title: Differential motion between mediastinal lymph nodes and primary tumor in radically irradiated lung cancer patients.
abstract: OBJECTIVE
  In patients with locally advanced lung cancer, planning target volume margins for mediastinal lymph nodes and tumor after a correction protocol based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed information about lymph node motion variability and differential motion with the primary tumor, however, is lacking from large series. In this study, lymph node and tumor position variability were analyzed in detail and correlated to the main carina to evaluate possible margin reduction.
  
  
  METHODS
  Small gold fiducial markers (0.35 × 5 mm) were placed in the mediastinal lymph nodes of 51 patients with non-small cell lung cancer during routine diagnostic esophageal or bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to the planning CT scan. Subsequently, systematic and random residual misalignments of the time-averaged lymph node and tumor position relative to the bony anatomy and carina were determined. Additionally, tumor and lymph node respiratory amplitude variability was quantified. Finally, required margins were quantified by use of a recipe for dual targets.
  
  
  RESULTS
  Relative to the bony anatomy, systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from 0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited correlation (0.17-0.71) owing to differential motion. A large variability in lymph node amplitude between patients was observed, with an average motion of 0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left-right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and -2%, 15%, and 7% for the tumor if an online carina registration protocol replaced a protocol based on bony anatomy registration.
  
  
  CONCLUSIONS
  Detailed analysis revealed considerable lymph node position variability, differential motion, and respiratory motion. Planning target volume margins can be reduced up to 27% in lung cancer patients when the carina registration replaces bony anatomy registration.
authors.affiliation: Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Eva E
authors.initials: EE
authors.lastname: Schaake
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Maddalena M G
authors.initials: MM
authors.lastname: Rossi
authors.affiliation: Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Wieneke A
authors.initials: WA
authors.lastname: Buikhuisen
authors.affiliation: Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jacobus A
authors.initials: JA
authors.lastname: Burgers
authors.affiliation: Department of Pulmonary Disease, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Adrianus A J
authors.initials: AA
authors.lastname: Smit
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: José S A
authors.initials: JS
authors.lastname: Belderbos
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: j.sonke@nki.nl.
authors.forename: Jan-Jakob
authors.initials: JJ
authors.lastname: Sonke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059925:Anatomic Landmarks / Q000000981:diagnostic imaging; D054893:Cone-Beam Computed Tomography; D019583:Dose Fractionation, Radiation; D005260:Female; D057918:Fiducial Markers; D056973:Four-Dimensional Computed Tomography; D006046:Gold; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D008198:Lymph Nodes / Q000000981:diagnostic imaging*; D008207:Lymphatic Metastasis; D008297:Male; D008482:Mediastinum / Q000000981:diagnostic imaging*; D008875:Middle Aged; D009068:Movement; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated; D012119:Respiration
chemical_list: D006046:Gold