Nonrandomized Comparison of Efficacy and Side Effects of Bicalutamide Compared With Luteinizing Hormone-Releasing Hormone (LHRH) Analogs in Combination With Radiation Therapy in the CHHiP Trial.

Purpose: CHHiP is a randomized trial evaluating moderately hypofractionated radiation therapy for treatment of localized prostate cancer. Of all participants, 97% of them had concurrent short-course hormone therapy (HT), either luteinizing hormone-releasing hormone analog (LHRHa) or 150 mg of bicalutamide daily. This exploratory analysis compares efficacy and side effects in a nonrandomized comparison.

Impact of Hypofractionated Radiotherapy on Patient-reported Outcomes in Prostate Cancer: Results up to 5 yr in the CHHiP trial (CRUK/06/016).

Background: Moderate hypofractionation is the recommended standard of care for localised prostate cancer following the results of trials including Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP). Evaluation of long-term patient-reported outcomes (PROs) is important to confirm safety and enhance patient information.

Objective: To determine whether 5-yr PROs from the CHHiP quality of life (QoL) substudy confirm 2-yr findings and assess patterns over follow-up.

Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer: 12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease.

Purpose: The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 (NCT00021450) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines.

Patient And Methods: Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.

Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial.

Background: Radical (chemo)radiotherapy offers potentially curative treatment for patients with locally advanced laryngeal or hypopharyngeal cancer. We aimed to show that dose-escalated intensity-modulated radiotherapy (DE-IMRT) improved locoregional control.

Methods: We performed a phase III open-label randomised controlled trial in patients with laryngeal or hypopharyngeal cancer (AJCC III-IVa/b, TNM 7).

Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.

Background: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.

Evaluation of erectile potency and radiation dose to the penile bulb using image guided radiotherapy in the CHHiP trial.

Background And Purpose: The penile bulb (PB) dose may be critical in development of post prostate radiotherapy erectile dysfunction (ED). This study aimed to generate PB dose constraints based on dose-volume histograms (DVHs) in patients treated with prostate radiotherapy, and to identify clinical and dosimetric parameters that predict the risk of ED post prostate radiotherapy.

Materials And Methods: Penile bulb DVHs were generated for 276 patients treated within the randomised IGRT substudy of the multicentre randomised trial, CHHiP.

A randomised assessment of image guided radiotherapy within a phase 3 trial of conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer.

Background And Purpose: Image-guided radiotherapy (IGRT) improves treatment set-up accuracy and provides the opportunity to reduce target volume margins. We introduced IGRT methods using standard (IGRT-S) or reduced (IGRT-R) margins in a randomised phase 2 substudy within CHHiP trial. We present a pre-planned analysis of the impact of IGRT on dosimetry and acute/late pelvic side effects using gastrointestinal and genitourinary clinician and patient-reported outcomes (PRO) and evaluate efficacy.

Forward- and Inverse-Planned Intensity-Modulated Radiotherapy in the CHHiP Trial: A Comparison of Dosimetry and Normal Tissue Toxicity.

Aims: The CHHiP (Conventional or Hypofractionated High-dose Intensity Modulated Radiotherapy In Prostate Cancer; CRUK/06/016) trial investigated hypofractionated radiotherapy for localised prostate cancer. Forward- (FP) or inverse-planned (IP) intensity-modulated techniques were permitted. Dose-volume histogram and toxicity data were compared to explore the effects of planning method.

Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL).

Purpose: To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers.

Methods And Materials: In this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence.

Patients And Methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.

The Efficacy and Safety of Conventional and Hypofractionated High-Dose Radiation Therapy for Prostate Cancer in an Elderly Population: A Subgroup Analysis of the CHHiP Trial.

Purpose: Outcome data on radiation therapy for prostate cancer in an elderly population are sparse. The CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer) trial provides a large, prospectively collected, contemporary dataset in which to explore outcomes by age.

Methods And Materials: CHHiP participants received 3 to 6 months of androgen deprivation therapy and were randomly assigned (1:1:1) to receive 74 Gy in 37 fractions (conventional fractionation), 60 Gy in 20 fractions, or 57 Gy in 19 fractions.

Two-years Postradiotherapy Biopsies: Lessons from MRC RT01 Trial.

Background: The importance of 2-yr postradiotherapy prostate biopsy status remains uncertain.

Objective: To assess the value of 2 year post treatment biopsies in a randomised trial of radiotherapy dose escalation.

Design, Setting, And Participants: Between 1998 and 2001, 843 men with localised prostate cancer were randomised to receive either control-64Gy or escalated-74Gy conformal radiotherapy (CFRT) in the MRC RT01 trial in combination with 3-6-mo neoadjuvant androgen deprivation therapy.

Clinical and patient-reported outcomes of SPARE - a randomised feasibility study of selective bladder preservation versus radical cystectomy.

Objectives: To test the feasibility of a randomised trial in muscle-invasive bladder cancer (MIBC) and compare outcomes in patients who receive neoadjuvant chemotherapy followed by radical cystectomy (RC) or selective bladder preservation (SBP), where definitive treatment [RC or radiotherapy (RT)] is determined by response to chemotherapy.

Patients And Methods: SPARE is a multicentre randomised controlled trial comparing RC and SBP in patients with MIBC staged T2-3 N0 M0, fit for both treatment strategies and receiving three cycles of neoadjuvant chemotherapy. Patients were randomised between RC and SBP before a cystoscopy after cycle three of neoadjuvant chemotherapy.

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial.

Background: Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up.

Methods: CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b-T3aN0M0).

Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991.

Purpose: Up to 30% of patients who undergo radiation for intermediate- or high-risk localized prostate cancer relapse biochemically within 5 years. We assessed if biochemical disease-free survival (DFS) is improved by adding 6 months of androgen suppression (AS; two injections of every-3-months depot of luteinizing hormone-releasing hormone agonist) to primary radiotherapy (RT) for intermediate- or high-risk localized prostate cancer.

Patients And Methods: A total of 819 patients staged: (1) cT1b-c, with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≥ 7, or (2) cT2a (International Union Against Cancer TNM 1997), with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread, with PSA ≤ 50 ng/mL, were centrally randomized 1:1 to either RT or RT plus AS started on day 1 of RT.

A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol.

Background: Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa.

Objective: To compare BMD change in men receiving either LHRHa or oestradiol patches (OP).

Consensus Guidelines and Contouring Atlas for Pelvic Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy.

Purpose: The purpose of this study was to establish reproducible guidelines for delineating the clinical target volume (CTV) of the pelvic lymph nodes (LN) by combining the freehand Royal Marsden Hospital (RMH) and Radiation Therapy Oncology Group (RTOG) vascular expansion techniques.

Methods And Materials: Seven patients with prostate cancer underwent standard planning computed tomography scanning. Four different CTVs (RMH, RTOG, modified RTOG, and Prostate and pelvIs Versus prOsTate Alone treatment for Locally advanced prostate cancer [PIVOTAL] trial) were created for each patient, and 6 different bowel expansion margins (BEM) were created to assess bowel avoidance by the CTV.

Quality assurance for the EORTC 22071-26071 study: dummy run prospective analysis.

Purpose: The phase III 22071-26071 trial was designed to evaluate the addition of panitumumab to adjuvant chemotherapy plus intensity modulated radiotherapy (IMRT) in locally advanced resected squamous cell head and neck cancer. We report the results of the dummy run (DR) performed to detect deviations from protocol guidelines.

Methods And Materials: DR datasets consisting of target volumes, organs at risk (OAR) and treatment plans were digitally uploaded, then compared with reference contours and protocol guidelines by six central reviewers.

Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial.

Background: The aim of this trial was to compare dose-escalated conformal radiotherapy with control-dose conformal radiotherapy in patients with localised prostate cancer. Preliminary findings reported after 5 years of follow-up showed that escalated-dose conformal radiotherapy improved biochemical progression-free survival. Based on the sample size calculation, we planned to analyse overall survival when 190 deaths occurred; this target has now been reached, after a median 10 years of follow-up.

Squamous cell carcinoma of the temporal bone: clinical outcomes from radical surgery and postoperative radiotherapy.

Objective: To review the treatment of squamous carcinoma of the temporal bone at a regional skull base unit for the period 1982-2012.

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Interobserver variation in clinical target volume and organs at risk segmentation in post-parotidectomy radiotherapy: can segmentation protocols help?

Objective: A study of interobserver variation in the segmentation of the post-operative clinical target volume (CTV) and organs at risk (OARs) for parotid tumours was undertaken. The segmentation exercise was performed as a baseline, and repeated after 3 months using a segmentation protocol to assess whether CTV conformity improved.

Methods: Four head and neck oncologists independently segmented CTVs and OARs (contralateral parotid, spinal cord and brain stem) on CT data sets of five patients post parotidectomy.

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial.

Background: Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy.

Methods: We did a multicentre, randomised study and recruited men with localised prostate cancer between Oct 18, 2002, and Aug 12, 2006, at 11 UK centres.

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial.

Background: Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.

Intensity modulated radiotherapy (IMRT) in the management of locally advanced oropharyngeal squamous cell carcinomata (SCC): disease control and functional outcome using the therapy outcome measure (TOM) score--report from a single U.K. institution.

Introduction: This paper evaluates tumour control and toxicity especially in relation to swallowing dysfunction in those patients with locally advanced oropharyngeal squamous cell carcinoma who have undergone either primary chemo-radiation or post-operative parotid sparing IMRT. The TOM scoring system was used to assess dysphagia.

Methods: All patients with locally advanced (stage 3/4) squamous cell oropharyngeal cancer and who required either primary or post-operative RT were identified.