We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy.
The ...present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis.
The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio HR, 0.598; 95% confidence interval CI, 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR AHR, 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM.
Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.
Given the concern for cardiopulmonary toxicity in patients with NSCLC undergoing postoperative radiation therapy (PORT), the purpose of this study was to evaluate the association between heart dose ...and overall survival (OS) in patients undergoing PORT with modern techniques.
This is a retrospective study of consecutive patients with NSCLC treated with PORT between May 2004 and January 2017. Clinical records were reviewed and radiation dose distributions were analyzed for association with OS.
A total of 284 patients were analyzed. At the time of surgery, most patients had pathologic American Joint Committee on Cancer seventh edition stage III disease (91.2 %) and received either preoperative or adjuvant chemotherapy (92.3 %). Most patients underwent a lobectomy (81.3 %) and had R0 (80.6 %) or R1 (19.4 %) resection. PORT was delivered with a median radiation dose of 54 Gy, and 70.4 % of patients were treated with intensity-modulated radiation therapy. Dosimetric variables across a large range of doses to the heart were highly significant (p < 0.05) for OS. The volume of the heart receiving 8 Gy (HV8) was the most significant dosimetric variable (p < 0.001), and the median HV8 was 35.5 %. The median OS was 33.2 versus 53.6 months (p < 0.005) for patients with HV8 above or below 35.5 %, respectively. On multivariable analysis accounting for other potential prognostic confounders, HV8 remained highly significant (p < 0.001).
The data reveal a strong correlation between increasing heart dose and OS in patients with NSCLC undergoing PORT. Taken together with the recently presented LungART trial, lowering heart dose in PORT patients may help to decrease the risk of morbidity and mortality and improve the therapeutic ratio of PORT.
Colorectal cancer, developing from malignant transformation of the distal gut epithelium, is the second leading cause of cancer death in the United States. We present a gentleman in his 60s who was ...diagnosed with colorectal cancer during a routine screening colonoscopy with no evidence of distant metastasis on subsequent staging with positron emission tomography and computed tomography (PET-CT). The outside rectal MR (magnetic resonance) imaging report localized a mass to the upper rectum. Review of the MRI at an institutional, Multidisciplinary Tumor Board designated the tumor as “rectosigmoid,” straddling the rectosigmoid junction at the level of the “sigmoid take-off” (STO) or alternatively at the level of the last sigmoid artery take-off (SAT) at the origin of the superior rectal artery. The anatomic differentiation between upper rectal and lower sigmoid colon cancers carries clinical importance which is highlighted in this case report and brief literature review. Optimal anatomic localization of colorectal cancers helps direct the clinical team to tailor an individualized patient care plan.
Abstract Given the burden of cardiovascular disease (CVD), increasing the prevalence of healthy lifestyle choices is a global imperative. Currently, cardiac rehabilitation programs are a primary way ...that modifiable risk factors are addressed in the secondary prevention setting after a cardiovascular (CV) event/diagnosis. Even so, there is wide consensus that primary prevention of CVD is an effective and worthwhile pursuit. Moreover, continual engagement with individuals who have already been diagnosed as having CVD would be beneficial. Implementing health and wellness programs in the workplace allows for the opportunity to continually engage a group of individuals with the intent of effecting a positive and sustainable change in lifestyle choices. Current evidence indicates that health and wellness programs in the workplace provide numerous benefits with respect to altering CV risk factor profiles in apparently healthy individuals and in those at high risk for or already diagnosed as having CVD. This review presents the current body of evidence demonstrating the efficacy of worksite health and wellness programs and discusses key considerations for the development and implementation of such programs, whose primary intent is to reduce the incidence and prevalence of CVD and to prevent subsequent CV events. Supporting evidence for this review was obtained from PubMed, with no date limitations, using the following search terms: worksite health and wellness , employee health and wellness , employee health risk assessments , and return on investment . The choice of references to include in this review was based on study quality and relevance.
Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction. ...Prior research in experimental and human heart failure has shown that CCM signals normalize phosphorylation of key proteins and expression of genes coding for proteins involved in regulation of calcium cycling and contraction. The results of prior clinical studies of CCM have supported its safety and efficacy. A large-scale clinical study, the FIX-HF-5 study, is currently underway to test the safety and efficacy of this treatment. In this article, we provide an overview of the system used to deliver CCM signals, the implant procedure, and the details and rationale of the FIX-HF-5 study design. Baseline characteristics for patients randomized in this trial are also presented.
Background Transplant of skeletal myoblasts is an attractive alternative to repair irreversibly damaged myocardium in ischemic heart failure. We investigated whether transplant of myoblasts ...overexpressing placental growth factor would stimulate angiogenesis and enhance myoblast survival in a rat heart failure model. Methods Three weeks after myocardial infarction, Sprague–Dawley rats in heart failure received intramyocardial injections of Ringer solution (control) or autologous myoblasts, unmodified or transfected with placental growth factor expression plasmid. Sham-operated animals served as noninfarct controls. Cardiac function was assessed by echocardiography to 86 days after engraftment. Immunocytochemistry and fluorescence imaging were used to investigate vessel formation, grafted myoblast survival, infarct wall thickness, and infarct size. Quantitative real-time reverse transcriptase polymerase chain reaction and Western blotting measured tissue messenger RNA and protein expressions. Results Left ventricular function significantly improved with time, and fractional shortening on day 86 was significantly enhanced in transfected myoblast group relative to control ( P < .01) and unmodified myoblast ( P < .05) groups. Vascular density ( P < .01) and myoblast survival ( P < .05) were enhanced in rats treated with transfected myoblasts relative to other groups ( P < .05). Mean fraction of fibrotic scar tissue was decreased in unmodified and transfected myoblast groups relative to controls on day 86 ( P < .05), and left ventricular wall thickness was significantly increased in transfected myoblast group relative to other groups ( P < .05). Conclusions Intramyocardial injections of autologous myoblasts overexpressing placental growth factor improved cardiac function, attenuated adverse cardiac remodeling, induced angiogenesis, and probably enhanced survival of grafted myoblasts.
Atherosclerosis in Survivors of Kawasaki Disease Gupta-Malhotra, Monesha, MBBS; Gruber, Dorota, MS, GC; Abraham, Seena S., MBBS ...
The Journal of pediatrics,
10/2009, Letnik:
155, Številka:
4
Journal Article
Recenzirano
Objectives To test the hypothesis that long-term survivors of low-risk Kawasaki disease (KD) have ongoing vascular inflammation and dysfunction and a higher risk of accelerated atherosclerosis than ...healthy control subjects. Study design Twenty-eight patients with KD (7-20 years after acute illness) and 27 age-matched healthy control subjects were examined for medical and dietary history, serum markers of atherosclerotic risk and inflammation, carotid intimal-medial thickness (CIMT) with vascular ultrasound scanning and arterial stiffness with applanation tonometry. Results Patients and control subjects were similar in age, sex, body mass index, waist-to-hip ratio, blood pressure, cigarette smoking, family history, diet, high-density lipoprotein cholesterol level, lipoprotein (a) level, homocysteine level, glucose level, insulin level, CIMT, arterial stiffness, C-reactive protein level, and inflammatory cytokine level. Levels of total cholesterol and apolipoprotein B were significantly higher in patients with KD than in control subjects. Conclusions There was no evidence of increased atherosclerosis. Small but significant differences in cholesterol and apolipoprotein B levels could suggest increased future risk for atherosclerosis and warrant further study.
The use of stereotactic body radiation therapy for ultracentral lung tumors is limited by increased toxicity. We hypothesized that using published normal tissue complication probability (NTCP) and ...tumor control probability (TCP) models could improve the therapeutic ratio between tumor control and toxicity. A proposed model-based approach was applied to virtually replan early-stage non-small cell lung cancer (NSCLC) tumors.
The analysis included 63 patients with ultracentral NSCLC tumors treated at our center between 2008 and 2017. Along with current clinical constraints, additional NTCP model-based criteria, including for grade 3+ radiation pneumonitis (RP3+) and grade 2+ esophagitis, were implemented using 4 different fractionation schemes. Scaled dose distributions resulting in the highest TCP without violating constraints were selected (optimal plan Planopt). Planopt predictions were compared with the observed local control and toxicities.
The observed 2-year local control rate was 72% (95% CI, 57%-88%) compared with 87% (range, 6%-93%) for Planopt TCP. Thirty-nine patients had Planopt with TCP > 80%, and 14 patients had Planopt TCP < 50%. The Planopt NTCPs for RP3+ were reduced by nearly half compared with patients’ observed RP3+. The RP3+ NTCP was the most frequent reason for TCP of Planopt < 80% (14/24 patients), followed by grade 2+ esophagitis NTCP (5/24 patients) due to larger tumors (>40 cc vs ≤40 cc; P = .002) or a shorter tumor to esophagus distance (≥5 cm vs <5 cm; P < .001).
We demonstrated the potential for model-based prescriptions to yield higher TCP while respecting NTCP for patients with ultracentral NSCLC. Individualizing treatments based on NTCP- and TCP-driven simulations halved the predicted relative to the observed rates of RP3+. Our simulations also identified patients whose TCP could not be improved without violating NTCP due to larger tumors or a near tumor to esophagus proximity.
Objective The risk of endoleak and reintervention after endovascular abdominal aortic aneurysm repair necessitates lifelong surveillance, which has associated costs, radiation exposure, and risk of ...nephrotoxicity. The best imaging method and timing of surveillance remain controversial. We sought to determine if a negative result of first postoperative imaging by computed tomography (CT) scan was predictive of decreased need for reintervention. We hypothesized that initial negative postoperative imaging could identify a low-risk cohort of patients who could be observed less frequently. Methods Retrospective review of prospectively collected institutional outcomes data (2004-2009) included stratification according to postoperative imaging results. Baseline characteristics and aneurysm morphology were compared between the two groups. Cox regression analysis was used to identify risk factors predictive for endoleak-related reintervention. Kaplan-Meier survival curves were used to plot freedom from all-cause reintervention and endoleak-related reintervention for the two groups. Results A total of 134 patients were included in the analysis. A total of 107 patients (80%) had negative initial postoperative imaging, whereas 27 patients (20%) had evidence of an endoleak. There were no significant differences between the two groups in terms of comorbidities or anticoagulation status. Kaplan-Meier survival curves showed that there was a significant difference between those patients who had a negative initial CT scan and those who had a positive scan for endoleak in terms of both overall reintervention rates and leak-related reintervention rates. Endoleak on the first postoperative CT scan was associated with a hazard ratio of 6.37 (confidence interval, 2.02-20.10; P = .002) for leak-related reintervention and a hazard ratio of 6.01 (confidence interval, 2.24-16.17; P < .001) for all-cause reintervention. Conclusions Patients with negative initial postoperative imaging were significantly less likely to require repeated interventions. These data suggest that these patients are candidates for less rigorous screening protocols.
PDF
