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

Endoscopy ◽  
2018 ◽  
Vol 51 (04) ◽  
pp. 326-332 ◽  
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.

scholarly journals Towards an Organ-Sparing Approach for Locally Advanced Esophageal Cancer

2018 ◽  
Vol 36 (6) ◽  
pp. 462-469 ◽  
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.

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

Endoscopy ◽  
2019 ◽  
Vol 52 (03) ◽  
pp. 186-192 ◽  
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.

scholarly journals Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 173
Author(s):  
Eelke L.A. Toxopeus ◽  
Femke M. de Man ◽  
Nanda Krak ◽  
Katharina Biermann ◽  
Annemieke J.M. Nieuweboer ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Treatment Response ◽  
Tumor Regression ◽  
Geometric Mean ◽  
Neoadjuvant Chemoradiotherapy ◽  
Systemic Exposure ◽  
Tumor Regression Grade ◽  
P Value ◽  
Response To Chemotherapy ◽  
Regression Grade

Inter-individual variability in paclitaxel pharmacokinetics may play a role in the response to chemotherapy. Therefore, we studied the association between paclitaxel clearance and treatment response in patients with esophageal cancer. All patients who received paclitaxel (plus carboplatin) treatment for esophageal cancer between 2007 and 2013 were included. The treatment was given as neoadjuvant chemoradiotherapy (nCRT), induction chemotherapy (iCT), or palliative chemotherapy (pCT). The treatment response was assessed by the tumor regression grade (TRG) or by the RECIST1.1 criteria, respectively. The unbound paclitaxel clearance (CL) was estimated with NONMEM. The log-transformed clearance was related to response with ANOVA and independent sample t-tests. A total of 166 patients were included, of whom 113 received nCRT, 23 iCT and 30 pCT. In patients receiving nCRT, paclitaxel clearance was not associated with tumor regression grade (p-value = 0.25), nor with pathologically complete response (geometric mean 561.6 L/h) and residual disease (geometric mean 566.1 L/h, p-value = 0.90). In patients who underwent iCT or pCT, also no association between paclitaxel clearance and RECIST outcome was identified (iCT: p-value = 0.08 and pCT: p-value = 0.81, respectively). In conclusion, systemic paclitaxel exposure was not associated with response to common paclitaxel-based treatment regimens for esophageal cancer. Future studies should focus on tumor exposure in relation to systemic exposure and treatment outcome.

Immunohistochemical analysis of tumor regression grade for rectal cancer after neoadjuvant chemoradiotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22089-e22089
Author(s):  
V. Moreno Garcia ◽  
P. Cejas ◽  
J. Feliu ◽  
J. De Castro ◽  
C. Belda-Iniesta ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cox Regression ◽  
Tumor Regression ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Rank Test ◽  
Tumor Regression Grade ◽  
Double Negative ◽  
Viable Tumor ◽  
Regression Grade

e22089 Background: Tumor regression grade (TRG) as defined by Rodel et al. has been suggested as an independent prognostic factor for rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT). However TRG 2 and 3 determination, semiquantitatively defined as more/less than 50% tumor regression, respectively, do not clearly correlate with prognosis. TRG 2 vs 3 discrimination is largely subjective hurdling prognostic analysis. The purpose of our study was to find an immunohistochemical pattern to better stratify these patients according to prognosis in term of disease free survival (DFS) and overall survival (OS). Methods: Immunohistochemistry of EGFR, VEGF, CD133, p53 and Ki67 was evaluated by tissue microarrays on surgical specimens from 88 patients. Preoperative chemotherapy was UFT-LV (30%) or oxaliplatin-based (70%) plus pelvic radiotherapy (50 Gy) followed by mesorectal excision. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 1 when regression was less than 25%. TRG 2 and 3 were defined as described above. Univariate analyses were performed according to the Kaplan-Meier method. Comparisons between curves were evaluated by the log-rank test. Cox regression was used for the multivariate analysis. Results: At a median follow-up of 39 months, the TRG was an independent predictor of DFS (p=0.05) and OS (p=0.001) but no differences were found between TRG 2 and 3 in terms of DFS (p=0.74) or OS (p=0.41). Our results show an immunohistochemical bad prognostic profile for tumors TRG 2 and 3 configured by double negativity of EGFR and CD133 expression (less than 5% of tumor cells membrane immunoreactivity for both antibodies). 3-year DFS and OS for these patients (vs. TRG 2 and 3 not-double negative) were 33 vs 65% (p=0.05) [HR=2.4 (95%CI, 0.9–6.1) p=0.06] and 77 vs 95% (p=0.06) [HR=4.1 (95%CI, 0.7–21.5) p=0.09]. Conclusions: The EGFR/CD133 double negative rectal tumors with TRG 2 or 3 after chemoradiotherapy show a higher risk of relapse or death. These results can help clinicians to determine better individual prognosis and are worth to confirm prospectively. No significant financial relationships to disclose.

Correlation between standardized uptake value in pre- and post-neoadjuvant chemoradiotherapy and tumor regression grade in patients with locally advanced esophageal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 150-150
Author(s):  
Kathryn Baksh ◽  
Khaldoun Almhanna
Keyword(s):  
Esophageal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Tumor Regression Grade ◽  
P Value ◽  
Advanced Esophageal Cancer ◽  
Pet Scans ◽  
Regression Grade ◽  
Locally Advanced Esophageal Cancer

150 Background: A multimodality approach with neoadjuvant chemotherapy and radiation is the standard of care in the United States in the treatment of patients with locally advanced esophageal cancer. It is well established that neoadjuvant chemoradiotherapy (CRT) in these patients can facilitate downstaging, correlating with pathologic response, and improving overall survival. Our clinical practice involves the use of positron emission tomography (PET) to assist with staging in patients prior to undergoing neoadjuvant CRT and surgery. While there has been evidence showing correlation between tumor regression grade (TRG) and increased overall survival in these patients, the relationship between standardized uptake values on PET scans and TRG has not been discerned. The purpose of this study was to determine whether pre and post-chemoradiotherapy SUV on PET scans correlate with TRG in esophageal cancer patients receiving neoadjuvant chemoradiotherapy. Methods: A retrospective review of 56 patients with stage II-III esophageal cancer treated with neo-adjuvant CRT followed by surgery was performed. Pre- and post- treatment PET scans were reviewed. Maximum SUV at the site of the primary tumor was recorded. Upon completion of surgery, tumor regression grade was determined by a specialized pathologist. Spearman correlation was used to compare pre, post, and change in max SUV, to the 4 level TRG variables. Results: The median follow-up was 24 months. No significant correlation was found between pre-treatment or post treatment SUV and TRG with p value of 0.73 and 0.94 respectively. There was no significant correlation between decreased FDG uptake following CRT and TRG with p value of 0.82. Consistent with previous data, TRG predicted the therapeutic efficacy and prognosis for patients with locally advanced esophageal carcinoma treated by neoadjuvant chemotherapy. Conclusions: Our results are preliminary and retrospective in nature. A larger sample is needed to confirm these findings. Decreased FDG uptake in sequential PET scans strongly correlates with tumor response, but is not accurate enough to predict pathological response.

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

Endoscopy ◽  
2021 ◽  
Author(s):  
Ruben D. van der Bogt ◽  
Berend J. van der Wilk ◽  
Suzan Nikkessen ◽  
Kausilia K. Krishnadath ◽  
Erik J. Schoon ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Positive Predictive Value ◽  
Active Surveillance ◽  
Predictive Value ◽  
Residual Disease ◽  
Neoadjuvant Chemoradiotherapy ◽  
Residual Tumor ◽  
Scar Tissue ◽  
Endoscopic Findings ◽  
Resection Specimen

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.

Rectal cancer – current treatment strategy and the tumor regression grade evaluation after neoadjuvant therapy in patients who underwent surgery at the I. Department of Surgery, General University Hospital in Prague between 2012 and 2016

2021 ◽  
Vol 100 (2) ◽  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Tumor Regression ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Current Treatment ◽  
University Hospital ◽  
Tumor Regression Grade ◽  
Oncological Treatment ◽  
Regression Grade

Introduction: The article contains a summary of the issues of staging and therapy with an emphasis on the neoadjuvant treatment and associated tumor regression grade with the analysis of our own group of patients. Methods: Retrospective analysis of patients with rectal cancer who underwent a surgery at the 1st Department of Surgery – Thoratic, Abdominal and Injury Surgery; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic, focusing on those who underwent neoadjuvant chemoradiotherapy and their pathologists evaluated tumor regression grade after the resection. Results: The group consists of 161 patients operated on between 2012 and 2016. 47 patients underwent neoadjuvant oncological treatment with further evaluation of the tumor regression grade by a pathologist, a scoring system according to Ryan was used. A complete pathological response was elicited in 10.4% of patients, no response in 35.4% of patients, and partial tumor regression in 54.2%. Conclusion: Although there is a difference in our results compared to foreign publications, the proportion of patients remains comparable. Studies evaluating the advantages versus disadvantages of neoadjuvant therapy will certainly follow, and the question of the suitability of surgical treatment as the only curative solution is partially raised.

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