Integrating quantitative morphological and intratumoural textural characteristics in FDG-PET for the prediction of prognosis in pharynx squamous cell carcinoma patients.

AIM: To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan-Meier method. RESULTS: In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan-Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. CONCLUSION: The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer.

BACKGROUND: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). METHODS: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg m(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). RESULTS: One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions. CONCLUSION: We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

SU-E-J-42: Motion Adaptive Image Filter for Low Dose X-Ray Fluoroscopy in the Real-Time Tumor-Tracking Radiotherapy System.

PURPOSE: In the real-time tumor-tracking radiotherapy system, fiducial markers are detected by X-ray fluoroscopy. The fluoroscopic parameters should be optimized as low as possible in order to reduce unnecessary imaging dose. However, the fiducial markers could not be recognized due to effect of statistical noise in low dose imaging. Image processing is envisioned to be a solution to improve image quality and to maintain tracking accuracy. In this study, a recursive image filter adapted to target motion is proposed. METHODS: A fluoroscopy system was used for the experiment. A spherical gold marker was used as a fiducial marker. About 450 fluoroscopic images of the marker were recorded. In order to mimic respiratory motion of the marker, the images were shifted sequentially. The tube voltage, current and exposure duration were fixed at 65 kV, 50 mA and 2.5 msec as low dose imaging condition, respectively. The tube current was 100 mA as high dose imaging. A pattern recognition score (PRS) ranging from 0 to 100 and image registration error were investigated by performing template pattern matching to each sequential image. The results with and without image processing were compared. RESULTS: In low dose imaging, theimage registration error and the PRS without the image processing were 2.15±1.21 pixel and 46.67±6.40, respectively. Those with the image processing were 1.48±0.82 pixel and 67.80±4.51, respectively. There was nosignificant difference in the image registration error and the PRS between the results of low dose imaging with the image processing and that of high dose imaging without the image processing. CONCLUSIONS: The results showed that the recursive filter was effective in order to maintain marker tracking stability and accuracy in low dose fluoroscopy.

How much margin reduction is possible through gating or breath hold?

We determined the relationship between intra-fractional breathing motion and safety margins, using daily real-time tumour tracking data of 40 patients (43 tumour locations), treated with radiosurgery at Hokkaido University. We limited our study to the dose-blurring effect of intra-fractional breathing motion, and did not consider differences in positioning accuracy or systematic errors. The additional shift in the prescribed isodose level (e.g. 95 %) was determined by convolving a one-dimensional dose profile, having a dose gradient representing an 8 MV beam through either lung or water, with the probability density function (PDF) of breathing. This additional shift is a measure for the additional margin that should be applied in order to maintain the same probability of tumour control as without intra-fractional breathing. We show that the required safety margin is a nonlinear function of the peak-to-peak breathing motion. Only a small reduction in the shift of isodose curves was observed for breathing motion up to 10 mm. For larger motion, 20 or 30 mm, control of patient breathing during irradiation, using either gating or breath hold, can allow a substantial reduction in safety margins of about 7 or 12 mm depending on the dose gradient prior to blurring. Clinically relevant random setup uncertainties, which also have a blurring effect on the dose distribution, have only a small effect on the margin needed for intra-fractional breathing motion. Because of the one-dimensional nature of our analysis, the resulting margins are mainly applicable in the superior-inferior direction. Most measured breathing PDFs were not consistent with the PDF of a simple parametric curve such as cos4, either because of irregular breathing or base-line shifts. Instead, our analysis shows that breathing motion can be modelled as Gaussian with a standard deviation of about 0.4 times the peak-to-peak breathing motion.

Magnetic resonance imaging system for three-dimensional conformal radiotherapy and its impact on gross tumor volume delineation of central nervous system tumors.

PURPOSE: We developed an MRI system for three-dimensional planning in radiotherapy. Its contribution on gross tumor volume (GTV) delineation of central nervous system (CNS) diseases was evaluated. METHODS AND MATERIALS: The MRI system, with corrected distortion, was registered on computed tomography (CT) by means of fiducial/anatomic landmarks. In 41 consecutive patients with various CNS diseases, GTVs determined by MRI/CT registration (MR/CT-GTV) and CT alone (CT-GTV) were compared. Hard copies of diagnostic MRI were shown to doctors when CT-GTV was determined to simulate a conventional planning situation. Multi-observer volumetric analysis was conducted, assessing interobserver deviations among four radiation oncologists and intermethodological deviations between MR/CT-GTV and CT-GTV. RESULTS: Overall, the mean of geometric distortion was significantly reduced from 1.08 mm to 0.3 mm by distortion correction (p < 0.0001). The contribution of the correction was apparent at >12.0 cm radius from the center of the magnetic field. Interobserver deviation was significantly reduced by MR/CT registration (p = 0.005). The improvement was significant for acoustic neurinoma (p = 0.038), astrocytomas (p = 0.043), and lesions at the cerebellum/brainstem (p = 0.008). The regression coefficient between MR/CT-GTV and CT-GTV was <0.9 for cerebellum/brainstem lesions, suggesting that MRI/CT-GTV was smaller than CT-GTV. CONCLUSIONS: This system is feasible for three-dimensional planning and was shown to reduce interobserver deviations in GTV delineation for CNS diseases.

Treatment outcome of single or hypofractionated single-isocentric stereotactic irradiation (STI) using a linear accelerator for intracranial arteriovenous malformation.

BACKGROUND AND PURPOSE: We investigated the use of hypofractionated stereotactic radiotherapy (HFSR) to reduce adverse radiation effects in comparison to single-fraction stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (AVMs). MATERIALS AND METHODS: This study includes 53 intracranial AVMs treated between 1991-1998. HFSR was selected for 26 AVMs with a maximum diameter > or 2.5 cm or at eloquent area. Twenty-seven patients were treated with SRS (18 AVMs < 2.5 cm at non-eloquent area, nine patients who were unfit for prolonged ring-wearing). The most frequent minimum dose (Dmin) was 20 Gy for SRS and 28 Gy for HFSR in four fractions. The mean follow-up duration was 34.6 months for SRS and 35.4 months for HFSR. RESULTS: As a whole, the 3 and 5-year actuarial obliteration rates were 64 and 92%. Age <20 years old (P=0.02) and a maximum diameter <2 cm were favorable factors (P=0.05). A difference in the distribution of patients was observed in size (> or =2.5 cm or not) (P<0.001) and location (eloquent or not) (P<0.001) between SRS and HFSR due to the treatment selection. However, no significant differences were observed in the actuarial rates of obliteration and transient increased signals with T2-weighted MR images between SRS and HFSR. Radiation necrosis occurred in two patients treated with SRS and in none with HFSR. Intracranial hemorrhage after treatment happened in two treated with SRS and three with HFSR. CONCLUSIONS: HFSR appears to be at least as effective as SRS in achieving complete obliteration of intracranial AVM, although its definitive role remains to be investigated.

[Prognosis and organ preservation in oropharyngeal cancer treated with radiotherapy].

The records of 102 patients with squamous cell carcinoma of the oropharynx treated at National Sapporo Hospital with external and/or interstitial radiotherapy between 1978 and 1996 were reviewed to evaluate the treatment results, focusing on primary control and functional preservation. Ninety-five patients had been primarily treated with curative intent initially. Of these 95 patients, 4% were in stage I, 19% in stage II, 42% in stage III and 34% in stage IV. Twenty-one patients (22%) had been treated with multidisciplinary chemotherapy, and 19 patients (20%) had been boosted with brachytherapy mainly using Au-198 grains. The cause-specific survival rates at 5 and 10 years were 63% and 52%, respectively. The local control rates at 5 and 10 years were 70% and 51%, respectively. The most important factors affecting local control were the subsite of the primary tumor and N stage. Based on these findings, it is considered that radiotherapy combined with/without chemotherapy except for N3 and the posterior wall type is an effective method of achieving tumor control and preserving organ function, compared with other methods including surgical procedures.

Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutations.

Recent studies suggest that a balance may exist between the cell cycle arrest and apoptosis-inducing functions of the p53 tumor suppressor gene. Adenoviral p21 transduction attenuates apoptosis, whereas deletion of the p21 gene promotes it, and p21-null xenografts respond better than isogenic p21-wild type tumors to irradiation. Hence, the role of p53 in dictating the clinical response to radiotherapy and chemotherapy may be more complex than previously thought. We have analyzed survival and radiation response (regrowth-free period) of 42 patients with glioblastomas whose p53 status was determined by a sensitive yeast functional assay. Multivariate analysis revealed that p53 mutation is associated with longer survival (P < 0.02). Among 36 radiation-treated patients, the regrowth-free period after treatment was significantly longer for tumors with p53 mutations (P < 0.0001), and p53 mutation was the sole independent factor predictive of radiotherapeutic response (P < 0.01). Survival time after regrowth was independent of p53 status, suggesting that the difference in survival was related to the treatment rather than to the intrinsic aggressiveness of the tumor. Thus, in this Northern Japanese population, p53 mutation is a marker for better radiation response in glioblastomas, and this results in significantly longer survival.