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Towards improved oncological treatment of esophageal and gastric cancer. Clinical and translational studies.

Borg, David LU (2019) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2019(123).
Abstract
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... (More)
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.
(Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • MB, BCh, MSc Smyth, Elizabeth, Cambridge University Hospitals, NHS Foundation Trust, Cambridge, UK
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Esophageal adenocarcinoma, Gastric cancer, PODXL, Prognosis, Prediction, Chemotherapy dose intensity, Dysphagia, Radiotherapy
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2019
issue
123
pages
73 pages
publisher
Lund University, Faculty of Medicine
defense location
Onkologiklinikens föreläsningssal, Klinikgatan 5, Skånes Universitetssjukhus i Lund
defense date
2019-12-20 09:00:00
ISSN
1652-8220
ISBN
978-91-7619-852-0
language
English
LU publication?
yes
id
281920ed-7ca0-4e16-a38a-6296aed1dd01
date added to LUP
2019-11-21 22:46:47
date last changed
2021-04-15 16:04:39
@phdthesis{281920ed-7ca0-4e16-a38a-6296aed1dd01,
  abstract     = {{Background<br/>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.    <br/>Methods<br/>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. <br/>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.<br/>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. <br/>Results<br/>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.<br/>Conclusions<br/>Promising steps have been taken towards improved treatment strategies but confirmation in additional studies is warranted.<br/>}},
  author       = {{Borg, David}},
  isbn         = {{978-91-7619-852-0}},
  issn         = {{1652-8220}},
  keywords     = {{Esophageal adenocarcinoma; Gastric cancer; PODXL; Prognosis; Prediction; Chemotherapy dose intensity; Dysphagia; Radiotherapy}},
  language     = {{eng}},
  number       = {{123}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Towards improved oncological treatment of esophageal and gastric cancer. Clinical and translational studies.}},
  url          = {{https://lup.lub.lu.se/search/files/72111744/David_Borg_WEBB.pdf}},
  volume       = {{2019}},
  year         = {{2019}},
}