Proceedings of the 50th Annual ASTRO Meeting S681

therapy with a dose of 2 joules/cm2. After laser therapy 38 patients answered a 10 multiple choice questionnaire listed below: (1)Inform pain scale from 0-10; (2) Have you got any immediate relief after laser therapy; (3) If yes, how long did the relief last; (4)Did the session take a long time to be completed; (5) After your last session do you think your mouth is less hurt; (6) Score your painsince the last session; (7) Are you able to swallow better since your last session; (8) Is your skin less sensitive since the last session;(9) Do you think you need less pain medications since you started laser therapy; (10) Would you recommend this treatment toanother patient (this question was done in the last session).

Results: Two patients declined to answer the questions in the middle of the treatment and each patient answered 7 questionnaires.Forty percent of the patient’s related relief of the pain immediately after the session and the median time of relief were 30 minutes(SD ± 4). Thirty percent of the patients described better swallowing after the third session and 50% related need of less medicationafter starting the sessions. One hundred percent of the patients were not uncomfortable with the time for the sessions and all wouldrecommend it to others.

Conclusions: In conclusions this questionnaire is important to measure the acceptability of the laser therapy frequency and if it isbeen helpful by the patient’s point of view.

Author Disclosure: D. Grabarz, None; J. VillaNova, None; P. Sarti, None; A. Ribeiro, None; F. Trombini de Souza, None.

3138 Feasibility of an Electron-specific Multileaf Collimator to Replace Patient-specific Cutouts

A. A. Eldib, L. Jin, Q. Xu, T. Lin, J. Fan, C. Ma

Fox Chase Cancer Center, Philadelphia, PA

Purpose/Objective(s): To investigate the use of an electron-specific multileaf collimator (eMLC) for electron beam shaping toreplace patient-specific cutouts.

Material/Methods: An eMLC has the potential to revolutionize electron therapy just as the photon multileaf collimator pMLC hasfor photon beam therapy. The pMLC has proven to be useful for shaping irregular fields, compensating for missing tissue, andallowing intensity modulated radiation therapy, thus replacing the need for the fabrication of patient-specific blocks and compen-sators. Similarly, an eMLC will be useful for shaping irregular fields and facilitating intensity modulated electron therapy. In thiswork a prototype eMLC was used. It consists of 25 tungsten leaf pairs. Each leaf is 0.6cm wide and 2cm thick. It can be mounted toour linac treatment head. Ion chamber measurements were performed in the study to obtain percentage depth doses and profiles forsquare fields formed by the eMLC and corresponding cutouts. Profiles were taken at two separate depths, one at the depth of themaximum dose and the other at the depth of the 90% dose (R 90). Dose profiles were also measured by film for different square fieldsformed by the eMLC. The penumbra was calculated for each field and plotted as a function of field size. Irregular fields shaped bythe eMLC and cutouts were also examined and the differences were analyzed.

Results: The electron PDD shaped with the eMLC are very similar to those shaped by electron cutouts in the build-up region. Onlyslight differences were observed after Dmax for all energies. The eMLC does not increase the surface dose at a 70 SSD compared tothe cutout. Profiles from the eMLC show similar penumbra to that from cutouts for all energies both at Dmax and at R90. For 6MeVand 9MeV profiles the eMLC result in the better flatness. The reason for this at lower electron energies may be due to the increasedscatter. This effect is not significant at higher energies. As the field size decreases from 13.7 cm x 13.7 cm to 1.95 cm x 1.95cm thebeam penumbra varies by about 0.8 to 1.5 mm depending upon the energy. For each field as the energy increases from 6 to 20 MeVthe penumbra decreases by about 4 to 6 mm depending on the field size. Comparisons of irregular fields shaped with cutouts andthose shaped with the eMLC demonstrate that the target to normal tissue delineation obtained by the eMLC is acceptably for bothconventional electron therapy and advanced beam modulation.

Conclusion: The preliminary results support the use of the eMLC as an alternative to patient-specific cutouts. The eMLC offersaccurate and efficient beam delivery for both conventional electron therapy and beam intensity modulation.

Author Disclosure: A.A. Eldib, None; L. Jin, None; Q. Xu, None; T. Lin, None; J. Fan, None; C. Ma, None.

3139 Syne1 Promoter Hypermethylation as a Predictor of Tumor Aggressiveness in Primary Breast Cancer

A. Rimner1, A. Y. Ho1, N. Ahuja2, K. E. Schuebel2, S. B. Baylin2, W. L. Gerald1, T. A. Chan1

1Memorial Sloan-Kettering Cancer Center, New York, NY, 2Johns Hopkins University School of Medicine, Baltimore, MD

Purpose/Objective(s): The vast majority of genetic and epigenetic changes in human malignancies remain unknown. Large-scalesequencing of the cancer genome has led to the identification of multiple candidate cancer genes. However, many of these genes werefound to be passenger mutations with low frequencies in each tumor type, and the mutational spectrum was highly tumor-type spe-cific. Thus, determining which genes play key roles in tumorigenesis has been challenging. Epigenetic silencing through hyperme-thylation is a prevalent mechanism for gene silencing that may cooperate with genetic alterations. Hypermethylation of CpG islandpromoter regions has been identified in many human malignancies. Here, a genome-wide analysis of genetic mutation and epigeneticmethylation was employed to address both mechanisms. We sought to identify new candidate genes involved in breast cancerdevelopment that may be useful for predicting a subset with aggressive behavior that may benefit from adjuvant radiation therapy.

Materials/Methods: Using comprehensive, genome-wide expression microarray profiling, a set of candidate tumor suppressorgenes that are common targets of both somatic mutations and epigenetic silencing by hypermethylation were identified. GenomicDNA was isolated from 30 paraffin-embedded breast tumors and treated with bisulfite. Methylation-specific PCR was performedand methylation status of 49 genes was tested in these tumors.

Results: Using methylation-specific PCR in 49 genes, 11 genes were found to be silenced by promoter hypermethylation inprimary breast tumors, but not in normal breast tissue. Among these candidates identified was Syne1, a nuclear membrane protein.Hypermethylation of Syne1 was tightly correlated with stage at presentation in an analysis of 30 primary breast tumors. While only1 out of 18 patients with early-stage breast cancer (stages 0-2) revealed hypermethylation of the Syne1 promoter, 6 out of 12advanced-stage breast cancers (stages 3-4) were hypermethylated (p = 0.02). Syne1 methylation did not correlate with grade,ER, PR, or Her2/neu status.

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Conclusions: Using a genome-wide approach, Syne1 was identified as a candidate tumor suppressor gene undergoing progressivepromoter hypermethylation with increasing stage of breast cancer at presentation. Further studies will be conducted to elucidate themechanisms and function of Syne1, its role in tumor progression, and its utility as a biomarker in breast cancer.

Author Disclosure: A. Rimner, None; A.Y. Ho, None; N. Ahuja, None; K.E. Schuebel, None; S.B. Baylin, None; W.L. Gerald,None; T.A. Chan, None.

3140 TGF-beta1 Gene Polymorphism and Quality of Life in Prostate Cancer Patients Treated with

Brachytherapy Seed Implantation

A. Meyer1, T. Dork1, N. Bogdanova1, M. Brinkhaus1, B. Wiese1, M. Bremer1, R. Baumann1, J. H. Karstens1, S. Machtens2

1Hannover Medical School, Hannover, Germany, 2Marien-Krankenhaus Bergisch-Gladbach, Bergisch-Gladbach, Germany

Purpose/Objective(s): Transforming growth factor beta1 (TGF-beta1) can act as a tumor suppressor by inhibiting cellular pro-liferation and as a stimulator of tumor progression by promoting cellular differentiation in the early phase of cancer development.A polymorphic TGF-beta1 variant, Leu10Pro (L10P), has previously been implicated in prostate cancer risk and in radiation-in-duced side-effects. We investigated whether the prevalence of the TGF-beta1 L10P polymorphism is increased in a hospital-basedseries of patients treated with I-125 brachytherapy (permanent seed implantation) for early stage prostate cancer vs. controls andwhether carriers are at increased risk for treatment-related side effects.

Materials/Methods: A series of 445 consecutive patients treated for early-stage prostate cancer receiving definitive I-125 brachy-therapy between 10/2000 and 10/2007 at our institution and a comparison group of 457 male healthy controls were screened for thepresence of the TGF-beta1 L10P (869T.C) polymorphism. Outcome regarding morbidity was assessed prospectively and com-pared between carriers vs. non-carriers with the International Prostate Symptom Score (IPSS-15), a Quality-of-Life-index (QoL)and the International Index of Erectile Function (IIEF-15) with its subgroups (IIEF-5 and EF).

Results: The Leu/Leu genotype was found in 150 prostate cancer patients (34%) vs. 180 controls (39%), the Pro/Pro genotype in75 patients (17%) vs. 65 controls (14%) and the Leu/Pro genotype in 220 patients (49%) and 212 controls (46%). TGFbeta-1genotype frequencies were not statistically significant different between the two groups, although there was a trend towards anincreased prevalence of the L10P substitution among cases with a per allele odds ratio of 1.19 (95% CI 0.99 - 1.44; p = 0.08). Aftera mean follow-up of 18 months there were no statistically significant differences regarding IPSS (p = 0.27), QoL (p = 0.79), IIEF-15score (p = 0.98), IIEF-5 score (p = 0.85), and EF score (p = 0.51), respectively.

Conclusions: The TGF-beta1 polymorphism L10P is not strongly associated with prostate cancer risk. After 18 months, there wasno evidence for an increased adverse radiotherapy response in heterozygote or rare homozygote carriers. Further studies of can-didate gene variants for radiosensitivity will be needed and might have important clinical implications for prostate cancer treatment.

Author Disclosure: A. Meyer, None; T. Dork, None; N. Bogdanova, None; M. Brinkhaus, None; B. Wiese, None; M. Bremer,None; R. Baumann, None; J.H. Karstens, None; S. Machtens, None.

3141 Automatic Segmentation of Functional Images for Radiotherapy Treatment Planning

M. Hatt1, N. Boussion1,2, C. Roux1, O. Pradier2, D. Visvikis1

1INSERM U650 LaTIM, Brest, France, 2Institut de Cancerolgie, Brest, France

Purpose/Objective(s): Automatic volume delineation methodologies previously developed for PET have been essentially thresh-old-based. We have developed a robust and automatic segmentation algorithm based on a combination of statistical and fuzzy mod-eling that was previously shown to perform accurately, independent of image noise and contrast characteristics, on a phantom withspherical lesions and uniform activity distributions. In the present study we investigate its ability to delineate inhomogeneous andnon-spherical tumors increasing its potential for use in radiotherapy treatment planning.

Materials/Methods: We compared two approaches; namely the current state-of-the-art adaptive thresholding (two differentmethods) and our FLAB (Fuzzy Locally Adaptive Bayesian) method. Twenty tumors and their simulated counterparts (generatedin 3D using PET images of patient lesions as models) were used in the evaluation. Voxels misclassifications and volume errors werecomputed with respect to the ground-truth of the simulated tumors. Results, including variability, observed with the simulated data-sets were also compared to the results obtained on the real tumors images.

Results: The two threshold-based methods lead to large errors with 20.5% and 29.8% mean volume errors respectively. Significantvariability was observed in the results, with large dependence upon noise, contrast or lesion size (standard deviations 20.7 and 19.6,respectively). On the other hand FLAB lead to the best results with low errors (8.5% mean volume error, standard deviation 10%)and good accuracy in volume delineation even when dealing with heterogeneous activity distribution and in the presence ofnecrotic lesions.

Conclusions: FLAB outperformed current state of the art methodologies for the complex task of delineating realistic, non sphericaltumors. Furthermore it is able to accurately deal with non-uniform activity distributions: it can identify regions of interest withvariable activity concentrations within the external contour of tumors providing a solution for future applications such as ‘‘dosepainting’’ in radiotherapy treatment planning.

Author Disclosure: M. Hatt, None; N. Boussion, None; C. Roux, None; O. Pradier, None; D. Visvikis, None.

3142 In Vitro 3D Modeling of Host Organ-specific Whole Tumor Responses to Radiation

A. Volgin, L. LeRoux, D. Maxwell, D. Schellingerhout, A. Thitai-Kumar, Y. He, J. Gelovani, D. L. Schwartz

UT M.D. Anderson Cancer Center, Houston, TX

Purpose/Objective(s): To model organ-specific tumor responses to radiation in vitro using multicellular tumor spheroids contain-ing stromal cells derived from different host tissue sites.