Predictive value of endoscopic esophageal findings for residual esophageal cancer after neoadjuvant chemoradiotherapy

Abstract Background Endoscopic evaluation of the esophageal mucosa may play a role in an active surveillance strategy after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study investigated the yield of endoscopic findings for detection of residual disease. Methods Patients from the multicenter preSANO cohort, who underwent nCRT followed by surgery for esophageal or junctional cancer, were included. Upper endoscopy was performed 6 and 12 weeks after nCRT. Patients with residual disease at 6 weeks underwent immediate surgery. Endoscopic records were reviewed for presence of stenosis, suspicion of residual tumor, scar tissue, and ulceration. Presence and type of endoscopic findings were compared with outcome of the resection specimen. Results 118 of 156 patients (76 %) had residual disease in the resection specimen. Endoscopic suspicion of residual tumor was significantly associated with presence of residual disease. At 6 weeks, 40/112 patients with residual disease and 4/33 patients with complete response had endoscopic suspicion of residual tumor (36 % vs. 12 %; P = 0.01), while this was reported in 16/73 and 0/28 patients, respectively, at 12 weeks (22 % vs. 0 %; P < 0.01). Positive predictive value of endoscopic suspicion of residual tumor was 91 % at 6 weeks and 100 % at 12 weeks. Endoscopic findings of non-passable stenosis, passable stenosis, scar tissue, or ulceration were not associated with residual disease. Conclusions Endoscopic suspicion of residual tumor was the only endoscopic finding associated with residual disease. Based on its positive predictive value, this endoscopic finding may contribute to the diagnostic strategy used in active surveillance.

Download Full-text

PS02.084: PROSPECTIVE EVALUATION OF 18F-FDG PET-CT AFTER NEOADJUVANT CHEMORADIOTHERAPY FOR DETECTING LYMPH NODE METASTASES NEAR THE CELIAC TRUNK IN PATIENTS WITH ESOPHAGEAL CANCER

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps02.084 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 144-144

Author(s):

Jasper Groen ◽

Suzanne Gisbertz ◽

Mark I Van Berge Henegouwen ◽

Annelijn E Slaman ◽

Sybren Meijer ◽

...

Keyword(s):

Esophageal Cancer ◽

Lymph Node ◽

Lymph Node Metastases ◽

Predictive Value ◽

Neoadjuvant Chemoradiotherapy ◽

Celiac Trunk ◽

Pet Ct ◽

Resection Specimen ◽

Node Metastases ◽

18F Fdg

Abstract Background Celiac trunk metastases are an independent factor for inferior survival in patients with esophageal cancer. Detecting these metastases before esophagostomy would aid clinical decision making. The aim of our study was to evaluate the accuracy of integrated PET and CT (PET-CT) using 18F-FDG in detecting these metastases in patients with esophageal cancer after neoadjuvant chemoradiotherapy (nCRTx) followed by esophagectomy. Methods All patients with a carcinoma of the mid-to-distal esophagus or the gastroesophageal junction (GEJ) who underwent esophageal resection with curative intent following nCRTx between January 2011 and January 2017 were included. The PET-CT scans after nCRTx were reviewed by nuclear radiologists and lymph nodes within a margin of 2 cm around the celiac trunk were expressed in SUVmax. Lymph nodes with SUVmax > 2.0 were deemed positive. The truncal nodes were extracted during esophagectomy and reviewed by different pathologists using standard pathology protocol. To assess the accuracy of the PET-CT in detecting lymph node metastases near the celiac trunk the sensitivity, specificity and positive and negative predictive value were calculated. Results A total of 448 patients were included. There were 24 patients (5.4%) with positive truncal nodes on the PET-CT versus 424 patients (90.6%) with negative truncal nodes on the PET-CT. Out of these 24 patients 20 (83.3%) had truncal node metastases confirmed in the resection specimen (positive predictive value of 83.3%). In the other 424 patients 40 (9.4%) had truncal node metastases confirmed in the resection specimen (negative predictive value of 90.6%). This results in a sensitivity of 33.3% and a specificity of 99.0%. Conclusion The sensitivity and specificity of the PET-CT in detecting lymph node metastases near the celiac trunk in patients with esophageal cancer who underwent nCRTx were respectively 33.3% and 99.0% This shows that the PET-CT is accurate in detecting truncal lymph node metastases in this patient group. Disclosure All authors have declared no conflicts of interest.

Download Full-text

Towards an Organ-Sparing Approach for Locally Advanced Esophageal Cancer

Digestive Surgery ◽

10.1159/000493435 ◽

2018 ◽

Vol 36 (6) ◽

pp. 462-469 ◽

Cited By ~ 3

Author(s):

Berend Jan van der Wilk ◽

Ben M. Eyck ◽

Manon C.W. Spaander ◽

Roelf Valkema ◽

Sjoerd M. Lagarde ◽

...

Keyword(s):

Esophageal Cancer ◽

Active Surveillance ◽

Residual Disease ◽

Tumor Regression ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Distant Metastases ◽

Phase Iii ◽

Tumor Regression Grade ◽

Surveillance Strategy

Background: Active surveillance after neoadjuvant therapies has emerged among several malignancies. During active surveillance, frequent assessments are performed to detect residual disease and surgery is only reserved for those patients in whom residual disease is proven or highly suspected without distant metastases. After neoadjuvant chemoradiotherapy (nCRT), nearly one-third of esophageal cancer patients achieve a pathologically complete response (pCR). Both patients that achieve a pCR and patients that harbor subclinical disseminated disease after nCRT could benefit from an active surveillance strategy. Summary: Esophagectomy is still the cornerstone of treatment in patients with esophageal cancer. Non-surgical treatment via definitive chemoradiotherapy (dCRT) is currently reserved only for patients not eligible for esophagectomy. Since salvage esophagectomy after dCRT (50–60 Gy) results in increased complications, morbidity and mortality compared to surgery after nCRT (41.4 Gy), the latter seems preferable in the setting of active surveillance. Clinical response evaluations can detect substantial (i.e., tumor regression grade [TRG] 3–4) tumors after nCRT with a sensitivity of 90%, minimizing the risk of development of non-resectable recurrences. Current scarce and retrospective literature suggests that active surveillance following nCRT might not jeopardize overall survival and postponed surgery could be performed safely. Key Message: Before an active surveillance approach could be considered standard treatment, results of phase III randomized trials should be awaited.

Download Full-text

PS02.083: CIRCULATING CELL FREE TUMOR DNA FOR DISEASE MONITORING AFTER NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER: PROOF-OF-PRINCIPLE

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps02.083 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 144-144

Author(s):

B Eyck ◽

B Noordman ◽

Berend Van Der Wilk ◽

M Jansen ◽

P Atmodimedjo ◽

...

Keyword(s):

Esophageal Cancer ◽

Surgical Resection ◽

Residual Disease ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Monitoring ◽

Blood Samples ◽

Tp53 Mutations ◽

Resection Specimen ◽

Tumor Biopsies ◽

Tumor Dna

Abstract Background An active surveillance approach has been proposed for patients with a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (SANO trial). To justify renouncing surgical resection, patients with residual disease after nCRT should be accurately identified. However, substantial residual disease (TRG3–4) cannot be detected in 10% of patients with current diagnostic tests (preSANO trial). Circulating cell free tumor DNA (ctDNA) potentially improves detection of residual malignancy after nCRT and could be used for disease monitoring. The objective of this study was to investigate the feasibility of using ctDNA as biomarker for disease status after nCRT in esophageal cancer. Methods Twelve typical patients from the preSANO trial with variable pathological responses to nCRT were included. Blood was drawn and processed pretreatment. The feasibility of detecting TP53 mutations in baseline tumor biopsies was investigated using a next generation sequencing (NGS) panel. Subsequently, baseline blood samples of patients in whom specific TP53 mutations could be identified in baseline tumor biopsies or the surgical resection specimen were analyzed for ctDNA using cell free DNA NGS kits with single molecule barcoding (Oncomine Thermo Fisher). Results Baseline biopsy samples were available in 8 out of 12 patients. In 7 of these 8 patients (88%) specific TP53 mutations could be identified in their baseline biopsies. In 11 out of 12 patients (92%) specific TP53 mutations could be identified in baseline biopsies or the resection specimen. Eight of these 11 mutations were potentially detectable by the Oncomine panel. The panel detected TP53 mutational ctDNA in 4 of these 8 samples (50%). Conclusion Specific and clonal TP53 mutations can be identified in pretreatment biopsy samples and in surgical resection specimens of patients with esophageal cancer. These mutations can be matched to ctDNA identified in blood samples. Hence, ctDNA analyses in blood samples can potentially be used for disease monitoring during active surveillance and for disease monitoring in follow-up after surgical resection. Disclosure All authors have declared no conflicts of interest.

Download Full-text

P84 LOCALIZATION OF UNDETECTED RESIDUAL TUMOR AFTER NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH ESOPHAGEAL CANCER

Diseases of the Esophagus ◽

10.1093/dote/doz092.84 ◽

2019 ◽

Vol 32 (Supplement_2) ◽

Author(s):

B J van der Wilk ◽

M Doukas ◽

B M Eyck ◽

M C W Spaander ◽

E J Schoon ◽

...

Keyword(s):

Esophageal Cancer ◽

Clinical Response ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Residual Tumor ◽

Esophageal Wall ◽

Submucosal Layer ◽

Submucosal Tumors ◽

Mucosal Layer ◽

Resection Specimen

Abstract Introduction The preSANO-trial aimed to determine accuracy of clinical response evaluations (CREs) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally-advanced esophageal cancer. After introduction of the ‘bite-on-bite’ biopsy-technique, most residual tumors were detected. Aim of this study was to determine the location of residual tumors that were not detected during CREs and whether or not endoscopic (bite-on-bite) biopsies had the theoretical potential to detect these tumors. Methods In this side-study of the prospective preSANO trial, biopsies and resection specimens were independently revised by two GI-pathologists. All patients were included that had residual tumor in the resection specimen that was not detected during two clinical response evaluations, 6 and 12 weeks after completion of nCRT. In the resection specimen, the tumor regression grade was defined for each esophageal wall layer. It was determined how often submucosal tumors under a tumor-free mucosal layer were missed during CREs. Biopsies taken during CREs were revised for the presence of submucosal tissue. This was defined as presence of submucosal structures, i.e. submucosal glands and/or thick-walled vessel-structures. Results Some 103 of 207 patients underwent CREs followed by surgery. Residual tumor was not detected during CREs in 33 patients. Resection specimens of 28 of these patients were available for revision. Missed residual tumors were located in the mucosal layer of the esophageal wall in 64% of these patients. Residual tumors were located in the submucosal layer, under a tumor-free mucosal layer, in 29% of patients. One patient still had tumor under a tumor-free mucosal- and submucosal layer. Submucosal structures were detected in two patients and it was uncertain whether submucosal tissue was present in six patients, while no specific submucosal structures were detected in 21 patients. Conclusion The majority of patients in whom residual tumor remained undetected during clinical response evaluations had tumor cells in the mucosal layer of the esophageal wall. Nearly one third of the patients had tumor in the submucosal layer under a tumor-free mucosa. Whether these submucosal tumors can be detected using endoscopic biopsies is uncertain. Further improvement of the accuracy of CREs should focus on sampling of larger mucosal areas, for example by using brush techniques.

Download Full-text

Endoscopic ultrasound measurements for detection of residual disease after neoadjuvant chemoradiotherapy for esophageal cancer

Endoscopy ◽

10.1055/a-0795-3220 ◽

2018 ◽

Vol 51 (04) ◽

pp. 326-332 ◽

Cited By ~ 1

Author(s):

Ruben van der Bogt ◽

Bo Noordman ◽

Kausilia Krishnadath ◽

Carlijn Roumans ◽

Erik Schoon ◽

...

Keyword(s):

Esophageal Cancer ◽

Tumor Cells ◽

Endoscopic Ultrasound ◽

Residual Disease ◽

Tumor Regression ◽

Neoadjuvant Chemoradiotherapy ◽

Residual Tumor ◽

Tumor Regression Grade ◽

Residual Thickness ◽

Absolute Measurements

Abstract Background Endoscopic ultrasound (EUS) measurements of residual thickness and residual area have been suggested to correlate with histopathological residual tumor after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study assessed the predictive value of EUS-based measurements using tumor thickness and tumor area before nCRT, and residual thickness and residual area 6 and 12 weeks after completion of nCRT for detection of residual disease. Methods This was a substudy of the diagnostic multicenter preSANO trial. The primary end point of the current study was the percentage of tumor regression grade (TRG) 3 – 4 (> 10 % vital tumor cells) residual disease that was detected using EUS-based measurements. Associations of absolute measurements of residual thickness/area and proportional change compared with baseline were evaluated. In the case of a statistically significant association, optimal cut-offs to distinguish TRG3 – 4 residual disease from TRG1 (no vital tumor cells) were determined using Youden’s J index. Results 138 patients were included. Residual thickness and residual area were statistically significantly associated with TRG3 – 4 residual disease 12 weeks after completion of nCRT (odds ratio 1.36, P < 0.01 and 1.64, P = 0.02, respectively). The cut-off for residual thickness was 4.5 mm, which correctly detected 87 % of TRG3 – 4 residual disease and 52 % of TRG1. The cut-off for residual area was 0.92 cm2, which detected 89 % of TRG3 – 4 residual disease and 40 % of TRG1. Conclusions EUS measurements of residual thickness and residual area adequately detected TRG3 – 4 residual disease with a sensitivity of almost 90 % 12 weeks after completion of nCRT. Hence, residual thickness and residual area may aid in the restaging of esophageal cancer after nCRT.

Download Full-text

Positive predictive value of mpmri in men under active surveillance: Can the biopsy history influence radiological assessment?

European Urology ◽

10.1016/s0302-2838(21)01291-4 ◽

2021 ◽

Vol 79 ◽

pp. S1286

Author(s):

L. Nocera ◽

A. Stabile ◽

R. Leni ◽

G. Gandaglia ◽

N. Fossati ◽

...

Keyword(s):

Positive Predictive Value ◽

Active Surveillance ◽

Predictive Value ◽

Radiological Assessment

Download Full-text

5-Aminolevulinic Acid-derived Tumor Fluorescence

Neurosurgery ◽

10.1227/neu.0000000000000267 ◽

2013 ◽

Vol 74 (3) ◽

pp. 310-320 ◽

Cited By ~ 150

Author(s):

Walter Stummer ◽

Jörg-Christian Tonn ◽

Claudia Goetz ◽

Winfried Ullrich ◽

Herbert Stepp ◽

...

Keyword(s):

Positive Predictive Value ◽

Predictive Value ◽

Aminolevulinic Acid ◽

Malignant Gliomas ◽

Residual Tumor ◽

Tissue Type ◽

Strong Fluorescence ◽

Tumor Bed ◽

Cell Densities ◽

Magnetic Resonance Imaging Mri

Abstract BACKGROUND: 5-Aminolevulinic acid is used for fluorescence-guided resections. During resection, different macroscopic fluorescence qualities (“strong,” “weak”) can be distinguished that help guide resections. OBJECTIVE: This prospective study was designed to assess the reliability of visible fluorescence qualities by spectrometry, pathology, and imaging. METHODS: Thirty-three patients with malignant gliomas received 5-aminolevulinic acid (20 mg/kg). After debulking surgery, standardized biopsies were obtained from tissues with “weak” and “strong” fluorescence and from nonfluorescing near and distant brain for blinded assessment of cell density and tissue type (necrosis, solid or infiltrating tumor, normal tissue). The positive predictive value was calculated. Unresected fluorescing tissue was navigated for blinded correlation to postoperative magnetic resonance imaging (MRI). Receiver operating characteristic curves were generated for assessing the classification efficiency of spectrometry. RESULTS: “Strong” fluorescence corresponded to greater spectrometric fluorescence, solidly proliferating tumor, and high cell densities, whereas “weak” fluorescence corresponded to lower spectrometric fluorescence, infiltrating tumor, and medium cell densities. The positive predictive value was 100% in strongly fluorescing tissue and 95% in weakly fluorescing tissue. Spectrometric fluorescence was detected in marginal tissue without macroscopic fluorescence. Depending on the threshold, spectrometry displayed greater sensitivity but lower specificity (accuracy 88.4%). Residual MRI enhancement in the tumor bed was detected in 15 of 23 (65%) patients with residual fluorescence, but in none of the patients without residual fluorescence. CONCLUSION: Macroscopic fluorescence qualities predict solid and infiltrating tumor, providing useful information during resection. Fluorescence appears superior to contrast enhancement on MRI for indicating residual tumor. Spectrometry, on the other hand, is more sensitive but less specific, depending on threshold definition.

Download Full-text

Administrative Data Fail to Accurately Identify Cases of Healthcare-Associated Infection

Infection Control and Hospital Epidemiology ◽

10.1086/502684 ◽

2006 ◽

Vol 27 (4) ◽

pp. 332-337 ◽

Cited By ~ 77

Author(s):

Eileen R. Sherman ◽

Kateri H. Heydon ◽

Keith H. St. John ◽

Eva Teszner ◽

Susan L. Rettig ◽

...

Keyword(s):

Positive Predictive Value ◽

Administrative Data ◽

Active Surveillance ◽

Predictive Value ◽

Healthcare Associated Infection ◽

Cross Sectional ◽

Policy Makers ◽

Predictive Values ◽

Healthcare Associated ◽

Very High

Objective.Some policy makers have embraced public reporting of healthcare-associated infections (HAIs) as a strategy for improving patient safety and reducing healthcare costs. We compared the accuracy of 2 methods of identifying cases of HAI: review of administrative data and targeted active surveillance.Design, Setting, and Participants.A cross-sectional prospective study was performed during a 9-month period in 2004 at the Children's Hospital of Philadelphia, a 418-bed academic pediatric hospital. “True HAI” cases were defined as those that met the definitions of the National Nosocomial Infections Surveillance System and that were detected by a trained infection control professional on review of the medical record. We examined the sensitivity and the positive and negative predictive values of identifying HAI cases by review of administrative data and by targeted active surveillance.Results.We found similar sensitivities for identification of HAI cases by review of administrative data (61%) and by targeted active surveillance (76%). However, the positive predictive value of identifying HAI cases by review of administrative data was poor (20%), whereas that of targeted active surveillance was 100%.Conclusions.The positive predictive value of identifying HAI cases by targeted active surveillance is very high. Additional investigation is needed to define the optimal detection method for institutions that provide HAI data for comparative analysis.

Download Full-text

Endoscopic ultrasound and fine-needle aspiration for the detection of residual nodal disease after neoadjuvant chemoradiotherapy for esophageal cancer

Endoscopy ◽

10.1055/a-1065-1759 ◽

2019 ◽

Vol 52 (03) ◽

pp. 186-192 ◽

Cited By ~ 1

Author(s):

Ruben D. van der Bogt ◽

Berend J. van der Wilk ◽

Jan-Werner Poley ◽

Kausilia K. Krishnadath ◽

Erik J. Schoon ◽

...

Keyword(s):

Esophageal Cancer ◽

Endoscopic Ultrasound ◽

Fine Needle Aspiration ◽

Residual Disease ◽

Histopathological Examination ◽

Neoadjuvant Chemoradiotherapy ◽

Needle Aspiration ◽

Fine Needle ◽

Specificity And Sensitivity ◽

Pet Ct

Abstract Background Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) are potential tools for the detection of residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study investigated yield of EUS and FNA for detection of malignant lymph nodes (LNs) after nCRT. Methods This was a post hoc analysis of the preSANO trial. EUS was performed 10 – 12 weeks after nCRT. 18F-fluorodeoxyglucose positron emission tomography – computed tomography (18F-FDG PET-CT) was used to guide targeting of suspicious LNs. Consecutive FNA sampling was performed for suspicious LNs identified on EUS and/or PET-CT. EUS nodal staging was compared with histopathological examination of the resection specimen. The primary outcome was the proportion of correctly identified patients with malignant LNs by radial EUS. Results 101 consecutive patients were included: 79 patients had no malignant LNs, of whom 62 were classified correctly by EUS (specificity 78 %); 22 patients had malignant LNs, of whom 11 were identified (sensitivity 50 %). Six of these patients had ≥ 1 suspicious LN not fulfilling EUS criteria (round, hypoechogenic, > 5 mm). Malignant LNs in falsely negative patients were predominantly located at distal LN stations. Specificity and sensitivity of conclusive FNA outcomes were 100 % (7/7) and 75 % (3/4), respectively. FNA outcome was uncertain in eight patients, half of whom appeared to have malignant LNs. Conclusions EUS only detected 50 % of patients with malignant LNs 10 – 12 weeks after nCRT. To optimize sensitivity and minimize the risk of missing residual disease, FNA of LNs should be performed even in cases of low endosonographic suspicion.

Download Full-text