Towards improved oncological treatment of esophageal and gastric cancer. Clinical and translational studies.
Author
Summary, in English
Background
The overall aim of this thesis was to improve the oncological treatment strategies in esophageal and gastric adenocarcinoma (EGAC). Podocalyxin-like protein 1 (PODXL) has been associated with poor prognosis in other cancers and we wanted to investigate its potential role as a prognostic and predictive biomarker in resectable EGAC. Another aim was to assess how dose reductions and treatment delays of neoadjuvant chemotherapy affect outcome. Lastly we aimed to explore a novel palliative treatment strategy in esophageal adenocarcinoma with the primary objective to achieve durable improvement of dysphagia.
Methods
Expression of PODXL was assessed using immunohistochemistry on material from two patient cohorts with EGAC: one with 174 patients treated with surgery up-front and the other with 148 patients treated with neoadjuvant chemotherapy ± adjuvant chemotherapy.
For 63 patients in the neoadjuvant cohort, treated with EOX (epirubicin, oxaliplatin and capecitabine) followed by resection, we calculated the ratio of actual to planned cumulative dose and the ratio of planned to actual total duration and then associations of these measures with histopathologic response were assessed.
In the phase II PALAESTRA trial the treatment consisted of external beam radiotherapy with 20 Gy in five fractions followed by four cycles of chemotherapy.
Results
In paper I we show that PODXL expression is an independent prognostic biomarker in EGAC and the results in paper II indicate that PODXL expression is predictive for benefit of neoadjuvant ± adjuvant chemotherapy. In paper III it is suggested that treatment delays of neoadjuvant chemotherapy should be avoided in order to achieve a major histopathologic response. In the PALAESTRA study (paper IV) with 29 patients enrolled, 79% experienced improvement of dysphagia and for these the median duration of improvement was 12 months.
Conclusions
Promising steps have been taken towards improved treatment strategies but confirmation in additional studies is warranted.
The overall aim of this thesis was to improve the oncological treatment strategies in esophageal and gastric adenocarcinoma (EGAC). Podocalyxin-like protein 1 (PODXL) has been associated with poor prognosis in other cancers and we wanted to investigate its potential role as a prognostic and predictive biomarker in resectable EGAC. Another aim was to assess how dose reductions and treatment delays of neoadjuvant chemotherapy affect outcome. Lastly we aimed to explore a novel palliative treatment strategy in esophageal adenocarcinoma with the primary objective to achieve durable improvement of dysphagia.
Methods
Expression of PODXL was assessed using immunohistochemistry on material from two patient cohorts with EGAC: one with 174 patients treated with surgery up-front and the other with 148 patients treated with neoadjuvant chemotherapy ± adjuvant chemotherapy.
For 63 patients in the neoadjuvant cohort, treated with EOX (epirubicin, oxaliplatin and capecitabine) followed by resection, we calculated the ratio of actual to planned cumulative dose and the ratio of planned to actual total duration and then associations of these measures with histopathologic response were assessed.
In the phase II PALAESTRA trial the treatment consisted of external beam radiotherapy with 20 Gy in five fractions followed by four cycles of chemotherapy.
Results
In paper I we show that PODXL expression is an independent prognostic biomarker in EGAC and the results in paper II indicate that PODXL expression is predictive for benefit of neoadjuvant ± adjuvant chemotherapy. In paper III it is suggested that treatment delays of neoadjuvant chemotherapy should be avoided in order to achieve a major histopathologic response. In the PALAESTRA study (paper IV) with 29 patients enrolled, 79% experienced improvement of dysphagia and for these the median duration of improvement was 12 months.
Conclusions
Promising steps have been taken towards improved treatment strategies but confirmation in additional studies is warranted.
Department/s
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Tumor microenvironment
Publishing year
2019
Language
English
Publication/Series
Lund University, Faculty of Medicine Doctoral Dissertation Series
Volume
2019
Issue
123
Full text
- Available as PDF - 10 MB
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Document type
Dissertation
Publisher
Lund University, Faculty of Medicine
Topic
- Cancer and Oncology
Keywords
- Esophageal adenocarcinoma
- Gastric cancer
- PODXL
- Prognosis
- Prediction
- Chemotherapy dose intensity
- Dysphagia
- Radiotherapy
Status
Published
Supervisor
- Anders Johnsson
- Jakob Eberhard
- Michael Hermansson
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-7619-852-0
Defence date
20 December 2019
Defence time
09:00
Defence place
Onkologiklinikens föreläsningssal, Klinikgatan 5, Skånes Universitetssjukhus i Lund
Opponent
- Elizabeth Smyth (MB, BCh, MSc)