Cell death in irradiated prostate epithelial cells: role of apoptotic and clonogenic cell kill.

Dose-escalated conformal radiotherapy is increasingly being used to radically treat prostate cancer with encouraging results and minimal long-term toxicity, yet little is known regarding the response of normal or malignant prostate cells to ionizing radiation (IR). To clarify the basis for cell killing during prostate cancer radiotherapy, we determined the IR-induced expression of several apoptotic- (bax, bcl-2, survivin and PARP) and G1-cell cycle checkpoint- (p53 and p21(WAF1/Cip1)) related proteins, in both normal (PrEC-epithelial and PrSC-stromal) and malignant (LNCaP, DU-145 and PC-3; all epithelial) prostate cells. For these experiments, we chose doses ranging from 2 to 10 Gy, to be representative of the 1.

Management and outcome differences in supraglottic cancer between Ontario, Canada, and the Surveillance, Epidemiology, and End Results areas of the United States.

Purpose: We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States.

Methods: Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265).

Controversies in the management of testicular seminoma.

Tremendous progress has been made in the treatment of testicular seminoma over the past 25 years. The advent of curative cytotoxic chemotherapy, even for patients with advanced metastatic disease, has led to a paradigm shift toward minimizing additional oncologic therapies and their potential side effects. Despite these advances, controversial issues still exist in managing patients with this disease.

Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis.

Purpose: Several management options are available to patients with stage I seminoma, including adjuvant radiotherapy, surveillance, and adjuvant chemotherapy. We performed a pooled analysis of patients from the four largest surveillance studies to better delineate prognostic factors associated with disease progression.

Patients And Methods: Individual patient data were obtained from each center (Princess Margaret Hospital, Danish Testicular Cancer Study Group, Royal Marsden Hospital, and Royal London Hospital) for 638 patients.

Surveillance in stage I testicular seminoma - risk of late relapse.

Introduction: Surveillance is an alternative to adjuvant radiotherapy for stage I testicular seminoma. We present the long-term results of seminoma surveillance, with emphasis on quantifying the risk of late relapse beyond 5 years.

Methods: From 1981 to 1993, of 431 men with stage I testicular seminoma, 203 were managed by surveillance following radical orchidectomy.

The prognostic significance of the tumour infiltrating lymphocyte count in stage I testicular seminoma managed by surveillance.

The degree of lymphocytic infiltration is a significant determinant of outcome for a variety of malignancies, but its role in seminoma is unknown. 150 men with stage I testicular seminoma presenting between 1981 and 1993 were managed by surveillance following orchidectomy. The presence of tumour infiltrating lymphocytes (TILs) in each case was classified as high, intermediate or low.

The use of conformal radiotherapy and the selection of radiation dose in T1 or T2 low or intermediate risk prostate cancer - a systematic review.

Background And Purpose: The purpose was to develop a systematic review that would address the following questions: (a) when single-modality treatment external-beam radiotherapy is selected as the modality of choice, what is the role of three-dimensional (3D) conformal radiotherapy in treating clinically localized (T1, T2/NO, NX/MO) prostate cancer? The outcomes of interest are biochemical freedom from failure (bNED) rates, clinical recurrence-free survival, disease-specific survival and acute and late toxicity; (b) what is the appropriate dose and fractionation prescription in this clinical setting?

Materials And Methods: A systematic review of the English published literature was undertaken to provide evidence relevant to the above outcomes.

Results: One randomized controlled trial comparing conventional radiotherapy to conformal therapy with dose escalation reported bNED rates. Three additional randomized controlled trials reported acute or chronic late outcome assessments.

A dose-volume histogram analysis of the seminal vesicles in men treated with conformal radiotherapy to 'prostate alone'.

Background And Purpose: There is no consensus on whether the seminal vesicles should be included in the clinical target volume (CTV) for radiotherapy of localized prostate cancer. To inform the debate, we have undertaken a dose-volume histogram (DVH) analysis of the seminal vesicles in patients treated with escalated dose conformal radiation to 'prostate alone'.

Material And Methods: Twenty-five consecutive patients receiving conformal radiation to the prostate, to a dose of 75.

Management preferences following radical inguinal orchidectomy for Stage I testicular seminoma in Australasia.

A survey to evaluate the preferred patterns of management of Stage I seminoma was conducted during March 2001. The questionnaire was distributed by the Royal Australian and New Zealand College of Radiologists to all qualified radiation oncologists, 74 out of 170 responded. All performed a staging CT scan of the abdomen and pelvis.

A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer.

Purpose: To test the hypothesis that the use of oral pilocarpine during and after radiotherapy (RT) for head-and-neck cancer would reduce the symptoms of post-RT xerostomia.

Methods And Materials: One hundred thirty patients were randomized in a double-blind method to receive either pilocarpine (5-mg tablets) or placebo three times daily starting on Day 1 of RT and continuing for 1 month after treatment. The eligibility criteria included a planned dose of >50 Gy as radical or postoperative RT for head-and-neck cancer, with at least 50% of both parotid glands included in the treatment fields.

Acute toxicity of conventional radiation therapy for high-risk prostate cancer in EORTC trial 22863.

Objectives: We analysed the acute toxicity observed in the European Organisation for Research and Treatment of Cancer (EORTC) randomised trial 22863 comparing conventional external irradiation with or without an agonist analogue of gonadotropin-releasing hormone in high-risk prostate cancer patients.

Methods: Four hundred five patients that received a dose of at least 30 Gy were considered evaluable for acute toxicity assessment. Toxicity was grouped in a few categories: general, genito-urinary, and lower gastro-intestinal.

Radiotherapy alone in patients with advanced nasopharyngeal cancer: comparison with an intergroup study. Is combined modality treatment really necessary?

Purpose: To examine the outcome of radiotherapy (RT) alone in patients with advanced nasopharyngeal cancer (NPC) and to compare the results with those reported by the Intergroup study 0099 (IGS) comparing RT to combined modality therapy (CMT).

Materials And Methods: During the period 1985-1992, 198 NPC patients presenting without distant metastatic disease were treated for cure. Of these, 172 had stage III/IV (UICC 1987, 1992).

The ten-year rule revisited: accuracy of clinicians' estimates of life expectancy in patients with localized prostate cancer.

Objectives: To determine the accuracy of clinicians' predictions of life expectancy in patients with localized prostate cancer, when provided with information about age and comorbidity, and to determine whether life expectancy estimates predict the choice of initial treatment.

Methods: A survey was sent by facsimile to 191 Canadian urologists and radiation oncologists asking them to estimate the life expectancy and choose the initial therapy (radical prostatectomy, radiation, or watchful waiting) for 18 patient scenarios: two prostate cancer scenarios, each with three ages and three levels of comorbidity.

Results: Life expectancy estimates were accurate within 1 year of the projections of a Markov model for 31% of the clinicians' responses and accurate within 3 years for 67% of the responses.

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.

Background: We did a randomised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone (LHRH) to investigate the added value of long-term androgen suppression in locally advanced prostate cancer.

Methods: Between 1987 and 1995, 415 patients were randomly assigned radiotherapy alone or radiotherapy plus immediate androgen suppression. Eligible patients had T1-2 tumours of WHO grade 3 or T3-4 N0-1 M0 tumours; the median age of participants was 71 years (range 51-80).

A comparison of published head and neck stage groupings in laryngeal cancer using data from two countries.

The combination of T, N, and M classifications into stage groupings is meant to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. We tested the UICC/AJCC fifth edition stage grouping and six other TNM-based groupings proposed for head and neck cancer for their ability to meet these expectations in laryngeal cancer using data from Ontario, Canada, and the area of Southern Norway surrounding Oslo. We defined four criteria to assess each grouping scheme: (1) the subgroups defined by T, N, and M comprising a given group within a grouping scheme have similar survival rates (hazard consistency); (2) the survival rates differ among the groups (hazard discrimination); (3) the prediction of cure is high (outcome prediction); and (4) the distribution of patients among the groups is balanced.

Survey of radiation oncologists: practice patterns of the management of stage I seminoma of testis in Canada and a selected group in the United States.

Objective: To evaluate practice patterns of the management of stage I seminoma of testis in Canada and a selected group in the United States.

Materials And Methods: Survey among radiation oncologists treating genitourinary (GU) tumors in Canada and the RTOG GU committee members in the United States between January and March 2001.

Results: Response rate was 78% (73/93) in Canada and 67% (24/36) in the United States.

Results of radiotherapy for primary subglottic squamous cell carcinoma.

Purpose: To retrospectively evaluate the outcome after radical radiotherapy (RT) and surgical salvage and assess the risk of late toxicity for patients with primary subglottic squamous cell carcinoma treated at our center.

Methods And Materials: Between 1971 and 1996, 43 patients with primary squamous cell carcinoma of the subglottis (35 men, 8 women) were treated with radical RT. All received megavoltage irradiation, most commonly to a dose of 50-52 Gy in 20 fractions during 4 weeks (39 patients).

Molecular pathology parameters in human nasopharyngeal carcinoma.

Background: To derive a better understanding of the biologic behavior of nasopharyngeal carcinoma (NPC), the authors evaluated a number of molecular variables to address the hypothesis that p53 dysfunction in NPC is associated with Epstein-Barr virus (EBV), increased tumor angiogenesis, lower likelihood of apoptosis, and poorer clinical outcome.

Materials: The biopsy samples from 87 NPC patients were obtained and sections were made to detect EBV, using in-situ hybridization; the authors used immunohistochemistry to assess p53, p21(WAF1/CIP1) expression, and microvessel density count (MVD). In situ end labelling was used to evaluate apoptosis and necrosis.

Clinical and biochemical outcome of conventional dose radiotherapy for localized prostate cancer.

Purpose: To retrospectively review the results of conventional dose radical radiotherapy for clinical stage T1 and T2 prostate cancer, and to identify the factors that predict the biochemical relapse-free rate.

Methods: The records were reviewed of 706 hormonally-naïve men with clinical stage T1T2 prostate cancer treated with radical radiotherapy (RT) between 1987-1994 at the Princess Margaret Hospital. The median prostate RT dose was 65 Gy in 35 fraction (range 52 Gy in 20 fractions to 67 Gy in 37 fractions).

Outcome of curative management of malignant tumours of the parotid gland.

Purpose: The optimal management of malignant parotid gland tumours remains to be defined precisely. Specifically, a further understanding of the tumour features that influence treatment outcome is needed.

Materials And Methods: A retrospective review was conducted on 184 patients who were registered at the Princess Margaret Hospital with a diagnosis of a primary malignant parotid gland tumour.

A comparison of published head and neck stage groupings in carcinomas of the tonsillar region.

Background: The combination of T, N, and M classifications into stage groupings was designed to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. The authors tested the UICC/AJCC 5th edition stage grouping and seven other TNM-based groupings proposed for head and neck cancer to determine their ability to meet these expectations in a specific site: carcinoma of the tonsillar region.

Methods: The authors defined four criteria to assess each stage grouping scheme: 1) The subgroups defined by T and N comprising a given group within a grouping scheme have similar survival rates (hazard consistency); 2) The survival rates differ across the groups (hazard discrimination); 3) The prediction of cure is high (outcome prediction); and 4) The distribution of patients among the groups is balanced.

Positioning errors and prostate motion during conformal prostate radiotherapy using on-line isocentre set-up verification and implanted prostate markers.

Purpose: To evaluate treatment errors from set-up and inter-fraction prostatic motion with port films and implanted prostate fiducial markers during conformal radiotherapy for localized prostate cancer.

Methods: Errors from isocentre positioning and inter-fraction prostate motion were investigated in 13 men treated with escalated dose conformal radiotherapy for localized prostate cancer. To limit the effect of inter-fraction prostate motion, patients were planned and treated with an empty rectum and a comfortably full bladder, and were instructed regarding dietary management, fluid intake and laxative use.

Salvage radiotherapy for PSA failure after radical prostatectomy.

Background And Purpose: Prostate-specific antigen (PSA) failure after radical prostatectomy is a common clinical scenario, and there is no consensus on how it should be managed. Salvage radiation to the prostatic bed is a potentially curative treatment option, and is the subject of this review. Patient selection, and the efficacy and toxicity of treatment will be discussed, and recommendations made for current practice and future studies.

The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region.

Purpose: Ipsilateral techniques designed to restrict treatment to the primary tumor and neck on the same side have been used in selected cases of cases of carcinoma of the tonsillar region at our institution for many years. The primary purpose of this study is to evaluate the risk of failure in the opposite neck in cases selected for unilateral radiotherapy over a 21-year period.

Methods And Materials: Ipsilateral radiotherapy techniques were used in 228 of 642 patients with carcinoma of the tonsillar region from 1970 to 1991.

Controversies in prostate cancer radiotherapy: consensus development.

The GU Radiation Oncologists of Canada (GUROC) had a consensus meeting in November 2000 to discuss and develop consensus on four controversial areas: risk assessment of localized prostate cancer, conformal radiotherapy, role of brachytherapy in prostate cancer and combined hormonal therapy and radiotherapy for prostate cancer. The meeting was a success and resulted in consensus being achieved on a number of areas. The group agreed on three risk groupings: low risk, intermediate risk and high risk localized prostate cancer based on clinical stage, Gleason score and PSA level.