PS02.111: A 5-YEAR EXPERIENCE IN ANASTOMOTIC LEAK AFTER NEODJUVANT FOLLOWED ESOPHAGECTOMY IN A BRAZILIAN UNIVERSITY HOSPITAL

Abstract Background Neoadjuvant treatment of esophageal cancer is world accepted since 2012 (1), showing benefits in long-term survival. However, there is still controversy relating to potential complications with the use of antineoplastic drugs and radiotherapy, notably because of the higher incidence of cervical esophageal leak. Our study describes a five-year experience in anastomotic leaks in esophagectomies after neoadjuvant therapy in a southern Brazilian referral center. Methods We have analyzed all patients submitted to the combined treatment of neoadjuvant therapy plus esophagectomy between 2012–2016, including patients with squamous cell carcinoma and adenocarcinoma. We describe the number of patients that experienced anastomotic leak after surgery. The diagnosis of an anastomotic leak is based in any quantity of digestive secretion in the neck wound, seen on the post-operative period. It did not secrete bacteriological analysis. McKeown and transhiatal esophagectomy were used, and esophagogastric anastomosis were conducted in the cervical region. Results Between the years of 2012–2016, thirty-six patients were submitted to a combined treatment of neoadjuvant therapy plus esophagectomy. Of these patients, 20 (55%) evolved with anastomotic leaks. All of these leaks occurred in the cervical region, and were treated in a conservative way. Conclusion The incidence of anastomotic leaks was exceptionally high, regardless of the usual care. Possible causes of this high number of leaks could be related to diagnostic criterion, the patient's own characteristics, local alterations associated to the neoadjuvant treatment, the surgical technique, or even microbiological factors. New studies are necessary with the goal to determine which of these factors contributes in the most significant way, with the means to improve the results of this unpleasant esofagectomy complication. 1) VAN HAGEN, P. et al. Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer. New England Journal Of Medicine,[s.l.], v. 366, n. 22, p.2074–2084, 31 maio 2012. New England Journal of Medicine (NEJM/MMS). http://dx.doi.org/10.1056/nejmoa1112088. Disclosure All authors have declared no conflicts of interest.

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Prognostic relevance of lymph node regression on survival in esophageal cancer: a systematic review and meta-analysis

Diseases of the Esophagus ◽

10.1093/dote/doab021 ◽

2021 ◽

Author(s):

Eliza Hagens ◽

Karina Tukanova ◽

Sara Jamel ◽

Mark van Berge Henegouwen ◽

George B Hanna ◽

...

Keyword(s):

Esophageal Cancer ◽

Lymph Node ◽

Neoadjuvant Therapy ◽

Tumor Regression ◽

Average Rate ◽

Meta Analysis ◽

Neoadjuvant Treatment ◽

Term Survival ◽

Number Of Patients ◽

The Impact

Summary Introduction The prognostic value of histomorphologic regression in primary esophageal cancer has been previously established, however the impact of lymph node (LN) response on survival still remains unclear. The aim of this review was to assess the prognostic significance of LN regression or downstaging following neoadjuvant therapy for esophageal cancer. Methods An electronic search was performed to identify articles evaluating LN regression or downstaging after neoadjuvant therapy. Random effects meta-analyses were performed to assess the influence of regression in the LNs and nodal downstaging on overall survival. Histomorphologic tumor regression in LNs was defined by the absence of viable cells or degree of fibrosis on histopathologic examination. Downstaged LNs were defined as pN0 nodes by the tumor, node, and metastasis classification, which were positive prior to treatment neoadjuvant. Results Eight articles were included, three of which assessed tumor regression (number of patients = 292) and five assessed downstaging (number of patients = 1368). Complete tumor regression (average rate of 29.1%) in the LNs was associated with improved survival, although not statistically significant (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.26–1.06; P = 0.17). LNs downstaging (average rate of 32.2%) was associated with improved survival compared to node positivity after neoadjuvant treatment (HR = 0.41, 95%CI = 0.22–0.77; P = 0.005). Discussion The findings of this meta-analysis have shown a survival benefit in patients with LN downstaging and are suggestive for considering LN downstaging to ypN0 as an additional prognostic marker in staging and in the comparative evaluation of differing neoadjuvant regimens in clinical trials. No statistically significant effect of histopathologic regression in the LNs on long-term survival was seen.

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Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials

Clinical Trials ◽

10.1177/1740774520949157 ◽

2020 ◽

Vol 17 (6) ◽

pp. 723-728

Author(s):

Behnood Bikdeli ◽

César Caraballo ◽

John Welsh ◽

Joseph S Ross ◽

Sanjay Kaul ◽

...

Keyword(s):

England Journal ◽

Clinical Outcome ◽

New England ◽

Clinical Outcomes ◽

Primary Endpoint ◽

European Heart Journal ◽

Surrogate Marker ◽

Surrogate Markers ◽

Primary Endpoints ◽

Number Of Patients

Background/aims Non-inferiority trials are increasing in cardiovascular medicine, with approval of many drugs and devices on the basis of such studies. Surrogate markers as primary endpoints have been also more frequently used for efficient assessment of cardiovascular interventions. However, there is uncertainty about their concordance with clinical outcomes. Non-inferiority design using a surrogate marker as a primary endpoint may pose particular challenges in clinical interpretation. We sought to explore the publication trends, methodology, and reporting features of non-inferiority cardiovascular trials that used a primary surrogate marker as the primary endpoint. Methods We searched six high-impact journals ( The New England Journal of Medicine, The Journal of the American Medical Association, The Lancet, The Journal of the American College of Cardiology, Circulation, and European Heart Journal) from 1 January 1990 to 31 December 2018 and identified non-inferiority cardiovascular trials that used a surrogate marker as the primary endpoint. We assessed the non-inferiority margin reported in the manuscript and other publicly available platforms (e.g. protocol, clinicaltrials.gov). We also determined whether the included non-inferiority trials with surrogate markers as primary endpoints were followed by clinical outcome trials. Results We screened 15,553 publications and identified 247 cardiovascular trials that used a non-inferiority design. Of these, 37 had a surrogate marker as a primary endpoint (18 drug trials, 13 device trials, 6 others). All of these non-inferiority trials with surrogate outcomes were published after 2000, mostly in cardiology journals (13 in The Journal of the American College of Cardiology, 9 in European Heart Journal, 8 in Circulation, 6 in The Lancet, 1 in The New England Journal of Medicine), and their publication rate increased over time (p < 0.001 for linear trend). The median number of patients in the primary analysis was 300 (interquartile range: 202–465). The study protocol or a methods paper was publicly available for only 13 (35.1%) trials, of which the non-inferiority margin was not reported in 4 trials. In 16 studies (43.2%), the manuscript did not acknowledge the limitations of using a surrogate endpoint or the need for a definitive clinical outcome trial. Thirty-four trials (91.9%) concluded that the tested intervention met non-inferiority criteria. However, only five (13.5%) were followed by clinical outcomes trials the results of which did not always confirm non-inferiority. Conclusion Non-inferiority trials that use a surrogate marker as the primary endpoint are being increasingly performed. However, these trials pose particular challenges with design, reporting, and interpretation, which are not systematically and consistently addressed or reported.

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Biomarker study in patients with resectable AJCC stage IIIc or stage IV (M1a) melanoma treated in a randomized phase II neoadjuvant trial.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9047 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9047-9047

Author(s):

Nitin Chakravarti ◽

Doina Ivan ◽

Merrick I. Ross ◽

Joseph L. Ilagan ◽

Carla L. Warneke ◽

...

Keyword(s):

Overall Survival ◽

Neoadjuvant Therapy ◽

Neoadjuvant Treatment ◽

Gene Array ◽

Stage Iiic ◽

Tumor Biopsy ◽

Term Survival ◽

Neoadjuvant Systemic Therapy ◽

Biomarker Analysis ◽

Definitive Surgery

9047 Background: Fewer than 30% of patients with resectable stage IIIC or IV (M1a) metastatic melanoma (MetM) who undergo surgical resection will achieve long-term survival. This study was designed to administer neoadjuvant systemic therapy prior to definitive surgery to explore potential predictive and prognostic biomarkers in patients with MetM. Methods: Fifty patients with resectable MetM were randomized to receive temozolomide (TMZ) alone at 150 mg/m2/day x 7 days every other week (Arm A, n=26) or with pegylated interferon (PGI) at 0.5 mcg/kg weekly (Arm B, n=24). After a pre-treatment tumor biopsy, patients received 8 weeks of neoadjuvant therapy before undergoing surgery. Endpoints were clinical response, tolerability, and biomarker analysis by immunohistochemistry and gene array. In particular, we examined PD-1, PD-L1, pAKT, pMAPK, Ki67, and caspase 3. Patients with response (complete-, partial-, or stable disease) received up to 3 additional cycles of the assigned regimen as adjuvant therapy. Results: Overall response to neoadjuvant therapy was 38% [1 CR, 15 PRs, 3 SDs]: 31% in Arm A (95% CI 14% - 52%) and 46% in Arm B (95% CI 26% - 67%). Estimated 4-year overall survival was 52.52% (95% CI 35.86 - 66.74%). Only 5 patients did not undergo definitive surgery after neoadjuvant treatment due to development of distant metastasis. Preliminary data indicate that in Arm B, responders had higher PD-1 membranous expression in tumor infiltrating lymphocytes (TILs) (p=0.029). Furthermore, low PD-L1 cytoplasmic expression in TILs (p=0.002) as well as low nuclear PD-L1 expression in tumor cells (p=0.025) had better overall survival. Conclusions: Comparing with historical data, neoadjuvant therapy has a potential to improve overall survival in patients with resectable MetM. Biomarker analysis may predict response to neoadjuvant treatment as well as overall survival. Clinical trial information: NCT00525031.

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Intra-tumoral genomic heterogeneity in rectal cancer: mutational status is dependent on preoperative biopsy depth and location.

10.21203/rs.3.rs-20696/v2 ◽

2020 ◽

Author(s):

Floris A. Vuijk ◽

Carlijn van de Water ◽

Shannon van Lent - van Vliet ◽

Maxime J.M. van der Valk ◽

Cornelis J.H. van de Velde ◽

...

Keyword(s):

Rectal Cancer ◽

Next Generation Sequencing ◽

Neoadjuvant Therapy ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Rectal Cancer ◽

Next Generation ◽

Mutational Status ◽

Number Of Patients ◽

Generation Sequencing

Abstract Background Neoadjuvant therapy is indicated for patients with locally advanced rectal cancer, even though a significant number of patients show minimal or no response. Adequate response prediction before the start of neoadjuvant treatment might reduce unnecessary waiting periods and therapy related toxicity in non-responders. Genomic mutational status might provide a means to predict response to neoadjuvant therapy. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing these genomic mutations to 4 other locations within the same tumor using next generation sequencing. Methods Rectal cancer patients undergoing primary resection, without neoadjuvant therapy, were included. Of all patients, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these 5 samples was assessed. Results  In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) disconcordant mutations were observed. Conclusions Evaluation of genomic mutational status on a single pre-operative biopsy shows disconcordance in a substantial amount of patients.

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Intra-Tumoral Genomic Heterogeneity in Rectal Cancer: Mutational Status Is Dependent on Preoperative Biopsy Depth and Location

Cancers ◽

10.3390/cancers13092271 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2271

Author(s):

Floris A. Vuijk ◽

Carlijn van de Water ◽

Shannon Lent-van Vliet ◽

Maxime J. M. van der Valk ◽

Femke Simmer ◽

...

Keyword(s):

Rectal Cancer ◽

Next Generation Sequencing ◽

Neoadjuvant Therapy ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Next Generation ◽

Biopsy Material ◽

Mutational Status ◽

Number Of Patients ◽

Generation Sequencing

Neoadjuvant therapy before surgical resection is indicated for patients with locally advanced rectal cancer. However, a significant number of patients show minimal or no response to neoadjuvant therapy. Unfortunately, we are currently unable to predict response and identify non-responding patients before neoadjuvant treatment is given. Genomic mutational status might provide valuable prognostic information. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing genomic mutations to four other locations within the same tumor using next generation sequencing. Rectal cancer patients undergoing primary resection without neoadjuvant therapy were included. From each patient, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these five samples was assessed. In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) discordant mutations were observed. In conclusion, assessment of mutational status on a single pre-operative biopsy shows discordance with tumor tissue from other locations in 36% of cases. These results warrant careful interpretation of biopsy material analysis, as these might be influenced by tumor heterogeneity.

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P80 LONG-TERM OUTCOMES OF CLINICAL AND PATHOLOGICAL-STAGED T3N3 ESOPHAGEAL CANCER

Diseases of the Esophagus ◽

10.1093/dote/doz092.80 ◽

2019 ◽

Vol 32 (Supplement_2) ◽

Author(s):

S K Kamarajah ◽

N Newton ◽

M Navidi ◽

S Wahed ◽

A Immanuel ◽

...

Keyword(s):

Overall Survival ◽

Esophageal Cancer ◽

Neoadjuvant Therapy ◽

Clinical Stage ◽

Neoadjuvant Treatment ◽

Stage Migration ◽

Pathological Stage ◽

Term Survival ◽

The Impact

Abstract Objective The aim of this study was to determine the outcomes of patients with T3N3 esophageal cancers and determine differences between the clinical stage and pathological stage. Background Locally advanced esophageal cancer is associated with poor long-term survival. Pre-treatment and post-treatment stage may differ due to the effect of neoadjuvant therapy and inaccuracies in staging. Multimodality staging followed by discussion at an MDT is considered the gold standard. Despite this, patients can be under-staged or over-staged leading to inadequate or unnecessary treatment associated with high levels of morbidity. Methods Consecutive patients from a single unit between 2010 - 2018 were included with either clinical (cT3N3) or pathological (pT3N3) esophageal cancer. Outcomes were compared between patients that underwent transthoracic esophagectomy and radical two field lymphadenectomy with or without neoadjuvant treatment and those patients staged cT3N3 treated non-surgically (NSR). Demographics, clinical and pathological stage, histological information and outcomes were recorded. Patients were staged using the TNM 8. Results This study included 156 patients, of which 63 had non-surgical treatment, only 3 of these had radical treatment. Of the remaining 93 patients who underwent esophagectomy, 34 were cT3N3, 54 were pT3N3 and five were unchanged before and after treatment. Median overall survival (OS) for surgical cT3N3 patients was significantly longer than pT3N3 and NSR (median: NR vs 19 vs 8 months, p<0.001). Twenty-seven patients with cT3N3 had lower staging following treatment whilst 3 had a higher stage. Conclusion T3N3 disease carries a poor prognosis. Within this cohort cT3N3 disease treated surgically has a high 5-year overall survival suggesting possible over-staging and stage migration due to neoadjuvant therapy. To contrast this those not having surgery have a dismal prognosis. The impact of neoadjuvant treatment cannot be predicted and, current staging modalities may be inaccurate. Clinical stage should be used with caution when counselling patients regarding management and prognosis.

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Long-term outcomes of clinical and pathological-staged T3 N3 esophageal cancer

Diseases of the Esophagus ◽

10.1093/dote/doz109 ◽

2020 ◽

Vol 33 (8) ◽

Cited By ~ 2

Author(s):

S K Kamarajah ◽

N Newton ◽

M Navidi ◽

S Wahed ◽

A Immanuel ◽

...

Keyword(s):

Esophageal Cancer ◽

Neoadjuvant Therapy ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Stage Migration ◽

Term Survival ◽

Carcinoma Of The Esophagus ◽

Dismal Prognosis ◽

The Impact

Summary Locally advanced esophageal cancer is associated with poor long-term survival. Pre- and post-treatment stages may differ because of neoadjuvant therapy and inaccuracies in staging. The aim of this study was to determine the outcomes of patients staged with clinical T3 N3 and pathological T3 N3 carcinoma of the esophagus and determine differences between the groups. Consecutive patients from a single unit between 2010 and 2018 were included with either clinical (cT3 N3) or pathological (pT3 N3) esophageal cancer. Outcomes were compared between patients that underwent esophagectomy with or without neoadjuvant treatment and those patients staged cT3 N3 treated non-surgically (NSR). Patients were staged using the TNM 8. This study included 156 patients, 63 patients were staged cT3 N3 initially and had NSR treatment, only three of these had radical treatment. Of the remaining 93 patients who underwent esophagectomy, 34 were initially staged as cT3 N3, 54 were found to be pT3 N3 having been staged earlier initially, and five were unchanged before and after treatment. Median overall survival (OS) for surgical cT3 N3 patients was significantly longer than pT3 N3 and NSR (median: NR vs 19 vs 8 months, P < 0.001). Twenty-seven patients with cT3 N3 had lower staging following treatment, while three had a higher stage. T3 N3 disease carries a poor prognosis. Within this cohort, cT3 N3 disease treated surgically has a high 5-year OS suggesting possible over-staging and stage migration due to neoadjuvant therapy. Those not having surgery, have a dismal prognosis. The impact of neoadjuvant treatment cannot be predicted and, current staging modalities may be inaccurate. Clinical stage should be used with caution when counseling patients regarding management and prognosis.

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Role of neoadjuvant treatment regimens for locally advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.444 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 444-444

Author(s):

Mohammad Alfayez ◽

Janet Shirley Graham ◽

Sally Hall ◽

David McIntosh ◽

Vivienne MacLaren ◽

...

Keyword(s):

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Pancreatic Cancer ◽

Case Series ◽

Ductal Adenocarcinoma ◽

Anatomical Location ◽

Term Survival

444 Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality worldwide. Lymph node involvement and resection margin status play important roles in predicting relapse. Resectable disease occurs in only 15–20% of total patients who present with PDAC. Unfortunately, margin involvement (R1) occurs in 70–80% of these patients. Emerging evidence has shown that the use of neoadjuvant chemotherapy and localised radiotherapy to downsize the tumours and increase the margin clearance (R0) rate may improve the overall survival of PDAC patients.We report a neoadjuvant therapy approach in the non-clinical trial setting of our large, tertiary cancer centre. Methods: We prospectively collected the outcome data and toxicity of 53 patients diagnosed with borderline resectable or initially non-resectable PDAC between 2012 and 2014. These patients received either FOLFIRINOX (FFX) or Gemcitabine/Capecitabine (GemCap) combination chemotherapies. Following restaging by computed tomography (CT), the patients proceeded to preo-operative 5-FU-based chemo-radiotherapy, immediate resection or subsequent palliativetherapies. Results: The median age was 65 (range 30 – 79) at PDAC diagnosis. Sixty-one percent (n=32) were male with the commonest anatomical location being the head of the pancreas (58%, n=31). The median follow up for survivors is 13.7 months (range: 5.3–24.4). The median overall survival was 18.3 months (95%, CI: 12.0–24.5). There was no statistical difference between overall survival in patients receiving FFX and GemCap chemotherapies. The margin clearance rate (R0) was 36% (4/11) in patients who proceeded to resection after neoadjuvant chemotherapy alone. The rate was 100% (4/4) in patients who received additional chemoradiation prior to surgery. Conclusions: This case series reveals that neoadjuvant therapy improved survival of patients with PDAC. In addition, we showed an increase in the R0 resection rate in patients who underwent chemoradiation prior to surgery. Further work is ongoing but based on historical data we believe that this neoadjuvant approach may lead to a long term survival benefit.

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Intra-tumoral genomic heterogeneity in rectal cancer: mutational status is dependent on preoperative biopsy depth and location.

10.21203/rs.3.rs-20696/v3 ◽

2020 ◽

Author(s):

Floris A. Vuijk ◽

Carlijn van de Water ◽

Shannon van Lent - van Vliet ◽

Maxime J.M. van der Valk ◽

Femke Simmer ◽

...

Keyword(s):

Rectal Cancer ◽

Next Generation Sequencing ◽

Neoadjuvant Therapy ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Next Generation ◽

Biopsy Material ◽

Mutational Status ◽

Number Of Patients ◽

Generation Sequencing

Abstract BackgroundNeoadjuvant therapy before surgical resection is indicated for patients with locally advanced rectal cancer. However, a significant number of patients show minimal or no response to neoadjuvant therapy. Unfortunately, we are currently unable to predict response and identify non-responding patients before neoadjuvant treatment is given. Genomic mutational status might provide valuable prognostic information. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing these genomic mutations to 4 other locations within the same tumor using next generation sequencing.Methods Rectal cancer patients undergoing primary resection, without neoadjuvant therapy, were included. Of all patients, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these 5 samples was assessed.Results In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) discordant mutations were observed. ConclusionsIn conclusion, assessment of mutational status on a single pre-operative biopsy shows discordance with tumor tissue from other locations in 36% of cases. These results warrant careful interpretation of biopsy material analysis, as these might be influenced by tumor heterogeneity.

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Intra-tumoral genomic heterogeneity in rectal cancer: mutational status is dependent on preoperative biopsy depth and location.

10.21203/rs.3.rs-20696/v1 ◽

2020 ◽

Author(s):

Floris A. Vuijk ◽

Carlijn van de Water ◽

Shannon van Lent - van Vliet ◽

Maxime J.M. van der Valk ◽

Cornelis J.H. van de Velde ◽

...

Keyword(s):

Rectal Cancer ◽

Next Generation Sequencing ◽

Neoadjuvant Therapy ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Rectal Cancer ◽

Next Generation ◽

Mutational Status ◽

Number Of Patients ◽

Generation Sequencing

Abstract Background Neoadjuvant therapy is indicated for all patients with locally advanced rectal cancer, even though a significant number of patients show minimal or no response. Adequate response prediction before the start of neoadjuvant treatment might reduce unnecessary waiting periods and therapy related toxicity in non-responders. Genomic mutational status might provide a means to predict response to neoadjuvant therapy. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing these genomic mutations to 4 other locations within the same tumor using next generation sequencing. Methods Rectal cancer patients undergoing primary resection, without neoadjuvant therapy, were included. Of all patients, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these 5 samples was assessed. Results  In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) disconcordant mutations were observed. Conclusions Evaluation of genomic mutational status on a single pre-operative biopsy is inadequate in a substantial amount of the patients and is therefore insufficient to predict response to neoadjuvant therapy. Predictive algorithms including multiple parameters might be required to further stratify patients to optimal treatment regimens.

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