In esophageal cancer (EC) patients who are not eligible for surgery, definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard chemotherapy ...regimen. Nowadays carboplatin/paclitaxel is also often used. In this study, we compared survival and toxicity rates between both regimens.
This multicenter study included 102 patients treated in five centers in the Northeast Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU (75 mg/m2 and 1 g/m2) and 55 patients carboplatin/paclitaxel (AUC2 and 50 mg/m2).
Overall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group {P = 0.879, hazard ratio (HR) 0.97 confidence interval (CI) 0.62–1.51}, with a median survival of 16.1 (CI 11.8–20.5) and 13.8 months (CI 10.8–16.9). Median disease-free survival (DFS) was comparable P = 0.760, HR 0.93 (CI 0.60–1.45) between the cisplatinum/5-FU group 11.1 months (CI 6.9–15.3) and the carboplatin/paclitaxel group 9.7 months (CI 5.1–14.4). Groups were comparable except clinical T stage was higher in the carboplatin/paclitaxel group (P = 0.008). High clinical T stage (cT4) was not related to OS and DFS in a univariate analysis (P = 0.250 and P = 0.201). A higher percentage of patients completed the carboplatin/paclitaxel regimen (82% versus 57%, P = 0.010). Hematological and nonhematological toxicity (≥grade 3) in the carboplatin/paclitaxel group (4% and 18%) was significantly lower than in the cisplatinum/5-FU (19% and 38%, P = 0.001).
In this study, we showed comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared with cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment of cisplatinum/5-FU is a good candidate regimen for further evaluation.
•An existing prediction model for 2-year mortality in lung cancer patients, based on the predictive factors gross tumor volume and mean heart dose, was externally validated for esophageal cancer ...patients and showed good performance.•Separate updated models for definitive and neo-adjuvant chemoradiotherapy were developed.•The current analyses provide support for the existence of an independent effect of mean heart dose on 2-year mortality.
Chemo-radiotherapy can improve the oncological outcome of esophageal cancer (EC) patients, but may cause long term radiation-induced toxicity, including an increased risk of non-cancer related death. For lung cancer patients, a model to predict 2-year total mortality using mean heart dose (MHD) and gross tumor volume (GTV) has previously been developed and validated. This project aimed to externally validate this model in EC patients.
Five EC patient cohorts from 3 different Dutch centres were used for model validation. External validity of the model was assessed separately in definitive (n = 170) and neo-adjuvant (n = 568) chemoradiotherapy (dCRT and nCRT) patients. External validity was assessed in terms of calibration by calibration plots, calibration-in-the-large (CITL) and calibration slope (CS), and discrimination by assessment of the c-statistic. If suboptimal model performance was observed, the model was further updated accordingly.
For the dCRT patients, good calibration was found after adjustment of the intercept (CITL 0.00; CS 1.08). The c-statistic of the adjusted model was 0.67 (95%CI: 0.58 to 0.75). For nCRT patients the model needed adjustment of both the slope and the intercept because of initial miscalibration in the validation population (CITL 0.00; CS 1.72). After recalibration, the model showed perfect calibration (i.e., CITL 0, CS 1), as is common after recalibration. The c-statistic of the recalibrated model equaled 0.62 (95%CI: 0.57 to 0.67).
The existing model for 2-year mortality prediction in lung cancer patients, based on the predictive factors MHD and GTV, showed good performance in EC patients after updating the intercept and/or slope of the original model.
Purpose
Blunt cerebrovascular injuries (BCVI), which can result in ischemic stroke, are identified in 1–2% of all blunt trauma patients. Computed tomography angiography (CTA) scanning has improved ...and is the diagnostic modality of choice in BCVI suspected patients. Data about long-term functional outcomes and the incidence of ischemic stroke after BCVI are limited. The aim of this study was to determine BCVI incidence in relation to imaging modality improvements and to determine long-term functional outcomes.
Methods
All consecutive trauma patients from 2007 to 2016 with BCVI were identified from the level 1 trauma center prospective trauma database. Three periods were identified where CTA diagnostic modalities for trauma patients were improved. Long-term functional outcomes using the EuroQol six-dimensional (EQ-6D™) were determined.
Results
Seventy-one BCVI patients were identified among the 12.122 (0.59%) blunt trauma patients. In the first period BCVI incidence among the overall study cohort, polytrauma, basilar skull fracture and cervical trauma subgroups was found to be 0.3%, 0.9%, 1.2%, 4.6%, respectively, which more than doubled towards the third period (0.8, 2.4, 1.9 and 8.5% respectively). Ischemic stroke as a result of BCVI was found in 20 patients (28%). In-hospital stroke rate was lower in patients receiving antiplatelet therapy (
p
< 0.01). Six in-hospital deaths were BCVI related. Long-term follow-up (follow-up rate of 83%) demonstrated lower functional outcomes compared to Dutch reference populations (
p
< 0.01). Ischemic stroke was identified as a major cause of functional impairment at long-term follow-up.
Conclusions
Improved CTA diagnostic modalities have increased BCVI incidence. Furthermore, BCVI patients reported significant functional impairment at long-term follow-up. Antiplatelet therapy showed a significant effect on in-hospital stroke rate reduction.
Isolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential ...indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients.
A systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method.
Of the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) 3.1; 18.7) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI 1.5; 10.2). The pooled estimated 30- and 90-day mortality was 2.6% 1.6; 3.6 and 8.0% 6.3; 9.8, respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: 35.8; 42.2) and 19.4% 95% CI:16.5; 22.4, respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion −5.7, 95% CI -13.7; 2.3).
Salvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted.
In the past, spinal trauma was frequent in high- and middle-income regions of the world with high rates of automobility and was considered a “young men’s disease.” However, over the last 2 decades, ...both of these factors have changed dramatically. This has had important implications for our methods of diagnosis, treatment, and the organization of care.
Purpose
To report on the development of AOSpine CROST (Clinician Reported Outcome Spine Trauma) and results of an initial reliability study.
Methods
The AOSpine CROST was developed using an iterative ...approach of multiple cycles of development, review, and revision including an expert clinician panel. Subsequently, a reliability study was performed among an expert panel who were provided with 20 spine trauma cases, administered twice with 4-week interval. The results of the developmental process were analyzed using descriptive statistics, the reliability per parameter using Kappa statistics, inter-rater rater agreement using intraclass correlation coefficient (ICC), and internal consistency using Cronbach’s
α
.
Results
The AOSpine CROST was developed and consisted of 10 parameters, 2 of which are only applicable for surgically treated patents (‘Wound healing’ and ‘Implants’). A dichotomous scoring system (‘yes’ or ‘no’ response) was incorporated to express expected problems for the short term and long term. In the reliability study, 16 (84.2%) participated in the first round and 14 (73.7%) in the second. Intra-rater reliability was fair to good for both time points (
κ
= 0.40–0.80 and
κ
= 0.31–0.67). Results of inter-rater reliability were lower (
κ
= 0.18–0.60 and
κ
= 0.16–0.46). Inter-rater agreement for total scores showed moderate results (ICC = 0.52–0.60), and the internal consistency was acceptable (
α
= 0.76–0.82).
Conclusions
The AOSpine CROST, an outcome tool for the surgeons, was developed using an iterative process. An initial reliability analysis showed fair to moderate results and acceptable internal consistency. Further clinical validation studies will be performed to further validate the tool.
Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon ...histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and
F-fluorodeoxyglucose positron emission tomography with computed tomography (
F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR.
The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and
F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival.
If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped.
The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .
Several classification systems exist for sacral fractures; however, these systems are primarily descriptive, are not uniformly used, have not been validated, and have not been associated with a ...treatment algorithm or prognosis. The goal of the present study was to demonstrate the reliability of the AOSpine Sacral Classification System among a group of international spine and trauma surgeons.
A total of 38 sacral fractures were reviewed independently by 18 surgeons selected from an expert panel of AOSpine and AOTrauma members. Each case was graded by each surgeon on 2 separate occasions, 4 weeks apart. Intrarater reproducibility and interrater agreement were analyzed with use of the kappa statistic (κ) for fracture severity (i.e., A, B, and C) and fracture subtype (e.g., A1, A2, and A3).
Seventeen reviewers were included in the final analysis, and a total of 1,292 assessments were performed (646 assessments performed twice). Overall intrarater reproducibility was excellent (κ = 0.83) for fracture severity and substantial (κ = 0.71) for all fracture subtypes. When comparing fracture severity, overall interrater agreement was substantial (κ = 0.75), with the highest agreement for type-A fractures (κ = 0.95) and the lowest for type-C fractures (κ = 0.70). Overall interrater agreement was moderate (κ = 0.58) when comparing fracture subtype, with the highest agreement seen for A2 subtypes (κ = 0.81) and the lowest for A1 subtypes (κ = 0.20).
To our knowledge, the present study is the first to describe the reliability of the AOSpine Sacral Classification System among a worldwide group of expert spine and trauma surgeons, with substantial to excellent intrarater reproducibility and moderate to substantial interrater agreement for the majority of fracture subtypes. These results suggest that this classification system can be reliably applied to sacral injuries, providing an important step toward standardization of treatment.
Objectives
Previous literature showed that the diagnostic accuracy of computed tomographic angiography (CTA) is not equally comparable with that of the rarely used golden standard of digital ...subtraction angiography (DSA) for detecting blunt cerebrovascular injuries (BCVI) in trauma patients. However, advances in CTA technology may prove CTA to become equally accurate. This study investigated the diagnostic accuracy of CTA in detecting BCVI in comparison with DSA in trauma patients.
Methods
An electronic database search was performed in PubMed, EMBASE, and Cochrane Library. Summary estimates of sensitivity, specificity, positive and negative likelihood, diagnostic odds ratio, and 95% confidence intervals were determined using a bivariate random-effects model.
Results
Of the 3293 studies identified, 9 met the inclusion criteria. Pooled sensitivity was 64% (95% CI, 53–74%) and specificity 95% (95% CI, 87–99%) The estimated positive likelihood ratio was 11.8 (95%, 5.6–24.9), with a negative likelihood ratio of 0.38 (95%, 0.30–0.49) and a diagnostic odds ratio of 31 (95%, 17–56).
Conclusion
CTA has reasonable specificity but low sensitivity when compared to DSA in diagnosing any BCVI. An increase in channels to 64 slices did not yield better sensitivity. There is a risk for underdiagnosis of BCVI when only using DSA to confirm CTA-positive cases, especially in those patients with low-grade injuries.
Key Points
•
Low sensitivity and high specificity were seen in identifying BCVI with CTA as compared to DSA.
•
Increased CTA detector channels (≤ 64) did not lead to higher sensitivity when detecting BCVI.
•
The use of CTA instead of DSA may lead to underdiagnosis and, consequently, undertreatment of BCVI.
Purpose
To evaluate feasibility, internal consistency, inter-rater reliability, and prospective validity of AO Spine CROST (Clinician Reported Outcome Spine Trauma) in the clinical setting.
Methods
...Patients were included from four trauma centers. Two surgeons with substantial amount of experience in spine trauma care were included from each center. Two separate questionnaires were administered at baseline, 6-months and 1-year: one to surgeons (mainly CROST) and another to patients (AO Spine PROST—Patient Reported Outcome Spine Trauma). Descriptive statistics were used to analyze patient characteristics and feasibility, Cronbach’s α for internal consistency. Inter-rater reliability through exact agreement, Kappa statistics and Intraclass Correlation Coefficient (ICC). Prospective analysis, and relationships between CROST and PROST were explored through descriptive statistics and Spearman correlations.
Results
In total, 92 patients were included. CROST showed excellent feasibility results. Internal consistency (
α
= 0.58–0.70) and reliability (ICC = 0.52 and 0.55) were moderate. Mean total scores between surgeons only differed 0.2–0.9 with exact agreement 48.9–57.6%. Exact agreement per CROST item showed good results (73.9–98.9%). Kappa statistics revealed moderate agreement for most CROST items. In the prospective analysis a trend was only seen when no concerns at all were expressed by the surgeon (CROST = 0), and moderate to strong positive Spearman correlations were found between CROST at baseline and the scores at follow-up (
r
s
= 0.41–0.64). Comparing the CROST with PROST showed no specific association, nor any Spearman correlations (
r
s
= −0.33–0.07).
Conclusions
The AO Spine CROST showed moderate validity in a true clinical setting including patients from the daily clinical practice.
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