Validation of a prognostic scoring system for locally recurrent nasopharyngeal carcinoma treated by stereotactic radiosurgery

<p>Abstract</p> <p>Background</p> <p>Selection of patients with local failure of nasopharyngeal carcinoma (NPC) for appropriate type of salvage treatment can be difficult due to the lack of data on comparative efficacy of different salvage treatments. The purpose of the present study was to validate a previously published prognostic scoring system for local failures of NPC treated by radiosurgery based on reported results in the literature.</p> <p>Methods</p> <p>A literature search yielded 3 published reports on the use of radiosurgery as salvage treatment of NPC that contained sufficient clinical information for validation of the scoring system. Prognostic scores of 18 patients from these reports were calculated and actuarial survival rates were estimated and compared to the original cohort used to design the prognostic scoring system. The area under the receiver operating characteristic curve was also determined and compared between the current and original patient groups.</p> <p>Results</p> <p>The calculated prognostic scores ranged from 0.32 to 1.21, with 15 patients assigned to the poor prognostic group and 3 to the intermediate prognostic group. The actuarial 3-year survival rates in the intermediate and poor prognostic groups were 67% and 0%, respectively. These results were comparable to the observed 3-year survival rates of 74% and 23% in the intermediate and poor prognostic group in the original reports. The area under the receiver operating characteristic curve for the current patient group was 0.846 which was similar to 0.841 in the original group.</p> <p>Conclusion</p> <p>The previously published prognostic scoring system demonstrated good prediction of treatment outcome after radiosurgery in a small group of NPC patients with poor prognosis. Prospective study to validate the scoring system is currently being carried out in our institution.</p

Comparison of single versus fractionated dose of stereotactic radiotherapy for salvaging local failures of nasopharyngeal carcinoma: a matched-cohort analysis

BACKGROUND: Local failure is an important cause of morbidity and mortality in nasopharyngeal carcinoma (NPC). Although surgery or brachytherapy may be feasible in selected cases, most patients with local failure require external beam re-irradiation. Stereotactic radiation using single or multiple fractions have been employed in re-irradiation of NPC, but the optimal fractionation scheme and dose are not clear. METHODS: Records of 125 NPC patients who received salvage stereotactic radiation were reviewed. A matched-pair design was used to select patients with similar prognostic factors who received stereotactic re-irradiation using single fraction (SRS) or multiple fractions (SRM). Eighty-six patients were selected with equal number in SRS and SRM groups. All patients were individually matched for failure type (persistent or recurrent), rT stage (rT1-2 or rT3-4), and tumor volume (5-10 cc, or >10 cc). Median dose was 12.5 Gy in single fraction by SRS, and 34 Gy in 2-6 fractions by SRM. RESULTS: Local control rate was better in SRM group although overall survival rates were similar. One- and 3-year local failure-free rates were 70% and 51% in SRS group compared with 91% and 83% in SRM group (p = 0.003). One- and 3-year overall survival rates were 98% and 66% in SRS group compared with 78% and 61% in SRM group (p = 0.31). The differences in local control were mainly observed in recurrent or rT2-4 disease. Incidence of severe late complications was 33% in SRS group vs. 21% in SRM group, including brain necrosis (16% vs. 12%) and hemorrhage (5% vs. 2%). CONCLUSION: Our study showed that SRM was superior to SRS in salvaging local failures of NPC, especially in the treatment of recurrent and rT2-4 disease. In patient with local failure of NPC suitable for stereotactic re-irradiation, use of fractionated treatment is preferred.link_to_subscribed_fulltex

Cost-analysis of XELOX and FOLFOX4 for treatment of colorectal cancer to assist decision- making on reimbursement

Abstract Background: XELOX (capecitabine + oxaliplatin) and FOLFOX 4 (5-FU + folinic acid + oxaliplatin) have shown similar improvements in survival in patients with metastatic colorectal cancer (MCRC). A US cost-minimization study found that the two regimens had similar costs from a healthcare provider perspective but XELOX had lower costs than FOLFOX4 from a societal perspective, while a Japanese cost-effectiveness study found XELOX had superior cost-effectiveness. This study compared the costs of XELOX and FOLFOX4 in patients with MCRC recently treated in two oncology departments in Hong Kong. Methods: Cost data were collected from the medical records of 60 consecutive patients (30 received XELOX and 30 FOLFOX4) from two hospitals. Drug costs, outpatient visits, hospital days and investigations were recorded and expressed as cost per patient from the healthcare provider perspective. Estimated travel and time costs were included in a societal perspective analysis. All costs were classed as either scheduled (associated with planned chemotherapy and follow-up) or unscheduled (unplanned visits or admissions and associated tests and medicines). Costs were based on government and hospital sources and expressed in US dollars (US$). Results: XELOX patients received an average of 7.3 chemotherapy cycles (of the 8 planned cycles) and FOLFOX4 patients received 9.2 cycles (of the 12 planned cycles). The scheduled cost per patient per cycle was$2,046 for XELOX and $2,152 for FOLFOX4, while the unscheduled cost was$240 and $421, respectively. Total treatment cost per patient was$16,609 for XELOX and $23,672 for FOLFOX4; the total cost for FOLFOX4 was 37$17,836 for XELOX and $27,455 for FOLFOX4. Sensitivity analyses showed XELOX was still less costly than FOLFOX4 when using full drug regimen costs, incorporating data from a US model with costs and adverse event data from their clinical trial and with the removal of oxaliplatin from both treatment arms. Capecitabine would have to cost around four times its present price in Hong Kong for the total resource cost of treatment with XELOX to equal that of FOLFOX4

A novel prostate cancer subtyping classifier based on luminal and basal phenotypes

Background: Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought. Methods: Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts. Results: Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01–0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09–0.51). Conclusions: With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features. Plain language summary: Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors—the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management

Machine learning versus classical electrocardiographic criteria for echocardiographic left ventricular hypertrophy in a pre-participation cohort

Background: Classical electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) are well studied in older populations and patients with hypertension. Their utility in young pre-participation cohorts is unclear.Aims: We aimed to develop machine learning models for detection of echocardiogram-diagnosed LVH from ECG, and compare these models with classical criteria.Methods: Between November 2009 and December 2014, pre-participation screening ECG and subsequent echocardiographic data was collected from 17 310 males aged 16 to 23, who reported for medical screening prior to military conscription. A final diagnosis of LVH was made during echocardiography, defined by a left ventricular mass index &gt;115 g/m2. The continuous and threshold forms of classical ECG criteria (Sokolow–Lyon, Romhilt–Estes, Modified Cornell, Cornell Product, and Cornell) were compared against machine learning models (Logistic Regression, GLMNet, Random Forests, Gradient Boosting Machines) using receiver-operating characteristics curve analysis. We also compared the important variables identified by machine learning models with the input variables of classical criteria.Results: Prevalence of echocardiographic LVH in this population was 0.82% (143/17310). Classical ECG criteria had poor performance in predicting LVH. Machine learning methods achieved superior performance: Logistic Regression (area under the curve [AUC], 0.811; 95% confidence interval [CI], 0.738–0.884), GLMNet (AUC, 0.873; 95% CI, 0.817–0.929), Random Forest (AUC, 0.824; 95% CI, 0.749–0.898), Gradient Boosting Machines (AUC, 0.800; 95% CI, 0.738–0.862).Conclusions: Machine learning methods are superior to classical ECG criteria in diagnosing echocardiographic LVH in the context of pre-participation screening

Cost-analysis of XELOX and FOLFOX4 for treatment of colorectal cancer to assist decision-making on reimbursement

<p>Abstract</p> <p>Background</p> <p>XELOX (capecitabine + oxaliplatin) and FOLFOX 4 (5-FU + folinic acid + oxaliplatin) have shown similar improvements in survival in patients with metastatic colorectal cancer (MCRC). A US cost-minimization study found that the two regimens had similar costs from a healthcare provider perspective but XELOX had lower costs than FOLFOX4 from a societal perspective, while a Japanese cost-effectiveness study found XELOX had superior cost-effectiveness. This study compared the costs of XELOX and FOLFOX4 in patients with MCRC recently treated in two oncology departments in Hong Kong.</p> <p>Methods</p> <p>Cost data were collected from the medical records of 60 consecutive patients (30 received XELOX and 30 FOLFOX4) from two hospitals. Drug costs, outpatient visits, hospital days and investigations were recorded and expressed as cost per patient from the healthcare provider perspective. Estimated travel and time costs were included in a societal perspective analysis. All costs were classed as either scheduled (associated with planned chemotherapy and follow-up) or unscheduled (unplanned visits or admissions and associated tests and medicines). Costs were based on government and hospital sources and expressed in US dollars (US$).</p> <p>Results</p> <p>XELOX patients received an average of 7.3 chemotherapy cycles (of the 8 planned cycles) and FOLFOX4 patients received 9.2 cycles (of the 12 planned cycles). The scheduled cost per patient per cycle was$2,046 for XELOX and $2,152 for FOLFOX4, while the unscheduled cost was$240 and $421, respectively. Total treatment cost per patient was$16,609 for XELOX and $23,672 for FOLFOX4; the total cost for FOLFOX4 was 37$17,836 for XELOX and $27,455 for FOLFOX4. Sensitivity analyses showed XELOX was still less costly than FOLFOX4 when using full drug regimen costs, incorporating data from a US model with costs and adverse event data from their clinical trial and with the removal of oxaliplatin from both treatment arms. Capecitabine would have to cost around four times its present price in Hong Kong for the total resource cost of treatment with XELOX to equal that of FOLFOX4.</p> <p>Conclusion</p> <p>XELOX costs less than FOLFOX4 for this patient group with MCRC from both the healthcare provider and societal perspectives.</p

Renal replacement therapy in acute kidney injury: controversy and consensus

Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta