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50 DETECTION OF CIRCULATING TUMOUR CELLS IN PROSTATE CANCER PATIENTS WITH RISING PSA POST-PROSTATECTOMY
S16 assessed before and after therapy using 25 MHz high frequency ultrasound (HFUS); raw radiofrequency (RF) data was recorded for spectroscopic analysis. Three spectral parameters were analyzed: 0 MHz-intercept, Spectral Slope, and Mid-band fit (MBF). Statistical analysis employed the paired Student’s ttest. P-values less than 0.05 were considered significant. Animals were euthanized 24 hours after treatment and specimens excised for histo-pathological assessment of response. Results: A minimum of four animals per treatment group were used (n=47). Mid-band Fit increased in all tumours treated with 8 Gy XRT with no microbubbles, low concentration and high concentration bubbles by 4.27 ± 0.88dB (p=0.005), 2.69 ± 0.83dB (p=0.048), 5.23 ± 1.41dB (p=0.014) respectively. For high concentration microbubbles alone and with 2 Gy, the MBF increased 2.37 ± 0.59dB (p=0.010) and 5.02 ± 0.63dB (p<0.001), respectively. No significant changes in MBF were seen with 2 Gy radiotherapy alone, low concentration microbubbles alone, or the two combined. The 0 MHz-intercept extrapolated from RF data demonstrated similar, statistically significant increases whereas spectral slope was invariant as observed with other cancer treatments. Conclusion: This study demonstrates the ability of HFUS to non-invasively monitor standard and microbubble enhanced radiotherapy treatments in vivo. Further research is required to determine potential clinical applications. 49 GOLD-NANOPARTICLES SENSITIZE RADIOTHERAPY OF PROSTATE CANCER CELLS BY REGULATION OF CELL CYCLE W. Roa1, X. Zhang1, S. Patel1, J. Amanie1, X. Sun1, J. Chen2, R. Moore1, J. Xing2 1 Cross Cancer Institute, Edmonton, AB 2 University of Alberta, Edmonton, AB Purpose: Nanotechnology can improve cellular targeting and radio-sensitization. Glucose-capped gold nanoparticles (GluGNPs) significantly increased cellular uptake compared to neutral nanoparticles. With 2 Gy of ortho-voltage irradiation, Glu-GNP showed a 1.5 to 2.0 fold enhancement in growth inhibition when compared to X-ray alone. In this study, we used Glu-GNPs as a model to explore the mechanism how GNPs enhance radiation sensitivity in radiation-resistant human prostate cancer cells. Materials and Methods: Cell survival and proliferation were measured using MTT assay and clonogenic assay. To uncover mechanisms of GNPs action, flow cytometer with staining by propidium iodide (PI) was performed to study the cell cycle changes induced by Glu-GNPs, and Western Blot was used to determine the expression of p53 and cyclin proteins that correlated to cell cycle regulation. Results: Cytoplasmic uptake of Glu-GNP resulted in significant growth inhibition in prostate cancer cells after being irradiated to 2 Gy with ionizing radiation. Comparing cell cycle arrest, Glu-GNPs induced an accumulation of cells in G2/M phase at 29.8% versus 18.4% for controls at 24 h. G2/M arrest was accompanied by decreased expression of p53 and Cyclin A, and increase of the expression of Cyclin B1 and Cyclin E. Two hour treatment with Glu-GNPs enhanced radiation sensitivity in the prostate cancer cells, with an inhibition rate of 74.9% versus 21.4% for irradiation alone. In the non-cancerous cells, GluGNPs did not enhance radiation sensitivity. Conclusion: We demonstrated that GNPs trigger activation of the CDK kinases leading to cell-cycle acceleration in the G0/G1 phase and accumulation in the G2/M phase. This is accompanied by sensitization to ionizing radiation. Taking into consideration the time dependence of the cell cycle changes induced by GNPs, optimized radiotherapy regimen was obtained. These studies suggest for the first time that regulation of p53 and the CDK kinases induced by GNPs is an important mechanism for the observed cell cycle changes.
CARO 2009 50 DETECTION OF CIRCULATING TUMOUR CELLS IN PROSTATE CANCER PATIENTS WITH RISING PSA POST-PROSTATECTOMY T. Sexton1, A. Allan2, B. Hedley1, G. Rodrigues1, V. Venkatesan1 1 University of Western Ontario, London, ON 2 London Regional Cancer Program, London, ON Introduction: The success of salvage radiation post radical prostatectomy can range from 20-70% and there are few good predictive factors for determining who will benefit from salvage treatment. In recent years, circulating tumour cells (CTCs) have been shown to correlate with overall survival in metastatic breast and prostate cancer patients, but it is not known whether these cells can be detected in postprostatectomy patients with rising PSA. We are conducting a pilot study to determine if CTCs can be detected in this patient population and if the numbers of CTCs change after salvage radiation. Methods: Twenty patients with rising PSA post-prostatectomy will have blood drawn for PSA and CTCs prior to and three months after salvage radiation. The number of CTCs will be determined using the FDA approved CellSearch system which is capable of detecting one CTC in 7.5 ml of blood. Results: To date, 3/4 controls and 4/20 patients have been enrolled on this study. The mean pre-RT PSA is 0.31. All patients have pT2-pT3 disease with risk factors for local recurrence. Half of all subjects have Gleason 7 disease and half have Gleason 8 disease. CTCs have not been detected in any control subjects as expected but only one patient has been found to have detectable numbers of CTCs so far (1 CTC/7.5ml). Conclusion: Based on these preliminary results, we can predict that the number of patients with detectable CTCs will be low, likely due to the low starting PSA values and therefore it may be helpful to look at a different patient population, with a higher PSA, in future studies. 51 DOSIMETRIC COMPARISON OF BOOST TECHNIQUES FOR ADJUVANT BREAST RADIOTHERAPY G. Mitera, M. Davidson, M. Cardoso, E. Rakovitch, J.-P. Pignol Odette Cancer Centre, Toronto, ON Purpose: To determine an appropriate boost regime (photons/electrons) for adjuvant left breast radiotherapy by identifying dosimetric parameters predictive of superior target coverage and decreased dose to organs at risk (OAR). Materials and Methods: Eighty patients received treatment plans of 50 Gy to the whole breast with forward IMRT. Contoured post-surgical cavities defined the clinical target volume (CTV), and an expansion of 2cm around the CTV defined the planning target volume (PTV), which received a 16 Gy boost dose. Photon boosts were planned using minitangents, and electron boosts with single direct fields. The heart, lungs, left anterior descending artery (LAD), and the portion of the PTV that excluded chest wall and 5mm of skin were evaluated dosimetrically. Data was stratified by breast size, PTV location and volume. Results: Dose volume histograms (DVH) were evaluated for 74 patients as six patients had clinically inacceptable distributions with electrons due to large PTV depths. Both boost techniques resulted in similar fractional PTV volumes encompassed by the 95% isodose. While PTV coverage was equivalent between techniques, photon boosts resulted in more irradiated normal breast beyond the PTV (p<0.01). Differences in DVH parameters for the heart (V40 Gy) and lungs (V20 Gy) were not significant between techniques. Dose to the LAD was 47% higher with electrons for inner quadrant lesions only (p=0.007). Stratification of dosimetric parameters by quadrant revealed no other significant trends. Breast size was not a significant predictor of dose to OAR.
CARO 2009 50 DETECTION OF CIRCULATING TUMOUR CELLS IN PROSTATE CANCER PATIENTS WITH RISING PSA POST-PROSTATECTOMY T. Sexton1, A. Allan2, B. Hedley1, G. Rodrigues1, V. Venkatesan1 1 University of Western Ontario, London, ON 2 London Regional Cancer Program, London, ON Introduction: The success of salvage radiation post radical prostatectomy can range from 20-70% and there are few good predictive factors for determining who will benefit from salvage treatment. In recent years, circulating tumour cells (CTCs) have been shown to correlate with overall survival in metastatic breast and prostate cancer patients, but it is not known whether these cells can be detected in postprostatectomy patients with rising PSA. We are conducting a pilot study to determine if CTCs can be detected in this patient population and if the numbers of CTCs change after salvage radiation. Methods: Twenty patients with rising PSA post-prostatectomy will have blood drawn for PSA and CTCs prior to and three months after salvage radiation. The number of CTCs will be determined using the FDA approved CellSearch system which is capable of detecting one CTC in 7.5 ml of blood. Results: To date, 3/4 controls and 4/20 patients have been enrolled on this study. The mean pre-RT PSA is 0.31. All patients have pT2-pT3 disease with risk factors for local recurrence. Half of all subjects have Gleason 7 disease and half have Gleason 8 disease. CTCs have not been detected in any control subjects as expected but only one patient has been found to have detectable numbers of CTCs so far (1 CTC/7.5ml). Conclusion: Based on these preliminary results, we can predict that the number of patients with detectable CTCs will be low, likely due to the low starting PSA values and therefore it may be helpful to look at a different patient population, with a higher PSA, in future studies. 51 DOSIMETRIC COMPARISON OF BOOST TECHNIQUES FOR ADJUVANT BREAST RADIOTHERAPY G. Mitera, M. Davidson, M. Cardoso, E. Rakovitch, J.-P. Pignol Odette Cancer Centre, Toronto, ON Purpose: To determine an appropriate boost regime (photons/electrons) for adjuvant left breast radiotherapy by identifying dosimetric parameters predictive of superior target coverage and decreased dose to organs at risk (OAR). Materials and Methods: Eighty patients received treatment plans of 50 Gy to the whole breast with forward IMRT. Contoured post-surgical cavities defined the clinical target volume (CTV), and an expansion of 2cm around the CTV defined the planning target volume (PTV), which received a 16 Gy boost dose. Photon boosts were planned using minitangents, and electron boosts with single direct fields. The heart, lungs, left anterior descending artery (LAD), and the portion of the PTV that excluded chest wall and 5mm of skin were evaluated dosimetrically. Data was stratified by breast size, PTV location and volume. Results: Dose volume histograms (DVH) were evaluated for 74 patients as six patients had clinically inacceptable distributions with electrons due to large PTV depths. Both boost techniques resulted in similar fractional PTV volumes encompassed by the 95% isodose. While PTV coverage was equivalent between techniques, photon boosts resulted in more irradiated normal breast beyond the PTV (p<0.01). Differences in DVH parameters for the heart (V40 Gy) and lungs (V20 Gy) were not significant between techniques. Dose to the LAD was 47% higher with electrons for inner quadrant lesions only (p=0.007). Stratification of dosimetric parameters by quadrant revealed no other significant trends. Breast size was not a significant predictor of dose to OAR.