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author:("chatton, C.")
1.  Plasma osteopontin as a biomarker of prostate cancer aggression: relationship to risk category and treatment response 
British Journal of Cancer  2012;107(5):840-846.
High plasma osteopontin (OPN) has been linked to tumour hypoxia, metastasis, and poor prognosis. This study aims to assess whether plasma osteopontin was a biomarker of increasing progression within prostate cancer (PCa) prognostic groups and whether it reflected treatment response to local and systemic therapies.
Baseline OPN was determined in men with localised (n=199), locally recurrent (n=9) and castrate-resistant, metastatic PCa (CRPC-MET; n=37). Receiver-operating curves (ROC) were generated to describe the accuracy of OPN for distinguishing between localised risk groups or localised vs metastatic disease. We also measured OPN pre- and posttreatment, following radical prostatectomy, external beam radiotherapy (EBRT), androgen deprivation (AD) or taxane-based chemotherapy.
The CRPC-MET patients had increased baseline values (mean 219; 56–513 ng ml−1; P<0.0001) compared with the localised, non-metastatic group (mean 72; 12–438 ng ml−1). The area under the ROC to differentiate localised vs metastatic disease was improved when OPN was added to prostate-specific antigen (PSA) (0.943–0.969). Osteopontin neither distinguished high-risk PCa from other localised PCa nor correlated with serum PSA at baseline. Osteopontin levels reduced in low-risk patients after radical prostatectomy (P=0.005) and in CRPC-MET patients after chemotherapy (P=0.027), but not after EBRT or AD.
Plasma OPN is as good as PSA at predicting treatment response in CRPC-MET patients after chemotherapy. Our data do not support the use of plasma OPN as a biomarker of increasing tumour burden within localised PCa.
PMCID: PMC3425969  PMID: 22871886
osteopontin; biomarkers; radiotherapy; chemotherapy; surgery; prostate cancer
2.  Topotecan and Cyclophosphamide in Adults with Relapsed Sarcoma 
Sarcoma  2012;2012:749067.
Background. The combination of topotecan and cyclophosphamide (TC) has activity in pediatric patients with recurrent sarcoma, especially Ewing's sarcoma (EWS). We sought to determine the toxicity of and response to TC in adults with recurrent sarcoma. Patients and Methods. Adults treated with TC from 2005 to 2010 were reviewed who received T = topotecan at 0.75 mg/m2/day (days 1–5) and C = cyclophosphamide at 250 mg/m2/day (days 1–5) every 21 days. Results. Fifteen patients, median age 31 years (range 17.5–56) had nonpleomorphic rhabdomyosarcoma (RMS, n = 6), EWS, n = 5, synovial sarcoma (SS, n = 2) leiomyosarcoma (LMS, n = 1), and desmoplastic small round cell tumour (DSRCT, n = 1). Median time to progression was 2.5 months (range 1.6–13.0). Partial responses were seen in 2/6 RMS and 1/2 SS. Stable disease was seen in 2/5 EWS, 1/2 SS and 1 DSRCT. The most common reason for stopping treatment was progressive disease 12/15, (80%). Hematologic toxicity was common; 7 (47%) patients required blood product transfusion, 5 (33%) patients had fever/neutropenia. At median follow-up time of 7.7 months, all but 1 patient had died of disease. Conclusion: TC combination is tolerable but has only modest activity in adults with recurrent sarcoma. Other regimens deserve exploration for this high-risk group of patients
PMCID: PMC3407653  PMID: 22851904
3.  Clinical Features, Treatment, and Outcome in 102 Adult and Pediatric Patients with Localized High-Grade Synovial Sarcoma 
Sarcoma  2011;2011:231789.
Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15–76) and 14 (range 0.4–18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.
PMCID: PMC3087894  PMID: 21559258
4.  Radiation therapy in prostate cancer: a risk-adapted strategy 
Current Oncology  2010;17(Suppl 2):S18-S24.
External-beam radiotherapy and brachytherapy, widely utilized as curative treatment modalities for prostate cancer, have undergone significant clinical and technological advances in recent decades. Contemporary radiotherapy treatment algorithms use pretreatment prognostic factors to stratify patients into low-, intermediate-, and high-risk groups that correlate with both pathologic stage of disease and risk of recurrence after treatment. The use of risk groups and additional prognostic factors guide selection of the optimal treatment modalities for individual patients. Here, the roles of external-beam radiotherapy, brachytherapy, and neoadjuvant or adjuvant androgen deprivation therapy are discussed in that context. Additional prognostic factors for recurrence in the post-prostatectomy setting and the role of adjuvant and salvage radiation therapy are also reviewed. The risk-adaptive approach in radiotherapy for prostate cancer aims to optimize cancer control outcomes while minimizing the morbidity of treatment.
PMCID: PMC2935704  PMID: 20882127
Prostatic neoplasms; radiotherapy; brachytherapy; nomogram; adjuvant androgen deprivation therapy
5.  Defining the optimal treatment strategy for localized prostate cancer patients: a survey of ongoing studies at the National Cancer Institute of Canada Clinical Trials Group 
Current Oncology  2008;15(4):179-184.
The designation “clinically localized prostate cancer” comprises a group of biologically heterogeneous tumours with different growth rates and risks of relapse. Because prostate cancer is primarily a disease of older men, treatment selection must take into account the prognosis of the tumour, patient age, comorbidities, side effects of treatment, and patient preferences. Clinical trials must identify the various prognostic groups and test the appropriate treatment strategies within these subgroups.
PMCID: PMC2528309  PMID: 18769611
Localized prostate cancer; risk estimation; clinical trials
6.  Studies of the in vivo radiosensitivity of human skin fibroblasts 
Background and Purpose
To examine the radiosensitivity of skin cells obtained directly from the irradiated skin of patients undergoing fractionated radiation treatment prior to surgery for treatment of soft tissue sarcoma (STS) and to determine if there was a relationship with the development of wound healing complications associated with the surgery post-radiotherapy.
Micronucleus (MN) formation was measured in cells (primarily dermal fibroblasts) obtained from human skin at their first division after being removed from STS patients during post radiotherapy surgery (2-9 weeks after the end of the radiotherapy). At the time of radiotherapy (planned tumor dose - 50 Gy in 25 daily fractions) measurements were made of surface skin dose at predetermined marked sites. Skin from these sites was obtained at surgery and cell suspensions were prepared directly for the cytokinesis-blocked MN assay. Cultured strains of the fibroblasts were also established from skin nominally outside the edge of the radiation beam and DNA damage (MN formation) was examined following irradiation in vitro for comparison with the results from the in situ irradiations.
Extensive DNA damage (MN) was detectable in fibroblasts from human skin at extended periods after irradiation (2-9 weeks after the end of the 5-week fractionated radiotherapy). Analysis of skin receiving a range of doses demonstrated that the level of damage observed was dose dependent. There was no clear correlation between the level of damage observed after irradiation in situ and irradiation of cell strains in culture. Similarly, there was no correlation between the extent of MN formation following in situ irradiation and the propensity for the patient to develop wound healing complications post surgery.
Despite the presence of DNA damage in dermal fibroblasts weeks after the end of the radiation treatment, there was no relationship between this damage and wound healing complications following surgery post irradiation. These results suggest that factors other than the radiosensitivity of the skin fibroblasts likely also play a role in wound healing in deep wound sites associated with surgery for STS following radiation therapy.
PMCID: PMC2034367  PMID: 17590467
fibroblasts; radiosensitivity in situ; micronuclei; wound healing; bystander effects

Results 1-7 (7)