title: Radiation-induced dose-dependent changes of the spleen following postoperative chemoradiotherapy for gastric cancer.
abstract: OBJECTIVE
  Abdominal (chemo-)radiotherapy is associated with dose-limiting toxicity of various normal structures. The purpose of this retrospective study was to investigate radiation-induced changes of the spleen and their clinical consequences.
  
  
  METHODS
  In gastric cancer patients treated with postoperative chemoradiotherapy, the spleen size and its functions were assessed at follow-up by spleen volume on CT-scan, serum leucocytes/thrombocytes, and the occurrence of infectious events consisting of pneumonia and fatal sepsis. To evaluate the effect of radiation dose, mixed effects and Cox regression models were used.
  
  
  RESULTS
  Forty-six out of 90 consecutive patients treated from 2006 to 2011 were evaluable. All patients received 45 Gy in 25 fractions with concurrent capecitabine (n=8), and capecitabine/cisplatin (n=38). Median Dmean to the spleen was 40 Gy (range 32-46). Mean relative spleen volume reduced to 37% (95% CI 32-42%) at 4-year follow-up, which was most strongly associated to the V44 (p<0.001). Median follow-up time was 67 (95% CI 57-78) months. Eleven patients had 13 pneumonias and 3 fatal sepsis. No association with dosimetric parameters was observed.
  
  
  CONCLUSIONS
  In postoperative chemoradiotherapy for gastric cancer, the spleen received a high radiation dose. This resulted in a progressive, radiation dose-dependent reduction of spleen volume. Pneumonia and fatal sepsis occurred frequently, possibly as a result of functional hyposplenia.
authors.affiliation: Department of Radiation Oncology, The Netherlands.
authors.forename: Anouk Kirsten
authors.initials: AK
authors.lastname: Trip
authors.affiliation: Department of Biometrics, The Netherlands.
authors.forename: Karolina
authors.initials: K
authors.lastname: Sikorska
authors.affiliation: Department of Surgery, The Netherlands.
authors.forename: Johanna W
authors.initials: JW
authors.lastname: van Sandick
authors.affiliation: Department of Radiation Oncology, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Heeg
authors.affiliation: Department of Gastroenterology and Hepatology, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Cats
authors.affiliation: Department of Gastroenterology and Hepatology, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Boot
authors.affiliation: Department of Radiation Oncology, The Netherlands.
authors.forename: Edwin Petrus Marianus
authors.initials: EP
authors.lastname: Jansen
authors.affiliation: Department of Radiation Oncology, The Netherlands. Electronic address: m.verheij@nki.nl.
authors.forename: Marcel
authors.initials: M
authors.lastname: Verheij
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy / Q000009:adverse effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013154:Spleen / Q000528:radiation effects*; D013274:Stomach Neoplasms / Q000628:therapy*
keywords: Gastric cancer; Hyposplenia; Normal tissue toxicity; Postoperative chemoradiotherapy; Spleen; Spleen/radiation effects