Radiomic analyses of CT images provide prognostic information that can potentially be used for personalized treatment. However, heterogeneity of acquisition- and reconstruction protocols influences ...robustness of radiomic analyses. The aim of this study was to investigate the influence of different CT-scanners, slice thicknesses, exposures and gray-level discretization on radiomic feature values and their stability.
A texture phantom with ten different inserts was scanned on nine different CT-scanners with varying tube currents. Scans were reconstructed with 1.5 mm or 3 mm slice thickness. Image pre-processing comprised gray-level discretization in ten different bin widths ranging from 5 to 50 HU and different resampling methods (i.e., linear, cubic and nearest neighbor interpolation to 1 × 1 × 3 mm
voxels) were investigated. Subsequently, 114 textural radiomic features were extracted from a 2.1 cm
sphere in the center of each insert. The influence of slice thickness, exposure and bin width on feature values was investigated. Feature stability was assessed by calculating the concordance correlation coefficient (CCC) in a test-retest setting and for different combinations of scanners, tube currents and slice thicknesses.
Bin width influenced feature values, but this only had a marginal effect on the total number of stable features (CCC > 0.85) when comparing different scanners, slice thicknesses or exposures. Most radiomic features were affected by slice thickness, but this effect could be reduced by resampling the CT-images before feature extraction. Statistics feature 'energy' was the most dependent on slice thickness. No clear correlation between feature values and exposures was observed.
CT-scanner, slice thickness and bin width affected radiomic feature values, whereas no effect of exposure was observed. Optimization of gray-level discretization to potentially improve prognostic value can be performed without compromising feature stability. Resampling images prior to feature extraction decreases the variability of radiomic features.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Esophageal surgery is associated with complications and mortality. It is highly important to develop tools predicting unfavorable postoperative outcome. Esophageal cancer and neoadjuvant ...chemoradiotherapy (CRT) induce skeletal muscle wasting, which leads to diminished physiologic reserves. The purpose of this study was to investigate whether the degree of muscle mass lost during neoadjuvant CRT predicts postoperative mortality.
Methods
A total of 123 consecutive patients undergoing surgery for esophageal malignancy in the period 2008–2012 were included, of whom 114 received neoadjuvant CRT. Skeletal muscle mass was measured on routinely performed CT scans by assessing L3 muscle index (according to the Prado method) before and after neoadjuvant CRT, and the amount of muscle mass lost during neoadjuvant CRT (muscle loss index) was calculated. It was investigated whether this amount was associated with postoperative 30-day or in-hospital mortality and morbidity.
Results
In the complete cohort, no significant association between loss of muscle mass and mortality was found. However, skeletal muscle mass was significantly lower in patients with stage III–IV tumors compared with stage I–II tumors, prior to neoadjuvant CRT. In the stage III–IV subgroup, the amount of muscle mass lost during neoadjuvant CRT was predictive of postoperative mortality: −13.5 % (standard deviation 6.2 %) in patients who died postoperatively compared with −5.0 % (standard deviation 8.3 %) in surviving patients,
p
= 0.02.
Conclusions
Measurement of muscle mass loss during neoadjuvant chemoradiotherapy may provide a readily available and inexpensive assessment to identify patients at risk for developing unfavorable postoperative outcome after resection of esophageal malignancies, especially in patients with stage III–IV tumors.
Quantitative tissue characteristics derived from medical images, also called radiomics, contain valuable prognostic information in several tumour-sites. The large number of features available ...increases the risk of overfitting. Typically test–retest CT-scans are used to reduce dimensionality and select robust features. However, these scans are not always available. We propose to use different phases of respiratory-correlated 4D CT-scans (4DCT) as alternative.
In test–retest CT-scans of 26 non-small cell lung cancer (NSCLC) patients and 4DCT-scans (8 breathing phases) of 20 NSCLC and 20 oesophageal cancer patients, 1045 radiomics features of the primary tumours were calculated. A concordance correlation coefficient (CCC) >0.85 was used to identify robust features. Correlation with prognostic value was tested using univariate cox regression in 120 oesophageal cancer patients.
Features based on unfiltered images demonstrated greater robustness than wavelet-filtered features. In total 63/74 (85%) unfiltered features and 268/299 (90%) wavelet features stable in the 4D-lung dataset were also stable in the test–retest dataset. In oesophageal cancer 397/1045 (38%) features were robust, of which 108 features were significantly associated with overall-survival.
4DCT-scans can be used as alternative to eliminate unstable radiomics features as first step in a feature selection procedure. Feature robustness is tumour-site specific and independent of prognostic value.
To investigate the reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing tumor response early in the course of neoadjuvant chemoradiotherapy in patients with operable ...esophageal cancer.
Eleven male patients (mean age 54.8 years) with newly diagnosed esophageal cancer underwent DW-MRI before and 10 days after start of chemoradiotherapy. Reproducibility of apparent diffusion coefficient (ADC) measurements by manual (freehand) and semi-automated volumetric methods was assessed.
Interobserver reproducibility for the assessment of mean tumor ADC by the manual measurement method was good, with an ICC of 0.69 (95% CI, 0.36 to 0.85; P = 0.001). Interobserver reproducibility for the assessment of mean tumor ADC by the semi-automated volumetric measurement method was very good, with an ICC of 0.96 (95% CI, 0.91 to 0.98; P<0.001).
Semi-automated volumetric ADC measurements have higher reproducibility than manual ADC measurements in assessing tumor response to chemoradiotherapy in patients with esophageal adenocarcinoma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
To assess whether extending the observation period in patients with a near clinical complete response (near cCR) after chemoradiation (CRT) leads to an impaired oncological outcome.
...Methods
Patients who had a clinical complete response (cCR) 8–10 weeks after CRT restaging with magnetic resonance imaging and endoscopy were offered a watch-and-wait strategy (W&W1), while patients with a near cCR were offered to undergo local excision or a second restaging 6–12 weeks later. Patients who achieved a cCR at the second restaging were also offered a watch-and-wait strategy (W&W2).
Results
Overall, 102 patients with a cCR at the first restaging immediately entered the W&W1, while the remaining 68 patients had a near cCR: 19 patients underwent transanal endoscopic microsurgery and 49 patients opted for a second restaging. Additionally, 44/49 (90%) patients showed a cCR at the second restaging and entered the W&W2. Patients in the W&W1 group had a 2-year local regrowth-free rate (LRFR) of 84% and 2-year overall survival (OS) of 99%, while patients in the W&W2 group had a 2-year LRFR of 73% and OS of 98% (
p
> 0.05). Multivariable Cox regression analyses showed that late inclusion was not a significant predictive factor for higher risk of LR or lower non-regrowth disease-free survival.
Conclusions
Overall, 90% of patients with a near cCR 8–10 weeks after CRT will proceed to a cCR 6–12 weeks later; therefore, it seems logical to extend the observation period rather than to proceed to surgery. Although there is a non-significant increase in local regrowth rate in these patients, it does not seem to impact the oncological outcome.
OBJECTIVE:This study compared outcomes of patients with esophageal cancer and clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) undergoing active surveillance or immediate ...surgery.
BACKGROUND:Since nearly one-third of patients with esophageal cancer show pathologically complete response after nCRT according to CROSS regimen, the oncological benefit of immediate surgery in cCR is topic of debate.
METHODS:Patients with cCR based on endoscopic biopsies and endoscopic ultrasonography with fine-needle aspiration initially declining or accepting immediate surgery after nCRT were identified between 2011 and 2018. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), rate and timing of distant dissemination, and postoperative outcomes.
RESULTS:Some 98 patients with cCR were identified31 in the active surveillance- and 67 in the immediate surgery group with median follow-up of survivors of 27.7 and 34.8 months, respectively. Propensity score matching resulted in 2 comparable groups (n = 29 in both groups). Patients undergoing active surveillance or immediate surgery had a 3-year OS of 77% and 55% (HR 0.41; 95% CI 0.14–1.20, P = 0.104), respectively. The 3-year PFS was 60% and 54% (HR 1.08; 95% CI 0.44–2.67, P = 0.871), respectively. Patients undergoing active surveillance or immediate surgery had a comparable distant dissemination rate (both groups 28%), radical resection rate (both groups 100%), and severity of postoperative complications (Clavien–Dindo grade≥343% vs 45%, respectively).
CONCLUSION:In this retrospective study, OS and PFS in patients with cCR undergoing active surveillance or immediate surgery were not significantly different. Active surveillance with postponed surgery for recurrent disease was not associated with a higher distant dissemination rate or more severe adverse postoperative outcomes.
IntroductionOesophageal cancer (EC) and gastric cancer (GC) are among the top 10 cancers worldwide. Both diseases impact the nutritional status of patients and their Quality of Life (QoL). ...Preoperative malnutrition is reported in 42%–80%. However, studies investigating postoperative nutritional status are limited, and postoperative identification and treatment of micronutrient and macronutrient deficiencies are currently lacking in (inter-)national guidelines. The aim of this study is to identify and target micronutrient deficiencies after surgery for oesophagogastric neoplasms.MethodsThis is a single-centre prospective intervention trial performed in Zuyderland Medical Centre. 248 patients who underwent oesophagectomy (n=124) or (sub)total gastrectomy (n=124) from 2011 until 2022 will be included. Both groups will receive Calcium Soft Chew D3 and a multivitamin supplement (MVS) specifically developed according to the type of operation patients underwent; the oesophagectomy group will receive Multi-E and the gastrectomy group will receive Multi-G. The MVSs will be taken once daily and Calcium Soft Chew D3 two times per day. Supplementation will start after baseline measurements. At baseline (T0), blood withdrawal for micronutrient analysis and faecal elastase-1 analysis for exocrine pancreatic insufficiency (EPI) will be performed. Additionally, patients will receive questionnaires regarding QoL and dietary behaviour. After 180 days of supplementation (T1), baseline measurements will be repeated, and the supplement tolerance questionnaire will be completed. Measurements will also be conducted after 360 days (T2) and after 720 days (T3) of supplementation. The main study parameter is micronutrient deficiency (yes/no) for all measurements. Secondary parameters include occurrence of EPI (n, %), diarrhoea (n, %), steatorrhoea (n, %) or bloating (n, %), time between surgery and start of supplementation (mean in months), and QoL at all time points.Ethics and disseminationThe study was approved by the Zuyderland Medical Centre Ethics Committee, Heerlen, the Netherlands. The findings will be disseminated through scientific congresses and in peer-reviewed journals.Trial registration number NCT05281380.
Radiomic features retrieved from standard CT-images have shown prognostic power in several tumor sites. In this study, we investigated the prognostic value of pretreatment CT radiomic features to ...predict overall survival of esophageal cancer patients after chemoradiotherapy.
Two datasets of independent centers were analyzed, consisting of esophageal cancer patients treated with concurrent chemotherapy (Carboplatin/Paclitaxel) and 41.4Gy radiotherapy, followed by surgery if feasible. In total, 1049 radiomic features were calculated from the primary tumor volume. Recursive feature elimination was performed to select the 40 most relevant predictors. Using these 40 features and six clinical variables as input, two random forest (RF) models predicting 3-year overall survival were developed.
In total 165 patients from center 1 and 74 patients from center 2 were used. The radiomics-based RF model yielded an area under the curve (AUC) of 0.69 (95%CI 0.61-0.77), with the top-5 most important features for 3-year survival describing tumor heterogeneity after wavelet filtering. In the validation dataset, the RF model yielded an AUC of 0.61 (95%CI 0.47-0.75). Kaplan Meier plots were significantly different between risk groups in the training dataset (p = .027) and borderline significant in the validation dataset (p = .053). The clinical RF model yielded AUCs of 0.63 (95%CI 0.54-0.71) and 0.62 (95%CI 0.49-0.76) in the training and validation dataset, respectively. Risk groups did not reach a significant correlation with pathological response in the primary tumor.
A RF model predicting 3-year overall survival based on pretreatment CT radiomic features was developed and validated in two independent datasets of esophageal cancer patients. The radiomics model had better prognostic power compared to the model using standard clinical variables.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant ...chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed.
The SANO trial protocol has been published ( https://doi.org/10.1186/s12885-018-4034-1 ). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations CREs) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival.
Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline.
Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care.
New treatment options and centralization of surgery have improved survival for patients with non‐metastatic esophageal or gastric cancer. It is unknown, however, which patients benefitted the most ...from treatment advances. The aim of this study was to identify best‐case, typical and worst‐case scenarios in terms of survival time, and to assess if survival associated with these scenarios changed over time. Patients with non‐metastatic potentially resectable esophageal or gastric cancer diagnosed between 2006 and 2020 were selected from the Netherlands Cancer Registry. Best‐case (20th percentile), upper‐typical (40th percentile), typical (median), lower‐typical (60th percentile) and worst‐case (80th percentile) survival scenarios were defined, and regression analysis was used to investigate the change in survival time for each scenario across years. For patients with esophageal cancer (N = 24 352) survival time improved on average 12.0 (until 2011), 1.5 (until 2018), 0.7, 0.4 and 0.2 months per year for the best‐case, upper‐typical, median, lower‐typical and worst‐case scenario, respectively. For patients with gastric cancer (N = 9993) survival time of the best‐case scenario remained constant, whereas the upper‐typical, median, lower‐typical and worst‐case scenario improved on average with 1.0 (until 2018), 0.5, 0.2 and 0.2 months per year, respectively. Subgroup analyses showed that, survival scenarios improved for nearly all patients across treatment groups and for patients with squamous cell carcinomas or adenocarcinomas. Survival improved for almost all patients suggesting that in clinical practice the vast majority of patients benefitted from treatment advances. The clinically most meaningful survival advantage was observed for the best‐case scenario of esophageal cancer.
What's new?
New treatment options and centralization of surgery have improved survival for patients with non‐metastatic esophageal or gastric cancer. It is unknown, however, which patients most benefited from treatment advances. This study analyzed survival trends in patients with non‐metastatic esophagogastric cancer in the Netherlands over the past 15 years using survival scenarios based on survival percentiles in addition to median survival. The findings showed that survival improved for almost all patients, suggesting that the vast majority of patients benefited from treatment advances in clinical practice. The greatest clinically meaningful survival advantage was observed for the best‐case survival scenario in esophageal cancer.
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