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Current inverse treatment planning methods that optimize both catheter positions and dwell times in prostate HDR brachytherapy use surrogate linear or quadratic objective functions that have no direct interpretation in terms of dose-volume histogram (DVH) criteria, do not result in an optimum or have long solution times. We decrease the solution time of the existing linear and quadratic dose-based programming models (LP and QP, respectively) to allow optimizing over potential catheter positions using mixed integer programming. An additional average speed-up of 75% can be obtained by stopping the solver at an early stage, without deterioration of the plan quality. For a fixed catheter configuration, the dwell time optimization model LP solves to optimality in less than 15 s, which confirms earlier results. We propose an iterative procedure for QP that allows us to prescribe the target dose as an interval, while retaining independence between the solution time and the number of dose calculation points. This iterative procedure is comparable in speed to the LP model and produces better plans than the non-iterative QP. We formulate a new dose-volume-based model that maximizes V(100%) while satisfying pre-set DVH criteria. This model optimizes both catheter positions and dwell times within a few minutes depending on prostate volume and number of catheters, optimizes dwell times within 35 s and gives better DVH statistics than dose-based models. The solutions suggest that the correlation between the objective value and the clinical plan quality is weak in the existing dose-based models.

Accelerated tumor cell proliferation is an important mechanism adversely affecting therapeutic outcome in head and neck cancer. 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT) is a PET tracer to noninvasively image tumor cell proliferation. The aims of this study were to monitor early tumor response based on repetitive 18 F-FLT PET/CT scans and to identify subvolumes with high proliferative activity eligible for dose escalation. Methods: Ten patients with oropharyngeal tumors underwent an 18 F-FLT PET/CT scan before and twice during radiotherapy. The primary tumor and metastatic lymph nodes (gross tumor volume, or GTV) were delineated on CT (GTV CT ) and after segmentation of the PET signal using the 50% isocontour of the maximum signal intensity or an adaptive threshold based on the signal-to-background ratio (GTV SBR ). GTVs were calculated, and similarity between GTV CT and GTV SBR was assessed. Within GTV SBR , the maximum and mean standardized uptake value (SUV max and SUV mean , respectively) was calculated. Within GTV CT , tumor subvolumes with high proliferative activity based on the 80% isocontour (GTV 80% ) were identified for radiotherapy planning with dose escalation. Results: The GTV CT decreased significantly in the fourth week but not in the initial phase of treatment. SUV max and SUV mean decreased significantly as early as 1 wk after therapy initiation and even further before the fourth week of treatment. For the primary tumor, the average (6SD) SUV mean of the GTV SBR was 4.7 6 1.6, 2.0 6 0.9, and 1.3 6 0.2 for the consecutive scans (P , 0.0001). The similarity between GTV CT and GTV SBR decreased during treatment, indicating an enlargement of GTV SBR outside GTV CT caused by the increasing difficulty of segmenting tracer uptake in the tumor from the background and by proliferative activity in the nearby tonsillar tissue. GTV 80% was successfully identified in all primary tumors and metastatic lymph nodes, and dose escalation based on the GTV 80% was demonstrated to be technically feasible. Conclusion: 18 F-FLT is a promising PET tracer for imaging tumor cell proliferation in head and neck carcinomas. Signal changes in 18 F-FLT PET precede volumetric tumor response and are therefore suitable for early response assessment. Definition of tumor subvolumes with high proliferative activity and dose escalation to these regions are technically feasible.