41 PREDICTIVE FACTORS FOR SEVERE LATE TOXICITY AFTER THORACIC CHEST WALL REIRRADIATION

CARO 2009 outcomes of a population-based cohort of young (<50 years) women diagnosed with DCIS treated with BCS+XRT. Methods: We identified all women diagnosed with DCIS in Ontario from 1994–2003, aged <50 years at diagnosis. We performed linkage of administrative databases to identify treatment (type of breast surgery, radiation) and outcomes, with validation of data through primary chart abstraction. Survival analyses were used to evaluate the outcomes of women treated with BCS + XRT. The median follow up period was 8.5 years. Results: From 1994-2003, 8203 women were diagnosed with DCIS in Ontario, 1015 women were <50 years at diagnosis and 583 received BCS+XRT (< 40 years, N=60; 40–44 years, N=184; 45–50 years, N=339). Most women received 50 Gy in 25 fractions and 121 (21%) women received a boost. Ninety-nine (17%) women developed a local recurrence corresponding to five- and ten-year actuarial local-recurrence free survival rates (LRFS) of 88% and 81% respectively. Thirty-eight (6.5%) women developed invasive local recurrence, for five- and 10-year actuarial invasive LRFS rates of 95% and 93% respectively. Women aged <44 years had significantly higher recurrence rates compared to women aged 45–50 years (23% for <40 years; 21% for 40–44 years; 14% 45-50 years) (unadjusted HR = 1.68 (1.13, 2.49) p = 0.01; 10-year actuarial LFRS 75% versus 85% (p=0.005). Conclusion: Younger women have a higher rate of local recurrence following BCS + XRT for DCIS. Multivariable analyses of factors associated with recurrence will be presented. 39 IN VITRO AND IN VIVO VASCULAR EFFECTS OF NOVEL RADIOSENSITIZING ULTRASOUND-ACTIVATED MICROBUBBLES A. Caissie1, A. Al-Mahrouki2, M. Furukawa3, R. Karshafian1, A. Giles2, J. Lee1, Y.-Q. Li2, S. Wong1, G. Czarnota1 1 University of Toronto, Sunnybrook Health Sciences Centre, Toronto, ON 2 Sunnybrook Health Sciences Centre, Toronto, ON 3 McMaster University, Hamilton, ON Purpose: Ultrasound (US)-activated microbubbles have recently been identified as radiosensitizers, enhancing cell kill in prostate cancer xenografts. Diagnostically, microbubbles are routinely used as intravascular US contrast agents. These in vitro and in vivo studies investigated potential vascular effects of US-activated microbubbles with or without radiation (RT). Materials and Methods: Study treatments (Rx) included USactivated microbubbles with and without RT. In vitro, human endothelial cells were used. Post-Rx isolated RNA was analyzed using microarray and real-time-RT-PCR. In vivo, human prostate cancer PC3 cells were implanted in the hind leg of SCID mice. Tumour vasculature was imaged with Doppler US prior to animal sacrifice 24 and 72 hours post-Rx. Tumour sections were stained to assess morphology (HandE), cell death (TUNEL), hypoxia (HIF-1a) and vascular markers (factor VIII and CD31). Results: In vitro, up-regulation of endothelial cell sphingomyelin phosphodiesterase 1 and 2 genes (ceramide cell death pathway) was seen with US-activated microbubbles. Further up-regulation was seen with combined Rx. In vivo, combined Rx showed greatest effect although both RT and USactivated microbubbles alone were associated with Doppler detected reduction in tumour vasculature and perfusion as well as increased factor VIII staining (interpreted as vascular leakiness) at 24 hours post-Rx. The observed effects decreased by 72 hours post-Rx. Endothelial cell apoptosis (TUNEL/CD31 co-staining) also increased with combined Rx. While not observed with RT alone, it was detected with US-activated microbubbles. Similar to other vascular disrupting agents, microbubbles caused central tumour cell kill with a residual peripheral rim of HIF-1a positive tumour. Combined Rx decreased this rim.

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Conclusion: These studies have identified vascular effects of US-activated microbubbles in vitro and in vivo. With US used to activate microbubbles locally within tumours, these radiosensitizing vascular disrupting agents show promise as novel therapeutic agents in oncology. 40 PRIMARY MALTOMA OF THE ORBIT AND SYSTEMIC MALT DISEASE D. Owen, R. Klasa, T. Pickles University of British Columbia, Vancouver, BC Purpose: Primary MALT lymphoma is the most common cancer in the orbit. It is often indolent and affects the elderly. However, the incidence of systemic disease is uncertain. Materials and Methods: The provincial lymphoma database and cancer registries were queried to extract all cases seen and treated since 1980. A retrospective review of staging, treatment and outcomes was performed. Results: A total of 101 cases were identified. The mean age at presentation was 67 and 61% of cases occurred in women. Seventy-one percent presented with unilateral orbital disease. Seventy-nine of 101 patients underwent a staging bone marrow biopsy and of these, 12% showed involvement with MALT. The risk of bone marrow involvement in unilateral was lower compared to bilateral MALTomas (11% versus 17%; p=0.03). Ninety-two patients underwent CT chest/abdomen/pelvis for staging, 21% showed lymphadenopathy. Of unilateral orbital MALTomas 15% (11/72) had lymph node involvement versus bilateral at 28% (8/29), p=0.06. Of the unilateral orbital MALTomas, 51 of 72 patients were treated with local RT. The most common dose used was 25 Gy in 10 fractions (24/51). Treatment techniques varied from three-field (37.5%) to direct anterior fields with hanging lens shield (20%). Two patients developed radiation retinopathy but both of these patients received higher doses of 30Gy in 10 fractions. Progression free survival (PFS) in unilateral MALTomas was significantly better than bilateral MALTomas; 85% versus 54% at five years and 68% versus 24% at ten years (p=0.003). There was no significant difference in overall or disease specific survival (OS at 5 years 97% versus 90%, OS at ten years 97% versus 78%, p =0.073; DSS at five years 100% versus 90%, DSS at 10 years 100% versus 78%, p=0.267). Conclusion: MALTomas most frequently present as unilateral localized disease with a higher frequency in women. Bilateral MALTomas have a greater risk of bone marrow involvement and poorer PFS. All patients require full staging as apparent unilateral cases have disseminated disease 20% of the time. 41 PREDICTIVE FACTORS FOR SEVERE LATE TOXICITY AFTER THORACIC CHEST WALL REIRRADIATION S. Kim, A. Nguyen, D.Tremblay, A. Dagnault Université Laval, Québec, QC Purpose: To describe side effects after reirradiation (re-RT) of the thoracic chest wall and to study predictive factors for severe late toxicity in order to provide insight into chest wall re-RT tolerance. Materials and Methods: Between 1987 and 2007, 345 overlap regions in 257 patients who underwent re-RT of the thoracic chest wall were identified. All data was collected through retrospective chart review. The biologically effective dose (BED) was calculated for late toxicity with an a/b ratio of 3. Toxicities were graded and grouped into categories: severe, mild and no toxicity until last follow up. Cox regression analysis was used to determine factors associated with severe toxicity. Results: Breast cancer was the predominant histology at initial RT (78.3%) and re-RT (74.8%), followed by lung cancer and lymphoma. The total median dose was 45 Gy (SD ± 11 Gy) at initial irradiation (RT) and was 30 Gy (SD ± 12 Gy) at re-RT. Of the 345 regions, 92% were the result of one retreatment, 7% of two retreatments (three consecutive courses) and 0.3% of three

S14 retreatments (four consecutive courses). Of the 297 patients, 74% had one overlap region, 20% had 2, 6% had three and 1% had four regions of overlap. The median cumulative BED to the overlap region was 139 Gy3 (SD ± 27 Gy3). The median interval to re-RT was 42 months (SD ± 88 months) for regions retreated once. Median follow up from re-RT for all regions was 10 months (SD ± 29 months). Acute and late severe toxicity occurred in nine and 11 overlap regions, respectively, all within 60 months of follow up. Moreover, severe toxicity only occurred in regions with a cumulative BED3 of 139 Gy3 or more. No grade 4 or 5 toxicity was reported. On multivariate analysis, cumulative BED was the most important factor for severe late toxicity (p <0.0001), followed by higher number of overlap regions per patient (p 0.0006). Conclusion: Chest wall re-RT resulted in acceptable toxicity. Re-RT may be given with less concern in patients with fewer predictors. Late severe toxicity seems less likely if the cumulative biologically effective dose is <139 Gy3. 42 FUNCTIONAL IMAGING OF NEOADJUVANT CHEMOTHERAPY AND CHEMORADIOTHERAPY IN WOMEN WITH LOCALLY ADVANCED BREAST CANCER (LABC) USING DIFFUSE OPTICAL SPECTROSCOPY H. Soliman1, A. Gunasekara2, M. Rycroft2, J. Zubovits2, R. Dent2, J. Spayne2, M. Yaffe2, G. Czarnota2 1 University of Toronto, Toronto, ON 2 Sunnybrook Health Sciences Centre, Toronto, ON Purpose: Functional imaging with tomographic near infrared diffuse optical spectroscopy (DOS) can quantitatively measure tissue parameters such as the concentration of deoxyhemoglobin (Hb), oxy-hemoglobin (HbO2), percent water (%water), and scattering power (SP). The purpose of this study was to evaluate the correlation between DOS functional parameters with pathologic outcomes. Methods: Patients with LABC undergoing neoadjuvant chemotherapy or chemoradiotherapy were recruited to this study (n=10). Five scans were conducted per patient: a baseline scan was taken up to three days prior to treatment and at one week, four weeks, eight weeks, and after neoadjuvant treatment prior to surgery. Patients lay prone with the breast suspended between immobilization plates in optical coupling medium. Pulsed near-infrared laser light was used to scan the breast at four different wavelengths. Volumeof-interest (VOI) weighted tissue Hb, HbO2, %water, and SP corresponding to the tumour was calculated and compared to clinical and full mount mastectomy pathology. Results: For all ten patients the tumour VOI was different than background tissue for all functional parameters (p<0.001). Five patients had a good clinical and pathologic response. Four patients were considered non-responders. One patient initially had a poor clinical response to chemotherapy but after a change in chemotherapy had a good clinical and radiographic response. Responders and non-responders were significantly different for all of the functional parameters (p<0.05) at the four week scan. In the five patients with a good response the mean drop in Hb, HbO2, %water, and SP from baseline to the four week scan was 70.4% (SD=18.6), 66.5% (SD=24.5), 59.6% (SD=30.9), and 60.7% (SD=29.2), respectively. In contrast, the four non-responders had a mean drop of 17.7% (SD=9.8), 18.0% (SD=20.8), 15.4% (SD=11.7), and 12.6% (SD=10.2), for Hb, HbO2, % water and SP, respectively. Conclusion: Functional imaging using DOS parameters of Hb, HbO2, %water and SP could be used as an early detector of final clinical and pathologic tumour response. 43 EFFICACY OF LOW-DOSE INVOLVED-FIELD RADIOTHERAPY FOLLOWING 3-4 CYCLES OF CHEMOTHERAPY FOR PATIENTS WITH STAGE I-II AGGRESSIVE NON-HODGKIN’S LYMPHOMA I. Gauthier, P. Després, I. Roy Université de Montréal, Montréal, QC

CARO 2009 Purpose: There is currently no consensus on the radiation dose required for limited-stage aggressive Non-Hodgkin’s Lymphomas (NHL) in the context of combined modality treatment. This retrospective study reports the efficacy of brief chemotherapy followed by low-dose involved-field radiotherapy (IFRT). Materials and Methods: Between 2001 and 2007, 52 patients with Stage I-II aggressive NHL were treated with three to four cycles of Cyclophosphamide, Doxorubicine, Vincristine, Prednisone (CHOP) chemotherapy regimen followed by IFRT at our institution. Rituximab was also administered in 20 patients (38%). The median radiation dose was 33.2 Gy (range 22.4-40 Gy). A dose in the range of 30-30.6 Gy in 15-17 fractions was administered in 46% of patients. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Results: Median age at diagnostic was 59 years. Thirty-nine patients (75%) had Stage I disease and 80% had stage modified International Prognostic Index (IPI) of 0 or 1. Only one patient had bulky disease. Complete response (CR) or uncertain CR was achieved in 98% of patients after completion of combined modality treatment. After a median follow up of 49 months, six patients have relapsed and four patients have died. The fiveyear estimates of overall survival (OS) and progression-free survival (PFS) for the entire cohort were 90.5% and 81.2%, respectively. For the 30-30.6 Gy group, 83% of patients had Stage I disease and 88% had stage modified IPI of 0 or 1. For this group, five-year estimates of OS and PFS were 95.7% and 82.4%. Local control was 100% for the entire cohort and was therefore not influenced by the radiation dose. Conclusion: IFRT in the range of 30 to 30.6 Gy after three to four cycles of chemotherapy is associated with excellent outcomes in patients with Stage I-II aggressive NHL. 44 COPY NUMBER ALTERATION PREDICTS FOR BIOCHEMICAL RECURRENCE IN LOCALIZED PROSTATE CANCER USING HIGHRESOLUTION ARRAY COMPARATIVE GENOMIC HYBRIDIZATION A. Ishkanian1, C. Malloff2, J. Ho1, A. Meng1, M. Albert1, T. van der Kwast1, M. Milosevic1, W. Lam2, R. Bristow1 1 University of Toronto, Princess Margaret Hospital, Toronto, ON 2 British Columbia Cancer Research Centre, Vancouver, BC Purpose: Recurrence of localized prostate cancer after radiotherapy may be due to genetic or microenvironmental factors or sub-clinical metastatic disease. Biomarkers of local and systemic recurrence are needed to individualize patient risk categories and better define treatment. We hypothesized that genomic copy number alteration (CNA) can predict for biochemical failure in intermediate risk prostate cancer. Materials and Methods: High-resolution array comparative genomic hybridization (array CGH) was used to identify CNA’s in 120 intermediate risk prostate cancer patients. Our cohort included 39 T1c tumours, 78 T2 tumours and 2 T3 tumours. Gleason score was 6 in 32 tumours, 7 in 82 tumours and 8-9 in 6 tumours. PSA ranged from 2.1-33 (median 8.0). Patients were treated with intensity modulated radiotherapy (IMRT) to the prostate gland alone with doses of 75.6-79.8 Gy in 1.8-2Gy fractions, or 60-66 Gy in 3 Gy fractions. Twenty-five percent of patients also received neoadjuvant-concurrent bicalutamide. Biochemical failure, defined by Phoenix criteria or the initiation of salvage therapy, was observed in 35 patients after median follow up of 5.4 years (range 0.9-8.8). Results: Array CGH showed significant variation in CNA in this cohort. CNA per sample ranged from one to 57, with a median of 11.5. Percentage of the genome altered (PGA) ranged from <1% to 35% (median 6.7%). Total genome altered (TGA) ranged from 2.8Mb to 1087Mb (median 210Mb). PSA and the use of hormonal therapy independently influenced biochemical relapse, and formed a baseline clinical model to which CNA was added. PGA was found to be a strong predictor of