K. Thomas

Diffusion-weighted magnetic resonance imaging for monitoring prostate cancer progression in patients managed by active surveillance

OBJECTIVES We studied patients managed by active surveillance to determine whether there was a difference over time in apparent diffusion coefficients (ADCs) derived from diffusion-weighted MRI in those who progressed to radical treatment (progressors, n = 17) compared with those who did not (non-progressors, n = 33). METHODS 50 consecutive patients (Stage T1/2a, Gleason grade ≤ 3+4, prostate-specific antigen (PSA) <15 ng ml⁻¹, <50% cores positive) were imaged endorectally (baseline and 1-3 years follow-up) with T₂ weighted (T₂W) and echo-planar diffusion-weighted MRI sequences. Regions of interest drawn on ADC maps with reference to the T₂W images yielded ADC(all) (b = 0-800), ADC(fast) (b = 0-300) and ADC(slow) (b = 300-800) for whole prostate (minus tumour) and tumour (low signal-intensity peripheral zone lesion in biopsy-positive octant). RESULTS Tumour and whole prostate ADC(all) and ADC(fast) were significantly reduced over time in progressors (p = 0.03 and 0.03 for tumours, respectively; p = 0.02 and 0.007 for the whole prostate, respectively). There were no significant changes in ADC over time in non-progressors. A 10% reduction in tumour ADC(all) indicated progression with a 93% sensitivity and 40% specificity (A(z) of receiver operating characteristic (ROC) curve = 0.68). Percentage reductions in whole prostate ADC(all), ADC(fast) and ADC(slow) were also significantly greater in progressors than in non-progressors (p = 0.01, 0.03 and 0.008, respectively). CONCLUSION This pilot study shows that DW-MRI has potential for monitoring patients with early prostate cancer who opt for active surveillance.

Simple nutritional intervention in patients with advanced cancers of the gastrointestinal tract, non-small cell lung cancers or mesothelioma and weight loss receiving chemotherapy: a randomised controlled trial

BACKGROUND Weight loss in patients with cancer is common and associated with a poorer survival and quality of life. Benefits from nutritional interventions are unclear. The present study assessed the effect of dietary advice and/or oral nutritional supplements on survival, nutritional endpoints and quality of life in patients with weight loss receiving palliative chemotherapy for gastrointestinal and non-small cell lung cancers or mesothelioma. METHODS Participants were randomly assigned to receive no intervention, dietary advice, a nutritional supplement or dietary advice plus supplement before the start of chemotherapy. Patients were followed for 1 year. Survival, nutritional status and quality of life were assessed. RESULTS In total, 256 men and 102 women (median age, 66 years; range 24-88 years) with gastrointestinal (n = 277) and lung (n = 81) cancers were recruited. Median (range) follow-up was 6 (0-49) months. One-year survival was 38.6% (95% confidence interval 33.3-43.9). No differences in survival, weight or quality of life between groups were seen. Patients surviving beyond 26 weeks experienced significant weight gain from baseline to 12 weeks, although this was independent of nutritional intervention. CONCLUSIONS Simple nutritional interventions did not improve clinical or nutritional outcomes or quality of life. Weight gain predicted a longer survival but occurred independently of nutritional intervention.

Lymphocyte-predominant Hodgkin lymphoma—clinical features and treatment outcomes from a 30-year experience

BACKGROUND Lymphocyte-predominant Hodgkin disease (LPHD) is a rare subtype of Hodgkin lymphoma, for which there is limited evidence regarding the presentation, natural history and treatment outcomes. PATIENTS AND METHODS We conducted a single-institution retrospective review all of patients diagnosed with LPHD over a 30-year period. RESULTS Eighty-eight patients were included. Median follow-up was 13 years. Local radiotherapy or chemoradiotherapy resulted in durable disease control in patients with stage I or II disease. Advanced stage at presentation, presence of B symptoms, low albumin, and either partial response or stable disease to first treatment were associated with worse treatment outcomes. Relapse rate for the entire cohort was 44%, with an 8% rate of transformation to large-cell lymphoma. Rituximab in combination with chemotherapy resulted in durable remission in a heavily pretreated subgroup. Outcomes with autologous transplant are discussed. CONCLUSION Our series has the longest follow-up of any report, includes the only series of patients treated with autologous transplant, and has the largest group of patients treated with rituximab and chemotherapy in this indication.

MR vs CT imaging: low rectal cancer tumour delineation for three-dimensional conformal radiotherapy

Modern three-dimentional radiotherapy is based upon CT. For rectal cancer, this relies upon target definition on CT, which is not the optimal imaging modality. The major limitation of CT is its low inherent contrast resolution. Targets defined by MRI could facilitate smaller, more accurate, tumour volumes than CT. Our study reviewed imaging and planning data for 10 patients with locally advanced low rectal cancer (defined as < 6 cm from the anal verge on digital examination). Tumour volume and location were compared for sagittal pre-treatment MRI and planning CT. CT consistently overestimated all tumour radiological parameters. Estimates of tumour volume, tumour length and height of proximal tumour from the anal verge were larger on planning CT than on MRI (p < 0.05). Tumour volumes defined on MRI are smaller, shorter and more distal from the anal sphincter than CT-based volumes. For radiotherapy planning, this may result in smaller treatment volumes, which could lead to a reduction in dose to organs at risk and facilitate dose escalation.

Can biological markers act as non-invasive, sensitive indicators of radiation-induced effects in the gastrointestinal mucosa?

Background  Reliable, non‐invasive biological markers of the severity of radiotherapy‐induced damage to the gastrointestinal tract are not available. Clinicians continue to use symptom scores as surrogate indicators of toxicity.

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.

Baseline urinary phytoestrogen levels and the natural history of untreated, localised prostate cancer in a British population

AIM To determine whether urinary concentrations of phytoestrogens are associated with the rate of disease progression in men with untreated, localised prostate cancer. PATIENTS AND METHODS Patients with untreated, localised prostatic adenocarcinoma on a prospective clinical study of active surveillance had urine samples collected at baseline. Patients underwent monitoring with serial PSA levels and repeat octant prostate biopsies. Disease progression was defined as either adverse histology on repeat biopsy (primary Gleason grade >or= 4, or >50% positive cores) or radical treatment for PSA velocity >1 ng/mL/year. Time to disease progression was analysed with respect to baseline urinary levels of genistein, enterolactone, daidzein and equol, assayed using liquid chromatography/tandem mass spectrometry. RESULTS 191 patients were evaluable, with a median follow-up of 2.5 years. 71 patients experienced disease progression. No significant association was seen between time to disease progression and baseline urinary levels of daidzein (p=0.85), genistein (p=0.81), enterolactone (p=0.085) or equol (p=0.33). No significant association was seen between adverse histology on repeat biopsy and urinary levels of either daidzein (p=0.85), genistein (p=0.58), enterolactone (p=0.88) or equol (p=0.71). There was no significant correlation between PSA velocity and urinary levels of daidzein (p=0.90), genistein (p=0.98), enterolactone (p=0.10) or equol (p=0.60). CONCLUSION These data do not support the hypothesis that phytoestrogens prevent disease progression in men with localised prostate cancer.

Pelvic Intensity-modulated Radiotherapy: Can we Better Quantify the Late Side-effects?

Increasingly, the prevention and management of radiotherapy side-effects have become a fundamental part of the care given to patients diagnosed with cancer. Pelvic IMRT in anal cancer allows sparing of normal tissues, such as genitalia, bowel and bladder, at least in terms of dose-volume data [2]. However, the effect on patient outcomes is what matters and for this reason it is important to quantify toxicity in these structures and collect specific data to provide a baseline against which the outcomes for future technical developments can be compared. Furthermore, at the present time we have few quantitative data to provide patients with more details regarding expected long-term consequences and to ensure that consent is truly informed [1e3]. We conducted a post-IMRT follow-up on a cohort of patientsdiagnosedwithanalcancerandtreatedwithIMRTsince late 2010 to assess late side-effects and chronic symptoms. We used validated questionnaires including Inflammatory Bowel Disease Questionnaire (IBDQ), IBDQ-B, Vaizey and a pelvic symptom questionnaire, which take into account not only symptoms but also the patient’s feelings and perception of disease and side-effects, and the effect on normal life [4,5]. From a preliminary analysis of our data, most patients maintained good bowel continence and the treatment was also well tolerated in terms of genitalia toxicity. Over a 3 year follow-up period, IBDQ, IBDQ-B and Vaizey scores appeared to be either stable or improving, indicating no progressive change in function.

PD-0272: Can CBCT image quality be improved to reduce inter observer error in patients receiving radiotherapy to the prostate?

position shifts 1.5 cm the CTV coverage drops rapidly for RA isotropic (V95(CTV) from 100% to 83%) whereas the RA anisotropic were more robust (V95(CTV) from 100% to 98%). The over dosage of ORs, e.g. the spinal cord, were in general of no clinical importance. In general, the most preferable method to increase the robustness was to use arcs with avoiding sectors in combination with arcs without avoiding sectors. If all arcs had avoiding sectors this limited the beam angles geometry at the expense of coverage of targets in the upper parts of the head and neck.