title: Radiotherapy for SMAD4-negative musculoskeletal lesions from pancreatic cancer: case report and review.
abstract: BACKGROUND
  Pancreatic cancer (PC) predominantly metastasizes to liver, lung, and peritoneum. Metastatic disease correlates with SMAD4 status. Musculoskeletal metastases (MSM) are rare in pancreatic cancer. The role of radiation therapy (RT) in patients with musculoskeletal metastases is not clear.
  
  
  METHODS
  We present a case of a woman with musculoskeletal metastases of PC evolving 4 years after Whipple's procedure and adjuvant therapy. She was treated with RT for 7 MSM. Radiation dose was 15-45 Gy, delivered in doses of 2.5-5 Gy per fraction. SMAD4 status was examined by immunohistochemistry. Furthermore we undertook a review of the literature to examine the value of RT in musculoskeletal metastasis of PC.
  
  
  RESULTS
  In the presented patient we treated 7 MSM of SMAD4-mutant PC with RT. RT achieved local control in 4 of the 7 MSM. At the resection margin of one MSM recurrent tumor was observed after RT. The status of one MSM was unknown and one MSM showed local progression. Follow-up revealed progression of pain in 1 of the 7 MSM. Except of hyperpigmentation no side effects occurred. There was no dose-correlation effect on tumor control observed. A review of the literature showed that a musculoskeletotrophic phenotype of metastases is rare in PC. MSM of PC are rapidly increasing soft tissue masses causing pain and loss of anatomical function. RT as a treatment option for musculoskeletal metastasis is described in the current literature in only 2 cases. Radiotherapy aims to achieve local control, pain relief, and to maintain anatomical function.
  
  
  CONCLUSIONS
  Radiotherapy is an effective and well-tolerated approach for multiple musculoskeletal metastases of PC.
authors.affiliation: Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg i. Br., Robert-Koch-Straße 3, 79106, Freiburg, Deutschland, constantinos.zamboglou@uniklinik-freiburg.de.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Zamboglou
authors.forename: Peter
authors.initials: P
authors.lastname: Bronsert
authors.forename: Simon
authors.initials: S
authors.lastname: Küsters
authors.forename: Natalie
authors.initials: N
authors.lastname: Salm
authors.forename: Marc
authors.initials: M
authors.lastname: Azèmar
authors.forename: Thomas
authors.initials: T
authors.lastname: Brunner
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D005260:Female; D006801:Humans; D019042:Muscle Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D051901:Smad4 Protein / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein