Princess Margaret Hospital Experience Research Articles

From trial to practice: The Princess Margaret Hospital (PMH) experience with docetaxel and prednisone for men with metastatic castration resistant prostate cancer (mCRPC).

125 Background: Docetaxel (75mg/m2every 3 weeks [q3w]) plus prednisone (5mg bid) is standard first-line chemotherapy for men with mCRPC since FDA approval in 2004. It is unclear how results from trials translate to daily practice. Our hypothesis was that patients (pts) treated in trials would have better outcome and less toxicity. Methods: We reviewed all pts with mCRPC treated with docetaxel at PMH until the end of 2011. Primary outcomes were overall survival (OS) and PSA response rate (confirmed decline ≥ 50%). Secondary outcomes were reasons for discontinuation, febrile neutropenia and predictive factors for the primary outcomes. Data were analyzed using the Kaplan-Meier method and Cox regression for OS. Results: 438 men were treated between 2001 and 2011. At start of treatment median age was 71 (range 44 – 90) years, 80 (18%) had visceral metastasis, and the median number of docetaxel cycles was 6 (range 1 – 15). Outcomes are shown in the table. Reasons for treatment discontinuation were progressive disease (38%), completion of treatment (27%), toxicity (22%), death within 30 days of last administration (5%), and other reasons (8%). In multivariate analysis better performance status (p < 0.0001), and more recent treatment (p < 0.0001) were baseline factors associated with longer OS for pts receiving primary treatment with docetaxel q3w. Conclusions: In less selected pts with CRPC treated with docetaxel/prednisone PSA response rates are similar, OS shorter and toxicity more frequent as compared to men treated in the pivotal or in other trials. Supported by a research grant from CIHR. [Table: see text]

Sebaceous gland carcinoma of the head and neck: The Princess Margaret Hospital experience

The purpose of this study was to identify prognostic factors predicting outcomes in sebaceous gland carcinomas. We conducted a retrospective medical chart review of patients with sebaceous carcinomas of periorbital (n = 33) and extraorbital sites (n = 13). Patients with periorbital tumors had higher recurrence rates than did patients with extraorbital tumors (64% vs 23%; p = .032). Patients who were older than 60 years (p = .035) and had lower eyelid tumors (p < .0001) had a lower disease-free survival rate than did patients with upper eyelid tumors. Patients with sebaceous carcinomas had a high rate (60%) of occult lymph node metastases. Periorbital tumors are associated with poorer outcomes than are extraorbital tumors. Lower eyelid carcinomas have the worst prognosis and should be treated more aggressively. Our findings of a high incidence of occult neck disease and a high rate of regional recurrence in patients with sebaceous carcinomas support the consideration of prophylactic elective neck dissections for treating such patients.

IMRT and Concurrent Chemotherapy for Anal and Perianal Cancer: The Princess Margaret Hospital Experience

IMRT and concurrent chemotherapy is standard treatment for anal and perianal cancer at our center. A research ethics board approved prospective cohort study was established to evaluate toxicity, clinical outcomes and quality of life (QoL). From June 2008, patients (pts) with anal and perianal cancer undergoing IMRT were enrolled. IMRT dose was 36 Gy/20f for elective and 54 Gy/30f - 63 Gy/35f for gross targets using standardized contouring, dose prescriptions and dose-volume criteria. Chemotherapy (weeks 1 and 5) consisted of continuous infusion 5-FU 1g/m2/d (max 1.5g/d), d1-4 and MMC 10 mg/m2, d1. Treatment breaks were not planned. Toxicity was graded using NCI CTC v3. Overall survival (OS), disease-free survival (DFS), and colostomy-free survival (CFS) were estimated using the Kaplan-Meier method. Locoregional failure (LRF) was estimated using the cumulative incidence function. QoL was assessed by the EORTC QLQ-C30 and CR29 questionnaires at baseline, treatment end, 3 and 6 months, and then yearly. QoL scores from different time points were compared using the Wilcoxon test. To date, 41 pts have completed treatment: median FU 1 year; median age 57 years; 20 female; 7 (17%) HIV+; 1 (2%) stage 0, 24 (59%) stage II, and 16 (39%) stage III. IMRT doses were 54 Gy - 14 pts (34%) and 63 Gy - 27 pts (66%) to primary; 54 Gy - 1 pt (2%), 58.5 Gy - 10 pts (24%) and 63 Gy - 9 pts (22%) to enlarged nodes. Fifteen (37%) pts required a treatment break (2 - 15d, median 8d) due to acute toxicity, mainly dermatitis (13/15). Acute toxicities were: grade 3 - skin 44%, hematologic 24%, GI 7%, cardiac 2%, pulmonary (MMC toxicity) 2% and GU 0%; grade 4 - skin 2%, hematologic 5% and pulmonary embolism 2%. Thirty-three (89%) pts achieved a complete response; 2 partial responses; 1 stable disease; 1 progressive disease (died); and 4 were not evaluable (1 died of stroke post treatment, 3 assessments pending). One pt developed a contralateral inguinal nodal recurrence 9 months post treatment, and another developed local recurrence at 10 months. Two pts did not complete treatment: 1 died of cardiac cause, and another refused. One-year OS, DFS, CFS, and LRF were 92%, 85%, 86%, and 7%, respectively. Global QoL, pain, skin, and defecation scores were clinically significantly worse at end of treatment compared to baseline (p = 0.001, p = 0.0002, p < 0.0001, and p = 0.04, respectively), but returned to baseline levels 3 months post treatment. At 6 months, pain scores improved significantly compared to baseline (p = 0.005). We report favorable acute grade 3+ hematologic (29%) and GI/GU toxicities (7%) compared to non-IMRT studies (RTOG 9811: 61% and 36%, respectively), but treatment breaks for dermatitis were common. Early clinical outcomes are promising, and there is no persistent negative impact on QoL.

Adjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma: Results From the Upper Tract Urothelial Carcinoma Collaboration

There is relatively little literature on adjuvant chemotherapy after radical nephroureterectomy in patients with upper tract urothelial carcinoma. We determined the incidence of adjuvant chemotherapy in high risk patients and the ensuing effect on overall and cancer specific survival. Using an international collaborative database we identified 1,390 patients who underwent nephroureterectomy for nonmetastatic upper tract urothelial carcinoma between 1992 and 2006. Of these cases 542 (39%) were classified as high risk (pT3N0, pT4N0 and/or lymph node positive). These patients were divided into 2 groups, including those who did and did not receive adjuvant chemotherapy, and stratified by gender, age group, performance status, and tumor grade and stage. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall and cancer specific survival in the cohorts. Of high risk patients 121 (22%) received adjuvant chemotherapy. Adjuvant chemotherapy was more commonly administered in the context of increased tumor grade and stage (p <0.001). Median survival in the entire cohort was 24 months (range 0 to 231). There was no significant difference in overall or cancer specific survival between patients who did and did not receive adjuvant chemotherapy. However, age, performance status, and tumor grade and stage were significant predictors of overall and cancer specific survival. Adjuvant chemotherapy is infrequently used to treat high risk upper tract urothelial carcinoma after nephroureterectomy. Despite this finding it appears that adjuvant chemotherapy confers minimal impact on overall or cancer specific survival in this group.

Esthesioneuroblastoma: The Princess Margaret Hospital experience.

Esthesioneuroblastoma: The Princess Margaret Hospital experience.

Esthesioneuroblastoma: The Princess Margaret Hospital experience

Esthesioneuroblastoma is rare. The aim of the study was to review our experience and to evaluate the staging system and treatment that best correlates with the patient outcome. Thirty-nine patients were identified between 1972 and 2006. At presentation 10% had cervical metastases. None had distant metastasis. Five were treated with surgery, 2 with chemotherapy, 1 with radiotherapy, and 30 with surgery and radiation. Local disease control was 82.6% at 5 years. Recurrence was seen in 33% with local and regional disease recurrence at 15% and 18%, respectively. The 5- and 10-year overall survival rates were 87.9% and 69.2%, respectively. Dulguerov classification correlated most closely to survival and recurrence. Dulguerov classification best correlates with the patient's outcome. A combined approach is the preferred treatment. It makes no difference whether radiotherapy is given pre or postsurgical resection. Recurrence can occur even 15 years after treatment. Therefore, long-term follow-up is essential.

Mucosal melanomas of the head and neck: The Princess Margaret Hospital experience

The aim of this study was to identify the prognostic variables in mucosal melanoma of the head and neck. A retrospective review of 61 cases over a 41-year period was undertaken. Local, regional, and distant failures were major outcome measures. Demographic, clinical, and pathological parameters were identified and correlated with outcomes. The median age at diagnosis was 68 years. Sinonasal cavity involvement occurred in 80.3% of patients and 16.4% occurred in the oral cavity. Local, regional, and distant recurrences were 60.7%, 19.7%, and 49.2%, respectively. Two-year and 5-year disease-free survivals were 25.8% and 8%, respectively. Disease-specific survival at 5 years was 28.7%. Age<50 years significantly correlated with a longer median survival time. The most common occurrence site was the sinonasal cavity. Local and distant recurrences are common irrespective of treatment modalities. Younger patients have a relatively better prognosis. Disseminated disease is common and the overall prognosis is poor.

The scholarly radiation therapist. Part two: developing an academic practice—the Princess Margaret Hospital experience

AbstractPart two of this two-part series presents the results of a departmental initiative implemented in 2003 at a large urban cancer centre, Princess Margaret Hospital (PMH) in Toronto, Ontario, Canada. This new model for radiation therapists was called Advanced Integrated Practice (AIP) and was developed, in part, to encourage and promote scholarship within radiation therapy. The AIP model incorporated integrated clinical specialty roles designed to blend exemplary clinical practice with focused academic activities. This paper discusses an evaluation of the AIP model undertaken to obtain a formal measure of how the model had evolved, how the radiation therapists and other stakeholders were responding to the new model, whether the initial outcomes were realized and to create plans for further development of the design. The evaluation utilized a mixture of traditional qualitative research methodologies such as focus groups, quantitative surveys and a variety of other available measurable outcomes. Outcomes from the model included increased opportunities for diverse roles that incorporated an element of academic practice and augmented career choice and scope for radiation therapists. In addition, academic output and research work also increased within the department. Lessons learned from the implementation and evaluation of the model are shared, and the authors offer some suggestions to increase scholarly activity within the profession.

Sorafenib for the treatment of metastatic renal cancer (MRC) in the real world: The Princess Margaret Hospital (PMH) experience

15568 Background: Sorafenib, an oral multi-kinase inhibitor, prolonged progression free survival (PFS) of MRC patients (pts) in second line when compared to placebo in a phase III trial (Escudier at al ECCO 2005). Grade 3/4 adverse events (AE) were reported in 12% of pts. Here we present sorafenib’s efficacy and safety in a less selected cohort of pts enrolled in the Bayer Expanded Access Program at PMH. Methods: Pts with MRC received Sorafenib 400 mg bid continuously until disease progression (PD) and/or clinical deterioration..Tumor response was measured by RECIST criteria. AE were graded by NCI common toxicity criteria. Summary statistics and logistic regression were used to describe the results. Results: From Nov 2005 to Aug 2006, 58 pts were enrolled: median age was 59 years (range 14–86), 47 (81%) were male, 48 (83%) had clear cell histology and 46 (79%) received Sorafenib in first line. None received prior kinase-inhibitors. Using the Motzer Prognostic Index, 29 pts (50%) were low risk, 21 (36%) intermediate and 8 (14%) poor risk. Grade 3/4 AE occurred in 37 pts (64%, 95% CI 50–76%): 15 (26%) pts had skin rash, 10 (17%) hand-foot syndrome, 4 (7%) hypertension, 4 (7%) fatigue, and 4 (7%) diarrhea. Thirty-six (62%) pts required dose reductions and/or treatment interruptions, most due to skin reactions and hand-foot syndrome. Median follow-up was 9 months (IQR range 2–11), the median PFS was 7.5 months (IQR range 5.4–11.3), and the best responses among 56 evaluable pts were: 10 (17%) confirmed partial responses (median duration: 6 months, range 4–11), 14 (24%) stable diseases for = 6 months and 10 (18%) early progression. Pts with bony mets progressed earlier than pts without bony mets. Abnormal creatinine clearance, age, performance status, line of treatment and presence of significant comorbid conditions were not associated with grade 3/4 AE in univariate analysis. Conclusions: Sorafenib is effective in a ”real world”, less selected patient population with MRC but leads to more toxicity than described previously. [Table: see text]

230 Extranodal NK/T lymphoma of nasal type: the Princess Margaret hospital experience

230 Extranodal NK/T lymphoma of nasal type: the Princess Margaret hospital experience

Radiation therapy and rectal carcinoma: The Princess Margaret Hospital experience.

Radiation therapy and rectal carcinoma: The Princess Margaret Hospital experience.

23 Patient-Reported Late Toxicity Following High-dose Radiation Therapy for Prostate Cancer: The Princess Margaret Hospital Experience

23 Patient-Reported Late Toxicity Following High-dose Radiation Therapy for Prostate Cancer: The Princess Margaret Hospital Experience

Integrating academic and clinical roles for radiation therapists: the princess margaret hospital experience

Integrating academic and clinical roles for radiation therapists: the princess margaret hospital experience

Computed tomographic simulation in palliative radiotherapy: the Princess Margaret Hospital experience.

To examine the pattern of palliative radiation planning and the use of computed tomographic simulation (CTSIM) for this purpose. We reviewed our department's external radiotherapy database for all courses of treatment with a palliative intent during the period of April to June 2002. Patient characteristics and treatment details were compared based on whether CTSIM had been used or not. During the above period, 593 courses of external radiation treatment were delivered with palliative intent in our department. Of these, 100 treatments (17%) were planned with the help of CTSIM. The mean age of patients with CTSIM (62.9 years) was not significantly different with the patients planned without CTSIM (63.6 years). CTSIM use varied by treatment location, being highest in mediastinum/oesophagus (48%) and pancreas/stomach (47%) treatments, and lowest in spine (6%), lung (3%) and long bones (4%) (P < 0.01). Only 3% of palliative treatments without CTSIM were prescribed using multiple/complex fields (all field arrangements more complex than a single field or two opposed parallel fields). Although significantly higher (P < 0.001), this proportion was also only 24% in the cases planned with CTSIM. Only 12% of treatments without CTSIM were prescribed with more than 5 fractions, whereas 32% of CT-simulated treatments included more than 5 fractions (P < 0.001). CTSIM was used much less frequently in our department's palliative radiotherapy compared with its use in radical treatments. The relatively low rate of multiple/complex fields planned in CT-simulated cases suggested that CTSIM was mostly used to improve tumour localisation. The optimal role of CTSIM in palliative radiotherapy will most probably evolve, based on an enhanced understanding of the implications from improved localisation and optimal planning techniques on clinical outcomes, patient convenience and resource accessibility.

Gemcitabine concurrent with continuous infusional 5-fluorouracil in advanced biliary cancers: a review of the Princess Margaret Hospital experience

BackgroundUnresectable biliary tract cancer has a very poor prognosis. A combination of weekly gemcitabine plus continuous infusional 5-fluorouracil (5-FU) (GEM/CVI 5-FU) was evaluated as therapy for this cancer. Patients and methodsThe charts of 27 patients with advanced biliary tract adenocarcinoma treated with GEM/CVI 5-FU at the Princess Margaret Hospital were evaluated for response, survival and toxicity. The treatment consisted of a 30-min infusion of gemcitabine at 900 mg/m2 on days 1, 8 and 15 of a 28-day cycle plus 5‐FU given via a peripherally inserted central line at 200 mg/m2/day continuously for 21 days, every 28 days. ResultsObjective responses were observed in nine patients (33%; 95% confidence interval 17% to 54%). An additional eight patients (30%) achieved stable disease for a median of 4 months (range 2.3–11). Median time to progression and overall survival were 3.7 and 5.3 months, respectively. Direct chemotherapy-related toxicity was mild, with only 11% grade ≥3 myelosuppression. Central venous catheter complications were common (26%). There were no treatment-related deaths. ConclusionsThis study shows that GEM/CVI 5-FU is active and well tolerated in advanced and metastatic biliary tract cancers.

87 A descriptive study on the use of computerized tomographic simulation in palliative radiotherapy: the Princess Margaret Hospital experience

87 A descriptive study on the use of computerized tomographic simulation in palliative radiotherapy: the Princess Margaret Hospital experience

Radiotherapy management for squamous cell carcinoma of the nasal skin: the Princess Margaret Hospital experience

Purpose: To evaluate the outcome of radiotherapy (RT) for squamous cell carcinoma (SCC) of the nasal skin.Methods and Materials: The charts of 100 patients referred and treated with RT during 1982 to 1993 for SCC of nasal skin were reviewed. Most patients (81%) were treated with orthovoltage X-rays. In general, lesions ≤2 cm were treated to 35 Gy in 5 fractions. For tumors 2–5 cm, 45 Gy in 10 fractions was commonly used. Lesions >5 cm or those associated with bone or cartilage invasion were typically treated to 50 Gy in 20 fractions. Six patients were lost to follow-up, leaving 94 patients assessable for local or regional failure analysis. Using the UICC staging system, the T stage at first presentation was as follows: T1, 60 patients; T2, 11 patients; T3, 0 patients, T4, 7 patients; TX, 16 patients. Only 1 patient had regional lymph node disease at presentation. Thirty-one patients were treated with surgery, followed by RT. Sixty-three patients were treated with primary RT.Results: The local relapse-free rate was 90% and 85% at 2 and 5 years, respectively. The actuarial 2 and 5-year overall survival rate was 75% and 51%, respectively. The cause-specific survival was 96% at both 2 and 5 years. No Radiation Therapy Oncology Group Grade 4 toxicities occurred. Univariate analysis could not identify any patient, tumor, or treatment factors that were statistically significant prognosticators.Conclusion: RT for SCC of nasal skin achieves excellent outcome, is well tolerated, and should continue to be recommended in the management of this disease.

GEMCITABINE PLUS CISPLATIN FOR ADVANCED TRANSITIONAL CELL CARCINOMA OF THE URINARY TRACT: A PHASE II MULTICENTER TRIAL

We determined the activity and toxicity of gemcitabine plus cisplatin in patients with inoperable or metastatic transitional cell carcinoma of the urinary tract. A total of 54 patients with transitional cell carcinoma, measurable disease and Eastern Cooperative Oncology Group performance status 2 or greater were enrolled in this multicenter phase II trial. Previous adjuvant or neoadjuvant therapy for locally advanced disease was acceptable if it had been completed more than 1 year before study entry. Every 4 weeks patients received 1,000 mg./m.2 gemcitabine intravenously on days 1, 8 and 15, and 70 mg./m.2 cisplatin intravenously on day 2. All patients were evaluable for response and toxicity. Notably only 7 of the 54 patients (13%) previously received chemotherapy in an adjuvant or neoadjuvant setting. Overall we observed 26 objective responses (48%), of which 15% were complete. Median time to progression was 23 weeks and median survival was 54 weeks. Treatment was well tolerated. The main toxicities were leukopenia (grade 3 in 28% and grade 4 in 11% of patients), anemia (grade 3 in 34% and grade 4 in 6%) and thrombocytopenia (grade 3 in 14% and grade 4 in 6%). Other relevant side effects were nausea and vomiting in 20% of cases, fever in 24%, alopecia in 22%, renal failure in 7.4% and mucositis in 2%. Combined cisplatin plus gemcitabine is highly active in advanced transitional cell carcinoma of the urinary tract with manageable toxicity. The response rate, time to treatment failure and overall survival appeared to be comparable to those achieved with combined methotrexate, vinblastine, doxorubicin and cisplatin. Conversely toxicity appeared lower. Evaluation of this regimen in randomized studies with methotrexate, vinblastine, doxorubicin and cisplatin is strongly suggested.

Results of radiotherapy for epithelial skin cancer of the pinna: the princess margaret hospital experience, 1982–1993

Purpose: To assess the treatment outcome, late toxicity, and prognostic factors for radiotherapy (RT) of carcinoma of the pinna. Methods and Materials: The charts of 313 patients treated between 01/82 and 12/93 were retrospectively reviewed. There were 334 lesions treated: 201 basal cell carcinoma (BCC), 122 squamous cell carcinoma (SCC), and 11 basosquamous carcinoma. RT was most commonly given by orthovoltage X-rays (278 lesions) or electrons (39 lesions). The most frequently used dose prescriptions were 35 Gy in 5 fractions (123 treatments with median field size = 4.9 cm 2), 42.5–45 Gy in 10 fractions (67 treatments with median field size = 10.5 cm 2), and 50–65 Gy in 20–30 fractions (42 treatments with median field size = 81 cm 2). Results: The actuarial 2- and 5-year local control rates were 86.6% and 79.2%. Multivariate analysis revealed two factors to be statistically significant for increased local failure: tumor size > 2 cm (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.16–6.08), and a low biological effective dose (BED) (for each decrease of 5 BED units, HR = 1.76, 95% CI = 1.07–2.88). The 5-year actuarial rate of significant Grade 4 late toxicity was 7.3%. Factors statistically significant for this endpoint on univariate analysis were tumor size ( p = 0.035), T-stage ( p = 0.02), field size ( p = 0.05), fraction size ( p = 0.003), and BED ( p = 0.05). Conclusions: RT is an effective treatment option for epithelial skin cancer of the pinna. Large tumor size and low BED were independently statistically significantly associated with increased local failure. Dose-fractionation schedules using fraction sizes < 4 Gy may reduce the risk of necrosis and ulceration, particularly for field sizes > 5 cm 2.

Primary gastric lymphoma: brief overview of the recent Princess Margaret Hospital experience.

Primary gastric lymphoma is the commonest form of presentation for gastrointestinal lymphomas and the stomach is one of the most frequent sites of extranodal lymphoma. We present a review of the Princess Margaret Hospital (PMH) experience to illustrate the favorable prognosis and examine the long-term outcomes in this disease. Between 1967 and 1996, 149 consecutive patients with gastric lymphoma were treated at the PMH. The majority (122 patients) presented with diffuse large-cell lymphoma and 78 had stage I disease. In the past, the standard treatment was surgery (partial gastrectomy) followed by post-operative radiation therapy (RT; 78 patients). The overall 10-year survival was 62%. For patients who were treated with surgery and post-operative RT (operable disease) between 1967 and 1985, the 10-year rates of overall survival and cause-specific survival were 66.2% and 88%, respectively. In the past decade, combined-modality therapy with chemotherapy followed by RT was introduced for large-cell lymphoma, while RT alone was used for mucosa-associated lymphoid tissue (MALT) lymphoma. In 45 patients treated in the past decade, the overall 5-year survival was 86%, the cause-specific survival was 95.5%, and the relapse-free rate was 87.3%. These results support the view that primary gastric lymphoma is a highly curable disease. Future efforts should focus on reducing treatment morbidity, while preserving excellent results.