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.
The aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive ...chemoradiation (CRT) for proximal esophageal cancer.
Patients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses.
In 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8–61.5 months), 58% (95% CI 48–66), and 49% (95% CI 40–57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31–48), and 45% (95% CI 36–54). Three- and five-year risk of LRR were 26% (95% CI 19–33), and 30% (95% CI 22–38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached).
In patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years.
•Five-year risk of recurrence after CRT for proximal esophageal cancer was 45%.•Most recurrences were locoregional and mainly in the primary involved tumor field.•Surgery or radiotherapy was performed in 75% of patients with a local recurrence.•Salvage surgery of isolated locoregional recurrence resulted in favorable outcome.•The recurrence pattern suggests that follow-up may be shortened to three years.
Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of ...this study was to compare the treatment outcomes of contemporary CRT regimens.
Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model.
Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9-77.2 months). Median OS (21.9 months; 95% CI: 16.9-27.0 months) was comparable between treatment groups (logrank p = .88), confirmed in the fully adjusted and PS weighted model (p > .05). Grades 3-5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31-10.87; p = .01). The occurrence of grades 3-5 late toxicities was not different between treatment groups.
Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC.
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.
PDF
