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Background: For patients with recurrent or second primary disease, re-irradiation can be challenging due to overlap with previously irradiated volumes. Dose painting may be attractive for these patients, as the focus is on delivering maximal dose to areas of high tumor activity. Here, we compare dose painting by contours (DPBC) treatment plans based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with conventional plans. Material and methods: We included 10 patients with recurrent or second primary head and neck cancer (HNC) eligible for re-irradiation. Our conventional re-irradiation regimen is hyperfractionated radiotherapy 1.5 Gy twice daily over 4 weeks, giving a total dose of 60 Gy. For DPBC, we defined two prescription volumes, PV33 and PV66, corresponding to 33 and 66% of the highest FDG uptake in the tumor. The clinical target volume (CTV) prescription dose was 60 Gy, PV33; 65–67 Gy and PV66; 70–73 Gy. The DPBC plan is to be given the first 20 fractions and the conventional plan the last 20 fractions. Dose to organs at risk (OARs) were compared for DPBC and conventional treatment. By summation of the initial curative plan and the re-irradiation plan, we also evaluated differences in dose to the 2 ccm hot spot (D2cc). Results: We achieved DPBC plans with adequate target coverage for all 10 patients. There were no significant differences in OAR doses between the standard plans and the DPBC plans (p=.7). Summation of the initial curative plan and the re-irradiation plan showed that the median D2cc increased from 130 Gy (range 113–132 Gy; conventional) to 140 Gy (range 115–145 Gy; DPBC). Conclusions: Our proposed DPBC could be straightforwardly implemented and all plans met the objectives. Re-irradiation of HNC with DPBC may increase tumor control without more side effects compared to conventional radiotherapy.

Gleason scores for prostate cancer correlates with an increased recurrence risk after radiotherapy (RT). Furthermore, higher Gleason scores correlates with decreasing apparent diffusion coefficient (ADC) data from diffusion weighted MRI (DWI-MRI). Based on these observations, we present a formalism for dose painting prescriptions of prostate volumes based on ADC images mapped to Gleason score driven dose-responses.The Gleason score driven dose-responses were derived from a learning data set consisting of pre-RT biopsy data and post-RT outcomes for 122 patients treated with a homogeneous dose to the prostate. For a test data set of 18 prostate cancer patients with pre-RT ADC images, we mapped the ADC data to the Gleason driven dose-responses by using probability distributions constructed from published Gleason score correlations with ADC data. We used the Gleason driven dose-responses to optimize dose painting prescriptions that maximize the tumor control probability (TCP) with equal average dose as for the learning sets homogeneous treatment dose.The dose painting prescriptions increased the estimated TCP compared to the homogeneous dose by 0-51% for the learning set and by 4-30% for the test set. The potential for individual TCP gains with dose painting correlated with increasing Gleason score spread and larger prostate volumes. The TCP gains were also found to be larger for patients with a low expected TCP for the homogeneous dose prescription.We have from retrospective treatment data demonstrated a formalism that yield ADC driven dose painting prescriptions for prostate volumes that potentially can yield significant TCP increases without increasing dose burdens as compared to a homogeneous treatment dose. This motivates further development of the approach to consider more accurate ADC to Gleason mappings, issues with delivery robustness of heterogeneous dose distributions, and patient selection criteria for design of clinical trials.

To identify predictive factors for the development of late grade 4 mucosal ulcers in adaptive dose-escalated treatments for head-and-neck cancer.Patient data of four dose-escalated three-phase adaptive dose-painting by numbers (DPBN) clinical trials were analyzed in this study. Correlations between the development of late grade 4 ulcers and factors related with the treatment, disease characteristics and the patient were investigated. Dosimetrical thresholds were searched among the highest doses received by 1.75 cmFrom 39 studied patients, nine developed late grade 4 mucosal ulcers. The continuation to either smoke or drink alcohol after therapy was the factor that showed a strong (eight out of nine patients) association with the occurrence of grade 4 ulcers. Six of the patients who continued to smoke or/and drink had DThe search for patterns provided strong reasons to apply a dosimetrical threshold for the peak-dose volume of 1.75 cm

BACKGROUND: The pre-treatment 18F-Fludeoxyglucose (FDG) avid sub-volume of the tumor has shown promise as a potential target for dose painting in patients with in head and neck squamous cell carcinomas. PURPOSE: The purposes of this study are (1) to assess the pre-treatment spatio-temporal variability of FDG PET/CT target volumes and (2) to assess the impact of this variability on dose distribution in dose painting plans in patients with head and neck squamous cell carcinoma. METHODS AND MATERIALS: Thirty patients were enrolled and scanned twice, three days apart, days prior to treatment. Delineation of the FDG avid sub-volume of the tumor and lymph nodes on both scans was performed by a specialist in nuclear medicine yielding GTV(PET1) and GTV(PET2) and segmentation based on SUV iso-contours were constructed yielding two metabolic target volumes, MTV1 and MTV2. Images were co-registered rigidly and dose painting plans with dose escalation up to 82 Gy to GTV(PET1) were planned and GTV(PET2) was copied from the co-registered images to the dose planning scan. Variation in dose to the target and modeled tumor control probability were assessed as measures of the impact of imaging variations in a dose painting scenario. RESULTS: Twenty-four patients were available for full analysis. The median mismatch between GTV(PET1) and GTV(PET2) was 14.2% (1.7 cc.). The median difference in dose to the FDG planning target volume was 0.3 Gy (PTV(PET)) and 0.4 Gy (PTV(MTV)). Median difference in the modeled tumor control probability (TCP) was

Background. The increasing complexity of radiotherapy (RT) has motivated research into three-dimensional (3D) dosimetry. In this study we investigate the use of 3D dosimetry with polymerizing gels and optical computed tomography (optical CT) as a verification tool for complex RT: dose painting and target tracking. Materials and Methods. For the dose painting studies, two dosimeters were irradiated with a seven-field intensity modulated radiotherapy (IMRT) plan with and without dose prescription based on a hypoxia image dataset of a head and neck patient. In the tracking experiments, two dosimeters were irradiated with a volumetric modulated arc therapy (VMAT) plan with and without clinically measured prostate motion and a third with both motion and target tracking. To assess the performance, 3D gamma analyses were performed between measured and calculated stationary dose distributions. Results. Gamma pass-rates of 95.3% and 97.3% were achieved for the standard and dose-painted IMRT plans. Gamma pass-rates of 91.4% and 54.4% were obtained for the stationary and moving dosimeter, respectively, while tracking increased the pass-rate for the moving dosimeter to 90.4%. Conclusions. This study has shown that the 3D dosimetry system can reproduce and thus verify complex dose distributions, also when influenced by motion.

Important limitations for dose painting are due to treatment planning and delivery constraints. The purpose of this study was to develop a methodology for creating voxel-based dose painting plans that are deliverable using the clinical TomoTherapy Hi-Art II treatment planning system (TPS). Material and methods. Uptake data from a head and neck patient who underwent a [(61)Cu]Cu-ATSM (hypoxia surrogate) PET/CT scan was retrospectively extracted for planning. Non-uniform voxel-based prescriptions were converted to structured-based prescriptions for compatibility with the Hi-Art II TPS. Optimized plans were generated by varying parameters such as dose level, structure importance, prescription point normalization, DVH volume, min/max dose, and dose penalty. Delivery parameters such as pitch, jaw width and modulation factor were also varied. Isodose distributions, quality volume histograms and planning target volume percentage receiving planned dose within 5% of the prescription (Q(0.95-1.05)) were used to evaluate plan conformity. Results. In general, the conformity of treatment plans to dose prescriptions was found to be adequate for delivery of dose painting plans. The conformity was better as the dose levels increased from three to nine levels (Q(0.95-1.05): 69% to 93%), jaw decreased in width from 5.0cm to 1.05cm (Q(0.95-1.05): 81% to 93%), and modulation factor increased up to 2.0 (Q(0.95-1.05): 36% to 92%). The conformity was invariant to changes in pitch. Plan conformity decreased as the prescription DVH constraint (Q(0.95-1.05): 93% vs. 89%) or the normalization point (Q(0.95-1.05): 93% vs. 90%) deviated from the means. Conclusion. This investigation demonstrated the ability of the Hi-Art II TPS to create voxel-based dose painting plans. Results indicated that agreement in prescription dose and planned dose distributions for all plans were sensitive to physical delivery parameter changes in jaw width and modulation factors, but insensitive to changes in pitch. Tight constraints on target structures also resulted in decreased plan conformity while under a relaxed set of optimization parameters, plan conformity was increased.

Our work on dose-painting based on the possible risk characteristics for local recurrence in tumor subvolumes and the optimization of treatment plans using biological objective functions that are region-specific are reviewed.A series of intensity modulated dose-painting techniques are compared to their corresponding intensity modulated plans in which the entire PTV is treated to a single dose level, delivering the same equivalent uniform dose (EUD) to the entire PTV. Iso-TCP and iso-NTCP maps are introduced as a tool to aid the planner in the evaluation of the resulting non-uniform dose distributions. Iso-TCP and iso-NTCP maps are akin to iso-dose maps in 3D conformal radiotherapy. The impact of the currently limited diagnostic accuracy of functional imaging on a series of dose-painting techniques is also discussed.Utilizing biological parameters (risk-adaptive optimization) in the generation of dose-painting plans results in an increase in the therapeutic ratio as compared to conventional dose-painting plans in which optimization techniques based on physical dose are employed.Dose-painting employing biological parameters appears to be a promising approach for individualized patient- and disease-specific radiotherapy.