P204 DETECTING PATHOLOGICAL COMPLETE RESPONSE IN ESOPHAGEAL CANCER AFTER NEOADJUVANT THERAPY BASED ON IMAGING TECHNIQUES: A DIAGNOSTIC SYSTEMATIC REVIEW AND META-ANALYSIS

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
D J J M de Gouw ◽  
B R Klarenbeek ◽  
M Dressen ◽  
S A W Bouwense ◽  
F van Workum ◽  
...  

Abstract Background Up to 32% of patients with esophageal cancer show a pathological complete response (ypCR) after neoadjuvant therapy. To prevent overtreatment, the indication to perform esophagectomy in these patients should be reconsidered. Implementing an organ-preserving strategy for patients with ypCR requires an accurate assessment of residual disease after neoadjuvant treatment. The aim of this study was to systematically review the effectiveness of imaging techniques used for detection of ypCR after neoadjuvant therapy but before resection in patients with esophageal cancer. Methods A systematic literature search of the Medline, Embase, and Cochrane Library databases was performed from January 1, 2000, to December 13, 2017. Eligible studies were diagnostic studies that compared results of imaging modalities after neoadjuvant therapy to histopathological findings in the resection specimen after esophagectomy. Methodological quality was assessed by the Cochrane Quality Assessment of Diagnostic Accuracy Studies, version 2, model. Primary outcome measures were true positive, false positive, false negative, and true negative values of imaging techniques predicting ypCR. A meta-analysis was performed by pooling sensitivities and specificities by using a bivariate model. Results A total of 4420 articles were identified. After exclusion of irrelevant titles and abstracts, 360 articles were reviewed in full text. In total, four imaging modalities (computed tomography [CT], positron emission tomography [PET-CT], endoscopic ultrasound [EUS], and magnetic resonance imaging [MRI]) were used for restaging. The meta-analysis was conducted with data from 56 studies involving 3625 patients. The pooled sensitivities of CT, PET-CT, EUS, and MRI for detecting ypCR were 0.35, 0.62, 0.01 and 0.80, respectively, whereas the pooled specificities were 0.83, 0.73, 0.99, and 0.83, respectively. The positive predictive value in detecting ypCR was 0.47 for CT, 0.41 for PET-CT, not applicable for EUS, and 0.61 for MRI. Conclusions Current imaging modalities such as CT, PET-CT, and EUS seem to be insufficiently accurate to identify complete responders. More accurate diagnostic tests are needed to improve restaging accuracy for patients with esophageal cancer.

2019 ◽  
Vol 14 (7) ◽  
pp. 1156-1171 ◽  
Author(s):  
Didi J.J.M. de Gouw ◽  
Bastiaan R. Klarenbeek ◽  
Mitchell Driessen ◽  
Stefan A.W. Bouwense ◽  
Frans van Workum ◽  
...  

2020 ◽  
Vol 46 (2) ◽  
pp. e139
Author(s):  
Didi De Gouw ◽  
Bastiaan Klarenbeek ◽  
Mitchell Driessen ◽  
Stefan Bouwense ◽  
Frans van Workum ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 429
Author(s):  
Julian Hipp ◽  
Blin Nagavci ◽  
Claudia Schmoor ◽  
Joerg Meerpohl ◽  
Jens Hoeppner ◽  
...  

Background: A substantial fraction of patients with esophageal cancer show post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients, although surveillance and surgery as needed in case of local recurrence may be a treatment alternative for patients with complete response (CR). Methods: We performed a scoping review to describe key characteristics of relevant clinical studies including adults with non-metastatic esophageal cancer receiving multimodal treatment. Until September 2020, relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library, Science Direct, ClinicalTrials, the German study register, and the WHO registry platform. Results: In total, three completed randomized controlled trials (RCTs, with 468 participants), three planned/ongoing RCTs (with a planned sample size of 752 participants), one non-randomized controlled study (NRS, with 53 participants), ten retrospective cohort studies (with 2228 participants), and one survey on patients’ preferences (with 100 participants) were identified. All studies applied neoadjuvant chemoradiation protocols. None of the studies examined neoadjuvant chemotherapeutic protocols. Studies investigated patient populations with esophageal squamous cell carcinoma, adenocarcinoma, and mixed cohorts. Important outcomes reported were overall, disease-free and local recurrence-free survival. Limitations of the currently available study pool include heterogeneous chemoradiation protocols, a lack of modern neoadjuvant treatment protocols in RCTs, short follow-up times, the use of heterogeneous diagnostic methods, and different definitions of clinical CR. Conclusion: Although post-neoadjuvant surveillance and surgery as needed compared with post-neoadjuvant surgery on principle has been investigated within different study designs, the currently available results are based on a wide variation of diagnostic tools to identify patients with pCR, short follow-up times, small sample sizes, and variations in therapeutic procedures. A thoroughly planned RCT considering the limitations in the currently available literature will be of great importance to provide patients with CR with the best and less harmful treatment.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 516
Author(s):  
Daan Linders ◽  
Marion Deken ◽  
Maxime van der Valk ◽  
Willemieke Tummers ◽  
Shadhvi Bhairosingh ◽  
...  

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.


2020 ◽  
Vol 27 (11) ◽  
pp. 4319-4336 ◽  
Author(s):  
S. Hoendervangers ◽  
J. P. M. Burbach ◽  
M. M. Lacle ◽  
M. Koopman ◽  
W. M. U. van Grevenstein ◽  
...  

Abstract Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 24-24
Author(s):  
Shuhei Koga ◽  
Yu Ohkura ◽  
Masaki Ueno ◽  
Harushi Udagawa

Abstract Background Treatment for patients who have achieved clinical complete response (cCR) after neoadjuvant therapy has not been established, with no consensus regarding the indications for either esophagectomy or non-surgical treatment. Methods Among 1545 patients with esophageal cancer at Toranomon Hospital between January 2006 and August 2017, 39 who achieved cCR after neoadjuvant treatment were divided into two groups according to treatment: esophagectomy group (n = 18) andtreatment group (n = 21) for comparison. Results No significant intergroup difference was observed in baseline characteristics. Pathological complete response was confirmed in 13 (72.2%) of the 18 patients who underwent esophagectomy, while residual tumor was detected at the location of primary tumor in 2 (11.1%) patients and lymph node metastasis was found in 3 (16.7%) patients. Recurrence-free survival (RFS) was significantly longer in the esophagectomy group than in the non-surgical group (P = 0.002). Disease-specific survival (DSS) was significantly longer in the esophagectomy group (P = 0.007). However, no significant intergroup difference was observed in overall survival estimated based on all deaths, including (P = 0.451). Conclusion With improved diagnostic accuracy, non-surgical treatment can be an option for patients estimated as cCR after treatment administered in a neoadjuvant setting. However, surgical resection is considered more appropriate because of residual tumor in some patients with cCR and because of superior DSS and RFS following esophagectomy compared with non-surgical treatment. Future studies must focus on ameliorating late postoperative complications such as respiratory failure and aspiration pneumonia. Disclosure All authors have declared no conflicts of interest.


2021 ◽  
Vol 11 ◽  
Author(s):  
Sheng-bo Jin ◽  
Zi-bin Tian ◽  
Xue-li Ding ◽  
Ying-jie Guo ◽  
Tao Mao ◽  
...  

BackgroundSarcopenia is a poor prognostic factor in patients with esophageal cancer (EC). It can be aggravated by neoadjuvant therapy (NAT) that improves the prognosis of patients with EC. Until now, the impact of preoperative sarcopenia on survival prognosis in patients receiving NAT for EC remains unclear.MethodsWe systematically researched relevant studies in the PubMed, EMBASE, Web of Science, the Cochrane Library databases up to March 8, 2020. Prevalence of sarcopenia before and after NAT, overall survival (OS) and disease-free survival (DFS) were collected for analysis. Finally, eleven cohort studies were included.ResultsPooled analysis indicated that preoperative sarcopenia was negatively associated with OS. (HR = 1.290; 95% CI [1.078–1.543]; P = 0.005; I2 = 0.0%) and DFS (HR = 1.554; 95% CI [1.177–2.052]; P = 0.002; I2 = 0.0%) in the patients with EC receiving NAT. The prevalence of sarcopenia increased by 15.4% following NAT (95%CI [12.9%-17.9%]). Further subgroup analysis indicated that sarcopenia diagnosed following NAT (HR = 1.359; 95% CI [1.036–1.739]; P = 0.015; I2 = 6.9%) and age &gt;65 years (HR = 1.381; 95% CI [1.090– 1.749]; P = 0.007; I2 = 0.0%) were the independent risk factors for decreased OS.ConclusionsClinicians should strengthen the screening of preoperative sarcopenia in patients of EC both receiving NAT and older than 65 years and give active nutritional support to improve the prognosis of patients.Systematic Review RegistrationInternational Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202050057.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 583-583
Author(s):  
Christine Brunner ◽  
Thomas Jaeger ◽  
Christoph Suppan ◽  
Elisabeth Mueller-Holzner ◽  
Zerina Jasarevic ◽  
...  

583 Background: Concurrent therapy of trastuzumab, anthracycline and taxane for the neoadjuvant treatment of breast cancer (BC) results in an improved rate of pathological complete response (pCR). However, there is considerable concern about the cardiac safety of this combination. The use of liposomal doxorubicin might be a valuable alternative with lower cardiotoxicity. We report cardiac safety and pCR-rate of a single arm, retrospective, multicenter analysis of neoadjuvant treatment for BC with liposomal doxorubicin, trastuzumab, and docetaxel. Methods: In this study 84 women with BC and HER2 overexpression were investigated in 3 oncological departments in Austria. All patients were treated with liposomal doxorubicin (50 - 60 mg/m²), docetaxel (75 mg/m²) and concurrent with trastuzumab for 6 cycles as neoadjuvant therapy. All patients were free of cardiovascular disease and had a left ventricular ejection fraction (LVEF) of ≥ 55%. Cardiac function was by LVEF and was examined at regular intervals(cycles 0-3, cycle 6, FU). Clinical response was evaluated by diagnostic breast imaging after cycles 3 and 6. All patients underwent surgery after neoadjuvant chemotherapy. The absence of any residual invasive cancer in the breast and axilla was defined as pathological complete response (pCR). Median follow up was 2.4 years. Results: Median age of the patients was 50 years. After 6 cycles of treatment the pCR rate was 46%. In this cohort a negative estrogen-and/or progesteron receptor was predictive for pCR (p<0.001). No patient progressed during treatment. None of the patients suffered symptomatic heart failure. Only one patient (1.6%) with asymptomatic LVEF of 45% was observed during follow-up. Conclusions: In this multicenter analysis we observed a considerably high rate of pCR in HER2-positive BC treated with liposomal doxorubicin, docetaxel and trastuzumab. The addition of liposomal doxorubicin instead of conventional doxorubicin or epirubicin entails a very favorable cardiotoxicity profile. This regimen is a safe treatment option in patients with HER-2 positive breast cancer.


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