The strength of female sex as a prognostic factor in small-cell lung cancer: a pooled analysis of chemotherapy trials from the Manchester Lung Group and Medical Research Council Clinical Trials Unit.

Background: Previous studies reported that women survive longer than men, but experience greater toxicity, when treated for small-cell lung cancer (SCLC).

Methods: Individual patient data from six randomized phase II/III chemotherapy trials, from the Manchester Lung Group and UK Medical Research Council, were pooled for analysis. End points included overall survival, response rate, toxicity, dose intensity (DI) and transfusion rates.

Quality-adjusted time without symptoms or toxicity analysis of adjuvant chemotherapy in non-small-cell lung cancer: an analysis of the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial.

Purpose: National Cancer Institute of Canada Clinical Trials Group JBR.10 demonstrated that adjuvant vinorelbine and cisplatin after resection of stage IB-II non-small-cell lung cancer (NSCLC) improved relapse-free and overall survival. However, many patients either are not referred for chemotherapy or decline treatment.

Resident preparedness in discussing prognosis in patients with advanced lung cancer.

Goals: Teaching delivery of bad news is part of the standard medical school curriculum. Lung cancer is a common disease with poor outcomes; therefore, "poor prognosis" discussions occur frequently. Trainee preparedness to conduct these has not been studied well to date.

High-resolution array CGH identifies novel regions of genomic alteration in intermediate-risk prostate cancer.

Approximately one-third of prostate cancer patients present with intermediate risk disease. Interestingly, while this risk group is clinically well defined, it demonstrates the most significant heterogeneity in PSA-based biochemical outcome. Further, the majority of candidate genes associated with prostate cancer progression have been identified using cell lines, xenograft models, and high-risk androgen-independent or metastatic patient samples.

A method to analyze the cord geometrical uncertainties during head and neck radiation therapy using cone beam CT.

We developed a method to analyze quantitatively the residual cord geometrical uncertainties after image registration during head and neck radiation therapy by using sequential cone beam CT (CBCT). The geometrical centroid line of cervical spinal canal was computed to serve as a cord surrogate. We found that the cord motions were non-uniform from C1 to C6, and that the patterns of motion were variable across patients.

Radiation effects and radioprotection in MC3T3-E1 mouse calvarial osteoblastic cells.

Background: Little is known about the mechanisms and treatment of radiation-induced inhibition of craniofacial bone growth. In an earlier study, the radioprotector amifostine (WR-2721) administered to rabbits before irradiation radioprotected cultured orbitozygomatic complex periosteal osteoblast-like cells. This study assessed the effects of amifostine and its active metabolite on the radiation survival, function, and phenotype of mouse calvarial osteoblast-like cells in a cell culture model.

Is Canada ready for patient accessible electronic health records? A national scan.

Background: Access to personal health information through the electronic health record (EHR) is an innovative means to enable people to be active participants in their own health care. Currently this is not an available option for consumers of health. The absence of a key technology, the EHR, is a significant obstacle to providing patient accessible electronic records.

Do allogeneic bone marrow transplant candidates match coping to controllability of pre-treatment stressors?

According to the Person x Situation theoretical framework, people adjust their coping to address the unique challenges of encountered stressors. Whether their strategies fit or appropriately address these stressor challenges influences adjustment. We examined the fit between pre-treatment stressors reported by hematological cancer patients awaiting allogeneic bone marrow transplantation (alloBMT) and their coping responses.

In vivo real time monitoring of vasoconstriction and vasodilation by a combined diffuse reflectance spectroscopy and Doppler optical coherence tomography approach.

Background And Objectives: A combined diffuse reflectance (DR) spectroscopy and doppler optical coherence tomography (DOCT) approach may offer a powerful means for assessment of tissue function, and potentially provide a way for earlier cancer detection through non-invasive local blood supply measurements. The goal of the study was to compare a DR-derived blood-content-related index to a measure of local blood supply flow as furnished by DOCT during manipulations with blood circulation (vasoconstriction and vasodilation), investigate similarities and differences, complementarity of techniques, and then applying these results to the underlying biology.

Study Design/materials And Methods: Simultaneous DR-DOCT measurements of local blood supply were conducted during drug and mechanically-induced vasoconstriction and vasodilatation on an externalized intact rat gut in vivo.

Biomarkers for DNA DSB inhibitors and radiotherapy clinical trials.

Major technical advances in radiotherapy, including IMRT and image-guided radiotherapy, have allowed for improved physical precision and increased dose delivery to the tumor, with better sparing of surrounding normal tissue. The development of inhibitors of the sensing and repair of DNA double-strand breaks (DSBs) is exciting and could be combined with precise radiotherapy targeting to improve local control following radiotherapy. However, caution must be exercised in order that DSB inhibitors are combined with radiotherapy in such a manner as to preserve the therapeutic ratio by exploiting repair deficiencies in malignant cells over that of normal cells.

Enhancing treatment decision-making: pilot study of a treatment decision aid in stage IV non-small cell lung cancer.

We developed a decision aid (DA) for patients with metastatic non-small cell lung cancer (NSCLC), to better inform patients of their prognosis and treatment options, and facilitate involvement in decision-making. In a pilot study, 20 patients with metastatic NSCLC attending outpatient clinics at a major cancer centre, who had already made a treatment decision, reviewed acceptability of the DA. The median age of the patients was 61 years (range 37-77 years), 35% were male, 20% had a university education, and most (75%) had English as a first language.

A phase I trial of pre-operative radiotherapy for prostate cancer: clinical and translational studies.

Background And Purpose: Selected patients undergoing radical prostatectomy for localized prostate cancer can be at high-risk for pT3 disease and require subsequent radiotherapy. In a phase I trial, we investigated the feasibility of pre-operative radiotherapy for this patient subset.

Materials And Methods: Eligibility criteria were: T1/T2N0M0 tumors plus (i) Gleason >or=7, PSA>10 ng/ml and <35 ng/ml, or (ii), PSA >15 ng/ml and less <35 ng/ml (any Gleason).

Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53.

Nutlin-3 is a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. Whether Nutlin-3 alters cell toxicity following DNA damage under oxic versus hypoxic conditions has not been studied. The potential radiosensitization (0-10 Gy) properties of Nutlin-3 (dose range, 2-10 micromol/L for up to 24 h) were investigated in vitro using three prostate cancer cell lines, 22RV1 [wild-type p53 (WTp53)], DU145 (mutated p53), and PC-3 (p53-null) under oxic (21% O(2)), hypoxic (0.

WTp53 induction does not override MTp53 chemoresistance and radioresistance due to gain-of-function in lung cancer cells.

New molecular cancer treatment strategies aim to reconstitute wild-type p53 (WTp53) function in mutant p53 (MTp53)-expressing tumors as a means of resensitizing cells to chemotherapy or radiotherapy. The success of this approach may depend on whether MTp53 proteins are acting in a dominant-negative or independent gain-of-function mode. Herein, we describe an isogenic, temperature-sensitive p53 model (p53(A138V)) in p53-null human H1299 lung cancer cells in which WTp53 can be selectively coexpressed with a temperature-sensitive MTp53 allele (A138V) during initial DNA damage and subsequent DNA repair.

Development and evaluation of a decision aid for patients considering first-line chemotherapy for metastatic breast cancer.

Objective: Treatment decisions in advanced breast cancer are complex, with enhanced quality of life and survival among important treatment goals. Patients with metastatic breast cancer face the decision of whether or not to have chemotherapy, and many wish to be involved in this decision. We report the development and evaluation of a decision aid (DA) designed to assist patients facing this treatment decision.

Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability.

Areas of hypoxic tumour tissue are known to be resistant to treatment and are associated with a poor clinical prognosis. There are several reasons why this might be, including the capacity of hypoxia to drive genomic instability and alter DNA damage repair pathways. Significantly, current models fail to distinguish between the complexities of the hypoxic microenvironment and the biological effects of acute hypoxia exposures versus longer-term, chronic hypoxia exposures on the transcription and translation of proteins involved in genetic stability and cell survival.

PRIMA-1(met) radiosensitizes prostate cancer cells independent of their MTp53-status.

The novel agent PRIMA-1(met) can reactivate WTp53 function in MTp53-expressing cells. We investigated PRIMA-1(met) as a radiosensitizer of WTp53, p53Null or MTp53 prostate cancer cells. Radiosensitization was observed in PC3 (p53Null) cells, even under hypoxia.

Chronic hypoxia decreases synthesis of homologous recombination proteins to offset chemoresistance and radioresistance.

Hypoxic and/or anoxic tumor cells can have increased rates of mutagenesis and altered DNA repair protein expression. Yet very little is known regarding the functional consequences of any hypoxia-induced changes in the expression of proteins involved in DNA double-strand break repair. We have developed a unique hypoxic model system using H1299 cells expressing an integrated direct repeat green fluorescent protein (DR-GFP) homologous recombination (HR) reporter system to study HR under prolonged chronic hypoxia (up to 72 h under 0.

A phase II and pharmacokinetic study of SB-715992, in patients with metastatic hepatocellular carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG IND.168).

Hepatocellular carcinoma (HCC) remains a lethal treatment-resistant cancer with a median survival of <6 months in patients not considered candidates for radical surgical treatments. SB-715992 is a novel cytotoxic agent implicated in the inhibition of mitotic kinesin spindle protein (KSP). Based on evidence from preclinical models and phase I trials, we conducted a phase II trial of SB-715992 in chemo-naïve patients with advanced HCC.

Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy: assessment of safety and treatment response.

Purpose: Tookad is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system.

A two isocenter IMRT technique with a controlled junction dose for long volume targets.

Most IMRT techniques have been designed to treat targets smaller than the field size of conventional linac accelerators. In order to overcome the field size restrictions in applying IMRT, we developed a two isocenter IMRT technique to treat long volume targets. The technique exploits an extended dose gradient throughout a junction region of 4-6 cm to minimize the impact of field match errors on a junction dose and manipulates the inverse planning and IMRT segments to fill in the dose gradient and achieve dose uniformity.

Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new therapies.

Increasingly, the tumor microenvironment and hypoxia are being studied as potential prognostic factors in prostate cancer given their effects on the hypoxia inducible factor-1alpha and vascular endothelial growth factor signaling pathways. Based on immunohistochemical studies using hypoxic cell markers and direct oxygen-electrode measurements, clinically relevant levels of hypoxia are detected in 30-90% of prostate cancers. Exciting new data suggest that hypoxia can alter cell-cycle checkpoints and DNA repair within the prostate epithelium, thereby driving genetic instability and tumor aggression.

Homologous recombination and prostate cancer: a model for novel DNA repair targets and therapies.

Using elegant targeting techniques such as IMRT, radiation oncology has improved the therapeutic ratio of prostate cancer radiotherapy through increased physical precision (e.g. increased local control through dose-escalation without increased normal tissue toxicity).