Image-guided volumetric arc radiotherapy of pancreatic cancer with simultaneous integrated boost: Optimization strategies and dosimetric results.

PURPOSE: To introduce volumetric modulated arc therapy treatments (VMAT) with simultaneous integrated boost (SIB) for pancreatic cancer and describe dosimetric results on a large patient series. METHODS AND MATERIALS: 45 patients with pancreatic malignancies were treated with 18 MV single-arc VMAT. Image guidance was performed with daily online kilo-volt cone-beam computed tomography (CBCT). The conformity index (CI) and homogeneity index (HI) to the target volumes, PTV45Gy and PTV54Gy, and dose-volume indices to OARs from the QUANTEC task group were reported. The risk of clinical nephritis was evaluated using normal tissue complication probability (NTCP). Treatments were verified in-phantom with the Delta4 system. RESULTS: Average CI was 1.06 with 95% confidence intervals (95% CI) of 0.97-1.22 for PTV45Gy and 1.17 (0.66-1.61) for PTV54Gy. HI of PTV54Gy was 1.06 (1.04-1.10). OAR constraints were achieved in all patients, except for kidneys V12Gy of 48 (35.4-72.3)%. NTCP of the kidneys was 0.98 (0.6-1.7)%. Kidneys V12Gy and V20Gy were inversely related to PTV54Gy CI and maximum dose. All in-phantom tests had gamma pass rates exceeding 95% with global 3% dose difference and 3 mm distance to agreement. Patient shifts measured with CBCT had 95% CI of -0.8, +0.8 in the RL, -0.7, +0.8 in the SI, and -0.8, +0.7 cm in the AP directions. CONCLUSIONS: Dosimetric results of VMAT were excellent on PTVs and organs at risk. The kidneys represent the dose-limiting organ at risk for this technique. NTCP indicates that this technique is safe from radiation-induced side effects to the kidneys.

Hypofractionation of partial breast irradiation using radiobiological models.

PURPOSE: To reduce the fraction number in Partial Breast Irradiation (PBI) with initial prescription of 40 Gy in 10 fractions using radiobiological models with specific focus on risk of moderate/severe radiation-induced fibrosis (RIF) and report clinical results. METHODS AND MATERIALS: 68 patients (patient group A) were treated with 40 Gy in 10 fractions delivered by field-in-field, forward-planned IMRT. Isotoxic regimens with decreasing number of fractions were calculated using Biological Effective Dose (BED) to the breast. Risk for RIF in hypofractionated treatment was predicted by calculating NTCP from DVHs of group A rescaled to fractions and dose of novel regimens. Moderate/severe RIF was prospectively scored during follow-up. Various NTCP models, with and without incomplete repair correction, were assessed from difference to observed incidence of RIF. In order to verify the value for α/ß of 3 Gy assumed for breast, we fitted α/ß to observed incidences of moderate/severe RIF. RESULTS: Treatments with 35 Gy/7f and 28 Gy/4f were selected for the fraction reduction protocol. 75 patients (group B) were treated in 35 Gy/7f. Incidence of moderate/severe RIF was 5.9% in group A, 5.3% in group B. The NTCP model with correction for incomplete repair had lowest difference from observed RIF. The α/ß obtained from fitting was 2.8 (95%CIs 1.1-10.7) Gy. CONCLUSIONS: The hypofractionated regimen was well tolerated. The model for NTCP corrected for incomplete repair was the most accurate and an assumed α/ß value of 3 Gy is consistent with our patient data. The hypofractionation protocol is continuing with patients treated with 28 Gy/4f.

Half-body irradiation with tomotherapy for pain palliation in metastatic breast cancer.

CONTEXT: Half-body irradiation (HBI) is the fastest and most effective tool against uncontrolled pain from widespread bone metastases but is somewhat toxic. OBJECTIVES: To assess the feasibility of lower HBI with helical tomotherapy in patients with metastatic breast cancer in terms of acute toxicity and delay in chemotherapy administration. METHODS: Thirteen breast cancer patients with multiple painful bone metastases to the lower half of the body were enrolled in this prospective trial. Eight patients were receiving chemotherapy. Target volume included all bones from the L3-L4 interface to the femoral shafts. Radiation consisted of 8 Gy in one fraction, delivered with helical tomotherapy. Patients were premedicated only with oral steroids. Pain intensity was scored using the Numeric Rating Scale from 0 to 10. Toxicity was scored using the Common Terminology Criteria for Adverse Events, version 3.0. Quality of life was scored with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, before and 21 days after the radiation course. This trial was approved by the local review board. RESULTS: Median follow-up was at seven months (range 2-12 months). All but two patients had pain relief in the radiated field. Six patients stopped their analgesic drug consumption. Toxicity was acceptable: two Grade 3 hematologic toxicities were registered (anemia and leukopenia). Grade 1-2 toxicities were hematologic = 13, fever = 3, nausea = 2, and diarrhea = 1. Three of the eight patients had a delay in chemotherapy administration because of leukopenia or anemia. Twelve patients answered to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and an improved quality of life was documented in eight cases. CONCLUSION: Lower HBI delivered with helical tomotherapy resulted in a well-tolerated regimen, without significant delay in chemotherapy schedule.

Dose to the skin in helical tomotherapy: results of in vivo measurements with radiochromic films.

PURPOSE: The aim of this study is to report results of measurements of dose to the skin in vivo with radiochromic EBT films in treatments with helical tomotherapy. METHODS AND MATERIALS: In vivo measurements were performed by applying pieces of radiochromic films to the skin or to the inner side of thermoplastic mask before the treatment. The sites of treatment included scalp, brain, head and neck, cranio-spinal axis and lower limbs. Skin dosimetry was performed in a patient who experienced grade 3-4 acute side effects to the skin shortly after the first treatment sessions. For each patient we measured the setup errors using the daily MVCT acquired for image guidance of the treatment. EBT films were read with a flatbed Epson Expression scanner and images were processed with an in-house written routine. RESULTS: A total of 96 measurements of dose to the skin performed on 14 patients. The mean difference and standard error of the mean difference between measured and TPS-calculated dose was -9.2% ± 2.6% for all treatments, -6.6% ± 2.6% for head and neck treatments. These differences were statistically significant at the 0.05 significance level (t-Student test). Planned dose and dose range in the region of measurements were not correlated with dose discrepancy. CONCLUSIONS: Radiochromic EBT films are suitable detectors for surface dose measurements in tomotherapy treatments. Results show that TPS overestimates dose to the skin measured with EBT radiochromic films. In vivo skin measurements with EBT films are a useful tool for quality assurance of tomotherapy treatments, as the treatment planning system may not give accurate dose values at the surface.

Complication probability model for subcutaneous fibrosis based on published data of partial and whole breast irradiation.

PURPOSE: To extend the application of current radiation therapy (RT) based normal tissue complication probability (NTCP) models of radiation-induced fibrosis (RIF) of the breast to include the effects of fractionation, inhomogeneous dose, incomplete recovery, and time after the end of radiotherapy in partial breast irradiation (PBI). MATERIALS AND METHODS: An NTCP Lyman model with biologically effective uniform dose (BEUD) with and without a correction for the effect of incomplete repair was used. The time to occurrence of RIF was also taken into account. The radiobiological parameters were determined by fitting incidences of moderate/severe RIF in published randomized studies on RT of the breast. The NTCP model was used to calculate the risk of toxicity in 35 patients treated with intensity modulated, non-accelerated PBI and the result was compared with observed incidence of RIF. RESULTS: With α/ß fixed at 3Gy the parameters of the model without correction for incomplete repair extracted from fitting were: 50% complication probability biologically effective dose BEUD(50) = 107.2 Gy (95%CI = 95.9-118.6 Gy), volume parameter n = 0.06 (95%CI = 0-0.23), and slope of dose response m = 0.22, (95%CI = 0.20-0.23). After including the correction for incomplete repair with repair halftime for subcutaneous tissue of τ = 4.4 h we obtained BEUD(50) = 105.8 Gy (95%CI = 96.9-114.6Gy), n = 0.15 (95%CI = 0-0.33), m = 0.22 (95%CI = 0.20-0.23). Average NTCP predicted by these models, 4.3% and 2.0% respectively, offered a good agreement with RIF incidence in our patients, 5.7%, after an average follow-up of 12 months. CONCLUSION: The NTCP models of RIF, incorporating the effects of fractionation, volume effect, and latency of toxicity look promising to model PBI. Clinical validation from a prospective PBI treatment study is under development and will help test this preliminary result.

Treatment of recurrent high-grade gliomas with GliaSite brachytherapy: a prospective mono-institutional Italian experience.

AIMS AND BACKGROUND: The present study evaluated toxicity, local control, and survival in patients with relapsed high-grade glioma after surgery and external beam radiation therapy and treated with re-operation and GliaSite brachytherapy. METHODS: Between 2006 and 2008, 15 patients with recurrent high-grade glioma underwent re-operation and GliaSite brachytherapy. Ten patients were males and 5 females. Median age was 40 years (range, 20-71). Karnofsky performance status was ≥70. All patients but one received GliaSite irradiation of the surgical cavity wall at the dose of 4500 cGy at a depth of 1 cm. RESULTS: No severe acute side effects were observed during GliaSite brachytherapy. Pathologically documented, symptomatic late radiation necrosis was observed in 3 patients (20%); 2 subsequently died of further complications. Two patients were alive at a median follow-up 13 months (range, 1-30). Median overall survival after GliaSite brachytherapy was 13 months. CONCLUSIONS: Patients with recurrent high-grade glioma can be treated with additional surgery and GliaSite brachytherapy, delivering 4500 cGy at 1 cm depth without significant acute side effects but with a significant rate (20%) of late radiation necrosis, resulting in 13% of treatment-related deaths. Compared with the literature, survival results in our study appear to be satisfactory, but they may be related to patient selection criteria. Re-intervention followed by GliaSite brachytherapy should not be offered as a standard treatment for recurrent high-grade glioma, because of the high rate of late complications, treatment-related deaths, and high treatment costs.

Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy.

PURPOSE: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). METHODS: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. RESULTS: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term alpha and the dose per fraction. The estimated values of alpha and OER from data fitting were 0.396 Gy(-1) and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). CONCLUSIONS: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.