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• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

ABSTRACT: Background:In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies. Method:Biomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of a phase II pilot study. Results:From 2007-2012, the • Pancho trial recruited 235 patients with operable esophageal cancer in Austria. A total of 181 patients were eligible and could be subjected to mark53 analysis and randomization. After randomizing 74 patients, the overall TP53 mutation rate was 79%. However, due to the high prevalence of marker positivity, the number of projected patients was increased to 181 patients in order to ensure a sufficient number of marker-negative patients. After completion of the trial, the overall TP53 mutation rate was 77.9%. Conclusion:Due to high medical need, the recruitment for the academic trial was excellent. Mark53 analysis clearly detected more mutations in the TP53 gene as compared to the cancer-specific p53 literature. Final analysis examining the interaction between the mark53 status and the effect of chemotherapies applied in the • Pancho trial is now awaited.

SUBMITTER: Kappel-Latif S

PROVIDER: S-EPMC6290852 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

Kappel-Latif Sonja S Zacherl Johannes J Hejna Michael M Westerhoff Maria M Tamandl Dietmar D Ba-Ssalamah Ahmed A Mittlböck Martina M Wolf Brigitte B Wrba Friedrich F Kührer Irene I Pluschnig Ursula U Schoppmann Sebastian F SF Függer Reinhold R Zwrtek Ronald R Glaser Karl K Karner Josef J Längle Friedrich F Wenzl Etienne E Roka Rudolf R Öfner Dietmar D Tschmelitsch Jörg J Hold Michael M Keil Felix F Gnant Michael M Kandioler Daniela D

European surgery : ACA : Acta chirurgica Austriaca 20180611 4

<h4>Background</h4>In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies.<h4>Method</h4>Biomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of ...[more]

PMID: 30559831

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Project description:BACKGROUND:We have previously shown that podocalyxin-like protein (PODXL) is a prognostic biomarker for poor survival in gastric and esophageal adenocarcinoma treated with surgery up-front. The aim of the present study was to assess PODXL expression in tumors from patients treated with neoadjuvant?±?adjuvant (i.e. preoperative with or without postoperative) chemotherapy, with regard to histopathologic response, time to recurrence (TTR) and overall survival (OS). METHODS:The neoadjuvant cohort encompasses 148 consecutive patients who received neoadjuvant?±?adjuvant chemotherapy for resectable gastric or esophageal adenocarcinoma between 2008 and 2014. Immunohistochemical expression of PODXL was assessed in pre-neoadjuvant biopsies, resected primary tumors and lymph node metastases. Histopathologic response was evaluated using the Chirieac grading. TTR and OS were estimated using Kaplan-Meier and Cox regression analyses. To investigate a potential predictive role for PODXL, the neoadjuvant cohort was pooled with the previously reported surgery up-front cohort. RESULTS:The majority (>?95%) of the patients were treated with fluoropyrimidine- and oxaliplatin-based chemotherapy. Patients with high PODXL expression in their pre-neoadjuvant biopsies had a superior histopathologic response (notably 36% with no residual cancer cells) compared to those with negative or low PODXL expression, and were all recurrence-free at last follow-up. In the pooled cohort, no benefit of chemotherapy could be shown for PODXL negative cases, whereas PODXL positive (low or high) cases had a prolonged TTR and OS when treated with neoadjuvant?±?adjuvant chemotherapy compared to surgery alone. The potential predictive role of PODXL was further strengthened for TTR in Cox regression analyses, especially for patients treated with neoadjuvant fluoropyrimidine and oxaliplatin for a minimum of 8 weeks, with a significant interaction term in both unadjusted (p?=?0.006) and adjusted (p?=?0.024) analyses. The interaction term was not statistically significant for overall survival. CONCLUSIONS:Patients with resectable gastric or esophageal adenocarcinoma with high PODXL expression in their diagnostic biopsies have an excellent prognosis when treated with neoadjuvant?±?adjuvant fluoropyrimidine- and oxaliplatin-based chemotherapy. If the suggested predictive role of PODXL for benefit of chemotherapy can be confirmed, patients with PODXL negative tumors could be spared chemotherapy and treated with surgery alone.

Project description:BackgroundThe efficacy and safety of neoadjuvant treatment over surgery alone and that of neoadjuvant chemoradiotherapy (NCRT) over neoadjuvant chemotherapy (NCT) in resectable esophageal carcinoma remains inconclusive. This study (NewEC) used global data to comprehensively evaluate these comparisons and to provide a preferable strategy for patient subsets.MethodsThis study included a meta-analysis of randomized controlled trials (RCTs) identified from inception to May 2019 from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congresses and a registry-based cohort study with patients from Massachusetts General Hospital (Massachusetts, USA) and Guangdong Provincial People's Hospital (Guangzhou, China) recruited from November 2000 and June 2017, to cross-validate the comparisons among NCRT versus NCT versus surgery. The GRADE approach was used to assessed quality of evidence in meta-analysis. Neural network machine learning propensity score-matched analysis was used to account for confounding by patient-level characteristics in the cohort study. The primary endpoint was overall survival (OS). The study was registered with PROSPERO CRD42017072242 and ClinicalTrials.gov NCT04027543.FindingsOf 22,070 studies assessed, there were 38 (n = 6,993 patients) eligible RCTs. Additionally, 423 out of 467 screened patients were included in the cohort study. The results from trials showed that NCT had a better OS than surgery alone (hazard ratio [HR] 0·88, 95% confidence interval [CI] 0·79-0·98; high quality) and was only favorable for adenocarcinoma (HR 0·83, 95% CI 0·72-0·96; moderate quality). High-quality evidence showed a significantly better OS for NCRT than surgery alone (HR 0·74, 95% CI 0·66-0·82) for both adenocarcinoma (HR 0·73, 95% CI 0·62-0·86) and squamous cell carcinoma (SCC) (HR 0·73, 95% CI 0·65-0·83). The OS benefit of NCRT over NCT was seen in the pairwise (HR 0·78, 95% CI 0·62-0·99; high quality) and network (HR 0·82, 95% CI 0·72-0·93; high quality) meta-analyses, with similar results before (HR 0·60, 95% CI 0·40-0·91) and after (HR 0·44, 95% CI 0·25-0·77) matching in the cohort study, leading to a significantly increased 5-year OS rate in both adenocarcinoma and SCC before and after matching. The increased benefits from NCT or NCRT were not associated with the risk of 30-day or in-hospital mortality.InterpretationNewEC Study provided high-quality evidence supporting the survival benefits of NCRT or NCT over surgery alone, with NCRT presenting the greatest benefit for resectable esophageal carcinoma.FundingNational Science and Technology Major Project, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Guangzhou Science and Technology Major Program, the Medical artificial intelligence project of Sun Yat-Sen Memorial Hospital, the Guangdong Science and Technology Department, the Guangdong Province Medical Scientific Research Foundation, and Guangdong Provincial People's Hospital Intermural Program.

Dataset Information

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

Publications

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

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