Prevalence and Prognostic Significance of Extramural Venous Invasion in Patients with Locally Advanced Esophageal Cancer

BACKGROUND: Extramural venous invasion (EMVI) is a known adverse prognostic factor in patients with colorectal carcinoma. The prevalence and significance of EMVI in esophageal cancer (EC) patients is still unclear. METHODS: From a prospectively maintained database, we retrospectively reviewed the resection specimens of patients with pathologic locally advanced (pT3/T4/N0-3) EC who were treated with curative intent between 2000 and 2015. Patients with previous malignancies and gastroesophageal junction (type II/III) tumors were excluded. Included were 81 patients who underwent surgery alone and 37 patients who underwent neoadjuvant chemoradiotherapy (nCRT). EMVI was assessed on hematoxylin and eosin slides and confirmed or excluded by additional Elastica van Gieson staining. Survival was analyzed using a multivariable Cox regression. RESULTS: EMVI was present in 23.5% (n = 19) of patients in the surgery-alone group and 21.6% (n = 8) of patients in the nCRT group. The prevalence of EMVI after surgery alone was significantly high in squamous cell carcinomas and among tumors located in the mid-esophagus, as well as those with lymphovascular invasion (p  pT3/N0-3 EC patients, EMVI was present in 23.5% of patients in the surgery-alone group and in 21.6% of patients after nCRT. EMVI was an independent adverse prognostic factor in patients after surgery alone

The diagnostic value of 124I-PET in patients with differentiated thyroid cancer

Background The purpose of this prospective study was to evaluate the clinical diagnostic value of iodine- 124 ( I-124)positron emission tomography ( PET) in patients with advanced differentiated thyroid carcinoma ( DTC) and to compare the I-124- PET imaging results with the I-131 wholebody scan ( WBS). Materials and methods Twenty patients with histologically proven advanced DTC ( including T4, extra- nodal tumour growth, or distant metastases) underwent diagnostic (IWBS)-I-131, I-124- PET scan, and post-treatment I-131- WBS 4 months after ablation. The findings on the I-124- PET were compared with the findings on the diagnostic and post-therapeutic I-131- WBS and were also correlated with radiologic and/ or cytological investigations. Results I-124- PET vs diagnostic I-131- WBS. Eleven patients showed uptake on the I-124- PET. Only 3 of these 11 patients also showed uptake on the diagnostic I-131 scan, but the uptake was more clearly visible and the abnormalities were more extensive on the I-124- PET. I-124- PET vs post-treatment I-131- WBS. Eleven patients showed uptake on the I-124- PET, which was also visible on the post-treatment scan in nine patients; in the other two patients, no uptake was observed on the post-treatment scan and no anatomical localisation could be confirmed. Two patients showed only uptake on the post-treatment scan without uptake on the I-124- PET: in one, the uptake was confirmed by MRI, and in the other, no anatomical localisation was found. In seven patients, no uptake was observed on both the scans. Conclusion I-124- PET proved to be a superior diagnostic tool as compared to low-dose diagnostic I-131 scans and adequately predicted findings on subsequent high-dose post-treatment I-131 scans

Impact of Endoscopic Ultrasonography on (18)F-FDG-PET/CT Upfront Towards Patient Specific Esophageal Cancer Treatment

INTRODUCTION: In patients with potentially resectable esophageal cancer (EC), the value of endoscopic ultrasonography (EUS) after fluorine-18 labeled fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) is questionable. Retrospectively, we assessed the impact of EUS after PET/CT on the given treatment in EC patients. METHODS: During the period 2009-2015, 318 EC patients were staged as T1-4aN0-3M0 with hybrid (18)F-FDG-PET/CT or (18)F-FDG-PET with CT and EUS if applicable in a nonspecific order. We determined the impact of EUS on the given treatment in 279 patients who also were staged with EUS. EUS had clinical consequences if it changed curability, extent of radiation fields or lymph node resection (AJCC stations 2-5), and when the performed fine-needle aspiration (FNA) provided conclusive information of suspicious lymph node. RESULTS: EUS had an impact in 80 (28.7%) patients; it changed the radiation field in 63 (22.6%), curability in 5 (1.8%), lymphadenectomy in 48 (17.2%), and FNA was additional in 21 (7.5%). In patients treated with nCRT (n = 194), EUS influenced treatment in 53 (27.3%) patients; in 38 (19.6%) the radiation field changed, in 3 (1.5%) the curability, in 35 (18.0%) the lymphadenectomy, and in 17 (8.8%) FNA was additional. EUS influenced both the extent of radiation field and nodal resection in 31 (16.0%) nCRT patients. CONCLUSIONS: EUS had an impact on the given treatment in approximately 29%. In most patients, the magnitude of EUS found expression in the extent of radiotherapy target volume delineation to upper/high mediastinal lymph nodes

Late cardiac toxicity of neo-adjuvant chemoradiation in esophageal cancer survivors:A prospective cross-sectional pilot study

Purpose: Although cure rates in esophageal cancer (EC) have improved since the introduction of neoadjuvant chemoradiation (nCRT), evidence for treatment-related cardiac toxicity is growing, of which the exact mechanisms remain unknown. The primary objective of this study was to identify (subclinical) cardiac dysfunction in EC patients after nCRT followed by surgical resection as compared to surgery alone. Materials and Methods: EC survivors followed for 5-15 years after curative resection with (n = 20) or without (n = 20) nCRT were enrolled in this prospective cross-sectional pilot study. All patients underwent several clinical and diagnostic tests in order to objectify (sub)clinical cardiac toxicity including cardiac CT and MRI, echocardiography, ECG, 6-minutes walking test, physical examination and EORTC questionnaires. Results: We found an increased rate of myocardial fibrosis (Linear late gadolinium enhancement (LGE) 4 vs. 1; p = 0.13; mean extracellular volume (ECV) 28.4 vs. 24.0; p < 0.01), atrial fibrillation (AF) (6 vs. 2; p = 0.07) and conduction changes in ECG among patients treated with nCRT as compared to those treated with surgery alone. The results suggested an impact on quality of life in terms of worse role functioning for this patient group (95.0 vs. 88.8; p = 0.03). Conclusion: Based on our analyses we hypothesize that in EC patients, radiation-induced myocardial fibrosis plays a central role in cardiac toxicity leading to AF, conduction changes and ultimately to decreased role functioning. The results emphasize the need to verify these findings in larger cohorts of patients. (C) 2021 The Author(s). Published by Elsevier B.V

Retrospective Denial as A Coping Method

Worldwide, gastric cancer is one of the most common and fatal cancers. The majority of patients present with an advanced stage of disease. Even with use of palliative chemotherapy most patients die within 1 year after diagnosis. Medical psychological attention after a diagnosis of incurable cancer is focused on end of life support. This paper presents the care of a patient treated with palliative intent with chemotherapy for an irresectable histologically confirmed gastric cancer. When, unexpectedly prolonged symptom free survival followed, the reaction of the patient came as a surprise to the attending medical team. In this case history we urge those who care for incurable cancer patients, that the rare patient who survives against all odds may require special psychological care

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE):a multicenter observational study

BACKGROUND: 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 (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)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. METHODS: 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 (18)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. DISCUSSION: 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. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341

Crystal IS on the move

Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis 18 years and follow-up 5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4% women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction <50% was found in one survivor, and median global longitudinal systolic strain was near normal. Diastolic dysfunction was present in 14 asymptomatic survivors (21.2%). Overall, diastolic function of survivors was lower compared with controls (emean 14.5 versus 15.8cm/s, P=0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed. Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac agin

Impact of Age and Comorbidity on Choice and Outcome of Two Different Treatment Options for Patients with Potentially Curable Esophageal Cancer

PURPOSE: This study was designed to assess the impact of age and comorbidity on choice and outcome of definitive chemoradiotherapy (dCRT) or neoadjuvant chemoradiotherapy plus surgery. METHODS: In this population-based study, all patients with potentially curable EC (cT1N+/cT2-3, TX, any cN, cM0) diagnosed in the South East of the Netherlands between 2004 and 2014 were included. Kaplan-Meier method with log-rank tests and multivariable Cox regression analysis were used to compare overall survival (OS). RESULTS: A total of 702 patients was included. Age ≥ 75 years and multiple comorbidities were associated with a higher probability for dCRT (odds ratio [OR] 8.58; 95% confidence interval [CI] 4.72-15.58; and OR 3.09; 95% CI 1.93-4.93). The strongest associations were found for the combination of hypertension plus diabetes (OR 3.80; 95% CI 1.97-7.32) and the combination of cardiovascular with pulmonary comorbidity (OR 3.18; 95% CI 1.57-6.46). Patients with EC who underwent dCRT had a poorer prognosis than those who underwent nCRT plus surgery, irrespective of age, number, and type of comorbidities. In contrast, for patients with squamous cell carcinoma with ≥ 2 comorbidities or age ≥ 75 years, OS was comparable between both groups (hazard ratio [HR] 1.52; 95% CI 0.78-2.97; and HR 0.73; 95% CI 0.13-4.14). CONCLUSIONS: Histological tumor type should be acknowledged in treatment choices for patients with esophageal cancer. Neoadjuvant chemoradiotherapy plus surgery should basically be advised as treatment of choice for operable esophageal adenocarcinoma patients. For patients with esophageal squamous cell carcinoma with ≥ 2 comorbidities or age ≥ 75 years, dCRT may be the preferred strategy