Optimizing induction chemotherapy regimens for radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) remains unresolved. This study aimed to quantitatively assess the changes in gross tumor volumes (GTVs) and to select the most optimal number of IC cycles. METHODS: We analyzed 54 patients who received a three-cycle IC before commencing radiotherapy, with the tumor and nodal responses assessed by a CT scan before IC and after each IC cycle. The gross tumor volumes of the nasopharynx primary lesion (GTV_T), involved retropharyngeal lymph node (GTV_RP), and involved cervical lymph node (GTV_N) were contoured on each scan. The volume change following each IC cycle was evaluated with Wilcoxon signed-rank test. The three-dimensional vector displacements of target centers were also calculated and compared. RESULTS: The volume reductions of GTVs following IC varied across different patients and showed different trends for the three GTV types. GTV_T and GTV_RP did not display further volume reduction after two IC cycles, whereas GTV_N showed monotonic volume decreases. For GTV_T and GTV_RP following the three IC cycles, the total volume reduction relative to the initial volume before IC was 12.0%, 22.5%, and 20.1% and 26.0%, 44.1%, and 42.2%, respectively. In contrast, for GTV_N, continuing volume reduction was observed with a total reduction of 25.3%, 43.2%, and 54.7% following the three cycles, and the reductions were all significant. Average displacements of the GTVs were <1.5 mm in all directions; their average three-dimensional displacements were 2.6, 4.0, and 1.7 mm, respectively. Acceptable toxicity was observed in most patients. CONCLUSION: This study supports two cycles of IC before radiotherapy for patients with LANPC if the initial metastatic cervical lymph node volume is not dominating. Otherwise, three cycles of IC is recommended to further reduce the cervical node volume.

Quantifying Tumor and Vasculature Deformations during Laryngoscopy.

Retractors and scopes used in head and neck surgery to provide adequate surgical exposure also deform critical structures in the region. Surgeons typically use preoperative imaging to plan and guide their tumor resections, however the large tissue deformation resulting from placement of retractors and scopes reduces the utility of preoperative imaging as a reliable roadmap. We quantify the extent of tumor and vasculature deformation in patients with tumors of the larynx and pharynx undergoing diagnostic laryngoscopy. A mean tumor displacement of 1.02 cm was observed between the patients' pre- and intra-operative states. Mean vasculature displacement at key bifurcation points was 0.99 cm. Registration to the hyoid bone can reduce tumor displacement to 0.67 cm and improve carotid stem angle deviations but increase overall vasculature displacement. The large deformation results suggest limitations in reliance on preoperative imaging and that using specific landmarks intraoperatively or having more intraoperative information could help to compensate for these deviations and ultimately improve surgical success.

Soft tissue deformation tracking by means of an optimized fiducial marker layout with application to cancer tumors.

OBJECTIVE: Interventional radiology methods have been adopted for intraoperative control of the surgical region of interest (ROI) in a wide range of minimally invasive procedures. One major obstacle that hinders the success of procedures using interventional radiology methods is the preoperative and intraoperative deformation of the ROI. While fiducial markers (FM) tracing has been shown to be promising in tracking such deformations, determining the optimal placement of the FM in the ROI remains a significant challenge. The current study proposes a computational framework to address this problem by preoperatively optimizing the layout of FM, thereby enabling an accurate tracking of the ROI deformations. METHODS: The proposed approach includes three main components: (1) creation of virtual deformation benchmarks, (2) method of predicting intraoperative tissue deformation based on FM registration, and (3) FM layout optimization. To account for the large variety of potential ROI deformations, virtual benchmarks are created by applying a multitude of random force fields on the tumor surface in physically based simulations. The ROI deformation prediction is carried out by solving the inverse problem of finding the smoothest force field that leads to the observed FM displacements. Based on this formulation, a simulated annealing approach is employed to optimize the FM layout that produces the best prediction accuracy. RESULTS: The proposed approach is capable of finding an FM layout that outperforms the rationally chosen layouts by 40% in terms of ROI prediction accuracy. For a maximum induced displacement of 20 mm on the tumor surface, the average maximum error between the benchmarks and our FM-optimized predictions is about 1.72 mm, which falls within the typical resolution of ultrasound imaging. CONCLUSIONS: The proposed framework can optimize FM layout to effectively reduce the errors in the intraoperative deformation prediction process, thus bridging the gap between preoperative imaging and intraoperative tissue deformation.

Reconstruction of a Deformed Tumor Based on Fiducial Marker Registration: A Computational Feasibility Study.

Interstitial photodynamic therapy has shown promising results in the treatment of locally advanced head and neck cancer. In this therapy, systemic administration of a light-sensitive drug is followed by insertion of multiple laser fibers to illuminate the tumor and its margins. Image-based pretreatment planning is employed in order to deliver a sufficient light dose to the complex locally advanced head-and-neck cancer anatomy, in order to meet clinical requirements. Unfortunately, the tumor may deform between pretreatment imaging for the purpose of planning and intraoperative imaging when the plan is executed. Tumor deformation may result from the mechanical forces applied by the light fibers and variation of the patient's posture. Pretreatment planning is frequently done with the assistance of computed tomography or magnetic resonance imaging in an outpatient suite, while treatment monitoring and control typically uses ultrasound imaging due to considerations of costs and availability in the operation room. This article presents a computational method designed to bridge the gap between the 2 imaging events by taking a tumor geometry, reconstructed during preplanning, and by following the displacement of fiducial markers, which are initially placed during the preplanning procedure. The deformed tumor shape is predicted by solving an inverse problem, seeking for the forces that would have resulted in the corresponding fiducial marker displacements. The computational method is studied on spheres of variable sizes and demonstrated on computed tomography reconstructed locally advanced head and neck cancer model. Results of this study demonstrate an average error of less than 1 mm in predicting the deformed tumor shape, where 1 mm is typically the order of uncertainty in distance measurements using magnetic resonance imaging or computed tomography imaging and high-quality ultrasound imaging. This study further demonstrates that the deformed shape can be calculated in a few seconds, making the proposed method clinically relevant.