New therapies for castrate-resistant prostate cancer Williams, Stephen B; Lay, Aaron H; Lau, Clayton S ...
Expert opinion on pharmacotherapy,
2011-September, 9/1/2011, 2011-Sep, 2011-09-00, 20110901, Letnik:
12, Številka:
13
Journal Article
Recenzirano
Introduction:
Prostate cancer is the second leading cause of cancer death in men in the USA, and most of these deaths will occur as a result of castrate-resistant prostate cancer (CRPC) that has ...progressed despite androgen deprivation therapy. There has been better understanding of castration resistance and molecular mechanisms of prostate cancer progression recently, leading to new treatment strategies.
Areas covered:
This review focuses on emerging and new therapies for castrate-resistant prostate cancer, including hormonal therapy, immunotherapy and cytotoxic agents.
Expert opinion:
New treatment strategies have been developed in recent years and, with improved understanding of advanced CRPC, additional targeted treatments are expected in the near future. Further cost effectiveness research of these treatments is warranted before dissemination of these promising agents.
: There have been few reports of the use of robotic surgery to resect lung malignancies. Feasibility and safety of robotic lung resection for malignant lung lesions will be assessed by performing a ...retrospective analysis.
: Between September 2004 and November 2006, 21 patients (11 male and 10 female patients) underwent robotic lung resection. Twenty resections were performed for primary nonsmall cell lung cancer and two for metastatic lesions. One patient had bilateral resections for two primary tumors. Fourteen lobectomies, five segementectomies, one wedge resection, and two bilobectomies were performed. Seventy-two percent of operative procedures included mediastinoscopy and/or bronchoscopy at the time of resection.
: Thirty-day mortality and conversion rate was 0%. The median operating room time and estimated blood loss was 3.6 hours and 100 mL, respectively. The median intensive care unit and total length of hospital stays were 2 and 4 days, respectively. Chest tubes were removed after a median of 2.0 days. The complication rate was 27%, which included atrial fibrillation, need for postoperative bronchoscopy, and pneumonia. The median tumor size and number of lymph nodes harvested was 2.3 cm and 16, respectively. All resection margins were negative. Median follow-up time was 9.8 months, with no local recurrences at this time.
: Robotic lung resection appears safe and feasible and allows for significant lymph node retrieval, offers short hospital stays and low morbidity for patients undergoing surgical resection of lung malignancies. Future studies are needed to define the role of robotic surgery in lung cancer treatment.
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410
Background: Bladder cancer is the second most common urologic malignancy with over 73,350 new cases diagnosed annually of which the incidence is increasing in the elderly. Radical ...cystectomy (RC), the gold standard for muscle invasive disease, carries a particularly high risk of morbidity and mortality, as well as a protracted length of stay (LOS) and increased readmission rates when compared with other major urologic procedures. Furthermore, in 2013, the Institute of Medicine (IOM) declared cancer care in the US a national crisis with a priority to improve quality of care through care coordination (CC). Simultaneously, enhanced recovery after surgery (ERAS) protocols have surfaced as coordinated, evidence-based models designed to standardize medical care, improve outcomes, and lower healthcare costs. At City of Hope (COH), we evaluated our ERAS and CC pathway. Methods: In April of 2014, an ERAS and CC pathway for bladder cancer was launched at COH with an emphasis on the perioperative care of patients (pts) from a multi-disciplinary team perspective. Preoperatively, pts undergo orientation on stoma education, goals of care, and treatment expectations. The pathway clinically focuses on avoidance of bowel preparation, early feeding, minimizing narcotics, and u-opioid antagonists. On discharge, pts are closely monitored via scheduled phone calls as well as clinic visits. Quality metrics including LOS, complications, and readmissions are reported as median and interquartile range along with descriptive statistics including chi-square and Wilcoxon rank-sum tests. Results: Since implementation, the median LOS was statistically significant between cohorts with 6 days for pts on pathway compared to 8 days for those preceding the pathway (p = 0.0007). Furthermore, the complication and readmission rates have decreased from 67.5% to 50% and from 35% to 30%, respectively. Dehydration and urinary tract infection (UTI) accounted for 17.9% and 21.4% of readmissions for those prior to the pathway, while UTI occurred in 5% of pts readmitted after adhering to the pathway. Conclusions: Our ERAS and CC pathway has reduced LOS without an increase in complication nor readmission rates.
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612
Background: Clear cell renal cell carcinoma (ccRCC) metastasis is associated with a dismal prognosis. Early identification of patients at high or low risk of metastasis may help to ...guide appropriate treatment. There are currently no reliable clinico-pathologic and laboratory modalities for this purpose in a routine clinical setting. We previously performed a microarray study using frozen ccRCC specimens and identified dysregulation of 4 microRNAs (miRNAs), miR-10b, miR-139-5p, miR-130b and miR-199b-5p, to be highly associated ccRCC metastasis and prognosis. Methods: We established a training cohort including formalin-fixed paraffin-embedded (FFPE) specimens of localized (n = 13; pT1) and metastatic (n = 15; M1) ccRCCs. We measured the expression of the 4 miRNAs of the training cohort samples by quantitative RT-PCR, normalized with miR-24, one of the most stably expressed miRNAs in human renal tissue as we previously reported. Using the risk score method, we rebuilt a mathematical formula with cutoff points to predict a patient to be at high, low or equivocal risk of metastasis. We validated the signature in an FFPE test cohort of 265-case primary ccRCCs. We examined the signature performance and its correlation with the cancer-specific survival. Results: Multivariate logistic regression analysis showed the signature to be highly associated with ccRCC metastasis (OR 7.67, 95%Cl 2.80-21.09, p < 0.0001), with the overall sensitivity and specificity of 80% and 76%. The sensitivities and specificities were 72% and 78%, 70% and 67%, and 78% and 75% for stage I, II or III patients, respectively. The signature predicted metastasis of small ccRCCs ( ≤ 4.0 cm), with the sensitivity of 60% and specificity of 77%. The overall positive and negative predictive values (PPV and NPV) were 61% and 89%. The area under the curve of ROC was 0.8. The signature was also found to be well correlated with worse cancer-specific survival (HR 3.06, 95%Cl 1.49-6.93, p < 0.01). Conclusions: This optimized miRNA signature can reliably predict ccRCC metastasis and prognosis and may help to stratify patients for more appropriate therapies and suitable clinical trials.
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