V. Khoo

Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study

Study Type – Diagnostic (validating cohort)
Level of Evidence 1b

Biological Dose Escalation and Hypofractionation: What is There to be Gained and How Will it Best be Done?

The evidence supporting dose escalation for localised prostate cancer is widely accepted, but in tandem with improvements in biochemical control, dose escalation increases side-effects. In a scenario where most patients achieve control of their cancer, quality of life concerns predominate. Here we examine the biological ways in which an effective dose can be escalated without an unacceptable increase in toxicity. Possible avenues include exploiting the unusual radiobiology of prostate cancer by hypofractionation, the use of image guidance, adaptive planning and prostate motion management. We await with anticipation the results of large randomised trials of hypofractionation, moderate and profound, to establish whether we can further improve the balance between cure and quality of life.

Prostate Stereotactic Body Radiotherapy - First UK Experience

AIMS Stereotactic body radiotherapy (SBRT) combines image-guided radiotherapy with hypofractionation, both of which will probably result in improvements in patient outcomes in prostate cancer. Most clinical experience with this technique resides in North America. Here we present the first UK cohort to receive SBRT for prostate cancer. MATERIALS AND METHODS Fifty-one prostate cancer patients (10 low risk, 35 intermediate risk and 6 high risk) were treated with 36.25 Gy in five fractions over 1-2 weeks and gold seed image guidance. All patients had toxicity International Prostate Symptom score (IPSS) and Radiation Therapy Oncology Group recorded prospectively and prostate-specific antigen was measured 3-6 monthly during follow-up. RESULTS The median IPSS was 6, 11, 8 and 5 at baseline, 1-3 weeks, 4-6 weeks and 7-12 weeks after treatment. Radiation Therapy Oncology Group genitourinary and gastrointestinal toxicity of grade 2 was seen in 22% and 14%, respectively, at 1-3 weeks after treatment; no patient had grade 3+ toxicity at this time point, although two patients had grade 3 urinary frequency recorded during treatment. The median follow-up for the 42 patients who did not receive androgen deprivation was 14.5 months. Prostate-specific antigen at 13-18 months after treatment was 1.3 ng/ml. CONCLUSION Prostate SBRT is a promising treatment for organ-confined prostate cancer and is currently being investigated in a UK-led phase III trial.

The utility of multimodality imaging with CT and MRI in defining rectal tumour volumes for radiotherapy treatment planning: a pilot study

Aims: This study compares the volumetric and spatial relationships of gross tumour volume (GTV) derived from CT (CT‐GTV) and GTV derived from MRI (MR‐GTV) to determine the utility of multi‐modality imaging for radiotherapy treatment planning in rectal cancer.

Initial UK Experience of Stereotactic Body Radiotherapy for Extracranial Oligometastases: Can We Change the Therapeutic Paradigm?

AIMS To retrospectively review the toxicity and early outcome data from patients who have received stereotactic body radiotherapy (SBRT) for extracranial oligometastases at a single UK institution. MATERIALS AND METHODS Eligible patients had ≤3 extracranial metastases and performance status ≤2. Prior systemic therapy and radical treatment of oligometastastic relapse with any standard treatment modality was permitted. Patients with synchronous metastatic disease were excluded unless they had evidence of controlled primary disease after radical therapy. Follow-up consisted of clinical examination, biochemical and radiological assessments in accordance with standard clinical care. Progression events were defined using RECIST. Toxicity was evaluated using CTCAE v4.0. Local control, progression-free survival (PFS), freedom from widespread distant metastasis (defined as disease not amenable to further radical salvage therapy) and overall survival were calculated. RESULTS Between July 2011 and April 2014, 73 patients with 87 metastases received SBRT (range 1-3 per patient). The median follow-up was 14.5 months (range 0-26.4). The median PFS was 14.5 months (1 year PFS 57%, 2 year 28%); 1 year overall survival 96%, 2 year 79.8%; 2 year local control 88%. At 2 years, 46% of patients were free from widespread distant metastases. No ≥ grade 3 acute or late toxicity was observed. CONCLUSION At this time point, observed toxicity is minimal with excellent local control rates. This promising treatment paradigm requires further investigation in the context of a randomised controlled trial to establish if the addition of SBRT to standard care improves survival outcomes.

The effect of antiemetics and reduced radiation fields on acute gastrointestinal morbidity of adjuvant radiotherapy in stage I seminoma of the testis: A randomized pilot study

The purpose of this pilot study was to evaluate the acute gastrointestinal morbidity of adjuvant radiotherapy (RT) for Stage I seminoma of the testis. Ten Stage I patients receiving para-aortic and ipsilateral pelvic nodal (dog-leg) RT provided a toxicity baseline (group A). Twenty Stage I patients, randomized to dog-leg RT or para-aortic RT (10 per group) were further randomized to received prophylactic ondansetron or expectant therapy with metoclopramide (group B). Daily patient-completed questionnaires evaluated acute toxicity. In group A (n = 10), nausea, vomiting, diarrhoea and abdominal discomfort were experienced in 90%, 80%, 70% and 90% respectively. Antiemetic and antidiarrhoeal agents were required in 70% and 10% respectively, with good response. For group B (n = 20), the overall incidences of nausea, vomiting diarrhoea and abdominal discomfort were 80%, 45%, 60% and 80% respectively. The ondansetron group experienced less nausea (P = 0.02) and less vomiting (P = 0.06). Both reduced field size and ondansetron groups appeared to have less diarrhoea (P = 0.06). The use of antiemetics in the expectant therapy groups resulted in at least a two-level reduction of toxicity grade in 86% of patients. A high incidence of lethargy, anorexia and headaches was noted for all groups. The incidence of headaches was not increased with ondansetron. Dog-leg RT for Stage I seminomas is associated with readily demonstrable gastrointestinal tract (GIT) toxicity. The number of patients in this study is too small to produce definitive results, but there appears to be reduced GIT toxicity with prophylactic antiemetics. The effect of reduced RT fields has been assessed further in the MRC randomized trial of field sizes (TE10).

Randomised pilot study of dose escalation using conformal radiotherapy in prostate cancer: long-term follow-up

Background:Radical three-dimensional conformal radiotherapy (CFRT) with initial androgen suppression (AS) is a standard management for localised prostate cancer (PC). This pilot study evaluated the role of dose escalation and appropriate target volume margin. Here, we report long-term follow-up.Methods:Eligible patients had T1b-T3b N0 M0 PC. After neoadjuvant AS, they were randomised to CFRT, giving (a) 64 Gy with either a 1.0- or 1.5-cm margin and (b) ±10 Gy boost to the prostate alone.Results:One hundred and twenty-six men were randomised and treated. Median follow-up was 13.7 years. The median age was 66.6 years at randomisation. Median presenting prostate-specific antigen (PSA) was 14 ng ml−1. Sixty-four out of 126 patients developed PSA failure. Forty-nine out of 126 patients restarted AS, 34 out of 126 developed metastases and 28 out of 126 developed castrate-resistant prostate cancer (CRPC). Fifty-one out of 126 patients died; 19 out of 51 died of PC. Median overall survival (OS) was 14.4 years. Although escalated dose results were favourable, no statistically significant differences were seen between the randomised groups; PSA control (hazard ratio (HR): 0.77 (95% confidence interval (CI): 0.47–1.26)), development of CRPC (HR: 0.81 (95% CI: 0.40–1.65)), PC-specific survival (HR: 0.59 (95% CI:0.23–1.49)) and OS (HR: 0.81 (95% CI: 0.47–1.40)). There was no evidence of a difference in PSA control according to margin size (HR: 1.01 (95% CI: 0.61–1.66)).Interpretation:Long-term follow-up of this small pilot study is compatible with a benefit from dose escalation, but confirmation from larger trials is required. There was no obvious detriment using the smaller radiotherapy margin.

Clinical trial: efficacy of a low or modified fat diet for the prevention of gastrointestinal toxicity in patients receiving radiotherapy treatment for pelvic malignancies

BACKGROUND Inflammatory responses to pelvic radiotherapy can result in severe changes to normal gastrointestinal function with potentially severe long-term effects. Reduced or modified fat diets may confer benefit. METHODS This randomised controlled trial recruited patients with gynaecological, urological or lower gastrointestinal malignancy due to receive radical radiotherapy. Patients were randomised to a low fat (20% total energy from long chain triglycerides), modified fat (20% from long chain triglycerides and 20% from medium chain triglycerides) or normal fat diet (40% total energy from long chain triglycerides). The primary outcome was a difference in change in Inflammatory Bowel Disease Questionnaire--Bowel (IBDQ-B) score, from the start to end of radiotherapy. RESULTS A total of 117 patients with pelvic tumours (48% urological; 32% gastrointestinal; 20% gynaecological), with mean (SD) age: 65 (11.0) years, male:female ratio: 79:38, were randomised. The mean (SE) fall in paired IBDQ-B score was -7.3 (0.9) points, indicating a worsening toxicity. Differences between groups were not significant: P = 0.914 (low versus modified fat), P = 0.793 (low versus normal fat) and P = 0.890 (modified versus normal fat). The difference in fat intake between low and normal fat groups was 29.5 g [1109 kJ (265 kcal)] amounting to 11% (of total energy intake) compared to the planned 20% differential. Full compliance with fat prescription was only 9% in the normal fat group compared to 93% in the low fat group. CONCLUSIONS A low or modified fat diet during pelvic radiotherapy did not improve gastrointestinal symptom scores compared to a normal fat intake. An inadequate differential in fat intake between the groups may have confounded the results.

Investigating the relationship between virtual cystoscopy image quality and CT slice thickness

OBJECTIVE To investigate the effect of reconstruction slice thickness on image quality at CT virtual cystoscopy (VC). METHODS Pelvic CT examinations in bladder cancer patients were reconstructed at different slice thicknesses (0.6-5 mm) and intervals, and resulting VC images assessed. Quality indicators were ridging, holes, floaters and dimpling artefacts, tumour definition, and an overall score, ranked 1 (best) to 7 (worst). CT number and standard deviation (SD) for bladder contents and bladder wall were recorded. The mean SD was used as a measure of noise, and the contrast-to-noise ratio (CNR) was calculated as the CT number difference between them divided by the average image noise. The mean CNR across the three levels was used for analysis. Each qualitative image quality measure was compared with CT number, noise and CNR measurements. RESULTS Dimpling artefacts increased with thinner slice reconstruction and correlated with increased noise, often resulting in poor tumour definition. The best overall image quality score was seen for VC images reconstructed at 1.2 mm slice thickness, probably because of the competing effects of spatial resolution and CNR. CONCLUSION A slice thickness reconstruction <1.2 mm does not provide for better image quality at VC owing to the presence of increased noise.

EP-1937: UK stereotactic ablative radiotherapy trials normal tissue dose constraints tolerance consensus

Results: A total of 1847 pts (904 right-sided and 943 leftsided) were treated with either 40 Gy/15 fx (912 pts) or 50 Gy/25 fx (935 pts). 388 of the left-sided pts were treated with gated RT, and 440 without. No information about gating was available for the remaining 115 pts. Dmax(CTV) was less than 110% of the prescription dose in 99.4% of the plans. More than 2 cm3 of the CTV received 107-110% of the dose in 1% of the hypo-fractionated plans. For the normofractionated plans, this deviation was observed in 3.5% of the plans. For 92.3% of the hypo-fractionated plans, less than 2% of the CTV was covered with doses above 105%, whereas 3.9% and 3.5% of the plans had minor and major deviations, respectively. For 80.8% of the pts, the part of the CTV covered with at least 95% of the prescription dose was in compliance with the guidelines. Minor and major deviations were observed for 12.6% and 6.6% of the pts, respectively. By taking laterality into consideration, 90.8% of the right-sided pts were in compliance with the guidelines compared to only 71.2% of the left-sided pts. For the left-sided pts with available information about gating, it was found that 87.4% and 59.3% of the pts treated with and without gated RT, respectively, were in compliance, thus indicating that shielding of the heart resulted in CTV under-dosage. This was supported by compliance to the protocol heart dose guidelines for 941 left-sided pts. Only one hypo-fractionated pt showed a major deviation in V35Gy and a minor deviation in V17Gy (data missing for one pt). The lung dose satisfied the protocol guidelines for 99.4% of the pts.