Microscopic tumor spread beyond (echo)endoscopically determined tumor borders in esophageal cancer

Abstract Objective The microscopic tumor spread (MS) beyond the macroscopic tumor borders of esophageal tumors is crucial for determining the clinical target volume (CTV) in radiotherapy. The question arises whether current voluminous CTV margins of 3–5 cm around the macroscopic gross tumor volume (GTV) to account for MS are still accurate when fiducial markers are used for GTV determination. We aimed to pathologically validate the use of fiducial markers placed on the (echo)endoscopically determined tumor border (EDTB) as a surrogate for macroscopic tumor borders and to analyse the MS beyond EDTBs. Methods Thirty-three consecutive esophageal cancer patients treated with neo-adjuvant chemoradiotherapy after (echo)endoscopic fiducial marker implantation at cranial and caudal EDTB were included in this study. Fiducial marker positions were detected in the surgical specimens under CT guidance and demarcated with beads, and subsequently analysed for macroscopic tumor spread and MS beyond the demarcations. A logistic regression analysis was performed to determine predicting factors for MS beyond EDTB. Results A total of 60 EDTBs were examined in 32 patients. In 50% of patients no or only partial regression of tumor in response to therapy (≥Mandard 3) or higher was seen (i.e., residual tumor group) and included for MS analysis. None had macroscopic tumor spread beyond EDTBs. In the residual tumor group, only 20 and 21% of the cranial and caudal EDTBs were crossed with a maximum of 9 mm and 16 mm MS, respectively. This MS was corrected for each individual determined contraction rate (mean: 93%). Presence of MS beyond EDTB was significantly associated with initial tumor length (p = 0.028). Conclusion Our results validate the use of fiducial markers on EDTB as a surrogate for macroscopic tumor and indicate that CTV margins around the GTV to compensate for MS along the esophageal wall can be limited to 1–1.5 cm, when the GTV is determined with fiducial markers.

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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.

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Volume computed tomography perfusion as a predictive marker for treatment response to concurrent chemoradiotherapy in cervical cancer: a prospective study

Acta Radiologica ◽

10.1177/0284185120919261 ◽

2020 ◽

pp. 028418512091926

Author(s):

Tong Dong Rui ◽

Yue Dong ◽

Ling Song Qing ◽

Rui Tong ◽

Fei Wang Fei ◽

...

Keyword(s):

Computed Tomography ◽

Cervical Cancer ◽

Treatment Response ◽

Concurrent Chemoradiotherapy ◽

Residual Tumor ◽

Response To Therapy ◽

Short Term ◽

Computed Tomography Perfusion ◽

Tumor Group ◽

Significant Difference

Background Computed tomography perfusion (CTP) can provide information on blood perfusion as a reliable marker of tumor response to therapy. Purpose To assess the role of volume CTP (vCTP) parameters in predicting treatment response to concurrent chemoradiotherapy (CCRT) for cervical cancer. Material and Methods Thirty-three patients with cervical cancer underwent vCTP. Three CTP parameters of cervical cancer—including arterial flow (AF), blood volume (BV), and permeability surface (PS)—were measured in two different ways: the region of interest incorporating the “local hot” with the highest enhancement and “cold spot” with the lowest enhancement; and “whole-tumor” measurements. The patients were divided into non-residual and residual tumor groups according to the short-term response to treatment. The clinical and perfusion parameters were compared between the two groups. Results There was no significant difference in age, body mass index, FIGO stage, pathological grade, or pretreatment tumor size between the two groups ( P > 0.05). The non-residual tumor group had higher pretreatment AF in high-perfusion and low-perfusion subregions than the residual tumor group ( P <0.05), but the AF in whole-tumor regions was not different between the two groups ( P > 0.05). There were no differences in BV and PS between the two groups ( P > 0.05). The diagnostic potency of AF in the low-perfusion subregion was higher than that in the high-perfusion subregion. Conclusion vCTP parameters are valuable for the prediction of short-term effects. The AF in the low-perfusion subregion was a more effective index for predicting treatment response to CCRT of cervical cancer.

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Risk Factors for Residual Tumors in Surgery Following Neoadjuvant Chemotherapy for Esophageal Cancer

International Surgery ◽

10.9738/intsurg-d-17-00048.1 ◽

2019 ◽

Vol 103 (11-12) ◽

pp. 572-577

Author(s):

Hiroshi Sato ◽

Takuji Kaburaki ◽

Masahiro Niihara ◽

Yasuhiro Tsubosa ◽

Yuataka Miyawaki ◽

...

Keyword(s):

Risk Factors ◽

Squamous Cell Carcinoma ◽

Esophageal Cancer ◽

Neoadjuvant Chemotherapy ◽

Cell Carcinoma ◽

Squamous Cell ◽

Residual Tumor ◽

Tumor Location ◽

Thoracic Esophageal Cancer ◽

Tumor Group

Neoadjuvant chemotherapy (NAC) followed by esophagectomy is considered the standard treatment for resectable advanced esophageal squamous cell carcinoma in Japan. The purpose of this study was to identify the risk factors for residual tumors in surgery following NAC. We herein described risk factors for residual tumors in surgery following neoadjuvant chemotherapy for thoracic esophageal cancer. We reviewed the medical records of patients in our institution selected by using the following criteria: (1) pathologically confirmed squamous cell carcinoma or adenosquamous carcinoma before treatment; (2) cT1 to cT3; and (3) receipt of thoracotomy performed between 2007 and 2010 with the intention of curative resection after NAC composed of 5-fluorouracil plus cisplatin. The patients were divided into the complete resection group (R0 group), and the macroscopic or microscopic residual tumor group [R(+) group]. A total of 88 patients were eligible (R0, 70 patients; R1, 9 patients; R2, 7 patients; and not resected, 2 patients). There were more cT3 cancers and clinical node-positive diseases in the R(+) group than in the R0 group. Multivariate analysis identified tumor depth (cT3) and tumor location (above the carina) as risk factors for residual tumor. Patients with cT3 esophageal cancer above the carina have a high risk of residual tumor in esophagectomy following NAC. In these patients, more intensive preoperative therapy will be required.

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Fiducial markers vs. PET/CT for esophageal cancer GTV delineation for radiotherapy treatment planning using a standard SUV threshold and background uptake method.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.70 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 70-70 ◽

Cited By ~ 1

Author(s):

Jasmine A Oliver ◽

Puja Venkat ◽

Jaime Montilla-Soler ◽

Jason Klapman ◽

Gautumy Chikiti Dhadham ◽

...

Keyword(s):

Esophageal Cancer ◽

Fiducial Marker ◽

Contour Method ◽

Fiducial Markers ◽

Liver Uptake ◽

Median Distance ◽

Pet Ct ◽

The Stability ◽

Fdg Pet Ct ◽

Uptake Method

70 Background: Often in esophageal targets that move with respiration, endoscopically implanted fiducial markers are placed under ultrasound guidance within 1 cm from the superior and inferior tumor border. Our group has previously reported the stability of this method. 3D 18F-FDG PET/CT is obtained for initial staging of esophageal cancer and has altered the tumor volume in many sites. The correlation of these two methods for GTV delineation is currently undefined. Methods: Twenty-one patients with esophageal cancer were selected for this retrospective, IRB-approved analysis. Each patient underwent fiducial placement (by one of six endoscopists) at the inferior and superior borders of the tumor and received PET/CT prior to Radiotherapy (RTx). PET/CT images were imported into an image analysis software system for measurements. The distance between fiducial markers and MTV defined by 2.5 SUV contour (method 1) and MTV using a threshold above mean liver uptake (method 2) was calculated. The fiducials were located on CT. The distance between the centroid and MTV border was measured. The Concordance Correlation Coefficient (CCC) was calculated to determine the correlation between results from the two methods. Results: In method 1 the median distance between MTV (2.5 SUV) and fiducials was 1.0 cm (0.0 cm - 2.8 cm) and 1.0 cm (0.0 cm - 6.9 cm) for inferior and superior borders, respectively. In method 2 median distance between MTV and fiducials was 1.14 cm (0.0 cm - 2.62 cm) and 1.64 cm (0.33 cm – 6.84 cm) for inferior and superior borders, respectively. The CCC indicated poor agreement between methods for both distances (0.57 and 0.87 for inferior fiducial distance and superior fiducial distance, respectively). There was no correlation between MTV-to-fiducial distances greater than 2 cm and the endoscopist that performed the fiducial implantation. Conclusions: Although the methods of defining the MTV had poor strength of agreement, both methods demonstrated a robust correlation between inferior fiducial marker placement and inferior PET/CT uptake. The superior fiducial marker and MTV border illustrated discordance – unrelated to the endoscopist.

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Spreading of the vestibular schwannoma into porus acusticus internus. Endoscopic removal possibilities

OTORHINOLARYNGOLOGY 2-3(2) 2019 - OTORHINOLARYNGOLOGY ◽

10.37219/2528-8253-2018-1-40 ◽

2018 ◽

pp. 40-44

Author(s):

Orest Palamar ◽

Andriy Huk ◽

Dmytro Okonskyi ◽

Ruslan Aksyonov ◽

Dmytro Teslenko

Keyword(s):

Vestibular Schwannoma ◽

Internal Auditory Canal ◽

Residual Tumor ◽

Endoscopic Technique ◽

Vestibular Schwannomas ◽

Endoscopic Removal ◽

Tumor Removal ◽

Tumor Spread ◽

Microsurgical Technique ◽

Tumor Visualization

Aim: To investigate the features of the vestibular schwannoma spread into the internal auditory canal and the possibilities of endoscopic removal. Objectives: To improve tumor visualization in the internal auditory canal; to create a sufficient view angle for tumor removal during endoscopic opening of the internal auditory canal. Materials and methods: The results of surgical treatment of 20 patients with vestibular schwannomas in which the tumor spread to the internal auditory canal were analyzed. Microsurgical tumor removal was performed in 14 cases; Fully endoscopic removal of vestibular schwannomas was performed in 6 cases. The internal auditory canal opening was performed in 14 cases using microsurgical technique and in 6 cases with fully the endoscopic technique. Results: Gross total removal was achieved in 18 cases, subtotal removal in 2 cases. The tumor spread into the internal auditory canal was removed in all cases (100%). Opening the internal auditory canal using the endoscopic technique allows to increase the view angle (up to 20%) and to visualize along the axis of canal. Conclusions: 1) Endoscopic assistance technique allows to improve residual tumor visualization much more better then microsurgical technique; 2) Internal auditory canal opening using endoscopic technique is much more effective than the microsurgical technique (trepanning depth is larger); 3) Endoscopic methods for the internal auditory canal opening allows to increase canal angle view up to 20% (comparing to the microsurgical view).

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PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy

Biology ◽

10.3390/biology10040266 ◽

2021 ◽

Vol 10 (4) ◽

pp. 266

Author(s):

Juan Alfonso Redondo ◽

Romain Bibes ◽

Alizée Vercauteren Drubbel ◽

Benjamin Dassy ◽

Xavier Bisteau ◽

...

Keyword(s):

Esophageal Cancer ◽

Circadian Rhythm ◽

Survival Rate ◽

Circadian Clock ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Human Cancer ◽

Response To Therapy ◽

Circadian Oscillation ◽

Resistance To Therapy

Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor relapse. To effectively reduce the mortality rate of this disease, we need to better understand the molecular mechanisms underlying the development of resistance to therapy and translate that knowledge into novel approaches for cancer treatment. The circadian clock orchestrates several physiological processes through the establishment and synchronization of circadian rhythms. Since cancer cells need to fuel rapid proliferation and increased metabolic demands, the escape from circadian rhythm is relevant in tumorigenesis. Although clock related genes may be globally repressed in human eSCC samples, PER2 expression still oscillates in some human eSCC cell lines. However, the consequences of this circadian rhythm are still unclear. In the present study, we confirm that PER2 oscillations still occur in human cancer cells in vitro in spite of a deregulated circadian clock gene expression. Profiling of eSCC cells by RNAseq reveals that when PER2 expression is low, several transcripts related to apoptosis are upregulated. Consistently, treating eSCC cells with cisplatin when PER2 expression is low enhances DNA damage and leads to a higher apoptosis rate. Interestingly, this process is conserved in a mouse model of chemically-induced eSCC ex vivo. These results therefore suggest that response to therapy might be enhanced in esophageal cancers using chronotherapy.

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Frequency of Pathological Complete Response with Neo-Adjuvant Chemoradiotherapy in Locally Advanced Esophageal Cancer

Annals of Oncology ◽

10.1093/annonc/mdt203.64 ◽

2013 ◽

Vol 24 ◽

pp. iv55

Author(s):

Tahir Mehmood ◽

Muhammad Ali ◽

Kamran Saeed ◽

Muhammad Irfan ◽

Abdul Ghaffar ◽

...

Keyword(s):

Esophageal Cancer ◽

Pathological Complete Response ◽

Locally Advanced ◽

Complete Response ◽

Adjuvant Chemoradiotherapy ◽

Advanced Esophageal Cancer ◽

Locally Advanced Esophageal Cancer

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Pretreatment Esophageal Wall Thickness Associated with Response to Chemoradiotherapy in Locally Advanced Esophageal Cancer

Journal of Gastrointestinal Cancer ◽

10.1007/s12029-019-00337-3 ◽

2019 ◽

Vol 51 (3) ◽

pp. 947-951 ◽

Cited By ~ 1

Author(s):

Kraipop Wongwaiyut ◽

Sakchai Ruangsin ◽

Supparerk Laohawiriyakamol ◽

Siriporn Leelakiatpaiboon ◽

Duangjai Sangthawan ◽

...

Keyword(s):

Esophageal Cancer ◽

Wall Thickness ◽

Locally Advanced ◽

Esophageal Wall ◽

Advanced Esophageal Cancer ◽

Locally Advanced Esophageal Cancer

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Detection of Incidental Esophageal Cancers on Chest CT by Deep Learning

Frontiers in Oncology ◽

10.3389/fonc.2021.700210 ◽

2021 ◽

Vol 11 ◽

Author(s):

He Sui ◽

Ruhang Ma ◽

Lin Liu ◽

Yaozong Gao ◽

Wenhai Zhang ◽

...

Keyword(s):

Esophageal Cancer ◽

Deep Learning ◽

Cancer Detection ◽

Ct Images ◽

Chest Ct ◽

Validation Dataset ◽

Esophageal Wall ◽

Detection Model ◽

Model Training ◽

Sensitivity Specificity

ObjectiveTo develop a deep learning-based model using esophageal thickness to detect esophageal cancer from unenhanced chest CT images.MethodsWe retrospectively identified 141 patients with esophageal cancer and 273 patients negative for esophageal cancer (at the time of imaging) for model training. Unenhanced chest CT images were collected and used to build a convolutional neural network (CNN) model for diagnosing esophageal cancer. The CNN is a VB-Net segmentation network that segments the esophagus and automatically quantifies the thickness of the esophageal wall and detect positions of esophageal lesions. To validate this model, 52 false negatives and 48 normal cases were collected further as the second dataset. The average performance of three radiologists and that of the same radiologists aided by the model were compared.ResultsThe sensitivity and specificity of the esophageal cancer detection model were 88.8% and 90.9%, respectively, for the validation dataset set. Of the 52 missed esophageal cancer cases and the 48 normal cases, the sensitivity, specificity, and accuracy of the deep learning esophageal cancer detection model were 69%, 61%, and 65%, respectively. The independent results of the radiologists had a sensitivity of 25%, 31%, and 27%; specificity of 78%, 75%, and 75%; and accuracy of 53%, 54%, and 53%. With the aid of the model, the results of the radiologists were improved to a sensitivity of 77%, 81%, and 75%; specificity of 75%, 74%, and 74%; and accuracy of 76%, 77%, and 75%, respectively.ConclusionsDeep learning-based model can effectively detect esophageal cancer in unenhanced chest CT scans to improve the incidental detection of esophageal cancer.

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