Limited role for biliary stent as surrogate fiducial marker in pancreatic cancer: stent and intratumoral fiducials compared.

Because of low soft-tissue contrast of cone beam computed tomography (CBCT), fiducial markers are often used for radiation therapy patient setup verification. For pancreatic cancer patients, biliary stents have been suggested as surrogate fiducials. Using intratumoral fiducials as standard for tumor position, this study aims to quantify the suitability of biliary stents for measuring interfractional and respiratory-induced position variations of pancreatic tumors. Eleven pancreatic cancer patients with intratumoral fiducials and a biliary stent were included in this study. Daily CBCT scans (243 in total) were registered with a reference CT scan, based on bony anatomy, on fiducial markers, and on the biliary stent, respectively. We analyzed the differences in tumor position (ie, markers center-of-mass position) among these 3 registrations. In addition, we measured for 9 patients the magnitude of respiratory-induced motion (MM) of the markers and of the stent on 4-dimensional CT (4DCT) and determined the difference between these 2 magnitudes (ΔMM). The stent indicated tumor position better than bony anatomy in 67% of fractions; the absolute difference between the markers and stent registration was >5 mm in 46% of fractions and >10 mm in 20% of fractions. Large PTV margins (superior-inferior direction, >19 mm) would be needed to account for this interfractional position variability. On 4DCT, we found in superior-inferior direction a mean ΔMM of 0.5 mm (range, -2.6 to 4.2 mm). For respiratory-induced motion, the mean ΔMM is small, but for individual patients the absolute difference can be >4 mm. For interfractional position variations, a stent is, on average, a better surrogate fiducial than bony anatomy, but large PTV margins would still be required. Therefore, intratumoral fiducials are recommended for online setup verification for all pancreatic patients scheduled for radiation therapy, including patients with a biliary stent.

van der Horst A ，Lens E ，Wognum S ，de Jong R ，van Hooft JE ，van Tienhoven G ，Bel A ... -  《-》

Interfractional position variation of pancreatic tumors quantified using intratumoral fiducial markers and daily cone beam computed tomography.

The aim of this study was to quantify interfractional pancreatic position variation using fiducial markers visible on daily cone beam computed tomography (CBCT) scans. In addition, we analyzed possible migration of the markers to investigate their suitability for tumor localization. For 13 pancreatic cancer patients with implanted Visicoil markers, CBCT scans were obtained before 17 to 25 fractions (300 CBCTs in total). Image registration with the reference CT was used to determine the displacement of the 2 to 3 markers relative to bony anatomy and to each other. We analyzed the distance between marker pairs as a function of time to identify marker registration error (SD of linear fit residuals) and possible marker migration. For each patient, we determined the mean displacement of markers relative to the reference CT (systematic position error) and the spread in displacements (random position error). From this, we calculated the group systematic error, Σ, and group random error, σ. Marker pair distances showed slight trends with time (range, -0.14 to 0.14 mm/day), possibly due to tissue deformation, but no shifts that would indicate marker migration. The mean SD of the fit residuals was 0.8 mm. We found large interfractional position variations, with for 116 of 300 (39%) fractions a 3-dimensional vector displacement of >10 mm. The spread in displacement varied significantly (P<.01) between patients, from a vector range of 9.1 mm to one of 24.6 mm. For the patient group, Σ was 3.8, 6.6, and 3.5 mm; and σ was 3.6, 4.7 and 2.5 mm, in left-right, superior-inferior, and anterior-posterior directions, respectively. We found large systematic displacements of the fiducial markers relative to bony anatomy, in addition to wide distributions of displacement. These results for interfractional position variation confirm the potential benefit of using fiducial markers rather than bony anatomy for daily online position verification for pancreatic cancer patients.

van der Horst A ，Wognum S ，Dávila Fajardo R ，de Jong R ，van Hooft JE ，Fockens P ，van Tienhoven G ，Bel A ... -  《-》

Differences in respiratory-induced pancreatic tumor motion between 4D treatment planning CT and daily cone beam CT, measured using intratumoral fiducials.

Lens E ，van der Horst A ，Kroon PS ，van Hooft JE ，Dávila Fajardo R ，Fockens P ，van Tienhoven G ，Bel A ... -  《-》

Evaluation of Bony Anatomy Versus Endobiliary Stents as Surrogates for Volumetric Image Guidance in Pancreatic Cancer.

Online treatment setup verification through cone-beam computed tomography (CBCT) in pancreatic cancer patients is limited by low soft tissue contrast. This study aims to quantify the relative positional displacements between bony anatomy and endobiliary stents as surrogates for pancreatic cancers. Under ethics approval, 258 localization CBCT images from 15 pancreatic patients with endobiliary stents were evaluated. CBCTs were registered through two methods to assess translations and rotations: target adjacent bony anatomy through automatic registration and automatic stent registration through a shaped region of interest. Displacement vector differences between surrogate registrations were calculated and analysed. Mean (±standard deviation) translational displacements in the right/left, superior/inferior, anterior/posterior directions were 0.9 ± 3.1 mm, 1.8 ± 4.2 mm, and 0.4 ± 2.5 mm for bone registrations, respectively, and 0.9 ± 5.6 mm, -1.5 ± 5.7 mm, and -0.5 ± 4.3 mm for stent registrations, respectively. Mean (±standard deviation) rotational displacements for pitch, roll, and yaw were 0.16 ± 0.97°, -0.32 ± 0.96°, and -0.77 ± 1.8° for bone registrations, respectively, and -0.94 ± 4.6°, -0.4 ± 7.4°, and -0.13 ± 6.64° for stent registrations, respectively. Mean displacement vector between surrogates was 4 mm, with 43% of fractions measuring displacement vectors >5 mm. A maximum displacement vector of 22.6 mm between surrogates was observed. Varying positional differences were observed between bone and stent registration for pancreas CBCT-image-guided radiation therapy. Setup errors for stent matching were larger than bone registrations. Further research is required to determine if endobiliary stent position is equivalent to the pancreas' location to determine its suitability as a surrogate.

Chortogiannos C ，Moseley D ，Chen J ，Pellizzari A ，Brierley J ，Li W ... -  《-》

Differential motion between mediastinal lymph nodes and primary tumor in radically irradiated lung cancer patients.

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. 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. 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. 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.

Schaake EE ，Rossi MM ，Buikhuisen WA ，Burgers JA ，Smit AA ，Belderbos JS ，Sonke JJ ... -  《-》