Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Whether adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) might prevent peritoneal metastases after curative surgery for high-risk colon cancer is an ongoing debate. This study aimed to determine 5-year oncologic outcomes of the randomized multicenter COLOPEC trial, which included patients with clinical or pathologic T4N0-2M0 or perforated colon cancer and randomly assigned (1:1) to either adjuvant systemic chemotherapy and HIPEC (n = 100) or adjuvant systemic chemotherapy alone (n = 102). HIPEC was performed using a one-time administration of oxaliplatin (460 mg/m 2 , 30 minutes, 42°C, concurrent fluorouracil/leucovorin intravenously), either simultaneously (9%) or within 5-8 weeks (91%) after primary tumor resection. Outcomes were analyzed according to the intention-to-treat principle. Long-term data were available of all 202 patients included in the COLOPEC trial, with a median follow-up of 59 months (IQR, 54.5-64.5). No significant difference was found in 5-year overall survival rate between patients assigned to adjuvant HIPEC followed by systemic chemotherapy or only adjuvant systemic chemotherapy (69.6% v 70.9%, log-rank; P = .692). Five-year peritoneal metastases-free survival rates were 63.9% and 63.2% ( P = .907) and 5-year disease-free survival was 55.7% and 52.3% (log-rank; P = .875), respectively. No differences in quality-of-life outcomes were found. Our findings implicate that adjuvant HIPEC should still be performed in trial setting only.
Live kidney donation has a clear economical benefit over dialysis and deceased-donor transplantation. Compared with mini-incision open donor nephrectomy, laparoscopic donor nephrectomy (LDN) is considered cost-effective. However, little is known on the cost-effectiveness of hand-assisted retroperitoneoscopic donor nephrectomy (HARP). This study evaluated the cost-effectiveness of HARP versus LDN.Alongside a randomized controlled trial, the cost-effectiveness of HARP versus LDN was assessed. Eighty-six donors were included in the LDN group and 82 in the HARP group. All in-hospital costs were recorded. During follow-up, return-to-work and other societal costs were documented up to 1 year. The EuroQol-5D questionnaire was administered up to 1 year postoperatively to calculate quality-adjusted life years (QALYs).Mean total costs from a healthcare perspective were $8935 for HARP and $8650 for LDN (P = 0.25). Mean total costs from a societal perspective were $16,357 for HARP and $16,286 for LDN (P = 0.79). On average, donors completely resumed their daytime jobs on day 54 in the HARP group and on day 52 in the LDN group (P = 0.65). LDN resulted in a gain of 0.005 QALYs.Absolute costs of both procedures are very low and the differences in costs and QALYs between LDN and HARP are very small. Other arguments, such as donor safety and pain, should determine the choice between HARP and LDN.
SUMMARY Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors and poorly-differentiated carcinomas. Treatment options for patients with NENs are limited, in part due to lack of accurate models. To address this need we established the first patient-derived tumor organoids (PDTOs) from pulmonary neuroendocrine tumors and derived PDTOs from an understudied NEN subtype, large cell neuroendocrine carcinoma (LCNEC). PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through drug sensitivity analyses, we uncover therapeutic sensitivities to an inhibitor of NAD salvage biosynthesis and to an inhibitor of BCL-2. Finally, we identify a dependency on EGF in pulmonary neuroendocrine tumor PDTOs. Consistent with these findings, analysis of an independent cohort showed that approximately 50% of pulmonary neuroendocrine tumors expressed EGFR. This study identifies a potentially actionable vulnerability for a subset of NENs, and further highlights the utility of these novel PDTO models for the study of NENs. Graphical abstract Highlights PDTOs of pulmonary NETs and LCNEC were established PDTOs recapitulate intra-tumoral heterogeneity and evolution of parental tumors Drug assays reveal therapeutic vulnerabilities and biomarkers Pulmonary NET PDTOs are dependent on EGF
Stereotactic Body Radiation Therapy (SBRT) is a treatment option for patients with liver metastases. This study evaluated the impact of high versus low dose image-guided SBRT of hepatic metastases.
Perioperative beta-blocker therapy has been proposed to improve outcome. Most of the trials conducted, however, lacked statistical power to evaluate the incidence of hard cardiac events and the relationship to the type of surgery. Therefore, we conducted a meta-analysis of all randomized controlled trials in which beta-blocker therapy was evaluated.An electronic search of published reports on Medline was undertaken to identify studies published between January 1980 and November 2004 in English language journals. All studies reported on at least one of three endpoints: perioperative myocardial ischemia, perioperative nonfatal myocardial infarction, and cardiac mortality. Type of surgery, defined as low, intermediate, and high risk according to the American College of Cardiology/American Heart Association guidelines, was noted.In total, 15 studies were identified, which enrolled 1,077 patient. No significant differences were observed in baseline clinical characteristics between patients randomized to beta-blocker therapy and control/placebo. Beta-blocker therapy was associated with a 65% reduction in perioperative myocardial ischemia (11.0% vs. 25.6%; odds ratio 0.35, 95% confidence interval 0.23-0.54; P<0.001). Furthermore, a 56% reduction in myocardial infarction (0.5% vs. 3.9%, odds ratio 0.44, 95% confidence interval 0.20-0.97; P=0.04) and a 67% reduction (1.1% vs. 6.1%, odds ratio 0.33, 95% confidence interval 0.17-0.67; P=0.002) in the composite endpoint of cardiac death and nonfatal myocardial infarction were observed. No statistical evidence was observed for heterogeneity in the treatment effect in subgroups according to type of surgery (P for heterogeneity 0.2).This meta-analysis shows that beta-blocker use in noncardiac surgical procedures is associated with a significant reduction of perioperative cardiac adverse events.
The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands.A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates.Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001).The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018–2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations.
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