NA, 17.3 +/- 4.8, p = .05). Affiliated patients also had lower depression scores (Gr 1: A, 10.9 +/- 10.4 versus NA, 20.4 +/- 13.6, p = .01; Gr 2: A, 12.5 +/- 9.6 versus NA, 18.5 +/- 10.8, p = .03) and a lower incidence of catheter-related infections (Gr 1: A, 0.10 +/- 0.3 versus NA, 0.60 +/- 0.55, p = .01; Gr 2: A, 0.27 +/- 0.55 versus NA, 0.71 +/- 0.64, p = .02) than nonaffiliated patients. CONCLUSIONS: Affiliation with an organization that provides ongoing HPN education and peer support was associated with significantly better HPN outcomes. Alternative explanations are discussed in relation to limitations of the case-control design.     

Comparison of thyrotropin-releasing hormone with melanocyte-stimulating-hormone-release-inhibiting factor as pentobarbital antagonists in monkeys

Thyrotropin-releasing hormone (TRH), 0.1 mg/kg, i.m., significantly counteracted pentobarbital narcosis in six monkeys, but melanocyte-stimulating-hormone-release-inhibiting factor (MIF), 0.1 mg/kg i.m., did not. Earlier dose-response studies in unanesthetized monkeys had shown that this dose of MIF stimulated motor activity; this dose of TRH had shown no stimulant effect, but a higher dose depressed activity. Thus, an MIF dose that stimulates unanesthetized monkeys does not reverse pentobarbital narcosis; a TRH dose that by itself is neither stimulant nor depressant does partially reverse pentobarbital narcosis.     

Valganciclovir as preemptive therapy for cytomegalovirus in cytomegalovirus-seronegative liver transplant recipients of cytomegalovirus-seropositive donor allografts.

The efficacy of valganciclovir as preemptive therapy for the prevention of cytomegalovirus (CMV) disease and its impact on indirect sequelae of CMV were assessed in recipient-negative/donor-positive (R-/D+) liver transplant recipients. Of 187 consecutive liver transplant recipients at our institution since July 2001, 36 (19.2%) belonged to the R-/D+ group. Surveillance tests for CMV were performed on all patients at weeks 2, 4, 6, 8, 10,12, and 16. In all, 27 patients with asymptomatic viremia received preemptive therapy with valganciclovir. At a total follow-up of 62.8 patient years (median: 19 months, range: 3 months to 5.6 years), no episodes of CMV disease were documented in these patients. The incidence of rejection, retransplantation, and bacterial or fungal infections and the probability of survival did not differ for R-/D+ patients and all non-R-/D+ patients treated preemptively with valganciclovir (P > 0.20 for all variables). Thus, preemptive therapy with valganciclovir in R-/D+ patients was not associated with CMV disease during the period of surveillance monitoring or at anytime thereafter (late-onset CMV disease). The indirect outcomes with the use of valganciclovir in R-/D+ patients were comparable to the outcomes of other subgroups of liver transplant recipients receiving preemptive therapy.     

The After Breast Cancer Pooling Project: rationale, methodology, and breast cancer survivor characteristics

The After Breast Cancer Pooling Project was established to examine the role of physical activity, adiposity, dietary factors, supplement use, and quality of life (QOL) in breast cancer prognosis. This paper presents pooled and harmonized data on post-diagnosis lifestyle factors, clinical prognostic factors, and breast cancer outcomes from four prospective cohorts of breast cancer survivors (three US-based and one from Shanghai, China) for 18,314 invasive breast cancer cases diagnosed between 1976 and 2006. Most participants were diagnosed with stage I-II breast cancer (84.7%). About 60% of breast tumors were estrogen receptor (ER)+/progesterone receptor (PR)+; 21% were ER-/PR-. Among 8,118 participants with information on HER-2 tumor status, 74.8% were HER-2- and 18.5% were HER-2+. At 1-2 years post-diagnosis (on average), 17.9% of participants were obese (BMI ≥ 30 kg/m2), 32.6% were overweight (BMI 25-29 kg/m2), and 59.9% met the 2008 Physical Activity Guidelines for Americans (≥ 2.5 h per week of moderate activity). During follow-up (mean = 8.4 years), 3,736 deaths (2,614 from breast cancer) and 3,564 recurrences have been documented. After accounting for differences in year of diagnosis and timing of post-diagnosis enrollment, five-year overall survival estimates were similar across cohorts. This pooling project of 18,000 breast cancer survivors enables the evaluation of associations of post-diagnosis lifestyle factors, QOL, and breast cancer outcomes with an adequate sample size for investigation of heterogeneity by hormone receptor status and other clinical predictors. The project sets the stage for international collaborations for the investigation of modifiable predictors for breast cancer outcomes.