112 Factors influencing late rectal toxicity after radiotherapy of localized prostate cancer

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M e t h o d s and Materials: Four volunteers were recruited: two patients who had undergone conventional radiotherapy for head and neck cancer with severe xerostomia, and two normal subjects. Each volunteer underwent MRI scans of the parotid glands. In the first scan, magnetization transfer contrast was generated by adding an off-resonance pre-pulse to the imaging sequence. A second scan was then done without the extra pulse. By dividing the two image sets, a ratio map was generated over the parotid glands that reflected the influence of magnetization transfer on the tissue: the lower the ratio, the greater the magnetization transfer effect. The ratio over the contoured volume of the glands was compared between the xerostomia group and the control group. Results: For the patients with xerostomia, the mean value of the calculated magnetization transfer ratio was 0.966, with a mean standard deviation of 0.165. The mean value for healthy subjects was 0.928, with a mean standard deviation of 0.050. Conclusions: In this pilot study, xerostomic patients who received radiotherapy for head and neck cancer exhibited a smaller magnetization transfer effect with a larger standard deviation, indicating a trend toward decreased salivary gland function and more heterogeneous salivary gland tissue. Magnetization transfer analysis with MRI represents a potential non-invasive imaging test for parotid injury, and will be tested on a larger cohort of patients and healthy volunteers. 110 A R e t r o s p e c t i v e Analysis of Clinical and M o l e c u l a r Characteristics of H e r 2 / n e u Breast Cancer Patients w i t h Brain M e t a s t a s e s T. Hijal, S. Dawood, T. Muanza McGill University, Montreal, Quebec thierry, muanza@muhc, mcaill, ca Background: Brain metastases continue to be an important cause of death among patients with metastatic breast cancer despite improved control of systemic disease with new agents. The current analysis was conducted to identify common clinical and molecular characteristics among patients suffering from metastatic breast cancer with brain metastases. Methods: We conducted a retrospective review of patients with metastatic breast cancer treated with whole brain radiation therapy from 1995 to 2005 at the McGill University Health Centre. Clinical data was extracted from file review and archived specimens were stained for a range of biomarkers. Results: Fifty-one patients that were tested for Her2/neu overexpression were analyzed. Currently, only clinical data and limited pathological data is available for analysis. Fifty-seven percent (n=29) of patients were Her2 positive. The median age of Her2 positive patients at primary diagnosis was 49.5 years (range 33-74); while it was 54 years (range 25-86) for Her2 negative patients. Average disease free interval (37 months vs 35 months; p=0.868) and average time from diagnosis to brain metastases (49 months in both groups; p=0.97) were non* statistically significant in the Her2 positive and Her2 negative patients. Interestingly, average time from brain metastasis to death was significantly lower in Her2 positive patients compared to Her2 negative patients (4.6 months vs 1 1 . 6 months; p=0.0349). Analysis of data also revealed similar proportion of stage at diagnosis and ER positive tumours in both groups. Conclusions: Based on the preliminary results presented above, Her2 positive and negative patients develop brain metastases at a similar time during the course of diseases although survival after that event is significantly lower in the former group. This data will be combined with molecular studies to better identify and define patients with a poor outcome after brain metastases, with the hope of offering better treatments to increase their survival. 111 H o w Good I s Clinical M a r k - u p in W h o l e Brain Radiation Therapy? Y. Wang, N. Makhani, M. Tsao Toronto Sunnybrook Regional Cancer Centre, University of Toronto, Toronto, Ontario

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yonqfin, wang # r m o . uhn. on. ca Objectives: To evaluate whether two types of clinical mark-up are adequate to cover the whole brain and spare the lens in whole brain radiation therapy (WBRT). Methods: CT simulation images of the brain from 20 random patients were included in this study. Two types of inferior field borders were generated to mimic the two types of clinical mark-up of WBRT which were based on bony landmarks: from superior orbital ridge (SOR) to tragus, and from SOR to inferior tragal notch (ITN). A field margin of lcm from contoured brain (along the base of skull) was used in CT simulation, except near the orbital globe where 0.5cm margin to eye shielding was used. Two opposed lateral fields with 6MV photon were used to generate 3 WBRT plans in each patient: clinical mark-up with SOR to tragus, SOR to ITN, and CT simulation. Dose volume histograms of the brain and lens were generated. Results: Patients with clinical mark-up using SOR to tragus or SOR to ITN had significantly larger median brain volume receiving less than 95% of the prescribed dose, 37.0mL and 7.8mL (respectively) compared to CT simulation 0mL (p<0.001). There was no significant difference in the dose to the tens between CT simulation and clinical mark-up using SOR to tragus (p=0.18) or SOR to ITN (p=0.90). All patients with clinical mark-up using SOR to tragus had underdosing in the regions of the inferior frontal lobe, temporal lobe and posterior fossa. Most patients (95%) with clinical mark-up using SOR to ITN also had underdosing in these three regions. Conclusions: Whole brain radiation therapy with clinical markup using either SOR to tragus or SOR to ITN results in underdosing at the inferior frontal lobe, temporal lobe and posterior fossa, but achieves good sparing of the lens. 112 Factors Influencing Late Rectal Toxicity After R a d i o t h e r a p y of Localized P r o s t a t e Cancer G. tim, H. Lau Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta aeraldli@cancerboard, ab. ca Background: Radiation injury to the rectum is a dose-limiting factor in prostate radiotherapy. Purpose: The objective of this article is to review our institutional experience and identify factors influencing late rectal toxicity after external beam radiotherapy for localized prostate cancer. Methods: The cohort consists of 418 patients with localized prostate cancer treated with external beam radiotherapy from September 2000 to March 2003. RTOG scales were used to evaluate late ano-rectal toxicity and a modified CTC/RTOG scale was used to grade late rectal bleeding at each follow-up visit. Patients were assessed six to eight weeks after radiation, and then every six months. The endpoints of interest included: rectal toxicity Grades 2-4, any late rectal bleeding, and late rectal bleeding Grades 2-4. Patient and treatment factors were analyzed. Results: The median ICRU prostate dose delivered was 73.7 Gy. Pelvic lymph node irradiation was given in 11.2% of patients. Neoadjuvant hormones were given in 80.4% of patients. Median follow-up was 30 months. No patient developed Grade 4 toxicity. The 30 month Kaplan-Meier rate of Grade 2-3 late rectal bleeding was 12.5%. Univariate analysis of patient factors including age, cardiovascular disease, diabetes, hypertension, and body mass index did not show any influence on rates of late rectal bleeding >= Grade 2. However, total prostate dose and use of adjuvant hormones were significant in increasing Grade 2-3 rectal bleeds. Diabetes and the percent of rectum receiving >60 Gy were significant in increasing the hazard ratio of Grade 2 and 3 ano-rectal toxicity. Conclusions: Totat prostate dose and use of adjuvant hormones increased the risk of Grade 2-3 late rectal bleeding. Diabetes and the percent of rectum receiving >60 Gy increased the rate of late Grade 2 and 3 ano-rectal toxicity. These factors

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113 Outcome Analysis of Prostate Cancer Patients Presenting With PSA >50 N g / M I E. Wiebe, G. Rodrigues, M. Lock, D. Dsouza, F. Whiston, L. Stitt London Regional Cancer Program, University of Western Ontario, London, Ontario 6688665(~qmail. corn

Objectives: To analyze prognostic factors associated with biochemical failure and survival in an ultra-high PSA (>50ng/ml) prostate cancer population. Materials and Methods: A single-institution retrospective chart review of 138 patients was performed. Median Gleason score was 8. Median PSA at presentation was 1159.7 ng/ml. Seventy-nine (57.3%) patients presented with clinical and/or radiological evidence of regional and/or metastatic disease. Forty-eight (34.7%) patients did not have metastatic disease and 11 (8.0%) had unknown metastatic status. Results: Median follow-up was 23.7 months. A total of 84 (60.9%) of patients have had either an ASTRO consensus guidelines (n=57, 41.3%) and/or Houston criteria (n=74, 53.6%) biochemical failure. Thirty-five (25.4%) patients had confirmed radiological evidence of progression. Median survival was 23.7 months. At last follow-up, 88 (63.8%) patients were alive, 43 (31.2%) were dead of prostate cancer, and seven (5.1%) patients were dead with unknown disease status. Univariable analysis demonstrated that T stage (p=0.01), Gleason grade (p=0.03), and metastatic disease at presentation (borderline p=0.08) were predictive of overall survival. Median survival for patients was 17.7 months (with metastases) compared to 29.7 months (no metastases). Houston biochemical recurrence after initial treatment was predicted by log PSA (p=0.004), Gleason Score (p=0.002), use of primary RT (p=0.001), presence of metastatic disease at presentation. Conclusions: Patients that present with ultra-high PSA without metastatic disease tend to have somewhat better overall and biochemical outcome when compared to a similar metastatic disease cohort. However, these data confirm that ultra-high PSA >50 ng/ml is a high risk parameter for micrometastatic disease and ultimate recurrence. 114 Stage IE and I I E Extranodal Non-Hodgkin Lymphomas: Results of Treatment with Radiotherapy N. Lessard, I. Vallires, A. Fortin HoteI-Dieu de Quebec, University Laval, Quebec City, Quebec nathalie, lessard. 1 (~ula val. ca

Objectives: The purpose of the study was to review our clinical experience of patients diagnosed with stage I-IIE extranodal Non-Hodgkin Lymphoma (NHL) treated with radiotherapy (RT). Materials and Methods: Data were collected for 108 patients treated with RT from January 1992 to December 2002 at HotelDieu de Quebec for Stage I or II extranodal NHL. Patients with primary disease of bone, CNS or skin were excluded from our study. Results: A total of 108 patients were identified. The median age at diagnosis was 67 years. There were 58 females (53.7%) and 50 males (46.4%). Presentation sites were: Waldeyer's ring (36 patients), orbit (21 patients), salivary gland (11 patients), breast (7 patients) and other sites (19 patients). 68.5% were Stage IE and 31.5% Stage IIE. All patients received RT with a mean dose of 34 Gy. 51.9% of patients also received chemotherapy. 34.5% had a low grade histology, 55.6% a high grade histology; 0.9% a very high grade histology and 9.3% were unknown. Only one patient had B symptoms. A complete response (CR) following RT was achieved in 105/108 (97%) patients. Among patients with CR, 25 (24%) had presented a relapse. Seventeen of those patients had a distant relapse. With a median follow-up of 3,9 years, the five-year overall survival was 72% and five-year disease-

free survival was 72%. The median survival and disease-free survival had not been reached. Age (60 years), tumour bulk before RT and having or not a surgery have been identified as prognostic factors in our series. Conclusions: Radiotherapy as a single modality or combined with chemotherapy has a curative potential for 72% of patients with extra-nodal NHL. The overall outcome of patients in this study is comparable to those reported in previous series. 115 Referral and Management Patterns of Malignant Spinal Cord Compression in Southern Alberta S. Smith 1, S. du Plessis 2, G. Lim 1, C. Newcomb 1, E. YanI Torn Baker Cancer Centre, University of Calgary, Calgary, Alberta1; University of Calgary, Calgary, Alberta 2 sallysmi@cancerboard, ab. ca

Background: Malignant spinal cord compression (MSCC) is a common cancer complication. Functional outcome is dependent on early diagnosis and treatment. Understanding limitations to appropriate diagnosis, referral, and management is essential to improving patient outcomes. Objectives: To explore patterns of referral and management of malignant spinal cord compression in Southern Alberta. Methods: A retrospective review of all cases of MSCC or nerve root compression presenting to our centre between January 2003 and June 2005 was performed. Two-hundred and fortynine cases were identified and classified as either, Frank Spinal Cord Compression (FSCC), Impending Spinal Cord Compression (ISCC), or Cauda Equina or Single Nerve Root Compression (CENR). Referral and management patterns were analyzed. Results: Fifty-six cases were classified as FSCC, 123 as ISCC and 70 as CENR. Referrals to the surgical service were 48.2% for FSCC, 29.3% for ISCC and 18.6% for CENR. Referrals to radiation oncology were 96.4%, 95.1% and 97.1% respectively. Management with surgical intervention was done in 16.1% of FSCC, 8.9% of ISCC and 5.7% of CENR cases whereas radiotherapy was delivered in 89.3%, 95.1% and 95.7% respectively. 6.8% of all patients received combined modality treatment. Time from diagnosis of MSCC to initiation of definitive treatment averaged five days for FSCC, six days for ISCC and five days for CENR. Conclusions: Cases of spinal cord, cauda equina or nerve root compression receive management within one week on average. Most are referred to radiation oncology and almost all of those referred receive radiotherapy. Much fewer are referred to surgery or receive surgical intervention. A small proportion of patients receive combined modality treatment. Determining which subset of patients most benefit from each treatment will be the focus of further analysis and studies. 116 Higher Incidence of Patients with a Positive Family History of Prostate Cancer than Expected Amongst French Canadians E. Filion, D. Taussky, _l-p. Bahary, C. Maugard University of Montreal, CHUM-Notre-Dame Hospital, Montreal, Quebec fiiab@hotmait, corn

Introduction: Prostate cancer is the most frequently diagnosed cancer and the second cause of cancer-related deaths amongst North American men. We aim to investigate the frequency of familial clustering in a French Canadian population of prostate cancer cases. Patients and Methods: Between October 2004 and September 2005, 179 consecutively seen patients with localized prostate identified both of their parents as of French Canadian descent. They were asked for their family history of cancers in first-degree relatives, age of diagnosis, if affected relatives were alive, age and cause of death and markers for tumour aggressiveness (PSA, Gleason, disease-stage). All p-values quoted are two-sided. Results: The mean age at diagnosis was 67 years old. Fortyseven patients (26.3%) have at least one first-degree relative with prostate cancer (previously reported 15% in Canadian