Ottawa Regional Cancer Centre Research Articles

Response to subsequent platinum-based chemotherapy post PARP inhibitor in recurrent epithelial ovarian cancer.

5578 Background: Maintenance therapy with PARP inhibitors (PARPi) can increase progression free survival (PFS) for recurrent or metastatic platinum-sensitive epithelial ovarian cancer (EOC). Little is known about disease trajectory following treatment with these agents, though some evidence suggests a decreased response to subsequent platinum-based chemotherapy. This retrospective cohort study assessed real-world response rates to platinum-based chemotherapy for recurrent high grade EOC following treatment with a PARPi. Methods: All patients prescribed a PARPi as maintenance therapy for recurrent or metastatic EOC at the Ottawa Regional Cancer Center (ORCC) from September 2017 to May 2022 were included. PFS following penultimate therapy (line of therapy preceding PARPi initiation) as well as the PFS following subsequent platinum-based chemotherapy in patients with disease progression more than 6 months after penultimate therapy were calculated. Incidence of platinum resistance in patients with disease progression following PARPi therapy was determined. Results: 91 patients were included in the analysis including 54 patients on niraparib and 36 patients on olaparib. Follow-up after initiation of PARPi ranged from 4.6 months to 62.0 months with a median of 16.3 months. 54 (59.3%) of patients experienced disease progression after initiation of PARPi therapy, including 10 (11.0%) who progressed within 6 months of their penultimate therapy. Of the 44 patients who experienced disease progression more than 6 months following penultimate therapy, 32 (72.7%) were rechallenged with platinum-based chemotherapy. Of these, 16 (50.0%) experienced further disease progression with 14 (43.8%) progressing within 6 months of their platinum rechallenge. Median PFS following platinum rechallenge was 4.4 months (from 0.8 months to 34.9 months), significantly lower than previous reports. Conclusions: Patients who experienced disease progression following PARPi therapy showed a poor response to subsequent platinum-based chemotherapy, even when progression occurred more than 6 months after completion of their penultimate platinum-based chemotherapy. This supports the theory that PARPi resistance may be a surrogate for platinum resistance and raises concern for possible contribution of PARPi in the induction of platinum resistance in recurrent EOC.

Metastatic Melanoma in Sentinel Node-Negative Patients: The Ottawa Experience.

Lymph node involvement is a major independent prognostic factor for survival in patients with malignant melanoma. Sentinel lymph node biopsy (SLNB) detection of microscopic nodal melanoma has been shown to improve both 5-year survival and 5-year disease-free survival. To determine the rate of metastatic melanoma in SLNB-negative patients at long-term follow-up. Study subjects include all 152 patients who had a negative SLNB and were followed at the Ottawa Regional Cancer Centre (ORCC) between 1999 and 2004. Patients with a follow-up period less than 6 months, more than 1 primary melanoma, and metastatic melanoma at diagnosis were excluded. Age at diagnosis, sex, Breslow thickness, ulceration, mitoses, regression, Clark level, anatomical location, development of metastatic melanoma, time to detection of metastatic disease, and time to death from melanoma were studied. In this retrospective study at the ORCC, 40 of 140 (28.6%) patients with a single primary melanoma developed metastatic melanoma following negative SLNB at a mean follow-up of 63 months. The rate of metastatic melanoma following negative SLNB at long-term follow-up at the ORCC is higher than the upper limit of rates reported in the literature (6%-24%). The reason for this is multifactorial, and the long follow-up period of 5 years allowed for detection of metastatic disease at a mean of 3.9 years. Long-term prognosis may be guarded in node-negative patients with a primary cutaneous melanoma, and surveillance by a multidisciplinary team is crucial.

Low dose-rate brachytherapy for the treatment of cervix cancer is outdated and should be discontinued.

Low dose-rate brachytherapy for the treatment of cervix cancer is outdated and should be discontinued.

Metastatic Squamous Cell Carcinoma of the Neck from Unknown Primary Sites: the Ottawa Regional Cancer Centre (ORCC) Experience

C l i n M e d International Library Citation: Marglani O, Alherabi AZ, Safar A, Alghamdi S, Eapen L, et al. (2015) Metastatic Squamous Cell Carcinoma of the Neck from Unknown Primary Sites: the Ottawa Regional Cancer Centre (ORCC) Experience. Int J Cancer Clin Res 2:027 Received: September 04, 2015: Accepted: September 23, 2015: Published: September 25, 2015 Copyright: © 2015 Marglani O. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Marglani et al. Int J Cancer Clin Res 2015, 2:3

Implementation and validation of a risk stratification method at The Ottawa Hospital to guide thromboprophylaxis in ambulatory cancer patients at intermediate-high risk for venous thrombosis

BackgroundCancer patients have a significantly higher risk of developing a venous thromboembolism (VTE) compared to non-cancer patients and yet studies suggest VTE risk among ambulatory cancer patients varies widely. Recently, predictive models capable of risk-stratifying a broad range of ambulatory cancer outpatients have been developed. Using the Khorana model a score of 2 was intermediate-high risk for VTE as reported by Ay and colleagues. However, validation in a broader population and methods to implement this model seamlessly into clinical practice are lacking. ObjectiveTo create and assess the feasibility of an innovative computerized Care Process Management System (CPMS) that would automatically access electronic medical records to calculate in real-time the risk of VTE in patients with active cancer using an established VTE risk scoring system. MethodsA prospective observational study of all newly referred cancer patients at the Ottawa Regional Cancer Center, the sole cancer care provider for 1.2 million inhabitants, was conducted. Results699 new referrals were determined to have a cancer diagnosis for the first time as identified by the computer software and qualified for our study and 580 were eligible. In total 25% had intermediate-high risk for VTE and during the 3-month follow up period, 16 of the 143 (11%) developed a VTE which further validates the Khorana model for identifying intermediate-high risk patients. Of the 437 patients in the low risk group 19 (4%) developed a VTE. ConclusionNewly diagnosed cancer patients can be readily stratified into intermediate-high and low risk of VTE using our novel CPMS system. This innovative tool can be used to facilitate customized management decisions regarding VTE prophylaxis for intermediate-high risk patients based their individual risk factors.

Interview of David J Stewart, on the Future of Lung Cancer Management

David J Stewart returned to Ottawa from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) in 2011 to assume the position of Head of the Division of Medical Oncology at The Ottawa Hospital and the University of Ottawa. He received his MD degree from Queen's University, Kingston, followed by training in Internal Medicine at McGill University and in medical oncology in the Department of Developmental Therapeutics at the UT MD Anderson Cancer Center. He first moved from MD Anderson to the University of Ottawa and the Cancer Care Ontario Ottawa Regional Cancer Center in 1980, and served as Chief of Medical Oncology at the Ottawa Civic Hospital from 1989 to 1999. He returned to the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center from 2003 to 2011 where he served as Chief of the Section of Experimental Therapeutics (2003–2005), Chair Ad Interim (2005), Deputy Chair (2006–2009) and Director of Translational Research (2009–2011). He was also the Principle Investigator of MD Anderson’ Phase II N01 contract with the National Cancer Institute, and was the clinical leader of a number of other federally funded translational research project. He has more than 300 peer-reviewed publications, with a research focus on Phase I and II trials of new anticancer agents, translational research and resistance to anticancer agents. He also has a major interest in and concern for issues impeding cancer clinical research, with publications that have included (among others): Cancer: the road to Amiens (J. Clin. Oncol. 27(3), 328–33 [2009]); Equipoise lost: ethics, costs and the regulation of cancer clinical research (J. Clin. Oncol. 28(17), 2925–35 [2010]); Fool's gold, lost treasures and the randomized clinical trial (BMC Cancer 13(1), 193 [2013]); and Redefining cancer: a new paradigm for better and faster treatment innovation (J. Popul. Ther. Clin. Pharmacol. 21(1), e56–e65 [2014]). His experience in both the American and Canadian healthcare systems has provided him a unique perspective on how common regulatory factors seriously impair access to effective new therapies and drive inordinately high clinical research costs in both countries.

Implementing a Computerized Care Process Management System To Determine The Feasibility Of Utilizing, and Concomitantly Validating, a Prediction Tool For The Risk Of Venous Thromboembolism In Cancer Patients

Cancer patients have a significantly higher risk of developing a venous thromboembolism (VTE) compared to non-cancer patients. VTE result in reduced quality of life, and increased morbidity and mortality. However, studies suggest VTE risk among ambulatory cancer patients varies widely. Therefore, although several studies demonstrate that prophylaxis is effective, given the cost and concomitant bleeding risk it is not the standard of care to administer prophylaxis. Khorana and colleagues have developed a predictive model for chemotherapy-associated VTE in cancer patients. However, Methods to implement this model into clinical practice have not been developed. The purpose of this study was to create and assess an innovative computerized Care Process Management System(CPMS ) (that would calculate in real-time the risk for VTE by utilizing clinical information and laboratory tests contained in patient electronic records, based on the proposed predictive model, notifying staff to enable patient education about VTE risk and to concomitantly validate the model.Over a four month period new cancer referrals to the Ottawa Regional Cancer Center, the sole provider of cancer care for a region of 1.2 million inhabitants, were assessed by the Khorana tool (Blood 2008;111:4902-7). This model consists of the following five predictive variables: (1) site of cancer (2 points for very high-risk site (brain, stomach, pancreas), 1 point for high-risk site (lung, lymphoma, gynecologic, bladder, and testicular), (2) platelet count ≥350 x 109/L, (3) hemoglobin <10 g/dL and/or use of erythropoiesis-stimulating agents, (4) leukocyte count >11 x 109/L, and (5) body mass index (BMI) ≥35 kg/m2 (1 point each). High risk was defined as a score or ≥2. We approached all new cancer patients but excluded patients if they were: (1) tumours not included as very high risk or high risk according to the prediction model; 2) to be followed up or treated at another facility other than The Ottawa Hospital; 3) had a confirmed VTE/arterial embolism (stroke or peripheral arterial embolism) within the prior 3 months; 4) were receiving continuous anticoagulation; 5) had previously been treated for cancer. Patients with a very high risk tumour site were approached first. Those with other tumour sites had the predictive variables calculated through the CPMS. In all cases the clinic nurse was notified electronically of when patients presented to clinic and of their risk. Patients' demographics, medical history, malignancy characteristics, diagnostic laboratory features, imaging information, BMI and plan of anti-cancer treatment were documented prior to initiation of their cancer treatment. Educational material was provided to high risk patients regarding the signs and symptoms of VTE and their risk for VTE, in order to prevent delayed diagnosis. Patients were followed-up at 3 months (±7 days) following the initial consult to determine if they were diagnosed with VTE.699 new referrals were determined to have a cancer diagnosis for the first time as identified by the computer software and qualified for our study and 580 were eligible. On the basis of very high risk tumour site alone, 71 patients were initially deemed at high risk of developing a VTE (score ≥2) and 509 patients were deemed at low risk (score ≤1). Among the initial cohort of patients at low risk, 72 were elevated to high risk based on BMI and pre-chemotherapy blood work. In total 25% had high risk for VTE and during the 3-month follow up period, 16 of the 143 (11%) developed a VTE which further validates the Khorana model for identifying high risk patients. Patients uniformly were receptive to receiving counseling about their VTE risk at enrolment. In summary, we have demonstrated the feasibility of utilizing a computerized CPMS linked to the electronic medical record to populate a predictive tool that is based on clinical information and laboratory data to identify and stratify cancer patients into high and low risk of developing a VTE. Our future aim is to utilize this innovative tool in clinical practice to enable 1) identification of all cancer patients at high risk for VTE, 2) education that will potentially decrease the time between symptom onset, VTE investigation, and treatment, and 3) enrollment in randomized trials of VTE prophylaxis. Disclosures:Wells:bayer healthcare: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Biomerieux: Honoraria.

The Impact of Prolonged Storage of Red Blood Cells on Cancer Survival

BackgroundThe duration of storage of transfused red blood cells (RBC) has been associated with poor clinical outcomes in some studies. We sought to establish whether prolonged storage of transfused RBC in cancer patients influences overall survival (OS) or cancer recurrence.Methods and FindingsPatients diagnosed with cancer at The Ottawa Regional Cancer Centre between January 01, 2000 and December 31, 2005 were included (n = 27,591) where 1,929 (7.0%) received RBC transfusions within one year from diagnosis. Transfused RBC units were categorized as “new” if stored for less than 14 days, “intermediate” if stored between 14 and 28 days and “old” if stored for more than 28 days. Baseline characteristics between the comparative groups were compared by ANOVA test. Categorical variables and continuous variables were compared using Chi-squared and Wilcoxan rank-sum tests respectively. Overall survival was not associated with duration of storage of transfused RBC with a median survival of 1.2, 1.7, 1.1 years for only new, intermediate and old RBC units respectively (p = 0.36). Cancer recurrence was significantly higher in patients who received a RBC transfusion than those who did not (56.3% vs 33.0% respectively; p<0.0001) but was not affected by the duration of storage of transfused RBC (p = 0.06). In multivariate analysis, lung cancer, advanced stage, chemotherapy, radiation, cancer-related surgery and cancer recurrence were associated with inferior OS (p<0.05), while age, advanced stage, lung cancer, and more than 6 units of blood transfused were associated with cancer recurrence (p<0.05). The duration of storage of RBC before transfusion was not associated with OS or cancer recurrence in multivariate analysis.ConclusionIn patients diagnosed with cancer, the duration of storage of transfused RBC had no impact on OS or cancer recurrence. This suggests that our current RBC storage policy of providing RBC of variable duration of storage for patients with malignancy is safe.

The Influence of the Duration of Storage of Red Blood Cells On Cancer Survival

AbstractAbstract 1184 Background:The duration of storage of red blood cells (RBC) has been associated with poor clinical outcomes amongst those receiving red cells. Patients with cancer are at risk of RBC transfusions and the effect of RBC storage is unknown in this population. We investigated the influence of duration of storage of RBC units transfused on overall survival (OS) and cancer recurrence in patients diagnosed with a new malignancy. We further described the transfusion requirements in this cohort of patients. Methods:Patients diagnosed with cancer at The Ottawa Regional Cancer Centre between January 01, 2000 and December 31, 2005 were included. Data was retrieved from the Ottawa Hospital Transfusion and Cancer database for analysis. RBC units were categorized as “new” if stored for less than 14 days, “intermediate” if stored between 14 to 28 days and “old” if stored for more than 28 days. Baseline characteristics between the comparative groups were compared by ANOVA test. Categorical variables and continuous variables were compared using Chi-squared and Wilcoxan rank-sum tests respectively. Kaplan-Meier analyses were used to examine differences in unadjusted survival while Cox-regression analyses were applied to adjust for potential confounding variables. Results:There were n=27,591 patients diagnosed with any cancer. The mean number of packed RBC units transfused was 3.42 (0.22, 6.62) with 1,929 (7.0%) patients receiving RBC within 1 year of diagnosis. Of these patients, 1335 (69.2%) received exclusively one “aged” category of RBC. The median OS was worse for patients who were transfused versus those not transfused (1.1 vs 7.5 years respectively, p<0.0001) as well as the number of RBC transfused (median OS for 1–2 units was 1.2 years, 3–5 units was 1.05 years and 6 or more units was 1.1 years; p=0.0017) in univariate analysis. Overall survival was not associated with duration of storage of transfused RBC with a median survival of 1.2, 1.7, 1.1 years for only new, intermediate and old RBC units respectively (p=0.36). Cancer recurrence was significantly higher in patients who received a RBC transfusion than those who did not (56.3% vs 33.0% respectively; p<0.0001) but was not affected by the duration of storage of transfused RBC (p=0.06). In multivariate analysis, a diagnosis of lung cancer, chemotherapy use, radiation use, cancer-related surgery and cancer recurrence were associated with inferior overall survival (p<0.05). In contrast, neither the number of RBC units transfused nor the duration of RBC storage before transfusion were associated with OS in multivariate analysis. Conclusion:In patients diagnosed with cancer, the duration of storage of transfused RBC had no impact on OS or cancer recurrence. However, the number of RBC transfused was associated with an increased risk for cancer recurrence. This suggests that current RBC storage policies are adequate for patients with malignancy requiring RBC transfusions. Disclosures:No relevant conflicts of interest to declare.

Socio-economic status and head and neck cancer incidence in Canada: A case-control study

In an earlier study we identified an increased incidence of head and neck cancer (HNC) in individuals with lower socio-economic status (SES) in the United States. The objective of this study was to determine if lower SES is associated with a similar increase in the incidence of HNC in Canadian patients. We obtained data on SES (income, education and immigration status), demographic characteristics, frequency of dental visits and smoking behavior for adult patients residing in the Eastern Ontario region who were referred to the Ottawa Regional Cancer Centre with HNC. We compared the SES and frequency of dental visits of these HNC patients with the SES and frequency of dental visits of a control sample in the same region from the 2004-2005 Statistics Canada Canadian Community Health Survey (CCHS 3.1). We then performed a logistic regression analysis on the combined sample of patients and controls using incidence of HNC as the dependent variable. This allowed us to eliminate confounding variables such as tobacco intake and to isolate the effect of SES, frequency of dental visits, and immigration status on HNC incidence. There was a statistically significant decrease in the incidence of HNC among adults with a higher median family income (OR=0.5429, CI=[.3352, .8795]). Also, adults with less than grade 8 education had significantly higher rates of HNC than adults who had completed high school (OR 3.65, CI=[1.88, 7.08]). As well, immigrants had a significantly lower incidence of HNC than Canadian born adults (OR=0.3825, CI=[.2063, .7090]). Lastly, we found that individuals who typically visited a dentist less than once per year had a significantly higher incidence of HNC than individuals who typically visited a dentist at least once per year (OR=1.69, CI=[1.01, 2.83]). Even when controlling for tobacco intake, the incidence of HNC in Eastern Ontario was higher in patients with lower median family income and less than grade 8 education. It was higher in individuals who visited a dentist less than once per year, and lower in immigrants to Canada. This was similar to what has been observed in the United States. Further study into the reason for this increased incidence of HNC in patients with lower SES is warranted.

Toxicities and adherence rates of hormone treatment in male breast cancer patients treated at a tertiary care center

e11613 Background: Male breast cancer (BC) comprises approximately 1% of all breast cancer cases, and over 80% of male BC tumours express the estrogen receptor (ER). Male BC patients (pts) are often offered hormonal treatment (HT) with tamoxifen (T), or more recently aromatase inhibitors (AI's). There is a paucity of information in the literature on the toxicities (Tx) and adherence rates of HT in this population. Methods: We conducted a retrospective chart review of 24 pts diagnosed with male BC at the Ottawa Regional Cancer Centre from 1986–2003. Data collected included pt age, ER status, progesterone receptor (PR) status, systemic chemotherapy, HT, and Tx of treatment. Results: Median age of 24 male BC pts was 70.0 years (r: 46–83 years). The majority (16/24) of pts had ER/PR testing: 12 (75.0%) ER/PR +, 1 (6.3%) ER +/PR-, 2 (12.5%) ER +/PR unknown, and 1 (6.3%) ER/PR-. Of the 15 pts who were ER +, 13 received T and 5 received anastrozole (A) monotherapy during their treatment. One ER - pt received adjuvant T. Three pts with ER status unknown received T. Median duration of treatment with T (17 pts) was 38.0 months (r: 2–79 months). Hot flashes (23.5 %) was the most common reported Tx. Decreased libido, weight gain, rash, and malaise were reported in 2 pts (11.8%) each. Increased liver enzymes, pulmonary embolism, and erectile dysfunction were reported in 1 pt (5.9%) each. Five pts (29.4%) terminated treatment early due to T toxicity (median treatment 15 months; r: 2–54 months). Five pts were treated with A (median 10 months; r: 3–60 months), 4 of whom received prior T treatment. One pt reported loss of libido, and 1 significant depression /suicidal ideation requiring psychiatric treatment. Conclusions: This study provides contemporary data on toxicities and adherence rates of HT in male BC pts in a non-clinical trial setting. Approximately 30 % of male BC pts discontinued T therapy due to Tx, potentially having a negative impact on clinical outcome. Future studies will examine differences in adherence rates and outcomes between T and A in male BC pts. No significant financial relationships to disclose.

Survival of patients diagnosed with either colorectal mucinous or non-mucinous adenocarcinoma: A population-based study in Canada

Previous studies have shown conflicting results on the prognosis of colorectal mucinous adenocarcinoma. This study compared prognostic characteristics of patients diagnosed with mucinous and non-mucinous adenocarcinomas in a Canadian series. Analyses were based on 165 colorectal mucinous and 1215 non-mucinous adenocarcinoma patients who were registered at the Ottawa Regional Cancer Centre from 1994 to 1997, with follow-up extending to December 31, 2001. Differences in survival were examined using the relative survival analysis and the Cox proportional hazards model. For colon, rectum and both combined, the distribution for age at diagnosis, stage and treatment of patients with mucinous adenocarcinoma was similar to that of non-mucinous patients (all p > or = 0.12). Patients with mucinous histology had fewer well- or moderately-differentiated tumours than non-mucinous patients (all p < 0.01). Overall, no statistically significant differences were noted in 5-year relative survival between mucinous and non-mucinous carcinoma for colon, rectum and their combination (p > or = 0.35 for each). However, when the stages were considered separately, patients with stage III mucinous carcinoma had worse survival than patients with non-mucinous carcinoma for both sites. Multivariate analysis of combined data for colon and rectal cancers indicated that independent significant prognostic factors were stage for mucinous, with age and grade as well as stage for non-mucinous carcinoma. In conclusion, no significant differences in stage distribution and overall survival were found between mucinous and non-mucinous patients for colorectal cancer.

Penile brachytherapy: Results for 60 patients

Purpose: Squamous cell carcinoma (SCC) of the penis is an uncommon but psychologically devastating malignancy. At the Ottawa Regional Cancer Center and the Princess Margaret Hospital in Toronto, brachytherapy has been used as the treatment of choice for penile preservation in T1 and T2 tumors.

Family physicians' perspectives regarding palliative radiotherapy

Purpose To assess family physicians' views on common indications for palliative radiotherapy and to determine whether this influences patient referral. Methods and materials A 30-item questionnaire evaluating radiotherapy knowledge and training developed at the Ottawa Regional Cancer Centre (ORCC) was mailed to a random sample of 400 family physicians in eastern Ontario, Canada. The completed surveys were collected and analyzed, and form the basis of this study. Results A total of 172 completed surveys were received for a net response rate of 50% among practicing family physicians. Almost all of the physicians (97%) had recently seen cancer patients in their offices, with 85% regularly caring for patient with advanced cancer. Fifty-four percent had referred patients in the past for radiotherapy and 53% had contacted a radiation oncologist for advice. Physicians who were more knowledgeable about the common indications for palliative radiotherapy were significantly more likely to refer patients for radiotherapy ( P<0.01). Inability to contact a radiation oncologist was correlated with not having referred patients for radiotherapy ( P<0.01). Only 10% of the physicians had received radiotherapy education during their formal medical training. Conclusions Many of the family physicians surveyed were unaware of the effectiveness of radiotherapy in a variety of common palliative situations, and radiotherapy referral was correlated with knowledge about the indications for palliative radiotherapy. This was not surprising given the limited education they received in this area and the limited contact they have had with radiation oncologists. Strategies need to be developed to improve continuing medical education opportunities for family physicians and to facilitate more interaction between these physicians and radiation oncologists.

Penile brachytherapy: Results for 49 patients

To report results for 49 men with squamous cell carcinoma (SCC) of the penis treated with primary penile interstitial brachytherapy at one of two institutions: the Ottawa Regional Cancer Center, Ottawa, and the Princess Margaret Hospital, Toronto, Ontario, Canada. From September 1989 to September 2003, 49 men (mean age, 58 years; range, 22-93 years) had brachytherapy for penile SCC. Fifty-one percent of tumors were T1, 33% T2, and 8% T3; 4% were in situ and 4% Tx. Grade was well differentiated in 31%, moderate in 45%, and poor in 2%; grade was unspecified for 20%. One tumor was verrucous. All tumors in Toronto had pulsed dose rate (PDR) brachytherapy (n = 23), whereas those in Ottawa had either Iridium wire (n = 22) or seeds (n = 4). Four patients had a single plane implant with a plastic tube technique, and all others had a volume implant with predrilled acrylic templates and two or three parallel planes of needles (median, six needles). Mean needle spacing was 13.5 mm (range, 10-18 mm), mean dose rate was 65 cGy/h (range, 33-160 cGy/h), and mean duration was 98.8 h (range, 36-188 h). Dose rates for PDR brachytherapy were 50-61.2 cGy/h, with no correction in total dose, which was 60 Gy in all cases. Median follow-up was 33.4 months (range, 4-140 months). At 5 years, actuarial overall survival was 78.3% and cause-specific survival 90.0%. Four men died of penile cancer, and 6 died of other causes with no evidence of recurrence. The cumulative incidence rate for never having experienced any type of failure at 5 years was 64.4% and for local failure was 85.3%. All 5 patients with local failure were successfully salvaged by surgery; 2 other men required penectomy for necrosis. The soft tissue necrosis rate was 16% and the urethral stenosis rate 12%. Of 8 men with regional failure, 5 were salvaged by lymph node dissection with or without external radiation. All 4 men with distant failure died of disease. Of 49 men, 42 had an intact and tumor-free penis at last follow-up or death. The actuarial penile preservation rate at 5 years was 86.5%. Brachytherapy is an effective treatment for T1, T2, and selected T3 SCC of the penis. Close follow-up is mandatory because local failures and many regional failures can be salvaged by surgery.

Radical radiotherapy for cervix cancer: The effect of waiting time on outcome

To assess the effect of treatment waiting time on clinical outcome for patients with cervix cancers treated with radical radiotherapy. A retrospective analysis was conducted on all cervix cancer patients treated with radical radiotherapy between 1990 and 2001 at the Ottawa Regional Cancer Centre. Analyses were performed according to the three following separate definitions of waiting times: interval from start of radiotherapy to (1) date of initial biopsy, (2) date of examination under anesthesia, and (3) date of radiation oncology consultation. Associations between waiting times and patient characteristics and disease control were investigated using t-tests, analyses of variance, and Cox regression analyses. A total of 195 patients were studied. The vast majority of patients were treated within 5, 6, and 8 weeks of their consultation (91%), examination under anesthesia (88%), and biopsy (81%), respectively. On average, delays between initial biopsy and treatment start were greater for older patients (p = 0.025) (5.8 weeks for <40 years old vs. 6.6 weeks for >70 years old) and those with smaller tumors (p < 0.001) (5.0 weeks for >4 cm vs. 6.3 weeks for < or =4 cm). Univariate analysis revealed no adverse effect of treatment delay on tumor control. Multivariate analysis, with the inclusion of multiple prognostic tumor and treatment parameters, revealed an adverse effect of treatment delay on survival outcomes. Longer radiotherapy waiting times were found to be associated with diminished survival outcomes for patients treated radically for cervix cancer. The significance of this observed association requires further investigation.

Genitourinary (GU) small cell carcinoma (SCC): A retrospective review of treatment and survival patterns at the Ottawa Regional Cancer Center (ORCC)

4545 Background: SCC of the bladder (SCCB), prostate (SCCP), and kidney (SCCK) remains a therapeutic challenge. Much debate exists in the literature about the ideal course of therapy. Methods: All charts of all patients seen at the ORCC between 1991–2002 for any GU diagnosis were manually reviewed to identify GUSCC. Demographic, staging, treatment and outcome data was extracted. The Veterans Administration small cell lung cancer classification of limited and extensive disease was adapted to the genitourinary system(limited:disease localized to the true and false pelvis, extensive:disease beyond the pelvis). Results: 555, 858 and 5066 new cases of primary renal, bladder and prostate cancer respectively, were identified. Of these cases, 22 patients were GUSCC: 12 SCCB, 10 SCCP and no SCCK. 8/12 SCCB had limited disease. 5 patients with SCCB are alive and were all limited at diagnosis. Surviving patients received similar therapy with transurethral resection of the bladder tumor, platinum chemotherapy, etoposide (4–6 cycles), and radical radiotherapy (56–60 Gray). All cases of SCCP have died. 2/10 had limited stage. Of these two patients one was treated with platinum chemotherapy and etoposide followed by radical radiotherapy (66 Gray), the other patient had a poor performance status at diagnosis and was treated with palliative hormonal ablation and radiotherapy. Our table illustrates the median survival according to site and stage (SCCB and SCCP combined) at diagnosis. Conclusions: Our findings support that GU SCC is an aggressive cancer. We have found that limited stage SCCB and SCCP, when treated with platinum/etoposide chemotherapy along with radical radiotherapy tends to have a more favourable outcome than that of extensive GUSCC. No significant financial relationships to disclose.

Genitourinary (GU) small cell carcinoma (SCC): A retrospective review of treatment and survival patterns at the Ottawa Regional Cancer Center (ORCC)

Genitourinary (GU) small cell carcinoma (SCC): A retrospective review of treatment and survival patterns at the Ottawa Regional Cancer Center (ORCC)

Death comes in small packages

Killer sunburns are detected by the smallest of genes, according to Bruce McKay and colleagues (Ottawa Regional Cancer Centre, Ottawa, ON). A bias toward damage of larger genes leaves intact only the tiny genes, which make sure that overdamaged cells die. Figure The transcription of survival genes (white boxes) doesn't survive high UV (right). UV rays create DNA lesions that block RNA polymerases. A little damage can be cleaned up by UV-induced repair pathways that remove the lesions. But too much UV—which may make more lesions than can be repaired—triggers apoptosis instead. McKay now shows that the small size of apoptotic genes means that they rule when UV levels are high. The authors find that fewer genes are transcribed as UV levels increase, and those that are transcribed are smaller, with fewer and shorter introns. These small genes include many known mitochondrial apoptotic genes, which were activated at the highest UV dose tested. Genes encoding repair proteins or survival proteins, such as Bcl-XL, were induced only at low UV levels, probably because they are larger and more likely to suffer from transcription-blocking lesions. “The shift in the pattern of gene expression is the result of a passive mechanism,” says McKay. So no extra energy is needed to convince highly injured cells to die. ▪ Reference: McKay, B., et al. 2004. Proc. Natl. Acad. Sci. USA. 10.1073/pnas.0308181101. [PMC free article] [PubMed]

Histology-related variation in the treatment and survival of patients with lung carcinoma in Canada

Objectives: The aim of the study was to examine histologic differences in lung cancer treatment and survival, and to define recent survival trends in Ottawa, Canada. Methods: From 1994 to 2000, 3237 patients with invasive lung cancer were registered at the Ottawa Regional Cancer Centre (ORCC) and were followed up to 31 December 2001. Five-year relative survival rates (RSRs) and relative excess risks (RERs) of dying were calculated by stage and dominant initial treatment modalities for major cellular histologies using a relative survival model. Results: The overall 5-year survival rate was 14%, and female patients had significantly better survival. Patients with stage I and II non-small cell lung cancer (NSCLC) who were treated by surgery alone were more likely to survive (5-year RSRs were 72 and 48%, respectively) than those who received other treatments. Patients with stage III NSCLC had a 5-year survival rate of 9% after chemotherapy plus radiotherapy, whereas stage IV patients who received only chemotherapy had better survival for up to 2 years than patients with other treatments. In cases of limited-stage small cell lung cancer (SCLC), survival was better for patients who received chemotherapy plus radiotherapy than for those who received only chemotherapy. Conclusions: The relatively superior survival of surgical patients with stage I NSCLC implies that a considerable number of patients have the potential to be treated successfully. The overall poor survival of lung cancer patients suggests a need for more national public health emphasis on lung cancer prevention, improved screening and early diagnosis, and better treatment.