18 research outputs found
Quality of Life in Older Adults After Major Cancer Surgery:The GOSAFE International Study
Abstract
Background
Accurate quality of life (QoL) data and functional results after cancer surgery are lacking for older patients. The international, multicenter Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) Study compares QoL before and after surgery and identifies predictors of decline in QoL.
Methods
GOSAFE prospectively collected data before and after major elective cancer surgery on older adults (≥70 years). Frailty assessment was performed and postoperative outcomes recorded (30, 90, and 180 days postoperatively) together with QoL data by means of the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L), including 2 components: an index (range = 0-1) generated by 5 domains (mobility, self-care, ability to perform the usual activities, pain or discomfort, anxiety or depression) and a visual analog scale.
Results
Data from 26 centers were collected (February 2017-March 2019). Complete data were available for 942/1005 consecutive patients (94.0%): 492 male (52.2%), median age 78 years (range = 70-95 years), and primary tumor was colorectal in 67.8%. A total 61.2% of all surgeries were via a minimally invasive approach. The 30-, 90-, and 180-day mortality was 3.7%, 6.3%, and 9%, respectively. At 30 and 180 days, postoperative morbidity was 39.2% and 52.4%, respectively, and Clavien-Dindo III-IV complications were 13.5% and 18.7%, respectively. The mean EQ-5D-3L index was similar before vs 3 months but improved at 6 months (0.79 vs 0.82; P < .001). Domains showing improvement were pain and anxiety or depression. A Flemish Triage Risk Screening Tool score greater than or equal to 2 (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.13 to 2.21, P = .007), palliative surgery (OR = 2.14, 95% CI = 1.01 to 4.52, P = .046), postoperative complications (OR = 1.95, 95% CI = 1.19 to 3.18, P = .007) correlated with worsening QoL.
Conclusions
GOSAFE shows that older adults’ preoperative QoL is preserved 3 months after cancer surgery, independent of their age. Frailty screening tools, patient-reported outcomes, and goals-of-care discussions can guide decisions to pursue surgery and direct patients’ expectations
Predicting functional recovery and quality of life in older patients undergoing colorectal cancer surgery : real-world data from the international GOSAFE Study
Purpose: The GOSAFE study evaluates risk factors for failing to achieve good quality of life (QoL) and functional recovery (FR) in older patients undergoing surgery for colon and rectal cancer. Methods: Patients age 70 years and older undergoing major elective colorectal surgery were prospectively enrolled. Frailty assessment was performed and outcomes, including QoL (EQ-5D-3L) recorded (3/6 months postoperatively). Postoperative FR was defined as a combination of Activity of Daily Living ≥5 + Timed Up & Go test <20 seconds + MiniCog >2. Results: Prospective complete data were available for 625/646 consecutive patients (96.9%; 435 colon and 190 rectal cancer), 52.6% men, and median age was 79.0 years (IQR, 74.6-82.9 years). Surgery was minimally invasive in 73% of patients (321/435 colon; 135/190 rectum). At 3-6 months, 68.9%-70.3% patients experienced equal/better QoL (72.8%-72.9% colon, 60.1%-63.9% rectal cancer). At logistic regression analysis, preoperative Flemish Triage Risk Screening Tool ≥2 (3-month odds ratio [OR], 1.68; 95% CI, 1.04 to 2.73; P = .034, 6-month OR, 1.71; 95% CI, 1.06 to 2.75; P = .027) and postoperative complications (3-month OR, 2.03; 95% CI, 1.20 to 3.42; P = .008, 6-month OR, 2.56; 95% CI, 1.15 to 5.68; P = .02) are associated with decreased QoL after colectomy. Eastern Collaborative Oncology Group performance status (ECOG PS) ≥2 is a strong predictor of postoperative QoL decline in the rectal cancer subgroup (OR, 3.81; 95% CI, 1.45 to 9.92; P = .006). FR was reported by 254/323 (78.6%) patients with colon and 94/133 (70.6%) with rectal cancer. Charlson Age Comorbidity Index ≥7 (OR, 2.59; 95% CI, 1.26 to 5.32; P = .009), ECOG ≥2 (OR, 3.12; 95% CI, 1.36 to 7.20; P = .007 colon; OR, 4.61; 95% CI, 1.45 to 14.63; P = .009 rectal surgery), severe complications (OR, 17.33; 95% CI, 7.30 to 40.8; P < .001), fTRST ≥2 (OR, 2.71; 95% CI, 1.40 to 5.25; P = .003), and palliative surgery (OR, 4.11; 95% CI, 1.29 to 13.07; P = .017) are risk factors for not achieving FR. Conclusion: The majority of older patients experience good QoL and stay independent after colorectal cancer surgery. Predictors for failing to achieve these essential outcomes are now defined to guide patients' and families' preoperative counseling
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CRISPR-Cas9 screen reveals a MYCN-amplified neuroblastoma dependency on EZH2
Pharmacologically difficult targets, such as MYC transcription factors, represent a major challenge in cancer therapy. For the childhood cancer neuroblastoma, amplification of the oncogene MYCN is associated with high-risk disease and poor prognosis. Here, we deployed genome-scale CRISPR-Cas9 screening of MYCN-amplified neuroblastoma and found a preferential dependency on genes encoding the polycomb repressive complex 2 (PRC2) components EZH2, EED, and SUZ12. Genetic and pharmacological suppression of EZH2 inhibited neuroblastoma growth in vitro and in vivo. Moreover, compared with neuroblastomas without MYCN amplification, MYCN-amplified neuroblastomas expressed higher levels of EZH2. ChIP analysis showed that MYCN binds at the EZH2 promoter, thereby directly driving expression. Transcriptomic and epigenetic analysis, as well as genetic rescue experiments, revealed that EZH2 represses neuronal differentiation in neuroblastoma in a PRC2-dependent manner. Moreover, MYCN-amplified and high-risk primary tumors from patients with neuroblastoma exhibited strong repression of EZH2-regulated genes. Additionally, overexpression of IGFBP3, a direct EZH2 target, suppressed neuroblastoma growth in vitro and in vivo. We further observed strong synergy between histone deacetylase inhibitors and EZH2 inhibitors. Together, these observations demonstrate that MYCN upregulates EZH2, leading to inactivation of a tumor suppressor program in neuroblastoma, and support testing EZH2 inhibitors in patients with MYCN-amplified neuroblastoma
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Software-Guided Insulin Dosing: Tight Glycemic Control and Decreased Glycemic Derangements in Critically Ill Patients
Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium
Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials
Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory or High-risk Leukemias: A Report from the LEAP Consortium.
Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence, Tier 1 or 2, recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance (VUS), performed ex vivo drug sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials