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

Sammanfattning: BackgroundThe 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. MethodsExpression 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. ResultsIn 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.ConclusionsPromising steps have been taken towards improved treatment strategies but confirmation in additional studies is warranted.