Significance of Histopathological Tumor Regression After Neoadjuvant Chemotherapy in Gastric Adenocarcinomas

Becker, Karen; Langer, Rupert; Reim, Daniel; Novotny, Alexander; Büschenfelde, Christian Meyer zum; Engel, Jutta; Friess, Helmut; Höfler, Heinz

doi:10.1097/sla.0b013e318216f449

Cited by 286 publications

(319 citation statements)

References 25 publications

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“…Overall, TOP2A aberrations are unlikely to be a determinant of responsiveness to anthracyclines. Furthermore, despite a slightly higher rate of grade 1 regressions [19] among HER2-positive patients, our findings suggest that the supposed benefit from anthracyclines is not reflected by the histopathological tumor regression. Assessment of HER2 expression in gastroesophageal cancers is challenged by the substantial intratumor heterogeneity of HER2 staining patterns [15,33].…”

Section: Discussioncontrasting

confidence: 64%

“…All tumors were classified according to the Laurén classification, and their TNM stage was reviewed on the basis of the seventh edition of the UICC guidelines [18] by one gastrointestinal pathologist who was blinded to outcome. In those patients receiving perioperative chemotherapy, histopathological tumor regression was evaluated according to Becker et al [19].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

et al. 2016

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Background HER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma. Methods HER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri-or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC. Results Eighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22-0.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13-0.83), P \ 0.018], independent of clinicalpathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared. Conclusions HER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2.

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Section: Discussioncontrasting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

et al. 2016

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“…However, up to 30 % of the histopathological responders die due to recurrence [4,22]. The rate of clinical response was not high, but realistic with a percentage of 30 and 24 %, which reflects the data obtained for histopathological response after chemotherapy [6].…”

Section: Discussionsupporting

confidence: 65%

“…Three different types of response evaluation have been studied: morphological response evaluation by histopathology, metabolic response evaluation by functional imaging, and clinical response evaluation by conventional imaging modalities. Histopathological response is regarded as a reference method according to recent studies [6]. A clear disadvantage is that information about histopathological regression can only be achieved after resection, and thus can only be used as a prognostic marker.…”

Section: Introductionmentioning

confidence: 99%

Post-therapeutic response evaluation by a combination of endoscopy and CT scan in esophagogastric adenocarcinoma after chemotherapy: better than its reputation

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Lordick

Bader³

et al. 2014

Gastric Cancer

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Background Neoadjuvant chemotherapy is an accepted standard of care for locally advanced esophagogastric cancer. As only a subgroup benefits, a response-based tailored treatment would be of interest. The aim of our study was the evaluation of the prognostic and predictive value of clinical response in esophagogastric adenocarcinomas. Methods Clinical response based on a combination of endoscopy and computed tomography (CT) scan was evaluated retrospectively within a prospective database in center A and then transferred to center B. A total of 686/740 (A) and 184/210 (B) patients, staged cT3/4, cN0/1 underwent neoadjuvant chemotherapy and were then restaged by endoscopy and CT before undergoing tumor resection. Of 184 patients, 118 (B) additionally had an interim response assessment 4-6 weeks after the start of chemotherapy. Results In A, 479 patients (70 %) were defined as clinical nonresponders, 207 (30 %) as responders. Median survival was 38 months (nonresponders: 27 months, responders: 108 months, log-rank, p \ 0.001). Clinical and histopathological response correlated significantly (p \ 0.001). In multivariate analysis, clinical response was an independent prognostic factor (HR for death 1.4, 95 %CI 1.0-1.8, p = 0.032). In B, 140 patients (76 %) were nonresponders and 44 (24 %) responded. Median survival was 33 months, (nonresponders: 27 months, responders: not reached, Electronic supplementary material The online version of this article

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“…6 Response (or lack ofthere) may be determined using tumour regression grade (TRG), which has been shown to correlate with survival in oesophagogastric cancer. 7,8 In many drug trials, the difference between study arms may be small and a lengthy follow-up period can be required to confirm any difference. TRG as a surrogate marker of survival might be useful in the research field to detect the success of novel drugs in clinical trials without the need for mature survival data but only if it can be shown to be sensitive enough to detect the relatively small benefits that might be expected when comparing two neoadjuvant regimens.…”

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confidence: 99%

Postoperative survival following perioperative MAGIC versus neoadjuvant OE02-type chemotherapy in oesophageal adenocarcinoma

Saunders

et al. 2017

annals

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The optimal management of resectable oesophageal adenocarcinoma is controversial, with many centres using neoadjuvant chemotherapy following the Medical Research Council (MRC) oesophageal working group (OE02) trial and the MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. The more intensive MAGIC regimen is used primarily in gastric cancer but some also use it for oesophageal cancer. A database of cancer resections (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013) provided information on survival of patients following either OE02 or MAGIC-type treatment. The data were compared using Kaplan-Meier analysis. Straight-to-surgery patients were also reviewed and divided into an 'early' cohort (2001( -2006 and a 'late ' cohort (2006' cohort ( -2013 to estimate changes in survival over time. Subgroup analysis was performed for responders (tumour regression grade [TRG] 1-3) versus non-responders (TRG 4 and 5) and for anatomical site (gastro-oesophageal junction [GOJ] vs oesophagus). An OE02 regimen was used for 97 patients and 275 received a MAGIC regimen. Those in the MAGIC group were of a similar age to those undergoing OE02 chemotherapy but the proportion of oesophageal cancers was higher among MAGIC patients than among those receiving OE02 treatment. MAGIC patients had a significantly lower stage following chemotherapy than OE02 patients and a higher median overall survival although TRG was similar. On subgroup analysis, this survival benefit was maintained for GOJ and oesophageal cancer patients as well as non-responders. Analysis of responders showed no difference between regimens. 'Late' group straight-to-surgery patients were significantly older than those in the 'early' group. Survival, however, was not significantly different for these two cohorts. Although the original MAGIC trial comprised few oesophageal cancer cases, our patients had better survival with MAGIC than with OE02 chemotherapy in all anatomical subgroups, even though there was no significant change in operative survival over the time period in which these patients were treated. The use of the MAGIC regimen should therefore be encouraged in cases of operable oesophagogastric adenocarcinoma.

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Significance of Histopathological Tumor Regression After Neoadjuvant Chemotherapy in Gastric Adenocarcinomas

Cited by 286 publications

References 25 publications

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

Post-therapeutic response evaluation by a combination of endoscopy and CT scan in esophagogastric adenocarcinoma after chemotherapy: better than its reputation

Postoperative survival following perioperative MAGIC versus neoadjuvant OE02-type chemotherapy in oesophageal adenocarcinoma

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