Aspects of neoadjuvant therapy in the curative treatment of cancer in the esophagus or gastroesophageal junction
Author: Klevebro, Fredrik
Date: 2016-09-02
Location: Föreläsningssal B64, Karolinska Universitetssjukhuset Huddinge
Time: 09.00
Department: Inst för klinisk vetenskap, intervention och teknik / Dept of Clinical Science, Intervention and Technology
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Thesis (1.810Mb)
Abstract
Malignant esophageal tumors are among the most severe cancers. Only about 30% of the patients are suitable for curative treatment at diagnosis. The treatment is extremely demanding and unfortunately has disappointing results. The staging of disease and the treatment for cancer of the esophagus and gastroesophageal junction need to be improved. It is currently well established that neoadjuvant therapy, either with chemotherapy or with combined chemo- and radiotherapy, followed by surgery, offers a better chance for a cure in stage II and III esophageal and gastroesophageal junction cancer, than surgery alone. Data directly comparing neoadjuvant chemotherapy and chemoradiotherapy are scarce and it is debatable which of these neoadjuvant treatment concepts offers the best chance for long-term survival.
This thesis aims to improve the knowledge about neoadjuvant treatment in the curative treatment of esophageal cancer. Papers I and III were based on the Neoadjuvant Chemotherapy versus Chemoradiotherapy in Resectable Cancer of the Esophagus and Gastric Cardia (NeoRes) trial, which was performed in Norway and Sweden during the period 2006– 2013. Patients with resectable squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction were randomized to either preoperative chemotherapy or preoperative combined chemoradiotherapy followed by surgical resection. Paper I showed an increased risk for severe postoperative complications after chemoradiotherapy compared to chemotherapy. In paper III we found that neoadjuvant chemoradiotherapy significantly increases the proportion of complete histological response, increases the occurrence of N0 lymph-node status, and increases the R0 resection rate, but there was no difference in overall survival compared to neoadjuvant chemotherapy.
Paper II is a retrospective cohort study of patients with cancer of the esophagus or gastro- esophageal junction, who was reconstructed with cervical anastomosis. The planned radiation dose to the site of the cervical anastomosis on the gastric fundus was estimated for each patient. This study suggests that nCRT exposes the future anastomotic site to doses of radiation that may impair healing of the subsequent cervical anastomosis. Our data further suggest that nCRT may increase the severity of cervical anastomotic complications.
Paper IV is a prospective population-based cohort study including all patients who underwent an esophagectomy operation due to cancer in Sweden, excluding T1N0, recorded in the Swedish National Register for Esophageal and Gastric Cancer, 2006-2014. The results showed that neoadjuvant chemoradiotherapy increases local tumor control, represented by increased R0 resection rates and pathological node-negative disease both compared to surgery alone and chemotherapy. For patients with the histological subtype squamous cell carcinoma, neoadjuvant treatment increases long-term survival but also increases the risk of postoperative morbidity and mortality compared to surgery alone. Neither of the two neoadjuvant treatment options seem to improve survival in adenocarcinomas, compared to surgery alone, in an unselected population of patients.
This thesis aims to improve the knowledge about neoadjuvant treatment in the curative treatment of esophageal cancer. Papers I and III were based on the Neoadjuvant Chemotherapy versus Chemoradiotherapy in Resectable Cancer of the Esophagus and Gastric Cardia (NeoRes) trial, which was performed in Norway and Sweden during the period 2006– 2013. Patients with resectable squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction were randomized to either preoperative chemotherapy or preoperative combined chemoradiotherapy followed by surgical resection. Paper I showed an increased risk for severe postoperative complications after chemoradiotherapy compared to chemotherapy. In paper III we found that neoadjuvant chemoradiotherapy significantly increases the proportion of complete histological response, increases the occurrence of N0 lymph-node status, and increases the R0 resection rate, but there was no difference in overall survival compared to neoadjuvant chemotherapy.
Paper II is a retrospective cohort study of patients with cancer of the esophagus or gastro- esophageal junction, who was reconstructed with cervical anastomosis. The planned radiation dose to the site of the cervical anastomosis on the gastric fundus was estimated for each patient. This study suggests that nCRT exposes the future anastomotic site to doses of radiation that may impair healing of the subsequent cervical anastomosis. Our data further suggest that nCRT may increase the severity of cervical anastomotic complications.
Paper IV is a prospective population-based cohort study including all patients who underwent an esophagectomy operation due to cancer in Sweden, excluding T1N0, recorded in the Swedish National Register for Esophageal and Gastric Cancer, 2006-2014. The results showed that neoadjuvant chemoradiotherapy increases local tumor control, represented by increased R0 resection rates and pathological node-negative disease both compared to surgery alone and chemotherapy. For patients with the histological subtype squamous cell carcinoma, neoadjuvant treatment increases long-term survival but also increases the risk of postoperative morbidity and mortality compared to surgery alone. Neither of the two neoadjuvant treatment options seem to improve survival in adenocarcinomas, compared to surgery alone, in an unselected population of patients.
List of papers:
I. Morbidity and mortality after surgery for cancer of the oesophagus and gastro-oesophageal junction: A randomized clinical trial of neoadjuvant chemotherapy vs. neoadjuvant chemoradiation. Klevebro F, Johnsen G, Johnson E, Viste A, Myrnas T, Szabo E, Jacobsen, A. B, Friesland, S, Tsai, J. A, Persson, S, Lindblad, M, Lundell, L, Nilsson, M. European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2015 Jul;41(7):920-6.
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II. Neoadjuvant chemoradiotherapy may increase the risk of severe anastomotic complications after esophagectomy with cervical anastomosis. Klevebro F, Friesland S, Hedman M, Tsai JA, Lindblad M, Rouvelas I, et al. Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. 2016 Mar 28.
Fulltext (DOI)
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III. A Randomised Clinical Trial of Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Cancer of the Oesophagus or Gastro-Oesophageal Junction. Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen A- B, Friesland S, Hatlevoll I, Glenjen NI, Lind P, Tsai JA, Lundell L, Nilsson M Annals of Oncology. 2016 Jan 17.
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IV. Neoadjuvant therapy for cancer of the oesophagus or gastro-oesophageal junction - Swedish population-based national register data. Fredrik Klevebro, Mats Lindblad, Jan Johansson, Lars Lundell, Magnus Nilsson. [Submitted]
I. Morbidity and mortality after surgery for cancer of the oesophagus and gastro-oesophageal junction: A randomized clinical trial of neoadjuvant chemotherapy vs. neoadjuvant chemoradiation. Klevebro F, Johnsen G, Johnson E, Viste A, Myrnas T, Szabo E, Jacobsen, A. B, Friesland, S, Tsai, J. A, Persson, S, Lindblad, M, Lundell, L, Nilsson, M. European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2015 Jul;41(7):920-6.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Neoadjuvant chemoradiotherapy may increase the risk of severe anastomotic complications after esophagectomy with cervical anastomosis. Klevebro F, Friesland S, Hedman M, Tsai JA, Lindblad M, Rouvelas I, et al. Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. 2016 Mar 28.
Fulltext (DOI)
Pubmed
III. A Randomised Clinical Trial of Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Cancer of the Oesophagus or Gastro-Oesophageal Junction. Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen A- B, Friesland S, Hatlevoll I, Glenjen NI, Lind P, Tsai JA, Lundell L, Nilsson M Annals of Oncology. 2016 Jan 17.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Neoadjuvant therapy for cancer of the oesophagus or gastro-oesophageal junction - Swedish population-based national register data. Fredrik Klevebro, Mats Lindblad, Jan Johansson, Lars Lundell, Magnus Nilsson. [Submitted]
Institution: Karolinska Institutet
Supervisor: Nilsson, Magnus
Issue date: 2016-06-09
Rights:
Publication year: 2016
ISBN: 978-91-7676-330-8
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